bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the (un)predictability of a large intragenic fitness landscape
Authors: Bank Claudia , Matuszewski Sebastian , Hietpas Ryan T. , Jensen Jeffrey D. 
Published: November 2016

SignificanceThe study of fitness landscapes is fundamentally concerned with understanding the relative roles of stochastic and deterministic processes in adaptive evolution. Here, the authors present a uniquely large and complete multiallelic intragenic fitness landscape of 640 systematically engineered mutations in the heat-shock protein Hsp90 in yeast. Using a combination of traditional and recently proposed theoretical approaches, they study the accessibility of the global fitness peak and the potential for predictability of the fitness landscape topography. They report local ruggedness of the landscape and the existence of epistatic hotspot mutations, which together make extrapolation and hence predictability inherently difficult if mutation-specific information is not considered.
Epstein–Barr virus super-enhancer eRNAs are essential for MYC oncogene expression and lymphoblast proliferation
Authors: Liang Jun , Zhou Hufeng , Gerdt Catherine , Tan Min , Colson Tyler , Kaye Kenneth M. , Kieff Elliott , Zhao Bo 
Published: November 2016

Significance
EBV infection causes African Burkitt's lymphoma; Hodgkin's disease; lymphomas in immune suppressed people, including HIV infected people; nasopharyngeal carcinoma; and ∼10% of gastric carcinomas. We recently found EBV super-enhancer (ESE) to be critical for lymphoblastoid cell (LCL) growth and survival. We now identified an ESE constituent, enhancer RNA (eRNA), that is important for ESE function. These eRNAs were activated by viral transactivator, EBV nuclear antigen 2 (EBNA2). MYC oncogene ESE eRNAs were able to enhance ESE activation of MYC expression and are essential for LCL growth. Targeting ESE eRNAs may lead to new therapeutics for EBV-associated malignancies.
Effect of Fe-rich particles and solutes on the creep behaviour of 8xxx alloys
Authors: Pan L. , Mirza F. A. , Liu K. , Chen X.-G. 
Published: November 2016

The creep behavior of 8xxx aluminum conductor alloys with different quantities of Fe-rich particles and solutes was investigated. Creep resistance was significantly improved with large amounts of Fe-rich particles and solutes. At 100 °C, a high Fe solute content (0.023 wt.%) had a stronger effect on creep resistance than FeAl3 particles. However, as the temperature increased to 150 and 200 °C, the effect of a high amount of FeAl3 particles (2.5 vol.%) was stronger. The threshold stress increased with increasing FeAl3 particle and Fe solute contents, with the effect of each factor being independent, but it decreased with increasing temperature. The true stress exponents were calculated to be 3.1, 3.8, and 4.5 at 100, 150 and 200 °C, respectively. GRAPHICAL ABSTRACT
The effects of high resistance–few repetitions and low resistance–high repetitions resistance training on climbing performance
Authors: Hermans Espen , Andersen Vidar , Saeterbakken Atle Hole 
Published: November 2016

AbstractThe aim of the study was to compare the effects of different strength training intensities on climbing performance, climbing‐specific tests and a general strength test. Thirty lower grade and intermediate‐level climbers participated in a 10‐week training programme. The participants were randomized into three groups: high resistance–few repetitions training groups (HR‐FR), low resistance–high repetitions training groups (LR‐HR) and a control group (CON) which continued climbing/training as usual. Post‐testing results demonstrated statistical tendencies for climbing performance improvements in the HR‐FR and LR‐HR (p = 0.088–0.090, effect size = 0.55–0.73), but no differences were observed between the groups (p = 0.950). For the climbing‐specific tests, no differences were observed between the groups (p = 0.507–1.000), but the HR‐FR and LR‐HR improved their time in both Dead‐hang (p = 0.004–0.026) and Bent‐arm hang (p < 0.001–0.002). The HR‐FR and LR‐HR improved their 12RM strength in pull‐down (p ≤ 0.001), but not the CON group (p = 0.250). No differences were observed in the CON group in any of the tests (p = 0.190–0.596) with the exception of improvement in Bent‐arm Hang (p = 0.018). The training groups reduced their climbing sessions during the intervention compared to the CON group (p = 0.057–0.074). In conclusion, HR‐FR and LR‐HR training programmes demonstrated an 11% and 12% non‐significant improvement in climbing performance despite a 50% reduction in climbing sessions, but improved the results in strength and climbing‐specific tests. None of the training intensities was superior compared to the others.
The effects of a three‐year integrated Olympic education programme on adolescents’ prosocial behaviours
Authors: Sukys Saulius , Majauskiene Daiva , Dumciene Audrone 
Published: November 2016

AbstractThe concept of Olympic education and its use of moral education to shape the development of personality have received insufficient empirical support. The aim of this study was to examine the effects of an integrated Olympic education programme on the development of prosocial behaviour in adolescents. A natural experimental research design was applied in this study. The pre‐test sample included 411 adolescents (aged 13–14) who were randomly selected from schools that had begun to apply an integrated Olympic education programme, along with 430 adolescents from schools without an Olympic education programme. The post‐test sample included 381 students from schools implementing the Olympic education programme and 402 students from schools without an Olympic education programme. The revised prosocial tendencies measure was administered to the participants at pre‐ and post‐test time points to assess changes in prosocial behaviour and specifically on six types of prosocial behaviour: public, anonymous, dire, emotional, compliant, and altruistic. The analyses showed significant improvements in prosocial behaviour in adolescents from schools that had implemented an integrated Olympic education programme. Changes in prosocial behaviour following the implementation of an integrated Olympic education programme were observed for the compliant, altruistic, and dire types of prosocial behaviour. In conclusion, these findings suggest that an integrated Olympic education programme effectively encourages prosocial behaviour in adolescents. This study expands our understanding of the efficiency of implementing an Olympic education programme in schools. We suggest that future research should investigate the behavioural changes in students of different ages from perspective of both teachers and students.
Sensory organisation and reactive balance control of amateur rugby players: A cross‐sectional study
Authors: Chow Gary C. C. , Chung Joanne W. Y. , Ma Ada W. W. , Macfarlane Duncan J. , Fong Shirley S. M. 
Published: November 2016

AbstractPurpose: This study compared the sensory organisation and reactive balance control of amateur rugby players and a control group. Methods: Forty‐one amateur rugby players (22 males: 19 females; mean height ± SD = 168.8 ± 8.8 cm; mean weight ± SD = 63.9 ± 12.5 kg) and 31 control participants (22 males: 9 females; mean height ± SD = 171.5 ± 10.3 cm; mean weight ± SD = 63.8 ± 10.3 kg) completed the study. Their sensory organisation and standing balance performance were evaluated using a sensory organisation test (SOT), and their reactive balance performance was quantified using a motor control test (MCT). The SOT equilibrium scores (ES) and sensory ratios and the MCT motor response latencies were the major outcome measures. Results: The results revealed that compared to the controls, amateur rugby players had lower SOT ESs under different sensory environments (P < .001, = 0.142–0.254) and prolonged reactive motor response times in the MCT (P < .001, d = 0.890). The vestibular and visual ratios were also lower in the rugby group (P = .005, = 0.107 and 0.108, respectively). No significant difference was found in the somatosensory ratio (P = .853, < 0.001) between the two groups. Conclusions: Amateur rugby players demonstrated inferior standing balance performance compared to their non‐trained counterparts. They relied less heavily on vestibular and visual inputs to maintain standing balance under different sensory environments. In addition, they reacted more slowly to postural disturbance, reflecting their suboptimal reactive balance ability in standing.
Markets, Transportation Infrastructure, and Food Prices in Nepal
Authors: Shively Gerald , Thapa Ganesh 
Published: November 2016

AbstractWe study transportation infrastructure and food markets in Nepal over the period 2002 to 2010, combining monthly price data from thirty‐seven local and regional markets, and seven Indian border markets. We use a series of autoregressive models to study price determination, spatial and temporal price transmission, and price variance. We account for district‐level agricultural production, correcting for bi‐directional causality between output and prices using ground station rainfall data. In addition, to test hypotheses regarding the importance of transportation infrastructure we incorporate information on road and bridge density and fuel costs. For both rice and wheat, we find strong evidence of local price intertemporal carryover and very weak evidence of price transmission from regional, central, and border markets to local markets, suggesting very low degrees of market integration. Fuel costs are positively correlated with food prices, and road and bridge density are negatively correlated with prices. We find evidence of asymmetric effects: positive price shocks are correlated with higher subsequent price volatility compared with negative price shocks of similar magnitude. Roads and bridges are important for moderating price levels and price volatility in Nepal's rice and wheat markets, which explains roughly half of the spatial and temporal variation in price mark‐ups between regional and local markets.
Predict drug permeability to blood–brain-barrier from clinical phenotypes: drug side effects and drug indications
Authors: Gao Zhen , Chen Yang , Cai Xiaoshu , Xu Rong 
Published: November 2016

Abstract

Motivation
Blood–Brain-Barrier (BBB) is a rigorous permeability barrier for maintaining homeostasis of Central Nervous System (CNS). Determination of compound’s permeability to BBB is prerequisite in CNS drug discovery. Existing computational methods usually predict drug BBB permeability from chemical structure and they generally apply to small compounds passing BBB through passive diffusion. As abundant information on drug side effects and indications has been recorded over time through extensive clinical usage, we aim to explore BBB permeability prediction from a new angle and introduce a novel approach to predict BBB permeability from drug clinical phenotypes (drug side effects and drug indications). This method can apply to both small compounds and macro-molecules penetrating BBB through various mechanisms besides passive diffusion.

Results
We composed a training dataset of 213 drugs with known brain and blood steady-state concentrations ratio and extracted their side effects and indications as features. Next, we trained SVM models with polynomial kernel and obtained accuracy of 76.0%, AUC 0.739, and F1 score (macro weighted) 0.760 with Monte Carlo cross validation. The independent test accuracy was 68.3%, AUC 0.692, F1 score 0.676. When both chemical features and clinical phenotypes were available, combining the two types of features achieved significantly better performance than chemical feature based approach (accuracy 85.5% versus 72.9%, AUC 0.854 versus 0.733, F1 score 0.854 versus 0.725; P &lt; e−90). We also conducted de novo prediction and identified 110 drugs in SIDER database having the potential to penetrate BBB, which could serve as start point for CNS drug repositioning research.

Availability and Implementation
https://github.com/bioinformatics-gao/CASE-BBB-prediction-Data

Supplementary information
Supplementary data are available at Bioinformatics online.
Hum-mPLoc 3.0: prediction enhancement of human protein subcellular localization through modeling the hidden correlations of gene ontology and functional domain features
Authors: Zhou Hang , Yang Yang , Shen Hong-Bin 
Published: November 2016

Abstract

Motivation
Protein subcellular localization prediction has been an important research topic in computational biology over the last decade. Various automatic methods have been proposed to predict locations for large scale protein datasets, where statistical machine learning algorithms are widely used for model construction. A key step in these predictors is encoding the amino acid sequences into feature vectors. Many studies have shown that features extracted from biological domains, such as gene ontology and functional domains, can be very useful for improving the prediction accuracy. However, domain knowledge usually results in redundant features and high-dimensional feature spaces, which may degenerate the performance of machine learning models.

Results
In this paper, we propose a new amino acid sequence-based human protein subcellular location prediction approach Hum-mPLoc 3.0, which covers 12 human subcellular localizations. The sequences are represented by multi-view complementary features, i.e. context vocabulary annotation-based gene ontology (GO) terms, peptide-based functional domains, and residue-based statistical features. To systematically reflect the structural hierarchy of the domain knowledge bases, we propose a novel feature representation protocol denoted as HCM (Hidden Correlation Modeling), which will create more compact and discriminative feature vectors by modeling the hidden correlations between annotation terms. Experimental results on four benchmark datasets show that HCM improves prediction accuracy by 5–11% and F1 by 8–19% compared with conventional GO-based methods. A large-scale application of Hum-mPLoc 3.0 on the whole human proteome reveals proteins co-localization preferences in the cell.

Availability and Implementation
www.csbio.sjtu.edu.cn/bioinf/Hum-mPLoc3/

Supplementary information
Supplementary data are available at Bioinformatics online.
Context-sensitive network-based disease genetics prediction and its implications in drug discovery
Authors: Chen Yang , Xu Rong 
Published: November 2016

Abstract

Motivation
Disease phenotype networks play an important role in computational approaches to identifying new disease-gene associations. Current disease phenotype networks often model disease relationships based on pairwise similarities, therefore ignore the specific context on how two diseases are connected. In this study, we propose a new strategy to model disease associations using context-sensitive networks (CSNs). We developed a CSN-based phenome-driven approach for disease genetics prediction, and investigated the translational potential of the predicted genes in drug discovery.

Results
We constructed CSNs by directly connecting diseases with associated phenotypes. Here, we constructed two CSNs using different data sources; the two networks contain 26 790 and 13 822 nodes respectively. We integrated the CSNs with a genetic functional relationship network and predicted disease genes using a network-based ranking algorithm. For comparison, we built Similarity-Based disease Networks (SBN) using the same disease phenotype data. In a de novo cross validation for 3324 diseases, the CSN-based approach significantly increased the average rank from top 12.6 to top 8.8% for all tested genes comparing with the SBN-based approach (p&lt;e−22). The area under the receiver operating characteristic curve for the CSN approach was also significantly higher than the SBN approach (0.91 versus 0.87, p&lt;e−3). In addition, we predicted genes for Parkinson’s disease using CSNs, and demonstrated that the top-ranked genes are highly relevant to PD pathologenesis. We pin-pointed a top-ranked drug target gene for PD, and found its association with neurodegeneration supported by literature. In summary, CSNs lead to significantly improve the disease genetics prediction comparing with SBNs and provide leads for potential drug targets.

Availability and Implementation
nlp.case.edu/public/data/
caspo: a toolbox for automated reasoning on the response of logical signaling networks families
Authors: Videla Santiago , Saez-Rodriguez Julio , Guziolowski Carito , Siegel Anne 
Published: November 2016

Abstract

Summary
We introduce the caspo toolbox, a python package implementing a workflow for reasoning on logical networks families. Our software allows researchers to (i) learn a family of logical networks derived from a given topology and explaining the experimental response to various perturbations; (ii) classify all logical networks in a given family by their input-output behaviors; (iii) predict the response of the system to every possible perturbation based on the ensemble of predictions; (iv) design new experimental perturbations to discriminate among a family of logical networks; and (v) control a family of logical networks by finding all interventions strategies forcing a set of targets into a desired steady state.

Availability and Implementation
caspo is open-source software distributed under the GPLv3 license. Source code is publicly hosted at http://github.com/bioasp/caspo.
Green listed—a CRISPR screen tool
Authors: Panda Sudeepta Kumar , Boddul Sanjay V , Jiménez-Andrade Guillermina Yanek , Jiang Long , Kasza Zsolt , Fernandez-Ricaud Luciano , Wermeling Fredrik 
Published: November 2016

Abstract

Motivation
Genome editing using versions of the bacterial CRISPR/Cas9 system can be used to probe the function of selected genes in any organism. Green Listed is a web-based tool that rapidly designs custom CRISPR screens targeting sets of genes defined by the user. It could thus be used to design screens targeting for example all genes differentially expressed during a specific stimuli or all genes related to a specific pathway or function, as well as to generate targeted secondary screens following a large-scale screen.

Availability and Implementation
The software, including a demo function as well as explanatory texts and videos, is available through greenlisted.cmm.ki.se.
SeqLib: a C ++ API for rapid BAM manipulation, sequence alignment and sequence assembly
Authors: Wala Jeremiah , Beroukhim Rameen 
Published: November 2016

Abstract
We present SeqLib, a C ++ API and command line tool that provides a rapid and user-friendly interface to BAM/SAM/CRAM files, global sequence alignment operations and sequence assembly. Four C libraries perform core operations in SeqLib: HTSlib for BAM access, BWA-MEM and BLAT for sequence alignment and Fermi for error correction and sequence assembly. Benchmarking indicates that SeqLib has lower CPU and memory requirements than leading C ++ sequence analysis APIs. We demonstrate an example of how minimal SeqLib code can extract, error-correct and assemble reads from a CRAM file and then align with BWA-MEM. SeqLib also provides additional capabilities, including chromosome-aware interval queries and read plotting. Command line tools are available for performing integrated error correction, micro-assemblies and alignment.
Availability and Implementation: SeqLib is available on Linux and OSX for the C ++98 standard and later at github.com/walaj/SeqLib. SeqLib is released under the Apache2 license. Additional capabilities for BLAT alignment are available under the BLAT license.
Association of Diabetes and Insulin Therapy With Risk of Hospitalization for Infection and 28-Day Mortality Risk
Authors: Donnelly John P. , Nair Sunil , Griffin Russell , Baddley John W. , Safford Monika M. , Wang Henry E. , Shapiro Nathan I. 
Published: November 2016

Abstract

Background.
Epidemiologic and experimental evidence suggests that individuals with diabetes are at increased risk of infection. We sought to examine the association of diabetes and insulin therapy with hospitalization for infection and 28-day mortality.

Methods.
We performed a prospective cohort study using data from 30 239 community-dwelling participants aged ≥45 years enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. We defined diabetes as a fasting glucose level ≥126 mg/L (or ≥200 mg/L for those not fasting), the use of insulin or oral hypoglycemic agents, or self-reported history. We identified infection-related hospitalizations over the years 2003–2012. We fit Cox proportional hazards models to assess the association of diabetes with hazard rates of infection and logistic regression models for 28-day mortality.

Results.
Among 29 683 patients from the REGARDS study with complete follow-up, 7375 had diabetes. Over a median follow-up period of 6.5 years, we identified 2593 first and 3411 total infection hospitalizations. In adjusted analyses, participants with diabetes had an increased hazard of infection (hazard ratio, 1.50; 95% confidence interval [CI], 1.37–1.64) compared with those without diabetes. Participants with diabetes hospitalized for infection did not have an increased odds of death within 28 days (odds ratio, 0.94; 95% CI, .67–1.32). Participants receiving insulin therapy had greater hazard of infection (hazard ratio, 2.18; 95% CI, 1.90–2.51) but no increased odds of mortality (odd ratio, 1.07; 95% CI, .67–1.71).

Conclusions.
Diabetes is associated with increased risk of hospitalization for infection. However, we did not find an association with 28-day mortality. Insulin therapy conferred an even greater risk of hospitalization, without increased mortality.
What Is the More Effective Antibiotic Stewardship Intervention: Preprescription Authorization or Postprescription Review With Feedback?
Authors: Tamma Pranita D. , Avdic Edina , Keenan John F. , Zhao Yuan , Anand Gobind , Cooper James , Dezube Rebecca , Hsu Steven , Cosgrove Sara E. 
Published: November 2016

Abstract

Background.
The optimal approach to conducting antibiotic stewardship interventions has not been defined. We compared days of antibiotic therapy (DOT) using preprescription authorization (PPA) vs postprescription review with feedback (PPRF) strategies.

Methods.
A quasi-experimental, crossover trial comparing PPA and PPRF for adult inpatients prescribed any antibiotic was conducted. For the first 4 months, 2 medicine teams were assigned to the PPA arm and the other 2 teams to the PPRF arm. The teams were then assigned to the alternate arm for an additional 4 months. Appropriateness of antibiotic use was adjudicated by at least 2 infectious diseases–trained clinicians and according to institutional guidelines.

Results. There were 2686 and 2693 patients admitted to the PPA and PPRF groups, with
29% and 27% of patients prescribed antibiotics, respectively. Initially, antibiotic DOTs remained relatively unchanged in the PPA arm. When changed to the PPRF arm, antibiotic use decreased (−2.45 DOT per 1000 patient-days [PD]). In the initial PPRF arm, antibiotic use decreased (slope of −5.73 DOT per 1000 PD) but remained constant when changed to the PPA arm. Median patient DOTs in the PPA and PPRF arms were 8 and 6 DOT per 1000 PD, respectively (P = .03). Antibiotic therapy was guideline-noncompliant in 34% and 41% of patients on days 1 and 3 in the PPA group (P &lt; .01) and in 57% and 36% of patients on days 1 and 3 in the PPRF group (P = .03).

Conclusions.
PPRF may have more of an impact on decreasing antibiotic DOTs compared with PPA. This information may be useful for institutions without sufficient resources to incorporate both stewardship approaches.