bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene–gene interaction analysis for the survival phenotype based on the Cox model
Authors: Lee Seungyeoun , Kwon Min-Seok , Oh Jung Mi , Park Taesung 
Published: September 2012

AbstractMotivation: For the past few decades, many statistical methods in genome-wide association studies (GWAS) have been developed to identify SNP–SNP interactions for case-control studies. However, there has been less work for prospective cohort studies, involving the survival time. Recently, Gui et al. (2011) proposed a novel method, called Surv-MDR, for detecting gene–gene interactions associated with survival time. Surv-MDR is an extension of the multifactor dimensionality reduction (MDR) method to the survival phenotype by using the log-rank test for defining a binary attribute. However, the Surv-MDR method has some drawbacks in the sense that it needs more intensive computations and does not allow for a covariate adjustment. In this article, we propose a new approach, called Cox-MDR, which is an extension of the generalized multifactor dimensionality reduction (GMDR) to the survival phenotype by using a martingale residual as a score to classify multi-level genotypes as high- and low-risk groups. The advantages of Cox-MDR over Surv-MDR are to allow for the effects of discrete and quantitative covariates in the frame of Cox regression model and to require less computation than Surv-MDR.Results: Through simulation studies, we compared the power of Cox-MDR with those of Surv-MDR and Cox regression model for various heritability and minor allele frequency combinations without and with adjusting for covariate. We found that Cox-MDR and Cox regression model perform better than Surv-MDR for low minor allele frequency of 0.2, but Surv-MDR has high power for minor allele frequency of 0.4. However, when the effect of covariate is adjusted for, Cox-MDR and Cox regression model perform much better than Surv-MDR. We also compared the performance of Cox-MDR and Surv-MDR for a real data of leukemia patients to detect the gene–gene interactions with the survival time.Contact: leesy@sejong.ac.kr; tspark@snu.ac.kr
Context-specific transcriptional regulatory network inference from global gene expression maps using double two-way t-tests
Authors: Qi Jianlong , Michoel Tom 
Published: September 2012

Abstract
Motivation: Transcriptional regulatory network inference methods have been studied for years. Most of them rely on complex mathematical and algorithmic concepts, making them hard to adapt, re-implement or integrate with other methods. To address this problem, we introduce a novel method based on a minimal statistical model for observing transcriptional regulatory interactions in noisy expression data, which is conceptually simple, easy to implement and integrate in any statistical software environment and equally well performing as existing methods.
Results: We developed a method to infer regulatory interactions based on a model where transcription factors (TFs) and their targets are both differentially expressed in a gene-specific, critical sample contrast, as measured by repeated two-way t-tests. Benchmarking on standard Escherichia coli and yeast reference datasets showed that this method performs equally well as the best existing methods. Analysis of the predicted interactions suggested that it works best to infer context-specific TF-target interactions which only co-express locally. We confirmed this hypothesis on a dataset of &gt;1000 normal human tissue samples, where we found that our method predicts highly tissue-specific and functionally relevant interactions, whereas a global co-expression method only associates general TFs to non-specific biological processes.
Availability: A software tool called TwixTrix is available from http://twixtrix.googlecode.com.
Supplementary information: Supplementary Material is available from http://www.roslin.ed.ac.uk/tom-michoel/supplementary-data.
Contact: tom.michoel@roslin.ed.ac.uk
Performance reproducibility index for classification
Authors: Yousefi Mohammadmahdi R. , Dougherty Edward R. 
Published: September 2012

Abstract
Motivation: A common practice in biomarker discovery is to decide whether a large laboratory experiment should be carried out based on the results of a preliminary study on a small set of specimens. Consideration of the efficacy of this approach motivates the introduction of a probabilistic measure, for whether a classifier showing promising results in a small-sample preliminary study will perform similarly on a large independent sample. Given the error estimate from the preliminary study, if the probability of reproducible error is low, then there is really no purpose in substantially allocating more resources to a large follow-on study. Indeed, if the probability of the preliminary study providing likely reproducible results is small, then why even perform the preliminary study?
Results: This article introduces a reproducibility index for classification, measuring the probability that a sufficiently small error estimate on a small sample will motivate a large follow-on study. We provide a simulation study based on synthetic distribution models that possess known intrinsic classification difficulties and emulate real-world scenarios. We also set up similar simulations on four real datasets to show the consistency of results. The reproducibility indices for different distributional models, real datasets and classification schemes are empirically calculated. The effects of reporting and multiple-rule biases on the reproducibility index are also analyzed.
Availability: We have implemented in C code the synthetic data distribution model, classification rules, feature selection routine and error estimation methods. The source code is available at http://gsp.tamu.edu/Publications/supplementary/yousefi12a/. Supplementary simulation results are also included.
Contact: edward@ece.tamu.edu
Supplementary Information: Supplementary data are available at Bioinformatics online.
Mendel-GPU: haplotyping and genotype imputation on graphics processing units
Authors: Chen Gary K. , Wang Kai , Stram Alex H. , Sobel Eric M. , Lange Kenneth 
Published: September 2012

Abstract
Motivation: In modern sequencing studies, one can improve the confidence of genotype calls by phasing haplotypes using information from an external reference panel of fully typed unrelated individuals. However, the computational demands are so high that they prohibit researchers with limited computational resources from haplotyping large-scale sequence data.
Results: Our graphics processing unit based software delivers haplotyping and imputation accuracies comparable to competing programs at a fraction of the computational cost and peak memory demand.
Availability: Mendel-GPU, our OpenCL software, runs on Linux platforms and is portable across AMD and nVidia GPUs. Users can download both code and documentation at http://code.google.com/p/mendel-gpu/.
Contact: gary.k.chen@usc.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
SAPIN: A framework for the structural analysis of protein interaction networks
Authors: Yang Jae-Seong , Campagna Anne , Delgado Javier , Vanhee Peter , Serrano Luis , Kiel Christina 
Published: September 2012

Abstract
Summary: Protein interaction networks are widely used to depict the relationships between proteins. These networks often lack the information on physical binary interactions, and they do not inform whether there is incompatibility of structure between binding partners. Here, we introduce SAPIN, a framework dedicated to the structural analysis of protein interaction networks. SAPIN first identifies the protein parts that could be involved in the interaction and provides template structures. Next, SAPIN performs structural superimpositions to identify compatible and mutually exclusive interactions. Finally, the results are displayed using Cytoscape Web.
Availability: The SAPIN server is available at http://sapin.crg.es.
Contact: jae-seong.yang@crg.eu or christina.kiel@crg.eu
Supplementary information: Supplementary data are available at Bioinformatics Online.
Increased age of transformed mouse neural progenitor/stem cells recapitulates age‐dependent clinical features of human glioma malignancy
Authors: Mikheev Andrei M. , Ramakrishna Rohan , Stoll Elizabeth A. , Mikheeva Svetlana A. , Beyer Richard P. , Plotnik David A. , Schwartz Jeffrey L. , Rockhill Jason K. , Silber John R. , Born Donald E. , Kosai Yoshito , Horner Philip J. , Rostomily Robert C. 
Published: September 2012

SummaryIncreasing age is the most robust predictor of greater malignancy and treatment resistance in human gliomas. However, the adverse association of clinical course with aging is rarely considered in animal glioma models, impeding delineation of the relative importance of organismal versus progenitor cell aging in the genesis of glioma malignancy. To address this limitation, we implanted transformed neural stem/progenitor cells (NSPCs), the presumed cells of glioma origin, from 3‐ and 18‐month‐old mice into 3‐ and 20‐month host animals. Transplantation with progenitors from older animals resulted in significantly shorter (P ≤ 0.0001) median survival in both 3‐month (37.5 vs. 83 days) and 20‐month (38 vs. 67 days) hosts, indicating that age‐dependent changes intrinsic to NSPCs rather than host animal age accounted for greater malignancy. Subsequent analyses revealed that increased invasiveness, genomic instability, resistance to therapeutic agents, and tolerance to hypoxic stress accompanied aging in transformed NSPCs. Greater tolerance to hypoxia in older progenitor cells, as evidenced by elevated HIF‐1 promoter reporter activity and hypoxia response gene (HRG) expression, mirrors the upregulation of HRGs in cohorts of older vs. younger glioma patients revealed by analysis of gene expression databases, suggesting that differential response to hypoxic stress may underlie age‐dependent differences in invasion, genomic instability, and treatment resistance. Our study provides strong evidence that progenitor cell aging is responsible for promoting the hallmarks of age‐dependent glioma malignancy and that consideration of progenitor aging will facilitate development of physiologically and clinically relevant animal models of human gliomas.
Geophagy by African ungulates: the case of the critically endangered giant sable antelope of Angola (Hippotragus niger variani)
Authors: Baptista Sendi Lara , Pinto Pedro Vaz , Freitas Maria da Conceição , Cruz Cristina , Palmeirim Jorge M. 
Published: September 2012

AbstractThe giant sable antelope (Hippotragus niger variani) is a critically endangered subspecies with a range restricted to a small area in the Angolan plateau. It is known to display geophagic behaviour, eating the soil of some Macrotermes termitaria. The aim of this study was to understand the importance of this behaviour for the giant sable and other ungulates sharing its range. We identified termite mounds used for geophagy based on local information confirmed by self‐triggering cameras. We collected and analysed soil samples of seven termitaria consumed by ungulates, the adjacent topsoil 50 m away from each, and seven control nonconsumed termitaria. Consumed termite mounds were richer in minerals than control mounds, and both were richer than the surrounding topsoil. Sodium levels showed the greatest contrasts and were about 20 times more abundant in consumed termitaria than in controls. The amount of sodium in background soil was extremely low (9.3 ppm), suggesting that this mineral is a limiting nutrient in the range of the giant sable. These results indicate that the observed geophagic habits may be driven by a need to compensate for a sodium deficiency. This situation should be considered in the planning of the species' conservation.
Child development at 5 years of age predicted mathematics ability and schooling outcomes in Malawian adolescents
Authors: Gandhi Mihir , Teivaanmaki Tiina , Maleta Kenneth , Duan Xiaolian , Ashorn Per , Cheung Yin Bun 
Published: September 2012

AbstractAim:  This study aimed to examine the association between child development at 5 years of age and mathematics ability and schooling outcomes at 12 years of age in Malawian children.Methods:  A prospective cohort study looking at 609 rural Malawian children. Outcome measures were percentage of correctly answered mathematics questions, highest school grade completed and number of times repeating school grades at 12 years of age. A child development summary score obtained at 5 years of age was the main exposure variable. Regression analyses were used to estimate the association and adjust for confounders. Sensitivity analysis was performed by handling losses to follow‐up with multiple imputation (MI) method.Results:  The summary score was positively associated with percentage of correctly answered mathematics questions (p = 0.057; p = 0.031 MI) and with highest school grade completed (p = 0.096; p = 0.070 MI), and negatively associated with number of times repeating school grades (p = 0.834; p = 0.339 MI). Fine motor score at 5 years was independently associated with the mathematic score (p = 0.032; p = 0.011 MI). The association between child development and mathematics ability did not depend on school attendance.Conclusion:  Child development at 5 years of age showed signs of positive association with mathematics ability and possibly with highest school grade completed at 12 years of age.
Parents' perceptions of contact with the Norwegian Child Welfare Services
Authors: Studsrød Ingunn , Willumsen Elisabeth , Ellingsen Ingunn T. 
Published: September 2012

AbstractListening to the opinions of service users is important in research. This study explored how parents cognitively and emotionally perceive contact with the Norwegian Child Welfare Services (CWS). It also compared the reports of parents recently referred to the CWS with reports of more experienced users. A content analysis was conducted on open‐ended survey responses from parents (n = 697). This study fills a gap in the literature on how parents perceive contact with the CWS and what they see as important factors when judging this contact. The findings showed that 40.6% of the parents reported exclusively positive experiences, 30.7% of the parents reported solely negative experiences, while 24% of the parents described both positive and negative experiences. The content of the positive and negative experiences were related to characteristics of the child welfare workers, the quality of the relationship, the help offered and the parent's feelings of insecurity and fear. New CWS users tended to view the contact as more positive than the more experienced ones. Practical implications are presented.
Prognostic significance of thymidylate synthase polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy
Authors: Arrazubi V. , Suárez J. , Guerrero D. , Gómez M. , Viúdez A. , Arias F. , Balén E. , Vera R. 
Published: September 2012

AbstractAim  There is a lack of prognostic factors of preoperative chemoradiation for locally advanced rectal cancer. Thymidylate synthase (TS) is the most important target of 5‐fluorouracil; three main genetic polymorphisms of TS have been described. We analysed the prognostic value of these in patients with locally advanced rectal cancer treated with fluoropyrimidine‐based chemoradiation.Method  Ninety‐nine patients treated between November 2001 and March 2009 were included. All were treated by radiotherapy (5040 cGy) and concomitant fluoropyrimidine‐based chemotherapy. Three polymorphisms were analysed: (i) a double (2R) or triple (3R) repeat of a 28 base pair (bp) tandem sequence upstream of the ATG codon initiation site in the 5′‐terminal regulatory region, (ii) a functional G > C single nucleotide polymorphism present in the second repeat of the 3R alleles and (iii) a 6 bp deletion at nucleotide 1494 in the 3′‐untranslated region. DNA was extracted from paraffin‐embedded core biopsies taken from the tumour and the genotype was analysed using polymerase chain reaction restriction fragment length polymorphism.Results  The 6 bp polymorphism was significantly associated with disease‐free survival (+ 6 bp/+ 6 bp vs−6 bp/−6 bp, P = 0.032 logistic regression). No differences were found in disease‐free survival according to the other polymorphisms studied. No relationship was observed between the different TS genotypes and pathological regression.Conclusion  The study suggests that the TS 6 bp polymorphism may be a predictor of disease‐free survival in patients with locally advanced rectal cancer treated with fluoropyrimidine‐based chemoradiation.
A systematic review of peripheral nerve injury following laparoscopic colorectal surgery
Authors: Codd R. J. , Evans M. D. , Sagar P. M. , Williams G. L. 
Published: September 2012

AbstractAim  The risk of peripheral nerve injury associated with laparoscopic colorectal surgery has not been well established. We aimed to identify the number and type of peripheral nerve injuries associated with patient positioning in laparoscopic surgery.Method  A systematic review of MEDLINE and Embase was undertaken of English and non‐English language articles. Search terms included the key words: laparoscopic, colorectal, nerve injury, nerve damage, brachial plexus, peripheral neuropathy, peripheral nerve injury, nerve and colonic injury. Articles were included where at least one peripheral nerve injury had been documented related to patient positioning at laparoscopic colorectal surgery. Data extraction for articles was conducted by two authors, using predefined data fields.Results  Ten cases have been reported in the literature. All injuries involved the brachial plexus. They were associated with a lengthy procedure and abduction of the arm.Conclusion  Although rare, the surgeon and theatre team must be aware of the risk of peripheral nerve injury when positioning patients for laparoscopic colorectal procedures.
Result of the implementation of multidisciplinary teams in rectal cancer
Authors: Wille‐Jørgensen P. , Sparre P. , Glenthøj A. , Holck S. , Nørgaard Petersen L. , Harling H. , Stub Højen H. , Bülow S. 
Published: September 2012

AbstractAim  In 2003 colorectal multidisciplinary teams (MDTs) were established in all major Danish hospitals treating colorectal cancer. The aim was to improve the prognosis by multidisciplinary evaluation and decision about surgical and oncological treatment, based on medical history, clinical examination, imaging, histology and comorbidity. The present study evaluates the effect of the introduction of colorectal MDTs on 1 August 2004 in two Danish hospitals.Method  A retrospective cohort study was conducted comparing the outcome during the last 3 years before introduction of MDTs with the first 2 years after (the MDT cohort). The national colorectal cancer database, with follow‐up recorded by the National Patient Registry in September 2010 was used. The end‐points included the incidence of preoperative radiochemotherapy offered according to the national guidelines, R0/R1/R2 resection, postoperative mortality, local recurrence, distant recurrence and over‐all and disease‐free survival.Results  Eight hundred and eleven patients were diagnosed with primary rectal cancer in Hvidovre and Bispebjerg hospitals between 1 May 2001 and 31 August 2006. The frequency of preoperative MRI scans increased in the MDT cohort and perioperative mortality decreased. More metachronous distant metastases were found in the MDT cohort but there was no difference in overall survival.Conclusion  There was an improved postoperative mortality but no other potential benefits for the patients were seen after the implementation of colorectal MDTs.
Effects of ezetimibe on visceral fat in the metabolic syndrome: a randomised controlled study
Authors: Takase Hiroyuki , Dohi Yasuaki , Okado Tateo , Hashimoto Tomomi , Goto Yoshie , Kimura Genjiro 
Published: September 2012

Eur J Clin Invest 2012; 42 (12): 1287–1294AbstractBackground  Although visceral obesity, a key abnormality in the metabolic syndrome, is an important risk for cardiovascular diseases, reduction in visceral fat is hard to achieve despite intensive efforts directed at lifestyle modification. The present study was designed to investigate whether ezetimibe, an inhibitor of intestinal cholesterol absorption through its binding to Niemann‐Pick C1‐like 1, reduces visceral fat in patients with metabolic syndrome.Materials and Methods  Seventy‐eight outpatients (63·7 ± 10·4 years old) with metabolic syndrome were enroled and randomly assigned to receive either ezetimibe (10 mg/day) or nothing for 6 months. Changes in visceral fat were assessed by computed tomography.Results  Treatment with ezetimibe significantly improved lipid profiles. Visceral fat was decreased 7·2%, from 161·3 ± 58·6 cm2 to 148·4 ± 52·7 cm2 (P < 0·05), and adiponectin was increased 7·7%, from 3·61 ± 3·10 μg/mL to 3·86 ± 3·62 μg/mL (P < 0·05), after ezetimibe therapy; these beneficial effects were not observed in the control group. The increase in the adiponectin level was correlated with the reduction in visceral fat after ezetimibe treatment. Furthermore, ezetimibe reduced fasting insulin levels (P < 0·05) and improved the homoeostasis model assessment of insulin resistance (HOMA‐IR) (P < 0·05).Conclusions  Ezetimibe reduces visceral fat with beneficial effects on adiponectin and insulin resistance in patients with metabolic syndrome, suggesting a new therapeutic approach in such patients.
Cystatin M/E knockdown by lentiviral delivery of shRNA impairs epidermal morphogenesis of human skin equivalents
Authors: Jansen Patrick A. M. , van den Bogaard Ellen H. , Kersten Ferry F. J. , Oostendorp Corien , van Vlijmen‐Willems Ivonne M. J. J. , Oji Vinzenz , Traupe Heiko , Hennies Hans C. , Schalkwijk Joost , Zeeuwen Patrick L. J. M. 
Published: September 2012

AbstractThe protease inhibitor cystatin M/E (CST6) regulates a biochemical pathway involved in stratum corneum homeostasis, and its deficiency in mice causes ichthyosis and neonatal lethality. Cystatin M/E deficiency has not been described in humans so far, and we did not detect disease‐causing mutations in the CST6 gene in a large number of patients with autosomal recessive congenital ichthyosis, who were negative for mutations in known ichthyosis‐associated genes. To investigate the phenotype of CST6 deficiency in human epidermis, we used lentiviral delivery of short hairpin RNAs that target CST6 in a 3D reconstructed skin model. Surprisingly, CST6 deficiency did not cause an ichthyosis‐like phenotype, but prevented the development of a multilayered epidermis. From this study, we conclude that CST6 deficiency may be incompatible with normal human foetal development.
GATA‐3 regulates differentiation‐specific loricrin gene expression in keratinocytes
Authors: Kawachi Yasuhiro , Ishitsuka Yosuke , Maruyama Hiroshi , Fujisawa Yasuhiro , Furuta Junichi , Nakamura Yasuhiro , Otsuka Fujio 
Published: September 2012

AbstractLoricrin is a major component of the epidermal cornified cell envelope and is expressed only in terminally differentiated keratinocytes. This cell differentiation‐specific expression pattern suggests specific regulatory mechanisms for activation of loricrin gene transcription in differentiated keratinocytes. Here, we identified a positive regulatory element in the proximal promoter region of the loricrin gene involved in activation of its expression in differentiated keratinocytes. A database search indicated that this sequence contained a GATA‐3 binding motif. Constructs with point mutations in the GATA‐3 binding motif showed decreased reporter activity, indicating that GATA‐3 positively regulates loricrin gene transcription. Western blotting analysis indicated that GATA‐3 is more abundant in differentiated than in undifferentiated keratinocytes. Cotransfection experiments indicated that GATA‐3 activates transcription of the loricrin gene in a cooperative manner with c‐Fos and Sp1. These findings indicate that GATA‐3 contributes to keratinocyte differentiation‐specific activation of loricrin gene transcription via interaction with c‐Fos and Sp1.