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Sample records for pathway predicts poor

  1. Poor Semen Quality Predicts Increased Mortality

    DEFF Research Database (Denmark)

    Jensen, Tina Kold; Bostofte, Erik; Jacobsen, Rune

    Objective: Over recent decades a possible decrease in semen quality and an increase in the incidence of testicular cancer have been reported. In addition, men with poor semen quality have been reported to be at increased risk of developing testicular cancer whereas the risk of other cancers...... is not increased. The long-term survival of men with poor semen quality is, however, unknown. We therefore studied the associations between semen characteristics and subsequent mortality. Back to Top Material and Methods: The Copenhagen Sperm Analysis Laboratory is one of several public semen analysis laboratories...... in Denmark and examines semen samples mostly from men in the area of Copenhagen. Men are referred to the clinic by general practitioners and urologists, and the investigations are paid for through the public health system. A total of 34.442 men had a semen analysis done at the laboratory during 1963 to 1995...

  2. Machine learning methods for metabolic pathway prediction

    Directory of Open Access Journals (Sweden)

    Karp Peter D

    2010-01-01

    Full Text Available Abstract Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations.

  3. Machine learning methods for metabolic pathway prediction

    Science.gov (United States)

    2010-01-01

    Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML) methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations. PMID:20064214

  4. Low plasma bicarbonate predicts poor outcome of cerebral malaria ...

    African Journals Online (AJOL)

    Malaria remains a major cause of morbidity and mortality in many sub Saharan countries and cerebral malaria is widely recognised as one of its most fatal forms. We studied the predictive value of routine biochemical laboratory indices in predicting the outcome of cerebral malaria in 50 Nigerian children ages 9 months to 6 ...

  5. Poor Response to Periodontal Treatment May Predict Future Cardiovascular Disease.

    Science.gov (United States)

    Holmlund, A; Lampa, E; Lind, L

    2017-07-01

    Periodontal disease has been associated with cardiovascular disease (CVD), but whether the response to the treatment of periodontal disease affects this association has not been investigated in any large prospective study. Periodontal data obtained at baseline and 1 y after treatment were available in 5,297 individuals with remaining teeth who were treated at a specialized clinic for periodontal disease. Poor response to treatment was defined as having >10% sites with probing pocket depth >4 mm deep and bleeding on probing at ≥20% of the sites 1 y after active treatment. Fatal/nonfatal incidence rate of CVD (composite end point of myocardial infarction, stroke, and heart failure) was obtained from the Swedish cause-of-death and hospital discharge registers. Poisson regression analysis was performed to analyze future risk of CVD. During a median follow-up of 16.8 y (89,719 person-years at risk), those individuals who did not respond well to treatment (13.8% of the sample) had an increased incidence of CVD ( n = 870) when compared with responders (23.6 vs. 15.3%, P 4 mm, and number of teeth, the incidence rate ratio for CVD among poor responders was 1.28 (95% CI, 1.07 to 1.53; P = 0.007) as opposed to good responders. The incidence rate ratio among poor responders increased to 1.39 (95% CI, 1.13 to 1.73; P = 0.002) for those with the most remaining teeth. Individuals who did not respond well to periodontal treatment had an increased risk for future CVD, indicating that successful periodontal treatment might influence progression of subclinical CVD.

  6. DEK protein overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Sun, Jie; Bi, Fangfang; Yang, Yang; Zhang, Yuan; Jin, Aihua; Li, Jinzi; Lin, Zhenhua

    2017-02-01

    DEK, a transcription factor, is involved in mRNA splicing, transcriptional control, cell division and differentiation. Recent studies suggest that DEK overexpression can promote tumorigenesis in a wide range of cancer cell types. However, little is known concerning the status of DEK in pancreatic ductal adenocarcinoma (PDAC). Based on the microarray data from Gene Expression Omnibus (GEO), the expression levels of DEK mRNA in PDAC tissues were significantly higher than levels in the adjacent non-tumor tissues. To explore the clinical features of DEK overexpression in PDAC, 87 PDAC and 52 normal pancreas tissues were selected for immunoenzyme staining of the DEK protein. Localization of the DEK protein was detected in PANC-1 pancreatic cancer cells using immunofluorescence (IF) staining. The correlations between DEK overexpression and the clinical features of PDAC were evaluated using the Chi-squared (χ2) and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. The expression levels of DEK mRNA in PDAC tissues were significantly higher than that in the adjacent non‑tumor tissues. The DEK protein showed a primarily nuclear staining pattern in PDAC. The positive rate of the DEK protein was 52.9% (46/87) in PDAC, which was significantly higher than that in the adjacent normal pancreatic tissues (7.7%, 4/52). DEK overexpression in PDAC was correlated with tumor size, histological grade, tumor‑node‑metastasis (TNM) stage and overall survival (OS) rates. In addition, multivariate analysis demonstrated that DEK overexpression was an independent prognostic factor along with histological grade and TNM stage in patients with PDAC. In conclusion, DEK overexpression is associated with PDAC progression and may be a potential biomarker for poor prognostic evaluation in PDAC.

  7. Comorbidity predicts poor prognosis in nasopharyngeal carcinoma: Development and validation of a predictive score model

    International Nuclear Information System (INIS)

    Guo, Rui; Chen, Xiao-Zhong; Chen, Lei; Jiang, Feng; Tang, Ling-Long; Mao, Yan-Ping; Zhou, Guan-Qun; Li, Wen-Fei; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Ma, Jun

    2015-01-01

    Background and purpose: The impact of comorbidity on prognosis in nasopharyngeal carcinoma (NPC) is poorly characterized. Material and methods: Using the Adult Comorbidity Evaluation-27 (ACE-27) system, we assessed the prognostic value of comorbidity and developed, validated and confirmed a predictive score model in a training set (n = 658), internal validation set (n = 658) and independent set (n = 652) using area under the receiver operating curve analysis. Results: Comorbidity was present in 40.4% of 1968 patients (mild, 30.1%; moderate, 9.1%; severe, 1.2%). Compared to an ACE-27 score ⩽1, patients with an ACE-27 score >1 in the training set had shorter overall survival (OS) and disease-free survival (DFS) (both P < 0.001), similar results were obtained in the other sets (P < 0.05). In multivariate analysis, ACE-27 score was a significant independent prognostic factor for OS and DFS. The combined risk score model including ACE-27 had superior prognostic value to TNM stage alone in the internal validation set (0.70 vs. 0.66; P = 0.02), independent set (0.73 vs. 0.67; P = 0.002) and all patients (0.71 vs. 0.67; P < 0.001). Conclusions: Comorbidity significantly affects prognosis, especially in stages II and III, and should be incorporated into the TNM staging system for NPC. Assessment of comorbidity may improve outcome prediction and help tailor individualized treatment

  8. Potential biological pathways linking Type-D personality and poor health: A cross-sectional investigation.

    Directory of Open Access Journals (Sweden)

    Vera K Jandackova

    Full Text Available Type-D personality, defined as a combination of high negative affect and high social isolation, has been associated with poor health outcomes. However, pathways underlying this association are largely unknown. We investigated the relationship between Type-D personality and several biological and behavioral pathways including the autonomic nervous system, the immune system, glucose regulation and sleep in a large, apparently healthy sample.Data from a total of 646 respondents (age 41.6±11.5, 12,2% women were available for analysis. Persons with Type-D (negative affect and social isolation score ≥10 were contrasted with those without Type-D. Measures of plasma fibrinogen levels, white blood cell count, high sensitivity C-reactive protein, fasting plasma glucose (FPG, cholesterol, high-density and low-density lipoprotein, glycated hemoglobin (HbA1c, creatinine, triglycerides, and albumin were derived from fasting blood samples. Urine norepinephrine and free cortisol were determined by high-performance liquid chromatography. Time-domain heart rate variability (HRV measures were calculated for the 24hr recording period and for nighttime separately.Persons with Type-D had higher HbA1c, FPG, and fibrinogen, and lower nighttime HRV than those without Type-D, suggesting worse glycemic control, systemic inflammation and poorer autonomic nervous system modulation in Type-D persons. In addition, those with Type-D reported less social support and greater sleep difficulties while no group differences were observed for alcohol and cigarette consumption, physical activity and body mass index.Findings provide some of the first evidence for multiple possible biological and behavioral pathways between Type-D personality and increased morbidity and mortality.

  9. Rule Mining Techniques to Predict Prokaryotic Metabolic Pathways

    KAUST Repository

    Saidi, Rabie

    2017-08-28

    It is becoming more evident that computational methods are needed for the identification and the mapping of pathways in new genomes. We introduce an automatic annotation system (ARBA4Path Association Rule-Based Annotator for Pathways) that utilizes rule mining techniques to predict metabolic pathways across wide range of prokaryotes. It was demonstrated that specific combinations of protein domains (recorded in our rules) strongly determine pathways in which proteins are involved and thus provide information that let us very accurately assign pathway membership (with precision of 0.999 and recall of 0.966) to proteins of a given prokaryotic taxon. Our system can be used to enhance the quality of automatically generated annotations as well as annotating proteins with unknown function. The prediction models are represented in the form of human-readable rules, and they can be used effectively to add absent pathway information to many proteins in UniProtKB/TrEMBL database.

  10. Rule Mining Techniques to Predict Prokaryotic Metabolic Pathways

    KAUST Repository

    Saidi, Rabie; Boudellioua, Imene; Martin, Maria J.; Solovyev, Victor

    2017-01-01

    It is becoming more evident that computational methods are needed for the identification and the mapping of pathways in new genomes. We introduce an automatic annotation system (ARBA4Path Association Rule-Based Annotator for Pathways) that utilizes rule mining techniques to predict metabolic pathways across wide range of prokaryotes. It was demonstrated that specific combinations of protein domains (recorded in our rules) strongly determine pathways in which proteins are involved and thus provide information that let us very accurately assign pathway membership (with precision of 0.999 and recall of 0.966) to proteins of a given prokaryotic taxon. Our system can be used to enhance the quality of automatically generated annotations as well as annotating proteins with unknown function. The prediction models are represented in the form of human-readable rules, and they can be used effectively to add absent pathway information to many proteins in UniProtKB/TrEMBL database.

  11. Ford Class Aircraft Carrier: Poor Outcomes Are the Predictable Consequences of the Prevalent Acquisition Culture

    Science.gov (United States)

    2015-10-01

    FORD CLASS AIRCRAFT CARRIER Poor Outcomes Are the Predictable Consequences of the Prevalent Acquisition Culture...2. REPORT TYPE 3. DATES COVERED 00-00-2015 to 00-00-2015 4. TITLE AND SUBTITLE Ford Class Aircraft Carrier: Poor Outcomes Are the Predictable...This Study The Navy set ambitious goals for the Ford -class program, including an array of new technologies and design features that were intended

  12. Predicting metabolic pathways by sub-network extraction.

    Science.gov (United States)

    Faust, Karoline; van Helden, Jacques

    2012-01-01

    Various methods result in groups of functionally related genes obtained from genomes (operons, regulons, syntheny groups, and phylogenetic profiles), transcriptomes (co-expression groups) and proteomes (modules of interacting proteins). When such groups contain two or more enzyme-coding genes, graph analysis methods can be applied to extract a metabolic pathway that interconnects them. We describe here the way to use the Pathway extraction tool available on the NeAT Web server ( http://rsat.ulb.ac.be/neat/ ) to piece together the metabolic pathway from a group of associated, enzyme-coding genes. The tool identifies the reactions that can be catalyzed by the products of the query genes (seed reactions), and applies sub-graph extraction algorithms to extract from a metabolic network a sub-network that connects the seed reactions. This sub-network represents the predicted metabolic pathway. We describe here the pathway prediction process in a step-by-step way, give hints about the main parametric choices, and illustrate how this tool can be used to extract metabolic pathways from bacterial genomes, on the basis of two study cases: the isoleucine-valine operon in Escherichia coli and a predicted operon in Cupriavidus (Ralstonia) metallidurans.

  13. MRI findings and spreading patterns of necrotizing external otitis: Is a poor outcome predictable?

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, B.J. [Department of Radiology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Han, M.H. [Department of Radiology, Seoul National University College of Medicine, Seoul (Korea, Republic of) and Clinical Research Institute, Seoul National University Hospital, Seoul (Korea, Republic of) and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul (Korea, Republic of)]. E-mail: hanmh@radcom.snu.ac.kr; Oh, S.H. [Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Song, J.J. [Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Chang, K.-H. [Department of Radiology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Clinical Research Institute, Seoul National University Hospital, Seoul (Korea, Republic of); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul (Korea, Republic of)

    2006-06-15

    AIM: To evaluate spreading patterns of necrotizing external otitis (NEO) by magnetic resonance imaging (MRI) and to identify spreading patterns related to a poor outcome. MATERIALS AND METHODS: Fourteen patients with NEO were divided into good and poor outcome groups according to their final clinical outcomes. Initial MRI images were retrospectively reviewed for regional abnormalities, and follow-up MRI images were reviewed for ICA flow void abnormality and for the following five spreading patterns: medial, crossed, anterior, intracranial, and combined. The frequencies of the abnormal flow void or spreading patterns were compared between the good and poor response groups. RESULTS: Seven (50%) and seven (50%) patients were respectively allocated to the good and poor outcome groups. Retrocondylar fat infiltration was the most commonest finding on initial MRI images (93%). The frequencies of the abnormal flow void and spreading patterns in the good and poor groups, respectively, were: abnormal flow void, 0 and four (57%); anterior, two (29%) and three (43%); medial, six (86%) and seven (100%); crossed, six (86%) and seven (100%); intracranial middle cranial fossa, one (14%) and four (57%); intracranial posterior cranial fossa, four (57%) and six (86%); intracranial foramen magnum, one (14%) and six (86%). CONCLUSIONS: NEO almost always involves the retrocondylar fat and spreads via various pathways to extracranial or intracranial spaces. The presence of an abnormal flow void and intracranial dural enhancement, particularly in the middle cranial fossa and foramen magnum, may indicate a poor prognosis.

  14. MRI findings and spreading patterns of necrotizing external otitis: Is a poor outcome predictable?

    International Nuclear Information System (INIS)

    Kwon, B.J.; Han, M.H.; Oh, S.H.; Song, J.J.; Chang, K.-H.

    2006-01-01

    AIM: To evaluate spreading patterns of necrotizing external otitis (NEO) by magnetic resonance imaging (MRI) and to identify spreading patterns related to a poor outcome. MATERIALS AND METHODS: Fourteen patients with NEO were divided into good and poor outcome groups according to their final clinical outcomes. Initial MRI images were retrospectively reviewed for regional abnormalities, and follow-up MRI images were reviewed for ICA flow void abnormality and for the following five spreading patterns: medial, crossed, anterior, intracranial, and combined. The frequencies of the abnormal flow void or spreading patterns were compared between the good and poor response groups. RESULTS: Seven (50%) and seven (50%) patients were respectively allocated to the good and poor outcome groups. Retrocondylar fat infiltration was the most commonest finding on initial MRI images (93%). The frequencies of the abnormal flow void and spreading patterns in the good and poor groups, respectively, were: abnormal flow void, 0 and four (57%); anterior, two (29%) and three (43%); medial, six (86%) and seven (100%); crossed, six (86%) and seven (100%); intracranial middle cranial fossa, one (14%) and four (57%); intracranial posterior cranial fossa, four (57%) and six (86%); intracranial foramen magnum, one (14%) and six (86%). CONCLUSIONS: NEO almost always involves the retrocondylar fat and spreads via various pathways to extracranial or intracranial spaces. The presence of an abnormal flow void and intracranial dural enhancement, particularly in the middle cranial fossa and foramen magnum, may indicate a poor prognosis

  15. Neurophysiological prediction of neurological good and poor outcome in post-anoxic coma.

    Science.gov (United States)

    Grippo, A; Carrai, R; Scarpino, M; Spalletti, M; Lanzo, G; Cossu, C; Peris, A; Valente, S; Amantini, A

    2017-06-01

    Investigation of the utility of association between electroencephalogram (EEG) and somatosensory-evoked potentials (SEPs) for the prediction of neurological outcome in comatose patients resuscitated after cardiac arrest (CA) treated with therapeutic hypothermia, according to different recording times after CA. Glasgow Coma Scale, EEG and SEPs performed at 12, 24 and 48-72 h after CA were assessed in 200 patients. Outcome was evaluated by Cerebral Performance Category 6 months after CA. Within 12 h after CA, grade 1 EEG predicted good outcome and bilaterally absent (BA) SEPs predicted poor outcome. Because grade 1 EEG and BA-SEPs were never found in the same patient, the recording of both EEG and SEPs allows us to correctly prognosticate a greater number of patients with respect to the use of a single test within 12 h after CA. At 48-72 h after CA, both grade 2 EEG and BA-SEPs predicted poor outcome with FPR=0.0%. When these neurophysiological patterns are both present in the same patient, they confirm and strengthen their prognostic value, but because they also occurred independently in eight patients, poor outcome is predictable in a greater number of patients. The combination of EEG/SEP findings allows prediction of good and poor outcome (within 12 h after CA) and of poor outcome (after 48-72 h). Recording of EEG and SEPs in the same patients allows always an increase in the number of cases correctly classified, and an increase of the reliability of prognostication in a single patient due to concordance of patterns. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Using Predictive Modelling to Identify Students at Risk of Poor University Outcomes

    Science.gov (United States)

    Jia, Pengfei; Maloney, Tim

    2015-01-01

    Predictive modelling is used to identify students at risk of failing their first-year courses and not returning to university in the second year. Our aim is twofold. Firstly, we want to understand the factors that lead to poor first-year experiences at university. Secondly, we want to develop simple, low-cost tools that would allow universities to…

  17. Poor outcome prediction by burst suppression ratio in adults with post-anoxic coma without hypothermia.

    Science.gov (United States)

    Yang, Qinglin; Su, Yingying; Hussain, Mohammed; Chen, Weibi; Ye, Hong; Gao, Daiquan; Tian, Fei

    2014-05-01

    Burst suppression ratio (BSR) is a quantitative electroencephalography (qEEG) parameter. The purpose of our study was to compare the accuracy of BSR when compared to other EEG parameters in predicting poor outcomes in adults who sustained post-anoxic coma while not being subjected to therapeutic hypothermia. EEG was registered and recorded at least once within 7 days of post-anoxic coma onset. Electrodes were placed according to the international 10-20 system, using a 16-channel layout. Each EEG expert scored raw EEG using a grading scale adapted from Young and scored amplitude-integrated electroencephalography tracings, in addition to obtaining qEEG parameters defined as BSR with a defined threshold. Glasgow outcome scales of 1 and 2 at 3 months, determined by two blinded neurologists, were defined as poor outcome. Sixty patients with Glasgow coma scale score of 8 or less after anoxic accident were included. The sensitivity (97.1%), specificity (73.3%), positive predictive value (82.5%), and negative prediction value (95.0%) of BSR in predicting poor outcome were higher than other EEG variables. BSR1 and BSR2 were reliable in predicting death (area under the curve > 0.8, P coma who do not undergo therapeutic hypothermia when compared to other qEEG parameters.

  18. Checkpoint Kinase 1 Expression Predicts Poor Prognosis in Nigerian Breast Cancer Patients.

    Science.gov (United States)

    Ebili, Henry Okuchukwu; Iyawe, Victoria O; Adeleke, Kikelomo Rachel; Salami, Babatunde Abayomi; Banjo, Adekunbiola Aina; Nolan, Chris; Rakha, Emad; Ellis, Ian; Green, Andrew; Agboola, Ayodeji Olayinka Johnson

    2018-02-01

    Checkpoint kinase 1 (CHEK1), a DNA damage sensor and cell death pathway stimulator, is regarded as an oncogene in tumours, where its activities are considered essential for tumourigenesis and the survival of cancer cells treated with chemotherapy and radiotherapy. In breast cancer, CHEK1 expression has been associated with an aggressive tumour phenotype, the triple-negative breast cancer subtype, an aberrant response to tamoxifen, and poor prognosis. However, the relevance of CHEK1 expression has, hitherto, not been investigated in an indigenous African population. We therefore aimed to investigate the clinicopathological, biological, and prognostic significance of CHEK1 expression in a cohort of Nigerian breast cancer cases. Tissue microarrays of 207 Nigerian breast cancer cases were tested for CHEK1 expression using immunohistochemistry. The clinicopathological, molecular, and prognostic characteristics of CHEK1-positive tumours were determined using the Chi-squared test and Kaplan-Meier and Cox regression analyses in SPSS Version 16. Nuclear expression of CHEK1 was present in 61% of breast tumours and was associated with tumour size, triple-negative cancer, basal-like phenotype, the epithelial-mesenchymal transition, p53 over-expression, DNA homologous repair pathway dysfunction, and poor prognosis. The rate expression of CHEK1 is high in Nigerian breast cancer cases and is associated with an aggressive phenotype and poor prognosis.

  19. Poor Gait Performance and Prediction of Dementia: Results From a Meta-Analysis.

    Science.gov (United States)

    Beauchet, Olivier; Annweiler, Cédric; Callisaya, Michele L; De Cock, Anne-Marie; Helbostad, Jorunn L; Kressig, Reto W; Srikanth, Velandai; Steinmetz, Jean-Paul; Blumen, Helena M; Verghese, Joe; Allali, Gilles

    2016-06-01

    Poor gait performance predicts risk of developing dementia. No structured critical evaluation has been conducted to study this association yet. The aim of this meta-analysis was to systematically examine the association of poor gait performance with incidence of dementia. An English and French Medline search was conducted in June 2015, with no limit of date, using the medical subject headings terms "Gait" OR "Gait Disorders, Neurologic" OR "Gait Apraxia" OR "Gait Ataxia" AND "Dementia" OR "Frontotemporal Dementia" OR "Dementia, Multi-Infarct" OR "Dementia, Vascular" OR "Alzheimer Disease" OR "Lewy Body Disease" OR "Frontotemporal Dementia With Motor Neuron Disease" (Supplementary Concept). Poor gait performance was defined by standardized tests of walking, and dementia was diagnosed according to international consensus criteria. Four etiologies of dementia were identified: any dementia, Alzheimer disease (AD), vascular dementia (VaD), and non-AD (ie, pooling VaD, mixed dementias, and other dementias). Fixed effects meta-analyses were performed on the estimates in order to generate summary values. Of the 796 identified abstracts, 12 (1.5%) were included in this systematic review and meta-analysis. Poor gait performance predicted dementia [pooled hazard ratio (HR) combined with relative risk and odds ratio = 1.53 with P analysis provides evidence that poor gait performance predicts dementia. This association depends on the type of dementia; poor gait performance is a stronger predictor of non-AD dementias than AD. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  20. Chronic Kidney Disease – Where Next? Predicting Outcomes and Planning Care Pathways

    Directory of Open Access Journals (Sweden)

    Angharad Marks

    2014-07-01

    Full Text Available With the introduction of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative chronic kidney disease (CKD guidelines, CKD has been identified as common, particularly in the elderly. The outcomes for those with CKD can be poor: mortality, initiation of renal replacement therapy, and progressive deterioration in kidney function, with its associated complications. In young people with CKD, the risk of poor outcome is high and the social cost substantial, but the actual number of patients affected is relatively small. In the elderly, the risk of poor outcome is substantially lower, but due to the high prevalence of CKD the actual number of poor outcomes attributable to CKD is higher. Predicting which patients are at greatest risk, and being able to tailor care appropriately, has significant potential benefits. Risk prediction models in CKD are being developed and show promise but thus far have limitations. In this review we describe the pathway for developing and evaluating risk prediction tools, and consider what models we have for CKD prediction and where next.

  1. Gene prediction validation and functional analysis of redundant pathways

    DEFF Research Database (Denmark)

    Sønderkær, Mads

    2011-01-01

    have employed a large mRNA-seq data set to improve and validate ab initio predicted gene models. This direct experimental evidence also provides reliable determinations of UTR regions and polyadenylation sites, which are not easily predicted in plants. Furthermore, once an annotated genome sequence...... is available, gene expression by mRNA-Seq enables acquisition of a more complete overview of gene isoform usage in complex enzymatic pathways enabling the identification of key genes. Metabolism in potatoes This information is useful e.g. for crop improvement based on manipulation of agronomically important...

  2. Models of alien species richness show moderate predictive accuracy and poor transferability

    Directory of Open Access Journals (Sweden)

    César Capinha

    2018-06-01

    Full Text Available Robust predictions of alien species richness are useful to assess global biodiversity change. Nevertheless, the capacity to predict spatial patterns of alien species richness remains largely unassessed. Using 22 data sets of alien species richness from diverse taxonomic groups and covering various parts of the world, we evaluated whether different statistical models were able to provide useful predictions of absolute and relative alien species richness, as a function of explanatory variables representing geographical, environmental and socio-economic factors. Five state-of-the-art count data modelling techniques were used and compared: Poisson and negative binomial generalised linear models (GLMs, multivariate adaptive regression splines (MARS, random forests (RF and boosted regression trees (BRT. We found that predictions of absolute alien species richness had a low to moderate accuracy in the region where the models were developed and a consistently poor accuracy in new regions. Predictions of relative richness performed in a superior manner in both geographical settings, but still were not good. Flexible tree ensembles-type techniques (RF and BRT were shown to be significantly better in modelling alien species richness than parametric linear models (such as GLM, despite the latter being more commonly applied for this purpose. Importantly, the poor spatial transferability of models also warrants caution in assuming the generality of the relationships they identify, e.g. by applying projections under future scenario conditions. Ultimately, our results strongly suggest that predictability of spatial variation in richness of alien species richness is limited. The somewhat more robust ability to rank regions according to the number of aliens they have (i.e. relative richness, suggests that models of aliens species richness may be useful for prioritising and comparing regions, but not for predicting exact species numbers.

  3. Black Hole Sign Predicts Poor Outcome in Patients with Intracerebral Hemorrhage.

    Science.gov (United States)

    Li, Qi; Yang, Wen-Song; Chen, Sheng-Li; Lv, Fu-Rong; Lv, Fa-Jin; Hu, Xi; Zhu, Dan; Cao, Du; Wang, Xing-Chen; Li, Rui; Yuan, Liang; Qin, Xin-Yue; Xie, Peng

    2018-01-01

    In spontaneous intracerebral hemorrhage (ICH), black hole sign has been proposed as a promising imaging marker that predicts hematoma expansion in patients with ICH. The aim of our study was to investigate whether admission CT black hole sign predicts hematoma growth in patients with ICH. From July 2011 till February 2016, patients with spontaneous ICH who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. The presence of black hole sign on admission non-enhanced CT was independently assessed by 2 readers. The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days. Univariate and multivariable logistic regression analyses were performed to assess the association between the presence of the black hole sign and functional outcome. A total of 225 patients (67.6% male, mean age 60.3 years) were included in our study. Black hole sign was identified in 32 of 225 (14.2%) patients on admission CT scan. The multivariate logistic regression analysis demonstrated that age, intraventricular hemorrhage, baseline ICH volume, admission Glasgow Coma Scale score, and presence of black hole sign on baseline CT independently predict poor functional outcome at 90 days. There are significantly more patients with a poor functional outcome (defined as mRS ≥4) among patients with black hole sign than those without (84.4 vs. 32.1%, p black hole sign independently predicts poor outcome in patients with ICH. Early identification of black hole sign is useful in prognostic stratification and may serve as a potential therapeutic target for anti-expansion clinical trials. © 2018 S. Karger AG, Basel.

  4. Increased Expression of microRNA-17 Predicts Poor Prognosis in Human Glioma

    Directory of Open Access Journals (Sweden)

    Shengkui Lu

    2012-01-01

    Full Text Available Aim. To investigate the clinical significance of microRNA-17 (miR-17 expression in human gliomas. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR analysis was used to characterize the expression patterns of miR-17 in 108 glioma and 20 normal brain tissues. The associations of miR-17 expression with clinicopathological factors and prognosis of glioma patients were also statistically analyzed. Results. Compared with normal brain tissues, miR-17 expression was significantly higher in glioma tissues (P<0.001. In addition, the increased expression of miR-17 in glioma was significantly associated with advanced pathological grade (P=0.006 and low Karnofsky performance score (KPS, P=0.01. Moreover, Kaplan-Meier survival and Cox regression analyses showed that miR-17 overexpression (P=0.008 and advanced pathological grade (P=0.02 were independent factors predicting poor prognosis for gliomas. Furthermore, subgroup analyses showed that miR-17 expression was significantly associated with poor overall survival in glioma patients with high pathological grades (for grade III~IV: P<0.001. Conclusions. Our data offer the convinced evidence that the increased expression of miR-17 may have potential value for predicting poor prognosis in glioma patients with high pathological grades, indicating that miR-17 may contribute to glioma progression and be a candidate therapeutic target for this disease.

  5. Measurement error and timing of predictor values for multivariable risk prediction models are poorly reported.

    Science.gov (United States)

    Whittle, Rebecca; Peat, George; Belcher, John; Collins, Gary S; Riley, Richard D

    2018-05-18

    Measurement error in predictor variables may threaten the validity of clinical prediction models. We sought to evaluate the possible extent of the problem. A secondary objective was to examine whether predictors are measured at the intended moment of model use. A systematic search of Medline was used to identify a sample of articles reporting the development of a clinical prediction model published in 2015. After screening according to a predefined inclusion criteria, information on predictors, strategies to control for measurement error and intended moment of model use were extracted. Susceptibility to measurement error for each predictor was classified into low and high risk. Thirty-three studies were reviewed, including 151 different predictors in the final prediction models. Fifty-one (33.7%) predictors were categorised as high risk of error, however this was not accounted for in the model development. Only 8 (24.2%) studies explicitly stated the intended moment of model use and when the predictors were measured. Reporting of measurement error and intended moment of model use is poor in prediction model studies. There is a need to identify circumstances where ignoring measurement error in prediction models is consequential and whether accounting for the error will improve the predictions. Copyright © 2018. Published by Elsevier Inc.

  6. Predictive Modelling Risk Calculators and the Non Dialysis Pathway.

    Science.gov (United States)

    Robins, Jennifer; Katz, Ivor

    2013-04-16

    This guideline will review the current prediction models and survival/mortality scores available for decision making in patients with advanced kidney disease who are being considered for a non-dialysis treatment pathway. Risk prediction is gaining increasing attention with emerging literature suggesting improved patient outcomes through individualised risk prediction (1). Predictive models help inform the nephrologist and the renal palliative care specialists in their discussions with patients and families about suitability or otherwise of dialysis. Clinical decision making in the care of end stage kidney disease (ESKD) patients on a non-dialysis treatment pathway is currently governed by several observational trials (3). Despite the paucity of evidence based medicine in this field, it is becoming evident that the survival advantages associated with renal replacement therapy in these often elderly patients with multiple co-morbidities and limited functional status may be negated by loss of quality of life (7) (6), further functional decline (5, 8), increased complications and hospitalisations. This article is protected by copyright. All rights reserved.

  7. Strength of Temporal White Matter Pathways Predicts Semantic Learning.

    Science.gov (United States)

    Ripollés, Pablo; Biel, Davina; Peñaloza, Claudia; Kaufmann, Jörn; Marco-Pallarés, Josep; Noesselt, Toemme; Rodríguez-Fornells, Antoni

    2017-11-15

    Learning the associations between words and meanings is a fundamental human ability. Although the language network is cortically well defined, the role of the white matter pathways supporting novel word-to-meaning mappings remains unclear. Here, by using contextual and cross-situational word learning, we tested whether learning the meaning of a new word is related to the integrity of the language-related white matter pathways in 40 adults (18 women). The arcuate, uncinate, inferior-fronto-occipital and inferior-longitudinal fasciculi were virtually dissected using manual and automatic deterministic fiber tracking. Critically, the automatic method allowed assessing the white matter microstructure along the tract. Results demonstrate that the microstructural properties of the left inferior-longitudinal fasciculus predict contextual learning, whereas the left uncinate was associated with cross-situational learning. In addition, we identified regions of special importance within these pathways: the posterior middle temporal gyrus, thought to serve as a lexical interface and specifically related to contextual learning; the anterior temporal lobe, known to be an amodal hub for semantic processing and related to cross-situational learning; and the white matter near the hippocampus, a structure fundamental for the initial stages of new-word learning and, remarkably, related to both types of word learning. No significant associations were found for the inferior-fronto-occipital fasciculus or the arcuate. While previous results suggest that learning new phonological word forms is mediated by the arcuate fasciculus, these findings show that the temporal pathways are the crucial neural substrate supporting one of the most striking human abilities: our capacity to identify correct associations between words and meanings under referential indeterminacy. SIGNIFICANCE STATEMENT The language-processing network is cortically (i.e., gray matter) well defined. However, the role of the

  8. High serum uric acid concentration predicts poor survival in patients with breast cancer.

    Science.gov (United States)

    Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min

    2017-10-01

    Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Dissociation predicts poor response to Dialectial Behavioral Therapy in female patients with Borderline Personality Disorder.

    Science.gov (United States)

    Kleindienst, Nikolaus; Limberger, Matthias F; Ebner-Priemer, Ulrich W; Keibel-Mauchnik, Jana; Dyer, Anne; Berger, Mathias; Schmahl, Christian; Bohus, Martin

    2011-08-01

    A substantial proportion of Borderline Personality Disorder (BPD) patients respond by a marked decrease of psychopathology when treated with Dialectical Behavioral Therapy (DBT). To further enhance the rate of DBT-response, it is useful to identify characteristics related to unsatisfactory response. As DBT relies on emotional learning, we explored whether dissociation-which is known to interfere with learning- predicts poor response to DBT. Fifty-seven Borderline Personality Disorder (BPD) patients (DSM-IV) were prospectively observed during a three-month inpatient DBT program. Pre-post improvements in general psychopathology (SCL-90-R) were predicted from baseline scores of the Dissociative Experiences Scale (DES) by regression models accounting for baseline psychopathology. High DES-scores were related to poor pre-post improvement (β = -0.017 ± 0.006, p = 0.008). The data yielded no evidence that some facets of dissociation are more important in predicting DBT-response than others. The results suggest that dissociation in borderline-patients should be closely monitored and targeted during DBT. At this stage, research on treatment of dissociation (e.g., specific skills training) is warranted.

  10. Leukoaraiosis predicts poor 90-day outcome after acute large cerebral artery occlusion.

    Science.gov (United States)

    Henninger, Nils; Lin, Eugene; Baker, Stephen P; Wakhloo, Ajay K; Takhtani, Deepak; Moonis, Majaz

    2012-01-01

    To date limited information regarding outcome-modifying factors in patients with acute intracranial large artery occlusion (ILAO) in the anterior circulation is available. Leukoaraiosis (LA) is a common finding among patients with ischemic stroke and has been associated with poor post-stroke outcomes but its association with ILAO remains poorly characterized. This study sought to clarify the contribution of baseline LA and other common risk factors to 90-day outcome (modified Rankin Scale, mRS) after stroke due to acute anterior circulation ILAO. We retrospectively analyzed 1,153 consecutive patients with imaging-confirmed ischemic stroke during a 4-year period (2007-2010) at a single academic institution. The final study cohort included 87 patients with acute ILAO subjected to multimodal CT imaging within 24 h of symptom onset. LA severity was assessed using the van Swieten scale on non-contrast CT. Leptomeningeal collaterals were graded using CT angiogram source images. Hemorrhagic transformation (HT) was determined on follow-up CT. Multivariate logistic regression controlling for HT, treatment modality, demographic, as well as baseline clinical and imaging characteristics was used to identify independent predictors of a poor outcome (90-day mRS >2). The median National Institutes of Health Stroke Scale (NIHSS) at baseline was 15 (interquartile range 9-21). Twenty-four percent of the studied patients had severe LA. They were more likely to have hypertension (p = 0.028), coronary artery disease (p = 0.015), poor collaterals (p Coexisting LA may predict poor functional outcome in patients with acute anterior circulation ILAO independent of other known important outcome predictors such as comorbid state, admission functional deficit, collateral status, hemorrhagic conversion, and treatment modality. Copyright © 2012 S. Karger AG, Basel.

  11. Aquatic pathways model to predict the fate of phenolic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Aaberg, R.L.; Peloquin, R.A.; Strenge, D.L.; Mellinger, P.J.

    1983-04-01

    Organic materials released from energy-related activities could affect human health and the environment. To better assess possible impacts, we developed a model to predict the fate of spills or discharges of pollutants into flowing or static bodies of fresh water. A computer code, Aquatic Pathways Model (APM), was written to implement the model. The computer programs use compartmental analysis to simulate aquatic ecosystems. The APM estimates the concentrations of chemicals in fish tissue, water and sediment, and is therefore useful for assessing exposure to humans through aquatic pathways. The APM will consider any aquatic pathway for which the user has transport data. Additionally, APM will estimate transport rates from physical and chemical properties of chemicals between several key compartments. The major pathways considered are biodegradation, fish and sediment uptake, photolysis, and evaporation. The model has been implemented with parameters for distribution of phenols, an important class of compounds found in the water-soluble fractions of coal liquids. Current modeling efforts show that, in comparison with many pesticides and polyaromatic hydrocarbons (PAH), the lighter phenolics (the cresols) are not persistent in the environment. The properties of heavier molecular weight phenolics (indanols, naphthols) are not well enough understood at this time to make similar judgements. For the twelve phenolics studied, biodegradation appears to be the major pathway for elimination from aquatic environments. A pond system simulation (using APM) of a spill of solvent refined coal (SRC-II) materials indicates that phenol, cresols, and other single cyclic phenolics are degraded to 16 to 25 percent of their original concentrations within 30 hours. Adsorption of these compounds into sediments and accumulation by fish was minor.

  12. Molecular pathways reflecting poor intrauterine growth are found in Wharton's jelly-derived mesenchymal stem cells.

    Science.gov (United States)

    Sukarieh, Rami; Joseph, Roy; Leow, Shi Chi; Li, Ying; Löffler, Mona; Aris, Izzuddin M; Tan, Jun Hao; Teh, Ai Ling; Chen, Li; Holbrook, Joanna D; Ng, Kai Lyn; Lee, Yung Seng; Chong, Yap Seng; Summers, Scott A; Gluckman, Peter D; Stünkel, Walter

    2014-10-10

    Are molecular pathways reflecting the biology of small for gestational age (SGA) neonates preserved in umbilical cord-derived mesenchymal stem cells (MSCs)? MSCs from SGA newborns were found to express an altered EGR-1-dependent gene network involved in the regulation of cell proliferation and oxidative stress. Individuals with suboptimal intrauterine development are at greater risk of metabolic diseases such as type II diabetes, obesity and cardiovascular disease. Umbilical cords (n = 283) from the GUSTO (growing up in Singapore towards healthy outcomes) birth cohort study, and primary MSC isolates established from SGA and matched control cases (n = 6 per group), were subjected to gene expression analysis and candidate genes were studied for functional validation. Umbilical cord specimens were derived from babies born at the National University Hospital (NUH) in Singapore. Local ethical approval was obtained. MSC isolates were established in Wharton's jelly and molecular analysis was conducted by gene expression microarrays and RT-PCR. Cells from SGA and control groups were compared in the presence and absence of insulin and candidate gene function was studied via siRNA-mediated gene knockdown and over-expression experiments in MSCs. Using repeated measure ANOVAs, proliferation rates of MSCs isolated from SGA neonates were found to be significantly increased (P < 0.01). In the absence of insulin, EGR-1 levels were found to be significantly reduced in the group of SGA-derived MSCs, whereas EGR-1 expression was found to be up-regulated in the same group in the presence of insulin (P < 0.01). EGR-1 was found to induce expression of COX-2 in the SGA group (P < 0.01) and both, EGR-1 and COX-2 stimulated glucose uptake in MSCs (P < 0.01). EGR-1 and COX-2 levels were associated in whole umbilical cords (n = 283, P < 0.01) and EGR-1 positively correlated with abdominal circumference and birthweight (n = 91, P < 0.01 and n = 91, P < 0.01). Cell models may not entirely

  13. Low free triiodothyronine predicts poor functional outcome after acute ischemic stroke.

    Science.gov (United States)

    Suda, Satoshi; Muraga, Kanako; Kanamaru, Takuya; Okubo, Seiji; Abe, Arata; Aoki, Junya; Suzuki, Kentaro; Sakamoto, Yuki; Shimoyama, Takashi; Nito, Chikako; Kimura, Kazumi

    2016-09-15

    The aim of this study was to investigate the association of admission serum thyroid hormone concentration with clinical characteristics and functional outcomes in patients after acute ischemic stroke. We retrospectively enrolled 398 consecutive patients admitted to our stroke center between July 2010 and April 2012. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were evaluated upon admission. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) upon admission and the modified Rankin Scale (mRS) upon discharge. Poor outcome was defined as a mRS score of 3-5 or death (mRS score 6). Separate analyses were conducted according to outcome and quartile serum FT3 concentration. In total, 164 patients (41.2%) demonstrated a poor outcome. Age, male gender, blood glucose level, arterial fibrillation, dyslipidemia, smoking, NIHSS score, cardioembolic stroke type, and periventricular hyperintensities, but not FT4 or TSH, were significantly associated with poor functional outcome. Furthermore, poor functional outcome was independently associated with low FT3 (<2.29pg/mL). In comparisons between FT3 quartiles (Q1 [≤2.11pg/mL], Q2 [2.12-2.45pg/mL], Q3 [2.46-2.77pg/mL], Q4 [≥2.78pg/mL]), patients with poor outcomes were more frequent in Q1 than in Q4 after multivariate adjustment. Death was more frequent in Q1 than in Q4 after adjustment for risk factors and comorbidities, but this difference was non-significant after additional adjustment for age and NIHSS score. Our data suggest that a lower FT3 value upon admission may predict a poor functional outcome in patients with acute ischemic stroke. Further large-scale prospective studies are required to clarify the role of thyroid hormone in the acute phase of ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Electroencephalography Predicts Poor and Good Outcomes After Cardiac Arrest: A Two-Center Study.

    Science.gov (United States)

    Rossetti, Andrea O; Tovar Quiroga, Diego F; Juan, Elsa; Novy, Jan; White, Roger D; Ben-Hamouda, Nawfel; Britton, Jeffrey W; Oddo, Mauro; Rabinstein, Alejandro A

    2017-07-01

    The prognostic role of electroencephalography during and after targeted temperature management in postcardiac arrest patients, relatively to other predictors, is incompletely known. We assessed performances of electroencephalography during and after targeted temperature management toward good and poor outcomes, along with other recognized predictors. Cohort study (April 2009 to March 2016). Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester, MN). Consecutive comatose adults admitted after cardiac arrest, identified through prospective registries. All patients were managed with targeted temperature management, receiving prespecified standardized clinical, neurophysiologic (particularly, electroencephalography during and after targeted temperature management), and biochemical evaluations. We assessed electroencephalography variables (reactivity, continuity, epileptiform features, and prespecified "benign" or "highly malignant" patterns based on the American Clinical Neurophysiology Society nomenclature) and other clinical, neurophysiologic (somatosensory-evoked potential), and biochemical prognosticators. Good outcome (Cerebral Performance Categories 1 and 2) and mortality predictions at 3 months were calculated. Among 357 patients, early electroencephalography reactivity and continuity and flexor or better motor reaction had greater than 70% positive predictive value for good outcome; reactivity (80.4%; 95% CI, 75.9-84.4%) and motor response (80.1%; 95% CI, 75.6-84.1%) had highest accuracy. Early benign electroencephalography heralded good outcome in 86.2% (95% CI, 79.8-91.1%). False positive rates for mortality were less than 5% for epileptiform or nonreactive early electroencephalography, nonreactive late electroencephalography, absent somatosensory-evoked potential, absent pupillary or corneal reflexes, presence of myoclonus, and neuron-specific enolase greater than 75 µg/L; accuracy was highest for

  15. A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors.

    Science.gov (United States)

    Loboda, Andrey; Nebozhyn, Michael; Klinghoffer, Rich; Frazier, Jason; Chastain, Michael; Arthur, William; Roberts, Brian; Zhang, Theresa; Chenard, Melissa; Haines, Brian; Andersen, Jannik; Nagashima, Kumiko; Paweletz, Cloud; Lynch, Bethany; Feldman, Igor; Dai, Hongyue; Huang, Pearl; Watters, James

    2010-06-30

    Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors.

  16. A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

    Directory of Open Access Journals (Sweden)

    Paweletz Cloud

    2010-06-01

    Full Text Available Abstract Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90% sensitivity but relatively low (50% specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical

  17. Coexpression of EGFR and CXCR4 predicts poor prognosis in resected pancreatic ductal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Huanwen Wu

    Full Text Available Epidermal growth factor receptor (EGFR is highly expressed in pancreatic ductal adenocarcinoma (PDAC and is involved in tumorigenesis and development. However, EGFR expression alone has limited clinical and prognostic significance. Recently, the cross-talk between EGFR and G-protein-coupled chemokine receptor CXCR4 has become increasingly recognized.In the present study, immunohistochemical staining of EGFR and CXCR4 was performed on paraffin-embedded specimens from 131 patients with surgically resected PDAC. Subsequently, the associations between EGFR expression, CXCR4 expression, EGFR/CXCR4 coexpression and clinicopathologic factors were assessed, and survival analyses were performed.In total, 64 (48.9% patients expressed EGFR, 68 (51.9% expressed CXCR4, and 33 (25.2% coexpressed EGFR and CXCR4. No significant association between EGFR and CXCR4 expression was observed (P = 0.938. EGFR expression significantly correlated with tumor differentiation (P = 0.031, whereas CXCR4 expression significantly correlated with lymph node metastasis (P = 0.001. EGFR/CXCR4 coexpression was significantly associated with lymph node metastasis (P = 0.026, TNM stage (P = 0.048, and poor tumor differentiation (P = 0.004. By univariate survival analysis, both CXCR4 expression and EGFR/CXCR4 coexpression were significant prognostic factors for poor disease-free survival (DFS and overall survival (OS. Moreover, EGFR/CXCR4 coexpression significantly increased the hazard ratio for both recurrence and death compared with EGFR or CXCR4 protein expression alone. Multivariate survival analysis demonstrated that EGFR/CXCR4 coexpression was an independent prognostic factor for DFS (HR = 2.33, P<0.001 and OS (HR = 2.48, P = 0.001.In conclusion, our data indicate that although EGFR expression alone has limited clinical and prognostic significance, EGFR/CXCR4 coexpression identified a subset of PDAC patients with more aggressive tumor characteristics and a significantly worse

  18. Identification and targeting of a TACE-dependent autocrine loopwhich predicts poor prognosis in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, Paraic A.; Bissell, Mina J.

    2005-06-15

    The ability to proliferate independently of signals from other cell types is a fundamental characteristic of tumor cells. Using a 3D culture model of human breast cancer progression, we have delineated a protease-dependent autocrine loop which provides an oncogenic stimulus in the absence of proto-oncogene mutation. Inhibition of this protease, TACE/ADAM17, reverts the malignant phenotype by preventing mobilization of two crucial growth factors, Amphiregulin and TGF{alpha}. We show further that the efficacy of EGFR inhibitors is overcome by physiological levels of growth factors and that successful EGFR inhibition is dependent on reducing ligand bioavailability. Using existing patient outcome data, we demonstrate a strong correlation between TACE and TGF{alpha} expression in human breast cancers that is predictive of poor prognosis.

  19. Poor sleep quality predicts deficient emotion information processing over time in early adolescence.

    Science.gov (United States)

    Soffer-Dudek, Nirit; Sadeh, Avi; Dahl, Ronald E; Rosenblat-Stein, Shiran

    2011-11-01

    There is deepening understanding of the effects of sleep on emotional information processing. Emotion information processing is a key aspect of social competence, which undergoes important maturational and developmental changes in adolescence; however, most research in this area has focused on adults. Our aim was to test the links between sleep and emotion information processing during early adolescence. Sleep and facial information processing were assessed objectively during 3 assessment waves, separated by 1-year lags. Data were obtained in natural environments-sleep was assessed in home settings, and facial information processing was assessed at school. 94 healthy children (53 girls, 41 boys), aged 10 years at Time 1. N/A. Facial information processing was tested under neutral (gender identification) and emotional (emotional expression identification) conditions. Sleep was assessed in home settings using actigraphy for 7 nights at each assessment wave. Waking > 5 min was considered a night awakening. Using multilevel modeling, elevated night awakenings and decreased sleep efficiency significantly predicted poor performance only in the emotional information processing condition (e.g., b = -1.79, SD = 0.52, confidence interval: lower boundary = -2.82, upper boundary = -0.076, t(416.94) = -3.42, P = 0.001). Poor sleep quality is associated with compromised emotional information processing during early adolescence, a sensitive period in socio-emotional development.

  20. On the temperatures, colours, and ages of metal-poor stars predicted by stellar models

    International Nuclear Information System (INIS)

    Van den Berg, D A

    2008-01-01

    Most (but not all) of the investigations that have derived the effective temperatures of metal-poor, solar-neighbourhood field stars, from analyses of their spectra or from the infrared flux method, favour a T eff scale that is ∼100-120 K cooler than that given by stellar evolutionary models. This seems to be at odds with photometric results, given that the application of current colour-T eff relations to the observed subdwarf colours suggests a preference for hotter temperatures. Moreover, the predicted temperatures for main-sequence stars at the lowest metallicities ([Fe/H] eff for them unless some fundamental modification is made to the adopted physics. No such problems are found if the temperatures of metal-poor field stars are ∼100-120 K warmer than most determinations. In this case, stellar models would appear to provide consistent interpretations of both field and globular cluster (GC) stars of low metallicity. However, this would imply, e.g. that M 92 has an [Fe/H] value of approximately - 2.2, which is obtained from analyses of Fe I lines, instead of approximately equal to - 2.4, as derived from Fe II lines (and favoured by studies of three-dimensional model atmospheres). Finally, the age of the local, Population II subgiant HD 140283 (and GCs having similar metal abundances) is estimated to be ∼13 Gyr, if diffusive processes are taken into account.

  1. Improving Flood Prediction By the Assimilation of Satellite Soil Moisture in Poorly Monitored Catchments.

    Science.gov (United States)

    Alvarez-Garreton, C. D.; Ryu, D.; Western, A. W.; Crow, W. T.; Su, C. H.; Robertson, D. E.

    2014-12-01

    Flood prediction in poorly monitored catchments is among the greatest challenges faced by hydrologists. To address this challenge, an increasing number of studies in the last decade have explored methods to integrate various existing observations from ground and satellites. One approach in particular, is the assimilation of satellite soil moisture (SM-DA) into rainfall-runoff models. The rationale is that satellite soil moisture (SSM) can be used to correct model soil water states, enabling more accurate prediction of catchment response to precipitation and thus better streamflow. However, there is still no consensus on the most effective SM-DA scheme and how this might depend on catchment scale, climate characteristics, runoff mechanisms, model and SSM products used, etc. In this work, an operational SM-DA scheme was set up in the poorly monitored, large (>40,000 km2), semi-arid Warrego catchment situated in eastern Australia. We assimilated passive and active SSM products into the probability distributed model (PDM) using an ensemble Kalman filter. We explored factors influencing the SM-DA framework, including relatively new techniques to remove model-observation bias, estimate observation errors and represent model errors. Furthermore, we explored the advantages of accounting for the spatial distribution of forcing and channel routing processes within the catchment by implementing and comparing lumped and semi-distributed model setups. Flood prediction is improved by SM-DA (Figure), with a 30% reduction of the average root-mean-squared difference of the ensemble prediction, a 20% reduction of the false alarm ratio and a 40% increase of the ensemble mean Nash-Sutcliffe efficiency. SM-DA skill does not significantly change with different observation error assumptions, but the skill strongly depends on the observational bias correction technique used, and more importantly, on the performance of the open-loop model before assimilation. Our findings imply that proper

  2. Aberrant membranous expression of β-catenin predicts poor prognosis in patients with craniopharyngioma.

    Science.gov (United States)

    Li, Zongping; Xu, Jianguo; Huang, Siqing; You, Chao

    2015-12-01

    The objective of this study is to investigate β-catenin expression in craniopharyngioma patients and determine its significance in predicting the prognosis of this disease. Fifty craniopharyngioma patients were enrolled in this study. Expression of β-catenin in tumor specimens collected from these patients was examined through immunostaining. In addition, mutation of exon 3 in the β-catenin gene, CTNNB1, was analyzed using polymerase chain reaction, denaturing high-pressure liquid chromatography, and DNA sequencing. Based on these results, we explored the association between membranous β-catenin expression, clinical and pathologic characteristics, and prognoses in these patients. Of all craniopharyngioma specimens, 31 (62.0%) had preserved membranous β-catenin expression, whereas the remaining 19 specimens (38.0%) displayed aberrant expression. Statistical analysis showed a significant correlation between aberrant membranous β-catenin expression and CTNNB1 exon 3 mutation, as well as between aberrant membranous β-catenin expression and the histopathologic type of craniopharyngioma and type of resection in our patient population. Furthermore, aberrant membranous β-catenin expression was found to be associated with poor patient survival. Results of Kaplan-Meier survival analysis and Cox regression analysis further confirmed this finding. In conclusion, our study demonstrated that aberrant membranous β-catenin expression was significantly correlated with poor survival in patients with craniopharyngioma. This raises the possibility for use of aberrant membranous β-catenin expression as an independent risk factor in predicting the prognosis of this disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Miao Yun

    Full Text Available Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC method in two independent cohorts of nasopharygeal carcinoma (NPC cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS (P<0.05. Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response could significantly stratify risk (low, intermediate and high for DSS in NPC patients (P<0.001. These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

  4. Structural Pathways between Child Abuse, Poor Mental Health Outcomes and Male-Perpetrated Intimate Partner Violence (IPV)

    Science.gov (United States)

    Machisa, Mercilene T.; Christofides, Nicola; Jewkes, Rachel

    2016-01-01

    Background Violent trauma exposures, including child abuse, are risk factors for PTSD and comorbid mental health disorders. Child abuse experiences of men exacerbate adult male-perpetrated intimate partner violence (IPV). The relationship between child abuse, poor mental health and IPV perpetration is complex but research among the general population is lacking. This study describes the relationship and pathways between history of child abuse exposure and male-perpetrated IPV while exploring the potentially mediating effect of poor mental health. Methods We analysed data from a randomly selected, two-stage clustered, cross-sectional household survey conducted with 416 adult men in Gauteng Province of South Africa. We used multinomial regression modelling to identify associated factors and Structural Equation Modelling (SEM) to test the primary hypothesis that poor mental health (defined as abusing alcohol or having PTSD or depressive symptoms) mediates the relationship between child abuse and IPV perpetration. Results Eighty eight percent of men were physically abused, 55% were neglected, 63% were emotionally abused and 20% were sexually abused at least once in their childhood. Twenty four percent of men had PTSD symptoms, 24% had depressive symptoms and 36% binge drank. Fifty six percent of men physically abused and 31% sexually abused partners at least once in their lifetime. Twenty two percent of men had one episode and 40% had repeat episodes of IPV perpetration. PTSD symptomatology risk increased with severity of child trauma and other trauma. PTSD severity increased the risk for binge drinking. Child trauma, other trauma and PTSD symptomatology increased the severity of depressive symptoms. PTSD symptomatology was comorbid with alcohol abuse and depressive symptoms. Child trauma, having worked in the year before the survey, other trauma and PTSD increased the risk of repeat episodes of IPV perpetration. Highly equitable gender attitudes were protective

  5. Structural Pathways between Child Abuse, Poor Mental Health Outcomes and Male-Perpetrated Intimate Partner Violence (IPV.

    Directory of Open Access Journals (Sweden)

    Mercilene T Machisa

    Full Text Available Violent trauma exposures, including child abuse, are risk factors for PTSD and comorbid mental health disorders. Child abuse experiences of men exacerbate adult male-perpetrated intimate partner violence (IPV. The relationship between child abuse, poor mental health and IPV perpetration is complex but research among the general population is lacking. This study describes the relationship and pathways between history of child abuse exposure and male-perpetrated IPV while exploring the potentially mediating effect of poor mental health.We analysed data from a randomly selected, two-stage clustered, cross-sectional household survey conducted with 416 adult men in Gauteng Province of South Africa. We used multinomial regression modelling to identify associated factors and Structural Equation Modelling (SEM to test the primary hypothesis that poor mental health (defined as abusing alcohol or having PTSD or depressive symptoms mediates the relationship between child abuse and IPV perpetration.Eighty eight percent of men were physically abused, 55% were neglected, 63% were emotionally abused and 20% were sexually abused at least once in their childhood. Twenty four percent of men had PTSD symptoms, 24% had depressive symptoms and 36% binge drank. Fifty six percent of men physically abused and 31% sexually abused partners at least once in their lifetime. Twenty two percent of men had one episode and 40% had repeat episodes of IPV perpetration. PTSD symptomatology risk increased with severity of child trauma and other trauma. PTSD severity increased the risk for binge drinking. Child trauma, other trauma and PTSD symptomatology increased the severity of depressive symptoms. PTSD symptomatology was comorbid with alcohol abuse and depressive symptoms. Child trauma, having worked in the year before the survey, other trauma and PTSD increased the risk of repeat episodes of IPV perpetration. Highly equitable gender attitudes were protective against single and

  6. Classical fluoroscopy criteria poorly predict right ventricular lead septal positioning by comparison with echocardiography.

    Science.gov (United States)

    Squara, Fabien; Scarlatti, Didier; Riccini, Philippe; Garret, Gauthier; Moceri, Pamela; Ferrari, Emile

    2018-03-13

    Fluoroscopic criteria have been described for the documentation of septal right ventricular (RV) lead positioning, but their accuracy remains questioned. Consecutive patients undergoing pacemaker or defibrillator implantation were prospectively included. RV lead was positioned using postero-anterior and left anterior oblique 40° incidences, and right anterior oblique 30° to rule out coronary sinus positioning when suspected. RV lead positioning using fluoroscopy was compared to true RV lead positioning as assessed by transthoracic echocardiography (TTE). Precise anatomical localizations were determined with both modalities; then, RV lead positioning was ultimately dichotomized into two simple clinically relevant categories: RV septal or RV free wall. Accuracy of fluoroscopy for RV lead positioning was then assessed by comparison with TTE. We included 100 patients. On TTE, 66/100 had a septal RV lead and 34/100 had a free wall RV lead. Fluoroscopy had moderate agreement with TTE for precise anatomical localization of RV lead (k = 0.53), and poor agreement for septal/free wall localization (k = 0.36). For predicting septal RV lead positioning, classical fluoroscopy criteria had a high sensitivity (95.5%; 63/66 patients having a septal RV lead on TTE were correctly identified by fluoroscopy) but a very low specificity (35.3%; only 12/34 patients having a free wall RV lead on TTE were correctly identified by fluoroscopy). Classical fluoroscopy criteria have a poor accuracy for identifying RV free wall leads, which are most of the time misclassified as septal. This raises important concerns about the efficacy and safety of RV lead positioning using classical fluoroscopy criteria.

  7. Chemometric approach for prediction of uranium pathways in the soil

    International Nuclear Information System (INIS)

    Stojanovic, Mirjana; Nihajlovic, Marija; Petrovic, Jelena; Petrovic, Marija; Sostaric, Tanja; Milojkovic, Jelena; Pezo, Lato

    2014-01-01

    Understanding the effect of soil parameters (pH, Eh and organic and inorganic ligands availability) on uranium mobility under different geochemical conditions is fundamental for reliable prediction of its behaviour and fate in the environment. In this study, the impact of total and available phosphorus content, humus and acidity of Serbian agricultural soils on the content of total and available uranium were evaluated by Response Surface Methodology (RSM), second order polynomial regression models (SOPs) and artificial neural networks (ANNs). The performance of ANNs was compared with the performance of SOPs and experimental results. SOPs showed high coefficients of determination (0.785-0.956), while ANN model performed high prediction accuracy: 0.8893-0.904. According to the results, total and available uranium content in the soil were mostly affected by pH, statistically significant at p < 0.05 level. For the same responses the total phosphorus was found to be also very influential, statistically significant at p < 0.05 and p < 0.10 levels. The impact of available phosphorus and humus was much more influential on total and available uranium content, compared to total phosphorus content. Proposed chemometric approach will be very helpful in preserving the natural resources and practical application for risk assessment modeling of uranium environmental pathways.

  8. Upregulation of B23 promotes tumor cell proliferation and predicts poor prognosis in glioma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jianguo [Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu Province (China); Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province (China); Sun, Jie; Yang, Liu; Yan, Yaohua; Shi, Wei; Shi, Jinlong; Huang, Qingfeng; Chen, Jian [Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province (China); Lan, Qing, E-mail: lanqingsj@163.com [Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu Province (China)

    2015-10-09

    B23 (also known as Nucleophosmin, NPM, numatrin or NO38) is a ubiquitously expressed phosphoprotein belonging to the nucleoplasmin family of chaperones. In this study we intended to investigate the clinical significance of B23 expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that B23 was overexpressed in glioma tissues and glioma cell lines. In addition, the expression level of B23 was positively correlated with glioma pathological grade and Ki-67 expression. Kaplan–Meier analysis revealed that a higher B23 expression in patients with glioma was associated with a poorer prognosis. In vitro, after the release of glioma cell lines from serum starvation, the expression of B23 was upregulated, as well as PCNA (Proliferating Cell Nuclear Antigen) and cyclin A. In addition, knockdown of B23 by small interfering RNA transfection diminished the expression of PCNA, cyclin D1 and arrested cell growth at G1 phase. Taken together, our results implied that B23 could be a candidate prognostic biomarker as well as a potential therapeutical target of glioma. - Highlights: • B23 expression increased as the malignant degree of glioma increased, which was consistent with Ki-67 expression. • High expression of B23 could be a strong determinant of poor prognosis in glioma. • B23 may be involved in the proliferation of glioma in a cell-cycle-dependent pathway. • Knockdown of B23 expression by siRNA could affect the progression of glioma. • B23 may be a potential prognosis biomarker and a possible therapeutic target for glioma.

  9. Persistent CXCR4 expression after preoperative chemoradiotherapy predicts early recurrence and poor prognosis in esophageal cancer

    Science.gov (United States)

    Koishi, Kenji; Yoshikawa, Reigetsu; Tsujimura, Tohru; Hashimoto-Tamaoki, Tomoko; Kojima, Syoudou; Yanagi, Hidenori; Yamamura, Takehira; Fujiwara, Yoshinori

    2006-01-01

    AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence of CXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway. PMID:17171785

  10. Deregulated HOXB7 expression predicts poor prognosis of patients with malignancies of digestive system.

    Science.gov (United States)

    Liu, Fang-Teng; Chen, Han-Min; Xiong, Ying; Zhu, Zheng-Ming

    2017-07-26

    Numerous studies have investigated the relationship between deregulated HOXB7 expression with the clinical outcome in patients with digestive stem cancers, HOXB7 has showed negative impacts but with varying levels. We aimed to comprehensively evaluate the prediction and prognostic value of HOXB7 in digestive stem cancers. Electronic databases updated to December 1, 2016 were retrieved to collect relevant eligible studies to quantitatively explore the potential roles of HOXB7 as a prognostic indicator in digestive system cancers. A total of 9 studies (n = 1298 patients) was included in this synthetical meta-analysis. The pooled hazard ratios suggested that high expression of HOXB7 protein was associated with poor prognosis of OS in patients with digestive system cancers (HR = 1.97, 95% CI: 1.65-2.28, p= 0.000), and HOXB7 protein could act as an independent prognostic factor for predicting OS of patients with digestive system cancers (HR: 2.02, 95% CI: 1.69-2.36, p = 0.000). Statistical significance was also observed in subgroup meta-analysis based on the cancer type, histology type, country, sample size and publication date. Furthermore, we examined the correlations between HOXB7 protein and clinicopathological features. It showed that altered expression of HOXB7 protein was correlated with tumor invasion (p = 0.000), lymph node status (p = 0.000), distant metastasis (p = 0.001) and TNM stage (p = 0.000). However, the expression of HOXB7 protein was not associated with age (p = 0.64), gender (p = 0.40) or levels of differentiation (p = 0.19). High expression of HOXB7 protein was associated with poor prognosis of patients with digestive system cancers, as well as clinicopathologic characteristics, including the tumor invasion, lymph node status, distant metastasis and TNM stage. The expression of HOXB7 protein was not associated with age, gender or levels of differentiation. HOXB7 protein expression level in tumor tissue might serve as a novel prognostic marker for

  11. Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients

    NARCIS (Netherlands)

    de Sousa E Melo, Felipe; Colak, Selcuk; Buikhuisen, Joyce; Koster, Jan; Cameron, Kate; de Jong, Joan H.; Tuynman, Jurriaan B.; Prasetyanti, Pramudita R.; Fessler, Evelyn; van den Bergh, Saskia P.; Rodermond, Hans; Dekker, Evelien; van der Loos, Chris M.; Pals, Steven T.; van de Vijver, Marc J.; Versteeg, Rogier; Richel, Dick J.; Vermeulen, Louis; Medema, Jan Paul

    2011-01-01

    Gene signatures derived from cancer stem cells (CSCs) predict tumor recurrence for many forms of cancer. Here, we derived a gene signature for colorectal CSCs defined by high Wnt signaling activity, which in agreement with previous observations predicts poor prognosis. Surprisingly, however, we

  12. After laparoscopic Heller myotomy, do emergency department visits or readmissions predict poor long-term outcomes?

    Science.gov (United States)

    Ross, Sharona; Villadolid, Desiree; Al-Saadi, Sam; Boyle, Robert; Cowgill, Sarah M; Rosemurgy, Alexander

    2008-12-01

    Laparoscopic Heller myotomy is a first-line treatment for achalasia. To improve outcomes after myotomy and to determine if poor early results predict later outcomes, emergency department (ED) visits and readmissions within 60 days following laparoscopic Heller myotomy were studied. Since 1992, 352 patients have undergone laparoscopic Heller myotomy and are followed through a prospectively maintained registry. Causes of ED visits and readmissions within 60 days after myotomy were determined. Patients scored their symptoms of achalasia before myotomy and at last follow-up; scores were compared to determine if the reasons leading to ED visits and/or readmissions impacted long-term outcome after myotomy. Fourteen (4%) patients had ED visits, and 18 (5%) patients had readmissions within 60 days following myotomy. Sixty-four percent of ED visits were for dysphagia/vomiting and 36% were for abdominal/chest pain, while 37% of readmissions were for dysphagia/vomiting. Pneumonia was complicated by empyema in four patients, all without leaks; two patients expired. Despite ED visits/readmissions, achalasia symptom (e.g., dysphagia, regurgitation, choking, heartburn, and chest pain) frequency and severity scores improved after myotomy (p Heller myotomy. ED visits were generally due to complaints related to achalasia or edema after myotomy, while readmissions were generally related to complications of operative intervention or chronic ill health. Despite ED visits or readmissions early after myotomy, symptoms of achalasia are well palliated by myotomy long-term.

  13. EMMPRIN co-expressed with matrix metalloproteinases predicts poor prognosis in patients with osteosarcoma.

    Science.gov (United States)

    Futamura, Naohisa; Nishida, Yoshihiro; Urakawa, Hiroshi; Kozawa, Eiji; Ikuta, Kunihiro; Hamada, Shunsuke; Ishiguro, Naoki

    2014-06-01

    Several studies have focused on the relationships between the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the prognosis of patients with malignant tumors. However, few of these have investigated the expression of EMMPRIN in osteosarcoma. We examined expression levels of EMMPRIN immunohistochemically in 53 cases of high-grade osteosarcoma of the extremities and analyzed the correlation of its expression with patient prognosis. The correlation between matrix metalloproteinases (MMPs) and EMMPRIN expression and the prognostic value of co-expression were also analyzed. Staining positivity for EMMPRIN was negative in 7 cases, low in 17, moderate in 19, and strong in 10. The overall and disease-free survivals (OS and DFS) in patients with higher EMMPRIN expression (strong-moderate) were significantly lower than those in the lower (weak-negative) group (0.037 and 0.024, respectively). In multivariate analysis, age (P=0.004), location (P=0.046), and EMMPRIN expression (P=0.038) were significant prognostic factors for overall survival. EMMPRIN expression (P=0.024) was also a significant prognostic factor for disease-free survival. Co-expression analyses of EMMPRIN and MMPs revealed that strong co-expression of EMMPRIN and membrane-type 1 (MT1)-MMP had a poor prognostic value (P=0.056 for DFS, P=0.006 for OS). EMMPRIN expression and co-expression with MMPs well predict the prognosis of patients with extremity osteosarcoma, making EMMPRIN a possible therapeutic target in these patients.

  14. Lack of pro-inflammatory cytokine mobilization predicts poor prognosis in patients with acute heart failure.

    Science.gov (United States)

    Vistnes, M; Høiseth, A D; Røsjø, H; Nygård, S; Pettersen, E; Søyseth, V; Hurlen, P; Christensen, G; Omland, T

    2013-03-01

    The aim of this study was to gain insight in the inflammatory response in acute heart failure (AHF) by assessing (1) plasma cytokine profiles and (2) prognostic value of circulating cytokines in AHF patients. Plasma levels of 26 cytokines were quantified by multiplex protein arrays in 36 patients with congestive AHF, characterized by echocardiographic, radiologic, and clinical examinations on admission, during hospitalization and at discharge. Recurrent AHF leading to death or readmission constituted the combined end point, and all patients were followed for 120 days after discharge. Levels of 15 of the measured cytokines were higher in AHF than in healthy subjects (n=22) on admission. Low levels of MCP-1, IL-1β and a low IL-1β/IL-1ra ratio predicted fatal and non-fatal AHF within 120 days. Patients with low circulating levels of IL-1β had lower left ventricular ejection fraction and higher levels of N-terminal pro-B-type natriuretic peptide, while patients with low levels of MCP-1 had higher E/E' and inferior caval vein diameter, than patients with high levels. Immune activation, reflected in increased cytokine levels, is present in AHF patients. Interestingly, failure to increase secretion of IL-1β and MCP-1 during AHF is associated with poor outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. A new risk scoring model for prediction of poor coronary collateral circulation in acute non-ST-elevation myocardial infarction.

    Science.gov (United States)

    İleri, Mehmet; Güray, Ümit; Yetkin, Ertan; Gürsoy, Havva Tuğba; Bayır, Pınar Türker; Şahin, Deniz; Elalmış, Özgül Uçar; Büyükaşık, Yahya

    2016-01-01

    We aimed to investigate the clinical features associated with development of coronary collateral circulation (CCC) in patients with acute non-ST-elevation myocardial infarction (NSTEMI) and to develop a scoring model for predicting poor collateralization at hospital admission. The study enrolled 224 consecutive patients with NSTEMI admitted to our coronary care unit. Patients were divided into poor (grade 0 and 1) and good (grade 2 and 3) CCC groups. In logistic regression analysis, presence of diabetes mellitus, total white blood cell (WBC) and neutrophil counts and neutrophil to lymphocyte ratio (NLR) were found as independent positive predictors of poor CCC, whereas older age (≥ 70 years) emerged as a negative indicator. The final scoring model was based on 5 variables which were significant at p risk score ≤ 1, 29 had good CCC (with a 97% negative predictive value). On the other hand, 139 patients had risk score ≥ 4; out of whom, 130 (with a 93.5% positive predictive value) had poor collateralization. Sensitivity and specificity of the model in predicting poor collateralization in patients with scores ≤ 1 and ≥ 4 were 99.2% (130/131) and +76.3 (29/38), respectively. This study represents the first prediction model for degree of coronary collateralization in patients with acute NSTEMI.

  16. ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

    Science.gov (United States)

    Xu, Qin; Ying, Mingang; Chen, Guilin; Lin, Ang; Xie, Yunqing; Ohara, Noriyuki; Zhou, Dongmei

    2014-08-01

    Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a molecular marker for predicting the progression and prognosis in cervical cancer.

  17. Prediction of novel target genes and pathways involved in irinotecan-resistant colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Precious Takondwa Makondi

    Full Text Available Acquired drug resistance to the chemotherapeutic drug irinotecan (the active metabolite of which is SN-38 is one of the significant obstacles in the treatment of advanced colorectal cancer (CRC. The molecular mechanism or targets mediating irinotecan resistance are still unclear. It is urgent to find the irinotecan response biomarkers to improve CRC patients' therapy.Genetic Omnibus Database GSE42387 which contained the gene expression profiles of parental and irinotecan-resistant HCT-116 cell lines was used. Differentially expressed genes (DEGs between parental and irinotecan-resistant cells, protein-protein interactions (PPIs, gene ontologies (GOs and pathway analysis were performed to identify the overall biological changes. The most common DEGs in the PPIs, GOs and pathways were identified and were validated clinically by their ability to predict overall survival and disease free survival. The gene-gene expression correlation and gene-resistance correlation was also evaluated in CRC patients using The Cancer Genomic Atlas data (TCGA.The 135 DEGs were identified of which 36 were upregulated and 99 were down regulated. After mapping the PPI networks, the GOs and the pathways, nine genes (GNAS, PRKACB, MECOM, PLA2G4C, BMP6, BDNF, DLG4, FGF2 and FGF9 were found to be commonly enriched. Signal transduction was the most significant GO and MAPK pathway was the most significant pathway. The five genes (FGF2, FGF9, PRKACB, MECOM and PLA2G4C in the MAPK pathway were all contained in the signal transduction and the levels of those genes were upregulated. The FGF2, FGF9 and MECOM expression were highly associated with CRC patients' survival rate but not PRKACB and PLA2G4C. In addition, FGF9 was also associated with irinotecan resistance and poor disease free survival. FGF2, FGF9 and PRKACB were positively correlated with each other while MECOM correlated positively with FGF9 and PLA2G4C, and correlated negatively with FGF2 and PRKACB after doing gene

  18. Predicting pathway cross-talks in ankylosing spondylitis through investigating the interactions among pathways.

    Science.gov (United States)

    Gu, Xiang; Liu, Cong-Jian; Wei, Jian-Jie

    2017-11-13

    Given that the pathogenesis of ankylosing spondylitis (AS) remains unclear, the aim of this study was to detect the potentially functional pathway cross-talk in AS to further reveal the pathogenesis of this disease. Using microarray profile of AS and biological pathways as study objects, Monte Carlo cross-validation method was used to identify the significant pathway cross-talks. In the process of Monte Carlo cross-validation, all steps were iterated 50 times. For each run, detection of differentially expressed genes (DEGs) between two groups was conducted. The extraction of the potential disrupted pathways enriched by DEGs was then implemented. Subsequently, we established a discriminating score (DS) for each pathway pair according to the distribution of gene expression levels. After that, we utilized random forest (RF) classification model to screen out the top 10 paired pathways with the highest area under the curve (AUCs), which was computed using 10-fold cross-validation approach. After 50 bootstrap, the best pairs of pathways were identified. According to their AUC values, the pair of pathways, antigen presentation pathway and fMLP signaling in neutrophils, achieved the best AUC value of 1.000, which indicated that this pathway cross-talk could distinguish AS patients from normal subjects. Moreover, the paired pathways of SAPK/JNK signaling and mitochondrial dysfunction were involved in 5 bootstraps. Two paired pathways (antigen presentation pathway and fMLP signaling in neutrophil, as well as SAPK/JNK signaling and mitochondrial dysfunction) can accurately distinguish AS and control samples. These paired pathways may be helpful to identify patients with AS for early intervention.

  19. Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer

    International Nuclear Information System (INIS)

    Arias-Pulido, Hugo; Chaher, Nabila; Gong, Yun; Qualls, Clifford; Vargas, Jake; Royce, Melanie

    2012-01-01

    Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens. Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration. From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01). To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to

  20. Prediction of Effective Drug Combinations by Chemical Interaction, Protein Interaction and Target Enrichment of KEGG Pathways

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2013-01-01

    Full Text Available Drug combinatorial therapy could be more effective in treating some complex diseases than single agents due to better efficacy and reduced side effects. Although some drug combinations are being used, their underlying molecular mechanisms are still poorly understood. Therefore, it is of great interest to deduce a novel drug combination by their molecular mechanisms in a robust and rigorous way. This paper attempts to predict effective drug combinations by a combined consideration of: (1 chemical interaction between drugs, (2 protein interactions between drugs’ targets, and (3 target enrichment of KEGG pathways. A benchmark dataset was constructed, consisting of 121 confirmed effective combinations and 605 random combinations. Each drug combination was represented by 465 features derived from the aforementioned three properties. Some feature selection techniques, including Minimum Redundancy Maximum Relevance and Incremental Feature Selection, were adopted to extract the key features. Random forest model was built with its performance evaluated by 5-fold cross-validation. As a result, 55 key features providing the best prediction result were selected. These important features may help to gain insights into the mechanisms of drug combinations, and the proposed prediction model could become a useful tool for screening possible drug combinations.

  1. Patient characteristics do not predict poor glycaemic control in type 2 diabetes patients treated in primary care

    NARCIS (Netherlands)

    Goudswaard, AN; Stolk, RP; Zuithoff, P; Rutten, GEHM

    Many diabetic patients in general practice do not achieve good glycaemic control. The aim of this study was to assess which characteristics of type 2 diabetes patients treated in primary care predict poor glycaemic control (HbA(1c) greater than or equal to7%). Data were collected from the medical

  2. Not self-focused attention but negative beliefs affect poor social performance in social anxiety : An investigation of pathways in the social anxiety-social rejection relationship

    NARCIS (Netherlands)

    Voncken, Marisol J.; Dijk, Corine; de Jong, Peter J.; Roelofs, Jeffrey

    2010-01-01

    Patients with social anxiety disorder (SAD) not only fear negative evaluation but are indeed less likeable than people without SAD. Previous research shows social performance to mediate this social anxiety-social rejection relationship. This study studied two pathways hypothesized to lead to poor

  3. Not self-focused attention but negative beliefs affect poor social performance in social anxiety: an investigation of pathways in the social anxiety - social rejection relationship

    NARCIS (Netherlands)

    Voncken, M.J.; Dijk, C.; de Jong, P.J.; Roelofs, J.

    2010-01-01

    Patients with social anxiety disorder (SAD) not only fear negative evaluation but are indeed less likeable than people without SAD. Previous research shows social performance to mediate this social anxiety-social rejection relationship. This study studied two pathways hypothesized to lead to poor

  4. Prediction of novel synthetic pathways for the production of desired chemicals

    Directory of Open Access Journals (Sweden)

    Park Jin

    2010-03-01

    Full Text Available Abstract Background There have been several methods developed for the prediction of synthetic metabolic pathways leading to the production of desired chemicals. In these approaches, novel pathways were predicted based on chemical structure changes, enzymatic information, and/or reaction mechanisms, but the approaches generating a huge number of predicted results are difficult to be applied to real experiments. Also, some of these methods focus on specific pathways, and thus are limited to expansion to the whole metabolism. Results In the present study, we propose a system framework employing a retrosynthesis model with a prioritization scoring algorithm. This new strategy allows deducing the novel promising pathways for the synthesis of a desired chemical together with information on enzymes involved based on structural changes and reaction mechanisms present in the system database. The prioritization scoring algorithm employing Tanimoto coefficient and group contribution method allows examination of structurally qualified pathways to recognize which pathway is more appropriate. In addition, new concepts of binding site covalence, estimation of pathway distance and organism specificity were taken into account to identify the best synthetic pathway. Parameters of these factors can be evolutionarily optimized when a newly proven synthetic pathway is registered. As the proofs of concept, the novel synthetic pathways for the production of isobutanol, 3-hydroxypropionate, and butyryl-CoA were predicted. The prediction shows a high reliability, in which experimentally verified synthetic pathways were listed within the top 0.089% of the identified pathway candidates. Conclusions It is expected that the system framework developed in this study would be useful for the in silico design of novel metabolic pathways to be employed for the efficient production of chemicals, fuels and materials.

  5. Does self-reported sleep quality predict poor cognitive performance among elderly living in elderly homes?

    Science.gov (United States)

    Amer, Motassem S; Hamza, Sarah A; El Akkad, Rania M; Abdel Galeel, Yamen I I

    2013-01-01

    Sleep complaints are common among elderly, especially institutionalized elderly, as they experience poorer sleep quality and higher use of sedative hypnotics, when compared to community-dwelling elderly. Recent findings suggest that there may be a relationship between poor quality of sleep and cognitive deficits. This study aimed at studying the relation between sleep quality and cognitive performance in older adults living in elderly homes. 100 elderly living in an elderly home in El Mansoura, Egypt, were recruited in this study, 50 cases with subjective poor quality of sleep and 50 controls with subjective good quality of sleep as assessed by Pittsburgh sleep quality index (PSQI). Each participant went through comprehensive geriatric assessment (CGA), including geriatric depression scale (GDS), assessment of cognitive function by mini mental state examination (MMSE). 52% of poor sleepers showed impaired MMSE, while only 24% of good sleepers had impaired MMSE. Both orientation and (attention and calculation) were more affected (P = 0.027 and 0.035, respectively). Linear correlation coefficient between PSQI and different variables revealed significant negative correlation with total MMSE score, attention and calculation. Poor quality of sleep is related to cognitive impairment among elderly living in elderly homes and this problem should be taken in consideration among this group of elders.

  6. Type D Personality Predicts Poor Medication Adherence in Patients with Heart Failure in the USA

    Science.gov (United States)

    Wu, Jia-Rong; Moser, Debra K.

    2015-01-01

    Background Type D (distressed) personality and medication nonadherence have been associated with poor health outcomes. Type D personality is associated with poor medication adherence in patients with coronary artery disease. However, the relationship between type D personality and medication adherence in patients with heart failure (HF) remains unknown. Purpose Therefore, the goal of this study was to examine the association between type D personality and medication adherence in patients with HF. Method This was a sub-analysis of baseline data from a randomized controlled trial with 84 patients with HF in the USA. Demographic, clinical, and psychological data were collected at baseline by interview, questionnaires, and medical record review. Type D personality was assessed using the Type D Personality Scale (DS14). Medication adherence was measured using both objective (Medication Event Monitoring System, MEMS) and self-reported (Morisky Medication Adherence Scale, MMAS-4) measures. Patients started medication adherence monitoring with the MEMS bottle at baseline and is used continuously for a month. Multiple regressions were used to explore the relationships between type D personality and medication adherence while adjusting for demographic, clinical, and psychological factors. Results Patients with type D personality were more likely to have poor medication adherence. Type D personality was associated with medication adherence before and after adjusting for covariates when it was analyzed as a categorical variable. However, type D personality was not associated with medication adherence when analyzed as a dimensional construct. Negative affectivity, a component of type D personality, was associated with medication adherence. Conclusion As a dimensional construct, type D personality may not reflect the components of the personality associated with poor outcomes. Negative affectivity was associated with medication adherence in patients with HF. Interventions aiming

  7. Our calibrated model has poor predictive value: An example from the petroleum industry

    International Nuclear Information System (INIS)

    Carter, J.N.; Ballester, P.J.; Tavassoli, Z.; King, P.R.

    2006-01-01

    It is often assumed that once a model has been calibrated to measurements then it will have some level of predictive capability, although this may be limited. If the model does not have predictive capability then the assumption is that the model needs to be improved in some way. Using an example from the petroleum industry, we show that cases can exit where calibrated models have limited predictive capability. This occurs even when there is no modelling error present. It is also shown that the introduction of a small modelling error can make it impossible to obtain any models with useful predictive capability. We have been unable to find ways of identifying which calibrated models will have some predictive capacity and those which will not

  8. Our calibrated model has poor predictive value: An example from the petroleum industry

    Energy Technology Data Exchange (ETDEWEB)

    Carter, J.N. [Department of Earth Science and Engineering, Imperial College, London (United Kingdom)]. E-mail: j.n.carter@ic.ac.uk; Ballester, P.J. [Department of Earth Science and Engineering, Imperial College, London (United Kingdom); Tavassoli, Z. [Department of Earth Science and Engineering, Imperial College, London (United Kingdom); King, P.R. [Department of Earth Science and Engineering, Imperial College, London (United Kingdom)

    2006-10-15

    It is often assumed that once a model has been calibrated to measurements then it will have some level of predictive capability, although this may be limited. If the model does not have predictive capability then the assumption is that the model needs to be improved in some way. Using an example from the petroleum industry, we show that cases can exit where calibrated models have limited predictive capability. This occurs even when there is no modelling error present. It is also shown that the introduction of a small modelling error can make it impossible to obtain any models with useful predictive capability. We have been unable to find ways of identifying which calibrated models will have some predictive capacity and those which will not.

  9. A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases

    Directory of Open Access Journals (Sweden)

    Karp Peter D

    2004-06-01

    Full Text Available Abstract Background The PathoLogic program constructs Pathway/Genome databases by using a genome's annotation to predict the set of metabolic pathways present in an organism. PathoLogic determines the set of reactions composing those pathways from the enzymes annotated in the organism's genome. Most annotation efforts fail to assign function to 40–60% of sequences. In addition, large numbers of sequences may have non-specific annotations (e.g., thiolase family protein. Pathway holes occur when a genome appears to lack the enzymes needed to catalyze reactions in a pathway. If a protein has not been assigned a specific function during the annotation process, any reaction catalyzed by that protein will appear as a missing enzyme or pathway hole in a Pathway/Genome database. Results We have developed a method that efficiently combines homology and pathway-based evidence to identify candidates for filling pathway holes in Pathway/Genome databases. Our program not only identifies potential candidate sequences for pathway holes, but combines data from multiple, heterogeneous sources to assess the likelihood that a candidate has the required function. Our algorithm emulates the manual sequence annotation process, considering not only evidence from homology searches, but also considering evidence from genomic context (i.e., is the gene part of an operon? and functional context (e.g., are there functionally-related genes nearby in the genome? to determine the posterior belief that a candidate has the required function. The method can be applied across an entire metabolic pathway network and is generally applicable to any pathway database. The program uses a set of sequences encoding the required activity in other genomes to identify candidate proteins in the genome of interest, and then evaluates each candidate by using a simple Bayes classifier to determine the probability that the candidate has the desired function. We achieved 71% precision at a

  10. Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma.

    Science.gov (United States)

    Lassus, Heini; Staff, Synnöve; Leminen, Arto; Isola, Jorma; Butzow, Ralf

    2011-01-01

    Aurora-A is a potential oncogene and therapeutic target in ovarian carcinoma. It is involved in mitotic events and overexpression leads to centrosome amplification and chromosomal instability. The objective of this study was to evaluate the clinical significance of Aurora-A and DNA ploidy in serous ovarian carcinoma. Serous ovarian carcinomas were analysed for Aurora-A protein by immunohistochemistry (n=592), Aurora-A copy number by CISH (n=169), Aurora-A mRNA by real-time PCR (n=158) and DNA ploidy by flowcytometry (n=440). Overexpression of Aurora-A was found in 27% of the tumors, cytoplasmic overexpression in 11% and nuclear in 17%. The cytoplasmic and nuclear overexpression were nearly mutually exclusive. Both cytoplasmic and nuclear overexpression were associated with shorter survival, high grade, high proliferation index and aberrant p53. Interestingly, only cytoplasmic expression was associated with aneuploidy and expression of phosphorylated Aurora-A. DNA ploidy was associated with poor patient outcome as well as aggressive clinicopathological parameters. In multivariate analysis, Aurora-A overexpression appeared as an independent prognostic factor for disease-free survival, together with grade, stage and ploidy. Aurora-A protein expression is strongly linked with poor patient outcome and aggressive disease characteristics, which makes Aurora-A a promising biomarker and a potential therapeutic target in ovarian carcinoma. Cytoplasmic and nuclear Aurora-A protein may have different functions. DNA aneuploidy is a strong predictor of poor prognosis in serous ovarian carcinoma. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. High CRP values predict poor survival in patients with penile cancer

    International Nuclear Information System (INIS)

    Steffens, Sandra; Kuczyk, Markus A; Schrader, Andres J; Al Ghazal, Andreas; Steinestel, Julie; Lehmann, Rieke; Wegener, Gerd; Schnoeller, Thomas J; Cronauer, Marcus V; Jentzmik, Florian; Schrader, Mark

    2013-01-01

    High levels of circulating C-reactive protein (CRP) have recently been linked to poor clinical outcome in various malignancies. The aim of this study was to evaluate the prognostic significance of the preoperative serum CRP level in patients with squamous cell carcinoma (SCC) of the penis. This retrospective analysis included 79 penile cancer patients with information about their serum CRP value prior to surgery who underwent either radical or partial penectomy at two German high-volume centers (Ulm University Medical Center and Hannover Medical School) between 1990 and 2010. They had a median (mean) follow-up of 23 (32) months. A significantly elevated CRP level (>15 vs. ≤ 15 mg/l) was found more often in patients with an advanced tumor stage (≥pT2) (38.9 vs. 11.6%, p=0.007) and in those with nodal disease at diagnosis (50.0 vs. 14.6%, p=0.007). However, high CRP levels were not associated with tumor differentiation (p=0.53). The Kaplan-Meier 5-year cancer-specific survival (CSS) rate was 38.9% for patients with preoperative CRP levels above 15 mg/l and 84.3% for those with lower levels (p=0.001). Applying multivariate analysis and focusing on the subgroup of patients without metastasis at the time of penile surgery, both advanced local tumor stage (≥pT2; HR 8.8, p=0.041) and an elevated CRP value (>15 mg/l; HR 3.3, p=0.043) were identified as independent predictors of poor clinical outcome in patients with penile cancer. A high preoperative serum CRP level was associated with poor survival in patients with penile cancer. If larger patient populations confirm its prognostic value, its routine use could enable better risk stratification and risk-adjusted follow-up of patients with SCC of the penis

  12. Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis

    Science.gov (United States)

    Xu, Sen-Lin; Liu, Sha; Cui, Wei; Shi, Yu; Liu, Qin; Duan, Jiang-Jie; Yu, Shi-Cang; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Bian, Xiu-Wu

    2015-01-01

    Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1+ tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the “classical-like” (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients’ outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1+ cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1- cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1+ cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma. PMID:26101711

  13. Poor self-control and harsh punishment in childhood prospectively predict borderline personality symptoms in adolescent girls.

    Science.gov (United States)

    Hallquist, Michael N; Hipwell, Alison E; Stepp, Stephanie D

    2015-08-01

    Developmental theories of borderline personality disorder (BPD) propose that harsh, invalidating parenting of a child with poor self-control and heightened negative emotionality often leads to a coercive cycle of parent-child transactions that increase risk for BPD symptoms such as emotion dysregulation. Although parenting practices and child temperament have previously been linked with BPD, less is known about the prospective influences of caregiver and child characteristics. Using annual longitudinal data from the Pittsburgh Girls Study (n = 2,450), our study examined how reciprocal influences among harsh parenting, self-control, and negative emotionality between ages 5 and 14 predicted the development of BPD symptoms in adolescent girls ages 14 to 17. Consistent with developmental theories, we found that harsh punishment, poor self-control, and negative emotionality predicted BPD symptom severity at age 14. Only worsening self-control between ages 12 and 14, however, predicted growth in BPD symptoms from 14 to 17. Furthermore, the effects of harsh punishment and poor self-control on age 14 BPD symptoms were partially mediated by their earlier reciprocal effects on each other between ages 5 and 14. Our findings underscore the need to address both child and parental contributions to dysfunctional transactions in order to stem the development of BPD symptoms. Moreover, problems with self-regulation in early adolescence may indicate heightened risk for subsequent BPD. Altogether, these results increase our understanding of developmental trajectories associated with BPD symptoms in adolescent girls. (c) 2015 APA, all rights reserved).

  14. Overexpression of GRK3, Promoting Tumor Proliferation, Is Predictive of Poor Prognosis in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Tao Jiang

    2017-01-01

    Full Text Available Deregulation of G protein-coupled receptor kinase 3 (GRK3, which belongs to a subfamily of kinases called GRKs, acts as a promoter mechanism in some cancer types. Our study found that GRK3 was significantly overexpressed in 162 pairs of colon cancer tissues than in the matched noncancerous mucosa (P<0.01. Based on immunohistochemistry staining of TMAs, GRK3 was dramatically stained positive in primary colon cancer (130/180, 72.22%, whereas it was detected minimally or negative in paired normal mucosa specimens (50/180, 27.78%. Overexpression of GRK3 was closely correlated with AJCC stage (P=0.001, depth of tumor invasion (P<0.001, lymph node involvement (P=0.004, distant metastasis (P=0.016, and histologic differentiation (P=0.004. Overexpression of GRK3 is an independent prognostic indicator that correlates with poor survival in colon cancer patients. Consistent with this, downregulation of GRK3 exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate, and impaired colon tumorigenicity in a xenograft model. Hence, a specific overexpression of GRK3 was observed in colon cancer, GRK3 potentially contributing to progression by mediating cancer cell proliferation and functions as a poor prognostic indicator in colon cancer and potentially represent a novel therapeutic target for the disease.

  15. Imitated prosodic fluency predicts reading comprehension ability in good and poor high school readers

    Directory of Open Access Journals (Sweden)

    Mara Breen

    2016-07-01

    Full Text Available Researchers have established a relationship between beginning readers’ silent comprehension ability and their prosodic fluency, such that readers who read aloud with appropriate prosody tend to have higher scores on silent reading comprehension assessments. The current study was designed to investigate this relationship in two groups of high school readers: Specifically Poor Comprehenders (SPCs, who have adequate word level and phonological skills but poor reading comprehension ability, and a group of age- and decoding skill-matched controls. We compared the prosodic fluency of the two groups by determining how effectively they produced prosodic cues to syntactic and semantic structure in imitations of a model speaker’s production of syntactically and semantically varied sentences. Analyses of pitch and duration patterns revealed that speakers in both groups produced the expected prosodic patterns; however, controls provided stronger durational cues to syntactic structure. These results demonstrate that the relationship between prosodic fluency and reading comprehension continues past the stage of early reading instruction. Moreover, they suggest that prosodically fluent speakers may also generate more fluent implicit prosodic representations during silent reading, leading to more effective comprehension.

  16. Accuracy of algorithms to predict accessory pathway location in children with Wolff-Parkinson-White syndrome.

    Science.gov (United States)

    Wren, Christopher; Vogel, Melanie; Lord, Stephen; Abrams, Dominic; Bourke, John; Rees, Philip; Rosenthal, Eric

    2012-02-01

    The aim of this study was to examine the accuracy in predicting pathway location in children with Wolff-Parkinson-White syndrome for each of seven published algorithms. ECGs from 100 consecutive children with Wolff-Parkinson-White syndrome undergoing electrophysiological study were analysed by six investigators using seven published algorithms, six of which had been developed in adult patients. Accuracy and concordance of predictions were adjusted for the number of pathway locations. Accessory pathways were left-sided in 49, septal in 20 and right-sided in 31 children. Overall accuracy of prediction was 30-49% for the exact location and 61-68% including adjacent locations. Concordance between investigators varied between 41% and 86%. No algorithm was better at predicting septal pathways (accuracy 5-35%, improving to 40-78% including adjacent locations), but one was significantly worse. Predictive accuracy was 24-53% for the exact location of right-sided pathways (50-71% including adjacent locations) and 32-55% for the exact location of left-sided pathways (58-73% including adjacent locations). All algorithms were less accurate in our hands than in other authors' own assessment. None performed well in identifying midseptal or right anteroseptal accessory pathway locations.

  17. Perioperative factors predicting poor outcome in elderly patients following emergency general surgery: a multivariate regression analysis

    Science.gov (United States)

    Lees, Mackenzie C.; Merani, Shaheed; Tauh, Keerit; Khadaroo, Rachel G.

    2015-01-01

    Background Older adults (≥ 65 yr) are the fastest growing population and are presenting in increasing numbers for acute surgical care. Emergency surgery is frequently life threatening for older patients. Our objective was to identify predictors of mortality and poor outcome among elderly patients undergoing emergency general surgery. Methods We conducted a retrospective cohort study of patients aged 65–80 years undergoing emergency general surgery between 2009 and 2010 at a tertiary care centre. Demographics, comorbidities, in-hospital complications, mortality and disposition characteristics of patients were collected. Logistic regression analysis was used to identify covariate-adjusted predictors of in-hospital mortality and discharge of patients home. Results Our analysis included 257 patients with a mean age of 72 years; 52% were men. In-hospital mortality was 12%. Mortality was associated with patients who had higher American Society of Anesthesiologists (ASA) class (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.43–10.33, p = 0.008) and in-hospital complications (OR 1.93, 95% CI 1.32–2.83, p = 0.001). Nearly two-thirds of patients discharged home were younger (OR 0.92, 95% CI 0.85–0.99, p = 0.036), had lower ASA class (OR 0.45, 95% CI 0.27–0.74, p = 0.002) and fewer in-hospital complications (OR 0.69, 95% CI 0.53–0.90, p = 0.007). Conclusion American Society of Anesthesiologists class and in-hospital complications are perioperative predictors of mortality and disposition in the older surgical population. Understanding the predictors of poor outcome and the importance of preventing in-hospital complications in older patients will have important clinical utility in terms of preoperative counselling, improving health care and discharging patients home. PMID:26204143

  18. Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer

    Science.gov (United States)

    SHAN, YAN-SHEN; HSU, HUI-PING; LAI, MING-DERG; YEN, MENG-CHI; LUO, YI-PEY; CHEN, YI-LING

    2015-01-01

    Aberrant expression of argininosuccinate synthetase (ASS1, also known as ASS) has been found in cancer cells and is involved in the carcinogenesis of gastric cancer. The aim of the present study was to investigate the level of ASS expression in human gastric cancer and to determine the possible correlations between ASS expression and clinicopathological findings. Immunohistochemistry was performed on paraffin-embedded tissues to determine whether ASS was expressed in 11 of 11 specimens from patients with gastric cancer. The protein was localized primarily to the cytoplasm of cancer cells and normal epithelium. In the Oncomine cancer microarray database, expression of the ASS gene was significantly increased in gastric cancer tissues. To investigate the clinicopathological and prognostic roles of ASS expression, we performed western blot analysis of 35 matched specimens of gastric adenocarcinomas and normal tissue obtained from patients treated at the National Cheng Kung University Hospital. The ratio of relative ASS expression (expressed as the ASS/β-actin ratio) in tumor tissues to that in normal tissues was correlated with large tumor size (P=0.007) and with the tumor, node, metastasis (TNM) stage of the American Joint Committee on Cancer staging system (P=0.031). Patients whose cancer had increased the relative expression of ASS were positive for perineural invasion and had poor recurrence-free survival. In summary, ASS expression in gastric cancer was associated with a poor prognosis. Further study of mechanisms to silence the ASS gene or decrease the enzymatic activity of ASS protein has the potential to provide new treatments for patients with gastric cancer. PMID:25333458

  19. Exposure to violence predicts poor educational outcomes in young children in South Africa and Malawi.

    Science.gov (United States)

    Sherr, L; Hensels, I S; Skeen, S; Tomlinson, M; Roberts, K J; Macedo, A

    2016-01-01

    Violence during childhood may affect short and long-term educational factors. There is scant literature on younger children from resource poor settings. This study assessed child violence experiences (harsh punishment and exposure to domestic or community violence) and school enrolment, progress and attendance in children attending community-based organisations in South Africa and Malawi (n=989) at baseline and at 15 months' follow-up, examining differential experience of HIV positive, HIV affected and HIV unaffected children. Violence exposure was high: 45.4% experienced some form of psychological violence, 47.8% physical violence, 46.7% domestic violence and 41.8% community violence. Primary school enrolment was 96%. Violence was not associated with school enrolment at baseline but, controlling for baseline, children exposed to psychological violence for discipline were more than ten times less likely to be enrolled at follow-up (OR 0.09; 95% CI 0.01 to 0.57). Harsh discipline was associated with poor school progress. For children HIV positive a detrimental effect of harsh physical discipline was found on school performance (OR 0.10; 95% CI 0.02 to 0.61). Violence experiences were associated with a number of educational outcomes, which may have long-term consequences. Community-based organisations may be well placed to address such violence, with a particular emphasis on the challenges faced by children who are HIV positive. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

  20. Pathway analysis of gene signatures predicting metastasis of node-negative primary breast cancer

    International Nuclear Information System (INIS)

    Yu, Jack X; Sieuwerts, Anieta M; Zhang, Yi; Martens, John WM; Smid, Marcel; Klijn, Jan GM; Wang, Yixin; Foekens, John A

    2007-01-01

    Published prognostic gene signatures in breast cancer have few genes in common. Here we provide a rationale for this observation by studying the prognostic power and the underlying biological pathways of different gene signatures. Gene signatures to predict the development of metastases in estrogen receptor-positive and estrogen receptor-negative tumors were identified using 500 re-sampled training sets and mapping to Gene Ontology Biological Process to identify over-represented pathways. The Global Test program confirmed that gene expression profilings in the common pathways were associated with the metastasis of the patients. The apoptotic pathway and cell division, or cell growth regulation and G-protein coupled receptor signal transduction, were most significantly associated with the metastatic capability of estrogen receptor-positive or estrogen-negative tumors, respectively. A gene signature derived of the common pathways predicted metastasis in an independent cohort. Mapping of the pathways represented by different published prognostic signatures showed that they share 53% of the identified pathways. We show that divergent gene sets classifying patients for the same clinical endpoint represent similar biological processes and that pathway-derived signatures can be used to predict prognosis. Furthermore, our study reveals that the underlying biology related to aggressiveness of estrogen receptor subgroups of breast cancer is quite different

  1. Predicting the susceptibility to gully initiation in data-poor regions

    Science.gov (United States)

    Dewitte, Olivier; Daoudi, Mohamed; Bosco, Claudio; Van Den Eeckhaut, Miet

    2015-01-01

    Permanent gullies are common features in many landscapes and quite often they represent the dominant soil erosion process. Once a gully has initiated, field evidence shows that gully channel formation and headcut migration rapidly occur. In order to prevent the undesired effects of gullying, there is a need to predict the places where new gullies might initiate. From detailed field measurements, studies have demonstrated strong inverse relationships between slope gradient of the soil surface (S) and drainage area (A) at the point of channel initiation across catchments in different climatic and morphological environments. Such slope-area thresholds (S-A) can be used to predict locations in the landscape where gullies might initiate. However, acquiring S-A requires detailed field investigations and accurate high resolution digital elevation data, which are usually difficult to acquire. To circumvent this issue, we propose a two-step method that uses published S-A thresholds and a logistic regression analysis (LR). S-A thresholds from the literature are used as proxies of field measurement. The method is calibrated and validated on a watershed, close to the town of Algiers, northern Algeria, where gully erosion affects most of the slopes. The gullies extend up to several kilometres in length and cover 16% of the study area. First we reconstruct the initiation areas of the existing gullies by applying S-A thresholds for similar environments. Then, using the initiation area map as the dependent variable with combinations of topographic and lithological predictor variables, we calibrate several LR models. It provides relevant results in terms of statistical reliability, prediction performance, and geomorphological significance. This method using S-A thresholds with data-driven assessment methods like LR proves to be efficient when applied to common spatial data and establishes a methodology that will allow similar studies to be undertaken elsewhere.

  2. Cell division cycle 20 overexpression predicts poor prognosis for patients with lung adenocarcinoma.

    Science.gov (United States)

    Shi, Run; Sun, Qi; Sun, Jing; Wang, Xin; Xia, Wenjie; Dong, Gaochao; Wang, Anpeng; Jiang, Feng; Xu, Lin

    2017-03-01

    The cell division cycle 20, a key component of spindle assembly checkpoint, is an essential activator of the anaphase-promoting complex. Aberrant expression of cell division cycle 20 has been detected in various human cancers. However, its clinical significance has never been deeply investigated in non-small-cell lung cancer. By analyzing The Cancer Genome Atlas database and using some certain online databases, we validated overexpression of cell division cycle 20 in both messenger RNA and protein levels, explored its clinical significance, and evaluated the prognostic role of cell division cycle 20 in non-small-cell lung cancer. Cell division cycle 20 expression was significantly correlated with sex (p = 0.003), histological classification (p overexpression of cell division cycle 20 was significantly associated with bigger primary tumor size (p = 0.0023), higher MKI67 level (r = 0.7618, p Overexpression of cell division cycle 20 is associated with poor prognosis in lung adenocarcinoma patients, and its overexpression can also be used to identify high-risk groups. In conclusion, cell division cycle 20 might serve as a potential biomarker for lung adenocarcinoma patients.

  3. TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas.

    Science.gov (United States)

    Gao, Ke; Li, Gang; Qu, Yiping; Wang, Maode; Cui, Bo; Ji, Meiju; Shi, Bingyin; Hou, Peng

    2016-02-23

    Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas.

  4. Synuclein gamma predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen

    Directory of Open Access Journals (Sweden)

    Xing Xiaofang

    2010-07-01

    Full Text Available Abstract Background Synuclein gamma (SNCG, initially identified as a breast cancer specific gene, is aberrantly expressed in many different malignant tumors but rarely expressed in matched nonneoplastic adjacent tissues. In this study, we investigated the prognostic potential of SNCG in colon cancer particularly in the patients with normal carcinoembryonic antigen (CEA levels. Methods SNCG levels were assessed immunohistochemically in cancer tissues from 229 colon adenocarcinoma patients with a mean follow-up of 44 months. Correlations between SNCG levels and clinicopathologic features, preoperative serum CEA level, and clinical outcome were analyzed statistically using SPSS. Results SNCG levels in colon adenocarcinoma were closely associated with intravascular embolus and tumor recurrence but independent of preoperative serum CEA levels. SNCG expression was an independent prognostic factor of a shorter disease-free survival (DFS and overall survival (OS (P P = 0.001, P = 0.001, 0.002 for 97 patients with normal preoperative serum CEA level. Conclusions Our results suggest for the first time that SNCG is a new independent predicator for poor prognosis in patients with colon adenocarcinoma, including those with normal CEA levels. Combination of CEA with SNCG improves prognostic evaluation for patients with colon adenocarcinoma.

  5. Low expression of Mel-18 predicts poor prognosis in patients with breast cancer.

    Science.gov (United States)

    Guo, B-H; Zhang, X; Zhang, H-Z; Lin, H-L; Feng, Y; Shao, J-Y; Huang, W-L; Kung, H-F; Zeng, M-S

    2010-12-01

    Our previous study suggested that melanoma nuclear protein 18 (Mel-18) acted as a tumor suppressor in human breast cancer. This study was designed to investigate the clinical and prognostic significance of Mel-18 in breast cancer patients. Mel-18 was detected by immunohistochemistry in paraffin-embedded tissues from 287 breast cancer patients, of which 287 were from primary cancer sites, 63 from matched adjacent noncancerous sites, and 35 from metastatic lymph nodes. Differences in Mel-18 expression and clinical characteristics were compared by χ² test. Prognostic outcomes correlated with Mel-18 were examined using Kaplan-Meier analysis and Cox proportional hazards model. The decreased Mel-18 expression is incremental depending upon the magnitude of cancer progression (P Mel-18 was conversely correlated with the pathological classifications (P Mel-18 showed prolonged overall survivals (P Mel-18 expression may be a risk factor for the patients' survival (P Mel-18 expression is correlated with advanced clinicopathologic classifications and a poor overall survival in breast cancer patients. These findings suggest that Mel-18 may serve as a useful marker in prognostic evaluation for patients.

  6. High expression of BAG3 predicts a poor prognosis in human medulloblastoma.

    Science.gov (United States)

    Yang, Dong; Zhou, Ji; Wang, Hao; Wang, Yutao; Yang, Ge; Zhang, Yundong

    2016-10-01

    Bcl2-associated athanogene 3 (BAG3), a co-chaperone of the heat shock protein (Hsp) 70, regulates various physiological and pathological processes. However, its role in human medulloblastoma has not been clarified. First of all, the expression of BAG3 was examined in formalin-fixed, paraffin-embedded specimens by immunohistochemical staining. And then, the prognostic role of BAG3 was analyzed in 51 medulloblastoma samples. Finally, the roles of BAG3 in the proliferation, migration, and invasion of Daoy medulloblastoma cell were investigated using a specific short hairpin RNA (shRNA). The expression of BAG3 in medulloblastoma tissues was higher than nontumorous samples. Furthermore, BAG3 overexpression significantly correlated with poor prognosis of patients with medulloblastoma. The overall survival and tumor-free survival in patients with BAG3 low expression were higher than high expression. Univariate and multivariate analysis showed that BAG3 overexpression was an independent prognostic marker for medulloblastoma. After the BAG3 knockdown, the Daoy cells exhibited decreased the ability to proliferate and form neurosphere. The preliminary mechanism study showed that overexpression of BAG3 might facilitate the cell cycle transition from G1 to S phase by modulating the cyclin-dependent kinase 2 (CDK2) and cyclin E expression. Additionally, we found that BAG3 might enhance the medulloblastoma cell migratory and invasive ability. In summary, BAG3 overexpression may regulate the survival and invasive properties of medulloblastoma and may serve as a potential therapy target for medulloblastoma.

  7. Multi-Marker Strategy in Heart Failure: Combination of ST2 and CRP Predicts Poor Outcome.

    Directory of Open Access Journals (Sweden)

    Anne Marie Dupuy

    Full Text Available Natriuretic peptides (BNP and NT-proBNP are recognized as gold-standard predictive markers in Heart Failure (HF. However, currently ST2 (member of the interleukin 1 receptor family has emerged as marker of inflammation, fibrosis and cardiac stress. We evaluated ST2 and CRP as prognostic markers in 178 patients with chronic heart failure in comparison with other classical markers such as clinical established parameters but also biological markers: NT-proBNP, hs-cTnT alone or in combination. In multivariate analysis, subsequent addition of ST2 led to age, CRP and ST2 as the only remaining predictors of all-cause mortality (HR 1.03, HR 1.61 and HR 2.75, respectively as well as of cardiovascular mortality (HR 1.00, HR 2.27 and HR 3.78, respectively. The combined increase of ST2 and CRP was significant for predicting worsened outcomes leading to identify a high risk subgroup that individual assessment of either marker. The same analysis was performed with ST2 in combination with Barcelona score. Overall, our findings extend previous data demonstrating that ST2 in combination with CRP as a valuable tool for identifying patients at risk of death.

  8. Pathways for sustainable development of mixed crop livestock systems: Taking a livestock and pro-poor approach

    NARCIS (Netherlands)

    Tarawali, S.A.; Herrero, M.; Descheemaeker, K.K.E.; Grings, E.; Blmmel, M.

    2011-01-01

    Mixed crop livestock systems provide the majority of the cereal and livestock domestic products for households in developing countries. We explore the question of whether such systems can respond to increasing demands for livestock products without compromising future livelihoods of the poor or the

  9. High Expression of PHGDH Predicts Poor Prognosis in Non–Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jinhong Zhu

    2016-12-01

    Full Text Available Tumors have exceptionally high demands for energy and anabolism because of their rapid growth. The de novo serine synthesis pathway initiated by phosphoglycerate dehydrogenase (PHGDH has been recognized as a hallmark of metabolic adaption in carcinogenesis. The oncogenic role and prognostic value of PHGDH have been investigated in multiple cancer types, including breast cancer, melanoma, cervical cancer, and colon cancer. Due to the importance of PHGDH in cancer, we attempted to determine the clinical significance of PHGDH in 319 patients with non–small cell lung cancer (NSCLC. We evaluated the mRNA and protein expression levels of PHGDH gene, using quantitative reverse transcriptase polymerase chain reaction and tissue array–based immunohistochemistry, respectively. Significantly increased PHGDH expression in mRNA and protein levels was identified in tumor tissues versus matched adjacent nontumor tissues. More interestingly, immunohistochemical expression of PHGDH was significantly associated with lymph node metastasis (P = .021 and TNM stage (P = .016. Kaplan-Meier survival analysis indicated that NSCLC patients with low levels of PHGDH outperformed patients with high levels of PHGDH regarding 5-year overall survival. Significantly longer survival in the former suggested the prognostic implication of PHGDH in NSCLC. Multivariate survival analysis using Cox regression model demonstrated that high PHGDH levels and advanced TNM stage (III + IV were independent predictors of prognosis in NSCLC. Moreover, bioinformatics analysis confirmed the increase in PHGDH transcripts (data from The Cancer Genome Atlas and its prognostic value (Kaplan-Meier plotter in NSCLC. In conclusion, this study suggested the clinical implication of PHGDH in NSCLC. PHGDH may be a promising therapeutic target in NSCLC.

  10. CEP55 overexpression predicts poor prognosis in patients with locally advanced esophageal squamous cell carcinoma.

    Science.gov (United States)

    Jiang, Wenpeng; Wang, Zhou; Jia, Yang

    2017-01-01

    Development of esophageal squamous cell carcinoma (ESCC) involves alterations in multiple genes with corresponding proteins. Recent studies have demonstrated that centrosomal protein 55 (CEP55) shares certain features with oncogenes, and CEP55 overexpression is associated with the development and progression of malignant tumors. The present study aimed to analyze, for the first time, whether CEP55 expression is related to clinicopothalogic features in the esophageal squamous cell carcinoma (ESCC), as well as patient survival. A total of 110 patients with mid-thoracic ESCC who suffered from Ivor-Lewis were enrolled. The CEP55 expression profile of these patients in tumour tissues and corresponding healthy esophageal mucosa (CHEM) was detected by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction analyses. Correlations between CEP55 expression and clinicopathological factors were analyzed using χ 2 test. The log-rank test was employed to calculate survival rate. A Cox regression multivariate analysis was performed to determine independent prognostic factors. The results demonstrated that CEP55 expression in ESCC was significantly higher than that of CHEM (POverexpression of CEP55 was significantly associated with differentiation degree (P=0.022), T stage (P=0.019), lymph node metastasis (P=0.033), clinicopathological staging (P=0.002) and tumor recurrence (P=0.021) in locally advanced ESCC patients. In addition, CEP55 overexpression was significantly associated with reduced overall survival of patients after surgery (P=0.012). The 5-year survival rate of patients without CEP55 overexpression was significantly higher than that of patients with CEP55 overexpression (P=0.012). Therefore, these findings suggest that CEP55 overexpression correlates with poor prognosis in locally advanced ESCC patients.

  11. Single nucleotide polymorphisms in MLH1 predict poor prognosis of hepatocellular carcinoma in a Chinese population.

    Science.gov (United States)

    Zhu, Xiaonian; Liu, Wei; Qiu, Xiaoqiang; Wang, Zhigang; Tan, Chao; Bei, Chunhua; Qin, Linyuan; Ren, Yuan; Tan, Shengkui

    2017-10-03

    Hepatocellular carcinoma (HCC) is a malignant cancer causing deleterious health effect worldwide, especially in China. So far clinical cure rate and long-term survival rate of HCC remains low. Most HCC patients after cancer resection have recurrence or metastasis within 5 years. This study aims to explore the genetic association of mutL homolog 1 ( MLH1 ) polymorphisms with HCC risk and prognosis. Four candidate MLH1 polymorphisms, rs1800734, rs10849, rs3774343 and rs1540354 were studied from a hospital-based case-control study including 1,036 cases (HCC patients) and 1,036 controls (non-HCC patients) in Guangxi, China. All these SNPs interacted with environmental risk factors, such as HBV infection, alcohol intake and smoking in the pathogenesis of HCC. However, only rs1800734 had significant difference between cases and controls. Compared to the AA genotype, patients with AG, GG and AG/GG genotype of rs1800734 had an increased risk of HCC [ORs (95% CI) = 1.217 (1.074∼1.536), 1.745 (1.301∼2.591) and 1.291 (1.126∼1.687)] and a decreased survival time [co-dominant, HR (95% CI) = 1.553 (1.257∼1.920); dominant, HR (95% CI) = 2.207 (1.572∼3.100)]. Furthermore, we found that tumor number, tumor staging, metastasis and rs1800734 were associated with the overall survival of HCC patients by multivariate COX regression analysis. No significant difference was found between the other three MLH1 polymorphisms with HCC risk and prognosis. Our study suggests MLH1 SNP, rs1800734 as a new predictor for poor prognosis of HCC patients.

  12. Cardiac auscultation poorly predicts the presence of valvular heart disease in asymptomatic primary care patients.

    Science.gov (United States)

    Gardezi, Syed K M; Myerson, Saul G; Chambers, John; Coffey, Sean; d'Arcy, Joanna; Hobbs, F D Richard; Holt, Jonathan; Kennedy, Andrew; Loudon, Margaret; Prendergast, Anne; Prothero, Anthony; Wilson, Joanna; Prendergast, Bernard D

    2018-05-24

    Cardiac auscultation is a key clinical skill, particularly for the diagnosis of valvular heart disease (VHD). However, its utility has declined due to the widespread availability of echocardiography and diminishing emphasis on the importance of clinical examination. We aim to determine the contemporary accuracy of auscultation for diagnosing VHD in primary care. Cardiac auscultation was undertaken by one of two experienced general practitioners (primary care/family doctors) in a subset of 251 asymptomatic participants aged >65 years undergoing echocardiography within a large community-based screening study of subjects with no known VHD. Investigators were blinded to the echocardiographic findings. Newly detected VHD was classified as mild (mild regurgitation of any valve or aortic sclerosis) or significant (at least moderate regurgitation or mild stenosis of any valve). Newly identified VHD was common, with mild disease in 170/251 participants (68%) and significant disease in 36/251 (14%). The sensitivity of auscultation was low for the diagnosis of mild VHD (32%) but slightly higher for significant VHD (44%), with specificities of 67% and 69%, respectively. Likelihood ratios were not statistically significant for the diagnosis of either mild or significant VHD in the overall cohort, but showed possible value for auscultation in non-overweight subjects (body mass index auscultation has limited accuracy for the detection of VHD in asymptomatic patients and is a poor diagnostic screening tool in primary care, particularly for overweight subjects. Ensuring easy access to echocardiography in patients with symptoms suggesting VHD is likely to represent a better diagnostic strategy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. Early-Onset Invasive Candidiasis in Extremely Low Birth Weight Infants: Perinatal Acquisition Predicts Poor Outcome.

    Science.gov (United States)

    Barton, Michelle; Shen, Alex; O'Brien, Karel; Robinson, Joan L; Davies, H Dele; Simpson, Kim; Asztalos, Elizabeth; Langley, Joanne; Le Saux, Nicole; Sauve, Reginald; Synnes, Anne; Tan, Ben; de Repentigny, Louis; Rubin, Earl; Hui, Chuck; Kovacs, Lajos; Yau, Yvonne C W; Richardson, Susan E

    2017-04-01

    Neonatal invasive candidiasis (IC) presenting in the first week of life is less common and less well described than later-onset IC. Risk factors, clinical features, and disease outcomes have not been studied in early-onset disease (EOD, ≤7 days) or compared to late-onset disease (LOD, >7 days). All extremely low birth weight (ELBW, candidiasis enrolled from 2001 to 2003 were included in this study. Factors associated with occurrence and outcome of EOD in ELBW infants were determined. Forty-five ELBW infants and their 84 matched controls were included. Fourteen (31%) ELBW infants had EOD. Birth weight <750 g, gestation <25 weeks, chorioamnionitis, and vaginal delivery were all strongly associated with EOD. Infection with Candida albicans, disseminated disease, pneumonia, and cardiovascular disease were significantly more common in EOD than in LOD. The EOD case fatality rate (71%) was higher than in LOD (32%) or controls (15%) (P = .0001). The rate of neurodevelopmental impairment and mortality combined was similar in EOD (86%) and LOD (72%), but higher than in controls (32%; P = .007). ELBW infants with EOD have a very poor prognosis compared to those with LOD. The role of perinatal transmission in EOD is supported by its association with chorioamnionitis, vaginal delivery, and pneumonia. Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered for ELBW infants delivered vaginally who have pneumonia and whose mothers have chorioamnionitis or an intrauterine foreign body. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  14. Poor response to antidepressants predicts new suicidal ideas and behavior in depressed outpatients.

    Science.gov (United States)

    Courtet, Philippe; Jaussent, Isabelle; Lopez-Castroman, Jorge; Gorwood, Philip

    2014-10-01

    Only a few studies have investigated the factors associated with suicidal behavior after antidepressant treatment onset in adults. We examined the specific predictors of de novo suicidal ideas or attempts among depressed patients in the community, including subjects potentially at risk of suicidal behaviors, who initiated a new antidepressant treatment. A large set of GPs and psychiatrists throughout France followed-up, for 6 weeks, 4357 outpatients for whom an antidepressant drug was prescribed. Dimensions related with antidepressant-induced suicidal events, such as depression, anxiety or hopelessness, were assessed longitudinally using univariate and multivariate approaches among subjects with treatment-emergent suicide ideation or attempts. New suicidal ideas were observed in 9% of patients with no suicidal ideation at baseline (n=81), while suicidal attempts were reported for 1.7% of the sample during the 6-week observation period (n=75). The onset of suicidal ideas and attempts was associated with the initial features of the patients (baseline level of anxiety, past history of suicide attempts and alcohol misuse) and the non-improvement of depression. Worsening of depressive symptoms during the follow-up increased the onset of new suicidal ideas (OR=5.67, pideas or attempts, the link between antidepressants and suicide risk might be more adequately explained by a poor response to antidepressant treatment rather than by a direct trigger-effect. This naturalistic study is limited by the use of non-structured diagnoses and self-report outcomes. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  15. Dysphagia risk, low muscle strength and poor cognition predict malnutrition risk in older adults athospital admission.

    Science.gov (United States)

    Chatindiara, Idah; Allen, Jacqueline; Popman, Amy; Patel, Darshan; Richter, Marilize; Kruger, Marlena; Wham, Carol

    2018-03-21

    Malnutrition in patients admitted to hospital may have detrimental effects on recovery and healing. Malnutrition is preceded by a state of malnutrition risk, yet malnutrition risk is often not detected during admission. The aim of the current study was to investigate the magnitude and potential predictors of malnutrition risk in older adults, at hospital admission. A cross-sectional was study conducted in 234 older adults (age ≥ 65 or ≥ 55 for Māori or Pacific ethnicity) at admission to hospital in Auckland, New Zealand. Assessment of malnutrition risk status was performed using the Mini Nutritional Assessment Short-Form (MNA®-SF), dysphagia risk by the Eating Assessment Tool (EAT-10), muscle strength by hand grip strength and cognitive status by the Montreal Cognitive Assessment (MoCA) tool. Among 234 participants, mean age 83.6 ± 7.6 years, 46.6% were identified as at malnutrition risk and 26.9% malnourished. After adjusting for age, gender and ethnicity, the study identified [prevalence ratio (95% confidence interval)] high dysphagia risk [EAT-10 score: 0.98 (0.97-0.99)], low body mass index [kg/m 2 : 1.02 (1.02-1.03)], low muscle strength [hand grip strength, kg: 1.01 (1.00-1.02)] and decline in cognition [MoCA score: 1.01 (1.00-1.02)] as significant predictors of malnutrition risk in older adults at hospital admission. Among older adults recently admitted to the hospital, almost three-quarters were malnourished or at malnutrition risk. As the majority (88%) of participants were admitted from the community, this illustrates the need for routine nutrition screening both at hospital admission and in community-dwelling older adults. Factors such as dysphagia, unintentional weight loss, decline in muscle strength, and poor cognition may indicate increased risk of malnutrition.

  16. Poor caregiver mental health predicts mortality of patients with neurodegenerative disease.

    Science.gov (United States)

    Lwi, Sandy J; Ford, Brett Q; Casey, James J; Miller, Bruce L; Levenson, Robert W

    2017-07-11

    Dementia and other neurodegenerative diseases cause profound declines in functioning; thus, many patients require caregivers for assistance with daily living. Patients differ greatly in how long they live after disease onset, with the nature and severity of the disease playing an important role. Caregiving can also be extremely stressful, and many caregivers experience declines in mental health. In this study, we investigated the role that caregiver mental health plays in patient mortality. In 176 patient-caregiver dyads, we found that worse caregiver mental health predicted greater patient mortality even when accounting for key risk factors in patients (i.e., diagnosis, age, sex, dementia severity, and patient mental health). These findings highlight the importance of caring for caregivers as well as patients when attempting to improve patients' lives.

  17. Disrupted rapid eye movement sleep predicts poor declarative memory performance in post-traumatic stress disorder.

    Science.gov (United States)

    Lipinska, Malgorzata; Timol, Ridwana; Kaminer, Debra; Thomas, Kevin G F

    2014-06-01

    Successful memory consolidation during sleep depends on healthy slow-wave and rapid eye movement sleep, and on successful transition across sleep stages. In post-traumatic stress disorder, sleep is disrupted and memory is impaired, but relations between these two variables in the psychiatric condition remain unexplored. We examined whether disrupted sleep, and consequent disrupted memory consolidation, is a mechanism underlying declarative memory deficits in post-traumatic stress disorder. We recruited three matched groups of participants: post-traumatic stress disorder (n = 16); trauma-exposed non-post-traumatic stress disorder (n = 15); and healthy control (n = 14). They completed memory tasks before and after 8 h of sleep. We measured sleep variables using sleep-adapted electroencephalography. Post-traumatic stress disorder-diagnosed participants experienced significantly less sleep efficiency and rapid eye movement sleep percentage, and experienced more awakenings and wake percentage in the second half of the night than did participants in the other two groups. After sleep, post-traumatic stress disorder-diagnosed participants retained significantly less information on a declarative memory task than controls. Rapid eye movement percentage, wake percentage and sleep efficiency correlated with retention of information over the night. Furthermore, lower rapid eye movement percentage predicted poorer retention in post-traumatic stress disorder-diagnosed individuals. Our results suggest that declarative memory consolidation is disrupted during sleep in post-traumatic stress disorder. These data are consistent with theories suggesting that sleep benefits memory consolidation via predictable neurobiological mechanisms, and that rapid eye movement disruption is more than a symptom of post-traumatic stress disorder. © 2014 European Sleep Research Society.

  18. Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma

    Science.gov (United States)

    Xu, Sen-Lin; Zeng, Dong-Zu; Dong, Wei-Guo; Ding, Yan-Qing; Rao, Jun; Duan, Jiang-Jie; Liu, Qing; Yang, Jing; Zhan, Na; Liu, Ying; Hu, Qi-Ping; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Yu, Shi-Cang; Bian, Xiu-Wu

    2014-01-01

    Purpose: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed as a candidate biomarker for colorectal carcinoma (CRC). However, the heterogeneity of its expression makes it difficult to predict the outcome of CRC. The aim of this study was to evaluate the diagnostic and prognostic value of this molecule in CRC. Methods and Results: In this study, we examined ALDH1A1 expression by immunohistochemistry including 406 cases of primary CRC with corresponding adjacent mucosa, with confirmation of real-time PCR and Western blotting. We found that the expression patterns of ALDH1A1 were heterogeneous in the CRC and corresponding adjacent tissues. We defined the ratio of ALDH1A1 level in adjacent mucosa to that in tumor tissues as RA/C and found that the capabilities of tumor invasion and metastasis in the tumors with RA/C < 1 were significantly higher than those with RA/C ≥ 1. Follow-up data showed the worse prognoses in the CRC patients with RA/C < 1. For understanding the underlying mechanism, the localization of β-catenin was detected in the CRC tissues with different patterns of ALDH1A1 expression from 221 patients and β-catenin was found preferentially expressed in cell nuclei of the tumors with RA/C < 1 and ALDH1A1high expression of HT29 cell line, indicating that nuclear translocation of β-catenin might contribute to the increased potentials of invasion and metastasis. Conclusion: Our results indicate that RA/C is a novel biomarker to reflect the distinct expression patterns of ALDH1A1 for predicting metastasis and prognosis of CRC. PMID:25031716

  19. Predictive factors for lymph node metastasis in poorly differentiated early gastric cancer and their impact on the surgical strategy

    Science.gov (United States)

    Li, Hua; Lu, Ping; Lu, Yang; Liu, Cai-Gang; Xu, Hui-Mian; Wang, Shu-Bao; Chen, Jun-Qing

    2008-01-01

    AIM: To identify the predictive clinicopathological factors for lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC) and to further expand the possibility of using endoscopic mucosal resection (EMR) for the treatment of poorly differentiated EGC. METHODS: Data were collected from 85 poorly-differentiated EGC patients who were surgically treated. Association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. RESULTS: Univariate analysis showed that tumor size (OR = 5.814, 95% CI = 1.050 - 32.172, P = 0.044), depth of invasion (OR = 10.763, 95% CI = 1.259 - 92.026, P = 0.030) and lymphatic vessel involvement (OR = 61.697, 95% CI = 2.144 - 175.485, P = 0.007) were the significant and independent risk factors for LNM. The LNM rate was 5.4%, 42.9% and 50%, respectively, in poorly differentiated EGC patients with one, two and three of the risk factors, respectively. No LNM was found in 25 patients without the three risk factors. Forty-four lymph nodes were found to have metastasis, 29 (65.9%) and 15 (34.1%) of the lymph nodes involved were within N1 and beyond N1, respectively, in 12 patients with LNM. CONCLUSION: Endoscopic mucosal resection alone may be sufficient to treat poorly differentiated intramucosal EGC (≤ 2.0 cm in diameter) with no histologically-confirmed lymphatic vessel involvement. When lymphatic vessels are involved, lymph node dissection beyond limited (D1) dissection or D1+ lymph node dissection should be performed depending on the tumor location. PMID:18636670

  20. Persistent Dysphagia After Induction Chemotherapy in Patients with Esophageal Adenocarcinoma Predicts Poor Post-Operative Outcomes.

    Science.gov (United States)

    McNamara, Michael J; Adelstein, David J; Allende, Daniela S; Bodmann, Joanna W; Ives, Denise I; Murthy, Sudish C; Raymond, Daniel; Raja, Siva; Rodriguez, Cristina P; Sohal, Davendra; Stephans, Kevin L; Videtic, Gregory M M; Rybicki, Lisa A

    2017-06-01

    Preoperative therapy is frequently employed in the management of esophageal adenocarcinoma. However, many patients are found to have advanced pathologic stage and have poor outcomes. A prognostic factor which identifies this patient population before surgery would be desirable, as alternative treatment strategies may be warranted. Between 2/08 and 1/12, 60 evaluable patients with locally advanced esophageal adenocarcinoma enrolled in single-arm phase II trial of induction chemotherapy, surgery, and post-operative adjuvant chemo-radiotherapy (CRT). A clinical stage of T3, N1, or M1a (AJCC 6th) was required for eligibility. Induction chemotherapy with epirubicin 50 mg/m 2 d1, oxaliplatin 130 mg/m 2 d1, and fluorouracil 200 mg/m 2 /day continuous infusion for 3 weeks, was given every 21 days for 3 cycles and was followed by surgical resection. Adjuvant CRT consisted of 50-55 Gy @ 1.8-2.0 Gy/day and 2 cycles of cisplatin (20 mg/m 2 /day) and fluorouracil (1000 mg/m 2 /day) given as 96-h infusions during weeks 1 and 4 of radiotherapy. Dysphagia was assessed at baseline and after induction chemotherapy. Persistent dysphagia was associated with worse distant metastatic control [HR 3.48 (1.43-8.43), p = 0.006], recurrence free survival [HR 3.04 (1.34-6.92), p = 0.008], and overall survival [HR 3.31 (1.43-7.66), p = 0.005]. Persistent dysphagia was associated with more advanced pathologic T descriptor (pT) (p = 0.048) and N descriptor (pN) (p = 0.002), a greater median number of involved lymph nodes (3 v 1, p = 0.003), and greater residual tumor viability (p = 0.05). No patients with persistent dysphagia had pT0-T2 or pN0 disease. Persistent dysphagia after induction chemotherapy is associated with more advanced pathologic stage and inferior outcomes.

  1. Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

    International Nuclear Information System (INIS)

    Sun, Fei; Ding, Wen; He, Jie-Hua; Wang, Xiao-Jing; Ma, Ze-Biao; Li, Yan-Fang

    2015-01-01

    factor for survival in epithelial ovarian cancer patients. SLP-2 mRNA and proteins were overexpressed in epithelial ovarian cancer tissues. SLP-2 protein overexpression was associated with advanced stage disease. Patients with higher SLP-2 protein expression had shorter progress free survival and poor overall survival times. Thus, SLP-2 protein expression was an independent prognostic factor for patients with epithelial ovarian cancer

  2. Hippo pathway phylogenetics predicts monoubiquitylation of Salvador and Merlin/Nf2.

    Directory of Open Access Journals (Sweden)

    Robert G Wisotzkey

    Full Text Available Recently we employed phylogenetics to predict that the cellular interpretation of TGF-β signals is modulated by monoubiquitylation cycles affecting the Smad4 signal transducer/tumor suppressor. This prediction was subsequently validated by experiments in flies, frogs and mammalian cells. Here we apply a phylogenetic approach to the Hippo pathway and predict that two of its signal transducers, Salvador and Merlin/Nf2 (also a tumor suppressor are regulated by monoubiquitylation. This regulatory mechanism does not lead to protein degradation but instead serves as a highly efficient "off/on" switch when the protein is subsequently deubiquitylated. Overall, our study shows that the creative application of phylogenetics can predict new roles for pathway components and new mechanisms for regulating intercellular signaling pathways.

  3. Mycorrhizal phosphate uptake pathway in maize: Vital for growth and cob development on nutrient poor agricultural and greenhouse soils

    Directory of Open Access Journals (Sweden)

    Martin eWillmann

    2013-12-01

    Full Text Available Arbuscular mycorrhizal fungi (AMF form a mutually beneficial symbiosis with plant roots providing predominantly phosphorus in the form of orthophosphate (Pi in exchange for plant carbohydrates on low P soils. The goal of this work was to generate molecular-genetic evidence in support of a major impact of the mycorrhizal Pi uptake (MPU pathway on the productivity of the major crop plant maize under field and controlled conditions. Here we show, that a loss-of-function mutation in the mycorrhiza-specific Pi transporter gene Pht1;6 correlates with a dramatic reduction of above-ground biomass and cob production in agro-ecosystems with low P soils. In parallel mutant pht1;6 plants exhibited an altered fingerprint of chemical elements in shoots dependent on soil P availability. In controlled environments mycorrhiza development was impaired in mutant plants when grown alone. The presence of neighbouring mycorrhizal nurse plants enhanced the reduced mycorrhiza formation in pht1;6 roots. Uptake of 33P-labelled orthophosphate via the MPU pathway was strongly impaired in colonized mutant plants. Moreover, repression of the MPU pathway resulted in a redirection of Pi to neighbouring plants. In line with previous results, our data highlight the relevance of the MPU pathway in Pi allocation within plant communities and in particular the role of Pht1;6 for the establishment of symbiotic Pi uptake and for maize productivity and nutritional value in low-input agricultural systems. In a first attempt to identify cellular pathways which are affected by Pht1;6 activity, gene expression profiling via RNA-Seq was performed and revealed a set of maize genes involved in cellular signalling which exhibited differential regulation in mycorrhizal pht1;6 and control plants. The RNA data provided support for the hypothesis that fungal supply of Pi and/or Pi transport across Pht1;6 affects cell wall biosynthesis and hormone metabolism in colonized root cells.

  4. Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients

    International Nuclear Information System (INIS)

    Noh, Sang Jae; Chung, Myoung Ja; Moon, Woo Sung; Kang, Myoung Jae; Jang, Kyu Yun; Bae, Jun Sang; Jamiyandorj, Urangoo; Park, Ho Sung; Kwon, Keun Sang; Jung, Sung Hoo; Youn, Hyun Jo; Lee, Ho; Park, Byung-Hyun

    2013-01-01

    Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown. We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma. Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time. This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients

  5. Foxp3 overexpression in tumor cells predicts poor survival in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Song, Jing-Jing; Zhao, Si-Jia; Fang, Juan; Ma, Da; Liu, Xiang-Qi; Chen, Xiao-Bing; Wang, Yun; Cheng, Bin; Wang, Zhi

    2016-01-01

    Forkhead Box P3 (Foxp3) is a regulatory T cells marker, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of Foxp3 expression with clinicopathological parameters and prognosis in oral squamous cell carcinoma (OSCC). Foxp3 expression was examined using immunohistochemistry (IHC) in paraffin-embedded tissue samples from 273 OSCC patients. Statistical analysis was performed to evaluate the associations between Foxp3 expression, the clinicopathologic characteristics and prognostic factors in OSCC. Foxp3 protein expression was significantly associated with lymph node metastasis (P <0.01). Both univariate and multivariate analyses revealed that Foxp3 was an independent factor for both 5 years overall survival (OS) and relapse-free survival (RFS) (both P <0.01). Patients with Foxp3 overexpression had shorter OS and RFS. Our results determined that elevated Foxp3 protein expression was a predictive factor of outcome in OSCC and could act as a promising therapeutic target

  6. Predicting protein folding pathways at the mesoscopic level based on native interactions between secondary structure elements

    Directory of Open Access Journals (Sweden)

    Sze Sing-Hoi

    2008-07-01

    Full Text Available Abstract Background Since experimental determination of protein folding pathways remains difficult, computational techniques are often used to simulate protein folding. Most current techniques to predict protein folding pathways are computationally intensive and are suitable only for small proteins. Results By assuming that the native structure of a protein is known and representing each intermediate conformation as a collection of fully folded structures in which each of them contains a set of interacting secondary structure elements, we show that it is possible to significantly reduce the conformation space while still being able to predict the most energetically favorable folding pathway of large proteins with hundreds of residues at the mesoscopic level, including the pig muscle phosphoglycerate kinase with 416 residues. The model is detailed enough to distinguish between different folding pathways of structurally very similar proteins, including the streptococcal protein G and the peptostreptococcal protein L. The model is also able to recognize the differences between the folding pathways of protein G and its two structurally similar variants NuG1 and NuG2, which are even harder to distinguish. We show that this strategy can produce accurate predictions on many other proteins with experimentally determined intermediate folding states. Conclusion Our technique is efficient enough to predict folding pathways for both large and small proteins at the mesoscopic level. Such a strategy is often the only feasible choice for large proteins. A software program implementing this strategy (SSFold is available at http://faculty.cs.tamu.edu/shsze/ssfold.

  7. An ensemble method to predict target genes and pathways in uveal melanoma

    Directory of Open Access Journals (Sweden)

    Wei Chao

    2018-04-01

    Full Text Available This work proposes to predict target genes and pathways for uveal melanoma (UM based on an ensemble method and pathway analyses. Methods: The ensemble method integrated a correlation method (Pearson correlation coefficient, PCC, a causal inference method (IDA and a regression method (Lasso utilizing the Borda count election method. Subsequently, to validate the performance of PIL method, comparisons between confirmed database and predicted miRNA targets were performed. Ultimately, pathway enrichment analysis was conducted on target genes in top 1000 miRNA-mRNA interactions to identify target pathways for UM patients. Results: Thirty eight of the predicted interactions were matched with the confirmed interactions, indicating that the ensemble method was a suitable and feasible approach to predict miRNA targets. We obtained 50 seed miRNA-mRNA interactions of UM patients and extracted target genes from these interactions, such as ASPG, BSDC1 and C4BP. The 601 target genes in top 1,000 miRNA-mRNA interactions were enriched in 12 target pathways, of which Phototransduction was the most significant one. Conclusion: The target genes and pathways might provide a new way to reveal the molecular mechanism of UM and give hand for target treatments and preventions of this malignant tumor.

  8. High ASMA+ Fibroblasts and Low Cytoplasmic HMGB1+ Breast Cancer Cells Predict Poor Prognosis.

    Science.gov (United States)

    Amornsupak, Kamolporn; Jamjuntra, Pranisa; Warnnissorn, Malee; O-Charoenrat, Pornchai; Sa-Nguanraksa, Doonyapat; Thuwajit, Peti; Eccles, Suzanne A; Thuwajit, Chanitra

    2017-10-01

    The influence of cancer-associated fibroblasts (CAFs) and high mobility group box 1 (HMGB1) has been recognized in several cancers, although their roles in breast cancer are unclear. The present study aimed to determine the levels and prognostic significance of α-smooth muscle actin-positive (ASMA + ) CAFs, plus HMGB1 and receptor for advanced glycation end products (RAGE) in cancer cells. A total of 127 breast samples, including 96 malignant and 31 benign, were examined for ASMA, HMGB1, and RAGE by immunohistochemistry. The χ 2 test and Fisher's exact test were used to test the association of each protein with clinicopathologic parameters. The Kaplan-Meier method or log-rank test and Cox regression were used for survival analysis. ASMA + fibroblast infiltration was significantly increased in the tumor stroma compared with that in benign breast tissue. The levels of cytoplasmic HMGB1 and RAGE were significantly greater in the breast cancer tissue than in the benign breast tissues. High ASMA expression correlated significantly with large tumor size, clinical stage III-IV, and angiolymphatic and perinodal invasion. In contrast, increased cytoplasmic HMGB1 correlated significantly with small tumor size, pT stage, early clinical stage, luminal subtype (but not triple-negative subtype), and estrogen receptor and progesterone receptor expression. The levels of ASMA (hazard ratio, 14.162; P = .010) and tumor cytoplasmic HMGB1 (hazard ratio, 0.221; P = .005) could serve as independent prognostic markers for metastatic relapse in breast cancer patients. The ASMA-high/HMGB1-low profile provided the most reliable prediction of metastatic relapse. We present for the first time, to the best of our knowledge, the potential clinical implications of the combined assessment of ASMA + fibroblasts and cytoplasmic HMGB1 in breast cancer. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Poor Positive Predictive Value of Lyme Disease Serologic Testing in an Area of Low Disease Incidence.

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    Lantos, Paul M; Branda, John A; Boggan, Joel C; Chudgar, Saumil M; Wilson, Elizabeth A; Ruffin, Felicia; Fowler, Vance; Auwaerter, Paul G; Nigrovic, Lise E

    2015-11-01

    Lyme disease is diagnosed by 2-tiered serologic testing in patients with a compatible clinical illness, but the significance of positive test results in low-prevalence regions has not been investigated. We reviewed the medical records of patients who tested positive for Lyme disease with standardized 2-tiered serologic testing between 2005 and 2010 at a single hospital system in a region with little endemic Lyme disease. Based on clinical findings, we calculated the positive predictive value of Lyme disease serology. Next, we reviewed the outcome of serologic testing in patients with select clinical syndromes compatible with disseminated Lyme disease (arthritis, cranial neuropathy, or meningitis). During the 6-year study period 4723 patients were tested for Lyme disease, but only 76 (1.6%) had positive results by established laboratory criteria. Among 70 seropositive patients whose medical records were available for review, 12 (17%; 95% confidence interval, 9%-28%) were found to have Lyme disease (6 with documented travel to endemic regions). During the same time period, 297 patients with a clinical illness compatible with disseminated Lyme disease underwent 2-tiered serologic testing. Six of them (2%; 95% confidence interval, 0.7%-4.3%) were seropositive, 3 with documented travel and 1 who had an alternative diagnosis that explained the clinical findings. In this low-prevalence cohort, fewer than 20% of positive Lyme disease tests are obtained from patients with clinically likely Lyme disease. Positive Lyme disease test results may have little diagnostic value in this setting. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. ITGBL1 promotes migration, invasion and predicts a poor prognosis in colorectal cancer.

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    Qiu, Xiao; Feng, Jue-Rong; Qiu, Jun; Liu, Lan; Xie, Yang; Zhang, Yu-Peng; Liu, Jing; Zhao, Qiu

    2018-05-14

    Colorectal cancer (CRC) is one of the most common malignancies worldwide; its progression and prognosis are associated with oncogenes. The present study aimed to identify differentially expressed genes (DEGs) and explore the role and potential mechanism of integrin subunit β like 1 (ITGBL1) in CRC. The microarray dataset GSE41258 was used to screen DEGs involved in CRC. Survival analysis was performed to predict the prognosis of CRC patients. To validate ITGBL1 expression, immunohistochemistry, quantitative real-time PCR and western blotting were performed in CRC tissues and cells. Subsequently, the effects of ITGBL1 were evaluated through colony formation, cell proliferation, migration and invasion assays. Finally, we took advantage of Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) to explore potential function and mechanism of ITGBL1 in CRC. In our study, 182 primary CRC tissues and 54 normal colon tissues were contained in GSE41258 dataset. A total of 318 DEGs were screened, among which ITGBL1 was found to be significantly up-regulated in CRC, and its high expression was associated with shortened survival of CRC patients. Moreover, knockdown of ITGBL1 promoted CRC cell proliferation, migration and invasion. Finally, GO analysis revealed that ITGBL1 was associated with cell adhesion. GSEA indicated that ITGBL1 was enriched in ECM receptor interaction and focal adhesion. In conclusion, a novel oncogene ITGBL1 was identified and demonstrated to be associated with the progression and prognosis of CRC, which might be a potential therapeutic target and prognostic biomarker for CRC patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Low expression of c-Myc protein predicts poor outcomes in patients with hepatocellular carcinoma after resection.

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    Ji, Fei; Zhang, Zhi-Heng; Zhang, Yi; Shen, Shun-Li; Cao, Qing-Hua; Zhang, Long-Juan; Li, Shao-Qiang; Peng, Bao-Gang; Liang, Li-Jian; Hua, Yun-Peng

    2018-04-24

    Embryonic Liver Fodrin (ELF) is an adaptor protein of transforming growth factor (TGF-β) signaling cascade. Disruption of ELF results in mislocalization of Smad3 and Smad4, leading to compromised TGF-β signaling. c-Myc is an important oncogenic transcription factor, and the disruption of TGF-β signaling promotes c-Myc-induced hepatocellular carcinoma (HCC) carcinogenesis. However, the prognostic significance of c-Myc in HCC is less understood METHODS: The expression of c-Myc protein and mRNA were measured by immunohistochemistry (IHC) and qRT- PCR, respectively. IHC was performed to detect TGF-β1 and ELF expression in HCC tissues. Their relationship with clinicopathological factors and overall survival (OS) and disease free survival (DFS) were examined. The expression of c-Myc protein and mRNA in HCC tissues were significantly higher in HCC area than those in normal liver tissues. However, the expression were low compared with those adjacent to HCC area. c-Myc protein was independently predictive of DFS and OS, and it was negatively correlated with tumor size (P = 0.031), tumor number (P = 0.038), and recurrence (P = 0.001). Low c-Myc expression was associated with short-term recurrence and poor prognosis. The predictive value of c-Myc combined with TGF-β1 or/and ELF was higher than that of any other single marker. Low c-Myc, high TGF-β1 or/and low ELF expression was associated with the worst DFS and OS. Low expression of c-Myc protein predicts poor outcomes in patients with HCC with hepatectomy. The combination of the expression of c-Myc, TGF-β1, and ELF can be used to accurately predict outcomes of patients with HCC.

  12. Poor attention rather than hyperactivity/impulsivity predicts academic achievement in very preterm and full-term adolescents.

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    Jaekel, J; Wolke, D; Bartmann, P

    2013-01-01

    Very preterm (VP) children are at particular risk for attention deficit/hyperactivity disorder (ADHD) of the inattentive subtype. It is unknown whether the neurodevelopmental pathways to academic underachievement are the same as in the general population. This study investigated whether middle childhood attention or hyperactivity/impulsivity problems are better predictors of VP adolescents' academic achievement. In a geographically defined prospective whole-population sample of VP (full-term control children (n = 286) in South Germany, ADHD subtypes were assessed at 6 years 3 months and 8 years 5 months using multiple data sources. Academic achievement was assessed at 13 years of age. Compared with full-term controls, VLBW/VP children were at higher risk for ADHD inattentive subtype [6 years 3 months: odds ratio (OR) 2.8, p attention measures predicted academic achievement in VLBW/VP and also full-term adolescents, whereas hyperactive/impulsive behaviour did not. Attention is an important prerequisite for learning and predicts long-term academic underachievement. As ADHD inattentive subtype and cognitive impairments are frequent in VLBW/VP children, their study may help to identify the neurofunctional pathways from early brain development and dysfunction to attention problems and academic underachievement.

  13. Predictive Effects of Good Self-Control and Poor Regulation on Alcohol-Related Outcomes: Do Protective Behavioral Strategies Mediate?

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    Pearson, Matthew R.; Kite, Benjamin A.; Henson, James M.

    2016-01-01

    In the present study, we examined whether use of protective behavioral strategies mediated the relationship between self-control constructs and alcohol-related outcomes. According to the two-mode model of self-control, good self-control (planfulness; measured with Future Time Perspective, Problem Solving, and Self-Reinforcement) and poor regulation (impulsivity; measured with Present Time Perspective, Poor Delay of Gratification, Distractibility) are theorized to be relatively independent constructs rather than opposite ends of a single continuum. The analytic sample consisted of 278 college student drinkers (68% women) who responded to a battery of surveys at a single time point. Using a structural equation model based on the two-mode model of self-control, we found that good self-control predicted increased use of three types of protective behavioral strategies (Manner of Drinking, Limiting/Stopping Drinking, and Serious Harm Reduction). Poor regulation was unrelated to use of protective behavioral strategies, but had direct effects on alcohol use and alcohol problems. Further, protective behavioral strategies mediated the relationship between good self-control and alcohol use. The clinical implications of these findings are discussed. PMID:22663345

  14. Human papillomavirus 16 infection predicts poor outcome in patients with esophageal squamous cell carcinoma

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    Xi R

    2015-03-01

    Full Text Available Ruxing Xi,1 Xiaozhi Zhang,1 Xin Chen,1 Shupei Pan,1 Beina Hui,1 Li Zhang,1 Shenbo Fu,1 Xiaolong Li,2 Xuanwei Zhang,1 Tuotuo Gong,1 Jia Guo,1 Shaomin Che1 1Department of Radiotherapy, The First Affiliated Hospital of Xi’an Jiao Tong University, 2Department of Radiotherapy, The People’s Liberation Army 323 Hospital, Xi’an, People’s Republic of China Background: Previous studies indicate that human papillomavirus 16 (HPV16 infection plays a pivotal role in the etiology of esophageal squamous cell carcinoma (ESCC. We aim to detect the influence of HPV16 infection on ESCC patient prognosis. Patients and methods: Immunohistochemical staining for HPV16 E6 oncoprotein, the low-affinity p75 neurotrophin receptor (p75NTR, and phosphatidylinositol 3-kinase (PI3K was performed on 103 archived surgical specimens from patients with ESCC and 54 control samples from patients with benign esophageal tumor or inflammatory lesions. All patients were from the Shaan Xi Province, People’s Republic of China. Results: HPV16 E6 expression was significantly higher in the ESCC group (P<0.05. HPV16 E6 expression was significantly higher in men than in women (P<0.05. p75NTR expression was higher in those aged >56 years (P<0.05. PI3K expression was higher in those with a more advanced histopathological grade (P<0.05. There was a positive correlation between HPV16 E6 and p75NTR expression (r=0.547, P<0.001 and between p75NTR and PI3K expression (r=0.364, P<0.001. In 100 evaluable patients, the 5-year overall survival (OS rate was 11%. In patients with ESCC, HPV16 E6 and PI3K expression were negatively correlated with the 3-year OS (P<0.05, 5-year OS (P<0.05, and progression-free survival (P<0.05. Conclusion: HPV16 infection likely contributes to the etiology of ESCC patients in Shaan Xi, People’s Republic of China. HPV16 infection status and PI3K expression levels could be useful for predicting prognosis in patients with ESCC. Keywords: low-affinity p75

  15. A CLDN1-negative phenotype predicts poor prognosis in triple-negative breast cancer.

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    Fei Ma

    Full Text Available INTRODUCTION: Triple-negative breast cancer (TNBC is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs. MATERIALS AND METHODS: The surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed. RESULTS: Positive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P = 0.014. The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P = 0.003. Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS in both lymph node positive (LN+ and negative (LN- cases (both P<0.001. Similarly it was also associated with shorter overall survival (OS(P = 0.003 in LN+ cases; P = 0.018 in LN- cases. In the LN+ subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P = 0.008. Multivariate analysis revealed that negative CLDN1 expression was an independent prognostic factor for high risk of both recurrence and death (HR 5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P = 0.002. However, neither CLDN4 nor CLDN7 expression was associated with survival. CONCLUSION: In TNBC, the CLDN1-negative phenotype predicts a high risk of recurrence and death. The absence of CLDN1 expression is strongly suggested to be an independent adverse prognostic factor

  16. Loss of secreted frizzled-related protein 4 correlates with an aggressive phenotype and predicts poor outcome in ovarian cancer patients.

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    Francis Jacob

    Full Text Available BACKGROUND: Activation of the Wnt signaling pathway is implicated in aberrant cellular proliferation in various cancers. In 40% of endometrioid ovarian cancers, constitutive activation of the pathway is due to oncogenic mutations in β-catenin or other inactivating mutations in key negative regulators. Secreted frizzled-related protein 4 (SFRP4 has been proposed to have inhibitory activity through binding and sequestering Wnt ligands. METHODOLOGY/PRINCIPAL FINDINGS: We performed RT-qPCR and Western-blotting in primary cultures and ovarian cell lines for SFRP4 and its key downstream regulators activated β-catenin, β-catenin and GSK3β. SFRP4 was then examined by immunohistochemistry in a cohort of 721 patients and due to its proposed secretory function, in plasma, presenting the first ELISA for SFRP4. SFRP4 was most highly expressed in tubal epithelium and decreased with malignant transformation, both on RNA and on protein level, where it was even more profound in the membrane fraction (p<0.0001. SFRP4 was expressed on the protein level in all histotypes of ovarian cancer but was decreased from borderline tumors to cancers and with loss of cellular differentiation. Loss of membrane expression was an independent predictor of poor survival in ovarian cancer patients (p = 0.02 unadjusted; p = 0.089 adjusted, which increased the risk of a patient to die from this disease by the factor 1.8. CONCLUSIONS/SIGNIFICANCE: Our results support a role for SFRP4 as a tumor suppressor gene in ovarian cancers via inhibition of the Wnt signaling pathway. This has not only predictive implications but could also facilitate a therapeutic role using epigenetic targets.

  17. High urinary albumin/creatinine ratio at admission predicts poor functional outcome in patients with acute ischaemic stroke.

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    Watanabe, Yoko; Suda, Satoshi; Kanamaru, Takuya; Katsumata, Toshiya; Okubo, Seiji; Kaneko, Tomohiro; Mii, Akiko; Sakai, Yukinao; Katayama, Yasuo; Kimura, Kazumi; Tsuruoka, Shuichi

    2017-03-01

    Albuminuria and a low estimated glomerular filtration rate (eGFR) are widely recognized indices of kidney dysfunction and have been linked to cardiovascular events, including stroke. We evaluated albuminuria, measured using the urinary albumin/creatinine ratio (UACR), and the eGFR in the acute phase of ischaemic stroke, and investigated the clinical characteristics of ischaemic stroke patients with and those without kidney dysfunction. The study included 422 consecutive patients admitted between June 2010 and May 2012. General blood and urine examinations were performed at admission. Kidney dysfunction was defined as a low eGFR (high albuminuria (≥30 mg/g creatinine), or both. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin scale (mRS) at discharge. A poor outcome was defined as a mRS score of 3-5 or death. The impacts of the eGFR and UACR on outcomes at discharge were evaluated using multiple logistic regression analysis. Kidney dysfunction was diagnosed in 278 of the 422 patients (65.9%). The eGFR was significantly lower and UACR was significantly higher in patients with a poor outcome than in those with a good outcome. In multivariate analyses performed after adjusting for confounding factors, UACR >31.2 mg/g creatinine (OR, 2.58; 95% CI, 1.52-4.43; P = 0.0005) was independently associated with a poor outcome, while a low eGFR was not associated. A high UACR at admission may predict a poor outcome at discharge in patients with acute ischaemic stroke. © 2016 Asian Pacific Society of Nephrology.

  18. Novel biomarkers in primary breast core biopsies to predict poor response to neoadjuvant chemotherapy and appearance of metastases.

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    Novell, Anna; Morales, Serafin; Valls, Joan; Panadés, Maria José; Salud, Antonieta; Iglesias, Edelmiro; Vilardell, Felip; Matias-Guiu, Xavier; Llombart-Cussac, Antonio

    2017-09-01

    Drug resistance has been one of the major obstacles limiting the success of cancer chemotherapy. In two thirds of breast cancer patients, large (>1cm) residual tumors are present after neoadjuvant chemotherapy (NCT). The residual tumor and involved nodes have been indicators of relapse and survival very important in breast cancer. The goal of this preliminary study was to assess the predictive significance of a panel of molecular biomarkers, related with the response to treatment or drug resistance to NCT, as determined on the diagnostic tumor. The expression of 22 proteins was examined using immunohistochemistry in tissue microarrays (TMA) from 115 patients of stage II-III breast cancer, treated with NCT. Among studied proteins, there are some that are anti-apoptotic, pro-proliferative, cancer stem cell markers and the Vitamin D Receptor. Other proteins are involved in the identification of molecular subtype, cell cycle regulation or DNA repair. Next, a predictive signature of poor response was generated from independent markers of predictive value. Tumors that expressed four or five conditions (biomarkers of chemoresistance with a determinated cutoff) were associated with a 9-fold increase in the chances of these patients of having a poor response to NCT. Additionally, we also found a worse prognostic signature, generated from independent markers of prognostic value. Tumors which expressed two or three conditions of worst prognostic, were associated with a 6-fold reduction in Distant Disease Free Survival. In conclusion, finding biomarkers of chemoresitance (ypTNM II-III) and metastases can become a stepping stone for future studies that will need to be assessed in a bigger scale.

  19. A Risk Prediction Model Based on Lymph-Node Metastasis in Poorly Differentiated-Type Intramucosal Gastric Cancer.

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    Jeung Hui Pyo

    Full Text Available Endoscopic submucosal dissection (ESD for undifferentiated type early gastric cancer is regarded as an investigational treatment. Few studies have tried to identify the risk factors that predict lymph-node metastasis (LNM in intramucosal poorly differentiated adenocarcinomas (PDC. This study was designed to develop a risk scoring system (RSS for predicting LNM in intramucosal PDC.From January 2002 to July 2015, patients diagnosed with mucosa-confined PDC, among those who underwent curative gastrectomy with lymph node dissection were reviewed. A risk model based on independent predicting factors of LNM was developed, and its performance was internally validated using a split sample approach.Overall, LNM was observed in 5.2% (61 of 1169 patients. Four risk factors [Female sex, tumor size ≥ 3.2 cm, muscularis mucosa (M3 invasion, and lymphatic-vascular involvement] were significantly associated with LNM, which were incorporated into the RSS. The area under the receiver operating characteristic curve for predicting LNM after internal validation was 0.69 [95% confidence interval (CI, 0.59-0.79]. A total score of 2 points corresponded to the optimal RSS threshold with a discrimination of 0.75 (95% CI 0.69-0.81. The LNM rates were 1.6% for low risk (<2 points and 8.9% for high-risk (≥2 points patients, with a negative predictive value of 98.6% (95% CI 0.98-1.00.A RSS could be useful in clinical practice to determine which patients with intramucosal PDC have low risk of LNM.

  20. Cytoplasmic Skp2 expression is associated with p-Akt1 and predicts poor prognosis in human breast carcinomas.

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    Jing Liu

    Full Text Available BACKGROUND: S-phase kinase protein 2 (Skp2, an oncogenic protein, is a key regulator in different cellular and molecular processes, through ubiquitin-proteasome degradation pathway. Increased levels of Skp2 are observed in various types of cancer and associated with poor prognosis. However, in human breast carcinomas, the underlying mechanism and prognostic significance of cytoplasmic Skp2 is still undefined. METHODS: To investigate the role of cytoplasmic Skp2 expression in human breast carcinomas, we immnohistochemically assessed cytoplasmic Skp2, p-Akt1, and p27 expression in 251 patients with invasive ductal carcinomas of the breast. Association of cytoplasmic Skp2 expression with p-Akt1 and p27 was analyzed as well as correspondence with other clinicopathological parameters. Disease-free survival and overall survival were determined based on the Kaplan-Meier method and Cox regression models. RESULTS: Cytoplasmic of Skp2 was detected in 165 out of 251 (65.7% patients. Cytoplasmic Skp2 expression was associated with larger tumor size, more advanced histological grade, and positive HER2 expression. Increased cytoplasmic Skp2 expression correlated with p-Akt1 expression, with 54.2% (51/94 of low p-Akt1-expressing breast carcinomas, but 72.6% (114/157 of high p-Akt1-expressing breast carcinomas exhibiting cytoplasmic Skp2 expression. Elevated cytoplasmic Skp2 expression with low p-Akt1 expression was associated with poor disease-free and overall survival (DFS and OS, and Cox regression models demonstrated that cytoplasmic Skp2 expression was an independent prognostic marker for invasive breast carcinomas. CONCLUSION: Cytoplasmic Skp2 expression is associated with aggressive prognostic factors, such as larger tumor size, and advanced histological grade of the breast cancers. Results demonstrate that combined cytoplasmic Skp2 and p-Akt1 expression may be prognostic for patients with invasive breast carcinomas, and cytoplasmic Skp2 may serve as a

  1. Differential Reliance on Lipid Metabolism as a Salvage Pathway Underlies Functional Differences of T Cell Subsets in Poor Nutrient Environments

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    Christopher Ecker

    2018-04-01

    Full Text Available Summary: T cells compete with malignant cells for limited nutrients within the solid tumor microenvironment. We found that effector memory CD4 T cells respond distinctly from other T cell subsets to limiting glucose and can maintain high levels of interferon-γ (IFN-γ production in a nutrient-poor environment. Unlike naive (TN or central memory T (TCM cells, effector memory T (TEM cells fail to upregulate fatty acid synthesis, oxidative phosphorylation, and reductive glutaminolysis in limiting glucose. Interference of fatty acid synthesis in naive T cells dramatically upregulates IFN-γ, while increasing exogenous lipids in media inhibits production of IFN-γ by all subsets, suggesting that relative ratio of fatty acid metabolism to glycolysis is a direct predictor of T cell effector activity. Together, these data suggest that effector memory T cells are programmed to have limited ability to synthesize and metabolize fatty acids, which allows them to maintain T cell function in nutrient-depleted microenvironments. : Ecker et al. distinguish unique metabolic and functional properties of naive and memory T cell subsets during glucose limitation. During glucose starvation, T cells begin to differentially rely on fatty acid synthesis and glutamine utilization to survive. Unexpectedly, reliance on fatty acid synthesis alters the ability to produce IFN-γ. Keywords: lipid droplets, IFN-γ, oxidative phosphorylation, reductive glutaminolysis, serum-free media, naive T cell, glycolysis, effector memory T cell, fatty acid synthesis

  2. Overexpression of GEFT, a Rho family guanine nucleotide exchange factor, predicts poor prognosis in patients with rhabdomyosarcoma.

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    Sun, Chao; Liu, Chunxia; Li, Shugang; Li, Hongan; Wang, Yuanyuan; Xie, Yuwen; Li, Bingcheng; Cui, Xiaobin; Chen, Yunzhao; Zhang, Wenjie; Li, Feng

    2014-01-01

    Rhabdomyosarcoma (RMS) is one of the most common soft-tissue sarcomas in children and adolescents with poor prognosis. Yet, there is lack of effective prognostic biomarkers for RMS. The present study, therefore, aimed to explore potential biomarkers for RMS based on our previous findings using array comparative genomic hybridization. We investigated guanine nucleotide exchange factor, GEFT, at expression level in 45 RMS patients and 36 normal striated muscle controls using immunohistochemistry using tissue microarrays. The expression rate of GEFT in RMS samples (42/45, 93.33%) was significantly higher (Prate of GEFT in RMS (31/45, 68.89%) was also significantly higher (P<0.05) than that in normal controls (0/36, 0.00%). Increased expression of GEFT correlated significantly with advanced disease stages (stages III/IV) (P=0.001), lymph node metastasis (P=0.019), and distant metastasis (P=0.004), respectively, in RMS patients. In addition, RMS patients having overexpressed GEFT experienced worse overall survival (OS) than those having low levels of GEFT (P=0.001). GEFT overexpression was determined to be an independent prognostic factor for poor OS in RMS patients (hazard ratio: 3.491, 95% confidence interval: 1.121-10.871, P=0.004). In conclusion, these observations provide the first evidence of GEFT overexpression in RMS and its correlations with disease aggressiveness and metastasis. These findings suggest that GEFT may serve as a promising biomarker predicting poor prognosis in RMS patients, thus implying its potential as a therapeutic target.

  3. Validation of a Dutch risk score predicting poor outcome in adults with bacterial meningitis in Vietnam and Malawi.

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    Ewout S Schut

    Full Text Available We have previously developed and validated a prognostic model to predict the risk for unfavorable outcome in Dutch adults with bacterial meningitis. The aim of the current study was to validate this model in adults with bacterial meningitis from two developing countries, Vietnam and Malawi. Demographic and clinical characteristics of Vietnamese (n = 426, Malawian patients (n = 465 differed substantially from those of Dutch patients (n = 696. The Dutch model underestimated the risk of poor outcome in both Malawi and Vietnam. The discrimination of the original model (c-statistic [c] 0.84; 95% confidence interval 0.81 to 0.86 fell considerably when re-estimated in the Vietnam cohort (c = 0.70 or in the Malawian cohort (c = 0.68. Our validation study shows that new prognostic models have to be developed for these countries in a sufficiently large series of unselected patients.

  4. Predictive value of cardiac magnetic resonance imaging-derived myocardial strain for poor outcomes in patients with acute myocarditis

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    Lee, Ji Won; Jeong, Yeon Joo; Lee, Gee Won; Lee, Nam Kyung; Lee, Hye Won; Kim, Jin You [Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of); Choi, Bum Sung; Choo, Ki Seok [Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2017-08-01

    To evaluate the utility of cardiovascular magnetic resonance (CMR)-derived myocardial strain measurement for the prediction of poor outcomes in patients with acute myocarditis We retrospectively analyzed data from 37 patients with acute myocarditis who underwent CMR. Left ventricular (LV) size, LV mass index, ejection fraction and presence of myocardial late gadolinium enhancement (LGE) were analyzed. LV circumferential strain (EccSAX), radial strain (ErrSAX) from mid-ventricular level short-axis cine views and LV longitudinal strain (EllLV), radial strain (ErrLax) measurements from 2-chamber long-axis views were obtained. In total, 31 of 37 patients (83.8%) underwent follow-up echocardiography. The primary outcome was major adverse cardiovascular event (MACE). Incomplete LV functional recovery was a secondary outcome. During an average follow-up of 41 months, 11 of 37 patients (29.7%) experienced MACE. Multivariable Cox proportional hazard regression analysis, which included LV mass index, LV ejection fraction, the presence of LGE, EccSAX, ErrSAX, EllLV, and ErrLax values, indicated that the presence of LGE (hazard ratio, 42.88; p = 0.014), together with ErrLax (hazard ratio, 0.77 per 1%, p = 0.004), was a significant predictor of MACE. Kaplan-Meier analysis demonstrated worse outcomes in patient with LGE and an ErrLax value ≤ 9.48%. Multivariable backward regression analysis revealed that ErrLax values were the only significant predictors of LV functional recovery (hazard ratio, 0.54 per 1%; p = 0.042). CMR-derived ErrLax values can predict poor outcomes, both MACE and incomplete LV functional recovery, in patients with acute myocarditis, while LGE is only a predictor of MACE.

  5. Hidden Hearing Loss and Computational Models of the Auditory Pathway: Predicting Speech Intelligibility Decline

    Science.gov (United States)

    2016-11-28

    Title: Hidden Hearing Loss and Computational Models of the Auditory Pathway: Predicting Speech Intelligibility Decline Christopher J. Smalt...representation of speech intelligibility in noise. The auditory-periphery model of Zilany et al. (JASA 2009,2014) is used to make predictions of...auditory nerve (AN) responses to speech stimuli under a variety of difficult listening conditions. The resulting cochlear neurogram, a spectrogram

  6. Integration of Pathway Knowledge and Dynamic Bayesian Networks for the Prediction of Oral Cancer Recurrence.

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    Kourou, Konstantina; Papaloukas, Costas; Fotiadis, Dimitrios I

    2017-03-01

    Oral squamous cell carcinoma has been characterized as a complex disease which involves dynamic genomic changes at the molecular level. These changes indicate the worth to explore the interactions of the molecules and especially of differentially expressed genes that contribute to cancer progression. Moreover, based on this knowledge the identification of differentially expressed genes and related molecular pathways is of great importance. In the present study, we exploit differentially expressed genes in order to further perform pathway enrichment analysis. According to our results we found significant pathways in which the disease associated genes have been identified as strongly enriched. Furthermore, based on the results of the pathway enrichment analysis we propose a methodology for predicting oral cancer recurrence using dynamic Bayesian networks. The methodology takes into consideration time series gene expression data in order to predict a disease recurrence. Subsequently, we are able to conjecture about the causal interactions between genes in consecutive time intervals. Concerning the performance of the predictive models, the overall accuracy of the algorithm is 81.8% and the area under the ROC curve 89.2% regarding the knowledge from the overrepresented pre-NOTCH Expression and processing pathway.

  7. Prediction of future hydrological regimes in poorly gauged high altitude basins: the case study of the upper Indus, Pakistan

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    D. Bocchiola

    2011-07-01

    Full Text Available In the mountain regions of the Hindu Kush, Karakoram and Himalaya (HKH the "third polar ice cap" of our planet, glaciers play the role of "water towers" by providing significant amount of melt water, especially in the dry season, essential for agriculture, drinking purposes, and hydropower production. Recently, most glaciers in the HKH have been retreating and losing mass, mainly due to significant regional warming, thus calling for assessment of future water resources availability for populations down slope. However, hydrology of these high altitude catchments is poorly studied and little understood. Most such catchments are poorly gauged, thus posing major issues in flow prediction therein, and representing in fact typical grounds of application of PUB concepts, where simple and portable hydrological modeling based upon scarce data amount is necessary for water budget estimation, and prediction under climate change conditions. In this preliminarily study, future (2060 hydrological flows in a particular watershed (Shigar river at Shigar, ca. 7000 km2, nested within the upper Indus basin and fed by seasonal melt from major glaciers, are investigated.

    The study is carried out under the umbrella of the SHARE-Paprika project, aiming at evaluating the impact of climate change upon hydrology of the upper Indus river. We set up a minimal hydrological model, tuned against a short series of observed ground climatic data from a number of stations in the area, in situ measured ice ablation data, and remotely sensed snow cover data. The future, locally adjusted, precipitation and temperature fields for the reference decade 2050–2059 from CCSM3 model, available within the IPCC's panel, are then fed to the hydrological model. We adopt four different glaciers' cover scenarios, to test sensitivity to decreased glacierized areas. The projected flow duration curves, and some selected flow descriptors are evaluated. The uncertainty of

  8. Poor sleep as a pathophysiological pathway underlying the association between stressful experiences and the diurnal cortisol profile among children and adolescents

    Science.gov (United States)

    Ly, Jinshia; McGrath, Jennifer J.; Gouin, Jean-Philippe

    2017-01-01

    Summary Recent evidence suggests that poor sleep is a potential pathway underlying the association between stressful experiences and the diurnal cortisol profile. However, existing findings are largely limited to adults. The present study examines whether poor sleep (duration, quality) mediates the relation between stressful experiences and the diurnal cortisol profile in children and adolescents. Children and adolescents (N = 220, Mage = 12.62) provided six saliva samples over two days to derive cortisol indices (bedtime, AUCAG, AUCTG, slopeMAX). Perceived stress, stressful life events, self-reported sleep duration, and sleep quality were measured. Using bootstrapping analyses, sleep quality mediated the relation between perceived stress and AUCTG (R2 = 0.10, F(7, 212) = 3.55, p = .001; 95% BCI[0.09, 1.15]), as well as the relation between stressful life events and AUCTG (R2 = 0.11, F(7, 212) = 3.69, p = .001; 95% BCI[0.40, 3.82]). These mediation models remained significant after adjusting for sleep duration, suggesting that poor sleep quality underlies the association between stressful experiences and the diurnal cortisol profile in children and adolescents. Longitudinal data combined with objectively-measured sleep is essential to further disentangle the complex association between sleep and stress. PMID:25889840

  9. Low Preoperative Prognostic Nutritional Index Predicts Poor Survival Post-gastrectomy in Elderly Patients with Gastric Cancer.

    Science.gov (United States)

    Sakurai, Katsunobu; Tamura, Tatsuro; Toyokawa, Takahiro; Amano, Ryosuke; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Yashiro, Masakazu; Maeda, Kiyoshi; Ohira, Masaichi; Hirakawa, Kosei

    2016-10-01

    Preoperative nutritional status may predict short- and long-term outcomes of patients with cancer. The aim of this study was to clarify the impact of preoperative nutritional status on outcomes of elderly patients who have undergone gastrectomy for gastric cancer (GC). A review examining 147 patients treated for GC by gastrectomy at our institution between January 2004 and December 2011 was conducted. Onodera's prognostic nutritional index (PNI) was invoked, using an optimal cutpoint to stratify patients by high (PNI > 43.8; n = 84) or low (PNI ≤ 43.8; n = 63) nutritional status. Clinicopathologic features and short- and long-term outcomes, including the cause of death, were compared. In multivariate analysis, low PNI was identified as an independent correlate of poor 5-year overall survival (OS). In subgroup analysis, 5-year OS rates for patients with stage 1 GC were significantly worse in the low PNI (vs. high PNI) patient subset, which also posed a significantly higher risk of death from other disease; however, 5-year cancer-specific survival and PNI were unrelated. Deaths from recurrence in both groups were statistically similar, and morbidity rates did not differ significantly by group. PNI is useful in predicting long-term outcomes of elderly patients surgically treated for GC, helping to identify those at high risk of death from other disease. In an effort to improve patient outcomes, nutritional status and oncologic staging merit attention.

  10. Poor fine-motor and visuospatial skills predict persistence of pediatric-onset obsessive-compulsive disorder into adulthood.

    Science.gov (United States)

    Bloch, Michael H; Sukhodolsky, Denis G; Dombrowski, Philip A; Panza, Kaitlyn E; Craiglow, Brittany G; Landeros-Weisenberger, Angeli; Leckman, James F; Peterson, Bradley S; Schultz, Robert T

    2011-09-01

    Half of pediatric-onset OCD cases remit by adulthood. Studies have demonstrated that initial response to pharmacotherapy, age of onset, prominent hoarding symptoms, and the presence of comorbid tic disorders are associated with long-term outcome. Our goal was to examine the association between childhood performance on neuropsychological testing and persistence of OCD into adulthood. Twenty-four children with OCD were followed for an average of 7.5 years into early adulthood. Neuropsychological performance in childhood (childhood performance on the Purdue pegboard task and the block design subscale of WISC-III was associated with persistence of OCD symptoms into adulthood. IQ, VMI, and nonverbal memory performance did not predict significantly the persistence of OCD. These results suggest that visuospatial and fine-motor skill deficits are predictive of poor long-term outcome in pediatric-onset OCD. Future longitudinal studies are needed to chart the course of these deficits relative to the course of symptoms in OCD and to determine whether the association of these neuropsychiatric deficits with long-term outcome is specific to pediatric-onset OCD or generalizes to other psychiatric disorders. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

  11. Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder.

    Science.gov (United States)

    van Tilborg, Theodora C; Torrance, Helen L; Oudshoorn, Simone C; Eijkemans, Marinus J C; Koks, Carolien A M; Verhoeve, Harold R; Nap, Annemiek W; Scheffer, Gabrielle J; Manger, A Petra; Schoot, Benedictus C; Sluijmer, Alexander V; Verhoeff, Arie; Groen, Henk; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M

    2017-12-01

    Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? In women with a predicted poor ovarian response (AFC IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8-10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78-1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562-1591)], standard FSH dosing was the dominant strategy in our economic analysis. Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC < 11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women. This

  12. High endothelin-converting enzyme-1 expression independently predicts poor survival of patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wu, Ching-Fang; Lee, Ching-Tai; Kuo, Yao-Hung; Chen, Tzu-Haw; Chang, Chi-Yang; Chang, I-Wei; Wang, Wen-Lun

    2017-09-01

    Patients with esophageal squamous cell carcinoma have poor survival and high recurrence rate, thus an effective prognostic biomarker is needed. Endothelin-converting enzyme-1 is responsible for biosynthesis of endothelin-1, which promotes growth and invasion of human cancers. The role of endothelin-converting enzyme-1 in esophageal squamous cell carcinoma is still unknown. Therefore, this study investigated the significance of endothelin-converting enzyme-1 expression in esophageal squamous cell carcinoma clinically. We enrolled patients with esophageal squamous cell carcinoma who provided pretreated tumor tissues. Tumor endothelin-converting enzyme-1 expression was evaluated by immunohistochemistry and was defined as either low or high expression. Then we evaluated whether tumor endothelin-converting enzyme-1 expression had any association with clinicopathological findings or predicted survival of patients with esophageal squamous cell carcinoma. Overall, 54 of 99 patients with esophageal squamous cell carcinoma had high tumor endothelin-converting enzyme-1 expression, which was significantly associated with lymph node metastasis ( p = 0.04). In addition, tumor endothelin-converting enzyme-1 expression independently predicted survival of patients with esophageal squamous cell carcinoma, and the 5-year survival was poorer in patients with high tumor endothelin-converting enzyme-1 expression ( p = 0.016). Among patients with locally advanced and potentially resectable esophageal squamous cell carcinoma (stage II and III), 5-year survival was poorer with high tumor endothelin-converting enzyme-1 expression ( p = 0.003). High tumor endothelin-converting enzyme-1 expression also significantly predicted poorer survival of patients in this population. In patients with esophageal squamous cell carcinoma, high tumor endothelin-converting enzyme-1 expression might indicate high tumor invasive property. Therefore, tumor endothelin-converting enzyme-1 expression

  13. Prediction of Metabolic Pathway Involvement in Prokaryotic UniProtKB Data by Association Rule Mining

    KAUST Repository

    Boudellioua, Imene; Saidi, Rabie; Hoehndorf, Robert; Martin, Maria J.; Solovyev, Victor

    2016-01-01

    The widening gap between known proteins and their functions has encouraged the development of methods to automatically infer annotations. Automatic functional annotation of proteins is expected to meet the conflicting requirements of maximizing annotation coverage, while minimizing erroneous functional assignments. This trade-off imposes a great challenge in designing intelligent systems to tackle the problem of automatic protein annotation. In this work, we present a system that utilizes rule mining techniques to predict metabolic pathways in prokaryotes. The resulting knowledge represents predictive models that assign pathway involvement to UniProtKB entries. We carried out an evaluation study of our system performance using cross-validation technique. We found that it achieved very promising results in pathway identification with an F1-measure of 0.982 and an AUC of 0.987. Our prediction models were then successfully applied to 6.2 million UniProtKB/TrEMBL reference proteome entries of prokaryotes. As a result, 663,724 entries were covered, where 436,510 of them lacked any previous pathway annotations.

  14. Prediction of Metabolic Pathway Involvement in Prokaryotic UniProtKB Data by Association Rule Mining

    KAUST Repository

    Boudellioua, Imene

    2016-07-08

    The widening gap between known proteins and their functions has encouraged the development of methods to automatically infer annotations. Automatic functional annotation of proteins is expected to meet the conflicting requirements of maximizing annotation coverage, while minimizing erroneous functional assignments. This trade-off imposes a great challenge in designing intelligent systems to tackle the problem of automatic protein annotation. In this work, we present a system that utilizes rule mining techniques to predict metabolic pathways in prokaryotes. The resulting knowledge represents predictive models that assign pathway involvement to UniProtKB entries. We carried out an evaluation study of our system performance using cross-validation technique. We found that it achieved very promising results in pathway identification with an F1-measure of 0.982 and an AUC of 0.987. Our prediction models were then successfully applied to 6.2 million UniProtKB/TrEMBL reference proteome entries of prokaryotes. As a result, 663,724 entries were covered, where 436,510 of them lacked any previous pathway annotations.

  15. Coregulation of terpenoid pathway genes and prediction of isoprene production in Bacillus subtilis using transcriptomics

    Energy Technology Data Exchange (ETDEWEB)

    Hess, Becky M.; Xue, Junfeng; Markillie, Lye Meng; Taylor, Ronald C.; Wiley, H. S.; Ahring, Birgitte K.; Linggi, Bryan E.

    2013-06-19

    The isoprenoid pathway converts pyruvate to isoprene and related isoprenoid compounds in plants and some bacteria. Currently, this pathway is of great interest because of the critical role that isoprenoids play in basic cellular processes as well as the industrial value of metabolites such as isoprene. Although the regulation of several pathway genes has been described, there is a paucity of information regarding the system level regulation and control of the pathway. To address this limitation, we examined Bacillus subtilis grown under multiple conditions and then determined the relationship between altered isoprene production and the pattern of gene expression. We found that terpenoid genes appeared to fall into two distinct subsets with opposing correlations with respect to the amount of isoprene produced. The group whose expression levels positively correlated with isoprene production included dxs, the gene responsible for the commitment step in the pathway, as well as ispD, and two genes that participate in the mevalonate pathway, yhfS and pksG. The subset of terpenoid genes that inversely correlated with isoprene production included ispH, ispF, hepS, uppS, ispE, and dxr. A genome wide partial least squares regression model was created to identify other genes or pathways that contribute to isoprene production. This analysis showed that a subset of 213 regulated genes was sufficient to create a predictive model of isoprene production under different conditions and showed correlations at the transcriptional level. We conclude that gene expression levels alone are sufficiently informative about the metabolic state of a cell that produces increased isoprene and can be used to build a model which accurately predicts production of this secondary metabolite across many simulated environmental conditions.

  16. Limited sampling strategies drawn within 3 hours postdose poorly predict mycophenolic acid area-under-the-curve after enteric-coated mycophenolate sodium.

    NARCIS (Netherlands)

    Winter, B.C. de; Gelder, T. van; Mathôt, R.A.A.; Glander, P.; Tedesco-Silva, H.; Hilbrands, L.B.; Budde, K.; Hest, R.M. van

    2009-01-01

    Previous studies predicted that limited sampling strategies (LSS) for estimation of mycophenolic acid (MPA) area-under-the-curve (AUC(0-12)) after ingestion of enteric-coated mycophenolate sodium (EC-MPS) using a clinically feasible sampling scheme may have poor predictive performance. Failure of

  17. Detecting Human Hydrologic Alteration from Diversion Hydropower Requires Universal Flow Prediction Tools: A Proposed Framework for Flow Prediction in Poorly-gauged, Regulated Rivers

    Science.gov (United States)

    Kibler, K. M.; Alipour, M.

    2016-12-01

    Achieving the universal energy access Sustainable Development Goal will require great investment in renewable energy infrastructure in the developing world. Much growth in the renewable sector will come from new hydropower projects, including small and diversion hydropower in remote and mountainous regions. Yet, human impacts to hydrological systems from diversion hydropower are poorly described. Diversion hydropower is often implemented in ungauged rivers, thus detection of impact requires flow analysis tools suited to prediction in poorly-gauged and human-altered catchments. We conduct a comprehensive analysis of hydrologic alteration in 32 rivers developed with diversion hydropower in southwestern China. As flow data are sparse, we devise an approach for estimating streamflow during pre- and post-development periods, drawing upon a decade of research into prediction in ungauged basins. We apply a rainfall-runoff model, parameterized and forced exclusively with global-scale data, in hydrologically-similar gauged and ungauged catchments. Uncertain "soft" data are incorporated through fuzzy numbers and confidence-based weighting, and a multi-criteria objective function is applied to evaluate model performance. Testing indicates that the proposed framework returns superior performance (NSE = 0.77) as compared to models parameterized by rote calibration (NSE = 0.62). Confident that the models are providing `the right answer for the right reasons', our analysis of hydrologic alteration based on simulated flows indicates statistically significant hydrologic effects of diversion hydropower across many rivers. Mean annual flows, 7-day minimum and 7-day maximum flows decreased. Frequency and duration of flow exceeding Q25 decreased while duration of flows sustained below the Q75 increased substantially. Hydrograph rise and fall rates and flow constancy increased. The proposed methodology may be applied to improve diversion hydropower design in data-limited regions.

  18. Effect of curcumin on aged Drosophila melanogaster: a pathway prediction analysis.

    Science.gov (United States)

    Zhang, Zhi-guo; Niu, Xu-yan; Lu, Ai-ping; Xiao, Gary Guishan

    2015-02-01

    To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis. A total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Genes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

  19. Different gene-expression profiles for the poorly differentiated carcinoma and the highly differentiated papillary adenocarcinoma in mammary glands support distinct metabolic pathways

    International Nuclear Information System (INIS)

    Eilon, Tali; Barash, Itamar

    2008-01-01

    Deregulation of Stat5 in the mammary gland of transgenic mice causes tumorigenesis. Poorly differentiated carcinoma and highly differentiated papillary adenocarcinoma tumors evolve. To distinguish the genes and elucidate the cellular processes and metabolic pathways utilized to preserve these phenotypes, gene-expression profiles were analyzed. Mammary tumors were excised from transgenic mice carrying a constitutively active variant of Stat5, or a Stat5 variant lacking s transactivation domain. These tumors displayed either the carcinoma or the papillary adenocarcinoma phenotypes. cRNAs, prepared from each tumor were hybridized to an Affymetrix GeneChip ® Mouse Genome 430A 2.0 array. Gene-ontology analysis, hierarchical clustering and biological-pathway analysis were performed to distinct the two types of tumors. Histopathology and immunofluorescence staining complemented the comparison between the tumor phenotypes. The nucleus-cytoskeleton-plasma membrane axis is a major target for differential gene expression between phenotypes. In the carcinoma, stronger expression of genes coding for specific integrins, cytoskeletal proteins and calcium-binding proteins highlight cell-adhesion and motility features of the tumor cells. This is supported by the higher expression of genes involved in O-glycan synthesis, TGF-β, activin, their receptors and Smad3, as well as the Notch ligands and members of the γ-secretase complex that enable Notch nuclear localization. The Wnt pathway was also a target for differential gene expression. Higher expression of genes encoding the degradation complex of the canonical pathway and limited TCF expression in the papillary adenocarcinoma result in membranal accumulation of β-catenin, in contrast to its nuclear translocation in the carcinoma. Genes involved in cell-cycle arrest at G1 and response to DNA damage were more highly expressed in the papillary adenocarcinomas, as opposed to favored G2/M regulation in the carcinoma tumors. At least

  20. Increased serum levels of tumour-associated trypsin inhibitor independently predict a poor prognosis in colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Gaber Alexander

    2010-09-01

    Full Text Available Abstract Background There is an insufficient number of reliable prognostic and response predictive biomarkers in colorectal cancer (CRC management. In a previous study, we found that high tumour tissue expression of tumour-associated trypsin inhibitor (TATI correlated with liver metastasis and an impaired prognosis in CRC. The aim of this study was to investigate the prognostic validity of serum TATI (s-TATI in CRC. We further assessed the prognostic value of carcino-embryonic antigen in serum (s-CEA and the interrelationship between s-TATI and TATI in tissue (t-TATI. Methods Using an immunofluorometric assay, s-TATI levels were analysed in 334 preoperatively collected serum samples from patients with CRC. Spearman's Rho and Chi-square test were used for analysis of correlations between s-TATI and clinicopathological parameters, s-CEA and t-TATI. Kaplan-Meier analysis and Cox uni- and multivariate regression analysis were used to estimate disease free survival (DFS and overall survival (OS according to quartiles of s-TATI and cut-offs derived from ROC-analysis of s-TATI and s-CEA. Results Increased levels of s-TATI were associated with a reduced DFS (HR = 2.00; 95% CI 1.40-2.84, P P P = 0.034 for DFS and HR = 1.78; 95% CI 1.25-2.53, P = 0.001 for OS. There was no significant association between s-TATI and t-TATI. The prognostic value of s-CEA was also evident, but somewhat weaker than for s-TATI. Conclusions High preoperative s-TATI levels predict a poor prognosis in patients with CRC, and the prognostic value is independent of established prognostic parameters and t-TATI expression. These data suggest that s-TATI might be a useful marker for prognostic stratification in CRC.

  1. Tyrosine kinase ETK/BMX is up-regulated in bladder cancer and predicts poor prognosis in patients with cystectomy.

    Directory of Open Access Journals (Sweden)

    Shengjie Guo

    2011-03-01

    Full Text Available Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors. In this report, we demonstrated that ETK expression is progressively increased during bladder cancer progression. We found that down-regulation of ETK in bladder cancer cells attenuated STAT3 and AKT activity whereas exogenous overexpression of ETK had opposite effects, suggesting that deregulation of ETK may attribute to the elevated activity of STAT3 and AKT frequently detected in bladder cancer. The survival, migration and invasion of bladder cancer cells were significantly compromised when ETK expression was knocked down by a specific shRNA. In addition, we showed that ETK localizes to mitochondria in bladder cancer cells through interacting with Bcl-XL and regulating ROS production and drug sensitivity. Therefore, ETK may play an important role in regulating survival, migration and invasion by modulating multiple signaling pathways in bladder cancer cells. Immunohistochemistry analysis on tissue microarrays containing 619 human bladder tissue samples shows that ETK is significantly upregulated during bladder cancer development and progression and ETK expression level predicts the survival rate of patients with cystectomy. Taken together, our results suggest that ETK may potentially serve as a new drug target for bladder cancer treatment as well as a biomarker which could be used to identify patients with higher mortality risk, who may be benefited from therapeutics targeting ETK activity.

  2. DEAD-box helicase 27 promotes colorectal cancer growth and metastasis and predicts poor survival in CRC patients.

    Science.gov (United States)

    Tang, Jieting; Chen, Huarong; Wong, Chi-Chun; Liu, Dabin; Li, Tong; Wang, Xiaohong; Ji, Jiafu; Sung, Joseph Jy; Fang, Jing-Yuan; Yu, Jun

    2018-03-14

    Copy number alterations (CNAs) are crucial for colorectal cancer (CRC) development. In this study, DEAD box polypeptide 27 (DDX27) was identified to be highly amplified in both TCGA CRC (474/615) and primary CRC (47/103), which was positively correlated with its mRNA overexpression. High DDX27 mRNA (N = 199) and protein expression (N = 260) predicted poor survival in CRC patients. Ectopic expression of DDX27 increased CRC cells proliferation, migration and invasion, but suppressed apoptosis. Conversely, silencing of DDX27 exerted opposite effects in vitro and significantly inhibited murine xenograft tumor growth and lung metastasis in vivo. Up-regulation of DDX27 enhanced and prolonged TNF-α-mediated NF-κB signaling. Nucleophosmin (NPM1) was identified as a binding partner of DDX27. DDX27 increased nuclear NPM1 and NF-κB-p65 interaction to enhance DNA binding activity of NF-κB. Silencing NPM1 abrogated DDX27-activating NF-κB signaling and its tumor-promoting function. Together, DDX27 is overexpressed and plays a pivotal oncogenic role in CRC.

  3. Poor predictive value of positive interim FDG-PET/CT in primary mediastinal large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Lazarovici, Julien; Petrovanu, Cynthia; Danu, Alina; Ferme, Christophe; Ribrag, Vincent; Ghez, David [Gustave Roussy, Villejuif (France). Dept. of Hematology; Paris Saclay Univ., Saint-Aubin (France); Terroir, Marie [Gustave Roussy, Villejuif (France). Dept. of Nuclear Medicine and Endocrine Oncology; Paris Saclay Univ., Saint-Aubin (France); Arfi-Rouche, Julia [Gustave Roussy, Villejuif (France). Dept. of Radiology; Paris Saclay Univ., Saint-Aubin (France); Michot, Jean-Marie [Gustave Roussy, Villejuif (France). Dept. of Drug Development (DITEP); Paris Saclay Univ., Saint-Aubin (France); Mussot, Sacha; Florea, Valentina [Marie Lannelongue Hospital, Le Plessis Robinson (France). Dept. of Thoracic Surgery; Ghigna, Maria-Rosa [Marie Lannelongue Hospital, Le Plessis Robinson (France). Dept. of Pathology; Dartigues, Peggy [Gustave Roussy, Villejuif (France). Dept. of Pathology; Paris Saclay Univ., Saint-Aubin (France)

    2017-11-15

    Though commonly used to assess response to therapy, the prognostic value of interim FDG-PET/CT in Primary Mediastinal Large B-cell Lymphoma (PMBCL) is unclear. We conducted a retrospective study on 36 consecutive patients treated at our institution for a PMBCL between 2006 and 2014. All patients with a positive interim FDG-PET/CT had undergone histological restaging consisting either in a surgical debulking of the residual lesion (15 patients) or a CT-guided core needle biopsy (two patients). All FDG-PET/CT were secondarily reviewed according to the more recent Deauville criteria. Interim FDG-PET/CT was considered positive in 17/36 patients using visual evaluation. Among these patients, 14 had a Deauville score of 4. Histological restaging was negative in all but one case, showing inflammation and/or fibrosis. After a median follow-up of 48.5 months, a total of five patients have relapsed, two patients in the positive FDG-PET/CT group, and three patients in the negative FDG-PET/CT group, respectively. These data indicate that a positive interim FDG-PET/CT does not reflect persistence of active disease in the vast majority of PMBCL cases. The relapse rate appears similar regardless of interim FDG-PET/CT results and interpretation criteria. This suggests that interim FDG-PET/CT has a poor positive predictive value, thus kt should be used with caution in PMBCL. (orig.)

  4. The more, the less: age and chemotherapy load are predictive of poor stem cell mobilization in patients with hematologic malignancies

    Institute of Scientific and Technical Information of China (English)

    YANG Shen-miao; CHEN Huan; CHEN Yu-hong; ZHU Hong-hu; ZHAO Ting; LIU Kai-yan

    2012-01-01

    Background Intensive treatment such as autologous peripheral blood stem cell (PBSC) transplantation is an important therapeutic strategy in many hematologic malignancies.A number of factors have been reported to impact PBSC mobilization,but the predictive factors varied from one study to another.This retrospective study assessed our current mobilization and collection protocols,and explored the factors predictive of PBSC mobilization in patients with hematologic malignancies.Methods Data of 64 consecutive patients with hematologic malignancies (multiple myeloma,n=22; acute leukemia,n=27; lymphoma,n=15) who underwent PBSC mobilization for over 1 year were analyzed.Four patients with response to treatment of near complete remission or better were administered granulocyte colony-stimulating factor (G-CSF) to mobilize PBSCs.Sixty patients received G-CSF followed by chemotherapy mobilizing regimens.Poor mobilization (PM) was defined as when ≤2.0×106 CD34+ cells/kg body weight were collected within three leukapheresis procedures.Results The incidence of PM at the first mobilization attempt was 19% (12/64).The PM group was older than the non-PM group (median age,51 vs.40 years; P=0.013).In univariate analysis,there were no significant differences in gender,diagnosis,and body weight between the PM and non-PM groups.A combination of chemotherapy and G-CSF was more effective than G-CSF alone as a mobilizing regimen (P=0.019).Grade Ⅲ or Ⅳ hematopoietic toxicity of chemotherapy had no significant effect on the mobilization efficacy.Supportive care and the incidence of febrile neutropenia were not significantly different between the two groups.In multivariate analysis,age (odds ratio (OR),9.536;P=-0.002) and number of previous chemotherapy courses (OR 3.132; P=0.024) were two independent negative predictive factors for CD34+ cell yield.PM patients could be managed well by remobilization.Conclusion Older age and a heavy load of previous chemotherapy are the negative

  5. The combined status of estrogen receptor (ER) and epidermal growth factor (EGFR) predicts a poor outcome in primary breast cancer

    International Nuclear Information System (INIS)

    Artagaveytia, N.; Román, E.; Alonso, I.; Sabini, G.; Garófalo, E.

    2004-01-01

    had significance prognostic (SVLE, p = 0.005 and SVG, p = 0.01, respectively). In conclusion, the content of RE is better than the status indicator evolutionary RE. The combined ER-positive status and REGFpositivo in primary breast cancer predicts a poor outcome of the disease-The RE-b is emerging as a potential marker of poor prognosis

  6. Developmental pathways of fitness, and not baseline, predict fitness status at the end of childhood

    OpenAIRE

    Rodrigues, Luis Paulo; Stodden, David F.; Lopes, Vítor P.

    2013-01-01

    It is generally described that children fitness levels increase along childhood. Complementary to this idea is the notion that the tracking of children’s fitness is good to moderate during this developmental time, and that baseline (initial values) of fitness are determinant on fitness development. The importance of developmental pathways has been recently reinforced by a theoretical argument that predicts that healthy lifestyle trajectories will evolve through either a positive or n...

  7. Subventricular zone predicts high velocity of tumor expansion and poor clinical outcome in patients with low grade astrocytoma.

    Science.gov (United States)

    Wen, Bing; Fu, Feixian; Hu, Liangbo; Cai, Qiuyi; Xie, Junshi

    2018-05-01

    The aim of this study is to clarify the association between subventricular zone (SVZ) involvement and velocity of diametric expansion(VDE) in patients with low-grade astrocytoma and also assessed the clinical outcome of those patients. A total of 168 adult patients with newly diagnosed supratentorial low-grade astrocytoma were studied retrospectively. There were 73 patients had SVZ involvement. Patients with SVZ involvement(7.16 ± 6.53 mm/y) had a higher VDE than patients without SVZ involvement(4.38 ± 5.35 mm/y). VDE was modeled as a categorical variable(<4, ≥4 and, <8, ≥8 and, <12, ≥12 mm/y). Logistic regression showed that SVZ involvement was associated with high VDE after adjusting by confounding variables. On the univariate analysis, the results showed that tumor involved with SVZ, VDE ≥ 4 mm/y, VDE ≥ 8 mm/y, and VDE ≥ 8 mm/y were significant predictors of a shorter OS, progression-free survival (PFS) and malignant progression-free survival (MFS)(all p <0.05). The categorical variables of VDE (<4 mm/y, ≥4 mm/y and, <8 mm/y, ≥8 mm/y and, <12 mm/y, ≥12 mm/y) were adjusted by confounding variables in multivariate analysis, respectively. The results indicated that VDE ≥ 8 mm/y, VDE ≥ 12 mm/y were worse prognostic factors for OS, while VDE ≥ 4 mm/y, VDE ≥ 8 mm/y and VDE ≥ 12 mm/y were related to shorter PFS and MFS. In addition, SVZ involvement was prognostic factors in predicting OS and PFS except MFS. Our results demonstrated that SVZ involvement predicted high VDE and worse clinical outcome, and high VDE was associated with poor prognosis in patients with low-grade astrocytoma. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Overexpression of RBBP6, alone or combined with mutant TP53, is predictive of poor prognosis in colon cancer.

    Directory of Open Access Journals (Sweden)

    Jian Chen

    Full Text Available Retinoblastoma binding protein 6 (RBBP6 plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of RBBP6 expression in colon cancer is unknown; in particular, the prognostic value of RBBP6 combined with TP53 expression has not been explored. Therefore, quantitative real-time PCR and western blot analyses were performed to detect RBBP6 expression in colon cancer tissues. RBBP6 and TP53 expression were assessed by immunohistochemistry in a tissue microarray format, in which the primary colon cancer tissue was paired with noncancerous tissue. Tissue specimens were obtained from 203 patients. We found that RBBP6 was overexpressed in colon tumorous tissues and was significantly associated with clinical stage, depth of tumor invasion, lymph node metastasis (LNM, distant metastasis, and histologic grade. Further studies revealed that a corresponding correlation between RBBP6 overexpression and mutant TP53 was evident in colon cancer (r = 0.450; P<0.001. RBBP6 expression was an independent prognostic factor for overall survival (OS and disease free survival (DFS. Interestingly, patients with tumors that had both RBBP6 overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P<0.001. Multivariate analysis showed that patients with LNM and patients with both RBBP6- and TP53-positive tumors had extremely poor OS (HR 6.75; 95% CI 2.63-17.35; P<0.001 and DFS (HR 8.08; 95% CI 2.80-23.30; P<0.001. These clinical findings indicate that the assessment of both RBBP6 and mutant TP53 expression will be helpful in predicting colon cancer prognosis.

  9. Short sleep duration and poor sleep quality predict next-day suicidal ideation: an ecological momentary assessment study.

    Science.gov (United States)

    Littlewood, Donna L; Kyle, Simon D; Carter, Lesley-Anne; Peters, Sarah; Pratt, Daniel; Gooding, Patricia

    2018-04-26

    Sleep problems are a modifiable risk factor for suicidal thoughts and behaviors. Yet, sparse research has examined temporal relationships between sleep disturbance, suicidal ideation, and psychological factors implicated in suicide, such as entrapment. This is the first in-the-moment investigation of relationships between suicidal ideation, objective and subjective sleep parameters, and perceptions of entrapment. Fifty-one participants with current suicidal ideation completed week-long ecological momentary assessments. An actigraph watch was worn for the duration of the study, which monitored total sleep time, sleep efficiency, and sleep latency. Daily sleep diaries captured subjective ratings of the same sleep parameters, with the addition of sleep quality. Suicidal ideation and entrapment were measured at six quasi-random time points each day. Multi-level random intercept models and moderation analyses were conducted to examine the links between sleep, entrapment, and suicidal ideation, adjusting for anxiety and depression severity. Analyses revealed a unidirectional relationship whereby short sleep duration (both objective and subjective measures), and poor sleep quality, predicted the higher severity of next-day suicidal ideation. However, there was no significant association between daytime suicidal ideation and sleep the following night. Sleep quality moderated the relationship between pre-sleep entrapment and awakening levels of suicidal ideation. This is the first study to report night-to-day relationships between sleep disturbance, suicidal ideation, and entrapment. Findings suggest that sleep quality may alter the strength of the relationship between pre-sleep entrapment and awakening suicidal ideation. Clinically, results underscore the importance of assessing and treating sleep disturbance when working with those experiencing suicidal ideation.

  10. Wealth, justice and freedom: Objective and subjective measures predicting poor mental health in a study across eight countries

    Directory of Open Access Journals (Sweden)

    Saskia Scholten

    2017-12-01

    Conclusion: Multiple subjective and objective MF should be combined to assess the macrosystem’s relationship with poor mental health more precisely. The relationship between MF and poor mental health indicates that the macrosystem should be taken into account as relevant context for mental health problems, too.

  11. DHX15 is associated with poor prognosis in acute myeloid leukemia (AML) and regulates cell apoptosis via the NF-kB signaling pathway.

    Science.gov (United States)

    Pan, Lili; Li, Yang; Zhang, Hai-Ying; Zheng, Yi; Liu, Xiao-Li; Hu, Zheng; Wang, Yi; Wang, Jing; Cai, Yuan-Hua; Liu, Qiao; Chen, Wan-Ling; Guo, Ying; Huang, Yuan-Mao; Qian, Feng; Jin, Li; Wang, Jiucun; Wang, Shao-Yuan

    2017-10-27

    The role of DHX15 , a newly identified DEAH-box RNA helicase, in leukemogenesis remains elusive. Here, we identified a recurrent mutation in DHX15 (NM_001358:c.664C>G: p.(R222G)) in one familial AML patient and 4/240 sporadic AML patients. Additionally, DHX15 was commonly overexpressed in AML patients and associated with poor overall survival (OS) (P=0.019) and relapse-free survival (RFS) (P=0.032). In addition, we found a distinct expression pattern of DHX15 . DHX15 was highly expressed in hematopoietic stem cells and leukemia cells but was lowly expressed in mature blood cells. DHX15 was down-regulated when AML patients achieved disease remission or when leukemia cell lines were induced to differentiate. DHX15 silencing greatly inhibited leukemia cell proliferation and induced cell apoptosis and G1-phase arrest. In contrast, the restoration of DHX15 expression rescued cell viability and reduced cell apoptosis. In addition, we found that DHX15 was down-regulated when cell apoptosis was induced by ATO (arsenic trioxide); overexpression of DHX15 caused dramatic resistance to ATO-induced cell apoptosis, suggesting an important role for DHX15 in cell apoptosis. We further explored the mechanism of DHX15 in apoptosis and found that overexpression of DHX15 activated NF-kB transcription. Knockdown of DHX15 inhibited the nuclear translocation and activation of the NF-kB subunit P65 in leukemia cells. Several downstream targets of the NF-kB pathway were also down-regulated, and apoptosis-associated genes CASP3 and PARP were activated. In conclusion, this study represents the first demonstration that DHX15 plays an important role in leukemogenesis via the NF-kB signaling pathway and may serve as an independent prognostic marker for AML.

  12. A multi-step pathway connecting short sleep duration to daytime somnolence, reduced attention, and poor academic performance: an exploratory cross-sectional study in teenagers.

    Science.gov (United States)

    Perez-Lloret, Santiago; Videla, Alejandro J; Richaudeau, Alba; Vigo, Daniel; Rossi, Malco; Cardinali, Daniel P; Perez-Chada, Daniel

    2013-05-15

    A multi-step causality pathway connecting short sleep duration to daytime somnolence and sleepiness leading to reduced attention and poor academic performance as the final result can be envisaged. However this hypothesis has never been explored. To explore consecutive correlations between sleep duration, daytime somnolence, attention levels, and academic performance in a sample of school-aged teenagers. We carried out a survey assessing sleep duration and daytime somnolence using the Pediatric Daytime Sleepiness Scale (PDSS). Sleep duration variables included week-days' total sleep time, usual bedtimes, and absolute weekday to-weekend sleep time difference. Attention was assessed by d2 test and by the coding subtest from the WISC-IV scale. Academic performance was obtained from literature and math grades. Structural equation modeling was used to assess the independent relationships between these variables, while controlling for confounding effects of other variables, in one single model. Standardized regression weights (SWR) for relationships between these variables are reported. Study sample included 1,194 teenagers (mean age: 15 years; range: 13-17 y). Sleep duration was inversely associated with daytime somnolence (SWR = -0.36, p academic results (SWR = 0.18, p academic achievements (SWR = -0.16, p sleep duration influenced attention through daytime somnolence (p academic achievements through reduced attention (p academic achievements correlated with reduced attention, which in turn was related to daytime somnolence. Somnolence correlated with short sleep duration.

  13. Prior failed ipsilateral percutaneous endovascular intervention in patients with critical limb ischemia predicts poor outcome after lower extremity bypass

    Science.gov (United States)

    Nolan, Brian W.; De Martino, Randall R.; Stone, David H.; Schanzer, Andres; Goodney, Philip P.; Walsh, Daniel W.; Cronenwett, Jack L.

    2017-01-01

    had a prior ipsilateral bypass (1 year major amputation, 29% vs 20%; P = .022; 1 year graft occlusion, 33% vs 18%; P = .001). Independent multivariate predictors of higher 1-year amputation and graft occlusion rates were prior iPVI, prior ipsilateral bypass, dialysis dependence, prosthetic conduit and distal (tibial and pedal) bypass target. Conclusions Prior iPVI is highly predictive for poor outcome in patients undergoing LEB for CLI with higher 1-year amputation and graft occlusion rates than those without prior revascularization, similar to prior ipsilateral bypass These findings provide information, which may help with the complex decisions surrounding revascularization options in patients with CLI. PMID:21802888

  14. Cytoplasmic localization of alteration/deficiency in activation 3 (ADA3) predicts poor clinical outcome in breast cancer patients.

    Science.gov (United States)

    Mirza, Sameer; Rakha, Emad A; Alshareeda, Alaa; Mohibi, Shakur; Zhao, Xiangshan; Katafiasz, Bryan J; Wang, Jun; Gurumurthy, Channabasavaiah Basavaraju; Bele, Aditya; Ellis, Ian O; Green, Andrew R; Band, Hamid; Band, Vimla

    2013-02-01

    ErbB2+/EGFR+ expression and together is a marker of poor prognosis. Thus, ADA3 cytoplasmic localization together with ErbB2+/EGFR+ status may serve as better prognostic marker than individual proteins to predict survival of patients.

  15. Wealth, justice and freedom: Objective and subjective measures predicting poor mental health in a study across eight countries.

    Science.gov (United States)

    Scholten, Saskia; Velten, Julia; Neher, Torsten; Margraf, Jürgen

    2017-12-01

    Macro-level factors (MF) such as wealth, justice and freedom measured with objective country-level indicators (objective MF), for instance the Gross Domestic Product (GDP), have been investigated in relation to health and well-being, but rarely in connection with depression, anxiety and stress subsumed as poor mental health. Also, a combination of different objective MF and of how individuals perceive those MF (subjective MF) has not been taken into consideration. In the present study, we combined subjective and objective measures of wealth, justice and freedom and examined their relationship with poor mental health. Population-based interviews were conducted in France, Germany, Poland, Russia, Spain, Sweden, U.K. and U.S.A. (n ≈ 1000 per country). GDP, GINI coefficient, Justice Index and Freedom Index were used as objective MF, whereas subjective MF were perceived wealth, justice and freedom measured at the individual level. Poor mental health was assessed as a combination of symptoms of depression, anxiety and stress. In a random-intercept-model, GINI coefficient and Freedom Index were significant positive country-level, and perceived wealth, justice, and freedom significant negative individual-level predictors of symptoms of poor mental health. Multiple subjective and objective MF should be combined to assess the macrosystem's relationship with poor mental health more precisely. The relationship between MF and poor mental health indicates that the macrosystem should be taken into account as relevant context for mental health problems, too.

  16. Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer

    Science.gov (United States)

    Makondi, Precious Takondwa; Lee, Chia-Hwa; Huang, Chien-Yu; Chu, Chi-Ming; Chang, Yu-Jia

    2018-01-01

    Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs). Functional and pathway enrichment analyses of the DEGs were performed using the Database for Annotation, Visualization, and Integrated Discovery(DAVID). Protein–protein interaction (PPI) networks were established using the Search Tool for the Retrieval of Interacting Genes/Proteins database(STRING) and visualized using Cytoscape software. A total of 124 DEGs were obtained, 57 of which upregulated and 67 were downregulated. PPI network analysis showed that seven upregulated genes and nine downregulated genes exhibited high PPI degrees. In the functional enrichment, the DEGs were mainly enriched in negative regulation of phosphate metabolic process and positive regulation of cell cycle process gene ontologies (GOs); the enriched pathways were the phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, bladder cancer, and microRNAs in cancer. Cyclin-dependent kinase inhibitor 1A(CDKN1A), toll-like receptor 4 (TLR4), CD19 molecule (CD19), breast cancer 1, early onset (BRCA1), platelet-derived growth factor subunit A (PDGFA), and matrix metallopeptidase 1 (MMP1) were the DEGs involved in the pathways and the PPIs. The clinical validation of the DEGs in mCRC (TNM clinical stages 3 and 4) revealed that high PDGFA expression levels were associated with poor overall survival, whereas high BRCA1 and MMP1 expression levels were associated with favorable progress free survival(PFS). The identified genes and pathways

  17. Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Precious Takondwa Makondi

    Full Text Available Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO database (dataset, GSE86525 was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs. Functional and pathway enrichment analyses of the DEGs were performed using the Database for Annotation, Visualization, and Integrated Discovery(DAVID. Protein-protein interaction (PPI networks were established using the Search Tool for the Retrieval of Interacting Genes/Proteins database(STRING and visualized using Cytoscape software. A total of 124 DEGs were obtained, 57 of which upregulated and 67 were downregulated. PPI network analysis showed that seven upregulated genes and nine downregulated genes exhibited high PPI degrees. In the functional enrichment, the DEGs were mainly enriched in negative regulation of phosphate metabolic process and positive regulation of cell cycle process gene ontologies (GOs; the enriched pathways were the phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, bladder cancer, and microRNAs in cancer. Cyclin-dependent kinase inhibitor 1A(CDKN1A, toll-like receptor 4 (TLR4, CD19 molecule (CD19, breast cancer 1, early onset (BRCA1, platelet-derived growth factor subunit A (PDGFA, and matrix metallopeptidase 1 (MMP1 were the DEGs involved in the pathways and the PPIs. The clinical validation of the DEGs in mCRC (TNM clinical stages 3 and 4 revealed that high PDGFA expression levels were associated with poor overall survival, whereas high BRCA1 and MMP1 expression levels were associated with favorable progress free survival(PFS. The identified genes and pathways

  18. Poor pregnancy outcome in women with type 1 diabetes is predicted by elevated HbA1c and spikes of high glucose values in the third trimester

    DEFF Research Database (Denmark)

    Damm, Peter; Mersebach, Henriette; Råstam, Jacob

    2014-01-01

    OBJECTIVE: To analyse data from a randomised, controlled study of prandial insulin aspart versus human insulin, both with NPH insulin, in pregnant women with type 1 diabetes for potential factors predicting poor pregnancy outcomes. RESEARCH DESIGN/METHOD: Post hoc analysis including 91 subjects r...

  19. Integrative Analysis of Gene Expression Data Including an Assessment of Pathway Enrichment for Predicting Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Pingzhao Hu

    2006-01-01

    biological pathways. In particular, we observed that by integrating information from the insulin signalling pathway into our prediction model, we achieved better prediction of prostate cancer. Conclusions: Our data integration methodology provides an efficient way to identify biologically sound and statistically significant pathways from gene expression data. The significant gene expression phenotypes identified in our study have the potential to characterize complex genetic alterations in prostate cancer.

  20. REDOX AND REDUCTION POTENTIALS AS PARAMETERS TO PREDICT THE DEGRADATION PATHWAY OF CHLORINATED BENZENES IN ANAEROBIC ENVIRONMENTS

    NARCIS (Netherlands)

    DOLFING, J; HARRISON, BK

    1993-01-01

    The anaerobic degradation pathway of hexachlorobenzene starts with a series of reductive dehalogenation steps. In the present paper it was evaluated whether the dehalogenation pathway observed in microbial ecosystems could be predicted by the redox potential and/or the reduction potential (the

  1. Comparison of the accuracy of three algorithms in predicting accessory pathways among adult Wolff-Parkinson-White syndrome patients.

    Science.gov (United States)

    Maden, Orhan; Balci, Kevser Gülcihan; Selcuk, Mehmet Timur; Balci, Mustafa Mücahit; Açar, Burak; Unal, Sefa; Kara, Meryem; Selcuk, Hatice

    2015-12-01

    The aim of this study was to investigate the accuracy of three algorithms in predicting accessory pathway locations in adult patients with Wolff-Parkinson-White syndrome in Turkish population. A total of 207 adult patients with Wolff-Parkinson-White syndrome were retrospectively analyzed. The most preexcited 12-lead electrocardiogram in sinus rhythm was used for analysis. Two investigators blinded to the patient data used three algorithms for prediction of accessory pathway location. Among all locations, 48.5% were left-sided, 44% were right-sided, and 7.5% were located in the midseptum or anteroseptum. When only exact locations were accepted as match, predictive accuracy for Chiang was 71.5%, 72.4% for d'Avila, and 71.5% for Arruda. The percentage of predictive accuracy of all algorithms did not differ between the algorithms (p = 1.000; p = 0.875; p = 0.885, respectively). The best algorithm for prediction of right-sided, left-sided, and anteroseptal and midseptal accessory pathways was Arruda (p algorithms were similar in predicting accessory pathway location and the predicted accuracy was lower than previously reported by their authors. However, according to the accessory pathway site, the algorithm designed by Arruda et al. showed better predictions than the other algorithms and using this algorithm may provide advantages before a planned ablation.

  2. Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer

    NARCIS (Netherlands)

    Blauwhoff-Buskermolen, Susanne; Versteeg, Kathelijn S.; de van der Schueren, Marian A. E.; den Braver, Nicole R.; Berkhof, Johannes; Langius, Jacqueline A. E.; Verheul, Henk M. W.

    2016-01-01

    Low muscle mass is present in approximately 40% of patients with metastatic colorectal cancer (mCRC) and may be associated with poor outcome. We studied change in skeletal muscle during palliative chemotherapy in patients with mCRC and its association with treatment modifications and overall

  3. The biomarkers neuron-specific enolase and S100b measured the day following admission for severe accidental hypothermia have high predictive values for poor outcome

    DEFF Research Database (Denmark)

    Wiberg, Sebastian; Kjaergaard, Jesper; Kjærgaard, Benedict

    2017-01-01

    was analyzed for NSE and S100b. Follow-up was conducted after 30days and poor neurologic outcome was defined as a Cerebral Performance Category (CPC) score of 3-5. The predictive value of NSE and S100b was assessed as the area under the receiver-operating characteristics curve (AUC). RESULTS: A total of 34......AIM: The aim of the present study was to assess the ability of the biomarkers neuron-specific enolase (NSE) and S100 calcium-binding protein b (S100b) to predict mortality and poor neurologic outcome after 30days in patients admitted with severe accidental hypothermia. METHODS: Consecutive patients...... in 30 unconscious and/or sedated patients. NSE and S100b achieved AUCs of 0.93 and 0.88, respectively, for prediction of 30day mortality and AUCs of 0.88 and 0.87, respectively, for prediction of poor neurologic outcome. CONCLUSIONS: In patients remaining unconscious the day following admission...

  4. Activation of the Serotonin Pathway is Associated with Poor Outcome in COPD Exacerbation: Results of a Long-Term Cohort Study.

    Science.gov (United States)

    Meier, Marc A; Ottiger, Manuel; Vögeli, Alaadin; Steuer, Christian; Bernasconi, Luca; Thomann, Robert; Christ-Crain, Mirjam; Henzen, Christoph; Hoess, Claus; Zimmerli, Werner; Huber, Andreas; Mueller, Beat; Schuetz, Philipp

    2017-06-01

    predictive of 18-month mortality. Whether therapeutic modulation of the serotonin pathway has positive effects on outcome needs further investigation.

  5. A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders.

    Science.gov (United States)

    DiLuigi, Andrea J; Engmann, Lawrence; Schmidt, David W; Benadiva, Claudio A; Nulsen, John C

    2011-06-30

    We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. 1 H MR spectroscopy in cervical carcinoma using external phase array body coil at 3.0 Tesla: Prediction of poor prognostic human papillomavirus genotypes.

    Science.gov (United States)

    Lin, Gigin; Lai, Chyong-Huey; Tsai, Shang-Yueh; Lin, Yu-Chun; Huang, Yu-Ting; Wu, Ren-Chin; Yang, Lan-Yan; Lu, Hsin-Ying; Chao, Angel; Wang, Chiun-Chieh; Ng, Koon-Kwan; Ng, Shu-Hang; Chou, Hung-Hsueh; Yen, Tzu-Chen; Hung, Ji-Hong

    2017-03-01

    To assess the clinical value of proton ( 1 H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT). 1 H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha-7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis. A 4.3-fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno-/adenosquamous carcinoma (Chi-square, P < 0.0001). In prediction of the four patients with persistent disease after CCRT, elevated methyl resonance demonstrated a sensitivity of 100%, a specificity of 74%, and an AUC of 0.82. 1 H MR spectroscopy at 3T can be used to depict the elevated lipid resonance levels in cervical carcinomas, as well as help to predict the poor prognostic HPV genotypes and persistent disease following CCRT. Further large studies with longer follow up times are warranted to validate our initial findings. 1 J. Magn. Reson. Imaging 2017;45:899-907. © 2016 International Society for Magnetic Resonance in Medicine.

  7. Co-occurrence of avoidant personality disorder and child sexual abuse predicts poor outcome in long-standing eating disorder.

    Science.gov (United States)

    Vrabel, Karianne R; Hoffart, Asle; Rø, Oyvind; Martinsen, Egil W; Rosenvinge, Jan H

    2010-08-01

    Few consistent predictive factors for eating disorder have been identified across studies. In the current 5-year prospective study, the objective was to examine whether (a) personality disorder and child sexual abuse predict the course of severity of eating disorder symptoms after inpatient treatment and (b) how the predictors interact. A total of 74 patients with long-standing eating disorder and mean age of 30 years were assessed at the beginning and end of inpatient therapy and at 1-, 2-, and 5-year follow-up. A mixed model was used to examine the predictors. Avoidant personality disorder and child sexual abuse interacted in predicting high levels of eating disorder over a long-term course. These results suggest that eating disorder, avoidant personality disorder, and sequelae after child sexual abuse are potential targets for treatment that need further investigation. Copyright 2010 APA, all rights reserved

  8. Kinetics of protein–ligand unbinding: Predicting pathways, rates, and rate-limiting steps

    Science.gov (United States)

    Tiwary, Pratyush; Limongelli, Vittorio; Salvalaglio, Matteo; Parrinello, Michele

    2015-01-01

    The ability to predict the mechanisms and the associated rate constants of protein–ligand unbinding is of great practical importance in drug design. In this work we demonstrate how a recently introduced metadynamics-based approach allows exploration of the unbinding pathways, estimation of the rates, and determination of the rate-limiting steps in the paradigmatic case of the trypsin–benzamidine system. Protein, ligand, and solvent are described with full atomic resolution. Using metadynamics, multiple unbinding trajectories that start with the ligand in the crystallographic binding pose and end with the ligand in the fully solvated state are generated. The unbinding rate koff is computed from the mean residence time of the ligand. Using our previously computed binding affinity we also obtain the binding rate kon. Both rates are in agreement with reported experimental values. We uncover the complex pathways of unbinding trajectories and describe the critical rate-limiting steps with unprecedented detail. Our findings illuminate the role played by the coupling between subtle protein backbone fluctuations and the solvation by water molecules that enter the binding pocket and assist in the breaking of the shielded hydrogen bonds. We expect our approach to be useful in calculating rates for general protein–ligand systems and a valid support for drug design. PMID:25605901

  9. Automated tool for virtual screening and pharmacology-based pathway prediction and analysis

    Directory of Open Access Journals (Sweden)

    Sugandh Kumar

    2017-10-01

    Full Text Available The virtual screening is an effective tool for the lead identification in drug discovery. However, there are limited numbers of crystal structures available as compared to the number of biological sequences which makes (Structure Based Drug Discovery SBDD a difficult choice. The current tool is an attempt to automate the protein structure modelling and automatic virtual screening followed by pharmacology-based prediction and analysis. Starting from sequence(s, this tool automates protein structure modelling, binding site identification, automated docking, ligand preparation, post docking analysis and identification of hits in the biological pathways that can be modulated by a group of ligands. This automation helps in the characterization of ligands selectivity and action of ligands on a complex biological molecular network as well as on individual receptor. The judicial combination of the ligands binding different receptors can be used to inhibit selective biological pathways in a disease. This tool also allows the user to systemically investigate network-dependent effects of a drug or drug candidate.

  10. Boolean network model for cancer pathways: predicting carcinogenesis and targeted therapy outcomes.

    Directory of Open Access Journals (Sweden)

    Herman F Fumiã

    Full Text Available A Boolean dynamical system integrating the main signaling pathways involved in cancer is constructed based on the currently known protein-protein interaction network. This system exhibits stationary protein activation patterns--attractors--dependent on the cell's microenvironment. These dynamical attractors were determined through simulations and their stabilities against mutations were tested. In a higher hierarchical level, it was possible to group the network attractors into distinct cell phenotypes and determine driver mutations that promote phenotypic transitions. We find that driver nodes are not necessarily central in the network topology, but at least they are direct regulators of central components towards which converge or through which crosstalk distinct cancer signaling pathways. The predicted drivers are in agreement with those pointed out by diverse census of cancer genes recently performed for several human cancers. Furthermore, our results demonstrate that cell phenotypes can evolve towards full malignancy through distinct sequences of accumulated mutations. In particular, the network model supports routes of carcinogenesis known for some tumor types. Finally, the Boolean network model is employed to evaluate the outcome of molecularly targeted cancer therapies. The major find is that monotherapies were additive in their effects and that the association of targeted drugs is necessary for cancer eradication.

  11. Increased ratio of serum matrix metalloproteinase-9 against TIMP-1 predicts poor wound healing in diabetic foot ulcers.

    Science.gov (United States)

    Li, Zhihong; Guo, Shuqin; Yao, Fang; Zhang, Yunliang; Li, Tingting

    2013-01-01

    Little is known about serum concentrations of Matrix Metalloproteinase-9 (MMP-9), MMP-2, TIMP-1 and TIMP-2 in diabetic patients with foot ulcers. This study demonstrates their relationship with wound healing. Ninety-four patients with diabetic foot ulcers were recruited in the study. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured at the first clinic visit and the end of 4-week treatment and followed up till 12 weeks. According to the decreasing rate of ulcer healing area at the fourth week, we divided those cases into good and poor healers. Through analyses, we explore the possible relationship among those factors and degree of wound healing. The median level of serum MMP-9 in good healers was lower than poor healers at first visit (124.2 μg/L vs 374.6 μg/L, phealing than MMP-9 alone before therapy and after 4 week treatment (r = -0.6475 vs -0.3251, r = -0.7096 vs -0.1231, respectively). Receiver Operator Curve (ROC) showed that the cutoff for MMP-9/TIMP-1 ratio at healing and might provide a novel target for the future therapy in diabetic foot ulcers. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. A Systematic Review on Prognostic Indicators of Acute Liver Failure and Their Predictive Value for Poor Outcome

    NARCIS (Netherlands)

    Wlodzimirow, Kama A.; Eslami, Saeid; Abu-Hanna, Ameen; Nieuwoudt, Martin; Chamuleau, Robert A. F. M.

    2014-01-01

    This review provides a large amount of information, including the extensive list of worldwide used indicators to predict outcome in patients with acute liver failure. There is large heterogeneity in prognostic indicators of acute liver failure, methods of measurement, complexity of calculation and

  13. Postprandial regulation of hepatic microRNAs predicted to target the insulin pathway in rainbow trout.

    Directory of Open Access Journals (Sweden)

    Jan A Mennigen

    Full Text Available Rainbow trout are carnivorous fish and poor metabolizers of carbohydrates, which established this species as a model organism to study the comparative physiology of insulin. Following the recent characterisation of key roles of several miRNAs in the insulin action on hepatic intermediary metabolism in mammalian models, we investigated the hypothesis that hepatic miRNA expression is postprandially regulated in the rainbow trout and temporally coordinated in the context of insulin-mediated regulation of metabolic gene expression in the liver. To address this hypothesis, we used a time-course experiment in which rainbow trout were fed a commercial diet after short-term fasting. We investigated hepatic miRNA expression, activation of the insulin pathway, and insulin regulated metabolic target genes at several time points. Several miRNAs which negatively regulate hepatic insulin signaling in mammalian model organisms were transiently increased 4 h after the meal, consistent with a potential role in acute postprandial negative feed-back regulation of the insulin pathway and attenuation of gluconeogenic gene expression. We equally observed a transient increase in omy- miRNA-33 and omy-miRNA-122b 4 h after feeding, whose homologues have potent lipogenic roles in the liver of mammalian model systems. A concurrent increase in the activity of the hepatic insulin signaling pathway and the expression of lipogenic genes (srebp1c, fas, acly was equally observed, while lipolytic gene expression (cpt1a and cpt1b decreased significantly 4 h after the meal. This suggests lipogenic roles of omy-miRNA-33 and omy-miRNA-122b may be conserved between rainbow trout and mammals and that these miRNAs may furthermore contribute to acute postprandial regulation of de novo hepatic lipid synthesis in rainbow trout. These findings provide a framework for future research of miRNA regulation of hepatic metabolism in trout and will help to further elucidate the metabolic

  14. Doses from aquatic pathways in CSA-N288.1: deterministic and stochastic predictions compared

    Energy Technology Data Exchange (ETDEWEB)

    Chouhan, S.L.; Davis, P

    2002-04-01

    The conservatism and uncertainty in the Canadian Standards Association (CSA) model for calculating derived release limits (DRLs) for aquatic emissions of radionuclides from nuclear facilities was investigated. The model was run deterministically using the recommended default values for its parameters, and its predictions were compared with the distributed doses obtained by running the model stochastically. Probability density functions (PDFs) for the model parameters for the stochastic runs were constructed using data reported in the literature and results from experimental work done by AECL. The default values recommended for the CSA model for some parameters were found to be lower than the central values of the PDFs in about half of the cases. Doses (ingestion, groundshine and immersion) calculated as the median of 400 stochastic runs were higher than the deterministic doses predicted using the CSA default values of the parameters for more than half (85 out of the 163) of the cases. Thus, the CSA model is not conservative for calculating DRLs for aquatic radionuclide emissions, as it was intended to be. The output of the stochastic runs was used to determine the uncertainty in the CSA model predictions. The uncertainty in the total dose was high, with the 95% confidence interval exceeding an order of magnitude for all radionuclides. A sensitivity study revealed that total ingestion doses to adults predicted by the CSA model are sensitive primarily to water intake rates, bioaccumulation factors for fish and marine biota, dietary intakes of fish and marine biota, the fraction of consumed food arising from contaminated sources, the irrigation rate, occupancy factors and the sediment solid/liquid distribution coefficient. To improve DRL models, further research into aquatic exposure pathways should concentrate on reducing the uncertainty in these parameters. The PDFs given here can he used by other modellers to test and improve their models and to ensure that DRLs

  15. Age-related Changes in Lateral Entorhinal and CA3 Neuron Allocation Predict Poor Performance on Object Discrimination

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    Andrew P. Maurer

    2017-06-01

    Full Text Available Age-related memory deficits correlate with dysfunction in the CA3 subregion of the hippocampus, which includes both hyperactivity and overly rigid activity patterns. While changes in intrinsic membrane currents and interneuron alterations are involved in this process, it is not known whether alterations in afferent input to CA3 also contribute. Neurons in layer II of the lateral entorhinal cortex (LEC project directly to CA3 through the perforant path, but no data are available regarding the effects of advanced age on LEC activity and whether these activity patterns update in response to environmental change. Furthermore, it is not known the extent to which age-related deficits in sensory discrimination relate to the inability of aged CA3 neurons to update in response to new environments. Young and aged rats were pre-characterized on a LEGO© object discrimination task, comparable to behavioral tests in humans in which CA3 hyperactivity has been linked to impairments. The cellular compartment analysis of temporal activity with fluorescence in situ hybridization for the immediate-early gene Arc was then used to identify the principal cell populations that were active during two distinct epochs of random foraging in different environments. This approach enabled the extent to which rats could discriminate two similar objects to be related to the ability of CA3 neurons to update across different environments. In both young and aged rats, there were animals that performed poorly on the LEGO object discrimination task. In the aged rats only, however, the poor performers had a higher percent of CA3 neurons that were active during random foraging in a novel environment, but this is not related to the ability of CA3 neurons to remap when the environment changed. Afferent neurons to CA3 in LEC, as identified with the retrograde tracer choleratoxin B (CTB, also showed a higher percentage of cells that were positive for Arc mRNA in aged poor performing rats

  16. Thermodynamic approach to improving solubility prediction of co-crystals in comparison with individual poorly soluble components

    International Nuclear Information System (INIS)

    Perlovich, German L.

    2014-01-01

    Highlights: • Thermodynamic approach for solubility improvement of co-crystal was developed. • The graphical technique for estimation of co-crystal solubility was elaborated. • Hydration enthalpies of some drugs and amino acids were calculated. • Applicability/operability of the approach was exemplified by some drugs and amino acids. - Abstract: A novel thermodynamic approach to compare poorly soluble components (active pharmaceutical ingredient (API)) both in co-crystals and individual compounds was developed. An algorithm of choosing potential co-crystals with improved solubility characteristics on the basis of the known solvation/hydration API and co-former enthalpies is described. The applicability and operability of the algorithm were tested exemplified by some drugs and amino acids

  17. B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer

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    Jiali Li

    2018-01-01

    Full Text Available Background/Aims: It is well established that many non-trophoblastic tumors secrete HCG (human chorionic gonadotropin and that such secretion is correlated with the poor prognosis of tumor patients. This study aims to analyze the correlation between β-HCG expression and outcome of colorectal cancer (CRC and understand its role in CRC pathology Methods: We detected the mRNA and protein expression of β-HCG in human CRC tissues with RT-qPCR and immunohistochemistry, and we compared the clinical-pathological characteristics, prognosis and progression between the β-HCG positive and negative groups. We also generated CRC cell lines with β-HCG over-expression as well as β-HCG stable knockout, and evaluated cell function and mechanism in vitro and in vivo. Results: Fifty out of 136 CRC patients (37% expressed β-HCG at the invasive front. Clinical-pathological data showed that β-HCG was positively correlated with Dukes staging (P=0.031 and lymph node metastasis (P=0.012. Survival analysis suggested that the patients with high expression of β-HCG had poorer prognosis than those with low β-HCG expression (P=0.0289. β-HCG expression level was also positively correlated with tumor invasion in early-stage CRC patient tissues (P=0.0227. Additionally β-HCG promoted the migration and invasion of CRC in vitro and in vivo but had no effect on the proliferation of tumor cells. Conclusion: Our study demonstrated that β-HCG was ectopically expressed in the CRC patients and its high expression correlated with poor prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes the migration and invasion of CRC by epithelial-mesenchymal transition (EMT.

  18. Rac1 overexpression is correlated with epithelial mesenchymal transition and predicts poor prognosis in non-small cell lung cancer.

    Science.gov (United States)

    Zhou, Yujuan; Liao, Qianjin; Han, Yaqian; Chen, Jie; Liu, Zhigang; Ling, Hang; Zhang, Jing; Yang, Wenjuan; Oyang, Linda; Xia, Longzheng; Wang, Li; Wang, Heran; Xue, Lei; Wang, Hui; Hu, Bingqiang

    2016-01-01

    Objective: Ras-related C3 botulinum toxin substrate1(Rac1) and epithelial mesenchymal transition (EMT) are key therapeutic targets in cancer. We investigated the clinical significance of Rac1 and markers of EMT expression in non-small cell lung cancer (NSCLC), and their possible correlation with EMT phenotype. Methods: Immunohistochemistry was used to assess the expression of Rac1, Snail1, Twist1, N-cadherin (N-cad), Vimentin (Vim), and E-cadherin (E-cad) in 153 NSCLC paraffin-embedded specimens and 45 normal specimens adjacent to tumors. The correlation of Rac1 and EMT markers with clinicopathological characteristics and the relationship between the protein levels and progression-free survival (PFS) and overall survival (OS) were analyzed. Results: Compared with non-tumor tissues, the NSCLC tissues showed marked elevation in the levels of Rac1, Snail1, Twist1, N-cad, and Vim levels, whereas the E-cad levels were significantly decreased (P Rac1 and EMT markers was significantly associated with TNM stage and metastasis (P Rac1 may be associated with poor OS and PFS compared with low expression (PRac1, Snail1, Twist1, N-cad, Vim, and E-cad was an independent prognostic factor in NSCLC. Interestingly, Rac1 expression was positively correlated with Snail1, Twist1, N-cad, and Vim levels (r=0.563, r=0.440, r=0.247 r=0.536, PRac1, Twist, Snail1, Vim and N-cad were highly expressed in lung cancer patients resistant to radiotherapy, while E-cad was poorly expressed. Conclusion: Rac1 may promote NSCLC progression and metastasis via EMT, which may be considered as a potential therapeutic target.

  19. Presence of Systemic Inflammatory Response Syndrome Predicts a Poor Clinical Outcome in Dogs with a Primary Hepatitis.

    Directory of Open Access Journals (Sweden)

    Scott Kilpatrick

    Full Text Available Primary hepatopathies are a common cause of morbidity and mortality in dogs. The underlying aetiology of most cases of canine hepatitis is unknown. Consequently, treatments are typically palliative and it is difficult to provide accurate prognostic information to owners. In human hepatology there is accumulating data which indicates that the presence of systemic inflammatory response syndrome (SIRS is a common and debilitating event in patients with liver diseases. For example, the presence of SIRS has been linked to the development of complications such as hepatic encephalopathy (HE and is associated with a poor clinical outcome in humans with liver diseases. In contrast, the relationship between SIRS and clinical outcome in dogs with a primary hepatitis is unknown. Seventy dogs with histologically confirmed primary hepatitis were enrolled into the study. Additional clinical and clinicopathological information including respiratory rate, heart rate, temperature, white blood cell count, sodium, potassium, sex, presence of ascites, HE score, alanine aminotransferase (ALT, alkaline phosphatase (ALP, bilirubin and red blood cell concentration were available in all cases. The median survival of dogs with a SIRS score of 0 or 1 (SIRS low was 231 days compared to a median survival of 7 days for dogs with a SIRS score of 2, 3 or 4 (SIRS high (p<0.001. A Cox proportional hazard model, which included all other co-variables, revealed that a SIRS high score was an independent predictor of a poor clinical outcome. The effect of modulating inflammation on treatment outcomes in dogs with a primary hepatitis is deserving of further study.

  20. Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild-type metastatic colorectal cancer.

    Science.gov (United States)

    Kim, Dalyong; Kim, Sun Young; Lee, Ji Sung; Hong, Yong Sang; Kim, Jeong Eun; Kim, Kyu-Pyo; Kim, Jihun; Jang, Se Jin; Yoon, Young-Kwang; Kim, Tae Won

    2017-11-23

    In metastatic colorectal cancer, the location of the primary tumor has been suggested to have biological significance. In this study, we investigated whether primary tumor location affects cetuximab efficacy in patients with RAS wild-type metastatic colorectal cancer. Genotyping by the SequenomMassARRAY technology platform (OncoMap) targeting KRAS, NRAS, PIK3CA, and BRAF was performed in tumors from 307 patients who had been given cetuximab as salvage treatment. Tumors with mutated RAS (KRAS or NRAS; n = 127) and those with multiple primary location (n = 10) were excluded. Right colon cancer was defined as a tumor located in the proximal part to splenic flexure. A total of 170 patients were included in the study (right versus left, 23 and 147, respectively). Patients with right colon cancer showed more mutated BRAF (39.1% vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs. 3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and rectal cancer. Right colon cancer showed poorer progression-free survival (2.0 vs.5.0 months, P = 0.002) and overall survival (4.1 months and 13.0 months, P < 0.001) than the left colon and rectal cancer. By multivariable analysis, BRAF mutation, right colon primary, poorly differentiated histology, and peritoneal involvement were associated with risk of death. In RAS wild-type colon cancer treated with cetuximab as salvage treatment, right colon primary was associated with poorer survival outcomes than left colon and rectal cancer.

  1. Quantitative power Doppler ultrasound measures of peripheral joint synovitis in poor prognosis early rheumatoid arthritis predict radiographic progression.

    Science.gov (United States)

    Sreerangaiah, Dee; Grayer, Michael; Fisher, Benjamin A; Ho, Meilien; Abraham, Sonya; Taylor, Peter C

    2016-01-01

    To assess the value of quantitative vascular imaging by power Doppler US (PDUS) as a tool that can be used to stratify patient risk of joint damage in early seropositive RA while still biologic naive but on synthetic DMARD treatment. Eighty-five patients with seropositive RA of power Doppler volume and 2D vascularity scores were the most useful US predictors of deterioration. These variables were modelled in two equations that estimate structural damage over 12 months. The equations had a sensitivity of 63.2% and specificity of 80.9% for predicting radiographic structural damage and a sensitivity of 54.2% and specificity of 96.7% for predicting structural damage on ultrasonography. In seropositive early RA, quantitative vascular imaging by PDUS has clinical utility in predicting which patients will derive benefit from early use of biologic therapy. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Type D Personality Predicts Poor Medication Adherence in Chinese Patients with Type 2 Diabetes Mellitus: A Six-Month Follow-Up Study.

    Directory of Open Access Journals (Sweden)

    Xuemei Li

    Full Text Available Type D personality and medication nonadherence have been shown to be associated with poor health outcomes. Type D personality is associated with poor medication adherence in patients with coronary artery disease, myocardial infarction, and heart failure. However, the relationship between type D personality and medication adherence in patients with Type 2 Diabetes Mellitus (T2DM remains unknown. This study aims to examine whether type D personality was associated with medication adherence in patients with T2DM.A follow-up study was conducted in general hospital of the People's Liberation Army in Beijing.412 T2DM patients (205 females, who were recruited by circular systematic random sampling, provided demographic and baseline data about medical information and completed measures of Type D personality. Then, 330 patients went on to complete a self-report measure of medication adherence at the sixth month after baseline data collection. Chi-square test, t tests, and hierarchical multiple regression analyses were conducted, as needed.Patients with type D personality were significantly more likely to have poor medication adherence (p<0.001. Type D personality predicts poor medication adherence before and after controlling for covariates when it was analyzed as a categorical variable. However, the dimensional construct of type D personality was not associated with medication adherence when analyzed as a continuous variable.Although, as a dimensional construct, type D personality may not reflect the components of the personality associated with poor medication adherence in patients with T2DM, screening for type D personality may help to identify those who are at higher risk of poor medication adherence. Interventions, aiming to improve medication adherence, should be launched for these high-risk patients.

  3. FREQUENT SUBGRAPH MINING OF PERSONALIZED SIGNALING PATHWAY NETWORKS GROUPS PATIENTS WITH FREQUENTLY DYSREGULATED DISEASE PATHWAYS AND PREDICTS PROGNOSIS.

    Science.gov (United States)

    Durmaz, Arda; Henderson, Tim A D; Brubaker, Douglas; Bebek, Gurkan

    2017-01-01

    Large scale genomics studies have generated comprehensive molecular characterization of numerous cancer types. Subtypes for many tumor types have been established; however, these classifications are based on molecular characteristics of a small gene sets with limited power to detect dysregulation at the patient level. We hypothesize that frequent graph mining of pathways to gather pathways functionally relevant to tumors can characterize tumor types and provide opportunities for personalized therapies. In this study we present an integrative omics approach to group patients based on their altered pathway characteristics and show prognostic differences within breast cancer (p network-based classifier algorithms and showed that our unsupervised approach generates more robust and biologically relevant clustering whereas previous approaches failed to report specific functions for similar patient groups or classify patients into prognostic groups. These results could serve as a means to improve prognosis for future cancer patients, and to provide opportunities for improved treatment options and personalized interventions. The proposed novel graph mining approach is able to integrate PPI networks with gene expression in a biologically sound approach and cluster patients in to clinically distinct groups. We have utilized breast cancer and glioblastoma multiforme datasets from microarray and RNA-Seq platforms and identified disease mechanisms differentiating samples. Supplementary methods, figures, tables and code are available at https://github.com/bebeklab/dysprog.

  4. Depressive symptoms predict head and neck cancer survival: Examining plausible behavioral and biological pathways.

    Science.gov (United States)

    Zimmaro, Lauren A; Sephton, Sandra E; Siwik, Chelsea J; Phillips, Kala M; Rebholz, Whitney N; Kraemer, Helena C; Giese-Davis, Janine; Wilson, Liz; Bumpous, Jeffrey M; Cash, Elizabeth D

    2018-03-01

    Head and neck cancers are associated with high rates of depression, which may increase the risk for poorer immediate and long-term outcomes. Here it was hypothesized that greater depressive symptoms would predict earlier mortality, and behavioral (treatment interruption) and biological (treatment response) mediators were examined. Patients (n = 134) reported depressive symptomatology at treatment planning. Clinical data were reviewed at the 2-year follow-up. Greater depressive symptoms were associated with significantly shorter survival (hazard ratio, 0.868; 95% confidence interval [CI], 0.819-0.921; P ratio, 0.865; 95% CI, 0.774-0.966; P = .010), and poorer treatment response (odds ratio, 0.879; 95% CI, 0.803-0.963; P = .005). The poorer treatment response partially explained the depression-survival relation. Other known prognostic indicators did not challenge these results. Depressive symptoms at the time of treatment planning predict overall 2-year mortality. Effects are partly influenced by the treatment response. Depression screening and intervention may be beneficial. Future studies should examine parallel biological pathways linking depression to cancer survival, including endocrine disruption and inflammation. Cancer 2018;124:1053-60. © 2018 American Cancer Society. © 2018 American Cancer Society.

  5. Quantifying the Pathway and Predicting Spontaneous Emulsification during Material Exchange in a Two Phase Liquid System.

    Science.gov (United States)

    Spooner, Stephen; Rahnama, Alireza; Warnett, Jason M; Williams, Mark A; Li, Zushu; Sridhar, Seetharaman

    2017-10-30

    Kinetic restriction of a thermodynamically favourable equilibrium is a common theme in materials processing. The interfacial instability in systems where rate of material exchange is far greater than the mass transfer through respective bulk phases is of specific interest when tracking the transient interfacial area, a parameter integral to short processing times for productivity streamlining in all manufacturing where interfacial reaction occurs. This is even more pertinent in high-temperature systems for energy and cost savings. Here the quantified physical pathway of interfacial area change due to material exchange in liquid metal-molten oxide systems is presented. In addition the predicted growth regime and emulsification behaviour in relation to interfacial tension as modelled using phase-field methodology is shown. The observed in-situ emulsification behaviour links quantitatively the geometry of perturbations as a validation method for the development of simulating the phenomena. Thus a method is presented to both predict and engineer the formation of micro emulsions to a desired specification.

  6. Up-regulation of 91H promotes tumor metastasis and predicts poor prognosis for patients with colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Qiwen Deng

    Full Text Available Long noncoding RNAs (lncRNAs play widespread roles in gene regulation and cellular processes. However, the functional roles of lncRNAs in colorectal cancer (CRC are not yet well elucidated. The aim of the present study was to measure the levels of lncRNA 91H expression in CRC and evaluate its clinical significance and biological roles in the development and progression of CRC.91H expression and copy number variation (CNV were measured in 72 CRC tumor tissues and adjacent normal tissues by real-time PCR. The biological roles of 91H were evaluated by MTT, scratch wound assay, migration and invasion assays, and flow cytometry.91H was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Moreover, 91H overexpression was closely associated with distant metastasis and poor prognosis in patients with CRC, except for CNV of 91H. Multivariate analysis indicated that 91H expression was an independent prognostic indicator, as well as distant metastasis. Our in vitro data indicated that knockdown of 91H inhibited the proliferation, migration, and invasiveness of CRC cells.91H played an important role in the molecular etiology of CRC and might be regarded as a novel prognosis indicator in patients with CRC.

  7. LncRNA-SNHG16 predicts poor prognosis and promotes tumor proliferation through epigenetically silencing p21 in bladder cancer.

    Science.gov (United States)

    Cao, Xianxiang; Xu, Jing; Yue, Dong

    2018-02-01

    More and more evidences have ensured the crucial functions of long non-coding RNAs (lncRNAs) in multiple tumors. It has been discovered that lncRNA-SNHG16 is involved in many tumors. Even so, it is still necessary to study SNHG16 comprehensively in bladder cancer. In terms of our study, the level of SNHG16 both in the tumor tissues and cell lines was measured and the relationship among SNHG16, clinicopathological traits and prognosis was explored. Interference assays were applied to determine the biological functions of SNHG16. It was discovered that the level of SNHG16 was evidently enhanced both in tissues and cell lines of bladder cancer. Patients with highly expressed SNHG16 suffered from poor overall survival. Multivariable Cox proportional hazards regression analysis implied that highly expressed SNHG16 could be used as an independent prognostic marker. It could be known from functional assays that silenced SNHG16 impaired cell proliferation, owing to the effects of SNHG16 on cell cycle and apoptosis. Finally, mechanism experiments revealed that SNHG16 could epigenetically silence the expression of p21. The facts above pointed out that lncRNA-SNHG16 might be quite vital for the diagnosis and development of bladder cancer, and could even become an important therapeutic target for bladder cancer.

  8. High expression of WWP1 predicts poor prognosis and associates with tumor progression in human colorectal cancer

    Science.gov (United States)

    Chen, Jian-Jun; Zhang, Wei

    2018-01-01

    WWP1 (WW domain-containing E3 ubiquitin protein ligase 1), which is frequently up-regulated in multiple human malignancies, has been demonstrated to play a critical function in cell proliferation, apoptosis and invasion. However, limited knowledge is known about the expression pattern and prognostic value of WWP1 in colorectal cancer (CRC). In this study, we firstly observed that WWP1 mRNA and protein is commonly up-regulated in CRC tissues compared with normal counterparts. Furthermore, by immunohistochemical analysis in 348 cases of CRC specimens, we demonstrated that the WWP1 protein expression is up-regulated in 58.91% (205/348) samples and detected increasing WWP1 expression is closely correlated with enhanced tumor size (P=0.022), CEA level (P=0.021), T classification (P=0.010), distant metastasis (P=0.021) and TNM stage (P=0.005). Meanwhile, Kaplan-Meier survival analysis showed CRC patients with a high WWP1 expression have a poorer overall survival (P<0.001) and disease-free survival (P=0.001) than those with a low WWP1 expression. Multivariate Cox regression analysis revealed WWP1 is the independent prognostic factors for overall survival rate of CRC patients. What’s more, by CCK-8 assays and Transwell assays, we found WWP1 depletion markedly inhibited tumor proliferation and invasion in CRC cells, and cells with WWP1 overexpression had a prominently higher proliferative and invasive capacity. Most notably, we illuminated WWP1 downregulation inactivated PTEN/Akt pathway in CRC cells. Taken together, our studies revealed the prognostic value of WWP1 in CRC and support that WWP1 may act as a molecular target for CRC treatment. PMID:29511596

  9. The chronic obstructive pulmonary disease assessment test improves the predictive value of previous exacerbations for poor outcomes in COPD.

    Science.gov (United States)

    Miravitlles, Marc; García-Sidro, Patricia; Fernández-Nistal, Alonso; Buendía, María Jesús; Espinosa de Los Monteros, María José; Esquinas, Cristina; Molina, Jesús

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) exacerbations have a negative impact on the quality of life of patients and the evolution of the disease. We have investigated the prognostic value of several health-related quality of life questionnaires to predict the appearance of a composite event (new ambulatory or emergency exacerbation, hospitalization, or death) over a 1-year follow-up. This was a multicenter, prospective, observational study. Patients completed four questionnaires after recovering from an exacerbation (COPD Assessment Test [CAT], a Clinical COPD Questionnaire [CCQ], COPD Severity Score [COPDSS], and Airways Questionnaire [AQ20]). Patients were followed-up until the appearance of the composite event or for 1 year, whichever came first. A total of 497 patients were included in the study. The majority of them were men (89.7%), with a mean age of 68.7 (SD 9.2) years, and a forced expiratory volume in 1 second of 47.1% (SD 17.5%). A total of 303 (61%) patients experienced a composite event. Patients with an event had worse mean scores of all questionnaires at baseline compared to patients without event: CAT=12.5 vs 11.3 (P=0.028); CCQ=2.2 vs 1.9 (P=0.013); COPDSS=12.3 vs 10.9 (P=0.001); AQ20=8.3 vs 7.5 (P=0.048). In the multivariate analysis, only previous history of exacerbations and CAT score ≥13.5 were significant risk factors for the composite event. A CAT score ≥13.5 increased the predictive value of previous exacerbations with an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.829-0.899; P=0.001). The predictive value of previous exacerbations significantly increased only in one of the four trialled questionnaires, namely in the CAT questionnaire. However, previous history of exacerbations was the strongest predictor of the composite event.

  10. Remnant cholesterol predicts periprocedural myocardial injury following percutaneous coronary intervention in poorly-controlled type 2 diabetes.

    Science.gov (United States)

    Zeng, Rui-Xiang; Li, Sha; Zhang, Min-Zhou; Li, Xiao-Lin; Zhu, Cheng-Gang; Guo, Yuan-Lin; Zhang, Yan; Li, Jian-Jun

    2017-08-01

    Remnant cholesterol (RC) is receiving increasing attention regarding its relation to cardiovascular risk. Whether RC is associated with periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) in type 2 diabetes (T2D) is currently unknown. We prospectively enrolled 1182 consecutive T2D patients who were scheduled for PCI but with baseline normal preprocedural cardiac troponin I (cTnI). Patients were divided according to their glycemic control status: group A [glycated hemoglobin (HbA1c)cholesterol ratio (RC/HDL-C) with PMI were investigated. The associations of RC and RC/HDL-C with PMI were observed in group B (both p0.05). Patients in group B, a 1-SD increase of RC produced 30% and 32% increased risk for postprocedural cTnI>3× upper limit of normal (ULN) and >5×ULN, respectively. The odds ratios for RC/HDL-C were the highest compared with any cholesterol fractions including total cholesterol (TC)/HDL-C, low density lipoprotein cholesterol (LDL-C)/HDL-C, nonHDL-C/HDL-C, and triglyceride/HDL-C with 1.43 [95% confidence interval (CI): 1.10-1.88] for >3× ULN and 1.49 (95% CI: 1.13-1.97) for >5× ULN. However, no such associations were found in group A. Furthermore, patients with RC >27.46mg/dL (third tertile) [RC≤14.15mg/dL (first tertile) as reference] were associated with a 1.57-fold and 2-fold increased risk for >3× ULN and >5× ULN in group B, respectively. RC and RC/HDL-C might be valuable, independent predictors for PMI in poorly-controlled diabetic patients undergoing PCI. Copyright © 2017. Published by Elsevier Ltd.

  11. Co-expression of podoplanin and fibroblast growth factor 1 predicts poor prognosis in patients with lung squamous cell carcinoma.

    Science.gov (United States)

    Li, Juan; Chen, Han; Li, Xiaoqing; Wang, Linlin; Gao, Aiqin; Zhang, Pei; Lin, Wenli; Gao, Wei; Yang, Dong; Guo, Xiaosun; Liu, Jie; Dang, Qi; Sun, Yuping

    2017-08-01

    demonstrated that podoplanin was co‑expressed with FGF1 in lung SQCC and this co‑expression was correlated with poor prognosis.

  12. Concurrent acute illness and comorbid conditions poorly predict antibiotic use in upper respiratory tract infections: a cross-sectional analysis

    Directory of Open Access Journals (Sweden)

    Perencevich Eli N

    2007-05-01

    Full Text Available Abstract Background Inappropriate antibiotic use promotes resistance. Antibiotics are generally not indicated for upper respiratory infections (URIs. Our objectives were to describe patterns of URI treatment and to identify patient and provider factors associated with antibiotic use for URIs. Methods This study was a cross-sectional analysis of medical and pharmacy claims data from the Pennsylvania Medicaid fee-for-service program database. We identified Pennsylvania Medicaid recipients with a URI office visit over a one-year period. Our outcome variable was antibiotic use within seven days after the URI visit. Study variables included URI type and presence of concurrent acute illnesses and chronic conditions. We considered the associations of each study variable with antibiotic use in a logistic regression model, stratifying by age group and adjusting for confounders. Results Among 69,936 recipients with URI, 35,786 (51.2% received an antibiotic. In all age groups, acute sinusitis, chronic sinusitis, otitis, URI type and season were associated with antibiotic use. Except for the oldest group, physician specialty and streptococcal pharyngitis were associated with antibiotic use. History of chronic conditions was not associated with antibiotic use in any age group. In all age groups, concurrent acute illnesses and history of chronic conditions had only had fair to poor ability to distinguish patients who received an antibiotic from patients who did not. Conclusion Antibiotic prevalence for URIs was high, indicating that potentially inappropriate antibiotic utilization is occurring. Our data suggest that demographic and clinical factors are associated with antibiotic use, but additional reasons remain unexplained. Insight regarding reasons for antibiotic prescribing is needed to develop interventions to address the growing problem of antibiotic resistance.

  13. Overexpression of Zwint predicts poor prognosis and promotes the proliferation of hepatocellular carcinoma by regulating cell-cycle-related proteins

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    Ying H

    2018-02-01

    Full Text Available Hanning Ying,1,2 Zhiyao Xu,3 Mingming Chen,1,2 Senjun Zhou,1,2 Xiao Liang,1,2 Xiujun Cai1,2 1Department of General Surgery, 2Key Laboratory of Endoscopic Technique Research of Zhejiang Province, 3Central Lab of Biomedical Research Center, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China Introduction: Zwint, a centromere-complex component required for the mitotic spindle checkpoint, has been reported to be overexpressed in different human cancers, but it has not been studied in human hepatocellular carcinoma (HCC.Materials and methods: The role of Zwint in hepatocellular carcinoma cell proliferation capacities was evaluated by using cell counting kit-8 (CCK8, flow cytometry, clone formation and tumor formation assay in nude mice. Western blot analysis and qPCR assay were performed to assess Zwint interacting with cell-cycle-related proteins.Results: We report that ZWINT mRNA and protein expression were upregulated in HCC samples and cell lines. An independent set of 106 HCC-tissue pairs and corresponding noncancerous tissues was evaluated for Zwint expression using immunohistochemistry, and elevated Zwint expression in HCC tissues was significantly correlated with clinicopathological features, such as tumor size and number. Kaplan–Meier survival and Cox regression analysis revealed that high expression of Zwint was correlated with poor overall survival and a greater tendency for tumor recurrence. Ectopic expression of Zwint promoted HCC-cell proliferation, and Zwint expression affected the expression of several cell-cycle proteins, including PCNA, cyclin B1, Cdc25C and CDK1.Conclusion: Our findings suggest that upregulation of Zwint may contribute to the progression of HCC and may be a prognostic biomarker and potential therapeutic target for treating HCC. Keywords: Zwint, hepatocellular carcinoma, HCC, prognosis, cell proliferation, cell cycle

  14. Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Dimitra T Stefanou

    Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780 and one resistant (A2780/C30 to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs from OC patients, sensitive (n = 7 or resistant (n = 4 to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9 were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05. Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03. Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05. We conclude

  15. Integrating publicly-available data to generate computationally-predicted adverse outcome pathways for hepatic steatosis

    Science.gov (United States)

    The adverse outcome pathway (AOP) framework provides a way of organizing knowledge related to the key biological events that result in a particular health outcome. For the majority of environmental chemicals, the availability of curated pathways characterizing potential toxicity ...

  16. Automated pathway and reaction prediction facilitates in silico identification of unknown metabolites in human cohort studies.

    Science.gov (United States)

    Quell, Jan D; Römisch-Margl, Werner; Colombo, Marco; Krumsiek, Jan; Evans, Anne M; Mohney, Robert; Salomaa, Veikko; de Faire, Ulf; Groop, Leif C; Agakov, Felix; Looker, Helen C; McKeigue, Paul; Colhoun, Helen M; Kastenmüller, Gabi

    2017-12-15

    Identification of metabolites in non-targeted metabolomics continues to be a bottleneck in metabolomics studies in large human cohorts. Unidentified metabolites frequently emerge in the results of association studies linking metabolite levels to, for example, clinical phenotypes. For further analyses these unknown metabolites must be identified. Current approaches utilize chemical information, such as spectral details and fragmentation characteristics to determine components of unknown metabolites. Here, we propose a systems biology model exploiting the internal correlation structure of metabolite levels in combination with existing biochemical and genetic information to characterize properties of unknown molecules. Levels of 758 metabolites (439 known, 319 unknown) in human blood samples of 2279 subjects were measured using a non-targeted metabolomics platform (LC-MS and GC-MS). We reconstructed the structure of biochemical pathways that are imprinted in these metabolomics data by building an empirical network model based on 1040 significant partial correlations between metabolites. We further added associations of these metabolites to 134 genes from genome-wide association studies as well as reactions and functional relations to genes from the public database Recon 2 to the network model. From the local neighborhood in the network, we were able to predict the pathway annotation of 180 unknown metabolites. Furthermore, we classified 100 pairs of known and unknown and 45 pairs of unknown metabolites to 21 types of reactions based on their mass differences. As a proof of concept, we then looked further into the special case of predicted dehydrogenation reactions leading us to the selection of 39 candidate molecules for 5 unknown metabolites. Finally, we could verify 2 of those candidates by applying LC-MS analyses of commercially available candidate substances. The formerly unknown metabolites X-13891 and X-13069 were shown to be 2-dodecendioic acid and 9

  17. Arginase II expressed in cancer-associated fibroblasts indicates tissue hypoxia and predicts poor outcome in patients with pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Yoshinori Ino

    Full Text Available An adequate level of arginine in the tissue microenvironment is essential for T cell activity and survival. Arginine levels are regulated by the arginine-catabolizing enzyme, arginase (ARG. It has been reported that arginase II (ARG2, one of two ARGs, is aberrantly expressed in prostate cancer cells, which convert arginine into ornithine, resulting in a lack of arginine that weakens tumor-infiltrating lymphocytes and renders them dysfunctional. However, immune suppression mediated by ARG2-expressing cancer cells in lung cancer has not been observed. Here we studied the expression of ARG2 in pancreatic ductal carcinoma (PDC tissue clinicopathologically by examining over 200 cases of PDC. In contrast to prostate cancer, ARG2 expression was rarely demonstrated in PDC cells by immunohistochemistry, and instead ARG2 was characteristically expressed in α-smooth muscle actin-positive cancer-associated fibroblasts (CAFs, especially those located within and around necrotic areas in PDC. The presence of ARG2-expressing CAFs was closely correlated with shorter overall survival (OS; P  = 0.003 and disease-free survival (DFS; P  = 0.0006. Multivariate Cox regression analysis showed that the presence of ARG2-expressing CAFs in PDC tissue was an independent predictor of poorer OS (hazard ratio [HR]  = 1.582, P  = 0.007 and DFS (HR  = 1.715, P  = 0.001 in PDC patients. In addition to the characteristic distribution of ARG2-expressing CAFs, such CAFs co-expressed carbonic anhydrase IX, SLC2A1, or HIF-1α, markers of hypoxia, in PDC tissue. Furthermore, in vitro experiments revealed that cultured fibroblasts extracted from PDC tissue expressed the ARG2 transcript after exposure to hypoxia, which had arginase activity. These results indicate that cancer cell-mediated immune suppression through ARG2 expression is not a general event and that the presence of ARG2-expressing CAFs is an indicator of poor prognosis, as well as hypoxia, in PDC

  18. Poor nutritional status of older subacute patients predicts clinical outcomes and mortality at 18 months of follow-up.

    Science.gov (United States)

    Charlton, K; Nichols, C; Bowden, S; Milosavljevic, M; Lambert, K; Barone, L; Mason, M; Batterham, M

    2012-11-01

    Older malnourished patients experience increased surgical complications and greater morbidity compared with their well-nourished counterparts. This study aimed to assess whether nutritional status at hospital admission predicted clinical outcomes at 18 months follow-up. A retrospective analysis of N=2076 patient admissions (65+ years) from two subacute hospitals, New South Wales, Australia. Analysis of outcomes at 18 months, according to nutritional status at index admission, was performed in a subsample of n = 476. Nutritional status was determined within 72 h of admission using the Mini Nutritional Assessment (MNA). Outcomes, obtained from electronic patient records, included hospital readmission rate, total Length of Stay (LOS), change in level of care at discharge and mortality. Survival analysis, using a Cox proportional hazards model, included age, sex, Major Disease Classification, mobility and LOS at index admission as covariates. At baseline, 30% of patients were malnourished and 53% were at risk of malnutrition. LOS was higher in malnourished and at risk, compared with well-nourished patients (median (interquartile range): 34 (21, 58); 26 (15, 41); 20 (14, 26) days, respectively; Pclinical outcomes and identifies a need to target this population for nutritional intervention following hospital discharge.

  19. Combining chemoinformatics with bioinformatics: in silico prediction of bacterial flavor-forming pathways by a chemical systems biology approach "reverse pathway engineering".

    Science.gov (United States)

    Liu, Mengjin; Bienfait, Bruno; Sacher, Oliver; Gasteiger, Johann; Siezen, Roland J; Nauta, Arjen; Geurts, Jan M W

    2014-01-01

    The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE), which combines chemoinformatics and bioinformatics analyses, to predict the "missing links" between compounds of interest and their possible metabolic precursors by providing plausible chemical and/or enzymatic reactions. We demonstrate the added-value of the approach by using flavor-forming pathways in lactic acid bacteria (LAB) as an example. Established metabolic routes leading to the formation of flavor compounds from leucine were successfully replicated. Novel reactions involved in flavor formation, i.e. the conversion of alpha-hydroxy-isocaproate to 3-methylbutanoic acid and the synthesis of dimethyl sulfide, as well as the involved enzymes were successfully predicted. These new insights into the flavor-formation mechanisms in LAB can have a significant impact on improving the control of aroma formation in fermented food products. Since the input reaction databases and compounds are highly flexible, the RPE approach can be easily extended to a broad spectrum of applications, amongst others health/disease biomarker discovery as well as synthetic biology.

  20. Pre- and in-therapy predictive score models of adult OSAS patients with poor adherence pattern on nCPAP therapy

    Directory of Open Access Journals (Sweden)

    Wang Y

    2015-05-01

    Full Text Available Yeying Wang,1,2 Alan F Geater,3 Yanling Chai,1 Jiahong Luo,2 Xiaoqun Niu,1 Bing Hai,1 Jingting Qin,1 Yongxia Li1 1Department of Respiratory Medicine, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China; 2Department of Epidemiology and Biostatistics, School of Public Health, Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China; 3Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand Objectives: To identify patterns of adherence to nasal continuous positive airway pressure (nCPAP use in the first 3 months of therapy among newly diagnosed adult patients with obstructive sleep apnea/hypopnea syndrome (OSAS and their predictors. To develop pretherapy and in-therapy scores to predict adherence pattern. Methods: Newly diagnosed adult OSAS patients were consecutively recruited from March to August 2013. Baseline clinical information and measures such as Epworth Sleepiness Scale (ESS, Fatigue Severity Scale (FSS, Zung’s Self-Rating Depression Scale (SDS, and The Pittsburgh Sleep Quality Index (PSQI at baseline and at the end of 3rd-week therapy were collected. Twelve weeks’ adherence data were collected from the nCPAP memory card, and K-means cluster analysis was used to explore adherence patterns. Predictive scores were developed from the coefficients of cumulative logit models of adherence patterns using variables available at baseline and after 3 weeks of therapy. Performance of the score was validated using 500 bootstrap resamples. Results: Seventy six patients completed a 12-week follow-up. Three patterns were revealed. Patients were identified as developing an adherence pattern that was poor (n=14, mean ± SD, 2.3±0.9 hours per night, moderate (n=19, 5.3±0.6 hours per night, or good (n=43, 6.8±0.3 hours per night. Cumulative logit regression models (good → moderate → poor revealed independent baseline

  1. Simulated rat intestinal fluid improves oral exposure prediction for poorly soluble compounds over a wide dose range

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    Joerg Berghausen

    2016-03-01

    Full Text Available Solubility can be the absorption limiting factor for drug candidates and is therefore a very important input parameter for oral exposure prediction of compounds with limited solubility. Biorelevant media of the fasted and fed state have been published for humans, as well as for dogs in the fasted state. In a drug discovery environment, rodents are the most common animal model to assess the oral exposure of drug candidates. In this study a rat simulated intestinal fluid (rSIF is proposed as a more physiologically relevant media to describe drug solubility in rats. Equilibrium solubility in this medium was tested as input parameter for physiologically-based pharmacokinetics (PBPK simulations of oral pharmacokinetics in the rat. Simulations were compared to those obtained using other solubility values as input parameters, like buffer at pH 6.8, human simulated intestinal fluid and a comprehensive dissolution assay based on rSIF. Our study on nine different compounds demonstrates that the incorporation of rSIF equilibrium solubility values into PBPK models of oral drug exposure can significantly improve the reliability of simulations in rats for doses up to 300 mg/kg compared to other media. The comprehensive dissolution assay may help to improve further simulation outcome, but the greater experimental effort as compared to equilibrium solubility may limit its use in a drug discovery environment. Overall, PBPK simulations based on solubility in the proposed rSIF medium can improve prioritizing compounds in drug discovery as well as planning dose escalation studies, e.g. during toxicological investigations.

  2. Low Annexin A1 expression predicts benefit from induction chemotherapy in oral cancer patients with moderate or poor pathologic differentiation grade

    International Nuclear Information System (INIS)

    Zhu, Dong-wang; Zhang, Chen-ping; Zhang, Zhi-yuan; Zhong, Lai-ping; Liu, Ying; Yang, Xiao; Yang, Cheng-zhe; Ma, Jie; Yang, Xi; Qiao, Jin-ke; Wang, Li-zhen; Li, Jiang

    2013-01-01

    The benefit of induction chemotherapy in locally advanced oral squamous cell carcinoma (OSCC) remains to be clearly defined. Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients and biomarker development might lead to identification of the patients whose tumors are to respond to a particular treatment. Annexin A1 may serve as a biomarker for responsiveness to induction chemotherapy. The aim of this study was to investigate Annexin A1 expression in pre-treatment biopsies from a cohort of OSCC patients treated with surgery and post-operative radiotherapy or docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by surgery and post-operative radiotherapy. Furthermore we sought to assess the utility of Annexin A1 as a prognostic or predictive biomarker. Immunohistochemical staining for Annexin A1 was performed in pre-treatment biopsies from 232 of 256 clinical stage III/IVA OSCC patients. Annexin A1 index was estimated as the proportion of tumor cells (low and high, <50% and ≥50% of stained cells, respectively) to Annexin A1 cellular membrane and cytoplasm staining. There was a significant correlation between Annexin A1 expression and pathologic differentiation grade (P=0.015) in OSCC patients. The proportion of patients with low Annexin A1 expression was significantly higher amongst those with moderate/poorly differentiated tumor (78/167) compared to those with well differentiated tumor (18/65). Multivariate Cox model analysis showed clinical stage (P=0.001) and Annexin A1 expression (P=0.038) as independent prognostic risk factors. Furthermore, a low Annexin A1 expression level was predictive of longer disease-free survival (P=0.036, HR=0.620) and locoregional recurrence-free survival (P=0.031, HR=0.607) compared to high Annexin A1 expression. Patients with moderate/poorly differentiated tumor and low Annexin A1 expression benefited from TPF induction chemotherapy as measured by distant metastasis

  3. Poor performances of EuroSCORE and CARE score for prediction of perioperative mortality in octogenarians undergoing aortic valve replacement for aortic stenosis.

    Science.gov (United States)

    Chhor, Vibol; Merceron, Sybille; Ricome, Sylvie; Baron, Gabriel; Daoud, Omar; Dilly, Marie-Pierre; Aubier, Benjamin; Provenchere, Sophie; Philip, Ivan

    2010-08-01

    Although results of cardiac surgery are improving, octogenarians have a higher procedure-related mortality and more complications with increased length of stay in ICU. Consequently, careful evaluation of perioperative risk seems necessary. The aims of our study were to assess and compare the performances of EuroSCORE and CARE score in the prediction of perioperative mortality among octogenarians undergoing aortic valve replacement for aortic stenosis and to compare these predictive performances with those obtained in younger patients. This retrospective study included all consecutive patients undergoing cardiac surgery in our institution between November 2005 and December 2007. For each patient, risk assessment for mortality was performed using logistic EuroSCORE, additive EuroSCORE and CARE score. The main outcome measure was early postoperative mortality. Predictive performances of these scores were assessed by calibration and discrimination using goodness-of-fit test and area under the receiver operating characteristic curve, respectively. During this 2-year period, we studied 2117 patients, among whom 134/211 octogenarians and 335/1906 nonoctogenarians underwent an aortic valve replacement for aortic stenosis. When considering patients with aortic stenosis, discrimination was poor in octogenarians and the difference from nonoctogenarians was significant for each score (0.58, 0.59 and 0.56 vs. 0.82, 0.81 and 0.77 for additive EuroSCORE, logistic EuroSCORE and CARE score in octogenarians and nonoctogenarians, respectively, P performances of these scores are poor in octogenarians undergoing cardiac surgery, especially aortic valve replacement. Risk assessment and therapeutic decisions in octogenarians should not be made with these scoring systems alone.

  4. The Relationship between Vocational Interests, Self-Efficacy, and Achievement in the Prediction of Educational Pathways

    Science.gov (United States)

    Patrick, Lyn; Care, Esther; Ainley, Mary

    2011-01-01

    The influence of vocational interest, self-efficacy beliefs, and academic achievement on choice of educational pathway is described for a cohort of Australian students. Participants were 189 students aged 14-15 years, who were considering either academic or applied learning pathways and subject choices for the final 3 years of secondary school.…

  5. Identifying the Gene Signatures from Gene-Pathway Bipartite Network Guarantees the Robust Model Performance on Predicting the Cancer Prognosis

    Directory of Open Access Journals (Sweden)

    Li He

    2014-01-01

    Full Text Available For the purpose of improving the prediction of cancer prognosis in the clinical researches, various algorithms have been developed to construct the predictive models with the gene signatures detected by DNA microarrays. Due to the heterogeneity of the clinical samples, the list of differentially expressed genes (DEGs generated by the statistical methods or the machine learning algorithms often involves a number of false positive genes, which are not associated with the phenotypic differences between the compared clinical conditions, and subsequently impacts the reliability of the predictive models. In this study, we proposed a strategy, which combined the statistical algorithm with the gene-pathway bipartite networks, to generate the reliable lists of cancer-related DEGs and constructed the models by using support vector machine for predicting the prognosis of three types of cancers, namely, breast cancer, acute myeloma leukemia, and glioblastoma. Our results demonstrated that, combined with the gene-pathway bipartite networks, our proposed strategy can efficiently generate the reliable cancer-related DEG lists for constructing the predictive models. In addition, the model performance in the swap analysis was similar to that in the original analysis, indicating the robustness of the models in predicting the cancer outcomes.

  6. Elevated admission microalbuminuria predicts poor myocardial blood flow and 6-month mortality in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

    Science.gov (United States)

    Chen, Jia Wei; Wang, Yong Liang; Li, Hong Wei

    2012-04-01

    Microalbuminuria (MA) is considered a major risk factor predisposing to cardiovascular morbidity and mortality. Outcomes after percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI) complicated by MA have been well described. However, data regarding admission MA and coronary and myocardial flow are scant. The aims of this study were to evaluate the effects of admission MA on coronary blood flow and prognosis in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. Did elevated admission microalbuminuria predict poor myocardial blood flow and 6-month mortality in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention? A total of 247 patients undergoing primary PCI for STEMI within 12 hours after symptom onset were studied. Patients were divided into 2 groups according to admission urinary albumin extraction rate (UAER): (1) an MA group (UAER 20-200 µg/min), and (2) a normoalbuminuria (NA) group (UAER < 20 µg/min). Microalbuminuria was observed in 108 patients. Univariate analyses showed statistical differences between the NA and MA groups in serum creatine level, plasma glucose level, and peak creatine kinase level on presentation. Thrombolysis In Myocardial Infarction (TIMI) flow grades (TFGs) 0-2 in the MA group were more frequent (9.4% vs 21.2%, P < 0.05) than in the NA group, and corrected TIMI frame count was higher (23.9 ± 18.5 vs 29.8 ± 23.5, P < 0.05). Admission MA was an independent predictor of poor myocardial perfusion (adjusted relative risk: 3.14, 95% confidence interval: 0.99-6.78) and a higher rate of 6-month mortality in STEMI patients undergoing primary PCI (adjusted relative risk: 1.58, 95% confidence interval: 0.74-3.39). Admission MA levels are associated with impaired myocardial flow and poor prognosis in STEMI patients undergoing primary PCI. © 2012 Wiley Periodicals, Inc.

  7. Optimal cutoff value of basal anti-mullerian hormone in iranian infertile women for prediction of ovarian hyper-stimulation syndrome and poor response to stimulation.

    Science.gov (United States)

    Aghssa, Malek Mansour; Tarafdari, Azam Manshadi; Tehraninejad, Ensieh Shahrokh; Ezzati, Mohammad; Bagheri, Maryam; Panahi, Zahra; Mahdavi, Saeed; Abbasi, Mehrshad

    2015-09-10

    We intended to establish the threshold of Anti-Mullerian Hormone (AMH) for detection of Ovarian Hyper-Stimulation Syndrome (OHSS) and poor response to treatment in Iranian infertile women. Pre-stimulation menstrual cycle day-3 hormonal indices including basal AMH values were measured in 105 infertile women aged 32.5 ± 4.3 years. Patients underwent long GnRH agonist Controlled Ovarian Hyperstimulation (COH) in a referral infertility center (Tehran, Iran). The gonadotropin dose was determined based on the age and basal serum Follicular Stimulating Hormone (FSH) level. The IVF/ICSI cycles were followed and the clinical and sonographic data were recorded. Sixteen cases developed OHSS. The prevalence of PCOS was higher in subjects with OHSS [62.5 % (38.8-86.2) vs. 17 % (9.2-24.9)]. The patients with OHSS had higher ovarian follicular count [23.7 (3.2) vs. 9.1 (0.5); p Basal AMH level and oocyte yields (but not age, BMI, and PCOS) correlated with occurrence of OHSS; and only the AMH levels were associated with poor ovarian response (oocytes yield ≤ 4). The optimal cutoff value for the prediction of OHSS was 6.95 ng/ml (area under the receiver operating characteristics curve: 0.86; CI: 0.78-0.95; sensitivity: 75 %; specificity: 84 %; odds ratio for occurrence of OHSS: 9 and p basal AMH level > 6.95 ng/ml are at high risk of developing OHSS and those with AMH level < 1.65 ng/ml are poor responders.

  8. High Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Breast Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Miao Zhang

    2017-01-01

    Full Text Available Background. We aimed to evaluate the correlation of platelet-to-lymphocyte ratio (PLR with prognosis and clinicopathological characteristics of breast cancer. Methods. The PubMed and Embase databases were searched. Hazard ratio (HR with 95% confidence interval (CI was used to summarize disease-free survival (DFS and overall survival (OS. Odds ratio (OR was used to summarize tumor clinicopathological characteristics. Results. High PLR was associated with poor DFS and OS (DFS: HR = 1.47, 95% CI = 1.16–1.85, and Tau2 = 0.070; OS: HR = 1.88, 95% CI = 1.27–2.80, and Tau2 = 0.192. A Galbraith plot indicated that the studies by Allan et al. and Cihan et al. contributed the heterogeneity of DFS and OS, respectively. There were significant differences in the incidence of high PLR between stage II–IV and stage I groups (OR = 1.86, 95% CI = 1.20–2.90, and Tau2 < 0.001, between lymph node-positive and lymph node-negative groups (OR = 1.52, 95% CI = 1.22–1.91, and Tau2 =0.014, and between metastasis-positive and metastasis-negative groups (OR = 4.24, 95% CI = 2.73–6.59, and Tau2 < 0.001. Conclusions. Our results indicated that PLR was associated with poor prognosis of breast cancer and adequately predicted clinicopathological characteristics.

  9. A framework for streamflow prediction in the world's most severely data-limited regions: Test of applicability and performance in a poorly-gauged region of China

    Science.gov (United States)

    Alipour, M. H.; Kibler, Kelly M.

    2018-02-01

    A framework methodology is proposed for streamflow prediction in poorly-gauged rivers located within large-scale regions of sparse hydrometeorologic observation. A multi-criteria model evaluation is developed to select models that balance runoff efficiency with selection of accurate parameter values. Sparse observed data are supplemented by uncertain or low-resolution information, incorporated as 'soft' data, to estimate parameter values a priori. Model performance is tested in two catchments within a data-poor region of southwestern China, and results are compared to models selected using alternative calibration methods. While all models perform consistently with respect to runoff efficiency (NSE range of 0.67-0.78), models selected using the proposed multi-objective method may incorporate more representative parameter values than those selected by traditional calibration. Notably, parameter values estimated by the proposed method resonate with direct estimates of catchment subsurface storage capacity (parameter residuals of 20 and 61 mm for maximum soil moisture capacity (Cmax), and 0.91 and 0.48 for soil moisture distribution shape factor (B); where a parameter residual is equal to the centroid of a soft parameter value minus the calibrated parameter value). A model more traditionally calibrated to observed data only (single-objective model) estimates a much lower soil moisture capacity (residuals of Cmax = 475 and 518 mm and B = 1.24 and 0.7). A constrained single-objective model also underestimates maximum soil moisture capacity relative to a priori estimates (residuals of Cmax = 246 and 289 mm). The proposed method may allow managers to more confidently transfer calibrated models to ungauged catchments for streamflow predictions, even in the world's most data-limited regions.

  10. Low Annexin A1 expression predicts benefit from induction chemotherapy in oral cancer patients with moderate or poor pathologic differentiation grade.

    Science.gov (United States)

    Zhu, Dong-wang; Liu, Ying; Yang, Xiao; Yang, Cheng-zhe; Ma, Jie; Yang, Xi; Qiao, Jin-ke; Wang, Li-zhen; Li, Jiang; Zhang, Chen-ping; Zhang, Zhi-yuan; Zhong, Lai-ping

    2013-06-21

    The benefit of induction chemotherapy in locally advanced oral squamous cell carcinoma (OSCC) remains to be clearly defined. Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients and biomarker development might lead to identification of the patients whose tumors are to respond to a particular treatment. Annexin A1 may serve as a biomarker for responsiveness to induction chemotherapy. The aim of this study was to investigate Annexin A1 expression in pre-treatment biopsies from a cohort of OSCC patients treated with surgery and post-operative radiotherapy or docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by surgery and post-operative radiotherapy. Furthermore we sought to assess the utility of Annexin A1 as a prognostic or predictive biomarker. Immunohistochemical staining for Annexin A1 was performed in pre-treatment biopsies from 232 of 256 clinical stage III/IVA OSCC patients. Annexin A1 index was estimated as the proportion of tumor cells (low and high, benefited from TPF induction chemotherapy as measured by distant metastasis-free survival (P=0.048, HR=0.373) as well as overall survival (P=0.078, HR=0.410). Annexin A1 can be used as a prognostic biomarker for OSCC. Patients with moderate/poorly differentiated OSCC and low Annexin A1 expression can benefit from the addition of TPF induction chemotherapy to surgery and post-operative radiotherapy. Annexin A1 expression can potentially be used as a predictive biomarker to select OSCC patients with moderate/poorly differentiated tumor who may benefit from TPF induction chemotherapy.

  11. Zinc finger AN1-type containing 4 is a novel marker for predicting metastasis and poor prognosis in oral squamous cell carcinoma.

    Science.gov (United States)

    Kurihara-Shimomura, Miyako; Sasahira, Tomonori; Nakamura, Hiroshi; Nakashima, Chie; Kuniyasu, Hiroki; Kirita, Tadaaki

    2018-05-01

    Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common cancer worldwide and has a high potential for locoregional invasion and nodal metastasis. Therefore, discovery of a useful molecular biomarker capable of predicting tumour progression and metastasis of OSCC is crucial. We have previously reported zinc finger AN1-type containing 4 (ZFAND4) as one of the most upregulated genes in recurrent OSCC using a cDNA microarray analysis. Although ZFAND4 has been shown to promote cell proliferation of gastric cancer, its expression and clinicopathological roles in OSCC remain unclear. In this study, we examined ZFAND4 expression by immunohistochemistry in 214 cases of OSCC. High cytoplasmic expression of ZFAND4 was observed in 45 out of 214 (21%) patients with OSCC. Expression levels of ZFAND4 were strongly associated with metastasis to the lymph nodes (p=0.0429) and distant organs (p=0.0068). Cases with high expression of ZFAND4 had a significantly unfavourable prognosis compared with patients with low expression of ZFAND4 (p<0.0001). Furthermore, ZFAND4 overexpression was an independent poor prognostic factor for OSCC as determined by multivariate analysis using the Cox proportional hazards model (p<0.0001). These results suggest that ZFAND4 is a useful marker for predicting metastasis and poor prognosis in patients with OSCC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. A novel model to combine clinical and pathway-based transcriptomic information for the prognosis prediction of breast cancer.

    Directory of Open Access Journals (Sweden)

    Sijia Huang

    2014-09-01

    Full Text Available Breast cancer is the most common malignancy in women worldwide. With the increasing awareness of heterogeneity in breast cancers, better prediction of breast cancer prognosis is much needed for more personalized treatment and disease management. Towards this goal, we have developed a novel computational model for breast cancer prognosis by combining the Pathway Deregulation Score (PDS based pathifier algorithm, Cox regression and L1-LASSO penalization method. We trained the model on a set of 236 patients with gene expression data and clinical information, and validated the performance on three diversified testing data sets of 606 patients. To evaluate the performance of the model, we conducted survival analysis of the dichotomized groups, and compared the areas under the curve based on the binary classification. The resulting prognosis genomic model is composed of fifteen pathways (e.g., P53 pathway that had previously reported cancer relevance, and it successfully differentiated relapse in the training set (log rank p-value = 6.25e-12 and three testing data sets (log rank p-value < 0.0005. Moreover, the pathway-based genomic models consistently performed better than gene-based models on all four data sets. We also find strong evidence that combining genomic information with clinical information improved the p-values of prognosis prediction by at least three orders of magnitude in comparison to using either genomic or clinical information alone. In summary, we propose a novel prognosis model that harnesses the pathway-based dysregulation as well as valuable clinical information. The selected pathways in our prognosis model are promising targets for therapeutic intervention.

  13. CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer.

    Science.gov (United States)

    Cepeda, Diana; Ng, Hwee-Fang; Sharifi, Hamid Reza; Mahmoudi, Salah; Cerrato, Vanessa Soto; Fredlund, Erik; Magnusson, Kristina; Nilsson, Helén; Malyukova, Alena; Rantala, Juha; Klevebring, Daniel; Viñals, Francesc; Bhaskaran, Nimesh; Zakaria, Siti Mariam; Rahmanto, Aldwin Suryo; Grotegut, Stefan; Nielsen, Michael Lund; Szigyarto, Cristina Al-Khalili; Sun, Dahui; Lerner, Mikael; Navani, Sanjay; Widschwendter, Martin; Uhlén, Mathias; Jirström, Karin; Pontén, Fredrik; Wohlschlegel, James; Grandér, Dan; Spruck, Charles; Larsson, Lars-Gunnar; Sangfelt, Olle

    2013-07-01

    SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCF(FBXO28) activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCF(FBXO28) plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  14. CDK-mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer

    Science.gov (United States)

    Cepeda, Diana; Ng, Hwee-Fang; Sharifi, Hamid Reza; Mahmoudi, Salah; Cerrato, Vanessa Soto; Fredlund, Erik; Magnusson, Kristina; Nilsson, Helén; Malyukova, Alena; Rantala, Juha; Klevebring, Daniel; Viñals, Francesc; Bhaskaran, Nimesh; Zakaria, Siti Mariam; Rahmanto, Aldwin Suryo; Grotegut, Stefan; Nielsen, Michael Lund; Szigyarto, Cristina Al-Khalili; Sun, Dahui; Lerner, Mikael; Navani, Sanjay; Widschwendter, Martin; Uhlén, Mathias; Jirström, Karin; Pontén, Fredrik; Wohlschlegel, James; Grandér, Dan; Spruck, Charles; Larsson, Lars-Gunnar; Sangfelt, Olle

    2013-01-01

    SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. PMID:23776131

  15. An Efficient Computational Model to Predict Protonation at the Amide Nitrogen and Reactivity along the C–N Rotational Pathway

    Science.gov (United States)

    Szostak, Roman; Aubé, Jeffrey

    2015-01-01

    N-protonation of amides is critical in numerous biological processes, including amide bonds proteolysis and protein folding, as well as in organic synthesis as a method to activate amide bonds towards unconventional reactivity. A computational model enabling prediction of protonation at the amide bond nitrogen atom along the C–N rotational pathway is reported. Notably, this study provides a blueprint for the rational design and application of amides with a controlled degree of rotation in synthetic chemistry and biology. PMID:25766378

  16. Sensitivity analysis of intracellular signaling pathway kinetics predicts targets for stem cell fate control.

    Directory of Open Access Journals (Sweden)

    Alborz Mahdavi

    2007-07-01

    Full Text Available Directing stem cell fate requires knowledge of how signaling networks integrate temporally and spatially segregated stimuli. We developed and validated a computational model of signal transducer and activator of transcription-3 (Stat3 pathway kinetics, a signaling network involved in embryonic stem cell (ESC self-renewal. Our analysis identified novel pathway responses; for example, overexpression of the receptor glycoprotein-130 results in reduced pathway activation and increased ESC differentiation. We used a systematic in silico screen to identify novel targets and protein interactions involved in Stat3 activation. Our analysis demonstrates that signaling activation and desensitization (the inability to respond to ligand restimulation is regulated by balancing the activation state of a distributed set of parameters including nuclear export of Stat3, nuclear phosphatase activity, inhibition by suppressor of cytokine signaling, and receptor trafficking. This knowledge was used to devise a temporally modulated ligand delivery strategy that maximizes signaling activation and leads to enhanced ESC self-renewal.

  17. Group spike-and-slab lasso generalized linear models for disease prediction and associated genes detection by incorporating pathway information.

    Science.gov (United States)

    Tang, Zaixiang; Shen, Yueping; Li, Yan; Zhang, Xinyan; Wen, Jia; Qian, Chen'ao; Zhuang, Wenzhuo; Shi, Xinghua; Yi, Nengjun

    2018-03-15

    Large-scale molecular data have been increasingly used as an important resource for prognostic prediction of diseases and detection of associated genes. However, standard approaches for omics data analysis ignore the group structure among genes encoded in functional relationships or pathway information. We propose new Bayesian hierarchical generalized linear models, called group spike-and-slab lasso GLMs, for predicting disease outcomes and detecting associated genes by incorporating large-scale molecular data and group structures. The proposed model employs a mixture double-exponential prior for coefficients that induces self-adaptive shrinkage amount on different coefficients. The group information is incorporated into the model by setting group-specific parameters. We have developed a fast and stable deterministic algorithm to fit the proposed hierarchal GLMs, which can perform variable selection within groups. We assess the performance of the proposed method on several simulated scenarios, by varying the overlap among groups, group size, number of non-null groups, and the correlation within group. Compared with existing methods, the proposed method provides not only more accurate estimates of the parameters but also better prediction. We further demonstrate the application of the proposed procedure on three cancer datasets by utilizing pathway structures of genes. Our results show that the proposed method generates powerful models for predicting disease outcomes and detecting associated genes. The methods have been implemented in a freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/). nyi@uab.edu. Supplementary data are available at Bioinformatics online.

  18. Pathways, mechanisms and predictability of vegetation change during tropical dry forest succession

    NARCIS (Netherlands)

    Lebrija Trejos, E.E.; Meave, J.; Poorter, L.; Pérez- García, E.A.; Bongers, F.

    2010-01-01

    The development of forest succession theory has been based on studies in temperate and tropical wet forests. As rates and pathways of succession vary with the environment, advances in successional theory and study approaches are challenged by controversies derived from such variation and by the

  19. Development of a Novel Quantitative Adverse Outcome Pathway Predictive Model for Lung Cancer

    Science.gov (United States)

    Traditional methods for carcinogenicity testing are resource-intensive, retrospective, and time consuming. An increasing testing burden has generated interest in the adverse outcome pathway (AOP) concept as a tool to evaluate chemical safety in a more efficient, rapid and effecti...

  20. Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients

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    See-Hyoung Park

    2015-08-01

    Full Text Available BACKGROUND: Poly(ADP-ribose polymerase 1 (PARP1, γH2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA tissue can provide more reliable prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, γH2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS, and relapse-free survival (RFS by univariate analysis. Multivariate analysis revealed the expression of PARP1, γH2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph was an additional independent prognostic predictor for OS (P < .001 and RFS (P < .001. The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1 subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4 subgroup. CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.

  1. β-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma.

    Science.gov (United States)

    Xu, Chuan; Xie, Dan; Yu, Shi-Cang; Yang, Xiao-Jun; He, Li-Ru; Yang, Jing; Ping, Yi-Fang; Wang, Bin; Yang, Lang; Xu, Sen-Lin; Cui, Wei; Wang, Qing-Liang; Fu, Wen-Juan; Liu, Qing; Qian, Cheng; Cui, You-Hong; Rich, Jeremy N; Kung, Hsiang-Fu; Zhang, Xia; Bian, Xiu-Wu

    2013-05-15

    Cancer stem-like cells (CSLC) are crucial in tumor initiation and progression; however, the underlying mechanism for the self-renewal of cancer cells remains undefined. In the study, immunohistochemical analysis of specimens freshly excised from patients with lung adenocarcinoma showed that high expression of insulin-like growth factor I receptor (IGF-IR) in lung adenocarcinoma cells was positively correlated with the expressions of cancer stem cell markers CD133 and aldehyde dehydrogenase 1 family member A1 (ALDH1A1). IGF-IR activation enhanced POU class 5 homeobox 1 (POU5F1) expression on human lung adenocarcinoma stem-like cells (LACSLC) through PI3K/AKT/GSK3β/β-catenin cascade. POU5F1 could form a novel complex with β-catenin and SOX2 to bind Nanog promoter for transcription to maintain self-renewal of LACSLCs, which was dependent on the functional IGF-IR. Genetic and pharmacologic inhibition of IGF-IR abrogated LACSLC capabilities for self-renewal and tumorigenicity in vitro. In an in vivo xenograft tumor model, knockdown of either IGF-IR or POU5F1 impeded tumorigenic potentials of LACSLCs. By analyzing pathologic specimens excised from 200 patients with lung adenocarcinoma, we found that colocalization of highly expressed IGF-IR with β-catenin and POU5F1 predicted poor prognosis. Taken together, we show that IGF-IR-mediated POU5F1 expression to form a complex with β-catenin and SOX2 is crucial for the self-renewal and oncogenic potentials of LACSLCs, and the integrative clinical detection of the expressions of IGF-IR, β-catenin, and POU5F1 is indicatory for predicting prognosis in the patients of lung adenocarcinoma. ©2013 AACR.

  2. Higher body mass index and lower intake of dairy products predict poor glycaemic control among Type 2 Diabetes patients in Malaysia.

    Science.gov (United States)

    Shu, Ping Soon; Chan, Yoke Mun; Huang, Soo Lee

    2017-01-01

    This cross-sectional study was designed to determine factors contributing to glyceamic control in order to provide better understanding of diabetes management among Type 2 Diabetes patients. A pre-tested structured questionnaire was used to obtain information on socio-demographic and medical history. As a proxy measure for glycaemic control, glycosylated haemoglobin (HbA1c) was obtained as secondary data from the medical reports. Perceived self-care barrier on diabetes management, diet knowledge and skills, and diet quality were assessed using pretested instruments. With a response rate of 80.3%, 155 subjects were recruited for the study. Mean HbA1c level of the subjects was 9.02 ± 2.25% with more than 70% not able to achieve acceptable level in accordance to WHO recommendation. Diet quality of the subjects was unsatisfactory especially for vegetables, fruits, fish and legumes as well as from the milk and dairy products group. Higher body mass index (BMI), poorer medication compliance, lower diet knowledge and skill scores and lower intake of milk and dairy products contributed significantly on poor glycaemic control. In conclusion, while perceived self-care barriers and diet quality failed to predict HbA1c, good knowledge and skill ability, together with appropriate BMI and adequate intake of dairy products should be emphasized to optimize glycaemic control among type 2 diabetes patients.

  3. Higher body mass index and lower intake of dairy products predict poor glycaemic control among Type 2 Diabetes patients in Malaysia.

    Directory of Open Access Journals (Sweden)

    Ping Soon Shu

    Full Text Available This cross-sectional study was designed to determine factors contributing to glyceamic control in order to provide better understanding of diabetes management among Type 2 Diabetes patients. A pre-tested structured questionnaire was used to obtain information on socio-demographic and medical history. As a proxy measure for glycaemic control, glycosylated haemoglobin (HbA1c was obtained as secondary data from the medical reports. Perceived self-care barrier on diabetes management, diet knowledge and skills, and diet quality were assessed using pretested instruments. With a response rate of 80.3%, 155 subjects were recruited for the study. Mean HbA1c level of the subjects was 9.02 ± 2.25% with more than 70% not able to achieve acceptable level in accordance to WHO recommendation. Diet quality of the subjects was unsatisfactory especially for vegetables, fruits, fish and legumes as well as from the milk and dairy products group. Higher body mass index (BMI, poorer medication compliance, lower diet knowledge and skill scores and lower intake of milk and dairy products contributed significantly on poor glycaemic control. In conclusion, while perceived self-care barriers and diet quality failed to predict HbA1c, good knowledge and skill ability, together with appropriate BMI and adequate intake of dairy products should be emphasized to optimize glycaemic control among type 2 diabetes patients.

  4. High Expression of FAM83B Predicts Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma and Correlates with Cell Cycle and Cell Proliferation.

    Science.gov (United States)

    Shen, Chao-Qin; Yan, Ting-Ting; Liu, Wei; Zhu, Xiao-Qiang; Tian, Xiang-Long; Fu, Xue-Liang; Hua, Rong; Zhang, Jun-Feng; Huo, Yan-Miao; Liu, De-Jun; Yang, Jian-Yu; Sun, Yong-Wei; Fang, Jing-Yuan; Chen, Hao-Yan; Hong, Jie

    2017-01-01

    FAM83B (family with sequence similarity 83, member B) seems to emerge as a new class of players involved in the development of a variety of malignant tumors. Yet the molecular mechanisms are not well understood. The present study is intended to investigate the expression and function of FAM83B in pancreatic ductal adenocarcinoma (PDAC). In this study, we found that the expression of FAM83B was significantly increased both in PDAC cell lines and PDAC tumor tissues. FAM83B expression was positively related with advanced clinical stage and poor vital status. Higher FAM83B expression predicted shorter overall survival in PDAC patients, regardless of lymphatic metastasis status and histological differentiation. Actually, FAM83B may act as an independent prognostic indicator as well. What's more, down-regulation of FAM83B in PDAC cells contributed to G0/G1 phase arrest and inhibition of cell proliferation. Finally, a subcutaneous xenograft model indicated that knockdown of FAM83B significantly reduced the tumor volume in vivo . Our findings have provided supporting evidence for the potential molecular biomarker role of FAM83B in PDAC. It's of great interest and broad significance to target FAM83B in PDAC, which may conduce to develop a meaningful and effective strategy in the diagnosis and treatment of PDAC.

  5. High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

    Directory of Open Access Journals (Sweden)

    Chien Chih-Yen

    2011-03-01

    Full Text Available Abstract Background This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1 expression on response to cisplatin-based induction chemotherapy (IC followed by concurrent chemoradiation (CCRT in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC patients. Methods Fifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records. Results The 12-month progression-free survival (PFS and 2-year overall survival (OS rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p Conclusions Our study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.

  6. Muscle Strength Is a Poor Screening Test for Predicting Lower Extremity Injuries in Professional Male Soccer Players: A 2-Year Prospective Cohort Study.

    Science.gov (United States)

    Bakken, Arnhild; Targett, Stephen; Bere, Tone; Eirale, Cristiano; Farooq, Abdulaziz; Mosler, Andrea B; Tol, Johannes L; Whiteley, Rod; Khan, Karim M; Bahr, Roald

    2018-03-01

    Lower extremity muscle strength tests are commonly used to screen for injury risk in professional soccer. However, there is limited evidence on the ability of such tests in predicting future injuries. To examine the association between hip and thigh muscle strength and the risk of lower extremity injuries in professional male soccer players. Case-control study; Level of evidence, 3. Professional male soccer players from 14 teams in Qatar underwent a comprehensive strength assessment at the beginning of the 2013/2014 and 2014/2015 seasons. Testing consisted of concentric and eccentric quadriceps and hamstring isokinetic peak torques, eccentric hip adduction and abduction forces, and bilateral isometric adductor force (squeeze test at 45°). Time-loss injuries and exposure in training and matches were registered prospectively by club medical staff throughout each season. Univariate and multivariate Cox regression analyses were used to calculate hazard ratios (HRs) with 95% CIs. In total, 369 players completed all strength tests and had registered injury and exposure data. Of these, 206 players (55.8%) suffered 538 lower extremity injuries during the 2 seasons; acute muscle injuries were the most frequent. Of the 20 strength measures examined, greater quadriceps concentric peak torque at 300 deg/s (HR, 1.005 [95% CI, 1.00-1.01]; P = .037) was the only strength measure identified as significantly associated with a risk of lower extremity injuries in multivariate analysis. Greater quadriceps concentric peak torque at 60 deg/s (HR, 1.004 [95% CI, 1.00-1.01]; P = .026) was associated with the risk of overuse injuries, and greater bilateral adductor strength adjusted for body weight (HR, 0.75 [95% CI, 0.57-0.97; P = .032) was associated with a lower risk for any knee injury. Receiver operating characteristic curve analyses indicated poor predictive ability of the significant strength variables (area under the curve, 0.45-0.56). There was a weak association with the risk of

  7. Wilms’ Tumor 1 Gene Mutations Independently Predict Poor Outcome in Adults With Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study

    Science.gov (United States)

    Paschka, Peter; Marcucci, Guido; Ruppert, Amy S.; Whitman, Susan P.; Mrózek, Krzysztof; Maharry, Kati; Langer, Christian; Baldus, Claudia D.; Zhao, Weiqiang; Powell, Bayard L.; Baer, Maria R.; Carroll, Andrew J.; Caligiuri, Michael A.; Kolitz, Jonathan E.; Larson, Richard A.; Bloomfield, Clara D.

    2008-01-01

    Purpose To analyze the prognostic impact of Wilms’ tumor 1 (WT1) gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods We studied 196 adults younger than 60 years with newly diagnosed primary CN-AML, who were treated similarly on Cancer and Leukemia Group B (CALGB) protocols 9621 and 19808, for WT1 mutations in exons 7 and 9. The patients also were assessed for the presence of FLT3 internal tandem duplications (FLT3-ITD), FLT3 tyrosine kinase domain mutations (FLT3-TKD), MLL partial tandem duplications (MLL-PTD), NPM1 and CEBPA mutations, and for the expression levels of ERG and BAALC. Results Twenty-one patients (10.7%) harbored WT1 mutations. Complete remission rates were not significantly different between patients with WT1 mutations and those with unmutated WT1 (P = .36; 76% v 84%). Patients with WT1 mutations had worse disease-free survival (DFS; P < .001; 3-year rates, 13% v 50%) and overall survival (OS; P < .001; 3-year rates, 10% v 56%) than patients with unmutated WT1. In multivariable analyses, WT1 mutations independently predicted worse DFS (P = .009; hazard ratio [HR] = 2.7) when controlling for CEBPA mutational status, ERG expression level, and FLT3-ITD/NPM1 molecular-risk group (ie, FLT3-ITDnegative/NPM1mutated as low risk v FLT3-ITDpositive and/or NPM1wild-type as high risk). WT1 mutations also independently predicted worse OS (P < .001; HR = 3.2) when controlling for CEBPA mutational status, FLT3-ITD/NPM1 molecular-risk group, and white blood cell count. Conclusion We report the first evidence that WT1 mutations independently predict extremely poor outcome in intensively treated, younger patients with CN-AML. Future trials should include testing for WT1 mutations as part of molecularly based risk assessment and risk-adapted treatment stratification of patients with CN-AML. PMID:18559874

  8. Baseline β-catenin, programmed death-ligand 1 expression and tumour-infiltrating lymphocytes predict response and poor prognosis in BRAF inhibitor-treated melanoma patients.

    Science.gov (United States)

    Massi, Daniela; Romano, Emanuela; Rulli, Eliana; Merelli, Barbara; Nassini, Romina; De Logu, Francesco; Bieche, Ivan; Baroni, Gianna; Cattaneo, Laura; Xue, Gongda; Mandalà, Mario

    2017-06-01

    The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome. Quantitative assessment of mRNA transcripts associated with Wnt/β-catenin pathway and immune response was performed in 51 patients. We found an inverse correlation between tumoural β-catenin expression and the level of CD8, CD103 or forkhead box protein P3 (FOXP3) positivity in the tumour microenvironment (TME). By multivariate analysis, PD-L1 <5% (odds ratio, OR 0.12, 95% confidence interval, CI 0.03-0.53, p = 0.005) and the presence of CD8+ T cells (OR 18.27, 95%CI 2.54-131.52, p = 0.004) were significantly associated with a higher probability of response to MAPKi monotherapy. Responding patients showed a significantly increased expression of mRNA transcripts associated with adaptive immunity and antigen presentation. By multivariate analysis, progression-free survival (PFS) (hazards ratio (HR) = 0.25 95%CI 0.10-0.61, p = 0.002) and overall survival (OS) (HR = 0.24 95%CI 0.09-0.67, p = 0.006) were longer in patients with high density of CD8+ T cells and β-catenin <10% than those without CD8+ T cells infiltration and β-catenin ≥10%. Our findings provide evidence that in the context of MAPKi monotherapy, immune subsets in the (TME) and

  9. Chemical agnostic hazard prediction: Statistical inference of toxicity pathways - data for Figure 2

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset comprises one SigmaPlot 13 file containing measured survival data and survival data predicted from the model coefficients selected by the LASSO...

  10. Sexualidade juvenil de classes populares em Cabo Verde: os caminhos para a prostituição de jovens urbanas pobres The sexual culture of marginalized youth in Cape Verde: pathways to the prostitution of poor young women

    Directory of Open Access Journals (Sweden)

    José Carlos Gomes dos Anjos

    2005-04-01

    Full Text Available O artigo apresenta apontamentos sobre comportamento de jovens marginalizados em Cabo Verde e busca integrar essas notas etnográficas a teorias da masculinidade. Explorando os caminhos que levam à prostituição entre meninas pobres, o artigo focaliza como mudanças nas experiências da sexualidade conduziram a uma reversão de arranjos sociais prévios nos quais os homens eram 'caçadores de saia' e provedores, para este novo regime em que as mulheres buscam seus parceiros com base no desejo e buscam, inclusive na prostituição, os meios econômicos para sustentar tais relações. O artigo usa dados de entrevistas detalhadas, algumas discussões de grupo focais e observação participante para examinar percepções masculinas de caminhos femininos para a prostituição.The paper provides insights into the behavior of marginalized youth in Cape Verde and integrates these insights into theories of masculinities. Exploring the pathways to prostitution among young poor urban women and their relationship to their peers, the poor young men they interact with, the paper focuses on how a change in sexual norms has led to a reversal of previous social arrangements, in which men were the 'skirt chasers' and the providers, to ones in which women seek partners based on desire and have the economic means to sustain such relationships. The paper uses data from some in-depth interviews, some focus group discussions, and participant observation to examine male perceptions of pathways to female prostitution.

  11. Inherent vulnerabilities in monoaminergic pathways predict the emergence of depressive impairments in an animal model of chronic epilepsy.

    Science.gov (United States)

    Medel-Matus, Jesús-Servando; Shin, Don; Sankar, Raman; Mazarati, Andrey

    2017-08-01

    The objective was to determine whether the depression comorbid with epilepsy could be predicted based on inherent premorbid patterns of monoaminergic transmission. In male Wistar rats, despair-like and anhedonia-like behaviors were examined using forced swimming and taste preference tests, respectively. Serotonergic raphe nucleus (RN)-prefrontal cortex (PFC) and dopaminergic ventral tegmental area (VTA)-nucleus accumbens (NAcc) pathways were interrogated by fast scan cyclic voltammetry (FSCV). The assays were performed before and 2 months after pilocarpine status epilepticus. In a subset of naive rats, FSCV, coupled with the intensity-dependent stimulation paradigm, detected specific deviations in each pathway (six rats for RN-PFC and seven rats for VTA-NAcc, with overlap in two, of 19 total subjects) in the absence of behavioral impairments. During epilepsy, animals with preexisting deviations in RN-PFC invariably developed despair, and rats with deviations in VTA-NAcc developed anhedonia. Serotonergic and dopaminergic pathways, respectively, showed signs of explicit deterioration. We suggest that epilepsy triggers decompensations in the already vulnerable depression-relevant neuronal circuits, which culminate in depression. The established connection between the identified specific signatures in monoamine transmission in naive rats and specific symptoms of epilepsy-associated depression may help in understanding causes of comorbidity and in developing its early biomarkers. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  12. Elevated serum levels of vascular endothelial growth factor predict a poor prognosis of platinum-based chemotherapy in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zang JL

    2017-01-01

    : In conclusion, the serum VEGF levels were found to be a poor prognostic biomarker for the efficacy of platinum-based chemotherapy in terms of PFS, but it was not shown to be a suitable predictive marker for clinical response to platinum-based chemotherapy. Keywords: non-small cell lung cancer, VEGF, progression-free survival, platinum, chemotherapy, Luminex multiplex, prognosis

  13. High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

    Science.gov (United States)

    Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

    2017-06-01

    Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. Compositional controls on early diagenetic pathways in fine-grained sedimentary rocks: Implications for predicting unconventional reservoir attributes of mudstones

    Science.gov (United States)

    Keller, Margaret A.; Macquaker, Joe H.S.; Taylor, Kevin G.; Polya, David

    2014-01-01

    Diagenesis significantly impacts mudstone lithofacies. Processes operating to control diagenetic pathways in mudstones are poorly known compared to analogous processes occurring in other sedimentary rocks. Selected organic-carbon-rich mudstones, from the Kimmeridge Clay and Monterey Formations, have been investigated to determine how varying starting compositions influence diagenesis.The sampled Kimmeridge Clay Formation mudstones are organized into thin homogenous beds, composed mainly of siliciclastic detritus, with some constituents derived from water-column production (e.g., coccoliths, S-depleted type-II kerogen, as much as 52.6% total organic carbon [TOC]) and others from diagenesis (e.g., pyrite, carbonate, and kaolinite). The sampled Monterey Formation mudstones are organized into thin beds that exhibit pelleted wavy lamination, and are predominantly composed of production-derived components including diatoms, coccoliths, and foraminifera, in addition to type-IIS kerogen (as much as 16.5% TOC), and apatite and silica cements.During early burial of the studied Kimmeridge Clay Formation mudstones, the availability of detrital Fe(III) and reactive clay minerals caused carbonate- and silicate-buffering reactions to operate effectively and the pore waters to be Fe(II) rich. These conditions led to pyrite, iron-poor carbonates, and kaolinite cements precipitating, preserved organic carbon being S-depleted, and sweet hydrocarbons being generated. In contrast, during the diagenesis of the sampled Monterey Formation mudstones, sulfide oxidation, coupled with opal dissolution and the reduced availability of both Fe(III) and reactive siliciclastic detritus, meant that the pore waters were poorly buffered and locally acidic. These conditions resulted in local carbonate dissolution, apatite and silica cements precipitation, natural kerogen sulfurization, and sour hydrocarbons generation.Differences in mud composition at deposition significantly influence subsequent

  15. A Critical Evaluation of Network and Pathway-Based Classifiers for Outcome Prediction in Breast Cancer

    NARCIS (Netherlands)

    C. Staiger (Christine); S. Cadot; R Kooter; M. Dittrich (Marcus); T. Müller (Tobias); G.W. Klau (Gunnar); L.F.A. Wessels (Lodewyk)

    2012-01-01

    htmlabstractRecently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically

  16. Pathways to School Readiness: Executive Functioning Predicts Academic and Social-Emotional Aspects of School Readiness

    Science.gov (United States)

    Mann, Trisha D.; Hund, Alycia M.; Hesson-McInnis, Matthew S.; Roman, Zachary J.

    2017-01-01

    The current study specified the extent to which hot and cool aspects of executive functioning predicted academic and social-emotional indicators of school readiness. It was unique in focusing on positive aspects of social-emotional readiness, rather than problem behaviors. One hundred four 3-5-year-old children completed tasks measuring executive…

  17. Elevated tumor-to-liver uptake ratio (TLR) from 18F-FDG-PET/CT predicts poor prognosis in stage IIA colorectal cancer following curative resection

    International Nuclear Information System (INIS)

    Huang, Jun; Huang, Liang; Zhou, Jiaming; Huang, Pinzhu; Tan, Shuyun; Wang, Jianping; Huang, Meijin; Duan, Yinghua; Zhang, Zhanwen; Hu, Ping; Wang, Xiaoyan

    2017-01-01

    The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from 18 F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent 18 F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative 18 F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with elevated TLR. Cox

  18. Elevated tumor-to-liver uptake ratio (TLR) from {sup 18}F-FDG-PET/CT predicts poor prognosis in stage IIA colorectal cancer following curative resection

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jun; Huang, Liang; Zhou, Jiaming; Huang, Pinzhu; Tan, Shuyun; Wang, Jianping; Huang, Meijin [6th Affiliated Hospital, Sun Yat-sen University, Department of Colorectal Surgery, Guangzhou, Guangdong (China); Duan, Yinghua [1st Affiliated Hospital, Sun Yat-sen University, Department of Traditional Chinese Medicine, Guangzhou (China); Zhang, Zhanwen; Hu, Ping [6th Affiliated Hospital, Sun Yat-sen University, Department of Nuclear Medicine, Guangzhou (China); Wang, Xiaoyan [1st Affiliated Hospital, Sun Yat-sen University, Department of Nuclear Medicine, Guangzhou (China)

    2017-11-15

    The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from {sup 18}F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent {sup 18}F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative {sup 18}F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with

  19. The value of {sup 18}F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Rossum, Peter S.N. van [The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX (United States); University Medical Center Utrecht, Department of Radiation Oncology, Utrecht (Netherlands); Fried, David V.; Zhang, Lifei; Court, Laurence E. [The University of Texas MD Anderson Cancer Center, Department of Radiation Physics, Houston, TX (United States); Hofstetter, Wayne L. [The University of Texas MD Anderson Cancer Center, Department of Thoracic and Cardiovascular Surgery, Houston, TX (United States); Ho, Linus [The University of Texas MD Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, Houston, TX (United States); Meijer, Gert J. [University Medical Center Utrecht, Department of Radiation Oncology, Utrecht (Netherlands); Carter, Brett W. [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Lin, Steven H. [The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX (United States)

    2017-01-15

    The purpose of our study was to determine the value of {sup 18}F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT). In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, {sup 18}F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUV{sub max}, SUV{sub mean}, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed. A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for a poor pathologic response at a threshold of -26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p = 0.02), but not OS (p = 0.18). {sup 18}F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early {sup 18}F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders. (orig.)

  20. The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

    International Nuclear Information System (INIS)

    Rossum, Peter S.N. van; Fried, David V.; Zhang, Lifei; Court, Laurence E.; Hofstetter, Wayne L.; Ho, Linus; Meijer, Gert J.; Carter, Brett W.; Lin, Steven H.

    2017-01-01

    The purpose of our study was to determine the value of 18 F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT). In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, 18 F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUV max , SUV mean , metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed. A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for a poor pathologic response at a threshold of -26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p = 0.02), but not OS (p = 0.18). 18 F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early 18 F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders. (orig.)

  1. Cloud computing approaches for prediction of ligand binding poses and pathways.

    Science.gov (United States)

    Lawrenz, Morgan; Shukla, Diwakar; Pande, Vijay S

    2015-01-22

    We describe an innovative protocol for ab initio prediction of ligand crystallographic binding poses and highly effective analysis of large datasets generated for protein-ligand dynamics. We include a procedure for setup and performance of distributed molecular dynamics simulations on cloud computing architectures, a model for efficient analysis of simulation data, and a metric for evaluation of model convergence. We give accurate binding pose predictions for five ligands ranging in affinity from 7 nM to > 200 μM for the immunophilin protein FKBP12, for expedited results in cases where experimental structures are difficult to produce. Our approach goes beyond single, low energy ligand poses to give quantitative kinetic information that can inform protein engineering and ligand design.

  2. Germline Polymorphisms of the VEGF Pathway Predict Recurrence in Nonadvanced Differentiated Thyroid Cancer.

    Science.gov (United States)

    Marotta, Vincenzo; Sciammarella, Concetta; Capasso, Mario; Testori, Alessandro; Pivonello, Claudia; Chiofalo, Maria Grazia; Gambardella, Claudio; Grasso, Marica; Antonino, Antonio; Annunziata, Annamaria; Macchia, Paolo Emidio; Pivonello, Rosario; Santini, Luigi; Botti, Gerardo; Losito, Simona; Pezzullo, Luciano; Colao, Annamaria; Faggiano, Antongiulio

    2017-02-01

    Tumor angiogenesis is determined by host genetic background rather than environment. Germline single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) pathway have demonstrated prognostic value in different tumors. Our main objective was to test the prognostic value of germline SNPs of the VEGF pathway in nonadvanced differentiated thyroid cancer (DTC). Secondarily, we sought to correlate analyzed SNPs with microvessel density (MVD). Multicenter, retrospective, observational study. Four referral centers. Blood samples were obtained from consecutive DTC patients. Genotyping was performed according to the TaqMan protocol, including 4 VEGF-A (-2578C>A, -460T>C, +405G>C, and +936C>T) and 2 VEGFR-2 (+1192 C>T and +1719 T>A) SNPs. MVD was estimated by means of CD34 staining. Rate of recurrent structural disease/disease-free survival (DFS). Difference in MVD between tumors from patients with different genotype. Two hundred four patients with stage I-II DTC (mean follow-up, 73 ± 64 months) and 240 patients with low- to intermediate-risk DTC (mean follow-up, 70 ± 60 months) were enrolled. Two "risk" genotypes were identified by combining VEGF-A SNPs -2578 C>A, -460 T>C, and +405 G>C. The ACG homozygous genotype was protective in both stage I-II (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01 to 1.43; P = 0.018) and low- to intermediate-risk (OR, 0.14; 95% CI, 0.01 to 1.13; P = 0.035) patients. The CTG homozygous genotype was significantly associated with recurrence in stage I-II (OR, 5.47; 95% CI, 1.15 to 26.04; P = 0.018) and was slightly deleterious in low- to intermediate-risk (OR, 3.39; 95% CI, 0.8 to 14.33; P = 0.079) patients. MVD of primary tumors from patients harboring a protective genotype was significantly lower (median MVD, 76.5 ± 12.7 and 86.7 ± 27.9, respectively; P = 0.024). Analysis of germline VEGF-A SNPs could empower a prognostic approach to DTC. Copyright © 2017 by the Endocrine Society

  3. Keratin 17 is overexpressed and predicts poor survival in estrogen receptor-negative/human epidermal growth factor receptor-2-negative breast cancer.

    Science.gov (United States)

    Merkin, Ross D; Vanner, Elizabeth A; Romeiser, Jamie L; Shroyer, A Laurie W; Escobar-Hoyos, Luisa F; Li, Jinyu; Powers, Robert S; Burke, Stephanie; Shroyer, Kenneth R

    2017-04-01

    Clinicopathological features of breast cancer have limited accuracy to predict survival. By immunohistochemistry (IHC), keratin 17 (K17) expression has been correlated with triple-negative status (estrogen receptor [ER]/progesterone receptor/human epidermal growth factor receptor-2 [HER2] negative) and decreased survival, but K17 messenger RNA (mRNA) expression has not been evaluated in breast cancer. K17 is a potential prognostic cancer biomarker, targeting p27, and driving cell cycle progression. This study compared K17 protein and mRNA expression to ER/progesterone receptor/HER2 receptor status and event-free survival. K17 IHC was performed on 164 invasive breast cancers and K17 mRNA was evaluated in 1097 breast cancers. The mRNA status of other keratins (16/14/9) was evaluated in 113 ER - /HER2 - ductal carcinomas. IHC demonstrated intense cytoplasmic and membranous K17 localization in myoepithelial cells of benign ducts and lobules and tumor cells of ductal carcinoma in situ. In ductal carcinomas, K17 protein was detected in most triple-negative tumors (28/34, 82%), some non-triple-negative tumors (52/112, 46%), but never in lobular carcinomas (0/15). In ductal carcinomas, high K17 mRNA was associated with reduced 5-year event-free survival in advanced tumor stage (n = 149, hazard ratio [HR] = 3.68, P = .018), and large (n = 73, HR = 3.95, P = .047), triple-negative (n = 103, HR = 2.73, P = .073), and ER - /HER2 - (n = 113, HR = 2.99, P = .049) tumors. There were significant correlations among keratins 17, 16, 14, and 9 mRNA levels suggesting these keratins (all encoded on chromosome 17) could be coordinately expressed in breast cancer. Thus, K17 is expressed in a subset of triple-negative breast cancers, and is a marker of poor prognosis in patients with advanced stage and ER - /HER2 - breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. NAViGaTing the micronome--using multiple microRNA prediction databases to identify signalling pathway-associated microRNAs.

    Directory of Open Access Journals (Sweden)

    Elize A Shirdel

    2011-02-01

    Full Text Available MicroRNAs are a class of small RNAs known to regulate gene expression at the transcript level, the protein level, or both. Since microRNA binding is sequence-based but possibly structure-specific, work in this area has resulted in multiple databases storing predicted microRNA:target relationships computed using diverse algorithms. We integrate prediction databases, compare predictions to in vitro data, and use cross-database predictions to model the microRNA:transcript interactome--referred to as the micronome--to study microRNA involvement in well-known signalling pathways as well as associations with disease. We make this data freely available with a flexible user interface as our microRNA Data Integration Portal--mirDIP (http://ophid.utoronto.ca/mirDIP.mirDIP integrates prediction databases to elucidate accurate microRNA:target relationships. Using NAViGaTOR to produce interaction networks implicating microRNAs in literature-based, KEGG-based and Reactome-based pathways, we find these signalling pathway networks have significantly more microRNA involvement compared to chance (p<0.05, suggesting microRNAs co-target many genes in a given pathway. Further examination of the micronome shows two distinct classes of microRNAs; universe microRNAs, which are involved in many signalling pathways; and intra-pathway microRNAs, which target multiple genes within one signalling pathway. We find universe microRNAs to have more targets (p<0.0001, to be more studied (p<0.0002, and to have higher degree in the KEGG cancer pathway (p<0.0001, compared to intra-pathway microRNAs.Our pathway-based analysis of mirDIP data suggests microRNAs are involved in intra-pathway signalling. We identify two distinct classes of microRNAs, suggesting a hierarchical organization of microRNAs co-targeting genes both within and between pathways, and implying differential involvement of universe and intra-pathway microRNAs at the disease level.

  5. Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival.

    Science.gov (United States)

    Yin, Jieyun; Liu, Hongliang; Liu, Zhensheng; Wang, Li-E; Chen, Wei V; Zhu, Dakai; Amos, Christopher I; Fang, Shenying; Lee, Jeffrey E; Wei, Qingyi

    2015-02-01

    Cutaneous melanoma (CM) is the most lethal skin cancer. The Fanconi anemia (FA) pathway involved in DNA crosslink repair may affect CM susceptibility and prognosis. Using data derived from published genome-wide association study, we comprehensively analyzed the associations of 2,339 common single-nucleotide polymorphisms (SNPs) in 14 autosomal FA genes with overall survival (OS) in 858 CM patients. By performing false-positive report probability corrections and stepwise Cox proportional hazards regression analyses, we identified significant associations between CM OS and four putatively functional SNPs: BRCA2 rs10492396 (AG vs. GG: adjusted hazard ratio (adjHR)=1.85, 95% confidence interval (CI)=1.16-2.95, P=0.010), rs206118 (CC vs. TT+TC: adjHR=2.44, 95% CI=1.27-4.67, P=0.007), rs3752447 (CC vs. TT+TC: adjHR=2.10, 95% CI=1.38-3.18, P=0.0005), and FANCA rs62068372 (TT vs. CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001). Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS). The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS. Additional investigations, preferably prospective studies, are needed to validate our findings.

  6. Apoptotic intrinsic pathway proteins predict survival in canine cutaneous mast cell tumours.

    Science.gov (United States)

    Barra, C N; Macedo, B M; Cadrobbi, K G; Pulz, L H; Huete, G C; Kleeb, S R; Xavier, J G; Catão-Dias, J L; Nishiya, A T; Fukumasu, H; Strefezzi, R F

    2018-03-01

    Mast cell tumours (MCTs) are the most frequent canine round cell neoplasms and show variable biological behaviours with high metastatic and recurrence rates. The disease is treated surgically and wide margins are recommended. Adjuvant chemotherapy and radiotherapy used in this disease cause DNA damage in neoplastic cells, which is aimed to induce apoptotic cell death. Resisting cell death is a hallmark of cancer, which contributes to the development and progression of tumours. The aim of this study was to investigate the expression of the proteins involved in the apoptotic intrinsic pathway and to evaluate their potential use as prognostic markers for canine cutaneous MCTs. Immunohistochemistry for BAX, BCL2, APAF1, Caspase-9, and Caspase-3 was performed in 50 canine cases of MCTs. High BAX expression was associated with higher mortality rate and shorter survival. BCL2 and APAF1 expressions offered additional prognostic information to the histopathological grading systems. The present results indicate that variations in the expression of apoptotic proteins are related to malignancy of cutaneous MCTs in dogs. © 2017 John Wiley & Sons Ltd.

  7. Poor Pre-Pregnancy and Antepartum Mental Health Predicts Postpartum Mental Health Problems among US Women: A Nationally Representative Population-Based Study

    Science.gov (United States)

    Witt, Whitney P.; Wisk, Lauren E.; Cheng, Erika R.; Hampton, John M.; Creswell, Paul; Hagen, Erika W.; Spear, Hilary A.; Maddox, Torsheika; DeLeire, Thomas

    2011-01-01

    Purpose Mental health problems disproportionately affect women, particularly during childbearing years. However, there is a paucity of research on the determinants of postpartum mental health problems using representative US populations. Taking a life course perspective, we determined the potential risk factors for postpartum mental health problems, with a particular focus on the role of mental health before and during pregnancy. Methods We examined data on 1,863 mothers from eleven panels of the 1996-2006 Medical Expenditure Panel Survey (MEPS). Poor postpartum mental health was defined using self-reports of mental health conditions, symptoms of mental health conditions, or global mental health ratings of “fair” or “poor.” Results 9.5% of women reported experiencing postpartum mental health problems, with over half of these women reporting a history of poor mental health. Poor pre-pregnancy mental health and poor antepartum mental health both independently increased the odds of having postpartum mental health problems. Staged multivariate analyses revealed that poor antepartum mental health attenuated the relationship between pre-pregnancy and postpartum mental health problems. Additionally, significant disparities exist in women's report of postpartum mental health status. Conclusions While poor antepartum mental health is the strongest predictor of postpartum mental health problems, pre-pregnancy mental health is also important. Accordingly, health care providers should identify, treat, and follow women with a history of poor mental health, as they are particularly susceptible to postpartum mental health problems. This will ensure that women and their children are in the best possible health and mental health during the postpartum period and beyond. PMID:21349740

  8. Combining Pathway Identification and Breast Cancer Survival Prediction via Screening-Network Methods

    Directory of Open Access Journals (Sweden)

    Antonella Iuliano

    2018-06-01

    Full Text Available Breast cancer is one of the most common invasive tumors causing high mortality among women. It is characterized by high heterogeneity regarding its biological and clinical characteristics. Several high-throughput assays have been used to collect genome-wide information for many patients in large collaborative studies. This knowledge has improved our understanding of its biology and led to new methods of diagnosing and treating the disease. In particular, system biology has become a valid approach to obtain better insights into breast cancer biological mechanisms. A crucial component of current research lies in identifying novel biomarkers that can be predictive for breast cancer patient prognosis on the basis of the molecular signature of the tumor sample. However, the high dimension and low sample size of data greatly increase the difficulty of cancer survival analysis demanding for the development of ad-hoc statistical methods. In this work, we propose novel screening-network methods that predict patient survival outcome by screening key survival-related genes and we assess the capability of the proposed approaches using METABRIC dataset. In particular, we first identify a subset of genes by using variable screening techniques on gene expression data. Then, we perform Cox regression analysis by incorporating network information associated with the selected subset of genes. The novelty of this work consists in the improved prediction of survival responses due to the different types of screenings (i.e., a biomedical-driven, data-driven and a combination of the two before building the network-penalized model. Indeed, the combination of the two screening approaches allows us to use the available biological knowledge on breast cancer and complement it with additional information emerging from the data used for the analysis. Moreover, we also illustrate how to extend the proposed approaches to integrate an additional omic layer, such as copy number

  9. How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J.; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M. E. (Bette); Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M.; Whelan, Maurice

    2016-12-19

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework has emerged as a systematic approach for organizing knowledge that supports such inference. We argue that this systematic organization of knowledge can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment.

  10. Single versus Serial Measurements of Neuron-Specific Enolase and Prediction of Poor Neurological Outcome in Persistently Unconscious Patients after Out-Of-Hospital Cardiac Arrest - A TTM-Trial Substudy

    DEFF Research Database (Denmark)

    Wiberg, Sebastian; Hassager, Christian; Stammet, Pascal

    2017-01-01

    were included from sites participating in the TTM-trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and follow-up was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5...... of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition....... RESULTS: A total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC...

  11. Pharmacogenomics of Methotrexate Membrane Transport Pathway: Can Clinical Response to Methotrexate in Rheumatoid Arthritis Be Predicted?

    Directory of Open Access Journals (Sweden)

    Aurea Lima

    2015-06-01

    Full Text Available Background: Methotrexate (MTX is widely used for rheumatoid arthritis (RA treatment. Single nucleotide polymorphisms (SNPs could be used as predictors of patients’ therapeutic outcome variability. Therefore, this study aims to evaluate the influence of SNPs in genes encoding for MTX membrane transport proteins in order to predict clinical response to MTX. Methods: Clinicopathological data from 233 RA patients treated with MTX were collected, clinical response defined, and patients genotyped for 23 SNPs. Genotype and haplotype analyses were performed using multivariate methods and a genetic risk index (GRI for non-response was created. Results: Increased risk for non-response was associated to SLC22A11 rs11231809 T carriers; ABCC1 rs246240 G carriers; ABCC1 rs3784864 G carriers; CGG haplotype for ABCC1 rs35592, rs2074087 and rs3784864; and CGG haplotype for ABCC1 rs35592, rs246240 and rs3784864. GRI demonstrated that patients with Index 3 were 16-fold more likely to be non-responders than those with Index 1. Conclusions: This study revealed that SLC22A11 and ABCC1 may be important to identify those patients who will not benefit from MTX treatment, highlighting the relevance in translating these results to clinical practice. However, further validation by independent studies is needed to develop the field of personalized medicine to predict clinical response to MTX treatment.

  12. Detection of phytohormones in temperate forest fungi predicts consistent abscisic acid production and a common pathway for cytokinin biosynthesis.

    Science.gov (United States)

    Morrison, Erin N; Knowles, Sarah; Hayward, Allison; Thorn, R Greg; Saville, Barry J; Emery, R J N

    2015-01-01

    The phytohormones, abscisic acid and cytokinin, once were thought to be present uniquely in plants, but increasing evidence suggests that these hormones are present in a wide variety of organisms. Few studies have examined fungi for the presence of these "plant" hormones or addressed whether their levels differ based on the nutrition mode of the fungus. This study examined 20 temperate forest fungi of differing nutritional modes (ectomycorrhizal, wood-rotting, saprotrophic). Abscisic acid and cytokinin were present in all fungi sampled; this indicated that the sampled fungi have the capacity to synthesize these two classes of phytohormones. Of the 27 cytokinins analyzed by HPLC-ESI MS/MS, seven were present in all fungi sampled. This suggested the existence of a common cytokinin metabolic pathway in fungi that does not vary among different nutritional modes. Predictions regarding the source of isopentenyl, cis-zeatin and methylthiol CK production stemming from the tRNA degradation pathway among fungi are discussed. © 2015 by The Mycological Society of America.

  13. CD147-CD98hc complex contributes to poor prognosis of non-small cell lung cancer patients through promoting cell proliferation via the PI3K/Akt signaling pathway.

    Science.gov (United States)

    Fei, Fei; Li, Xiaofei; Xu, Li; Li, Deyang; Zhang, Zhipei; Guo, Xu; Yang, Hushan; Chen, Zhinan; Xing, Jinliang

    2014-12-01

    It has been reported that CD147 and CD98 heavy chain (CD98hc) form a complex on the cell plasma membrane of several cancers; however, whether this complex exists in non-small cell lung cancer (NSCLC) cells and affects the prognosis of patients remains to be elucidated. The expression of CD147 and CD98hc was assessed in tissue samples from 241 NSCLC patients and NSCLC cell lines. The correlation between CD147 and CD98hc expression and their association with the prognosis of NSCLC patients were analyzed. We also evaluated the impact of CD147 and CD98hc on the growth of NSCLC cells as well as Akt phosphorylation. Both CD147 and CD98hc were significantly upregulated in NSCLC cells, and their expression levels were significantly correlated (p CD147 and CD98hc could form a complex on NSCLC cells. Compared with NSCLC patients with CD147-/CD98hc-, those with CD147+/CD98hc+ exhibited a significantly poor overall survival (OS) with a hazard ratio (HR) of 1.92 (p = 0.010), and a significantly increased risk of recurrence with a HR of 1.97 (p = 0.004). Also, we demonstrated that the proliferation of lung cancer cell lines was significantly affected by knockdown and force-expression of the CD147-CD98hc complex. Western blot analysis indicated that the phosphorylation of Akt in NSCLC cells was significantly affected by knockdown and overexpression of either or both CD147 and CD98hc. Our findings indicate that the CD147-CD98hc complex significantly contributes to poor prognosis of NSCLC patients through promoting cell proliferation via the PI3K/Akt pathway.

  14. Concurrent disruption of p16INK4a and the ARF-p53 pathway predicts poor prognosis in aggressive non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Grønbaek, K; de Nully Brown, P; Møller, Michael Boe

    2000-01-01

    . By using a panel of PCR-based methods, we have examined the status of the p16INK4a, ARF and p53 genes in 123 cases of non-Hodgkin's lymphoma (NHL) at diagnosis. Alterations of one or more of these genes were detected in seven of 36 (19%) cases with low- to intermediate-grade histology, and in 35 of 87 (40...

  15. How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology.

    Science.gov (United States)

    Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M E Bette; Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M; Whelan, Maurice

    2017-02-01

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework provides a systematic approach for organizing knowledge that may support such inference. Likewise, computational models of biological systems at various scales provide another means and platform to integrate current biological understanding to facilitate inference and extrapolation. We argue that the systematic organization of knowledge into AOP frameworks can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. This concept was explored as part of a workshop on AOP-Informed Predictive Modeling Approaches for Regulatory Toxicology held September 24-25, 2015. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development is described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

  16. Post-trauma ratings of pre-collision pain and psychological distress predict poor outcome following acute whiplash trauma: A 12-month follow-up study

    DEFF Research Database (Denmark)

    Carstensen, Tina

    2008-01-01

    emergency departments or primary care after car accidents in four counties in Denmark. After the collision patients received a questionnaire on psychological distress, unspecified pain and socio-demographics and 12months later a follow-up on work capability and neck pain was performed. Risk factors were...... were not associated with poor outcome. In conclusion unspecified as opposed to specified pain (neck pain) before the collision is associated with poor recovery and high accumulation of pre-collision psychological distress is associated with considerable neck pain at follow-up. However, no conclusions...... on causality can be drawn. Personal characteristics before the collision are important for recovery and attention to pre-collision characteristics may contribute to the prevention of poor recovery after acute whiplash trauma....

  17. Post-trauma ratings of pre-collision pain and psychological distress predict poor outcome following acute whiplash trauma: A 12-month follow-up study

    DEFF Research Database (Denmark)

    Carstensen, Tina; Frostholm, Lisbeth; Ørnbøl, Eva

    2008-01-01

    emergency departments or primary care after car accidents in four counties in Denmark. After the collision patients received a questionnaire on psychological distress, unspecified pain and socio-demographics and 12 months later a follow-up on work capability and neck pain was performed. Risk factors were...... of accident were not associated with poor outcome. In conclusion unspecified as opposed to specified pain (neck pain) before the collision is associated with poor recovery and high accumulation of pre-collision psychological distress is associated with considerable neck pain at follow-up. However......, no conclusions on causality can be drawn. Personal characteristics before the collision are important for recovery and attention to pre-collision characteristics may contribute to the prevention of poor recovery after acute whiplash trauma....

  18. In vitro assays for predicting tumor cell response to radiation by apoptotic pathways

    International Nuclear Information System (INIS)

    Algan, Oe.; Hanks, G.E.; Biade, S.; Chapman, J.D.

    1995-01-01

    Purpose: We had previously shown that the rate of spontaneous and radiation-induced apoptosis was significantly greater in well-differentiated compared to anaplastic Dunning prostate carcinomas. The goal of this study was to define the most useful assay for quantifying radiation-induced apoptotic cell death and to determine if measured rates of radiation-induced apoptosis in tumor cell populations can predict treatment outcome. Materials and Methods: The time course and extent of radiation-induced apoptosis after single doses of Cesium-137 gamma-rays were measured by five different assays. These included gross DNA degradation, nucleosome ladder formation, labeling of 3'-OH ends in DNA with an immunofluorescence probe, immunofluorescence vital stains (LIVE/DEAD[reg] EUKOLIGHT TM ) and trypan blue. The majority of these studies were performed with DU-145 human prostate cells. Data was analyzed to determine the component of cell inactivation resulting from apoptosis with the modified linear quadratic equation, -1n (SF) = (α a + α p ) D + β p D 2 , were α a represents cell inactivation by radiation-induced apoptosis, α p and β p represent cell death by proliferative mechanisms and D represents radiation dose. Results: These studies indicated that DU-145 cell death after radiation occurs over two distinct time periods. The first phase of death begins shortly after irradiation and plateaus within 16-24 hr. This process of cell death has properties consistent with apoptosis as determined by 3'-OH DNA end-labeling and nucleosome ladder assays. The second phase of cell death (determined by viability staining) begins approximately 48 hr after irradiation and continues until the remainder of inactivated cells express their death. This longer phase of cell inactivation probably represents proliferative cell death and other non-apoptotic mechanisms. The five different assays were performed on DU-145 cells 24 hr after irradiation with 10 Gy. Significant nucleosome ladders

  19. Development of computationally predicted Adverse Outcome Pathway (AOP) networks through data mining and integration of publicly available in vivo, in vitro, phenotype, and biological pathway data

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  20. Generation of computationally predicted Adverse Outcome Pathway networks through integration of publicly available in vivo, in vitro, phenotype, and biological pathway data.

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is becoming a widely used tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse ecological and human health outcomes. However, the conventional process...

  1. Perceived Stress and Coffee and Energy Drink Consumption Predict Poor Sleep Quality in Podiatric Medical Students A Cross-sectional Study.

    Science.gov (United States)

    Sawah, Mohomad Al; Ruffin, Naeemah; Rimawi, Mohammad; Concerto, Carmen; Aguglia, Eugenio; Chusid, Eileen; Infortuna, Carmenrita; Battaglia, Fortunato

    2015-09-01

    A cross-sectional survey administered to first- and second-year podiatric medical students aimed to investigate the effect of coffee intake, energy drink consumption, and perceived stress on sleep quality in medical students during their preclinical studies. Ninety-eight of 183 students contacted (53.6%) completed a questionnaire comprising standard instruments measuring sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth Sleepiness scale), and perceived stress (ten-item Perceived Stress Scale). Furthermore, we investigated coffee and energy drink consumption. Logistic regression was conducted to identify factors associated with poor sleep quality and the relation between sleep quality and academic performance (grade point average). High prevalences of poor sleep quality, excessive daytime sleepiness, and perceived stress were reported. In addition, higher odds of developing poor sleep quality were associated with coffee and energy drink intake, perceived stress, and excessive daytime sleepiness. The total Pittsburgh Sleep Quality Index score was inversely correlated with grade point average. First- and second-year podiatric medical students have poor sleep quality. Further research is needed to identify effective strategies to reduce stress and decrease coffee and energy drink intake to minimize their negative effect on sleep quality and academic performance in podiatric medical students.

  2. Pathways to Structure-Property Relationships of Peptide-Materials Interfaces: Challenges in Predicting Molecular Structures.

    Science.gov (United States)

    Walsh, Tiffany R

    2017-07-18

    challenges in their successful application to model the biotic-abiotic interface, related to several factors. For instance, simulations require a plausible description of the chemistry and the physics of the interface, which comprises two very different states of matter, in the presence of liquid water. Also, it is essential that the conformational ensemble be comprehensively characterized under these conditions; this is especially challenging because intrinsically disordered peptides do not typically admit one single structure or set of structures. Moreover, a plausible structural model of the substrate is required, which may require a high level of detail, even for single-element materials such as Au surfaces or graphene. Developing and applying strategies to make credible predictions of the conformational ensemble of adsorbed peptides and using these to construct structure-property relationships of these interfaces have been the goals of our efforts. We have made substantial progress in developing interatomic potentials for these interfaces and adapting advanced conformational sampling approaches for these purposes. This Account summarizes our progress in the development and deployment of interfacial force fields and molecular simulation techniques for the purpose of elucidating these insights at biomolecule-materials interfaces, using examples from our laboratories ranging from noble-metal interfaces to graphitic substrates (including carbon nanotubes and graphene) and oxide materials (such as titania). In addition to the well-established application areas of plasmonic materials, biosensing, and the production of medical implant materials, we outline new directions for this field that have the potential to bring new advances in areas such as energy materials and regenerative medicine.

  3. Determination of HER2 phosphorylation at tyrosine 1221/1222 improves prediction of poor survival for breast cancer patients with hormone receptor-positive tumors

    DEFF Research Database (Denmark)

    Frogne, Thomas; Laenkholm, Anne-Vibeke; Lyng, Maria B

    2009-01-01

    INTRODUCTION: High expression of total HER2 protein confers poor prognosis for breast cancer patients. HER2 is a member of the HER family consisting of four receptors, HER1 to HER4. HER receptor activity is regulated by a variety of mechanisms, and phosphorylation of the C-terminal part of the HER...... metastases, by evaluating the expression of phosphorylated HER1, HER2, HER3, Erk, Akt and the total level of HER4 and HER2. METHODS: Immunohistochemical analysis was performed on 268 primary breast tumors and 30 paired metastatic lesions from postmenopausal women with hormone receptor-positive breast tumors...... of Akt and Erk were quite uniformly expressed in the categories; negative, moderate or strong. In univariate analysis, expression of total HER2, pHER1, pHER2 and pHER3 was significantly associated with poor disease-free survival. Strong HER4 expression was associated with prolonged disease-free as well...

  4. The Number of Pathologically Positive Lymph Nodes and Pathological Tumor Depth Predicts Prognosis in Patients With Poorly Differentiated Squamous Cell Carcinoma of the Oral Cavity

    International Nuclear Information System (INIS)

    Kang, Chung-Jan; Lin, Chien-Yu; Wang, Hung-Ming; Fan, Kang-Hsing; Ng, Shu-Hang; Lee, Li-Yu; Chen, I-How; Huang, Shiang-Fu

    2011-01-01

    Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%), neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes (≥4 vs. ≤3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of ≥11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth ≥11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches.

  5. The prediction of poor outcome in young adults: comparison of the Young Adult Self-Report, the General Health Questionnaire and the Symptom Checklist.

    Science.gov (United States)

    Ferdinand, R F; Verhulst, F C

    1994-06-01

    The ability of the Young Adult Self-Report (YASR), the Symptom Checklist (SCL-90) and the General Health Questionnaire (GHQ-28) to predict maladjustment across a 2-year time-span was assessed in a general population sample of 528 18- to 22-year-olds. Referral for mental health services and need for professional help were predicted by total problem scores of the YASR, the GHQ-28 and the SCL-90 and by the internalizing scale of the YASR. Furthermore, the internalizing scale predicted suicide attempts or suicidal ideation, whereas the externalizing scale predicted police contacts. The YASR delinquent behavior syndrome was the only significant predictor of alcohol abuse. The findings supported the validity of the YASR as an instrument for the assessment of psychopathology in young adults.

  6. Improvement of a predictive model of castration-resistant prostate cancer: functional genetic variants in TGFβ1 signaling pathway modulation.

    Directory of Open Access Journals (Sweden)

    Ana L Teixeira

    Full Text Available Prostate cancer (PC is the most frequently diagnosed cancer in men. The acquisition of castration-resistant (CR phenotype is associated with the activation of signaling pathways mediated by growth factors. The TGFβ1 and its receptors have an important role in tumor progression, being the pro-apoptotic function modulated by the expression of TGFBR2. A single nucleotide polymorphism -875 G > A in TGFBR2 gene has been described, which may influence the expression levels of the receptor. Our purpose was to investigate the potential role of TGFBR2-875G>A in PC risk and in the response to androgen deprivation therapy (ADT. TGFBR2-875G>A polymorphism was studied by allelic discrimination using real-time polymerase chain reaction (PCR in 891 patients with PC and 874 controls. A follow-up study was undertaken to evaluate response to ADT. The TGFBR2 and SMAD7 mRNA expression were analyzed by a quantitative real-time PCR. We found that TGFBR2-875GG homozygous patients present lower expression levels of TGFBR2 mRNA (AA/AG: 2(-ΔΔCT =1.5, P=0.016. GG genotype was also associated with higher Gleason grade (OR=1.51, P=0.019 and increased risk of an early relapse after ADT (HR=1.47, P=0.024. The concordance (c index analysis showed that the definition of profiles that contains information regarding tumor characteristics associated with genetic information present an increased capacity to predict the risk for CR development (c-index model 1: 0.683 vs model 2: 0.736 vs model 3: 0.746 vs model 4: 0.759. The TGFBR2-875G>A contribution to an early relapse in ADT patients, due to changes in mRNA expression, supports the involvement of TGFβ1 pathway in CRPC. Furthermore, according to our results, we hypothesize the potential benefits of the association of genetic information in predictive models of CR development.

  7. Combining in vitro and in silico methods for better prediction of surfactant effects on the absorption of poorly water soluble drugs-a fenofibrate case example.

    Science.gov (United States)

    Berthelsen, Ragna; Sjögren, Erik; Jacobsen, Jette; Kristensen, Jakob; Holm, René; Abrahamsson, Bertil; Müllertz, Anette

    2014-10-01

    The aim of this study was to develop a sensitive and discriminative in vitro-in silico model able to simulate the in vivo performance of three fenofibrate immediate release formulations containing different surfactants. In addition, the study was designed to investigate the effect of dissolution volume when predicting the oral bioavailability of the formulations. In vitro dissolution studies were carried out using the USP apparatus 2 or a mini paddle assembly, containing 1000 mL or 100mL fasted state biorelevant medium, respectively. In silico simulations of small intestinal absorption were performed using the GI-Sim absorption model. All simulation runs were performed twice adopting either a total small intestinal volume of 533 mL or 105 mL, in order to examine the implication of free luminal water volumes for the in silico predictions. For the tested formulations, the use of a small biorelevant dissolution volume was critical for in vitro-in silico prediction of drug absorption. Good predictions, demonstrating rank order in vivo-in vitro-in silico correlations for Cmax, were obtained with in silico predictions utilizing a 105 mL estimate for the human intestinal water content combined with solubility and dissolution data performed in a mini paddle apparatus with 100mL fasted state simulated media. Copyright © 2014. Published by Elsevier B.V.

  8. Long-Term Clinical Outcomes and Factors That Predict Poor Prognosis in Athletes After a Diagnosis of Acute Spondylolysis: A Retrospective Review With Telephone Follow-up.

    Science.gov (United States)

    Selhorst, Mitchell; Fischer, Anastasia; Graft, Kristine; Ravindran, Reno; Peters, Eric; Rodenberg, Richard; MacDonald, James

    2016-12-01

    Study Design Retrospective review with telephone follow-up. Background Acute spondylolytic injuries have a dramatic impact on the young athlete. Excellent short-term clinical outcomes have been observed, but not enough is known about long-term clinical outcomes. Objectives (1) To report long-term clinical outcomes for patients diagnosed with acute spondylolysis, and (2) to assess the prognostic ability of retrospective variables for long-term outcomes. Methods Patients from 2010 through 2013 were retrospectively reviewed to identify patients and to obtain demographic, baseline, and short-term outcomes. Long-term follow-up data were collected by telephone from patients diagnosed with acute spondylolysis to assess recurrence rate of low back pain, perceived outcome, pain, and functional ability. Patients were categorized as having a good or poor long-term outcome based on these measures. Logistic regression analysis was performed to assess the prognostic ability of the retrospective variables for long-term outcomes 3.4 years (range, 1.5-5.6 years) after treatment. Results One hundred twenty-one (71.6%) patients completed the follow-up questionnaire (48 female; mean age at baseline, 14.4 years). At follow-up, 81 (66.9%) patients were able to maintain their same or a higher level of sport. Recurrence of significant symptoms was reported by 55 (45.5%) patients, with 41 (33.9%) requiring medical treatment. The final logistic regression model revealed that female sex, adverse reaction during care, and multilevel injury were significant predictors of poor long-term outcome (R 2 = 0.22). Conclusion Although excellent short-term outcomes were noted, 42% of patients reported a poor outcome at long-term follow-up. Female sex, multilevel injury, and experiencing an adverse reaction during care were significant predictors of poor long-term clinical outcome for patients diagnosed with acute spondylolysis. Level of Evidence Prognosis, level 4. Registered January 15, 2015 at www

  9. Extending and Applying Spartan to Perform Temporal Sensitivity Analyses for Predicting Changes in Influential Biological Pathways in Computational Models.

    Science.gov (United States)

    Alden, Kieran; Timmis, Jon; Andrews, Paul S; Veiga-Fernandes, Henrique; Coles, Mark

    2017-01-01

    Through integrating real time imaging, computational modelling, and statistical analysis approaches, previous work has suggested that the induction of and response to cell adhesion factors is the key initiating pathway in early lymphoid tissue development, in contrast to the previously accepted view that the process is triggered by chemokine mediated cell recruitment. These model derived hypotheses were developed using spartan, an open-source sensitivity analysis toolkit designed to establish and understand the relationship between a computational model and the biological system that model captures. Here, we extend the functionality available in spartan to permit the production of statistical analyses that contrast the behavior exhibited by a computational model at various simulated time-points, enabling a temporal analysis that could suggest whether the influence of biological mechanisms changes over time. We exemplify this extended functionality by using the computational model of lymphoid tissue development as a time-lapse tool. By generating results at twelve- hour intervals, we show how the extensions to spartan have been used to suggest that lymphoid tissue development could be biphasic, and predict the time-point when a switch in the influence of biological mechanisms might occur.

  10. Overexpression of the E2F target gene CENPI promotes chromosome instability and predicts poor prognosis in estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Thangavelu, Pulari U; Lin, Cheng-Yu; Vaidyanathan, Srividya; Nguyen, Thu H M; Dray, Eloise; Duijf, Pascal H G

    2017-09-22

    During cell division, chromosome segregation is facilitated by the mitotic checkpoint, or spindle assembly checkpoint (SAC), which ensures correct kinetochore-microtubule attachments and prevents premature sister-chromatid separation. It is well established that misexpression of SAC components on the outer kinetochores promotes chromosome instability (CIN) and tumorigenesis. Here, we study the expression of CENP-I, a key component of the HIKM complex at the inner kinetochores, in breast cancer, including ductal, lobular, medullary and male breast carcinomas. CENPI mRNA and protein levels are significantly elevated in estrogen receptor-positive (ER+) but not in estrogen receptor-negative (ER-) breast carcinoma. Well-established prognostic tests indicate that CENPI overexpression constitutes a powerful independent marker for poor patient prognosis and survival in ER+ breast cancer. We further demonstrate that CENPI is an E2F target gene. Consistently, it is overexpressed in RB1 -deficient breast cancers. However, CENP-I overexpression is not purely due to cell cycle-associated expression. In ER+ breast cancer cells, CENP-I overexpression promotes CIN, especially chromosome gains. In addition, in ER+ breast carcinomas the degree of CENPI overexpression is proportional to the level of aneuploidy and CENPI overexpression is one of the strongest markers for CIN identified to date. Our results indicate that overexpression of the inner kinetochore protein CENP-I promotes CIN and forecasts poor prognosis for ER+ breast cancer patients. These observations provide novel mechanistic insights and have important implications for breast cancer diagnostics and potentially therapeutic targeting.

  11. Poor value of surveillance cultures for prediction of septicaemia caused by coagulase-negative staphylococci in patients undergoing haemodialysis with central venous catheters

    DEFF Research Database (Denmark)

    Nielsen, J; Kolmos, H J; Rosdahl, V T

    1998-01-01

    Surveillance cultures for the demonstration of coagulase-negative staphylococci in patients on catheter haemodialysis were performed in an attempt to predict dialysis catheter-related septicaemia. In all, 43 patients with 67 haemodialysis catheters were followed for a 1-y period. Once a week, swab...

  12. Elevated Fasting Blood Glucose Is Predictive of Poor Outcome in Non-Diabetic Stroke Patients: A Sub-Group Analysis of SMART.

    Directory of Open Access Journals (Sweden)

    Ming Yao

    Full Text Available Although increasing evidence suggests that hyperglycemia following acute stroke adversely affects clinical outcome, whether the association between glycaemia and functional outcome varies between stroke patients with\\without pre-diagnosed diabetes remains controversial. We aimed to investigate the relationship between the fasting blood glucose (FBG and the 6-month functional outcome in a subgroup of SMART cohort and further to assess whether this association varied based on the status of pre-diagnosed diabetes.Data of 2862 patients with acute ischemic stroke (629 with pre-diagnosed diabetics enrolled from SMART cohort were analyzed. Functional outcome at 6-month post-stroke was measured by modified Rankin Scale (mRS and categorized as favorable (mRS:0-2 or poor (mRS:3-5. Binary logistic regression model, adjusting for age, gender, educational level, history of hypertension and stroke, baseline NIHSS and treatment group, was used in the whole cohort to evaluate the association between admission FBG and functional outcome. Stratified logistic regression analyses were further performed based on the presence/absence of pre-diabetes history.In the whole cohort, multivariable logistical regression showed that poor functional outcome was associated with elevated FBG (OR1.21 (95%CI 1.07-1.37, p = 0.002, older age (OR1.64 (95% CI1.38-1.94, p<0.001, higher NIHSS (OR2.90 (95%CI 2.52-3.33, p<0.001 and hypertension (OR1.42 (95%CI 1.13-1.98, p = 0.04. Stratified logistical regression analysis showed that the association between FBG and functional outcome remained significant only in patients without pre-diagnosed diabetes (OR1.26 (95%CI 1.03-1.55, p = 0.023, but not in those with premorbid diagnosis of diabetes (p = 0.885.The present results demonstrate a significant association between elevated FBG after stroke and poor functional outcome in patients without pre-diagnosed diabetes, but not in diabetics. This finding confirms the importance of glycemic

  13. CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer

    DEFF Research Database (Denmark)

    Cepeda, Diana; Ng, Hwee-Fang; Sharifi, Hamid Reza

    2013-01-01

    SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCF(FBXO28...... results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCF(FBXO28) plays an important role...... in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer....

  14. Mathematical Modeling Predicts that Increased HSV-2 Shedding in HIV-1 Infected Persons Is Due to Poor Immunologic Control in Ganglia and Genital Mucosa.

    Directory of Open Access Journals (Sweden)

    Joshua T Schiffer

    Full Text Available A signature feature of HIV infection is poor control of herpes virus infections, which reactivate from latency and cause opportunistic infections. While the general mechanism underlying this observation is deficient CD4+T-cell function, it is unknown whether increased severity of herpes virus infections is due primarily to poor immune control in latent or lytic sites of infection, or whether CD4+ immunodeficiency leads to more critical downstream deficits in humoral or cell-mediated immunologic responses. Here we compare genital shedding patterns of herpes simplex virus-2 (HSV-2 in 98 HIV infected and 98 HIV uninfected men matched on length of infection, HSV-1 serostatus and nationality. We demonstrate that high copy HSV-2 shedding is more frequent in HIV positive men, particularly in participants with CD4+ T-cell count <200/μL. Genital shedding is more frequent due to higher rate of shedding episodes, as well as a higher proportion of prolonged shedding episodes. Peak episode viral load was not found to differ between HIV infected and uninfected participants regardless of CD4+ T-cell count. We simulate a mathematical model which recapitulates these findings and identifies that rate of HSV-2 release from neural tissue increases, duration of mucosal cytolytic immune protection decreases, and cell-free viral lifespan increases in HIV infected participants. These results suggest that increased HSV-2 shedding in HIV infected persons may be caused by impaired immune function in both latent and lytic tissue compartments, with deficits in clearance of HSV-2 infected cells and extracellular virus.

  15. Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios Are More Effective than the Fournier's Gangrene Severity Index for Predicting Poor Prognosis in Fournier's Gangrene.

    Science.gov (United States)

    Yim, Sang Un; Kim, Sun Woo; Ahn, Ji Hoon; Cho, Yang Hyun; Chung, Hoseok; Hwang, Eu Chang; Yu, Ho Song; Oh, Kyung Jin; Kim, Sun-Ouck; Jung, Seung Il; Kang, Taek Won; Kwon, Dong Deuk; Park, Kwangsung

    2016-04-01

    We investigated the value of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as markers of mortality in patients with Fournier's gangrene. Records from 62 patients treated for Fournier's gangrene between 2003 and 2014 were reviewed retrospectively. Data were collected regarding medical history, symptoms, physical examination findings, admission laboratory tests, and the extent of body surface area involved (%). Fournier's Gangrene Severity Index score, NLR, and PLR were calculated. The data were assessed separately for surviving and deceased patients. Of the 62 patients, 36 survived (58%, group 1) and 26 died (42%, group 2). Parameters that were statistically different between the two groups (p Fournier's Gangrene Severity Index score, and admission laboratory parameters, including body temperature, heart rate, bicarbonate, albumin, and serum calcium. The average body surface area affected in group 2 was statistically different from that of group 1 (6.0% versus 2.3%, p = 0.001). A high Fournier's Gangrene Severity Index score (>9), high NLR (>8), and high PLR (>140) were associated more frequently with group 2 patients. Multivariable regression analysis showed that high NLR (adjusted odds ratio [OR], 4.66; 95% confidence interval [CI], 1.25-17.3; p = 0.022) and high PLR (adjusted OR, 11.6; 95% CI, 2.7-49.5; p = 0.001) were independent prognostic factors for poor prognosis from Fournier's gangrene. However, the Fournier's Gangrene Severity Index score did not shown any statistically significant effect on mortality (p = 0.086). The Fournier's Gangrene Severity Index scoring system was not associated with determining poor prognosis, however, high NLR and high PLR were associated with predictors of mortality in patients with Fournier's gangrene.

  16. lncRNA H19 predicts poor prognosis in patients with melanoma and regulates cell growth, invasion, migration and epithelial–mesenchymal transition in melanoma cells

    Directory of Open Access Journals (Sweden)

    Shi G

    2018-06-01

    Full Text Available Gaofeng Shi,1,2 Hu Li,2 Fengshan Gao,2 Qian Tan1 1Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Plastic Surgery, the Affiliated Wuxi No 4 People’s Hospital of Jiangnan University, Wuxi, People’s Republic of China Introduction: Melanoma is a deadly malignancy and the poor prognosis of patients with advanced disease is relatively poor. Recent studies indicate that long non-coding RNAs are involved in the pathogenesis of malignant melanoma. This study aims to investigate the role of the long non-coding RNA H19 in melanoma and to explore the underlying molecular mechanisms. Materials and methods: The expression levels of H19 in clinical samples and melanoma cells were determined by quantitative real-time PCR. The cell growth and cell metastasis were assessed by Cell Counting Kit 8, cell invasion and wound healing assays. Cell apoptosis and cell cycle were determined by flow cytometry. Protein levels were determined by Western blotting assay. Results: H19 was highly expressed in melanoma tissues compared to normal adjacent skin tissues, and the tissue expression level of H19 from melanoma patients with metastasis was significantly higher than that from patients without distant metastasis. In addition, the high expression of H19 in melanoma tissues was associated with advanced tumor invasion and TNM stage, distal metastasis, lymph node metastasis and shorter overall survival in patients with melanoma. The in vitro functional assays showed that knockdown of H19 inhibited cell growth, invasion and migration and also induced cell apoptosis as well as G0/G1 arrest in melanoma cells. Further quantitative real-time PCR and Western blot experiments showed that knockdown of H19 differentially regulated the epithelial–mesenchymal transition (EMT-related gene expressions and reversed EMT in melanoma cell lines. Knockdown of H19 suppressed in vivo tumor growth and modulated the

  17. Tissue factor pathway inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study.

    Directory of Open Access Journals (Sweden)

    Aurélie Di Bartolomeo

    Full Text Available The study aimed to evaluate if the rate of tissue factor pathway inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women.This was a prospective multicentre cohort study of 200 patients at a high risk of occurrence or recurrence of placenta-mediated adverse pregnancy outcomes conducted between June 2008 and October 2010. Measurements of tissue factor pathway inhibitor resistance (normalized ratio and tissue factor pathway inhibitor activity were performed for the last 72 patients at 20, 24, 28, 32, and 36 weeks of gestation and during the postpartum period.Overall, 15 patients presented a placenta-mediated adverse pregnancy outcome. There was no difference in normalized tissue factor pathway inhibitor ratios between patients with and without placenta-mediated adverse pregnancy outcomes during pregnancy and in the post-partum period. Patients with placenta-mediated adverse pregnancy outcomes had tissue factor pathway inhibitor activity rates that were significantly higher than those in patients without at as early as 24 weeks of gestation. The same results were observed following delivery.Among high-risk women, the tissue factor pathway inhibitor activity of patients with gestational vascular complications is higher than that in other patients. Hence, these markers could augment a screening strategy that includes an analysis of angiogenic factors as well as clinical and ultrasound imaging with Doppler measurement of the uterine arteries.

  18. High defect stage, contralateral defects, and poor flexibility are negative predictive factors of bone union in pediatric and adolescent athletes with spondylolysis.

    Science.gov (United States)

    Yamazaki, Kazufumi; Kota, Shintaro; Oikawa, Daisuke; Suzuki, Yoshiji

    2018-01-01

    To identify predisposition to spondylolysis and physical characteristics associated with "bone union" following conservative spondylolysis treatment among pediatric and adolescent athletes. We retrospectively analyzed pediatric and adolescent athletes with spondylolysis who underwent conservative treatment and rehabilitation for three or more consecutive months following sports activity cessation. Patients with terminal spondylolysis or who did not discontinue sports activities were excluded. We compared physical fitness factors in the union and nonunion groups and examined the association between bone union and spondylolysis severity by logistic regression analysis. Of 183 patients with spondylolysis who underwent rehabilitation over a four-year period, 127 patients with 227 defects were included in the final analysis. Bone union was achieved in 66.5% (151/227) of the pars interarticularis defects and 70.1% (89/127) of the patients. On multivariate analysis, stage of pars interarticularis defect (odds ratio [OR], 0.26;p = 0.0027), stage of contralateral pars interarticularis defect (OR, 0.51;p = 0.00026), and straight leg-raising test (OR, 1.06;p = 0.028) were significantly associated with bone union. High defect stage, stage of the contralateral pars interarticularis defect, and poor flexibility were negative prognostic factors of bone healing in athletes with spondylolysis. J. Med. Invest. 65:126-130, February, 2018.

  19. Poor peer relations predict parent- and self-reported behavioral and emotional problems of adolescents with gender dysphoria: a cross-national, cross-clinic comparative analysis.

    Science.gov (United States)

    de Vries, Annelou L C; Steensma, Thomas D; Cohen-Kettenis, Peggy T; VanderLaan, Doug P; Zucker, Kenneth J

    2016-06-01

    This study is the third in a series to examine behavioral and emotional problems in children and adolescents with gender dysphoria in a comparative analysis between two clinics in Toronto, Ontario, Canada and Amsterdam, the Netherlands. In the present study, we report Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) data on adolescents assessed in the Toronto clinic (n = 177) and the Amsterdam clinic (n = 139). On the CBCL and the YSR, we found that the percentage of adolescents with clinical range behavioral and emotional problems was higher when compared to the non-referred standardization samples but similar to the referred adolescents. On both the CBCL and the YSR, the Toronto adolescents had a significantly higher Total Problem score than the Amsterdam adolescents. Like our earlier studies of CBCL data of children and Teacher's Report Form data of children and adolescents, a measure of poor peer relations was the strongest predictor of CBCL and YSR behavioral and emotional problems in gender dysphoric adolescents.

  20. The dilatation of main pulmonary artery and right ventricle observed by enhanced chest computed tomography predict poor outcome in inoperable chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Ema, Ryogo; Sugiura, Toshihiko; Kawata, Naoko; Tanabe, Nobuhiro; Kasai, Hajime; Nishimura, Rintaro; Jujo, Takayuki; Shigeta, Ayako; Sakao, Seiichiro; Tatsumi, Koichiro

    2017-09-01

    Dilatation of the pulmonary artery and right ventricle on chest computed tomography images is often observed in patients with pulmonary hypertension. The clinical significance of these image findings has not been defined in chronic thromboembolic pulmonary hypertension. We investigated whether the pulmonary arterial and right ventricle dilatation was associated with poor outcome in chronic thromboembolic pulmonary hypertension. This was a retrospective cohort investigation in 60 subjects with inoperable chronic thromboembolic pulmonary hypertension diagnosed consecutively between 1997 and 2010 at Chiba University Hospital. Digital scout multi-detector chest computed tomography images were obtained. The main pulmonary arterial to ascending aortic diameter ratio and the right ventricular to left ventricular diameter ratio were calculated. Main pulmonary arterial to ascending aortic diameter ratio ranged from 0.85 to 1.84, and right ventricular to left ventricular diameter ratio ranged from 0.71 to 2.88. During the observation period of 1284.5days (range, 21-4550days), 13 patients required hospitalization due to worsening; 6 of them died. Kaplan-Meier analysis showed significant differences in hospitalization between the patients with main pulmonary arterial to ascending aortic diameter ratio of ≥1.1 and pulmonary hypertension. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Systemic immune-inflammation index predicting chemoradiation resistance and poor outcome in patients with stage III non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Yu-Suo Tong

    2017-10-01

    Full Text Available Abstract Background There is increasing evidence that the existence of systemic inflammation response is correlated with poor prognosis in several solid tumors. The aim of this retrospective study was to investigate the association between systemic immune-inflammation index (SII and therapy response and overall survival in patients with stage III non-small cell lung cancer (NSCLC. The prognostic values of neutrophil to lymphocyte ratio (NLR, platelet to lymphocyte ratio (PLR, and prognostic nutritional index (PNI were also evaluated. Methods In total, 332 patients with new diagnosis of stage III NSCLC were included in this retrospective analysis. SII was defined as platelet counts × neutrophil counts/lymphocyte counts. Receiver operating characteristic (ROC curve was used to evaluate the optimal cut-off value for SII, NLR, PLR and PNI. Univariate and multivariate survival analysis were performed to identify the factors correlated with overall survival. Results Applying cut-offs of ≥ 660 (SII, ≥ 3.57 (NLR, ≥ 147 (PLR, ≤ 52.95 (PNI, SII ≥ 660 was significantly correlated with worse ECOG PS (< 0.001, higher T stage (< 0.001, advanced clinical stage (p = 0.019, and lower response rate (p = 0.018. In univariate analysis, SII ≥ 660, NLR ≥ 3.57, PLR ≥ 147, and PNI ≤ 52.95 were significantly associated with worse overall survival (p all < 0.001. Patients with SII ≥ 660 had a median overall survival of 10 months, and patients with SII < 660 showed a median overall survival of 30 months. In multivariate analysis only ECOG PS (HR, 1.744; 95% CI 1.158–2.626; p = 0.008, T stage (HR, 1.332; 95% CI 1.032–1.718; p = 0.028, N stage (HR, 1.848; 95% CI 1.113–3.068; p = 0.018, SII (HR, 2.105; 95% CI 1.481–2.741; p < 0.001 and NLR ≥ 3.57 (HR, 1.934; 95% CI 1.448–2.585; p < 0.001 were independently correlated with overall survival. Conclusions This study demonstrates that the SII is an

  2. Downregulation of miR-15a due to LMP1 promotes cell proliferation and predicts poor prognosis in nasal NK/T-cell lymphoma.

    Science.gov (United States)

    Komabayashi, Yuki; Kishibe, Kan; Nagato, Toshihiro; Ueda, Seigo; Takahara, Miki; Harabuchi, Yasuaki

    2014-01-01

    Nasal NK/T-cell lymphoma (NNKTL) is an Epstein-Barr virus (EBV)-associated malignancy and has distinct clinical and histological features. However, its genetic features are hitherto unclear. MicroRNAs (miRNAs) play a crucial role in the pathogenesis of several malignancies via regulating gene expression. In this study, we investigated whether the specific microRNAs were related to the tumor behaviors in NNKTL. MiRNA array and Quantitative RT-PCR analyses revealed that miR-15a was expressed at a much lower level in NNKTL cells (SNK-1, SNK-6, and SNT-8) than in normal peripheral NK cells and EBV-negative NK cell line KHYG-1. Quantitative PCR and western blot analyses showed that the expression of MYB and cyclin D1, which are validated targets of miR-15a, was higher in NNKTL cells. Transfection of NNKTL cells (SNK-6 and SNT-8) with a miR-15a precursor decreased MYB and cyclin D1 levels, thereby blocking G1/S transition and cell proliferation. Knockdown of EBV-encoded latent membrane protein 1 (LMP1) significantly increased miR-15a expression in SNK-6 cells. In NNKTL tissues, we found that reduced miR-15a expression, which correlated with MYB and cyclin D1 expression, was associated with poor prognosis of NNKTL patients. These data suggest that downregulation of miR-15a, possibly due to LMP1, implicates in the pathogenesis of NNKTL by inducing cell proliferation via MYB and cyclin D1. Thus, miR-15a could be a potential target for antitumor therapy and a prognostic predictor for NNKTL. Copyright © 2013 Wiley Periodicals, Inc.

  3. High preoperative serum CA19-9 level is predictive of poor prognosis for patients with colorectal liver oligometastases undergoing hepatic resection.

    Science.gov (United States)

    Lu, Zhenhai; Peng, Jianhong; Wang, Zhiqiang; Pan, Zhizhong; Yuan, Yunfei; Wan, Desen; Li, Binkui

    2016-11-01

    Oligometastasis is defined as a transitional state between localized and widespread systemic metastatic cancers. In colorectal cancer, the prognostic factors and prognostic value of preoperative serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) for patients with colorectal liver oligometastases (CLOM) undergoing hepatic resection have not been well explored. Therefore, the present study included 141 patients with CLOM (≤5 liver metastases) who underwent R0 resection from 2005 to 2012. The association of clinicopathological factors including preoperative CA19-9 and CEA levels with overall survival (OS) was analyzed with univariate and multivariate analyses. Kaplan-Meier analysis showed that patients with high CA19-9 levels tended to have poorer OS than those with low levels (median OS 21.5 vs. 64.0 months, P = 0.002). Preoperative CEA levels were not significantly associated with OS (P > 0.05). Univariate and multivariate analyses demonstrated that larger tumor size of liver metastases (HR 1.911; 95 % CI 1.172-3.114; P = 0.009), bilobar distribution (HR 1.776; 95 % CI 1.097-2.873; P = 0.019), and higher preoperative CA19-9 levels (HR 1.954; 95 % CI 1.177-3.242; P = 0.010) were independent predictors of poor OS for patients with CLOM. Our study identified tumor size, distribution, and preoperative CA19-9 levels as independent prognostic factors for OS of patients with CLOM. In particular, measurement of preoperative CA19-9 levels offers an easy tool that could help identify high-risk patients and aid in improving the management of patients with CLOM.

  4. Handgrip strength is associated with, but poorly predicts, disability in older women with acute low back pain: A 12-month follow-up study.

    Science.gov (United States)

    Felício, Diogo Carvalho; Diz, Juliano Bergamaschine Mata; Pereira, Daniele Sirineu; Queiroz, Bárbara Zille de; Silva, Juscélio Pereira de; Moreira, Bruno de Souza; Oliveira, Vinícius Cunha; Pereira, Leani Souza Máximo

    2017-10-01

    Older women with low back pain (LBP) constitute a special subpopulation at risk of severe and permanent disability. It is important to identify factors limiting functionality in this population in order to reduce costs and improve both prevention and intervention. Handgrip strength (HGS) is a biomarker of aging associated with several adverse health outcomes, but long-term associations with disability in older patients with LBP are not known. To examine whether HGS predicts disability in older women with acute low back pain (LBP). Longitudinal analyses were conducted with a sample of 135 older women from the international multicenter study Back Complaints in the Elders (BACE-Brazil). Women aged 60 years and over with a new episode of acute LBP were included. HGS was assessed with Jamar ® dynamometer, and disability was assessed using the Roland Morris questionnaire and gait speed test. Variables were assessed at baseline and at 12-month follow-up. Linear regression models explored associations between HGS and disability measures. Significant association was found between HGS at baseline and gait speed at 12-month follow-up (r=-0.24; p=0.004). A multivariable-adjusted model showed that this association was independent of age, body mass index, and pain intensity (adjusted R 2 =0.13; pinclusion of HGS as an independent variable. No association was found between HGS and score on the Roland Morris questionnaire. Caution is needed regarding the use of HGS as a predictive measure of disability in older women with acute LBP. Changes in gait speed were very small and unlikely to be of clinical relevance. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. High E6 Gene Expression Predicts for Distant Metastasis and Poor Survival in Patients With HPV-Positive Oropharyngeal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Khwaja, Shariq S.; Baker, Callie; Haynes, Wesley; Spencer, Christopher R.; Gay, Hiram; Thorstad, Wade [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Adkins, Douglas R. [Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri (United States); Nussenbaum, Brian [Department of Otolaryngology – Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Chernock, Rebecca D. [Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri (United States); Lewis, James S. [Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee (United States); Wang, Xiaowei, E-mail: xwang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2016-07-15

    Purpose: Patients with human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC) have a favorable prognosis. As a result, de-escalation clinical trials are under way. However, approximately 10% of patients will experience distant recurrence even with standard-of-care treatment. Here, we sought to identify novel biomarkers to better risk-stratify HPV-positive patients with OPSCC. Methods and Materials: Gene expression profiling by RNA sequencing (RNA-seq) and quantitative polymerase chain reaction was performed on HPV-positive OPSCC primary tumor specimens from patients with and without distant metastasis (DM). Results: RNA-seq analysis of 39 HPV-positive OPSCC specimens revealed that patients with DM had 2-fold higher E6 gene expression levels than did patients without DM (P=.029). This observation was confirmed in a validation cohort comprising 93 patients with HPV-positive OPSCC. The mean normalized E6 expression level in the 17 recurring primary specimens was 13 ± 2 compared with 8 ± 1 in the remaining 76 nonrecurring primaries (P=.001). Receiver operating characteristic analysis established an E6 expression level of 7.3 as a cutoff for worse recurrence-free survival (RFS). Patients from this cohort with high E6 gene expression (E6-high) (n=51, 55%) had more cancer-related deaths (23% vs 2%, P<.001) and DM (26% vs 5%, P<.001) than did patients with low E6 gene expression (E6-low) (n=42, 45%). Kaplan-Meier survival analysis revealed that E6-high had worse RFS (95% vs 69%, P=.004) and cancer-specific survival (97% vs 79%, P=.007). E6-high maintained statistical significance in multivariate regression models balancing surgery, chemotherapy, nodal stage, and smoking status. Gene set enrichment analysis demonstrated that tumors with high E6 expression were associated with P53, epidermal growth factor receptor, activating transcription factor-2, and transforming growth factor-β signaling pathways. Conclusion: High E6 gene expression

  6. Splenic hilar lymph node metastasis independently predicts poor survival for patients with gastric cancers in the upper and/or the middle third of the stomach.

    Science.gov (United States)

    Zhu, Guo-Lian; Sun, Zhe; Wang, Zhen-Ning; Xu, Ying-Ying; Huang, Bao-Jun; Xu, Yan; Zhu, Zhi; Xu, Hui-Mian

    2012-06-15

    Effectiveness of splenectomy for advanced gastric cancers occupying the upper and/or the middle third of the stomach is still in debate. The aim of the present study is to elucidate the impact of splenectomy on patient survival by investigating the pathological characteristics and prognostic significance of splenic hilar lymph node metastasis. Clinicopathologic and prognostic data of 265 patients with gastric cancer in the upper and/or the middle third of the stomach who underwent the operation of en bloc resection of primary cancer and D2/D3 lymphadenectomy combined with splenectomy were retrospectively reviewed. Multivariate analysis revealed pT category, pN category, and distant lymph node metastasis independently correlated with the presence of splenic hilar lymph node metastasis. Prognoses of patients with positive splenic hilar lymph nodes were significantly poorer than that of patients with negative splenic hilar lymph nodes for the entire study population and for those who underwent R0 resection, but not for those who underwent R1-2 resection. There was no significant difference in survival between patients who underwent R0 resection with positive splenic hilar lymph nodes and those who underwent R1-2 resection. Splenic hilar lymph node metastasis was one of independent indicators predicting worse prognosis and the presence of distant metastasis after surgery. Subset analysis according to the TNM stage revealed there were significant differences in survival between patients with and without splenic hilar lymph node metastasis. Splenic hilar lymph node metastasis should be considered as one of incurable factors. Consequently, the efficiency of splenectomy aiming at prolonging survival for patients with high risk of splenic hilar lymph nodes metastasis should be questioned, although resection of invasive organs form gastric cancers has been recommended if R0 surgery could be achieved. Copyright © 2011 Wiley Periodicals, Inc.

  7. CD63 and GLUT-1 Overexpression Could Predict a Poor Clinical Outcome in GIST: A Study of 54 Cases with Follow-Up

    Directory of Open Access Journals (Sweden)

    Piotr Lewitowicz

    2016-01-01

    Full Text Available Background and Goals. In light of current knowledge, it seems that alternations underlying GISTs are well explained, although all that is enhanced by various aspects on a daily basis. More recently, attention has been pointed towards exosomes as important particles able to modify healthy and also diseased tissues including cancer. The goal of the present study was an analysis of CD9, CD63, and GLUT-1 as a marker of hypoxia status within 54 cases of GIST and evaluation of their predictive value. Methods. 54 cases of patients suffering from GIST were enrolled into the study, predominantly in the gastric location. All operated cases had no Imatinib and other chemotherapies up to the day of operation. Expression of targeted proteins was performed by immunohistochemistry and, after that, the results with tabulated clinical data were compared by Kaplan-Meier method and multivariate Cox proportional hazard model of statistical analysis. Results. Our results presented a marked dependence of worsening clinical outcome with high expression CD63 (p=0.008 as well as with GLUT-1 (p=0.014. We noted a strict correlation of GLUT-1 expression with CD63 expression (p=0.03, which could confirm the thesis about the contribution of exosomes in intratumoural hypoxia status. The collected material did not confirm CD9 contribution. Conclusions. As presented here, CD63 and GLUT-1 have a prognostic value in GIST cases. The results confirm the other studies in this scope and can be used in future as an additional prognostic factor.

  8. c-erbB2 and topoisomerase IIα protein expression independently predict poor survival in primary human breast cancer: a retrospective study

    International Nuclear Information System (INIS)

    Fritz, Peter; Cabrera, Cristina M; Dippon, Jürgen; Gerteis, Andreas; Simon, Wolfgang; Aulitzky, Walter E; Kuip, Heiko van der

    2005-01-01

    c-erbB2 (also known as HER-2/neu) and topoisomerase IIα are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIα protein influences the long-term outcome of patients with primary breast cancer. In this study c-erbB2 and topoisomerase IIα protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed. Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIα protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIα overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIα was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIα showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIα or c-erbB2 overexpression. The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIα in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer

  9. Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure

    Science.gov (United States)

    Peck, Amy R.; Witkiewicz, Agnieszka K.; Liu, Chengbao; Stringer, Ginger A.; Klimowicz, Alexander C.; Pequignot, Edward; Freydin, Boris; Tran, Thai H.; Yang, Ning; Rosenberg, Anne L.; Hooke, Jeffrey A.; Kovatich, Albert J.; Nevalainen, Marja T.; Shriver, Craig D.; Hyslop, Terry; Sauter, Guido; Rimm, David L.; Magliocco, Anthony M.; Rui, Hallgeir

    2011-01-01

    Purpose To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy. Patients and Methods Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays. Results Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). Conclusion Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy. PMID:21576635

  10. Poor performance of quick-SOFA (qSOFA) score in predicting severe sepsis and mortality - a prospective study of patients admitted with infection to the emergency department.

    Science.gov (United States)

    Askim, Åsa; Moser, Florentin; Gustad, Lise T; Stene, Helga; Gundersen, Maren; Åsvold, Bjørn Olav; Dale, Jostein; Bjørnsen, Lars Petter; Damås, Jan Kristian; Solligård, Erik

    2017-06-09

    trigger tool for sepsis at arrival. In this observational cohort study, qSOFA failed to identify two thirds of the patients admitted to an ED with severe sepsis. Further, qSOFA failed to be a risk stratification tool as the sensitivity to predict 7-day and 30-day mortality was low. The sensitivity was poorer than the other warning scores already in use at the study site, RETTS-triage and the SIRS criteria.

  11. REMO poor man's reanalysis

    Science.gov (United States)

    Ries, H.; Moseley, C.; Haensler, A.

    2012-04-01

    Reanalyses depict the state of the atmosphere as a best fit in space and time of many atmospheric observations in a physically consistent way. By essentially solving the data assimilation problem in a very accurate manner, reanalysis results can be used as reference for model evaluation procedures and as forcing data sets for different model applications. However, the spatial resolution of the most common and accepted reanalysis data sets (e.g. JRA25, ERA-Interim) ranges from approximately 124 km to 80 km. This resolution is too coarse to simulate certain small scale processes often associated with extreme events. In addition, many models need higher resolved forcing data ( e.g. land-surface models, tools for identifying and assessing hydrological extremes). Therefore we downscaled the ERA-Interim reanalysis over the EURO-CORDEX-Domain for the time period 1989 to 2008 to a horizontal resolution of approximately 12 km. The downscaling is performed by nudging REMO-simulations to lower and lateral boundary conditions of the reanalysis, and by re-initializing the model every 24 hours ("REMO in forecast mode"). In this study the three following questions will be addressed: 1.) Does the REMO poor man's reanalysis meet the needs (accuracy, extreme value distribution) in validation and forcing? 2.) What lessons can be learned about the model used for downscaling? As REMO is used as a pure downscaling procedure, any systematic deviations from ERA-Interim result from poor process modelling but not from predictability limitations. 3.) How much small scale information generated by the downscaling model is lost with frequent initializations? A comparison to a simulation that is performed in climate mode will be presented.

  12. Voltammetry coupled to mass spectrometry in the presence of isotope {sup 18}O labeled water for the prediction of oxidative transformation pathways of activated aromatic ethers: Acebutolol

    Energy Technology Data Exchange (ETDEWEB)

    Bussy, Ugo; Tea, Illa [LUNAM Université de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse et Modélisation (CEISAM), UMR 6230, 2 rue de la Houssinière, BP 92208, F-44322 Nantes cedex 3 (France); Ferchaud-Roucher, Véronique; Krempf, Michel [Université de Nantes, Plateforme Spectrométrie de Masse, CRNH, SFR Santé F. Bonamy, Institut du Thorax, UMR S1087, IRT-UN, BP 70721, 8 Quai Moncousu, 44007 Nantes cedex 1 (France); Silvestre, Virginie; Galland, Nicolas [LUNAM Université de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse et Modélisation (CEISAM), UMR 6230, 2 rue de la Houssinière, BP 92208, F-44322 Nantes cedex 3 (France); Jacquemin, Denis [LUNAM Université de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse et Modélisation (CEISAM), UMR 6230, 2 rue de la Houssinière, BP 92208, F-44322 Nantes cedex 3 (France); Institut Universitaire de France, 103, Boulevard Saint-Michel, 75005 Cedex 5 France (France); Andresen-Bergström, Moa; Jurva, Ulrik [CVGI iMed DMPK, AstraZeneca R and D Mölndal, Mölndal (Sweden); and others

    2013-01-31

    Highlights: ► Voltammetry coupled to mass spectrometry method as a useful tool for on-line predictions of electrochemical transformations. ► Evidence of the O-dealkoxylation reaction pathway of acebutolol in the presence of labeled water. ► New approach for on line EC-MS applications. -- Abstract: The coupling between an electrochemical cell (EC) and a mass spectrometer (MS) is a useful screening tool (EC-MS) to study the oxidative transformation pathways of various electroactive species. For that purpose, we showed that the EC-MS method, carried out in the presence and absence of isotope {sup 18}O labeled water leads not only to a fast identification of oxidation products but also leads to a fast elucidation of the mechanism pathway reaction. We examined herein the case of the electrochemical hydrolysis of activated aromatic ether. Acebutolol (β-blockers) was selected herein as model of activated aromatic ether, and its electrochemical oxidation was examined in both the presence and absence of isotope {sup 18}O labeled water. To elucidate electrochemical hydrolysis pathway reaction: O-dealkylation or O-dealkoxylation, our approach was used to prove its applicability. The electrochemical oxidation mechanism was then elucidated showing an O-dealkoxylation reaction. In addition, density functional theory (DFT) calculations fully support the experimental conclusions.

  13. Developing confidence in adverse outcome pathway-based toxicity predictions effects of the fungicide imazalil on fathead minnow reproduction (Poster)

    Science.gov (United States)

    An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD. An intended application of the AOP framework is to support the use of me...

  14. Optimizing Technical Education Pathways: Does Dual-Credit Course Completion Predict Students' College and Labor Market Success?

    Science.gov (United States)

    Phelps, L. Allen; Chan, Hsun-Yu

    2016-01-01

    Post-recession Federal policy initiatives, such as secondary/postsecondary career pathways and gainful employment higher education accountability standards, prioritize the alignment of education practices with market-driven outcomes. Using longitudinal student record data merged from college and state K-12 data systems with the Unemployment…

  15. Developing confidence in adverse outcome pathway-based toxicity predictions effects of the fungicide imazalil on fathead minnow reproduction

    Science.gov (United States)

    An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD (https://aopwiki.org/wiki/index.php/Aop:25). An intended application of t...

  16. Irregular vascular pattern by contrast-enhanced ultrasonography and high serum Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level predict poor outcome after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma.

    Science.gov (United States)

    Takada, Hitomi; Tsuchiya, Kaoru; Yasui, Yutaka; Nakakuki, Natsuko; Tamaki, Nobuharu; Suzuki, Shoko; Nakanishi, Hiroyuki; Itakura, Jun; Takahashi, Yuka; Kurosaki, Masayuki; Asahina, Yasuhiro; Enomoto, Nobuyuki; Izumi, Namiki

    2016-11-01

    Radiofrequency ablation (RFA) is considered the most effective treatment for early-stage hepatocellular carcinoma (HCC) patients unsuitable for resection. However, poor outcome after RFA has occasionally been reported worldwide. To predict such an outcome, we investigated imaging findings using contrast-enhanced ultrasonography (CEUS) with Sonazoid and serum tumor markers before RFA. This study included 176 early-stage HCC patients who had initially achieved successful RFA. Patients were examined using CEUS; their levels of alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin before RFA were measured. Sonazoid provided parenchyma-specific contrast imaging and facilitated tumor vascular architecture imaging through maximum intensity projection (MIP). Kaplan-Meier analysis examined cumulative rates of local tumor progression, intrasubsegmental recurrence, and survival; factors associated with these were determined with Cox proportional hazards analysis. Local tumor progression (n = 15), intrasubsegmental recurrence (n = 46), and death (n = 18) were observed. Irregular pattern in MIP classification and serum AFP-L3 level (>10%) before RFA were identified as independent risk factors for local tumor progression and intrasubsegmental recurrence. These two factors were independently associated with poor survival after RFA (irregular pattern in MIP: hazard ratio, (HR) = 8.26; 95% confidence interval, (CI) = 2.24-30.3; P = 0.002 and AFP-L3 > 10%: HR = 2.94; 95% CI = 1.09-7.94; P = 0.033). Irregular MIP pattern by CEUS and high level of serum AFP-L3 were independent risk factors for poor outcome after successful RFA. The Patients with these findings should be considered as special high-risk group in early-stage HCC. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. Generation of an atlas for commodity chemical production in Escherichia coli and a novel pathway prediction algorithm, GEM-Path

    DEFF Research Database (Denmark)

    Campodonico, Miguel A.; Andrews, Barbara A.; Asenjo, Juan A.

    2014-01-01

    The production of 75% of the current drug molecules and 35% of all chemicals could be achieved through bioprocessing (Arundel and Sawava, 2009). To accelerate the transition from a petroleum based chemical industry to a sustainable bio-based industry, systems metabolic engineering has emerged...... to computationally design metabolic pathways for chemical production. Although algorithms able to provide specific metabolic interventions and heterologous production pathways are available, a systematic analysis for all possible production routes to commodity chemicals in Escherichia call is lacking. Furthermore...... could be identified for 1271 of the 6615 conditions evaluated. This study characterizes the potential for E coli to produce commodity chemicals, and outlines a generic strain design workflow to design production strains. (C) 2014 international Metabolic Engineering Society. Published by Elsevier Inc...

  18. Inference in `poor` languages

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, S.

    1996-10-01

    Languages with a solvable implication problem but without complete and consistent systems of inference rules (`poor` languages) are considered. The problem of existence of finite complete and consistent inference rule system for a ``poor`` language is stated independently of the language or rules syntax. Several properties of the problem arc proved. An application of results to the language of join dependencies is given.

  19. Predictive role of computer simulation in assessing signaling pathways of crizotinib-treated A549 lung cancer cells.

    Science.gov (United States)

    Xia, Pu; Mou, Fei-Fei; Wang, Li-Wei

    2012-01-01

    Non-small-cell lung cancer (NSCLC) is a leading cause of cancer deaths worldwide. Crizotinib has been approved by the U.S. Food and Drug Administration for the treatment of patients with advanced NSCLC. However, understanding of mechanisms of action is still limited. In our studies, we confirmed crizotinib-induced apoptosis in A549 lung cancer cells. In order to assess mechanisms, small molecular docking technology was used as a preliminary simulation of signaling pathways. Interesting, our results of experiments were consistent with the results of computer simulation. This indicates that small molecular docking technology should find wide use for its reliability and convenience.

  20. Clofarabine in the treatment of poor risk acute myeloid leukaemia.

    LENUS (Irish Health Repository)

    Krawczyk, Janusz

    2010-09-01

    Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24-76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17-120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients.

  1. Pathway evidence of how musical perception predicts word-level reading ability in children with reading difficulties.

    Directory of Open Access Journals (Sweden)

    Hugo Cogo-Moreira

    Full Text Available To investigate whether specific domains of musical perception (temporal and melodic domains predict the word-level reading skills of eight- to ten-year-old children (n = 235 with reading difficulties, normal quotient of intelligence, and no previous exposure to music education classes.A general-specific solution of the Montreal Battery of Evaluation of Amusia (MBEA, which underlies a musical perception construct and is constituted by three latent factors (the general, temporal, and the melodic domain, was regressed on word-level reading skills (rate of correct isolated words/non-words read per minute.General and melodic latent domains predicted word-level reading skills.

  2. Exploiting the Poor

    DEFF Research Database (Denmark)

    Kamp Justesen, Mogens; Bjørnskov, Christian

    2014-01-01

    While extant research has focused on the causes and consequences of corruption at the macro-level, less effort has been devoted to understanding the micro-foundation of corruption. We argue that poor people are more likely to be victims of corrupt behavior by street-level bureaucrats as the poor...... often rely heavily on services provided by governments. We test this proposition using micro-level survey data from the Afrobaromenter. Multilevel regressions across 18 countries show that poor people are much more prone to experience having to pay bribes to government officials....

  3. How adverse outcome pathways can aid the development and use of computational prediction models for regulatory toxicology

    Science.gov (United States)

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumu...

  4. PATHWAY: a dynamic foodchain model to predict radionuclide ingestion after fallout deposition. Final report, September 17, 1979-December 31, 1985

    International Nuclear Information System (INIS)

    Whicker, F.W.; Kirchner, T.B.

    1986-01-01

    This paper describes the structure and basis for parameter values of a computerized foodchain transport model for radionuclides. The model, called ''PATHWAY,'' estimates the time-integrated intake by humans of twenty radionuclides after a single deposition of radioactive material from the atmosphere to the landscape. The model solves a set of differential equations to estimate the inventories and concentrations of radionuclides in three soil layers and numerous types of vegetation, animal tissues and animal products as a function of time following a deposition event. Dynamic processes considered in the model include foliar interception, weathering and absorption; plant growth, uptake, harvest and senescence; soil resuspension, percolation, leaching and tillage; radioactive decay; livestock ingestion, absorption, excretion; and etc. An age- and sex-specific human diet is embodied in the model to permit calculation of time-dependent radionuclide ingestion rates, which are then numerically integrated. 3 figs., 10 tabs

  5. Accounting for the Poor

    OpenAIRE

    Robert M. Townsend

    2013-01-01

    Economists and other social scientists have long tried to understand the nature of poverty and how poor people make decisions. For example, T.W. Schultz, a Nobel Laureate, former professor of economics at the University of Chicago, and former president of the American Economic Association, spent his career working in development and agricultural economics. In his 1980 Nobel Prize acceptance speech, Schultz suggests that there is some accounting for the behavior of the poor in agriculture. "Fa...

  6. Dispositional pathways to trust: Self-esteem and agreeableness interact to predict trust and negative emotional disclosure.

    Science.gov (United States)

    McCarthy, Megan H; Wood, Joanne V; Holmes, John G

    2017-07-01

    Expressing our innermost thoughts and feelings is critical to the development of intimacy (Reis & Shaver, 1988), but also risks negative evaluation and rejection. Past research suggests that people with high self-esteem are more expressive and self-disclosing because they trust that others care for them and will not reject them (Gaucher et al., 2012). However, feeling good about oneself may not always be enough; disclosure may also depend on how we feel about other people. Drawing on the principles of risk regulation theory (Murray et al., 2006), we propose that agreeableness-a trait that refers to the positivity of interpersonal motivations and behaviors-is a key determinant of trust in a partner's caring and responsiveness, and may work in conjunction with self-esteem to predict disclosure. We examined this possibility by exploring how both self-esteem and agreeableness predict a particularly risky and intimate form of self-disclosure, the disclosure of emotional distress. In 6 studies using correlational, partner-report, and experimental methods, we demonstrate that self-esteem and agreeableness interact to predict disclosure: People who are high in both self-esteem and agreeableness show higher emotional disclosure. We also found evidence that trust mediates this effect. People high in self-esteem and agreeableness are most self-revealing, it seems, because they are especially trusting of their partners' caring. Self-esteem and agreeableness were particularly important for the disclosure of vulnerable emotions (i.e., sadness; Study 5) and disclosures that were especially risky (Study 6). These findings illustrate how dispositional variables can work together to explain behavior in close relationships. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. Further increased production of free fatty acids by overexpressing a predicted transketolase gene of the pentose phosphate pathway in Aspergillus oryzae faaA disruptant.

    Science.gov (United States)

    Tamano, Koichi; Miura, Ai

    2016-09-01

    Free fatty acids are useful as source materials for the production of biodiesel fuel and various chemicals such as pharmaceuticals and dietary supplements. Previously, we attained a 9.2-fold increase in free fatty acid productivity by disrupting a predicted acyl-CoA synthetase gene (faaA, AO090011000642) in Aspergillus oryzae. In this study, we achieved further increase in the productivity by overexpressing a predicted transketolase gene of the pentose phosphate pathway in the faaA disruptant. The A. oryzae genome is predicted to have three transketolase genes and overexpression of AO090023000345, one of the three genes, resulted in phenotypic change and further increase (corresponding to an increased production of 0.38 mmol/g dry cell weight) in free fatty acids at 1.4-fold compared to the faaA disruptant. Additionally, the biomass of hyphae increased at 1.2-fold by the overexpression. As a result, free fatty acid production yield per liter of liquid culture increased at 1.7-fold by the overexpression.

  8. Integration of metabolomic and transcriptomic networks in pregnant women reveals biological pathways and predictive signatures associated with preeclampsia.

    Science.gov (United States)

    Kelly, Rachel S; Croteau-Chonka, Damien C; Dahlin, Amber; Mirzakhani, Hooman; Wu, Ann C; Wan, Emily S; McGeachie, Michael J; Qiu, Weiliang; Sordillo, Joanne E; Al-Garawi, Amal; Gray, Kathryn J; McElrath, Thomas F; Carey, Vincent J; Clish, Clary B; Litonjua, Augusto A; Weiss, Scott T; Lasky-Su, Jessica A

    2017-01-01

    Preeclampsia is a leading cause of maternal and fetal mortality worldwide, yet its exact pathogenesis remains elusive. This study, nested within the Vitamin D Antenatal Asthma Reduction Trial (VDAART), aimed to develop integrated omics models of preeclampsia that have utility in both prediction and in the elucidation of underlying biological mechanisms. Metabolomic profiling was performed on first trimester plasma samples of 47 pregnant women from VDAART who subsequently developed preeclampsia and 62 controls with healthy pregnancies, using liquid-chromatography tandem mass-spectrometry. Metabolomic profiles were generated based on logistic regression models and assessed using Received Operator Characteristic Curve analysis. These profiles were compared to profiles from generated using third trimester samples. The first trimester metabolite profile was then integrated with a pre-existing transcriptomic profile using network methods. In total, 72 (0.9%) metabolite features were associated (pIntegration with the transcriptomic signature refined these results suggesting a particular role for lipid imbalance, immune function and the circulatory system. These findings suggest it is possible to develop a predictive metabolomic profile of preeclampsia. This profile is characterized by changes in lipid and amino acid metabolism and dysregulation of immune response and can be refined through interaction with transcriptomic data. However validation in larger and more diverse populations is required.

  9. Utilization of machine learning for prediction of post-traumatic stress: a re-examination of cortisol in the prediction and pathways to non-remitting PTSD

    Science.gov (United States)

    Galatzer-Levy, I R; Ma, S; Statnikov, A; Yehuda, R; Shalev, A Y

    2017-01-01

    To date, studies of biological risk factors have revealed inconsistent relationships with subsequent post-traumatic stress disorder (PTSD). The inconsistent signal may reflect the use of data analytic tools that are ill equipped for modeling the complex interactions between biological and environmental factors that underlay post-traumatic psychopathology. Further, using symptom-based diagnostic status as the group outcome overlooks the inherent heterogeneity of PTSD, potentially contributing to failures to replicate. To examine the potential yield of novel analytic tools, we reanalyzed data from a large longitudinal study of individuals identified following trauma in the general emergency room (ER) that failed to find a linear association between cortisol response to traumatic events and subsequent PTSD. First, latent growth mixture modeling empirically identified trajectories of post-traumatic symptoms, which then were used as the study outcome. Next, support vector machines with feature selection identified sets of features with stable predictive accuracy and built robust classifiers of trajectory membership (area under the receiver operator characteristic curve (AUC)=0.82 (95% confidence interval (CI)=0.80–0.85)) that combined clinical, neuroendocrine, psychophysiological and demographic information. Finally, graph induction algorithms revealed a unique path from childhood trauma via lower cortisol during ER admission, to non-remitting PTSD. Traditional general linear modeling methods then confirmed the newly revealed association, thereby delineating a specific target population for early endocrine interventions. Advanced computational approaches offer innovative ways for uncovering clinically significant, non-shared biological signals in heterogeneous samples. PMID:28323285

  10. Flower bud transcriptome analysis of Sapium sebiferum (Linn.) Roxb. and primary investigation of drought induced flowering: pathway construction and G-quadruplex prediction based on transcriptome.

    Science.gov (United States)

    Yang, Minglei; Wu, Ying; Jin, Shan; Hou, Jinyan; Mao, Yingji; Liu, Wenbo; Shen, Yangcheng; Wu, Lifang

    2015-01-01

    Sapium sebiferum (Linn.) Roxb. (Chinese Tallow Tree) is a perennial woody tree and its seeds are rich in oil which hold great potential for biodiesel production. Despite a traditional woody oil plant, our understanding on S. sebiferum genetics and molecular biology remains scant. In this study, the first comprehensive transcriptome of S. sebiferum flower has been generated by sequencing and de novo assembly. A total of 149,342 unigenes were generated from raw reads, of which 24,289 unigenes were successfully matched to public database. A total of 61 MADS box genes and putative pathways involved in S. sebiferum flower development have been identified. Abiotic stress response network was also constructed in this work, where 2,686 unigenes are involved in the pathway. As for lipid biosynthesis, 161 unigenes have been identified in fatty acid (FA) and triacylglycerol (TAG) biosynthesis. Besides, the G-Quadruplexes in RNA of S. sebiferum also have been predicted. An interesting finding is that the stress-induced flowering was observed in S. sebiferum for the first time. According to the results of semi-quantitative PCR, expression tendencies of flowering-related genes, GA1, AP2 and CRY2, accorded with stress-related genes, such as GRX50435 and PRXⅡ39562. This transcriptome provides functional genomic information for further research of S. sebiferum, especially for the genetic engineering to shorten the juvenile period and improve yield by regulating flower development. It also offers a useful database for the research of other Euphorbiaceae family plants.

  11. A Six-Year Predictive Test of Adolescent Family Relationship Quality and Effortful Control Pathways to Emerging Adult Social and Emotional Health

    Science.gov (United States)

    Fosco, Gregory M.; Caruthers, Allison S.; Dishion, Thomas J.

    2012-01-01

    This longitudinal study examined how a multimethod (youth report, parent report, direct observation) assessment of family relationship quality (cohesion and conflict) in adolescence (age 16 –17) predicted growth and maintenance of effortful control across ages 17, 22, and 23 years old, and, ultimately, subjective well-being, emotional distress, and aggressive behavior in emerging adulthood (23). A diverse sample of 792 youth at age 17 and their families, and youth at ages 22 and 23, were studied to examine family cohesion and conflict and the growth and maintenance of effortful control as predictors of emerging adult social and emotional health. Results indicated that family cohesion and conflict during late adolescence and mean-level effortful control at age 22 each served as unique pathways to emerging adult adjustment. These findings underscore the importance of family functioning during adolescence and the maintenance of effortful control into emerging adulthood for understanding adjustment during the emerging adulthood period. PMID:22709261

  12. Discovery of a Novel Inhibitor of the Hedgehog Signaling Pathway through Cell-based Compound Discovery and Target Prediction.

    Science.gov (United States)

    Kremer, Lea; Schultz-Fademrecht, Carsten; Baumann, Matthias; Habenberger, Peter; Choidas, Axel; Klebl, Bert; Kordes, Susanne; Schöler, Hans R; Sterneckert, Jared; Ziegler, Slava; Schneider, Gisbert; Waldmann, Herbert

    2017-10-09

    Cell-based assays enable monitoring of small-molecule bioactivity in a target-agnostic manner and help uncover new biological mechanisms. Subsequent identification and validation of the small-molecule targets, typically employing proteomics techniques, is very challenging and limited, in particular if the targets are membrane proteins. Herein, we demonstrate that the combination of cell-based bioactive-compound discovery with cheminformatic target prediction may provide an efficient approach to accelerate the process and render target identification and validation more efficient. Using a cell-based assay, we identified the pyrazolo-imidazole smoothib as a new inhibitor of hedgehog (Hh) signaling and an antagonist of the protein smoothened (SMO) with a novel chemotype. Smoothib targets the heptahelical bundle of SMO, prevents its ciliary localization, reduces the expression of Hh target genes, and suppresses the growth of Ptch +/- medulloblastoma cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 9. Poor medication

    African Journals Online (AJOL)

    Sitwala

    Majority (60%) of the patients were reviewed at least twice in the last 6 months at the time of the interview. 195 (83%) patients reported that drugs prescribed were not available at the hospital pharmacy, but 186 (79%) of. Factors Associated With Poor Medication Adherence. In Hypertensive Patients In Lusaka, Zambia. 1,4. 1.

  14. PREDICTING NORMATIVE AND PROBLEMATIC FAMILY PATHWAYS TO THE TRANSITION TO SIBLINGHOOD: COMMENTARY ON VOLLING ET AL.'S MONOGRAPH.

    Science.gov (United States)

    Howe, Nina

    2017-09-01

    Volling et al.'s monograph provides a rich, thoughtful, and rigorous account of how the transition to siblinghood is experienced by the first-born child and the family. In their comprehensive longitudinal study, they followed 241 families from the prenatal period before the second-born's birth until this child was 12-months old. Siblings are a critical, but understudied, relationship in children's development; the challenges posed in researching sibling dynamics in the context of the family are discussed. Prior psychodynamic and developmental research literature is critiqued, which places the current study into perspective and indicates the important theoretical frameworks (i.e., developmental psychopathology and developmental ecological systems) employed by Volling et al. to advance our understanding of this critical transition in the life of the family. The longitudinal study design, sample characteristics, identification of possible trajectories of adjustment (or not) to the birth of the sibling, and selection of family and child variables are addressed. The sophisticated statistical methods (Growth Mixture Modeling and data mining procedures) employed to predict child adjustment in association with parenting variables over time and sibling relationship quality at 12 months identified low- and high-risk trajectories on the seven subscales of the Child Behavior Check List (CBCL). This afforded a nuanced investigation of a variety of potentially problematic child behaviors (e.g., aggression, withdrawal, negative emotionality, somatic problems) in association with parenting behaviors. A final discussion included study limitations, significant strengths, and implications for clinicians and other professionals. The study's conclusion is that most children and families are resilient, take the birth of a sibling in their stride, and do not exhibit empirical evidence of a developmental crisis, as argued by earlier psychodynamic authors. © 2017 The Society for Research

  15. Flower bud transcriptome analysis of Sapium sebiferum (Linn. Roxb. and primary investigation of drought induced flowering: pathway construction and G-quadruplex prediction based on transcriptome.

    Directory of Open Access Journals (Sweden)

    Minglei Yang

    Full Text Available Sapium sebiferum (Linn. Roxb. (Chinese Tallow Tree is a perennial woody tree and its seeds are rich in oil which hold great potential for biodiesel production. Despite a traditional woody oil plant, our understanding on S. sebiferum genetics and molecular biology remains scant. In this study, the first comprehensive transcriptome of S. sebiferum flower has been generated by sequencing and de novo assembly. A total of 149,342 unigenes were generated from raw reads, of which 24,289 unigenes were successfully matched to public database. A total of 61 MADS box genes and putative pathways involved in S. sebiferum flower development have been identified. Abiotic stress response network was also constructed in this work, where 2,686 unigenes are involved in the pathway. As for lipid biosynthesis, 161 unigenes have been identified in fatty acid (FA and triacylglycerol (TAG biosynthesis. Besides, the G-Quadruplexes in RNA of S. sebiferum also have been predicted. An interesting finding is that the stress-induced flowering was observed in S. sebiferum for the first time. According to the results of semi-quantitative PCR, expression tendencies of flowering-related genes, GA1, AP2 and CRY2, accorded with stress-related genes, such as GRX50435 and PRXⅡ39562. This transcriptome provides functional genomic information for further research of S. sebiferum, especially for the genetic engineering to shorten the juvenile period and improve yield by regulating flower development. It also offers a useful database for the research of other Euphorbiaceae family plants.

  16. Savings for the Poor

    OpenAIRE

    Ignacio Mas

    2010-01-01

    This paper reviews the relevance of formal financial services – in particular, savings – to poor people, the economic factors that have hindered the mass-scale delivery of such services in developing countries, and the technology-based opportunities that exist today to make massive gains in financial inclusion. It also highlights the benefits to government from universal financial access, as well as the key policy enablers that would need to be put in place to allow the necessary innovati...

  17. Poorly Differentiated Thyroid Carcinoma.

    Science.gov (United States)

    Setia, Namrata; Barletta, Justine A

    2014-12-01

    Poorly differentiated thyroid carcinoma (PDTC) has been recognized for the past 30 years as an entity showing intermediate differentiation and clinical behavior between well-differentiated thyroid carcinomas (ie, papillary thyroid carcinoma and follicular thyroid carcinoma) and anaplastic thyroid carcinoma; however, there has been considerable controversy around the definition of PDTC. In this review, the evolution in the definition of PDTC, current diagnostic criteria, differential diagnoses, potentially helpful immunohistochemical studies, and molecular alterations are discussed with the aim of highlighting where the diagnosis of PDTC currently stands. Published by Elsevier Inc.

  18. [Poor insight and psychosis].

    Science.gov (United States)

    Giotakos, O

    2017-01-01

    A variety of phenomena might be considered as reflecting impaired insight in psychosis, like failure to recognize signs, symptoms or disease, failure to derive appropriate cognitive representations, despite recognition of the disease, and misattribution of the source or cause of the disease. The unawareness of tardive dyskinesia symptoms in schizophrenic patients points that self-awareness deficits in schizophrenia may be domain specific. Poor insight is an independent phenomenological and a prevalent feature in psychotic disorders in general, and in schizophrenia in particular, but we don't know yet if delusions in schizophrenia are the result of an entirely normal attempt to account for abnormal perceptual experiences or a product of abnormal experience but of normal reasoning. The theoretical approaches regarding impaired insight include the disturbed perceptual input, the impaired linkage between thought and emotion and the breakdown of the process of self-monitoring and error checking. The inability to distinguish between internally and externally generated mental events has been described by the metarepresentation theory. This theory includes the awareness of ones' goals, which leads to disorders of willed action, the awareness of intention, which leads to movement disorders, and the awareness of intentions of others, which leads to paranoid delusions. The theory of metarepresentation implies mainly output mechanisms, like the frontal cortex, while the input mechanism implies posterior brain systems, including the parietal lobe. There are many similarities between the disturbances of awareness seen in schizophrenia and those seen as a result of known neurological impairment. Neuropsychological models of impaired insight typically attribute the disturbance to any of a variety of core deficits in the processing of information. In this respect, lack of insight is on conceptual par with alogia, apraxia or aphasia in reflecting disturbed cognitive processing. In

  19. The 'poor man's laryngogram'

    International Nuclear Information System (INIS)

    Bartelt, D.

    1991-01-01

    This paper is reassessment of an old method improved by well-directed application of well-known maneuvers of laryngo-pharyngeal function. Although not as visually attractive as a dedicated laryngogram (now hardly ever requested), it does render similarly reliable diagnostic information, which, supported, as occasionally necessary, by conventional tomography, can even surpass that given by the older technique. Its main advantage lies in providing cheap, quick, noninvasive studies with minimal descomfort for the patient. Should further investigation be necessary, for analysis of deep extension, modern cross-sectional imaging methods (especially MR) far surpass even dedicated laryngography in diagnostic value and can be based adequately on 'poor mans's laryngography'. Ways in which this method may be optimised, especially those involving laryngopharyngeal function, are briefly presented - with emphasis on relevant practical aspects - as are normal and abnormal findings. (orig.) [de

  20. Signal peptide prediction suggests Mycobacterium tuberculosis curli pilin subunit secretion via the Sec pathway may hinder MTP overexpression in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo, N.; Pillay, B.; Bubb, M.; Kumar, A.; Chiliza, T.; Pillay, M.

    2017-07-01

    pure protein fraction was unsuccessful. Mass spectrometry did not detect any fragments belonging to MTP, but only those of E.coli membrane proteins for the pet101/mtp clone and fragments of the GST tag in the case of the pGEX-6P-1/mtp clone. The bioinformatics secretion analyses of MTP predicted a strong Sec regulated secretion pathway and the absence of non-classical “mycobacterial specific” secretion. Discussion M. tuberculosis membrane and secretory proteins often contain signal peptides. In this study, excluding the signal peptide region and using a GST tag greatly enhanced the expression of the protein in the soluble fraction. However, purification of the MTP peptide remained problematic due to a lower available peptide concentration resulting from the lower molecular weight, in the purified fraction compared to the GST tag. Alternately, the predicted Sec regulated secretion pathway may play a role in inhibition of MTP overexpression in E.coli. Thus, alternatives to E. coli expression systems or more efficient purification strategies are required for the acquisition of high quality M. tuberculosis antigens.

  1. Signal peptide prediction suggests Mycobacterium tuberculosis curli pilin subunit secretion via the Sec pathway may hinder MTP overexpression in Escherichia coli

    International Nuclear Information System (INIS)

    Naidoo, N.; Pillay, B.; Bubb, M.; Kumar, A.; Chiliza, T.; Pillay, M.

    2017-01-01

    pure protein fraction was unsuccessful. Mass spectrometry did not detect any fragments belonging to MTP, but only those of E.coli membrane proteins for the pet101/mtp clone and fragments of the GST tag in the case of the pGEX-6P-1/mtp clone. The bioinformatics secretion analyses of MTP predicted a strong Sec regulated secretion pathway and the absence of non-classical “mycobacterial specific” secretion. Discussion M. tuberculosis membrane and secretory proteins often contain signal peptides. In this study, excluding the signal peptide region and using a GST tag greatly enhanced the expression of the protein in the soluble fraction. However, purification of the MTP peptide remained problematic due to a lower available peptide concentration resulting from the lower molecular weight, in the purified fraction compared to the GST tag. Alternately, the predicted Sec regulated secretion pathway may play a role in inhibition of MTP overexpression in E.coli. Thus, alternatives to E. coli expression systems or more efficient purification strategies are required for the acquisition of high quality M. tuberculosis antigens.

  2. De novo pathway-based biomarker identification

    DEFF Research Database (Denmark)

    Alcaraz, Nicolas; List, Markus; Batra, Richa

    2017-01-01

    in a large cohort of breast cancer samples from The Cancer Genome Atlas (TCGA) revealed that MGs are considerably more stable than SG models, while also providing valuable insight into the cancer hallmarks that drive them. In addition, when tested on an independent benchmark non-TCGA dataset, MG features......Gene expression profiles have been extensively discussed as an aid to guide the therapy by predicting disease outcome for the patients suffering from complex diseases, such as cancer. However, prediction models built upon single-gene (SG) features show poor stability and performance on independent...... on their molecular subtypes can provide a detailed view of the disease and lead to more personalized therapies. We propose and discuss a novel MG approach based on de novo pathways, which for the first time have been used as features in a multi-class setting to predict cancer subtypes. Comprehensive evaluation...

  3. The dyslipidemia-associated SNP on the APOA1/C3/A5 gene cluster predicts post-surgery poor outcome in Taiwanese breast cancer patients: a 10-year follow-up study

    International Nuclear Information System (INIS)

    Hsu, Mei-Chi; Lee, Kuo-Ting; Hsiao, Wei-Chiang; Wu, Chih-Hsing; Sun, Hung-Yu; Lin, I-Ling; Young, Kung-Chia

    2013-01-01

    Post-surgery therapies are given to early-stage breast cancer patients due to the possibility of residual micrometastasis, and optimized by clincopathological parameters such as tumor stage, and hormone receptor/lymph node status. However, current efficacy of post-surgery therapies is unsatisfactory, and may be varied according to unidentified patient genetic factors. Increases of breast cancer occurrence and recurrence have been associated with dyslipidemia, which can attribute to other known risk factors of breast cancer including obesity, diabetes and metabolic syndrome. Thus we reasoned that dyslipidemia-associated nucleotide polymorphisms (SNPs) on the APOA1/C3/A5 gene cluster may predict breast cancer risk and tumor progression. We analyzed the distribution of 5 selected APOA1/C3/A5 SNPs in recruited Taiwanese breast cancer patients (n=223) and healthy controls (n=162). The association of SNP (APOA1 rs670) showing correlation with breast cancer with baseline and follow-up parameters was further examined. APOA1 rs670 A allele carriage was higher in breast cancer patients than controls (59.64% vs. 48.77%, p=0.038). The rs670 A allele carrying patients showed less favorable baseline phenotype with positive lymph nodes (G/A: OR=3.32, 95% CI=1.77-6.20, p<0.001; A/A: OR=2.58, 95% CI=1.05-6.32, p=0.039) and negative hormone receptor expression (A/A: OR=4.85, 95%CI=1.83-12.83, p=0.001) in comparison to G/G carriers. Moreover, rs670 A/A carrying patients had higher risks in both tumor recurrence (HR=3.12, 95% CI=1.29-7.56, p=0.012) and mortality (HR=4.36, 95% CI=1.52-12.47, p=0.006) than patients with no A alleles after adjustments for associated baseline parameters. Furthermore, the prognostic effect of rs670 A/A carriage was most evident in lymph node-negative patients, conferring to the highest risks of recurrence (HR=4.98, 95% CI=1.40-17.70, p=0.013) and mortality (HR=9.87, 95%CI=1.60-60.81, p=0.014) than patients with no A alleles. APOA1 rs670 A/A carriage showed

  4. The dyslipidemia-associated SNP on the APOA1/C3/A5 gene cluster predicts post-surgery poor outcome in Taiwanese breast cancer patients: a 10-year follow-up study

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Mei-Chi [Research Center for Medical Laboratory Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Lee, Kuo-Ting [Department of Surgery, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Hsiao, Wei-Chiang [Department of Surgery, Yang Ming Hospital, Chiayi, Taiwan (China); Wu, Chih-Hsing [Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Sun, Hung-Yu [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Lin, I-Ling [Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Young, Kung-Chia [Research Center for Medical Laboratory Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China)

    2013-07-05

    Post-surgery therapies are given to early-stage breast cancer patients due to the possibility of residual micrometastasis, and optimized by clincopathological parameters such as tumor stage, and hormone receptor/lymph node status. However, current efficacy of post-surgery therapies is unsatisfactory, and may be varied according to unidentified patient genetic factors. Increases of breast cancer occurrence and recurrence have been associated with dyslipidemia, which can attribute to other known risk factors of breast cancer including obesity, diabetes and metabolic syndrome. Thus we reasoned that dyslipidemia-associated nucleotide polymorphisms (SNPs) on the APOA1/C3/A5 gene cluster may predict breast cancer risk and tumor progression. We analyzed the distribution of 5 selected APOA1/C3/A5 SNPs in recruited Taiwanese breast cancer patients (n=223) and healthy controls (n=162). The association of SNP (APOA1 rs670) showing correlation with breast cancer with baseline and follow-up parameters was further examined. APOA1 rs670 A allele carriage was higher in breast cancer patients than controls (59.64% vs. 48.77%, p=0.038). The rs670 A allele carrying patients showed less favorable baseline phenotype with positive lymph nodes (G/A: OR=3.32, 95% CI=1.77-6.20, p<0.001; A/A: OR=2.58, 95% CI=1.05-6.32, p=0.039) and negative hormone receptor expression (A/A: OR=4.85, 95%CI=1.83-12.83, p=0.001) in comparison to G/G carriers. Moreover, rs670 A/A carrying patients had higher risks in both tumor recurrence (HR=3.12, 95% CI=1.29-7.56, p=0.012) and mortality (HR=4.36, 95% CI=1.52-12.47, p=0.006) than patients with no A alleles after adjustments for associated baseline parameters. Furthermore, the prognostic effect of rs670 A/A carriage was most evident in lymph node-negative patients, conferring to the highest risks of recurrence (HR=4.98, 95% CI=1.40-17.70, p=0.013) and mortality (HR=9.87, 95%CI=1.60-60.81, p=0.014) than patients with no A alleles. APOA1 rs670 A/A carriage showed

  5. Long noncoding RNA CASC2 predicts the prognosis of glioma patients and functions as a suppressor for gliomas by suppressing Wnt/β-catenin signaling pathway

    Directory of Open Access Journals (Sweden)

    Wang R

    2017-07-01

    Full Text Available Ronglin Wang,1,* Yuqian Li,1,* Gang Zhu,1,* Bo Tian,1 Wen Zeng,1 Yang Yang,2 Zhihong Li1 1Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, 2Department of Neurosurgery, The 451th hospital of PLA, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Background: Previous studies have demonstrated that long noncoding RNA cancer susceptibility candidate 2 (lncRNA CASC2 is frequently downregulated in several types of tumors and functions as a tumor-suppressive factor. However, the clinical significance and function of CASC2 in human glioma remain largely unknown. The purpose of this study was to identify the clinical values of CASC2, as well as investigate the potential molecular mechanisms in glioma. Methods: This retrospective study first analyzed the expression levels of CASC2 using quantitative real-time polymerase chain reaction. Then, CASC2 expression levels were associated with various clinicopathologic characteristics and the survival rate of patients with glioma. Finally, the function and underlying molecular mechanisms of CASC2 in human glioma were investigated in U251 cell line. Results: By quantitative real-time polymerase chain reaction analysis, our data showed that CASC2 expression was significantly downregulated in glioma tissues and cell lines (U87 and U251 compared to adjacent normal brain tissues or normal human astrocytes. Moreover, its expression negatively correlated with tumor grade in glioma patients. Furthermore, Kaplan–Meier curves with log-rank analysis revealed a close correlation between downregulated CASC2 and shorter survival time in glioma patients. In addition, Cox regression analysis indicated that CASC2 could be considered as an independent risk factor for poor prognosis. Finally, in vitro experiment demonstrated that CASC2 overexpression remarkably suppressed glioma cell proliferation, migration, and invasion through suppressing Wnt

  6. Cerebral oxygen transport failure?: decreasing hemoglobin and hematocrit levels after ischemic stroke predict poor outcome and mortality: STroke: RelevAnt Impact of hemoGlobin, Hematocrit and Transfusion (STRAIGHT)--an observational study.

    Science.gov (United States)

    Kellert, Lars; Martin, Evgenia; Sykora, Marek; Bauer, Harald; Gussmann, Philipp; Diedler, Jennifer; Herweh, Christian; Ringleb, Peter A; Hacke, Werner; Steiner, Thorsten; Bösel, Julian

    2011-10-01

    Although conceivably relevant for penumbra oxygenation, the optimal levels of hemoglobin (Hb) and hematocrit (Hct) in patients with acute ischemic stroke are unknown. We identified patients from our prospective local stroke database who received intravenous thrombolysis based on multimodal magnet resonance imaging during the years 1998 to 2009. A favorable outcome at 3 months was defined as a modified Rankin Scale score≤2 and a poor outcome as a modified Rankin Scale score≥3. The dynamics of Hemoglobin (Hb), Hematocrit (Hct), and other relevant laboratory parameters as well as cardiovascular risk factors were retrospectively assessed and analyzed between these 2 groups. Of 217 patients, 114 had a favorable and 103 a poor outcome. In a multivariable regression model, anemia until day 5 after admission (odds ratio [OR]=2.61; 95% CI, 1.33 to 5.11; P=0.005), Hb nadir (OR=0.81; 95% CI, 0.67 to 0.99; P=0.038), and Hct nadir (OR=0.93; 95% CI, 0.87 to 0.99; P=0.038) remained independent predictors for poor outcome at 3 months. Mortality after 3 months was independently associated with Hb nadir (OR=0.80; 95% CI, 0.65 to 0.98; P=0.028) and Hb decrease (OR=1.34; 95% CI, 1.01 to 1.76; P=0.04) as well as Hct decrease (OR=1.12; 95% CI, 1.01 to 1.23; P=0.027). Poor outcome and mortality after ischemic stroke are strongly associated with low and further decreasing Hb and Hct levels. This decrease of Hb and Hct levels after admission might be more relevant and accessible to treatment than are baseline levels.

  7. Value of local electrogram characteristics predicting successful catheter ablation of left-versus right-sided accessory atrioventricular pathways by radiofrequency current.

    Science.gov (United States)

    Lin, J L; Schie, J T; Tseng, C D; Chen, W J; Cheng, T F; Tsou, S S; Chen, J J; Tseng, Y Z; Lien, W P

    1995-01-01

    Despite similar guidance by local electrogram criteria, catheter ablation of right-sided accessory atrioventricular (AV) pathways by radiofrequency current has been less effective than that of left-sided ones. In order to elucidate the possible diversities in local electrosignal criteria, we systematically analyzed the morphological and timing characteristics of 215 bipolar local electrograms from catheter ablation sites of 65 left-sided accessory AV pathways and of 356 from those of 37 right-sided ones in 92 consecutive patients with Wolff-Parkinson-White syndrome or AV reentrant tachycardia incorporating concealed accessory AV pathways. After stepwise multivariate analysis, we selected the presence of a possible accessory pathway potential, local ventricular activation preceding QRS complex for 20 ms or more during ventricular insertion mapping, and the local retrograde ventriculoatrial (VA) continuity, local retrograde VA interval right-sided targets only) during atrial insertion mapping, as independent local electrogram predictors for successful ablation of left- and right-sided accessory AV pathways. Combination of all local electrogram predictors could have moderate chance of success (80 and 51%) for the ventricular and atrial insertion ablation of left-sided accessory AV pathways, but only low probability of success (40% in ventricular insertion ablation) or very low sensitivity (12.5% in atrial insertion ablation) for right-sided ones. In conclusion, with the present approach, successful catheter ablation of right-sided accessory AV pathways, compared to left-sided ones, still necessitate a breakthrough in the precision mapping and the efficiency of energy delivery.

  8. Do perceived job insecurity and annoyance due to air and noise pollution predict incident self-rated poor health? A prospective analysis of independent and joint associations using a German national representative cohort study.

    Science.gov (United States)

    Riedel, Natalie; Loerbroks, Adrian; Bolte, Gabriele; Li, Jian

    2017-01-23

    Current economic and social change has contributed to increasing job insecurity and traffic-related pollution in residential areas. Both job insecurity and exposure to noise and air pollution are known determinants of population health and can concur in peoples' lives. This may hold true particularly for socially disadvantaged subpopulations. Nevertheless, the potential independent and joint links of those exposures to health have been rarely examined so far. We aimed to contribute to the scarce body of evidence. Information on perceived job insecurity and exposures to noise and air pollution as expressed by annoyance as well as on self-rated health were gathered from 2 waves of the population-based German Socio-Economic Panel (2009 and 2011, N=6544). We performed multivariable Poisson regression to examine the independent and joint risk of poor health in 2011 by perceived job insecurity and annoyance due to noise and air pollution in 2009. After the 2-year follow-up in 2011, 571 (8.7%) participants rated their health as poor. The risk of reporting incident poor health was increased by roughly 40% in employees reporting high versus low perceived job insecurity and annoyance due to noise and air pollution, respectively. This risk increased when both exposures were present at higher levels (risk ratio=1.95 (1.49 to 2.55)). Work-related and environmental exposures may accumulate and have a joint health impact. Elaboration on the link between occupational and residential exposures is warranted in the light of their concurrence and their implications for health inequities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Migration pathways in soils

    International Nuclear Information System (INIS)

    Gronow, J.R.

    1986-01-01

    This study looked at diffusive migration through three types of deformation; the projectile pathways, hydraulic fractures of the sediments and faults, and was divided into three experimental areas: autoradiography, the determination of diffusion coefficients and electron microscopy of model projectile pathways in clay. For the autoradiography, unstressed samples were exposed to two separate isotopes, Pm-147 (a possible model for Am behaviour) and the poorly sorbed iodide-125. The results indicated that there was no enhanced migration through deformed kaolin samples nor through fractured Great Meteor East (GME) sediment, although some was evident through the projectile pathways in GME and possibly through the GME sheared samples. The scanning electron microscopy of projectile pathways in clay showed that emplacement of a projectile appeared to have no effect on the orientation of particles at distances greater than two projectile radii from the centre of a projectile pathway. It showed that the particles were not simply aligned with the direction of motion of the projectile but that, the closer to the surface of a particular pathway, the closer the particles lay to their original orientation. This finding was of interest from two points of view: i) the ease of migration of a pollutant along the pathway, and ii) possible mechanisms of hole closure. It was concluded that, provided that there is no advective migration, the transport of radionuclides through sediments containing these defects would not be significantly more rapid than in undeformed sediments. (author)

  10. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish

    NARCIS (Netherlands)

    Groh, K.J.; Carvalho, R.N.; Chipman, J.K.; Denslow, N.D.; Halder, M.; Murphy, C.A.; Roelofs, D.; Rolaki, A.; Schirmer, K.; Watanabe, K.H.

    2015-01-01

    Adverse outcome pathways (AOPs) organize knowledge on the progression of toxicity through levels of biological organization. By determining the linkages between toxicity events at different levels, AOPs lay the foundation for mechanism-based alternative testing approaches to hazard assessment. Here,

  11. Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death

    DEFF Research Database (Denmark)

    Ghasemzedah, Nima; Hayek, Salim; Ko, Yi-An

    2017-01-01

    BACKGROUND: Inflammation, coagulation, and cell stress contribute to atherosclerosis and its adverse events. A biomarker risk score (BRS) based on the circulating levels of biomarkers C-reactive protein, fibrin degradation products, and heat shock protein-70 representing these 3 pathways was a st...

  12. Imprecision of dose predictions for radionuclides released to the atmosphere: an application of the Monte Carlo-simulation-technique for iodine transported via the pasture-cow-milk pathway

    International Nuclear Information System (INIS)

    Schwarz, G.; Hoffman, F.O.

    1979-01-01

    The shortcomings of using mathematical models to determine compliance with regulatory standards are discussed. Methods to determine the reliability of radiation assessment models are presented. Since field testing studies are impractical, a deficiency method, which analyzes the variability of input parameters and the impact of their variability on the predicted dose, is used. The Monte Carlo technique is one of these methods. This technique is based on statistical properties of the model output when input parameters inserted in the model are selected at random from a prescribed distribution. The one big assumption one must make is that the model is a correct formulation of reality. The Gaussian plume model for atmospheric transport of airborne effluents was used to study the pasture-cow-milk-man exposure pathway and the dose calculated from radioiodine ( 131 I) transported over this pathway

  13. Imprecision of dose predictions for radionuclides released to the atmosphere: an application of the Monte Carlo-simulation-technique for iodine transported via the pasture-cow-milk pathway

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, G.; Hoffman, F.O.

    1979-01-01

    The shortcomings of using mathematical models to determine compliance with regulatory standards are discussed. Methods to determine the reliability of radiation assessment models are presented. Since field testing studies are impractical, a deficiency method, which analyzes the variability of input parameters and the impact of their variability on the predicted dose, is used. The Monte Carlo technique is one of these methods. This technique is based on statistical properties of the model output when input parameters inserted in the model are selected at random from a prescribed distribution. The one big assumption one must make is that the model is a correct formulation of reality. The Gaussian plume model for atmospheric transport of airborne effluents was used to study the pasture-cow-milk-man exposure pathway and the dose calculated from radioiodine (/sup 131/I) transported over this pathway. (DMC)

  14. Low pretreatment levels of myeloid-related protein-8/14 and C-reactive protein predict poor adherence to treatment with tumor necrosis factor inhibitors in juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Alberdi-Saugstrup, Mikel; Nielsen, Susan; Mathiessen, Pernille

    2017-01-01

    inhibitor treatment in JIA patients naive to biologics and investigated if baseline myeloid-related protein (MRP)-8/14 and C-reactive protein (CRP) were predictive of treatment response. One hundred fifty-two patients were included in a unicenter observational, prospective study from 2002 to 2015, excluding......, and 90 were achieved by 61, 55, 38, and 10 % of the patients, and 23 % achieved a status of ID. Treatment adherence: 51 % withdrew from treatment due to lack of clinical effect, while 32 % continued treatment or withdrew due to disease remission. Increased MRP-8/14 concentrations at treatment initiation...... was associated with ID after 1 year (OR 1.55, CI 1.06–2.25, p = 0.02). Treatment withdrawal due to lack of effect was associated with low baseline levels of both MRP-8/14 (685 vs. 1235 ng/ml, p 

  15. Dual role of CD44 isoforms in ampullary adenocarcinoma: CD44s predicts poor prognosis in early cancer and CD44ν is an indicator for recurrence in advanced cancer

    International Nuclear Information System (INIS)

    Wu, Cheng-Lin; Chao, Ying-Jui; Yang, Ta-Ming; Chen, Yi-Ling; Chang, Kung-Chao; Hsu, Hui-Ping; Shan, Yan-Shen; Lai, Ming-Derg

    2015-01-01

    Although postoperative adjuvant chemoradiotherapies prevent recurrence for some patients with ampullary cancer, the recurrence rate is as high as 29 % in patients with stage I cancer. In an effort to identify predictors of recurrence in patients with ampullary adenocarcinoma, we investigated the clinical value of assessing standard and variant forms of CD44. Immunohistochemistry staining and reverse-transcription polymerase chain reaction (RT-PCR) was used to detect standard and variant forms of CD44 in samples of ampullary adenocarcinoma. The cDNA microarray analysis comparing tumors with or without pancreatic invasion was undertaken and analyzed by Ingenuity Pathway Analysis. The standard CD44 (CD44s) isoform was detected in 76 of 98 patients with ampullary adenocarcinoma, and the negative or weak expression of CD44s was correlated with pancreatic invasion, lymphovascular invasion, advanced stage and bone metastasis. Moderate to dense expression of CD44s was correlated with shorter overall survival in patients with localized cancer (T1 or T2 disease, P = 0.0268). The patients with advanced cancer (T3 or T4 disease) and moderate or dense CD44s expression had a trend toward better survival. Alternative splicing of CD44 was confirmed using RT-PCR, which revealed that the CD44ν3-10 isoform was only expressed in patients with cancer recurrence. Fold change of CD44ν6-10 was also increased. In addition, networks containing CD44, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), transforming growth factor-β (TGF-β), matrix metalloproteinase 2 (MMP2), AKT, extracellular signal-regulated protein kinase 1 and 2 (ERK1/2), p38 MAPK, activated protein 1 (AP1)‚ and CTNNB1 were constructed after comparing microarray data from patients with and without pancreatic invasion. Whereas CD44s functions as tumor-promoting oncoprotein in early localized ampullary adenocarcinoma, CD44 variants are expressed in advanced cancer and patients with

  16. Are the energy poor also income poor? Evidence from India

    International Nuclear Information System (INIS)

    Khandker, Shahidur R.; Barnes, Douglas F.; Samad, Hussain A.

    2012-01-01

    The energy poverty line is defined as the threshold point at which energy consumption begins to rise with increases in household income. This approach is applied to cross-sectional data from a comprehensive 2005 household survey representative of both urban and rural India. The objective is to determine if the energy poor are also income poor and whether and how energy policies help reduce energy poverty, independent of income. The findings suggest that in rural areas some 57% of households are energy poor, versus 22% that are income poor. But in urban areas the energy poverty rate is 28% compared to 20% that are income poor. That is, energy policies are expected to play some roles in mitigating energy poverty. We find that reducing energy poverty requires not only support for rural electrification, but also more use of modern cooking fuels such as LPG. While income growth matters, a combination of energy related programs can play an independent and substantial role in reducing energy poverty. - Highlights: ► This paper applies a new approach to measuring energy poverty to rural and urban India. ► It also compares and contrasts income poverty with energy poverty in the context of India. ► Findings suggest that income poverty tracks energy poverty in urban India, but not in rural India. ► Income growth is very important in reducing energy poverty. ► In addition, access to and reliability of modern sources (electricity, LPG) are also helpful.

  17. Young patients with colorectal cancer have poor survival in the first twenty months after operation and predictable survival in the medium and long-term: Analysis of survival and prognostic markers

    Directory of Open Access Journals (Sweden)

    Wickramarachchi RE

    2010-09-01

    Full Text Available Abstract Objectives This study compares clinico-pathological features in young (50 years with colorectal cancer, survival in the young and the influence of pre-operative clinical and histological factors on survival. Materials and methods A twelve year prospective database of colorectal cancer was analysed. Fifty-three young patients were compared with forty seven consecutive older patients over fifty years old. An analysis of survival was undertaken in young patients using Kaplan Meier graphs, non parametric methods, Cox's Proportional Hazard Ratios and Weibull Hazard models. Results Young patients comprised 13.4 percent of 397 with colorectal cancer. Duration of symptoms and presentation in the young was similar to older patients (median, range; young patients; 6 months, 2 weeks to 2 years, older patients; 4 months, 4 weeks to 3 years, p > 0.05. In both groups, the majority presented without bowel obstruction (young - 81%, older - 94%. Cancer proximal to the splenic flexure was present more in young than in older patients. Synchronous cancers were found exclusively in the young. Mucinous tumours were seen in 16% of young and 4% of older patients (p Conclusion If patients, who are less than 40 years old with colorectal cancer, survive twenty months after operation, the prognosis improves and their survival becomes predictable.

  18. Children's labour as a risky pathways to resilience: children's growth in contexts of poor resources Trabalho infantil como um caminho em direção à resiliência marcado por riscos: o crescimento de crianças e adolescentes em contextos pobres em recursos

    Directory of Open Access Journals (Sweden)

    Michael Ungar

    2010-01-01

    Full Text Available In this paper we explore children's labor as a complex phenomenon encompassing risk factors on one hand and possible positive outcomes on the other. Based on the theory of resilience and on literature review that details children's own experiences of work, we show that children who are inserted in environments which are poor in social and physical resources may report labor as pathways to ensure their own resources to overcome adversity. Understanding children's subjective accounts of their experience permits us to see children's labor as a culturally-embedded construction. Though exploitation of children is not in the best interest of children, there is evidence that children use whatever opportunities are available, including labor, to search for the resources they need and negotiate for an identity as resilient. Implications for public policies and practices are discussed.Nesse artigo, analisamos a questão do trabalho infantil como um fenômeno complexo, englobando fatores de risco por um lado e possíveis resultados positivos por outro. Baseados na teoria da resiliência e a partir de uma revisão de literatura, centrada em pesquisas que analisam a própria experiência de crianças sobre o trabalho desenvolvido, mostramos que quando inseridos em ecologias socialmente e fisicamente pobres em recursos, crianças associam sua experiência de trabalho como um caminho para assegurar recursos próprios para superação de adversidades. A compreensão de aspectos subjetivos da experiência de crianças trabalhadores nos permite considerar o trabalho como uma construção culturalmente embasada. Apesar da exploração de crianças não se configurar como o melhor para elas, há evidências de que elas usam quaisquer oportunidades disponíveis, incluindo o trabalho, para navegar em busca de recursos que necessitam e negociam por uma identidade associada à resiliência. Implicações para políticas públicas e intervenções também s

  19. Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/β-thalassemia patients.

    Science.gov (United States)

    Chalikiopoulou, Constantina; Tavianatou, Anastasia-Gerasimoula; Sgourou, Argyro; Kourakli, Alexandra; Kelepouri, Dimitra; Chrysanthakopoulou, Maria; Kanelaki, Vasiliki-Kaliopi; Mourdoukoutas, Evangelos; Siamoglou, Stavroula; John, Anne; Symeonidis, Argyris; Ali, Bassam R; Katsila, Theodora; Papachatzopoulou, Adamantia; Patrinos, George P

    2016-03-01

    Hemoglobinopathies exhibit a remarkable phenotypic diversity that restricts any safe association between molecular pathology and clinical outcomes. Herein, we explored the role of genes involved in the nitric oxide biosynthesis and signaling pathway, implicated in the increase of fetal hemoglobin levels and response to hydroxyurea treatment, in 119 Hellenic patients with β-type hemoglobinopathies. We show that two ASS1 genomic variants (namely, rs10901080 and rs10793902) can serve as pharmacogenomic biomarkers to predict hydroxyurea treatment efficacy in sickle cell disease/β-thalassemia compound heterozygous patients. These markers may exert their effect by inducing nitric oxide biosynthesis, either via altering splicing and/or miRNA binding, as predicted by in silico analysis, and ultimately, increase γ-globin levels, via guanylyl cyclase targeting.

  20. Pathways to Late-Life Suicidal Behavior: Cluster Analysis and Predictive Validation of Suicidal Behavior in a Sample of Older Adults With Major Depression.

    Science.gov (United States)

    Szanto, Katalin; Galfalvy, Hanga; Vanyukov, Polina M; Keilp, John G; Dombrovski, Alexandre Y

    Clinical heterogeneity is a key challenge to understanding suicidal risk, as different pathways to suicidal behavior are likely to exist. We aimed to identify such pathways by uncovering latent classes of late-life depression cases and relating them to prior and future suicidal behavior. Data were collected from June 2010 to September 2015. In this longitudinal study we examined distinct associations of clinical and cognitive/decision-making factors with suicidal behavior in 194 older (50+ years) nondemented, depressed patients; 57 nonpsychiatric healthy controls provided benchmark data. The DSM-IV was used to establish diagnostic criteria. We identified multivariate patterns of risk factors, defining clusters based on personality traits, perceived social support, cognitive performance, and decision-making in an analysis blinded to participants' history of suicidal behavior. We validated these clusters using past and prospective suicidal ideation and behavior. Of 5 clusters identified, 3 were associated with high risk for suicidal behavior: (1) cognitive deficits, dysfunctional personality, low social support, high willingness to delay future rewards, and overrepresentation of high-lethality attempters; (2) high-personality pathology (ie, low self-esteem), minimal or no cognitive deficits, and overrepresentation of low-lethality attempters and ideators; (3) cognitive deficits, inability to delay future rewards, and similar distribution of high- and low-lethality attempters. There were significant between-cluster differences in number (P suicide attempts and in the likelihood of future suicide attempts (P = .010, 30 attempts by 22 patients, 2 fatal) and emergency psychiatric hospitalizations to prevent suicide (P = .005, 31 participants). Three pathways to suicidal behavior in older patients were found, marked by (1) very high levels of cognitive and dispositional risk factors suggesting a dementia prodrome, (2) dysfunctional personality traits, and (3) impulsive

  1. Axial diffusivity changes in the motor pathway above stroke foci and functional recovery after subcortical infarction.

    Science.gov (United States)

    Liu, Gang; Peng, Kangqiang; Dang, Chao; Tan, Shuangquan; Chen, Hongbing; Xie, Chuanmiao; Xing, Shihui; Zeng, Jinsheng

    2018-01-01

    Secondary degeneration of the fiber tract of the motor pathway below infarct foci and functional recovery after stroke have been well demonstrated, but the role of the fiber tract above stroke foci remains unclear. This study aimed to investigate diffusion changes in motor fibers above the lesion and identify predictors of motor improvement within 12 weeks after subcortical infarction. Diffusion tensor imaging and the Fugl-Meyer (FM) scale were conducted 1, 4, and 12 weeks (W) after a subcortical infarct. Proportional recovery model residuals were used to assign patients to proportional recovery and poor recovery groups. Region of interest analysis was used to assess diffusion changes in the motor pathway above and below a stroke lesion. Multivariable linear regression was employed to identify predictors of motor improvement within 12 weeks after stroke. Axial diffusivity (AD) in the underlying white matter of the ipsilesional primary motor area (PMA) and cerebral peduncle (CP) in both proportional and poor recovery groups was lower at W1 compared to the controls and values in the contralesional PMA and CP (all P motor improvement within 12 weeks after stroke in patients with proportional or poor recovery. Increases of AD in the motor pathway above stroke foci may be associated with motor recovery after subcortical infarction. Early measurement of diffusion metrics in the ipsilesional non-ischemic motor pathway has limited value in predicting future motor improvement patterns (proportional or poor recovery).

  2. Wolf-Parkinson-White syndrome in young men presenting with palpitation: the pattern of delta waves in predicting location of accessory pathway

    Directory of Open Access Journals (Sweden)

    Miryanti Cahyaningtias

    2011-11-01

    Full Text Available Palpitation is a common presenting symptom in the emergency department. Wolf-Parkinson White (WPW syndrome is a cardiac conduction disorder that may present with palpitation and lead to sudden cardiac death. WPW could be detected by  electrocardiogram (ECG. In this case report, we present two young male patients with WPW syndrome admitted to our hospital with history of repeated and progressive palpitation. ECG of the first patient revealed supraventricular tachycardia which converted to sinus rhythm after propanolol treatment. ECG showed sinus rhythm with delta wave in lead II,III,aVF, V1 suggesting the presence of accessory pathway (AP in left lateral wall. Electrophysiology study confirmed the presence of AP and radio frequency catheter ablation was successfully done resulted in disappearance of delta on outpatient clinic ECG. Patient has no symptom and he do not have to take medication. ECG of the second patient revealed supraventricular tachycardia with abberancy. After amiodarone infusion, ECG showed sinus rhythm with delta wave in lead I,II,aVL suggesting the presence of accessory pathway in anteroseptal wall. Electrophysiology study and catheter ablation did not perform for this patient because of financial problem, however amidarone has to be taken regularly to prevent the recurrence of supraventricular tachycardia. (Med J Indones 2011; 20:298-301Keywords: ECG, palpitation, supraventricular tachycardia, Wolf- Parkinson White syndrome

  3. Application of pathways analyses for site performance prediction for the Gas Centrifuge Enrichment Plant and Oak Ridge Central Waste Disposal Facility

    International Nuclear Information System (INIS)

    Pin, F.G.; Oblow, E.M.

    1984-01-01

    The suitability of the Gas Centrifuge Enrichment Plant and the Oak Ridge Central Waste Disposal Facility for shallow-land burial of low-level radioactive waste is evaluated using pathways analyses. The analyses rely on conservative scenarios to describe the generation and migration of contamination and the potential human exposure to the waste. Conceptual and numerical models are developed using data from comprehensive laboratory and field investigations and are used to simulate the long-term transport of contamination to man. Conservatism is built into the analyses when assumptions concerning future events have to be made or when uncertainties concerning site or waste characteristics exist. Maximum potential doses to man are calculated and compared to the appropriate standards. The sites are found to provide adequate buffer to persons outside the DOE reservations. Conclusions concerning site capacity and site acceptability are drawn. In reaching these conclusions, some consideration is given to the uncertainties and conservatisms involved in the analyses. Analytical methods to quantitatively assess the probability of future events to occur and the sensitivity of the results to data uncertainty may prove useful in relaxing some of the conservatism built into the analyses. The applicability of such methods to pathways analyses is briefly discussed. 18 refs., 9 figs

  4. Poor nutritional status on admission predicts poor outcomes after stroke: observational data from the FOOD trial.

    Science.gov (United States)

    2003-06-01

    Previous studies suggest that undernourished patients with acute stroke do badly. The data, however, are not robust. We aimed to reliably assess the importance of baseline nutritional status as an independent predictor of long-term outcome after stroke in a large prospective cohort enrolled in the Feed Or Ordinary Diet (FOOD) trial, a multicenter randomized trial evaluating various feeding policies. Patients admitted to hospital with a recent stroke were enrolled in the FOOD trial. Data on nutritional status and other clinical predictors of outcome were collected at trial entry. At 6 months, the coordinating center collected data on survival and functional status (modified Rankin Scale). Outcome assessment was done by researchers blinded to baseline assessments and treatment allocation. Between November 1996 and November 2001, 3012 patients were enrolled, and 2955 (98%) were followed up. Of the 275 undernourished patients, 102 (37%) were dead by final follow-up compared with only 445 (20%) of 2194 patients of normal nutritional status (odds ratio [OR], 2.32; 95% CI, 1.78 to 3.02). After adjustment for age, prestroke functional state, and stroke severity, this relationship, although weakened, still held (OR, 1.82; 95% CI, 1.34 to 2.47). Undernourished patients were more likely to develop pneumonia, other infections, and gastrointestinal bleeding during their hospital admission than other patients. These data provide reliable evidence that nutritional status early after stroke is independently associated with long-term outcome. It supports the rationale for the FOOD trial, which continues to recruit and aims to estimate the effect of different feeding regimes on outcome after stroke and thus determine whether the association observed in this study is likely to be causal.

  5. The use of adverse outcome pathway-based toxicity predictions: A case study evaluating the effects of imazalil on fathead minnow reproduction

    Science.gov (United States)

    Product Description: As a means to increase the efficiency of chemical safety assessment, there is an interest in using data from molecular and cellular bioassays, conducted in a highly automated fashion using modern robotics, to predict toxicity in humans and wildlife. The prese...

  6. Next Generation Sequencing and Transcriptome Analysis Predicts Biosynthetic Pathway of Sennosides from Senna (Cassia angustifolia Vahl., a Non-Model Plant with Potent Laxative Properties.

    Directory of Open Access Journals (Sweden)

    Nagaraja Reddy Rama Reddy

    Full Text Available Senna (Cassia angustifolia Vahl. is a world's natural laxative medicinal plant. Laxative properties are due to sennosides (anthraquinone glycosides natural products. However, little genetic information is available for this species, especially concerning the biosynthetic pathways of sennosides. We present here the transcriptome sequencing of young and mature leaf tissue of Cassia angustifolia using Illumina MiSeq platform that resulted in a total of 6.34 Gb of raw nucleotide sequence. The sequence assembly resulted in 42230 and 37174 transcripts with an average length of 1119 bp and 1467 bp for young and mature leaf, respectively. The transcripts were annotated using NCBI BLAST with 'green plant database (txid 33090', Swiss Prot, Kyoto Encylcopedia of Genes & Genomes (KEGG, Cluster of Orthologous Gene (COG and Gene Ontology (GO. Out of the total transcripts, 40138 (95.0% and 36349 (97.7% from young and mature leaf, respectively, were annotated by BLASTX against green plant database of NCBI. We used InterProscan to see protein similarity at domain level, a total of 34031 (young leaf and 32077 (mature leaf transcripts were annotated against the Pfam domains. All transcripts from young and mature leaf were assigned to 191 KEGG pathways. There were 166 and 159 CDS, respectively, from young and mature leaf involved in metabolism of terpenoids and polyketides. Many CDS encoding enzymes leading to biosynthesis of sennosides were identified. A total of 10,763 CDS differentially expressing in both young and mature leaf libraries of which 2,343 (21.7% CDS were up-regulated in young compared to mature leaf. Several differentially expressed genes found functionally associated with sennoside biosynthesis. CDS encoding for many CYPs and TF families were identified having probable roles in metabolism of primary as well as secondary metabolites. We developed SSR markers for molecular breeding of senna. We have identified a set of putative genes involved in

  7. Next Generation Sequencing and Transcriptome Analysis Predicts Biosynthetic Pathway of Sennosides from Senna (Cassia angustifolia Vahl.), a Non-Model Plant with Potent Laxative Properties.

    Science.gov (United States)

    Rama Reddy, Nagaraja Reddy; Mehta, Rucha Harishbhai; Soni, Palak Harendrabhai; Makasana, Jayanti; Gajbhiye, Narendra Athamaram; Ponnuchamy, Manivel; Kumar, Jitendra

    2015-01-01

    Senna (Cassia angustifolia Vahl.) is a world's natural laxative medicinal plant. Laxative properties are due to sennosides (anthraquinone glycosides) natural products. However, little genetic information is available for this species, especially concerning the biosynthetic pathways of sennosides. We present here the transcriptome sequencing of young and mature leaf tissue of Cassia angustifolia using Illumina MiSeq platform that resulted in a total of 6.34 Gb of raw nucleotide sequence. The sequence assembly resulted in 42230 and 37174 transcripts with an average length of 1119 bp and 1467 bp for young and mature leaf, respectively. The transcripts were annotated using NCBI BLAST with 'green plant database (txid 33090)', Swiss Prot, Kyoto Encylcopedia of Genes & Genomes (KEGG), Cluster of Orthologous Gene (COG) and Gene Ontology (GO). Out of the total transcripts, 40138 (95.0%) and 36349 (97.7%) from young and mature leaf, respectively, were annotated by BLASTX against green plant database of NCBI. We used InterProscan to see protein similarity at domain level, a total of 34031 (young leaf) and 32077 (mature leaf) transcripts were annotated against the Pfam domains. All transcripts from young and mature leaf were assigned to 191 KEGG pathways. There were 166 and 159 CDS, respectively, from young and mature leaf involved in metabolism of terpenoids and polyketides. Many CDS encoding enzymes leading to biosynthesis of sennosides were identified. A total of 10,763 CDS differentially expressing in both young and mature leaf libraries of which 2,343 (21.7%) CDS were up-regulated in young compared to mature leaf. Several differentially expressed genes found functionally associated with sennoside biosynthesis. CDS encoding for many CYPs and TF families were identified having probable roles in metabolism of primary as well as secondary metabolites. We developed SSR markers for molecular breeding of senna. We have identified a set of putative genes involved in various

  8. Signaling flux redistribution at toll-like receptor pathway junctions.

    Directory of Open Access Journals (Sweden)

    Kumar Selvarajoo

    Full Text Available Various receptors on cell surface recognize specific extracellular molecules and trigger signal transduction altering gene expression in the nucleus. Gain or loss-of-function mutations of one molecule have shown to affect alternative signaling pathways with a poorly understood mechanism. In Toll-like receptor (TLR 4 signaling, which branches into MyD88- and TRAM-dependent pathways upon lipopolysaccharide (LPS stimulation, we investigated the gain or loss-of-function mutations of MyD88. We predict, using a computational model built on the perturbation-response approach and the law of mass conservation, that removal and addition of MyD88 in TLR4 activation, enhances and impairs, respectively, the alternative TRAM-dependent pathway through signaling flux redistribution (SFR at pathway branches. To verify SFR, we treated MyD88-deficient macrophages with LPS and observed enhancement of TRAM-dependent pathway based on increased IRF3 phosphorylation and induction of Cxcl10 and Ifit2. Furthermore, increasing the amount of MyD88 in cultured cells showed decreased TRAM binding to TLR4. Investigating another TLR4 pathway junction, from TRIF to TRAF6, RIP1 and TBK1, the removal of MyD88-dependent TRAF6 increased expression of TRAM-dependent Cxcl10 and Ifit2. Thus, we demonstrate that SFR is a novel mechanism for enhanced activation of alternative pathways when molecules at pathway junctions are removed. Our data suggest that SFR may enlighten hitherto unexplainable intracellular signaling alterations in genetic diseases where gain or loss-of-function mutations are observed.

  9. Testosterone for Poor Ovarian Responders

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Davis, Susan R; Drakopoulos, Panagiotis

    2016-01-01

    Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before...... ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect...... stages. In addition, extreme testosterone excess is not only likely to induce adverse events but has also the potential to be ineffective and even detrimental. Thus, evidence from clinical studies is not enough to either "reopen" or "close" the "androgen chapter" in poor responders, mainly because...

  10. Entitlement Attitudes Predict Students' Poor Performance in Challenging Academic Conditions

    Science.gov (United States)

    Anderson, Donna; Halberstadt, Jamin; Aitken, Robert

    2013-01-01

    Excessive entitlement--an exaggerated or unrealistic belief about what one deserves--has been associated with a variety of maladaptive behaviors, including a decline in motivation and effort. In the context of tertiary education, we reasoned that if students expend less effort to obtain positive outcomes to which they feel entitled, this should…

  11. Poor mental health status and aggression are associated with poor driving behavior among male traffic offenders

    Directory of Open Access Journals (Sweden)

    Abdoli N

    2015-08-01

    Full Text Available Nasrin Abdoli,1,2 Vahid Farnia,3 Ali Delavar,4 Alirez Esmaeili,5 Fariborz Dortaj,4 Noorali Farrokhi,4 Majid Karami,6 Jalal Shakeri,3 Edith Holsboer-Trachsler,7 Serge Brand7,8 1International University of Imam Reza, Mashhad, 2Kermanshah University of Medical Sciences, Kermanshah, 3Substance Abuse Prevention Research Center, Psychiatry Department, Kermanshah University of Medical Sciences, Kermanshah, 4Allameh Tabataba’i University, Tehran, 5Police University, Tehran, 6Baharestan Research Center, Kermanshah Transportation Terminal, Kermanshah, Iran, 7Center for Affective, Stress and Sleep Disorders, Psychiatric Clinics of the University of Basel, Basel, 8Department of Sport and Health Science, Sport Science Section, University of Basel, Basel, Switzerland Background: In Iran, traffic accidents and deaths from traffic accidents are among the highest in the world, and generally driver behavior rather than either technical failures or environmental conditions are responsible for traffic accidents. In the present study, we explored the extent to which aggressive traits, health status, and sociodemographic variables explain driving behavior among Iranian male traffic offenders. Method: A total of 443 male driving offenders (mean age: M =31.40 years, standard deviation =9.56 from Kermanshah (Iran took part in the study. Participants completed a questionnaire booklet covering sociodemographic variables, traits of aggression, health status, and driving behavior. Results: Poor health status, such as symptoms of depression, anxiety, insomnia, and social dysfunction, and also higher levels of trait aggression explained poor driving behavior. Multiple regressions indicated that poor health status, but not aggression, independently predicted poor driving behavior. Conclusion: Results suggest that health status concerns are associated with poor driving behavior. Prevention and intervention might therefore focus on drivers reporting poor mental health status

  12. Energy poor or fuel poor: What are the differences?

    International Nuclear Information System (INIS)

    Li, Kang; Lloyd, Bob; Liang, Xiao-Jie; Wei, Yi-Ming

    2014-01-01

    Energy poverty and fuel poverty are descriptors of problems of households' energy consumption, they are both distinct problems and have been addressed by many researchers, organizations and governments. Cross use of the terms of energy poverty and fuel poverty in published papers is common. As an accurate descriptor is the presupposition of research and policy development, especially for those who just started to pay attention to this issue, this paper compares the definitions, research priorities, status quo, and problems of these two concepts, and summarizes the relationship between them. The paper suggests that only when the research targets are households who are living in a cold climate and have difficulty in getting access to electricity or modern cooking facilities, and in supplying indoor heating with appropriate cost, the concepts of energy poverty and fuel poverty have the chance to be broadened and mutually integrated. - Highlights: • Address energy poverty and fuel poverty simultaneously. • Compare energy poverty and fuel poverty from 4 perspectives. • Summarize the relationship between energy poverty and fuel poverty. • Divide energy poor and fuel poor into three categories

  13. A Perceptual Pathway to Bias: Interracial Exposure Reduces Abrupt Shifts in Real-Time Race Perception That Predict Mixed-Race Bias.

    Science.gov (United States)

    Freeman, Jonathan B; Pauker, Kristin; Sanchez, Diana T

    2016-04-01

    In two national samples, we examined the influence of interracial exposure in one's local environment on the dynamic process underlying race perception and its evaluative consequences. Using a mouse-tracking paradigm, we found in Study 1 that White individuals with low interracial exposure exhibited a unique effect of abrupt, unstable White-Black category shifting during real-time perception of mixed-race faces, consistent with predictions from a neural-dynamic model of social categorization and computational simulations. In Study 2, this shifting effect was replicated and shown to predict a trust bias against mixed-race individuals and to mediate the effect of low interracial exposure on that trust bias. Taken together, the findings demonstrate that interracial exposure shapes the dynamics through which racial categories activate and resolve during real-time perceptions, and these initial perceptual dynamics, in turn, may help drive evaluative biases against mixed-race individuals. Thus, lower-level perceptual aspects of encounters with racial ambiguity may serve as a foundation for mixed-race prejudice. © The Author(s) 2016.

  14. Drug-like properties and the causes of poor solubility and poor permeability.

    Science.gov (United States)

    Lipinski, C A

    2000-01-01

    There are currently about 10000 drug-like compounds. These are sparsely, rather than uniformly, distributed through chemistry space. True diversity does not exist in experimental combinatorial chemistry screening libraries. Absorption, distribution, metabolism, and excretion (ADME) and chemical reactivity-related toxicity is low, while biological receptor activity is higher dimensional in chemistry space, and this is partly explainable by evolutionary pressures on ADME to deal with endobiotics and exobiotics. ADME is hard to predict for large data sets because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates. Currently, screening for biological receptor activity precedes or is concurrent with screening for properties related to "drugability." In the future, "drugability" screening may precede biological receptor activity screening. The level of permeability or solubility needed for oral absorption is related to potency. The relative importance of poor solubility and poor permeability towards the problem of poor oral absorption depends on the research approach used for lead generation. A "rational drug design" approach as exemplified by Merck advanced clinical candidates leads to time-dependent higher molecular weight, higher H-bonding properties, unchanged lipophilicity, and, hence, poorer permeability. A high throughput screening (HTS)-based approach as exemplified by unpublished data on Pfizer (Groton, CT) early candidates leads to higher molecular weight, unchanged H-bonding properties, higher lipophilicity, and, hence, poorer aqueous solubility.

  15. Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival.

    Science.gov (United States)

    Liu, Yanhong; Shete, Sanjay; Etzel, Carol J; Scheurer, Michael; Alexiou, George; Armstrong, Georgina; Tsavachidis, Spyros; Liang, Fu-Wen; Gilbert, Mark; Aldape, Ken; Armstrong, Terri; Houlston, Richard; Hosking, Fay; Robertson, Lindsay; Xiao, Yuanyuan; Wiencke, John; Wrensch, Margaret; Andersson, Ulrika; Melin, Beatrice S; Bondy, Melissa

    2010-05-10

    Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment. Among 590 patients with primary GBM, we evaluated associations of survival with the 100 top-ranking glioma susceptibility single nucleotide polymorphisms from our previous genome-wide association study using Cox regression models. We also compared differences in genetic variation between short-term survivors (STS; or= 36 months), and explored classification and regression tree analysis for survival data. We tested results using two independent series totaling 543 GBMs. We identified LIG4 rs7325927 and BTBD2 rs11670188 as predictors of STS in GBM and CCDC26 rs10464870 and rs891835, HMGA2 rs1563834, and RTEL1 rs2297440 as predictors of LTS. Further survival tree analysis revealed that patients >or= 50 years old with LIG4 rs7325927 (V) had the worst survival (median survival time, 1.2 years) and exhibited the highest risk of death (hazard ratio, 17.53; 95% CI, 4.27 to 71.97) compared with younger patients with combined RTEL1 rs2297440 (V) and HMGA2 rs1563834 (V) genotypes (median survival time, 7.8 years). Polymorphisms in the LIG4, BTBD2, HMGA2, and RTEL1 genes, which are involved in the double-strand break repair pathway, are associated with GBM survival.

  16. Divergent responses of the amygdala and ventral striatum predict stress-related problem drinking in young adults: possible differential markers of affective and impulsive pathways of risk for alcohol use disorder.

    Science.gov (United States)

    Nikolova, Y S; Knodt, A R; Radtke, S R; Hariri, A R

    2016-03-01

    Prior work suggests that there may be two distinct pathways of alcohol use disorder (AUD) risk: one associated with positive emotion enhancement and behavioral impulsivity, and another associated with negative emotion relief and coping. We sought to map these two pathways onto individual differences in neural reward and threat processing assessed using blood-oxygen-level-dependent functional magnetic resonance imaging in a sample of 759 undergraduate students (426 women, mean age 19.65±1.24 years) participating in the Duke Neurogenetics Study. We demonstrate that problem drinking is highest in the context of stress and in those with one of two distinct neural phenotypes: (1) a combination of relatively low reward-related activity of the ventral striatum (VS) and high threat-related reactivity of the amygdala; or (2) a combination of relatively high VS activity and low amygdala reactivity. In addition, we demonstrate that the relationship between stress and problem alcohol use is mediated by impulsivity, as reflected in monetary delay discounting rates, for those with high VS-low amygdala reactivity, and by anxious/depressive symptomatology for those with the opposite neural risk phenotype. Across both neural phenotypes, we found that greater divergence between VS and amygdala reactivity predicted greater risk for problem drinking. Finally, for those individuals with the low VS-high amygdala risk phenotype we found that stress not only predicted the presence of AUD diagnosis at the time of neuroimaging but also subsequent problem drinking reported 3 months following study completion. These results offer new insight into the neural basis of AUD risk and suggest novel biological targets for early individualized treatment or prevention.

  17. Divergent responses of the amygdala and ventral striatum predict stress-related problem drinking in young adults: Possible differential markers of affective and impulsive pathways of risk for alcohol use disorder

    Science.gov (United States)

    Nikolova, Yuliya S.; Knodt, Annchen R.; Radtke, Spenser R.; Hariri, Ahmad R.

    2015-01-01

    Prior work suggests there may be two distinct pathways of alcohol use disorder (AUD) risk: one associated with positive emotion enhancement and behavioral impulsivity, and one associated with negative emotion relief and coping. We sought to map these two pathways onto individual differences in neural reward and threat processing assessed using BOLD fMRI in a sample of 759 undergraduate students (426 women, mean age 19.65±1.24) participating in the Duke Neurogenetics Study. We demonstrate that problem drinking is highest in the context of stress and in those with one of two distinct neural phenotypes: 1) a combination of relatively low reward-related activity of the ventral striatum (VS) and high threat-related reactivity of the amygdala; or 2) a combination of relatively high VS activity and low amygdala reactivity. In addition, we demonstrate that the relationship between stress and problem alcohol use is mediated by impulsivity, as reflected in monetary delay discounting rates, for those with high VS-low amygdala reactivity, and by anxious/depressive symptomatology for those with the opposite neural risk phenotype. Across both neural phenotypes, we found that greater divergence between VS and amygdala reactivity predicted greater risk for problem drinking. Finally, for those individuals with the low VS-high amygdala risk phenotype we found that stress not only predicted the presence of a DSM-IV diagnosed AUD at the time of neuroimaging, but also subsequent problem drinking reported three months following study completion. These results offer new insight into the neural basis of AUD risk and suggest novel biological targets for early individualized treatment or prevention. PMID:26122584

  18. Poorly studied phenomena in geoelectrics

    Directory of Open Access Journals (Sweden)

    В. С. Могилатов

    2016-12-01

    Full Text Available Undoubtedly, modern geoelectric technologies emerge in the result of the development of traditional approaches and techniques. However of more interest is the appearance of completely new technologies based on new effects and new models of interaction of geological medium and electromagnetic field. The author does not commit to indicate principally new directions, but only wants to discuss some poorly known facts from the theory and practice of geoelectrics. The outcome of this study could be considered attracting the attention of experts to non-traditional signals in geoelectrics. The reviewed phenomena of interest, not fully implemented in practice in the author’s opinion, are field split into two polarizations: transverse electric (the ТЕ-field and transverse magnetic (the ТМ-field, then some poorly known properties of ТМ-field, the role of bias currents, the anisotropy of horizontal resistances, the role of geomagnetic field in geoelectric sounding, the unique resolution of CSEM (Controlled Source Electro-Magnetic techniques at sea.

  19. Different Roles of Direct and Indirect Frontoparietal Pathways for Individual Working Memory Capacity.

    Science.gov (United States)

    Ekman, Matthias; Fiebach, Christian J; Melzer, Corina; Tittgemeyer, Marc; Derrfuss, Jan

    2016-03-09

    The ability to temporarily store and manipulate information in working memory is a hallmark of human intelligence and differs considerably across individuals, but the structural brain correlates underlying these differences in working memory capacity (WMC) are only poorly understood. In two separate studies, diffusion MRI data and WMC scores were collected for 70 and 109 healthy individuals. Using a combination of probabilistic tractography and network analysis of the white matter tracts, we examined whether structural brain network properties were predictive of individual WMC. Converging evidence from both studies showed that lateral prefrontal cortex and posterior parietal cortex of high-capacity individuals are more densely connected compared with low-capacity individuals. Importantly, our network approach was further able to dissociate putative functional roles associated with two different pathways connecting frontal and parietal regions: a corticocortical pathway and a subcortical pathway. In Study 1, where participants were required to maintain and update working memory items, the connectivity of the direct and indirect pathway was predictive of WMC. In contrast, in Study 2, where participants were required to maintain working memory items without updating, only the connectivity of the direct pathway was predictive of individual WMC. Our results suggest an important dissociation in the circuitry connecting frontal and parietal regions, where direct frontoparietal connections might support storage and maintenance, whereas subcortically mediated connections support the flexible updating of working memory content. Copyright © 2016 the authors 0270-6474/16/362894-10$15.00/0.

  20. EXTREMELY METAL-POOR GALAXIES: THE ENVIRONMENT

    Energy Technology Data Exchange (ETDEWEB)

    Filho, M. E. [Universidad de Las Palmas de Gran Canaria–Universidad de La Laguna, CIE Canarias: Tri-Continental Atlantic Campus, Canary Islands (Spain); Almeida, J. Sánchez; Muñoz-Tuñón, C. [Instituto Astrofísica de Canarias, E-38200 La Laguna, Tenerife (Spain); Nuza, S. E.; Kitaura, F.; Heß, S., E-mail: mfilho@astro.up.pt [Leibniz-Institut für Astrophysik Potsdam (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany)

    2015-04-01

    We have analyzed bibliographical observational data and theoretical predictions, in order to probe the environment in which extremely metal-poor dwarf galaxies (XMPs) reside. We have assessed the H i component and its relation to the optical galaxy, the cosmic web type (voids, sheets, filaments and knots), the overdensity parameter and analyzed the nearest galaxy neighbors. The aim is to understand the role of interactions and cosmological accretion flows in the XMP observational properties, particularly the triggering and feeding of the star formation. We find that XMPs behave similarly to Blue Compact Dwarfs; they preferably populate low-density environments in the local universe: ∼60% occupy underdense regions, and ∼75% reside in voids and sheets. This is more extreme than the distribution of irregular galaxies, and in contrast to those regions preferred by elliptical galaxies (knots and filaments). We further find results consistent with previous observations; while the environment does determine the fraction of a certain galaxy type, it does not determine the overall observational properties. With the exception of five documented cases (four sources with companions and one recent merger), XMPs do not generally show signatures of major mergers and interactions; we find only one XMP with a companion galaxy within a distance of 100 kpc, and the H i gas in XMPs is typically well-behaved, demonstrating asymmetries mostly in the outskirts. We conclude that metal-poor accretion flows may be driving the XMP evolution. Such cosmological accretion could explain all the major XMP observational properties: isolation, lack of interaction/merger signatures, asymmetric optical morphology, large amounts of unsettled, metal-poor H i gas, metallicity inhomogeneities, and large specific star formation.

  1. ComPath: comparative enzyme analysis and annotation in pathway/subsystem contexts

    Directory of Open Access Journals (Sweden)

    Kim Sun

    2008-03-01

    Full Text Available Abstract Background Once a new genome is sequenced, one of the important questions is to determine the presence and absence of biological pathways. Analysis of biological pathways in a genome is a complicated task since a number of biological entities are involved in pathways and biological pathways in different organisms are not identical. Computational pathway identification and analysis thus involves a number of computational tools and databases and typically done in comparison with pathways in other organisms. This computational requirement is much beyond the capability of biologists, so information systems for reconstructing, annotating, and analyzing biological pathways are much needed. We introduce a new comparative pathway analysis workbench, ComPath, which integrates various resources and computational tools using an interactive spreadsheet-style web interface for reliable pathway analyses. Results ComPath allows users to compare biological pathways in multiple genomes using a spreadsheet style web interface where various sequence-based analysis can be performed either to compare enzymes (e.g. sequence clustering and pathways (e.g. pathway hole identification, to search a genome for de novo prediction of enzymes, or to annotate a genome in comparison with reference genomes of choice. To fill in pathway holes or make de novo enzyme predictions, multiple computational methods such as FASTA, Whole-HMM, CSR-HMM (a method of our own introduced in this paper, and PDB-domain search are integrated in ComPath. Our experiments show that FASTA and CSR-HMM search methods generally outperform Whole-HMM and PDB-domain search methods in terms of sensitivity, but FASTA search performs poorly in terms of specificity, detecting more false positive as E-value cutoff increases. Overall, CSR-HMM search method performs best in terms of both sensitivity and specificity. Gene neighborhood and pathway neighborhood (global network visualization tools can be used

  2. Molecular Pathways

    Science.gov (United States)

    Lok, Benjamin H.; Powell, Simon N.

    2012-01-01

    The Rad52 protein was largely ignored in humans and other mammals when the mouse knockout revealed a largely “no-effect” phenotype. However, using synthetic lethal approaches to investigate context dependent function, new studies have shown that Rad52 plays a key survival role in cells lacking the function of the BRCA1-BRCA2 pathway of homologous recombination. Biochemical studies also showed significant differences between yeast and human Rad52, in which yeast Rad52 can promote strand invasion of RPA-coated single-stranded DNA in the presence of Rad51, but human Rad52 cannot. This results in the paradox of how is human Rad52 providing Rad51 function: presumably there is something missing in the biochemical assays that exists in-vivo, but the nature of this missing factor is currently unknown. Recent studies have suggested that Rad52 provides back-up Rad51 function for all members of the BRCA1-BRCA2 pathway, suggesting that Rad52 may be a target for therapy in BRCA pathway deficient cancers. Screening for ways to inhibit Rad52 would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to PARP inhibitors. PMID:23071261

  3. Pivotal role of the muscle-contraction pathway in cryptorchidism and evidence for genomic connections with cardiomyopathy pathways in RASopathies

    KAUST Repository

    Cannistraci, Carlo

    2013-02-14

    Background: Cryptorchidism is the most frequent congenital disorder in male children; however the genetic causes of cryptorchidism remain poorly investigated. Comparative integratomics combined with systems biology approach was employed to elucidate genetic factors and molecular pathways underlying testis descent. Methods. Literature mining was performed to collect genomic loci associated with cryptorchidism in seven mammalian species. Information regarding the collected candidate genes was stored in MySQL relational database. Genomic view of the loci was presented using Flash GViewer web tool (http://gmod.org/wiki/Flashgviewer/). DAVID Bioinformatics Resources 6.7 was used for pathway enrichment analysis. Cytoscape plug-in PiNGO 1.11 was employed for protein-network-based prediction of novel candidate genes. Relevant protein-protein interactions were confirmed and visualized using the STRING database (version 9.0). Results. The developed cryptorchidism gene atlas includes 217 candidate loci (genes, regions involved in chromosomal mutations, and copy number variations) identified at the genomic, transcriptomic, and proteomic level. Human orthologs of the collected candidate loci were presented using a genomic map viewer. The cryptorchidism gene atlas is freely available online: http://www.integratomics-time.com/cryptorchidism/. Pathway analysis suggested the presence of twelve enriched pathways associated with the list of 179 literature-derived candidate genes. Additionally, a list of 43 network-predicted novel candidate genes was significantly associated with four enriched pathways. Joint pathway analysis of the collected and predicted candidate genes revealed the pivotal importance of the muscle-contraction pathway in cryptorchidism and evidence for genomic associations with cardiomyopathy pathways in RASopathies. Conclusions: The developed gene atlas represents an important resource for the scientific community researching genetics of cryptorchidism. The

  4. Serving the world's poor, profitably.

    Science.gov (United States)

    Prahalad, C K; Hammond, Allen

    2002-09-01

    By stimulating commerce and development at the bottom of the economic pyramid, multi-nationals could radically improve the lives of billions of people and help create a more stable, less dangerous world. Achieving this goal does not require MNCs to spearhead global social-development initiatives for charitable purposes. They need only act in their own self-interest. How? The authors lay out the business case for entering the world's poorest markets. Fully 65% of the world's population earns less than $2,000 per year--that's 4 billion people. But despite the vastness of this market, it remains largely untapped. The reluctance to invest is easy to understand, but it is, by and large, based on outdated assumptions of the developing world. While individual incomes may be low, the aggregate buying power of poor communities is actually quite large, representing a substantial market in many countries for what some might consider luxury goods like satellite television and phone services. Prices, and margins, are often much higher in poor neighborhoods than in their middle-class counterparts. And new technologies are already steadily reducing the effects of corruption, illiteracy, inadequate infrastructure, and other such barriers. Because these markets are in the earliest stages of economic development, revenue growth for multi-nationals entering them can be extremely rapid. MNCs can also lower costs, not only through low-cost labor but by transferring operating efficiencies and innovations developed to serve their existing operations. Certainly, succeeding in such markets requires MNCs to think creatively. The biggest change, though, has to come from executives: Unless business leaders confront their own preconceptions--particularly about the value of high-volume, low-margin businesses--companies are unlikely to master the challenges or reap the rewards of these developing markets.

  5. Targeting Signaling Pathways in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Johannes Haybaeck

    2013-05-01

    Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies. Purpose: We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets. In Depth Review of Existing Data: In 2012, the vascular endothelial growth factor (VEGF inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR inhibitors, poly-ADP-ribose polymerase (PARP inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy. Conclusion: Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity.

  6. Prediction of compounds activity in nuclear receptor signaling and stress pathway assays using machine learning algorithms and low dimensional molecular descriptors

    Directory of Open Access Journals (Sweden)

    Filip eStefaniak

    2015-12-01

    Full Text Available Toxicity evaluation of newly synthesized or used compounds is one of the main challenges during product development in many areas of industry. For example, toxicity is the second reason - after lack of efficacy - for failure in preclinical and clinical studies of drug candidates. To avoid attrition at the late stage of the drug development process, the toxicity analyses are employed at the early stages of a discovery pipeline, along with activity and selectivity enhancing. Although many assays for screening in vitro toxicity are available, their massive application is not always time and cost effective. Thus the need for fast and reliable in silico tools, which can be used not only for toxicity prediction of existing compounds, but also for prioritization of compounds planned for synthesis or acquisition. Here I present the benchmark results of the combination of various attribute selection methods and machine learning algorithms and their application to the data sets of the Tox21 Data Challenge. The best performing method: Best First for attribute selection with the Rotation Forest/ADTree classifier offers good accuracy for most tested cases. For 11 out of 12 targets, the AUROC value for the final evaluation set was ≥0.72, while for three targets the AUROC value was ≥ 0.80, with the average AUROC being 0.784±0.069. The use of two-dimensional descriptors sets enables fast screening and compound prioritization even for a very large database. Open source tools used in this project make the presented approach widely available and encourage the community to further improve the presented scheme.

  7. Activated neuro-oxidative and neuro-nitrosative pathways at the end of term are associated with inflammation and physio-somatic and depression symptoms, while predicting outcome characteristics in mother and baby.

    Science.gov (United States)

    Roomruangwong, Chutima; Barbosa, Decio Sabbatini; Matsumoto, Andressa Keiko; Nogueira, André de Souza; Kanchanatawan, Buranee; Sirivichayakul, Sunee; Carvalho, André F; Duleu, Sebastien; Geffard, Michel; Moreira, Estefania Gastaldello; Maes, Michael

    2017-12-01

    To examine oxidative & nitrosative stress (O&NS) biomarkers at the end of term in relation to perinatal affective symptoms, neuro-immune biomarkers and pregnancy-related outcome variables. We measured plasma advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical trapping antioxidant parameter (TRAP), -sulfhydryl (-SH), peroxides (LOOH) and paraoxonase (PON)1 activity in pregnant women with and without prenatal depression and non-pregnant controls. Pregnancy is accompanied by significantly increased AOPP and NOx, and lowered TRAP, -SH and LOOH. Increased O&NS and lowered LOOH and -SH levels are associated with prenatal depressive and physio-somatic symptoms (fatigue, pain, dyspepsia, gastro-intestinal symptoms). Increased AOPP and NOx are significantly associated with lowered -SH, TRAP and zinc, and with increased haptoglobin and C-reactive protein levels. Increased O&NS and lowered TRAP and PON 1 activity, at the end of term predict mother (e.g. hyperpigmentation, labor duration, caesarian section, cord length, breast milk flow) and baby (e.g. sleep and feeding problems) outcome characteristics. Pregnancy is accompanied by interrelated signs of O&NS, lowered antioxidant defenses and activated neuro-immune pathways. Increased O&NS at the end of term is associated with perinatal depressive and physio-somatic symptoms and may predict obstetric and behavioral complications in mother and baby. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Network Expansion and Pathway Enrichment Analysis towards Biologically Significant Findings from Microarrays

    Directory of Open Access Journals (Sweden)

    Wu Xiaogang

    2012-06-01

    Full Text Available In many cases, crucial genes show relatively slight changes between groups of samples (e.g. normal vs. disease, and many genes selected from microarray differential analysis by measuring the expression level statistically are also poorly annotated and lack of biological significance. In this paper, we present an innovative approach - network expansion and pathway enrichment analysis (NEPEA for integrative microarray analysis. We assume that organized knowledge will help microarray data analysis in significant ways, and the organized knowledge could be represented as molecular interaction networks or biological pathways. Based on this hypothesis, we develop the NEPEA framework based on network expansion from the human annotated and predicted protein interaction (HAPPI database, and pathway enrichment from the human pathway database (HPD. We use a recently-published microarray dataset (GSE24215 related to insulin resistance and type 2 diabetes (T2D as case study, since this study provided a thorough experimental validation for both genes and pathways identified computationally from classical microarray analysis and pathway analysis. We perform our NEPEA analysis for this dataset based on the results from the classical microarray analysis to identify biologically significant genes and pathways. Our findings are not only consistent with the original findings mostly, but also obtained more supports from other literatures.

  9. Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.

    Science.gov (United States)

    Murlidhar, Vasudha; Reddy, Rishindra M; Fouladdel, Shamileh; Zhao, Lili; Ishikawa, Martin K; Grabauskiene, Svetlana; Zhang, Zhuo; Lin, Jules; Chang, Andrew C; Carrott, Philip; Lynch, William R; Orringer, Mark B; Kumar-Sinha, Chandan; Palanisamy, Nallasivam; Beer, David G; Wicha, Max S; Ramnath, Nithya; Azizi, Ebrahim; Nagrath, Sunitha

    2017-09-15

    Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe ( P ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. Pro Poor Growth in Cameroon

    Directory of Open Access Journals (Sweden)

    Samuel Fambon

    2017-06-01

    Full Text Available The purpose of this paper is to analyze the relationship between economic growth, poverty and income distribution in Cameroon, using both the data derived from three Cameroonian household surveys and the Poverty Equivalent Growth Rate (PEGR methodology developed by Kakwani et al. (2004, The study found that economic growth in Cameroon was pro poor over the period 1996–2007, which suggests that instead of increasing the economic growth rate alone, the poverty equivalent growth rate should also be maximized to achieve the poverty reduction objective, meaning that on the one hand, the growth rate should be boosted, and on the other, the distribution of income should also be concurrently improved. A decomposition of changes in poverty using the Kakwani (1997 approach reveal that the growth component dominates the redistribution component in the reduction of poverty. This suggests that the fall in absolute poverty over the survey period may be attributed to an increase in average household income, and not to the redistributive policies of the government.

  11. Sensorimotor Mismapping in Poor-pitch Singing.

    Science.gov (United States)

    He, Hao; Zhang, Wei-Dong

    2017-09-01

    This study proposes that there are two types of sensorimotor mismapping in poor-pitch singing: erroneous mapping and no mapping. We created operational definitions for the two types of mismapping based on the precision of pitch-matching and predicted that in the two types of mismapping, phonation differs in terms of accuracy and the dependence on the articulation consistency between the target and the intended vocal action. The study aimed to test this hypothesis by examining the reliability and criterion-related validity of the operational definitions. A within-subject design was used in this study. Thirty-two participants identified as poor-pitch singers were instructed to vocally imitate pure tones and to imitate their own vocal recordings with the same articulation as self-targets and with different articulation from self-targets. Definitions of the types of mismapping were demonstrated to be reliable with the split-half approach and to have good criterion-related validity with findings that pitch-matching with no mapping was less accurate and more dependent on the articulation consistency between the target and the intended vocal action than pitch-matching with erroneous mapping was. Furthermore, the precision of pitch-matching was positively associated with its accuracy and its dependence on articulation consistency when mismapping was analyzed on a continuum. Additionally, the data indicated that the self-imitation advantage was a function of articulation consistency. Types of sensorimotor mismapping lead to pitch-matching that differs in accuracy and its dependence on the articulation consistency between the target and the intended vocal action. Additionally, articulation consistency produces the self-advantage. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  12. The Reactome pathway knowledgebase.

    Science.gov (United States)

    Croft, David; Mundo, Antonio Fabregat; Haw, Robin; Milacic, Marija; Weiser, Joel; Wu, Guanming; Caudy, Michael; Garapati, Phani; Gillespie, Marc; Kamdar, Maulik R; Jassal, Bijay; Jupe, Steven; Matthews, Lisa; May, Bruce; Palatnik, Stanislav; Rothfels, Karen; Shamovsky, Veronica; Song, Heeyeon; Williams, Mark; Birney, Ewan; Hermjakob, Henning; Stein, Lincoln; D'Eustachio, Peter

    2014-01-01

    Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation.

  13. Validation of models using Chernobyl fallout data from the Central Bohemia region of the Czech Republic. Scenario CB. First report of the VAMP Multiple Pathways Assessment Working Group. Part of the IAEA/CEC Co-ordinated Research Programme on the Validation of Environmental Model Predictions (VAMP)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-04-01

    The VAMP Multiple Pathways Assessment Working Group is an international forum for the testing and comparison of model predictions. The emphasis is on evaluating transfer from the environment to human via all pathways which are relevant in the environment being considered. This document is the first report of the Group and contains the results of the first test exercise on the validation of multiple pathways assessment models using Chernobyl fallout data obtained from the Central Bohemia (CB) region of the Czech Republic (Scenario CB). The report includes the following three appendixes: Documentation and evaluation of model validation data used in scenario CB (3 papers), Description of models used in scenario CB (1 paper), Individual evaluations of model predictions for scenario CB (13 papers). A separate abstract was prepared for each paper. Refs, figs and tabs.

  14. Validation of models using Chernobyl fallout data from the Central Bohemia region of the Czech Republic. Scenario CB. First report of the VAMP Multiple Pathways Assessment Working Group. Part of the IAEA/CEC Co-ordinated Research Programme on the Validation of Environmental Model Predictions (VAMP)

    International Nuclear Information System (INIS)

    1995-04-01

    The VAMP Multiple Pathways Assessment Working Group is an international forum for the testing and comparison of model predictions. The emphasis is on evaluating transfer from the environment to human via all pathways which are relevant in the environment being considered. This document is the first report of the Group and contains the results of the first test exercise on the validation of multiple pathways assessment models using Chernobyl fallout data obtained from the Central Bohemia (CB) region of the Czech Republic (Scenario CB). The report includes the following three appendixes: Documentation and evaluation of model validation data used in scenario CB (3 papers), Description of models used in scenario CB (1 paper), Individual evaluations of model predictions for scenario CB (13 papers). A separate abstract was prepared for each paper. Refs, figs and tabs

  15. Pro-poor growth and gender inequality

    OpenAIRE

    Klasen, Stephan

    2006-01-01

    This paper examines to what extent gender gaps in education, health, employment, productive assets and inputs can affect pro poor growth (in the sense of increasing monetary incomes of the poor). After discussing serious methodological problems with examining gender issues in the context of an income-based pro-poor growth framework, the paper considers theory and evidence on the impact of gender inequality on pro poor growth. While there is a considerable literature suggesting negative impact...

  16. Identifying pathways affected by cancer mutations.

    Science.gov (United States)

    Iengar, Prathima

    2017-12-16

    Mutations in 15 cancers, sourced from the COSMIC Whole Genomes database, and 297 human pathways, arranged into pathway groups based on the processes they orchestrate, and sourced from the KEGG pathway database, have together been used to identify pathways affected by cancer mutations. Genes studied in ≥15, and mutated in ≥10 samples of a cancer have been considered recurrently mutated, and pathways with recurrently mutated genes have been considered affected in the cancer. Novel doughnut plots have been presented which enable visualization of the extent to which pathways and genes, in each pathway group, are targeted, in each cancer. The 'organismal systems' pathway group (including organism-level pathways; e.g., nervous system) is the most targeted, more than even the well-recognized signal transduction, cell-cycle and apoptosis, and DNA repair pathway groups. The important, yet poorly-recognized, role played by the group merits attention. Pathways affected in ≥7 cancers yielded insights into processes affected. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Applying adverse outcome pathways and species sensitivity-weighted distribution to predicted-no-effect concentration derivation and quantitative ecological risk assessment for bisphenol A and 4-nonylphenol in aquatic environments: A case study on Tianjin City, China.

    Science.gov (United States)

    Wang, Ying; Na, Guangshui; Zong, Humin; Ma, Xindong; Yang, Xianhai; Mu, Jingli; Wang, Lijun; Lin, Zhongsheng; Zhang, Zhifeng; Wang, Juying; Zhao, Jinsong

    2018-02-01

    Adverse outcome pathways (AOPs) are a novel concept that effectively considers the toxic modes of action and guides the ecological risk assessment of chemicals. To better use toxicity data including biochemical or molecular responses and mechanistic data, we further developed a species sensitivity-weighted distribution (SSWD) method for bisphenol A and 4-nonylphenol. Their aquatic predicted-no-effect concentrations (PNECs) were derived using the log-normal statistical extrapolation method. We calculated aquatic PNECs of bisphenol A and 4-nonylphenol with values of 4.01 and 0.721 µg/L, respectively. The ecological risk of each chemical in different aquatic environments near Tianjin, China, a coastal municipality along the Bohai Sea, was characterized by hazard quotient and probabilistic risk quotient assessment techniques. Hazard quotients of 7.02 and 5.99 at 2 municipal sewage sites using all of the endpoints were observed for 4-nonylphenol, which indicated high ecological risks posed by 4-nonylphenol to aquatic organisms, especially endocrine-disrupting effects. Moreover, a high ecological risk of 4-nonylphenol was indicated based on the probabilistic risk quotient method. The present results show that combining the SSWD method and the AOP concept could better protect aquatic organisms from adverse effects such as endocrine disruption and could decrease uncertainty in ecological risk assessment. Environ Toxicol Chem 2018;37:551-562. © 2017 SETAC. © 2017 SETAC.

  18. The long-term effects of maternal depression: early childhood physical health as a pathway to offspring depression.

    Science.gov (United States)

    Raposa, Elizabeth; Hammen, Constance; Brennan, Patricia; Najman, Jake

    2014-01-01

    Cross-sectional and retrospective studies have highlighted the long-term negative effects of maternal depression on offspring physical, social, and emotional development, but longitudinal research is needed to clarify the pathways by which maternal depression during pregnancy and early childhood affects offspring outcomes. The current study tested one developmental pathway by which maternal depression during pregnancy might negatively impact offspring mental health in young adulthood, via poor physical health in early childhood. The sample consisted of 815 Australian youth and their mothers who were followed for 20 years. Mothers reported on their own depressive symptoms during pregnancy and offspring early childhood. Youth completed interviews about health-related stress and social functioning at age 20 years, and completed a questionnaire about their own depressive symptoms 2 to 5 years later. Path analysis indicated that prenatal maternal depressive symptoms predicted worse physical health during early childhood for offspring, and this effect was partially explained by ongoing maternal depression in early childhood. Offspring poor physical health during childhood predicted increased health-related stress and poor social functioning at age 20. Finally, increased health-related stress and poor social functioning predicted increased levels of depressive symptoms later in young adulthood. Maternal depression had a significant total indirect effect on youth depression via early childhood health and its psychosocial consequences. Poor physical health in early childhood and its effects on young adults' social functioning and levels of health related stress is one important pathway by which maternal depression has long-term consequences for offspring mental health. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  19. Mapping onto Eq-5 D for patients in poor health

    Directory of Open Access Journals (Sweden)

    Brazier John E

    2010-11-01

    Full Text Available Abstract Background An increasing amount of studies report mapping algorithms which predict EQ-5 D utility values using disease specific non-preference-based measures. Yet many mapping algorithms have been found to systematically overpredict EQ-5 D utility values for patients in poor health. Currently there are no guidelines on how to deal with this problem. This paper is concerned with the question of why overestimation of EQ-5 D utility values occurs for patients in poor health, and explores possible solutions. Method Three existing datasets are used to estimate mapping algorithms and assess existing mapping algorithms from the literature mapping the cancer-specific EORTC-QLQ C-30 and the arthritis-specific Health Assessment Questionnaire (HAQ onto the EQ-5 D. Separate mapping algorithms are estimated for poor health states. Poor health states are defined using a cut-off point for QLQ-C30 and HAQ, which is determined using association with EQ-5 D values. Results All mapping algorithms suffer from overprediction of utility values for patients in poor health. The large decrement of reporting 'extreme problems' in the EQ-5 D tariff, few observations with the most severe level in any EQ-5 D dimension and many observations at the least severe level in any EQ-5 D dimension led to a bimodal distribution of EQ-5 D index values, which is related to the overprediction of utility values for patients in poor health. Separate algorithms are here proposed to predict utility values for patients in poor health, where these are selected using cut-off points for HAQ-DI (> 2.0 and QLQ C-30 ( Conclusion Mapping algorithms overpredict utility values for patients in poor health but are used in cost-effectiveness analyses nonetheless. Guidelines can be developed on when the use of a mapping algorithms is inappropriate, for instance through the identification of cut-off points. Cut-off points on a disease specific questionnaire can be identified through association

  20. What characterizes persons with poor mental health?

    DEFF Research Database (Denmark)

    Christensen, Anne Illemann; Davidsen, Michael; Kjøller, Mette

    2014-01-01

    analysed by means of logistic regression models. Results: Men and women with poor mental health are characterized by being single, having a long-term illness, not being able to rely on help from others in case of illness and by feeling that family and friends demand too much of them. Men with poor mental...... health were further characterized by being a heavy smoker, and having a BMI below 25. Women with poor mental health were further characterized by being 16-44 years old and sedentary in leisure time. CONCLUSIONS THE PREVALENCE OF POOR MENTAL HEALTH IS HIGHER AMONG WOMEN THAN MEN, AND DIFFERENT FACTORS...... CHARACTERIZE MEN AND WOMEN WITH POOR MENTAL HEALTH THE PRESENT FINDINGS SUPPORT THE NOTION THAT BOTH SOCIO-DEMOGRAPHICS AND LIFESTYLE FACTORS ARE INDEPENDENTLY RELATED WITH POOR MENTAL HEALTH WE SUGGEST TAKING INTO ACCOUNT ALL THESE AREAS OF LIFE WHEN PLANNING ACTIVITIES TO PREVENT POOR MENTAL HEALTH AND WHEN...

  1. Metabolic pathways for the whole community.

    Science.gov (United States)

    Hanson, Niels W; Konwar, Kishori M; Hawley, Alyse K; Altman, Tomer; Karp, Peter D; Hallam, Steven J

    2014-07-22

    A convergence of high-throughput sequencing and computational power is transforming biology into information science. Despite these technological advances, converting bits and bytes of sequence information into meaningful insights remains a challenging enterprise. Biological systems operate on multiple hierarchical levels from genomes to biomes. Holistic understanding of biological systems requires agile software tools that permit comparative analyses across multiple information levels (DNA, RNA, protein, and metabolites) to identify emergent properties, diagnose system states, or predict responses to environmental change. Here we adopt the MetaPathways annotation and analysis pipeline and Pathway Tools to construct environmental pathway/genome databases (ePGDBs) that describe microbial community metabolism using MetaCyc, a highly curated database of metabolic pathways and components covering all domains of life. We evaluate Pathway Tools' performance on three datasets with different complexity and coding potential, including simulated metagenomes, a symbiotic system, and the Hawaii Ocean Time-series. We define accuracy and sensitivity relationships between read length, coverage and pathway recovery and evaluate the impact of taxonomic pruning on ePGDB construction and interpretation. Resulting ePGDBs provide interactive metabolic maps, predict emergent metabolic pathways associated with biosynthesis and energy production and differentiate between genomic potential and phenotypic expression across defined environmental gradients. This multi-tiered analysis provides the user community with specific operating guidelines, performance metrics and prediction hazards for more reliable ePGDB construction and interpretation. Moreover, it demonstrates the power of Pathway Tools in predicting metabolic interactions in natural and engineered ecosystems.

  2. Elucidating poor decision-making in a rat gambling task.

    Directory of Open Access Journals (Sweden)

    Marion Rivalan

    Full Text Available Although poor decision-making is a hallmark of psychiatric conditions such as attention deficit/hyperactivity disorder, pathological gambling or substance abuse, a fraction of healthy individuals exhibit similar poor decision-making performances in everyday life and specific laboratory tasks such as the Iowa Gambling Task. These particular individuals may provide information on risk factors or common endophenotypes of these mental disorders. In a rodent version of the Iowa gambling task--the Rat Gambling Task (RGT, we identified a population of poor decision makers, and assessed how these rats scored for several behavioral traits relevant to executive disorders: risk taking, reward seeking, behavioral inflexibility, and several aspects of impulsivity. First, we found that poor decision-making could not be well predicted by single behavioral and cognitive characteristics when considered separately. By contrast, a combination of independent traits in the same individual, namely risk taking, reward seeking, behavioral inflexibility, as well as motor impulsivity, was highly predictive of poor decision-making. Second, using a reinforcement-learning model of the RGT, we confirmed that only the combination of extreme scores on these traits could induce maladaptive decision-making. Third, the model suggested that a combination of these behavioral traits results in an inaccurate representation of rewards and penalties and inefficient learning of the environment. Poor decision-making appears as a consequence of the over-valuation of high-reward-high-risk options in the task. Such a specific psychological profile could greatly impair clinically healthy individuals in decision-making tasks and may predispose to mental disorders with similar symptoms.

  3. High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zijian; Huang, Shanzhou [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Wang, Huanyu [Department of Thyroid and Breast Surgery, Nanshan District People’s Hospital, Shenzhen, 518000 (China); Wu, Jian [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Chen, Dong [Department of Biliopancreatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Peng, Baogang [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Zhou, Qi, E-mail: hnzhouqi@163.com [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China)

    2016-06-10

    Rapid progress and metastasis remain the major treatment failure modes of hepatocarcinoma (HCC). Unfortunately, the underlying molecular mechanisms of hepatoma cell proliferation and migration are poorly understood. Metabolic abnormalities play critical roles in tumorigenesis and progression. Hexokinase domain containing 1 (HKDC1) catalyzes the phosphorylation of glucose. However, the functions and mechanisms of HKDC1 in cancer remain unknown. In this study, real-time RT-PCR and Western blotting assays were used to detect the HKDC1 expression levels in HCC tissues and cell lines. The Oncomine™ Cancer Microarray Database was applied to analysis the correlations between HKDC1 expression and HCC clinical characteristics. MTT and Transwell migration assays were performed to determine the functions of HKDC1 in HCC cells. The effect of HKDC1 on Wnt/β-catenin signaling pathway was assessed using Western blotting assay. In this study, we found that HKDC1 expression levels were elevated in HCC tissues compared with the adjacent tissues. HCC patients with high expression levels of HKDC1 had poor overall survival (OS). Furthermore, higher HKDC1 levels also predicted a worse OS of patients within solitary, elevated pre-operated serum alpha fetoprotein (AFP) level and higher tumor diameter. Moreover, silencing HKDC1 suppressed HCC cells proliferation and migration in vitro. Downregulated HKDC1 expression repressed β-Catenin and c-Myc expression, which indicates that silencing HKDC1 may reduce proliferation and migration via inhibiting the Wnt/β-catenin signaling pathway in HCC. In summary, HKDC1 provides further insight into HCC tumor progression and may provide a novel prognostic biomarker and therapeutic target for HCC treatment. -- Highlights: •HKDC1 is upregulated in HCC. •Patients with high HKDC1 expressions perform worse OS. •Silencing HKDC1 suppresses proliferation and migration. •Silencing HKDC1 represses Wnt/β-catenin signaling pathway.

  4. High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma

    International Nuclear Information System (INIS)

    Zhang, Zijian; Huang, Shanzhou; Wang, Huanyu; Wu, Jian; Chen, Dong; Peng, Baogang; Zhou, Qi

    2016-01-01

    Rapid progress and metastasis remain the major treatment failure modes of hepatocarcinoma (HCC). Unfortunately, the underlying molecular mechanisms of hepatoma cell proliferation and migration are poorly understood. Metabolic abnormalities play critical roles in tumorigenesis and progression. Hexokinase domain containing 1 (HKDC1) catalyzes the phosphorylation of glucose. However, the functions and mechanisms of HKDC1 in cancer remain unknown. In this study, real-time RT-PCR and Western blotting assays were used to detect the HKDC1 expression levels in HCC tissues and cell lines. The Oncomine™ Cancer Microarray Database was applied to analysis the correlations between HKDC1 expression and HCC clinical characteristics. MTT and Transwell migration assays were performed to determine the functions of HKDC1 in HCC cells. The effect of HKDC1 on Wnt/β-catenin signaling pathway was assessed using Western blotting assay. In this study, we found that HKDC1 expression levels were elevated in HCC tissues compared with the adjacent tissues. HCC patients with high expression levels of HKDC1 had poor overall survival (OS). Furthermore, higher HKDC1 levels also predicted a worse OS of patients within solitary, elevated pre-operated serum alpha fetoprotein (AFP) level and higher tumor diameter. Moreover, silencing HKDC1 suppressed HCC cells proliferation and migration in vitro. Downregulated HKDC1 expression repressed β-Catenin and c-Myc expression, which indicates that silencing HKDC1 may reduce proliferation and migration via inhibiting the Wnt/β-catenin signaling pathway in HCC. In summary, HKDC1 provides further insight into HCC tumor progression and may provide a novel prognostic biomarker and therapeutic target for HCC treatment. -- Highlights: •HKDC1 is upregulated in HCC. •Patients with high HKDC1 expressions perform worse OS. •Silencing HKDC1 suppresses proliferation and migration. •Silencing HKDC1 represses Wnt/β-catenin signaling pathway.

  5. A geographically-diverse collection of 418 human gut microbiome pathway genome databases

    KAUST Repository

    Hahn, Aria S.; Altman, Tomer; Konwar, Kishori M.; Hanson, Niels W.; Kim, Dongjae; Relman, David A.; Dill, David L.; Hallam, Steven J.

    2017-01-01

    the Pathway Tools software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GutCyc provides consistent annotations and metabolic pathway predictions

  6. Three-dimensional models of metal-poor stars

    OpenAIRE

    Collet, R.

    2008-01-01

    I present here the main results of recent realistic, 3D, hydrodynamical simulations of convection at the surface of metal-poor red giant stars. I discuss the application of these convection simulations as time-dependent, 3D, hydrodynamical model atmospheres to spectral line formation calculations and abundance analyses. The impact of 3D models on derived elemental abundances is investigated by means of a differential comparison of the line strengths predicted in 3D under the assumption of loc...

  7. Nanosuspension Technology for Solubilizing Poorly Soluble Drugs

    OpenAIRE

    Deoli Mukesh

    2012-01-01

    Poor water solubility for many drugs and drug candidates remains a major obstacle to their development and clinical application. It is estimated that around 40% of drugs in the pipeline cannot be delivered through the preferred route or in some cases, at all owing to poor water solubility. Conventional formulations to improve solubility suffer from low bioavailability and poor pharmacokinetics, with some carriers rendering systemic toxicities (e.g. Cremophor1 EL). To date, nanoscale systems f...

  8. Pathway Distiller - multisource biological pathway consolidation.

    Science.gov (United States)

    Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

    2012-01-01

    One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

  9. Method for determining heterologous biosynthesis pathways

    KAUST Repository

    Gao, Xin

    2017-08-10

    The present invention relates to a method and system for dynamically analyzing, determining, predicting and displaying ranked suitable heterologous biosynthesis pathways for a specified host. The present invention addresses the problem of finding suitable pathways for the endogenous metabolism of a host organism because the efficacy of heterologous biosynthesis is affected by competing endogenous pathways. The present invention is called MRE (Metabolic Route Explorer), and it was conceived and developed to systematically and dynamically search for, determine, analyze, and display promising heterologous pathways while considering competing endogenous reactions in a given host organism.

  10. Different forms of effective connectivity in primate frontotemporal pathways.

    Science.gov (United States)

    Petkov, Christopher I; Kikuchi, Yukiko; Milne, Alice E; Mishkin, Mortimer; Rauschecker, Josef P; Logothetis, Nikos K

    2015-01-23

    It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex.

  11. Exposures from aquatic pathways

    International Nuclear Information System (INIS)

    Berkovski, V.; Voitsekhovitch, O.; Nasvit, O.; Zhelezniak, M.; Sansone, U.

    1996-01-01

    Methods for estimation aquatic pathways contribution to the total population exposure are discussed. Aquatic pathways are the major factor for radionuclides spreading from the Chernobyl Exclusion zone. An annual outflow of 90 Sr and 137 Cs comprised 10-20 TBq and 2-4 TBq respectively and the population exposed by this effluence constitutes almost 30 million people. The dynamic of doses from 90 Sr and ' C s, which Dnieper water have to delivered, is calculated. The special software has been developed to simulate the process of dose formation in the of diverse Dnieper regions. Regional peculiarities of municipal tap, fishing and irrigation are considered. Seventy-year prediction of dose structure and function of dose forming is performed. The exposure is estimated for 12 regions of the Dnieper basin and the Crimea. The maximal individual annual committed effective doses due to the use of water by ordinary members of the population in Kiev region from 90 Sr and 137 Cs in 1986 are 1.7*10 -5 Sv and 2.7*10 -5 Sv respectively. A commercial fisherman on Kiev reservoir in 1986 received 4.7*10 -4 Sv and 5*10 -3 Sv from 90 Sr and 137 Cs, respectively. The contributions to the collective cumulative (over 70 years) committed effective dose (CCCED 70 ) of irrigation, municipal tap water and fish consumption for members of the population respectively are 18%, 43%, 39% in Kiev region, 8%, 25%, 67% in Poltava region, and 50%, 50%, 0% (consumption of Dnieper fish is absent) in the Crimea. The predicted contribution of the Strontium-90 to CCCED 70 resulting from the use of water is 80%. The CCCED 70 to the population of the Dnieper regions (32.5 million people) is 3000 person-Sv due to the use the Dnieper water

  12. Is It Lateralization, Processing Strategies, or Both That Distinguishes Good And Poor Readers?

    Science.gov (United States)

    Watson, E. Selman; Engle, Randall W.

    1982-01-01

    Two experiments investigated whether poor readers eventually establish a dichotic right ear advantage as predicted by a maturational lag theory. The first studied developmental differences in dichotic listening for normal and poor readers when the order of reporting simultaneously presented items was unconstrained; the second controlled for order…

  13. Factors associated with poor sleep during menopause: results from the Midlife Women's Health Study.

    Science.gov (United States)

    Smith, Rebecca L; Flaws, Jodi A; Mahoney, Megan M

    2018-05-01

    Poor sleep is one of the most common problems reported during menopause, and is known to vary throughout the menopause transition. The objective of this study was to describe the dynamics of poor sleep among participants of the Midlife Women's Health Study and to identify risk factors associated with poor sleep during the menopausal transition. Annual responses to surveys that included questions about the frequency of sleep disturbances and insomnia were analyzed to determine the likelihood of persistent poor sleep throughout the menopausal transition and the correlation of responses to the different sleep-related questions, including frequency of restless sleep during the first year of the study. Responses to questions about a large number of potential risk factors were used to identify risk factors for poor sleep. Poor sleep in premenopause was not predictive of poor sleep in perimenopause, and poor sleep in perimenopause was not predictive of poor sleep in postmenopause. Frequencies of each of the measures of poor sleep were highly correlated. For all sleep outcomes, high frequency of depression was related to a high frequency of poor sleep. Vasomotor symptoms were also significantly related with a higher frequency of all poor sleep outcomes. A history of smoking was also associated with higher frequencies of insomnia and sleep disturbances. The risk factors identified for poor sleep, depression and vasomotor symptoms, were consistently associated with poor sleep throughout the menopausal transition. The likelihood of these risk factors changed from premenopause, through perimenopause, and into postmenopause, however, which could explain changes in sleep difficulties across the menopausal transition. Treatment of these risk factors should be considered when addressing sleep difficulties in menopausal women. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Henoch schonlein purpura--a 5-year review and proposed pathway.

    Directory of Open Access Journals (Sweden)

    Louise Watson

    Full Text Available Henoch Schonlein Purpura (HSP is the commonest systemic vasculitis of childhood typically presenting with a palpable purpuric rash and frequently involving the renal system. We are the first group to clinically assess, critically analyse and subsequently revise a nurse led monitoring pathway for this condition.A cohort of 102 children presenting with HSP to a secondary/tertiary level UK paediatric hospital over a five year period, were monitored using a nurse led care pathway. Using this cohort, the incidence (6.21 cases per 100,000 children per year and natural disease course of HSP nephritis (46% initial renal inflammation; 9% subsequent renal referral; 1% renal biopsy and immunosuppression was determined. Older patients were at higher risk of requiring a renal referral (renal referral 12.3 (8.4-13.5 years vs. normal outcome 6.0 (3.7-8.5 years; p<0.01. A normal urinalysis on day 7 had a 97% (confidence interval 90 to 99% negative predictive value in predicting a normal renal outcome.Using this data and existing literature base, The Alder Hey Henoch Schonlein Purpura Pathway was developed, a revised pathway for the screening of poor renal outcome in HSP. This is based on a six-month monitoring period for all patients presenting with HSP, which importantly prioritises patients according to the urine findings on day 7 and thus intensively monitors those at higher risk of developing nephritis. The pathway could be easily adapted for use in different settings and resources.The introduction of a standardised pathway for the monitoring of HSP will facilitate the implementation of disease registries to further our understanding of the condition and permit future clinical trials.

  15. A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.

    Directory of Open Access Journals (Sweden)

    Timothy G Lesnick

    2007-06-01

    Full Text Available While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics. The goal of this study was to determine whether polymorphism in a candidate pathway (axon guidance predisposed to a complex disease (Parkinson disease [PD]. We mined a whole-genome association dataset and identified single nucleotide polymorphisms (SNPs that were within axon-guidance pathway genes. We then constructed models of axon-guidance pathway SNPs that predicted three outcomes: PD susceptibility (odds ratio = 90.8, p = 4.64 x 10(-38, survival free of PD (hazards ratio = 19.0, p = 5.43 x 10(-48, and PD age at onset (R(2 = 0.68, p = 1.68 x 10(-51. By contrast, models constructed from thousands of random selections of genomic SNPs predicted the three PD outcomes poorly. Mining of a second whole-genome association dataset and mining of an expression profiling dataset also supported a role for many axon-guidance pathway genes in PD. These findings could have important implications regarding the pathogenesis of PD. This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers.

  16. Childhood maltreatment and adulthood poor sleep quality: a longitudinal study.

    Science.gov (United States)

    Abajobir, Amanuel A; Kisely, Steve; Williams, Gail; Strathearn, Lane; Najman, Jake M

    2017-08-01

    Available evidence from cross-sectional studies suggests that childhood maltreatment may be associated with a range of sleep disorders. However, these studies have not controlled for potential individual-, familial- and environmental-level confounders. To determine the association between childhood maltreatment and lower sleep quality after adjusting for potential confounders. Data for the present study were obtained from a pre-birth cohort study of 3778 young adults (52.6% female) of the Mater Hospital-University of Queensland Study of Pregnancy follow up at a mean age of 20.6 years. The Mater Hospital-University of Queensland Study of Pregnancy is a prospective Australian pre-birth cohort study of mothers consecutively recruited during their first obstetric clinic visit at Brisbane's Mater Hospital in 1981-1983. Participants completed the Pittsburgh Sleep Quality Index at the 21-year follow up. We linked this dataset to agency-recorded substantiated cases of childhood maltreatment. A series of separate logistic regression models was used to test whether childhood maltreatment predicted lower sleep quality after adjustment for selected confounders. Substantiated physical abuse significantly predicted lower sleep quality in males. Single and multiple forms of childhood maltreatment, including age of maltreatment and number of substantiations, did not predict lower sleep quality in either gender in both crude and adjusted models. Not being married, living in a residential problem area, cigarette smoking and internalising were significantly associated with lower sleep quality in a fully adjusted model for the male-female combined sample. Childhood maltreatment does not appear to predict young adult poor sleep quality, with the exception of physical abuse for males. While childhood maltreatment has been found to predict a range of mental health problems, childhood maltreatment does not appear to predict sleep problems occurring in young adults. Poor sleep quality was

  17. Three-dimensional models of metal-poor stars

    International Nuclear Information System (INIS)

    Collet, R

    2008-01-01

    I present here the main results of recent realistic, three-dimensional (3D), hydrodynamical simulations of convection at the surface of metal-poor red giant stars. I discuss the application of these convection simulations as time-dependent, 3D, hydrodynamical model atmospheres to spectral line formation calculations and abundance analyses. The impact of 3D models on derived elemental abundances is investigated by means of a differential comparison of the line strengths predicted in 3D under the assumption of local thermodynamic equilibrium (LTE) with the results of analogous line formation calculations performed with classical, 1D, hydrostatic model atmospheres. The low surface temperatures encountered in the upper photospheric layers of 3D model atmospheres of very metal-poor stars cause spectral lines of neutral metals and molecules to appear stronger in 3D than in 1D calculations. Hence, 3D elemental abundances derived from such lines are significantly lower than estimated by analyses with 1D models. In particular, differential 3D-1D LTE abundances for C, N and O derived from CH, NH and OH lines are found to be in the range -0.5 to - 1 dex. Large negative differential 3D-1D corrections to the Fe abundance are also computed for weak low-excitation Fe i lines. The application of metal-poor 3D models to the spectroscopic analysis of extremely iron-poor halo stars is discussed.

  18. Mongo Beti's The Poor Christ of Bomba

    African Journals Online (AJOL)

    2016-03-28

    Mar 28, 2016 ... discovered the Harlem Renaissance Movement or New Negro Movement ... Beti picks up as a subject for his satire in The Poor Christ of Bomba. ..... slave driver, and the indigenous man into an instrument of production” (6).

  19. Prospective associations of social isolation and loneliness with poor sleep quality in older adults.

    Science.gov (United States)

    Yu, Bin; Steptoe, Andrew; Niu, Kaijun; Ku, Po-Wen; Chen, Li-Jung

    2018-03-01

    There is evidence for negative associations between social isolation and loneliness and sleep quality in older adults. However, it is unclear to what extent these two factors independently affect sleep quality. This study examined the simultaneous associations of social isolation and loneliness with sleep quality in a longitudinal study of older adults. Data were analyzed from the Social Environment and Biomarkers of Aging Study in Taiwan collected in 2000 and 2006, involving a cohort of 639 participants (mean age = 66.14, SD 7.26). Poisson regression models were conducted to examine the association of social isolation and/or loneliness with sleep quality at follow-up after adjusting for multiple confounding variables. Univariate analysis showed that sleep quality was inversely associated with both social isolation and loneliness. After demographic, health, cognitive factors, and depressive symptoms were controlled in multivariable analysis, social isolation at the baseline still predicted poor sleep quality 6 years later (incident rate ratio, IRR 1.14; 95% CI 1.04-1.24; p social isolation on the sleep quality of older adults, but indicate that this effect is independent of loneliness. Social isolation and loneliness seem to have distinct pathways in affecting the sleep quality of older adults.

  20. Where are the poor in International Economics?

    OpenAIRE

    Luis Carvalho; Aurora A.C. Teixeira

    2011-01-01

    Despite the fact that a very significant proportion of the human population is living with financial difficulties and other constraints typical of poverty, scientific studies in the areas of Economics and especially in International Economics that address the issue of poverty and of poor countries are very few. Using bibliometric techniques, we measured the attention paid by authors from the field of International Economics to poverty and poor countries. To this end, we sorted and analyzed al...

  1. Hydrogen-Poor Core-Collapse Supernovae

    Science.gov (United States)

    Pian, Elena; Mazzali, Paolo A.

    Hydrogen-poor core-collapse supernovae (SNe) signal the explosive death of stars more massive than the progenitors of hydrogen-rich core-collapse supernovae, i.e., approximately in the range 15-50 M⊙ in main sequence. Since hydrogen-poor core-collapse supernovae include those that accompany gamma-ray bursts (GRBs), which were all rigorously identified with type Ic supernovae, their explosion energies cover almost two decades. The light curves and spectra are consequently very heterogeneous and often bear the signature of an asymmetric, i.e., aspherical, explosion. Asphericity is best traced by early-time (within days of the explosion) optical spectropolarimetry and by late-epoch (more than ˜ 100 days after explosion) low-resolution spectroscopy. While the relationship between hydrogen-poor core-collapse supernovae to hydrogen-poor super-luminous supernovae is not understood, a known case of association between an ultra-long gamma-ray burst and a very luminous hydrogen-poor supernova may help unraveling the connection. This is tantalizingly pointing to a magnetar powering source for both phenomena, although this scenario is still highly speculative. Host galaxies of hydrogen-poor supernovae are always star forming; in those of completely stripped supernovae and gamma-ray burst supernovae, the spatial distribution of the explosions follows the blue/ultraviolet light, with a correlation that is more than linear.

  2. Management of metastatic renal cell carcinoma in patients with poor prognosis

    International Nuclear Information System (INIS)

    Bullock, Andrea; McDermott, David F; Atkins, Michael B

    2010-01-01

    An improved understanding of renal cell carcinoma (RCC) biology has translated into major advances in the treatment of patients with metastatic RCC in recent years. Clinical and pathologic criteria can be used to identify RCC patients with poor prognoses. Such patients, however, are often excluded from the cancer clinical trials that guide treatment recommendations. This article reviews available information on the management of patients with metastatic RCC and poor risk features, focusing on the role of vascular endothelial growth factor (VEGF) pathway and mammalian target of rapamycin (mTOR) inhibitors. While patients with poor risk features have a more guarded outcome, treatment with temsirolimus has produced meaningful improvements in overall survival for this population. Definitive phase III trial data are lacking for the VEGF pathway inhibitors in patients with poor prognostic features. However, available data suggest that such patients tolerate VEGF pathway blockade reasonably well and are likely to achieve some benefit relative to treatment with interferon. Ongoing translational research efforts may help to define novel treatment approaches specific for patients with metastatic RCC and poor prognostic features

  3. Application of the Lifshitz Theory to Poor Conductors

    International Nuclear Information System (INIS)

    Svetovoy, Vitaly B.

    2008-01-01

    The Lifshitz formula for dispersive forces is generalized to the materials, which cannot be described with the local dielectric response. The principal nonlocality of poor conductors is related to the finite screening length of the penetrating field and collisional relaxation; at low temperatures the role of collisions plays the Landau damping. Spatial dispersion makes the theory self-consistent. Our predictions are compared with the recent experiment. It is demonstrated that at low temperatures Casimir-Lifshitz entropy disappears as T in the case of degenerate plasma and as T 2 for the nondegenerate one

  4. Integrated genomic analyses identify KDM1A's role in cell proliferation via modulating E2F signaling activity and associate with poor clinical outcome in oral cancer.

    Science.gov (United States)

    Narayanan, Sathiya Pandi; Singh, Smriti; Gupta, Amit; Yadav, Sandhya; Singh, Shree Ram; Shukla, Sanjeev

    2015-10-28

    The histone demethylase KDM1A specifically demethylates lysine residues and its deregulation has been implicated in the initiation and progression of various cancers. However, KDM1A's molecular role and its pathological consequences, and prognostic significance in oral cancer remain less understood. In the present study, we sought to investigate the expression of KDM1A and its downstream role in oral cancer pathogenesis. By comparing mRNA expression profiles, we identified an elevated KDM1A expression in oral tumors when compared to normal oral tissues. In silico pathway prediction identified the association between KDM1A and E2F1 signaling in oral cancer. Pathway scanning, functional annotation analysis and In vitro assays showed the KDM1A's involvement in oral cancer cell proliferation and the cell cycle. Moreover, real time PCR and luciferase assays confirmed KDM1A's role in regulation of E2F1 signaling activity in oral cancer. Elevated KDM1A expression is associated with poor clinical outcome in oral cancer. Our data indicate that deregulated KDM1A expression is positively associated with proliferative phenotype of oral cancer and confers poor clinical outcome. These cumulative data suggest that KDM1A might be a potential diagnostic and therapeutic target for oral cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Development and testing of watershed-scale models for poorly drained soils

    Science.gov (United States)

    Glenn P. Fernandez; George M. Chescheir; R. Wayne Skaggs; Devendra M. Amatya

    2005-01-01

    Watershed-scale hydrology and water quality models were used to evaluate the crrmulative impacts of land use and management practices on dowrzstream hydrology and nitrogen loading of poorly drained watersheds. Field-scale hydrology and nutrient dyyrutmics are predicted by DRAINMOD in both models. In the first model (DRAINMOD-DUFLOW), field-scale predictions are coupled...

  6. The poorly explored impact of uncontrolled asthma

    DEFF Research Database (Denmark)

    O'Byrne, Paul M; Pedersen, Søren; Schatz, Michael

    2013-01-01

    The goal of asthma management is to achieve disease control; however, despite the availability of effective and safe medications, for many patients asthma remains uncontrolled. One reason for this is the fear of long-term side effects from the regular use of inhaled corticosteroids (ICSs). Adverse...... effects of poorly controlled asthma (for example, obesity, pneumonia, and risks to the fetus) can be perceived as side effects of ICSs. Poorly controlled asthma adversely affects children's cardiovascular fitness, while children with well-controlled asthma perform at the same level as their peers....... Children with uncontrolled asthma also have a higher frequency of obesity than children with controlled asthma. Stress can affect asthma control, and children with poorly controlled asthma are more likely to have learning disabilities compared with those with good control. In adults, focused attention...

  7. Poor housing quality: Prevalence and health effects.

    Science.gov (United States)

    Baker, Emma; Lester, Laurence H; Bentley, Rebecca; Beer, Andrew

    2016-01-01

    Housing is a central component of productive, healthy, and meaningful lives, and a principle social determinant of health and well-being. Surprisingly, though, evidence on the ways that housing influences health in Australia is poorly developed. This stems largely from the fact that the majority of the population are accommodated in good quality housing. The dominance of a "good housing paradigm" means that households living in poor quality and unhealthy housing are doubly disadvantaged-by the quality of their housing and because policy makers in Australia do not acknowledge the health effects of housing. In this article, we examine the relationship between health outcomes and quality of housing. We base our analysis on data from the Household Income and Labour Dynamics in Australia (HILDA) survey, a panel dataset that is representative across Australia. We find a sizeable, policy-important, and to date under-acknowledged cohort of Australians whose health is influenced by poor-condition dwellings.

  8. Survival pathways under stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Survival pathways under stress. Bacteria survive by changing gene expression. pattern. Three important pathways will be discussed: Stringent response. Quorum sensing. Proteins performing function to control oxidative damage.

  9. Is American business working for the poor?

    Science.gov (United States)

    Bane, M J; Ellwood, D T

    1991-01-01

    At first glance, poverty seems to have little to do with business. When most people--managers included--think about poverty, they assume that people are poor because they are isolated from the mainstream economy, not productive participants in it. But according to Harvard University professors Mary Jo Bane and David Ellwood, this is a misleading image of the true face of poverty in the United States today. Most poor adults--and a full 90% of poor children--live in families where work is the norm, not the exception. Poor people often work or want to work. But at the low-wage end of the American economy, having a job is no guarantee of avoiding poverty. Poverty is a business issue, then, because the American poor are part of the American work force. And this poses a problem for managers. In a more competitive and fast-changing economic environment, the performance of companies increasingly depends on the capabilities of their employees. In response to this human-resource challenge, more and more managers are embracing the language of "empowerment". And yet how can low-wage employees believe empowerment when their experience of work is, quite literally, impoverishment? It is unlikely that American companies can create the work force of the future with the poverty policies of the past. Fortunately, there are some simple policy mechanisms that can assist the working poor without putting an undue burden on business. Enacting them, however, requires managers to see poverty policy as one part of a national human-resource strategy that links the strategic concerns of companies to a broad social agenda.

  10. Model of the pathway of −1 frameshifting: Long pausing

    Directory of Open Access Journals (Sweden)

    Ping Xie

    2016-03-01

    Full Text Available It has been characterized that the programmed ribosomal −1 frameshifting often occurs at the slippery sequence on the presence of a downstream mRNA pseudoknot. In some prokaryotic cases such as the dnaX gene of Escherichia coli, an additional stimulatory signal—an upstream, internal Shine–Dalgarno (SD sequence—is also necessary to stimulate the efficient −1 frameshifting. However, the molecular and physical mechanism of the −1 frameshifting is poorly understood. Here, we propose a model of the pathway of the −1 translational frameshifting during ribosome translation of the dnaX −1 frameshift mRNA. With the model, the single-molecule fluorescence data (Chen et al. (2014 [29] on the dynamics of the shunt either to long pausing or to normal translation, the tRNA transit and sampling dynamics in the long-paused rotated state, the EF-G sampling dynamics, the mean rotated-state lifetimes, etc., are explained quantitatively. Moreover, the model is also consistent with the experimental data (Yan et al. (2015 [30] on translocation excursions and broad branching of frameshifting pathways. In addition, we present some predicted results, which can be easily tested by future optical trapping experiments.

  11. Pathways Intern Report

    Science.gov (United States)

    Huggett, Daniel James

    2017-01-01

    The National Aeronautics and Space Administration (NASA) provides a formal training program for prospective employees titled, Pathways Intern Employment. The Pathways program targets graduate and undergraduate students who strive to become an active contributor to NASA's goal of space exploration. The report herein provides an account of Daniel Huggett's Pathways experience for the Spring and Summer 2017 semesters.

  12. Neurophysiology and itch pathways.

    Science.gov (United States)

    Schmelz, Martin

    2015-01-01

    As we all can easily differentiate the sensations of itch and pain, the most straightforward neurophysiologic concept would consist of two specific pathways that independently encode itch and pain. Indeed, a neuronal pathway for histamine-induced itch in the peripheral and central nervous system has been described in animals and humans, and recently several non-histaminergic pathways for itch have been discovered in rodents that support a dichotomous concept differentiated into a pain and an itch pathway, with both pathways being composed of different "flavors." Numerous markers and mediators have been found that are linked to itch processing pathways. Thus, the delineation of neuronal pathways for itch from pain pathways seemingly proves that all sensory aspects of itch are based on an itch-specific neuronal pathway. However, such a concept is incomplete as itch can also be induced by the activation of the pain pathway in particular when the stimulus is applied in a highly localized spatial pattern. These opposite views reflect the old dispute between specificity and pattern theories of itch. Rather than only being of theoretic interest, this conceptual problem has key implication for the strategy to treat chronic itch as key therapeutic targets would be either itch-specific pathways or unspecific nociceptive pathways.

  13. Who speaks for the poor (question mark)

    International Nuclear Information System (INIS)

    Wyatt, Alan

    1981-01-01

    Nuclear energy benefits the poor, because it alleviates a shortage of petroleum. Less-developed countries suffer directly from a shortage of petroleum; also petroleum is necessary to raise food in the developed countries for export to the less-developed countries. (L.L.)

  14. Text comprehension strategy instruction with poor readers

    NARCIS (Netherlands)

    Van den Bos, K.P.; Aarnoudse, C.C.; Brand-Gruwel, S.

    1998-01-01

    The goal of this study was to investigate the effects of teaching text comprehension strategies to children with decoding and reading comprehension problems and with a poor or normal listening ability. Two experiments are reported. Four text comprehension strategies, viz., question generation,

  15. University Students with Poor Reading Comprehension

    Science.gov (United States)

    Georgiou, George K.; Das, J. P.

    2015-01-01

    The present study aimed to examine the nature of the working memory and general cognitive ability deficits experienced by university students with a specific reading comprehension deficit. A total of 32 university students with poor reading comprehension but average word-reading skills and 60 age-word-matched controls with no comprehension…

  16. Adult Literacy and the Poor Farming People.

    Science.gov (United States)

    Mathur, J. C.

    1978-01-01

    In discussing Rafe-uz-Zaman's essay on adult literacy and national development (see v9, n1 of this journal), the author cites examples to support his thesis that mass literacy campaigns in predominately agricultural countries can be successful only if there is simultaneous undertaking of economic development programs focused on the rural poor. (MF)

  17. Planning Behaviour in Good and Poor Readers

    Science.gov (United States)

    Mahapatra, Shamita

    2016-01-01

    A group of 50 good readers and a group of 50 poor readers of Grade 5 matched for age and intelligence and selected on the basis of their proficiency in reading comprehension were tested for their competence in word reading and the process of planning at three different levels, namely, perceptual, memory and conceptual in order to study the…

  18. Getting to Know L2 Poor Comprehenders

    Science.gov (United States)

    Zoghi, Masoud; Mustapha, Ramlee; Maasum, Tengku Nor Rizan BT Tengku Mohamad

    2011-01-01

    Among the plethora of studies conducted thus far to explore the factors affecting EFL reading effectiveness, scant attention seems to be paid to the why of poor reading comprehension of most EFL learners. In this regard, the present article capitalized on qualitative research on a small scale, for the purpose of addressing the not-so-often debated…

  19. Dealing with living in poor neighbourhoods

    NARCIS (Netherlands)

    Kleinhans, R.; Van der Land, M.; Doff, W.

    2010-01-01

    In this prologue to the special issue, the guest editors place the contributions in the context of current debates on living in concentrated poverty neighbourhoods. These debates concern two broad categories of residents: poor households that are assisted to move from concentrations of poverty to

  20. Correcting Poor Posture without Awareness or Willpower

    Science.gov (United States)

    Wernik, Uri

    2012-01-01

    In this article, a new technique for correcting poor posture is presented. Rather than intentionally increasing awareness or mobilizing willpower to correct posture, this approach offers a game using randomly drawn cards with easy daily assignments. A case using the technique is presented to emphasize the subjective experience of living with poor…

  1. Poor migrants in Bandung: settlement and employment

    NARCIS (Netherlands)

    Bruinessen, M.M. van

    1989-01-01

    Sukapakir is the real but appropriate name of a poor urban kampung in southwestern Bandung. It is one of the most densely populated neighbourhoods of the town now, although some forty years ago it was still a largely rural district. On the fringes of Sukapakir, one finds even today a few sawah

  2. EGFR and AKT1 overexpression are mutually exclusive and associated with a poor survival in resected gastric adenocarcinomas.

    Science.gov (United States)

    Petrini, Iacopo; Lencioni, Monica; Vasile, Enrico; Fornaro, Lorenzo; Belluomini, Lorenzo; Pasquini, Giulia; Ginocchi, Laura; Caparello, Chiara; Musettini, Gianna; Vivaldi, Caterina; Caponi, Sara; Ricci, Sergio; Proietti, Agenese; Fontanini, Gabriella; Naccarato, Antonio Giuseppe; Nardini, Vincenzo; Santi, Stefano; Falcone, Alfredo

    2018-02-14

    The evaluation of molecular targets in gastric cancer has demonstrated the predictive role of HER2 amplification for trastuzumab treatment in metastatic gastric cancer. Besides HER2, other molecular targets are under evaluation in metastatic gastric tumors. However, very little is known about their role in resected tumors. We evaluated the expression of HER2, EGFR, MET, AKT1 and phospho-mTOR in resected stage II-III adenocarcinomas. Ninety-two patients with resected stomach (63%) or gastro-esophageal adenocarcinomas (27%) were evaluated. Antibodies anti-HER2, EGFR, MET, AKT1 and phospho-mTOR were used for immunostaining of formalin-fixed paraffin-embedded slides. Using FISH, HER2 amplification was evaluated in cases with an intermediate (+2) staining. EGFR overexpression (11%) was a poor prognostic factor for overall survival (3-year OS: 47% vs 77%; Log-Rank p= 0.033). MET overexpression (36%) was associated with a trend for a worse survival (3-year OS: 65% vs 77%; Log-Rank p= 0.084). HER2 amplification/overexpression and mTOR hyper-phosphorylation were observed in 13% and 48% of tumors, respectively. AKT1 overexpression (8%) was not a prognostic factor by itself (p= 0.234). AKT1 and EGFR overexpression was mutually exclusive and patients with EGFR or AKT1 overexpression experienced a poor prognosis (3-year OS: 52% vs. 79%, Log-Rank p= 0.005). EGFR is confirmed a poor prognostic factor in resected gastric cancers. We firstly describe a mutually exclusive overexpression of EGFR and AKT1 with potential prognostic implications, suggesting the relevance of this pathway for the growth of gastric cancers.

  3. Pathways to man

    International Nuclear Information System (INIS)

    Harley, J.H.

    1980-01-01

    The study of radionuclide pathways leading to man generally has the goal of allowing us to predict human exposure from measurements of the radionuclide concentration in some segment of the environment. This modelling process provides a valuable tool in both the regulatory and health protection fields. However, most of the models in the regulatory field and in the health physics profession were designed to maximize exposure estimates. It is preferable to have scientifically defensible estimates and to add suitable safety factors at the end. Thus we are still faced with the development and validation of suitable models for many of the radionuclides of interest. The most useful models will include means of assessing variability and uncertainty. In this case variability might be considered as the differences in behavior due to age, sex or other factors in animals or man and those differences among plant species or animal species that determine their uptake factors. The uncertainty, on the other hand, would be the estimate of possible error in the experimental measurements. Model parameters would always have some variability even for site-specific cases and broad averages for population groups would have to include a factor expressing the possible variabilty and uncertainity. Thus any exposure calculation would have to be expressed with some range and valid assessments of this range are required

  4. Predictive Models and Computational Embryology

    Science.gov (United States)

    EPA’s ‘virtual embryo’ project is building an integrative systems biology framework for predictive models of developmental toxicity. One schema involves a knowledge-driven adverse outcome pathway (AOP) framework utilizing information from public databases, standardized ontologies...

  5. Parenting Efficacy and the Early School Adjustment of Poor and Near-Poor Black Children

    Science.gov (United States)

    Jackson, Aurora P.; Choi, Jeong-Kyun; Bentler, Peter M.

    2009-01-01

    This short-term longitudinal study investigates whether maternal educational attainment, maternal employment status, and family income affect African American children's behavioral and cognitive functioning over time through their impacts on mothers' psychological functioning and parenting efficacy in a sample of 100 poor and near-poor single…

  6. Predicting disease risk using bootstrap ranking and classification algorithms.

    Directory of Open Access Journals (Sweden)

    Ohad Manor

    Full Text Available Genome-wide association studies (GWAS are widely used to search for genetic loci that underlie human disease. Another goal is to predict disease risk for different individuals given their genetic sequence. Such predictions could either be used as a "black box" in order to promote changes in life-style and screening for early diagnosis, or as a model that can be studied to better understand the mechanism of the disease. Current methods for risk prediction typically rank single nucleotide polymorphisms (SNPs by the p-value of their association with the disease, and use the top-associated SNPs as input to a classification algorithm. However, the predictive power of such methods is relatively poor. To improve the predictive power, we devised BootRank, which uses bootstrapping in order to obtain a robust prioritization of SNPs for use in predictive models. We show that BootRank improves the ability to predict disease risk of unseen individuals in the Wellcome Trust Case Control Consortium (WTCCC data and results in a more robust set of SNPs and a larger number of enriched pathways being associated with the different diseases. Finally, we show that combining BootRank with seven different classification algorithms improves performance compared to previous studies that used the WTCCC data. Notably, diseases for which BootRank results in the largest improvements were recently shown to have more heritability than previously thought, likely due to contributions from variants with low minimum allele frequency (MAF, suggesting that BootRank can be beneficial in cases where SNPs affecting the disease are poorly tagged or have low MAF. Overall, our results show that improving disease risk prediction from genotypic information may be a tangible goal, with potential implications for personalized disease screening and treatment.

  7. Current stress and poor oral health

    OpenAIRE

    Vasiliou, A.; Shankardass, K.; Nisenbaum, R.; Qui?onez, C.

    2016-01-01

    Background Psychological stress appears to contribute to poor oral health systemically in combination with other chronic diseases. Few studies directly examine this relationship. Methods Data from a cross-sectional study of 2,412 participants between the ages of 25?64 years old living in the City of Toronto between 2009 and 2012 were used to examine the relationship between current stress and two self-rated oral health outcomes (general oral health and oral pain). Dental care utilization and ...

  8. Stereotactic Radiosurgery for Poor Performance Status Patients

    Energy Technology Data Exchange (ETDEWEB)

    Kubicek, Gregory J., E-mail: kubicek-gregory@cooperhealth.edu [Department of Radiation Oncology, Cooper University Hospital, Camden, New Jersey (United States); Turtz, Alan [Department of Neurological Surgery, Cooper University Hospital, Camden, New Jersey (United States); Xue, Jinyu; Patel, Ashish; Richards, Gregory; LaCouture, Tamara [Department of Radiation Oncology, Cooper University Hospital, Camden, New Jersey (United States); Cappelli, Louis; Diestelkamp, Tim [Rowan Graduate School, Camden, New Jersey (United States); Saraiya, Piya [Department of Diagnostic Radiology, Cooper University Hospital, Camden, New Jersey (United States); Bexon, Anne [Department of Neurological Surgery, Cooper University Hospital, Camden, New Jersey (United States); Lerman, Nati [Department of Medical Oncology, Cooper University Hospital, Camden, New Jersey (United States); Goldman, Howard Warren [Department of Neurological Surgery, Cooper University Hospital, Camden, New Jersey (United States)

    2016-07-01

    Purpose: Patients with poor performance status (PS), usually defined as a Karnofsky Performance Status of 60 or less, were not eligible for randomized stereotactic radiosurgery (SRS) studies, and many guidelines suggest that whole-brain radiation therapy (WBRT) is the most appropriate treatment for poor PS patients. Methods and Materials: In this retrospective review of our SRS database, we identified 36 patients with PS of 60 or less treated with SRS for central nervous system (CNS) metastatic disease. PS, as defined by the Karnofsky Performance Status, was 60 (27 patients), 50 (8 patients), or 40 (1 patient). The median number of CNS lesions treated was 3. Results: Median overall survival (OS) was 7.2 months (range, 0.73-25.6 months). Fifteen patients (41%) were alive at 6 months, and 6 patients (16.6%) were alive at 1 year. There was no difference in OS in patients who underwent previous WBRT. There were no local failures or cases of radiation toxicity. Distant CNS failures were seen in 9 patients (25%). Conclusions: Our patients with poor PS had reasonable median OS and relatively low distant CNS failure rates. Patients in this patient population may be ideal candidates for SRS compared with WBRT given the low incidence of distant failure over their remaining lives and the favorable logistics of single-fraction treatment for these patients with debility and their caregivers.

  9. Lipid-based formulations for oral administration of poorly water-soluble drugs

    DEFF Research Database (Denmark)

    Mu, Huiling; Holm, René; Müllertz, Anette

    2013-01-01

    Lipid-based drug delivery systems have shown great potentials in oral delivery of poorly water-soluble drugs, primarily for lipophilic drugs, with several successfully marketed products. Pre-dissolving drugs in lipids, surfactants, or mixtures of lipids and surfactants omits the dissolving....../dissolution step, which is a potential rate limiting factor for oral absorption of poorly water-soluble drugs. Lipids not only vary in structures and physiochemical properties, but also in their digestibility and absorption pathway; therefore selection of lipid excipients and dosage form has a pronounced effect...

  10. Modelling and Decision Support of Clinical Pathways

    Science.gov (United States)

    Gabriel, Roland; Lux, Thomas

    The German health care market is under a rapid rate of change, forcing especially hospitals to provide high-quality services at low costs. Appropriate measures for more effective and efficient service provision are process orientation and decision support by information technology of clinical pathway of a patient. The essential requirements are adequate modelling of clinical pathways as well as usage of adequate systems, which are capable of assisting the complete path of a patient within a hospital, and preferably also outside of it, in a digital way. To fulfil these specifications the authors present a suitable concept, which meets the challenges of well-structured clinical pathways as well as rather poorly structured diagnostic and therapeutic decisions, by interplay of process-oriented and knowledge-based hospital information systems.

  11. Medicaid eligibility policy in the 1980s: medical utilitarianism and the "deserving" poor.

    Science.gov (United States)

    Tanenbaum, S J

    1995-01-01

    Between 1981 and the early 1990s, the Medicaid program grew substantially, in part because, for the first time in the program's history, eligibility for medical assistance was severed from eligibility for income-maintenance payments. Program participation had always been reserved for the "deserving poor," and these were originally defined as persons excluded from market relationships through no fault of their own. The Medicaid expansion of the 1980s, however, created a new constituency of poor, and not-so-poor, persons whose actual or predictable medical problems promised a calculable return on program funds.

  12. A 'Scottish Poor Law of Lunacy'? Poor Law, Lunacy Law and Scotland's parochial asylums.

    Science.gov (United States)

    Farquharson, Lauren

    2017-03-01

    Scotland's parochial asylums are unfamiliar institutional spaces. Representing the concrete manifestation of the collision between two spheres of legislation, the Poor Law and the Lunacy Law, six such asylums were constructed in the latter half of the nineteenth century. These sites expressed the enduring mandate of the Scottish Poor Law 1845 over the domain of 'madness'. They were institutions whose very existence was fashioned at the directive of the local arm of the Poor Law, the parochial board, and they constituted a continuing 'Scottish Poor Law of Lunacy'. Their origins and operation significantly subverted the intentions and objectives of the Lunacy Act 1857, the aim of which had been to institute a public district asylum network with nationwide coverage.

  13. Current stress and poor oral health.

    Science.gov (United States)

    Vasiliou, A; Shankardass, K; Nisenbaum, R; Quiñonez, C

    2016-09-02

    Psychological stress appears to contribute to poor oral health systemically in combination with other chronic diseases. Few studies directly examine this relationship. Data from a cross-sectional study of 2,412 participants between the ages of 25-64 years old living in the City of Toronto between 2009 and 2012 were used to examine the relationship between current stress and two self-rated oral health outcomes (general oral health and oral pain). Dental care utilization and access to dental insurance were examined as effect modifiers. A positive relationship between current stress and poor oral health was observed for both outcomes (oral pain coefficient 0.32, 95 % CI 0.26-0.38; general oral health coefficient 0.28, 95 % CI 0.19-0.36). Effects on oral pain were stronger for the uninsured, while effects on general oral health were stronger with decreasing socioeconomic position. Our findings suggest that individuals with greater perceived stress also report poorer oral health, and that this relationship is modified by dental insurance and socioeconomic position. These findings warrant a greater focus on the role of psychological stress in the development of oral disease, including how perceived stress contributes to health inequities in self-reported oral health status. Patients experiencing stressful lives may differentially require closer monitoring and more vigilant maintenance of their oral health, above and beyond that which is needed to achieve a state of health in the oral environment of less stressed individuals. There may be health promoting effects of addressing psychosocial concerns related to dental care - particularly for the poor and uninsured.

  14. Justice, Work, and the Ghetto Poor

    OpenAIRE

    Shelby, Tommie

    2012-01-01

    In view of the explanatory significance of joblessness, some social scientists, policymakers,and commentators have advocated strong measures to ensure that the ghetto poor work, includingmandating work as a condition of receiving welfare benefits. Indeed, across the ideological po-litical spectrum, work is often seen as a moral or civic duty and as a necessary basis for personaldignity. And this normative stance is now instantiated in federal and state law, from the tax schemeto public benefits....

  15. Bureaucracy and Pro-poor Change

    OpenAIRE

    Ali Cheema; Asad Sayeed

    2006-01-01

    Based on the premise that a functioning state is a necessary pre-requisite for pro-poor change, it is critical to investigate the role of the bureaucracy as a key catalyst in this process. Weber (1968) ascribes bureaucracies to be anchors of the modern nation state as their conduct is based on rational-legal norms. Bureaucracies, according to this ideal type, temper the populist urges of politicians who wish to execute policy unencumbered by rules and procedures. State success or failure in m...

  16. Access to energy for the poor

    International Nuclear Information System (INIS)

    Huntjens, E.; Van Bussel, F.; Raats, M.

    2005-01-01

    Paper dealing with the topic E nergy consumption and economic development (in developed / wealthy and undeveloped / poor regions; energy price, social influence and energy efficiency. 'Brothers and sisters, I want to tell you this. The greatest thing on earth is to have the love of God in your heart, and the next greatest thing is to have electricity in your house.' In the early 1940s a farmer, who had just been connected to the electric grid, gave witness in a rural church in the United States of America(author)

  17. Model description and evaluation of model performance, scenario S. Multiple pathways assessment of the IAEA/CEC co-ordinated research programme on validation of environmental model predictions (VAMP)

    International Nuclear Information System (INIS)

    Suolanen, V.

    1996-12-01

    A modelling approach was used to predict doses from a large area deposition of 137 Cs over southern and central Finland. The assumed deposition profile and quantity were both similar to those resulting from the Chernobyl accident. In the study, doses via terrestrial and aquatic environments have been analyzed. Additionally, the intermediate results of the study, such as concentrations in various foodstuffs and the resulting body burdents, were presented. The contributions of ingestion, inhalation and external doses to the total dose were estimated in the study. The considered deposition scenario formed a modelling exercise in the IAEA coordinated research programme on Validation of Environmental Model Predictions, the VAMP project. (21 refs.)

  18. Seychelles Fisheries Connectivity and Transport Pathways

    Science.gov (United States)

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Seychelles Fisheries Connectivity and Transport Pathways...overarching goal for the proposed work is to develop predictive capabilities for physical oceanography for the Seychelles region in support of locally...for ocean observations in the Seychelles region that will lead to long-term data collection efforts. In collaboration with local partnerships, we

  19. Association of diarrhoea, poor hygiene and poor social conditions in childhood with blood pressure in adulthood.

    Science.gov (United States)

    Kauhanen, L; Lynch, J W; Lakka, H-M; Kauhanen, J; Smith, G D

    2010-05-01

    Previous research has suggested that dehydration in infancy may lead to high blood pressure in later life because of sodium retention. The purpose of this study was to examine the effect of poor hygiene of the child, poor social and poor housing conditions at home and diarrhoea in childhood as proxies for dehydration on high blood pressure in later life. Data were from a subset of participants in the Kuopio Ischaemic Heart Disease Risk Factor Study, a population-based cohort study in eastern Finland. Information on childhood factors was collected from school health records (n=952), from the 1930s to the 1950s. Adult data were obtained from baseline examinations of the Kuopio Ischaemic Heart Disease Risk Factor Study cohort (n=2682) in 1984-1989. Men who had poor hygiene in childhood had on average 4.07 mm Hg (95% CI 0.53 to 7.61) higher systolic blood pressure than men who had good or satisfactory hygiene in childhood in the age-adjusted analysis. Reports of diarrhoea were not associated with adult blood pressure. The authors' findings suggest that poor hygiene and living in poor social conditions in childhood are associated with higher systolic blood pressure in adulthood. Reported childhood diarrhoea did not explain the link between hygiene and high blood pressure in adulthood.

  20. Main causes of poor welfare in intensively reared dairy cows

    Directory of Open Access Journals (Sweden)

    Fabio Abeni

    2010-01-01

    Full Text Available The aim of this review is to summarise the main causes of poor welfare in intensively reared dairy cows. Intensive farming systems are considered, both from a structural and a managerial point of view, for their constraints that may limit animal welfare: possible physical activity; acceptable interactions with humans and other animals; feeding and watering, protection from climate, parasites, and diseases. The dairy farms managed according to the organic rules do not always guarantee, per se, better welfare conditions; organic or low input dairy farming needs to consider the right interaction among cattle breed and herd management, focusing on the actual quality of feedstuffs meet face cow requirements. The considered structural aspects evidence how special care must be given to the rest area (straw yard or cubicle; to the floors that should be not too hard or abrasive and not slippery; to the cubicle bedding material to ensure hygiene, softness, and dryness; to the feeding (and watering area to reduce conflicts; to a microclimate control system, to avoid heat stress during summer time. The importance of proper management for animal welfare is evidenced for buildings and equipment, to have clean and comfortable stables and well functioning milking machines; nutritive and storage quality of feeds; diet suitability (energy, protein, physically efficient fibre, buffers etc., in the different phases of a dairy cow’s life (dry period, close-up, transition, and lactation; feed distribution (frequency and time, and 24h availability. Special attention has to be paid to the social aspects, regarding both animal competition (stocking density, group size, and human/animal interactions (methods of management and manipulation. The interaction between welfare and health requires special attention. Poor welfare can cause immune depression, thus increasing the risk of disease. In turn, any disease that causes an inflammatory response may determine depression

  1. Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

    DEFF Research Database (Denmark)

    Huang, Sijia; Chong, Nicole; Lewis, Nathan

    2016-01-01

    diagnosis. We applied this method to predict breast cancer occurrence, in combination with correlation feature selection (CFS) and classification methods. Results: The resulting all-stage and early-stage diagnosis models are highly accurate in two sets of testing blood samples, with average AUCs (Area Under.......993. Moreover, important metabolic pathways, such as taurine and hypotaurine metabolism and the alanine, aspartate, and glutamate pathway, are revealed as critical biological pathways for early diagnosis of breast cancer. Conclusions: We have successfully developed a new type of pathway-based model to study...... metabolomics data for disease diagnosis. Applying this method to blood-based breast cancer metabolomics data, we have discovered crucial metabolic pathway signatures for breast cancer diagnosis, especially early diagnosis. Further, this modeling approach may be generalized to other omics data types for disease...

  2. Pathways from Poverty.

    Science.gov (United States)

    Baldwin, Barbara, Ed.

    1995-01-01

    Articles in this theme issue are based on presentations at the Pathways from Poverty Workshop held in Albuquerque, New Mexico, on May 18-25, 1995. The event aimed to foster development of a network to address rural poverty issues in the Western Rural Development Center (WRDC) region. Articles report on outcomes from the Pathways from Poverty…

  3. Education of quality to the poor

    Directory of Open Access Journals (Sweden)

    H.M. van der Merwe

    2011-09-01

    Full Text Available Quality education often eludes South African learners from poverty- stricken environments. There are, however, some notable exceptions. This article looks at how quality education based on social capital is provided to the poor. The author reports on a qualitative investigation based on both focus group and individual interviews conducted at a resource-poor KwaZulu- Natal school serving learners from Grade R to 9. The findings show that quality education at the research site relates to the moral agency of the school principal and teaching staff. Through their ethics of being and doing, the school principal and teaching staff ensure that sufficient resources, sound home-school relations, and a high premium on moral values result in a receptive learner corps. This environment encourages these learners to act with diligence, honesty, politeness, respect and service to the community. The findings contribute to research that maintains that quality education is indicative of the school principal and teachers‟ ethics of being and of doing.

  4. Alleviating energy poverty for the world's poor

    International Nuclear Information System (INIS)

    Sagar, Ambuj D.

    2005-01-01

    Improving energy services for poor households in developing countries remains one of the most pressing challenges facing the development community. The dependence of these households on traditional forms of energy leads to significant health impacts as well as other major disbenefits, yet there has been little progress in meeting this challenge. This viewpoint argues for an 'energy-poverty alleviation' fund to help provide modern energy services to these households. It also proposes an approach through which to create such a fund, namely by introducing an incremental levy on petroleum. Notably, this scheme does not need a global agreement since a levy could be introduced by major oil-exporting countries. The implementation of this mechanism would result in a climate-friendly outcome (even before taking into account the elimination of products of incomplete combustion resulting from the traditional household use of biomass-based fuels) while providing immense socio-economic benefits to the world's poor. Such an approach would allow significant progress on the sustainable development front while reducing global greenhouse gas emissions, and therefore is very much consistent with the United Nations Framework Convention on Climate Change

  5. Crisis and Communication among Rural Poor People

    Directory of Open Access Journals (Sweden)

    Agus Ganjar Runtiko

    2015-07-01

    Full Text Available The effect of the crisis is often multiple on people in rural poverty that secluded and away from the reach of government. Main factor cannot be ignored in crisis is communication. Prolonged crisis will occur when the channels of communication in society clogged. This study establishes three specific targets: (1 To obtain a comprehensive overview of the rural poor people’s knowledge about the crisis and the potential impact, (2 To discover crisis problems faced by the rural people poor, (3 To enlist communication problems in a crisis situation. This study used a qualitative method with a case study approach. Research data collect by conducting FGD of 40 informants selected based on purposive sampling, furthermore eight people were interviewed in depth, plus other supporting informant. The results of the research show people on those two locations have understood the crisis based on their experience of dealing with it. They believe the economic crisis as the first aspect that must be resolved. The completion of crisis should consider indigenous wisdom to avoid a new crisis.

  6. Crystallization Pathways in Biomineralization

    Science.gov (United States)

    Weiner, Steve; Addadi, Lia

    2011-08-01

    A crystallization pathway describes the movement of ions from their source to the final product. Cells are intimately involved in biological crystallization pathways. In many pathways the cells utilize a unique strategy: They temporarily concentrate ions in intracellular membrane-bound vesicles in the form of a highly disordered solid phase. This phase is then transported to the final mineralization site, where it is destabilized and crystallizes. We present four case studies, each of which demonstrates specific aspects of biological crystallization pathways: seawater uptake by foraminifera, calcite spicule formation by sea urchin larvae, goethite formation in the teeth of limpets, and guanine crystal formation in fish skin and spider cuticles. Three representative crystallization pathways are described, and aspects of the different stages of crystallization are discussed. An in-depth understanding of these complex processes can lead to new ideas for synthetic crystallization processes of interest to materials science.

  7. Investigating a multigene prognostic assay based on significant pathways for Luminal A breast cancer through gene expression profile analysis.

    Science.gov (United States)

    Gao, Haiyan; Yang, Mei; Zhang, Xiaolan

    2018-04-01

    The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation. The multigene prognostic assay was exploited based on the statistically significant pathways and its prognostic function was tested using train set and verified using the gene expression data and survival data of Luminal A breast cancer patients downloaded from the Gene Expression Omnibus. A total of 300 DEGs were identified between good and poor outcome groups, including 176 upregulated genes and 124 downregulated genes. The DEGs may be used to effectively distinguish Luminal A samples with different prognoses verified by hierarchical clustering analysis. There were 9 pathways screened as significant pathways and a total of 18 DEGs involved in these 9 pathways were identified as prognostic biomarkers. According to the survival analysis and receiver operating characteristic curve, the obtained 18-gene prognostic assay exhibited good prognostic function with high sensitivity and specificity to both the train and test samples. In conclusion the 18-gene prognostic assay including the key genes, transcription factor 7-like 2, anterior parietal cortex and lymphocyte enhancer factor-1 may provide a new method for predicting outcomes and may be conducive to the promotion of precision medicine for Luminal A breast cancer.

  8. Low Cerebral Blood Volume Identifies Poor Outcome in Stent Retriever Thrombectomy

    International Nuclear Information System (INIS)

    Protto, Sara; Pienimäki, Juha-Pekka; Seppänen, Janne; Numminen, Heikki; Sillanpää, Niko

    2017-01-01

    BackgroundMechanical thrombectomy (MT) is an efficient treatment of acute stroke caused by large-vessel occlusion. We evaluated the factors predicting poor clinical outcome (3-month modified Rankin Scale, mRS >2) although MT performed with modern stent retrievers.MethodsWe prospectively collected the clinical and imaging data of 105 consecutive anterior circulation stroke patients who underwent MT after multimodal CT imaging. Patients with occlusion of the internal carotid artery and/or middle cerebral artery up to the M2 segment were included. We recorded baseline clinical, procedural and imaging variables, technical outcome, 24-h imaging outcome and the clinical outcome. Differences between the groups were studied with appropriate statistical tests and binary logistic regression analysis.ResultsLow cerebral blood volume Alberta stroke program early CT score (CBV-ASPECTS) was associated with poor clinical outcome (median 7 vs. 9, p = 0.01). Lower collateral score (CS) significantly predicted poor outcome in regression modelling with CS = 0 increasing the odds of poor outcome 4.4-fold compared to CS = 3 (95% CI 1.27–15.5, p = 0.02). Lower CBV-ASPECTS significantly predicted poor clinical outcome among those with moderate or severe stroke (OR 0.82, 95% CI 0.68–1, p = 0.05) or poor collateral circulation (CS 0–1, OR 0.66, 95% CI 0.48–0.90, p = 0.009) but not among those with mild strokes or good collaterals.ConclusionsCBV-ASPECTS estimating infarct core is a significant predictor of poor clinical outcome among anterior circulation stroke patients treated with MT, especially in the setting of poor collateral circulation and/or moderate or severe stroke.

  9. Low Cerebral Blood Volume Identifies Poor Outcome in Stent Retriever Thrombectomy

    Energy Technology Data Exchange (ETDEWEB)

    Protto, Sara, E-mail: sara.protto@pshp.fi; Pienimäki, Juha-Pekka; Seppänen, Janne [Tampere University Hospital, Medical Imaging Center (Finland); Numminen, Heikki [Tampere University Hospital, Department of Neurology (Finland); Sillanpää, Niko [Tampere University Hospital, Medical Imaging Center (Finland)

    2017-04-15

    BackgroundMechanical thrombectomy (MT) is an efficient treatment of acute stroke caused by large-vessel occlusion. We evaluated the factors predicting poor clinical outcome (3-month modified Rankin Scale, mRS >2) although MT performed with modern stent retrievers.MethodsWe prospectively collected the clinical and imaging data of 105 consecutive anterior circulation stroke patients who underwent MT after multimodal CT imaging. Patients with occlusion of the internal carotid artery and/or middle cerebral artery up to the M2 segment were included. We recorded baseline clinical, procedural and imaging variables, technical outcome, 24-h imaging outcome and the clinical outcome. Differences between the groups were studied with appropriate statistical tests and binary logistic regression analysis.ResultsLow cerebral blood volume Alberta stroke program early CT score (CBV-ASPECTS) was associated with poor clinical outcome (median 7 vs. 9, p = 0.01). Lower collateral score (CS) significantly predicted poor outcome in regression modelling with CS = 0 increasing the odds of poor outcome 4.4-fold compared to CS = 3 (95% CI 1.27–15.5, p = 0.02). Lower CBV-ASPECTS significantly predicted poor clinical outcome among those with moderate or severe stroke (OR 0.82, 95% CI 0.68–1, p = 0.05) or poor collateral circulation (CS 0–1, OR 0.66, 95% CI 0.48–0.90, p = 0.009) but not among those with mild strokes or good collaterals.ConclusionsCBV-ASPECTS estimating infarct core is a significant predictor of poor clinical outcome among anterior circulation stroke patients treated with MT, especially in the setting of poor collateral circulation and/or moderate or severe stroke.

  10. From Oxidative Stress Damage to Pathways, Networks, and Autophagy via MicroRNAs

    Directory of Open Access Journals (Sweden)

    Nikolai Engedal

    2018-01-01

    Full Text Available Oxidative stress can alter the expression level of many microRNAs (miRNAs, but how these changes are integrated and related to oxidative stress responses is poorly understood. In this article, we addressed this question by using in silico tools. We reviewed the literature for miRNAs whose expression is altered upon oxidative stress damage and used them in combination with various databases and software to predict common gene targets of oxidative stress-modulated miRNAs and affected pathways. Furthermore, we identified miRNAs that simultaneously target the predicted oxidative stress-modulated miRNA gene targets. This generated a list of novel candidate miRNAs potentially involved in oxidative stress responses. By literature search and grouping of pathways and cellular responses, we could classify these candidate miRNAs and their targets into a larger scheme related to oxidative stress responses. To further exemplify the potential of our approach in free radical research, we used our explorative tools in combination with ingenuity pathway analysis to successfully identify new candidate miRNAs involved in the ubiquitination process, a master regulator of cellular responses to oxidative stress and proteostasis. Lastly, we demonstrate that our approach may also be useful to identify novel candidate connections between oxidative stress-related miRNAs and autophagy. In summary, our results indicate novel and important aspects with regard to the integrated biological roles of oxidative stress-modulated miRNAs and demonstrate how this type of in silico approach can be useful as a starting point to generate hypotheses and guide further research on the interrelation between miRNA-based gene regulation, oxidative stress signaling pathways, and autophagy.

  11. Cross-regulation of signaling pathways: An example of nuclear hormone receptors and the canonical Wnt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Beildeck, Marcy E. [Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057 (United States); Gelmann, Edward P. [Columbia University, Department of Medicine, New York, NY (United States); Byers, Stephen W., E-mail: byerss@georgetown.edu [Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057 (United States)

    2010-07-01

    Predicting the potential physiological outcome(s) of any given molecular pathway is complex because of cross-talk with other pathways. This is particularly evident in the case of the nuclear hormone receptor and canonical Wnt pathways, which regulate cell growth and proliferation, differentiation, apoptosis, and metastatic potential in numerous tissues. These pathways are known to intersect at many levels: in the intracellular space, at the membrane, in the cytoplasm, and within the nucleus. The outcomes of these interactions are important in the control of stem cell differentiation and maintenance, feedback loops, and regulating oncogenic potential. The aim of this review is to demonstrate the importance of considering pathway cross-talk when predicting functional outcomes of signaling, using nuclear hormone receptor/canonical Wnt pathway cross-talk as an example.

  12. Cross-regulation of signaling pathways: An example of nuclear hormone receptors and the canonical Wnt pathway

    International Nuclear Information System (INIS)

    Beildeck, Marcy E.; Gelmann, Edward P.; Byers, Stephen W.

    2010-01-01

    Predicting the potential physiological outcome(s) of any given molecular pathway is complex because of cross-talk with other pathways. This is particularly evident in the case of the nuclear hormone receptor and canonical Wnt pathways, which regulate cell growth and proliferation, differentiation, apoptosis, and metastatic potential in numerous tissues. These pathways are known to intersect at many levels: in the intracellular space, at the membrane, in the cytoplasm, and within the nucleus. The outcomes of these interactions are important in the control of stem cell differentiation and maintenance, feedback loops, and regulating oncogenic potential. The aim of this review is to demonstrate the importance of considering pathway cross-talk when predicting functional outcomes of signaling, using nuclear hormone receptor/canonical Wnt pathway cross-talk as an example.

  13. Poverty and behavior problems trajectories from 1.5 to 8 years of age: Is the gap widening between poor and non-poor children?

    Science.gov (United States)

    Mazza, Julia Rachel S E; Boivin, Michel; Tremblay, Richard E; Michel, Gregory; Salla, Julie; Lambert, Jean; Zunzunegui, Maria Victoria; Côté, Sylvana M

    2016-08-01

    Poverty has been associated with high levels of behavior problems across childhood, yet patterns of associations over time remain understudied. This study aims: (a) to examine whether poverty predicts changes in behavior problems between 1.5 and 8 years of age; (b) to estimate potential selection bias for the observed associations. We used the 1998-2006 waves of the Quebec Longitudinal Study of Child Development (N = 2120). Main outcomes were maternal ratings of hyperactivity, opposition and physical aggression from 1.5 to 8 years of age. Linear mixed-effects models were used to assess the longitudinal association between poverty and behavior problems. Models were re-estimated adjusting for wave nonresponse and using multiple imputation to account for attrition. Poverty predicted higher levels of behavior problems between 1.5 and 8 years of age. Poverty predicted hyperactivity and opposition in a time dependent manner. Hyperactivity [Bpoverty*age = 0.052; CI 95 % (0.002; 0.101)] and opposition [Bpoverty*age = 0.049; CI 95 % (0.018; 0.079)] increased at a faster rate up to age 5 years, and then decreased at a slower rate for poor than non-poor children. Physical aggression decreased at a steady rate over time for all children [Bpoverty*age = -0.030; p = 0.064). Estimates remained similar when accounting for attrition. Poverty predicted higher levels of behavior problems between 1.5 and 8 years of age. The difference between poor and non-poor children was stable over time for physical aggression, but increased with age for hyperactivity and opposition. Attrition among poor children did not compromise the validity of results.

  14. How poor are women in rural India?

    Science.gov (United States)

    Rajuladevi, A K

    1992-07-01

    The assessment of poor women in India as dependent and exploited regardless of poverty focused strategies is reflected in this review of relevant literature. The scholarly approaches to the problems of poor women involve redirection and expansion of resources to women (increase bank credit) through policy and institutional changes, and involve improving women's welfare through changes in class and gender hierarchies; both pertain to restructuring power groups. A little ascribed to belief is that the organization of women's numbers will empower women; the constraints are stated. There is also some argument over whether to design women-specific programs or integrate women into existing programs; some examples are given of successes and difficulties. The regionalization of poverty in eastern and central India is discussed. The growth of the poor has been among the landless, wage-dependent households. 9.6% of households (7.5 million) are headed by women. Women work fewer hours and at lower wage scales and have fewer employment opportunities. Lower earnings are coupled with differentials in demand for female and male labor in agriculture and a crowded labor market. There is a concentration of women in less visible, nonmonetary subsistence production and domestic work. Women are undercounted in employment studies. Women predominate in agricultural activity. Women's status is influenced by economic status, caste, and ethnic background. Domestic work increases status for women and households. The poorer households have greater labor force participation, particularly as wage laborers rather than unpaid family workers. Regional factors affecting rural household strategies are factors affecting the economy (topography, rainfall, climate) and the degree of development, plus sociocultural variables (kinship and religious beliefs whic