bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical database analysis of the role of loop dynamics for protein–protein complex formation and allostery
Authors: Gu Yina , Li Da-Wei , Brüschweiler Rafael 
Published: February 2017

Abstract

Motivation
Protein loops show rich conformational dynamics properties on a wide range of timescales as they play an essential role for many cellular functions during protein–protein interactions and recognition processes. However, little is known about the detail behavior of loops upon protein binding including allostery.

Results
We report the loop motions and their dominant timescales for a library of 230 proteins that form protein–protein complexes using the ToeLoop predictor of loop dynamics. We applied the analysis to proteins in both their complex and free state and relate specific loop properties to their role in protein recognition. We observe a strong tendency of loops that move on relatively slow timescales of tens of ns to sub-μs to be directly involved in binding and recognition processes. Complex formation leads to a significant reduction in loop flexibility at the binding interface, but in a number of cases it can also trigger increased flexibility in distal loops in response to allosteric conformational changes. The importance of loop dynamics and allostery is highlighted by a case study of an antibody-antigen complex. Furthermore, we explored the relationship between loop dynamics and experimental binding affinities and found that a prevalence of high loop rigidity at the binding interface is an indicator of increased binding strength.

Availability and Implementation
http://spin.ccic.ohio-state.edu/index.php/toeloopppi

Supplementary information
Supplementary data are available at Bioinformatics online.
Genome-wide genetic heterogeneity discovery with categorical covariates
Authors: Llinares-López Felipe , Papaxanthos Laetitia , Bodenham Dean , Roqueiro Damian ,   COPDGene Investigators, Borgwardt Karsten 
Published: February 2017

Abstract

Motivation
Genetic heterogeneity is the phenomenon that distinct genetic variants may give rise to the same phenotype. The recently introduced algorithm Fast Automatic Interval Search (FAIS) enables the genome-wide search of candidate regions for genetic heterogeneity in the form of any contiguous sequence of variants, and achieves high computational efficiency and statistical power. Although FAIS can test all possible genomic regions for association with a phenotype, a key limitation is its inability to correct for confounders such as gender or population structure, which may lead to numerous false-positive associations.

Results
We propose FastCMH, a method that overcomes this problem by properly accounting for categorical confounders, while still retaining statistical power and computational efficiency. Experiments comparing FastCMH with FAIS and multiple kinds of burden tests on simulated data, as well as on human and Arabidopsis samples, demonstrate that FastCMH can drastically reduce genomic inflation and discover associations that are missed by standard burden tests.

Availability and Implementation
An R package fastcmh is available on CRAN and the source code can be found at: https://www.bsse.ethz.ch/mlcb/research/bioinformatics-and-computational-biology/fastcmh.html

Supplementary information
Supplementary data are available at Bioinformatics online.
Threshold-seq: a tool for determining the threshold in short RNA-seq datasets
Authors: Magee Rogan , Loher Phillipe , Londin Eric , Rigoutsos Isidore 
Published: February 2017

Abstract

Summary
We present ‘Threshold-seq,’ a new approach for determining thresholds in deep-sequencing datasets of short RNA transcripts. Threshold-seq addresses the critical question of how many reads need to support a short RNA molecule in a given dataset before it can be considered different from ‘background.’ The proposed scheme is easy to implement and incorporate into existing pipelines.

Availability and Implementation
Source code of Threshold-seq is freely available as an R package at: http://cm.jefferson.edu/threshold-seq/

Supplementary information
Supplementary data are available at Bioinformatics online.
PMAnalyzer: a new web interface for bacterial growth curve analysis
Authors: Cuevas Daniel A , Edwards Robert A 
Published: February 2017

Abstract

Summary
Bacterial growth curves are essential representations for characterizing bacteria metabolism within a variety of media compositions. Using high-throughput, spectrophotometers capable of processing tens of 96-well plates, quantitative phenotypic information can be easily integrated into the current data structures that describe a bacterial organism. The PMAnalyzer pipeline performs a growth curve analysis to parameterize the unique features occurring within microtiter wells containing specific growth media sources. We have expanded the pipeline capabilities and provide a user-friendly, online implementation of this automated pipeline. PMAnalyzer version 2.0 provides fast automatic growth curve parameter analysis, growth identification and high resolution figures of sample-replicate growth curves and several statistical analyses.

Availability and Implementation
PMAnalyzer v2.0 can be found at https://edwards.sdsu.edu/pmanalyzer/. Source code for the pipeline can be found on GitHub at https://github.com/dacuevas/PMAnalyzer. Source code for the online implementation can be found on GitHub at https://github.com/dacuevas/PMAnalyzerWeb.

Supplementary information
Supplementary data are available at Bioinformatics online.
MotifMap-RNA: a genome-wide map of RBP binding sites
Authors: Liu Yu , Sun Sha , Bredy Timothy , Wood Marcelo , Spitale Robert C , Baldi Pierre 
Published: February 2017

Abstract

Motivation
RNA plays a critical role in gene expression and its regulation. RNA binding proteins (RBPs), in turn, are important regulators of RNA. Thanks to the availability of large scale data for RBP binding motifs and in vivo binding sites results in the form of eCLIP experiments, it is now possible to computationally predict RBP binding sites across the whole genome.

Results
We describe MotifMap-RNA, an extension of MotifMap which predicts binding sites for RBP motifs across human and mouse genomes and allows large scale querying of predicted binding sites.

Availability and Implementation
The data and corresponding web server are available from: http://motifmap-rna.ics.uci.edu/ as part of the MotifMap web portal.

Supplementary information
Supplementary data are available at Bioinformatics online.
Glimma: interactive graphics for gene expression analysis
Authors: Su Shian , Law Charity W , Ah-Cann Casey , Asselin-Labat Marie-Liesse , Blewitt Marnie E , Ritchie Matthew E 
Published: February 2017

Abstract

Motivation
Summary graphics for RNA-sequencing and microarray gene expression analyses may contain upwards of tens of thousands of points. Details about certain genes or samples of interest are easily obscured in such dense summary displays. Incorporating interactivity into summary plots would enable additional information to be displayed on demand and facilitate intuitive data exploration.

Results
The open-source Glimma package creates interactive graphics for exploring gene expression analysis with a few simple R commands. It extends popular plots found in the limma package, such as multi-dimensional scaling plots and mean-difference plots, to allow individual data points to be queried and additional annotation information to be displayed upon hovering or selecting particular points. It also offers links between plots so that more information can be revealed on demand. Glimma is widely applicable, supporting data analyses from a number of well-established Bioconductor workflows (limma, edgeR and DESeq2) and uses D3/JavaScript to produce HTML pages with interactive displays that enable more effective data exploration by end-users. Results from Glimma can be easily shared between bioinformaticians and biologists, enhancing reporting capabilities while maintaining reproducibility.

Availability and Implementation
The Glimma R package is available from http://bioconductor.org/packages/Glimma/.
BCFtools/csq: haplotype-aware variant consequences
Authors: Danecek Petr , McCarthy Shane A 
Published: February 2017

Abstract

Motivation
Prediction of functional variant consequences is an important part of sequencing pipelines, allowing the categorization and prioritization of genetic variants for follow up analysis. However, current predictors analyze variants as isolated events, which can lead to incorrect predictions when adjacent variants alter the same codon, or when a frame-shifting indel is followed by a frame-restoring indel. Exploiting known haplotype information when making consequence predictions can resolve these issues.

Results
BCFtools/csq is a fast program for haplotype-aware consequence calling which can take into account known phase. Consequence predictions are changed for 501 of 5019 compound variants found in the 81.7M variants in the 1000 Genomes Project data, with an average of 139 compound variants per haplotype. Predictions match existing tools when run in localized mode, but the program is an order of magnitude faster and requires an order of magnitude less memory.

Availability and Implementation
The program is freely available for commercial and non-commercial use in the BCFtools package which is available for download from http://samtools.github.io/bcftools.

Supplementary information
Supplementary data are available at Bioinformatics online.
Supervised multiblock sparse multivariable analysis with application to multimodal brain imaging genetics
Authors: Kawaguchi Atsushi , Yamashita Fumio 
Published: February 2017

SUMMARYThis article proposes a procedure for describing the relationship between high-dimensional data sets, such as multimodal brain images and genetic data. We propose a supervised technique to incorporate the clinical outcome to determine a score, which is a linear combination of variables with hieratical structures to multimodalities. This approach is expected to obtain interpretable and predictive scores. The proposed method was applied to a study of Alzheimer’s disease (AD). We propose a diagnostic method for AD that involves using whole-brain magnetic resonance imaging (MRI) and positron emission tomography (PET), and we select effective brain regions for the diagnostic probability and investigate the genome-wide association with the regions using single nucleotide polymorphisms (SNPs). The two-step dimension reduction method, which we previously introduced, was considered applicable to such a study and allows us to partially incorporate the proposed method. We show that the proposed method offers classification functions with feasibility and reasonable prediction accuracy based on the receiver operating characteristic (ROC) analysis and reasonable regions of the brain and genomes. Our simulation study based on the synthetic structured data set showed that the proposed method outperformed the original method and provided the characteristic for the supervised feature.
Management and outcomes of patients with atrial fibrillation and a history of cancer: the ORBIT-AF registry
Authors: Melloni Chiara , Shrader Peter , Carver Joseph , Piccini Jonathan P. , Thomas Laine , Fonarow Gregg C. , Ansell Jack , Gersh Bernard , Go Alan S. , Hylek Elaine , Herling Irving M. , Mahaffey Kenneth W. , Yu Anthony F. , Peterson Eric D. , Kowey Peter R. ,   on behalf of the ORBIT-AF Steering Committee
Published: February 2017

Abstract

Aims
The presence of cancer can complicate treatment choices for patients with atrial fibrillation (AF) increasing both the risk of thrombotic and bleeding events.

Methods and results
Using data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we aimed to characterize AF patients with cancer, to describe their management and to assess the association between cancer and cardiovascular (CV) outcomes. Among 9749 patients, 23.8% had history of cancer (57% solid malignancy, 1.3% leukaemia, 3.3% lymphoma, 40% other type, and 2.2% metastatic cancer). Patients with history of cancer were older, more likely to have CV disease, CV risk factors, and prior gastrointestinal bleeding. No difference in antiarrhythmic and antithrombotic therapy was observed between those with and without cancer. Patients with history of cancer had a significantly higher risk of death (7.8 vs. 4.9 deaths per 100 patient-years follow-up, P = 0.0003) mainly driven by non-CV death (4.2 vs. 2.4 per 100 patient-years follow-up; P = 0.0004) and higher risk of major bleeding (5.1 vs. 3.5 per 100 patient-years follow-up; P = 0.02) compared with non-cancer patients; no differences were observed in risks of strokes/non-central nervous system embolism (1.96 vs. 1.48, P = 0.74) and CV death (2.89 vs. 2.07, P = 0.35) between the two groups.

Conclusion
A history of cancer is common among AF patients with up to one in four patients having both. Antithrombotic therapy, rates of cerebrovascular accident, other thrombotic events and cardiac death were similar in AF patients with or without a history of cancer. Patients with cancer, however, were at higher risk of major bleeding and non-CV death.
Acute coronary syndrome in women: rising hospitalizations in middle-aged French women, 2004–14
Authors: Gabet Amélie , Danchin Nicolas , Juillière Yves , Olié Valérie 
Published: February 2017

Aims
We aimed to analyse trends in annual incidence of hospitalized acute coronary syndrome (ACS) in France from 2004 to 2014.

Methods and results
Primary diagnosis of ACS and subtypes on admissions were selected in national and exhaustive French Hospitalization Database from 2004 to 2014. Age-standardized rates were computed using standardization on the census of the 2010 European population and mean annual percent changes were estimated by using Poisson regression model. In 2014, 113 407 patients, 36 480 women (32.2%) and 76 927 men (67.8%) were hospitalized for ACS. Among women, the proportion aged under 65 years was 25.2% (n = 9206) and there was 34.4% of STEMI, 18.2% of NSTEMI and 47.4% of UA. From 2004 to 2014, the rates of age-standardized admissions for ACS in women less than 65 years old increased by 6.3%.This rise in ACS was driven by significant increases in STEMI (+21.7%) and NSTEMI (+53.7%). The largest increase in STEMI mean annual percent change was observed among women aged 45–54 years old (+3.6%/per year). After 65 years of age, significant decreases in all ACS types were observed.

Conclusion
This nationwide study showed substantial rising trends in STEMI annual incidence, especially among younger women. This increase could be attributed to increase in smoking and obesity. Efforts to strengthen primary prevention of CVD in younger women is needed as the main risk factors are modifiable, and as there is a growing evidence of higher short-term mortality of CHD in women.
Making space for shellfish farming along the Adriatic coast
Authors: Brigolin Daniele , Porporato Erika Maria Diletta , Prioli Giuseppe , Pastres Roberto 
Published: February 2017

Abstract
This work focuses on the selection of new areas for shellfish farming along the coast of the Northern Adriatic Sea (Italy). Shellfish site suitability was assessed by means of a methodology based on Spatial Multi-Criteria Evaluation (SMCE), which provided the framework to combine mathematical models and operational oceanography products. Intermediate level criteria considered in the analysis included optimal growth conditions, environmental interactions, and socio-economic evaluation (e.g. organic carbon deposition; distance to harbour). Results showed that the whole coastal area comprised within 0 and 3 nm is highly suitable for farming of mussel, while the area comprised between 3 and 12 nm is divided between a highly suitable northern part, and a less suitable southern one. Seven different scenarios of development of shellfish aquaculture industry were explored. The introduction of a new species, and the assessment of the exposure to storm events are specific aspects taken into account in development scenarios. Results show that the degree of suitability for shellfish aquaculture in this area would not change dramatically with the introduction of oyster farming. Furthermore, results highlight that: (i) the growth potential in this area is high; (ii) the space with suitability index &gt;0.5 increases when prioritizing the optimal growth condition criteria, and (iii) the socio-economic is the most restrictive Intermediate Level Criteria. Results were discussed by deriving general lessons concerning the use of SMCE in aquaculture space allocation, from the specific application in the Northern Adriatic Sea. Challenges and opportunities related to the proposed methodological framework, with particular reference to the use of resources provided by remote sensing and operational oceanography by means of mathematical models, were also discussed. Results can support a science-based identification of allocated zones for aquaculture in order to avoid conflicts, and promote sustainable aquaculture in the Mediterranean Sea, where the space for these activities is becoming increasingly limited.
Meaningful use in the safety net: a rapid ethnography of patient portal implementation at five community health centers in California
Authors: Ackerman Sara L , Sarkar Urmimala , Tieu Lina , Handley Margaret A , Schillinger Dean , Hahn Kenneth , Hoskote Mekhala , Gourley Gato , Lyles Courtney 
Published: February 2017

Abstract
Objective:US health care institutions are implementing secure websites (patient portals) to achieve federal Meaningful Use (MU) certification. We sought to understand efforts to implement portals in “safety net” health care systems that provide services for low-income populations.
Materials and Methods:Our rapid ethnography involved visits at 4 California safety net health systems and in-depth interviews at a fifth. Visits included interviews with clinicians and executives (n = 12), informal focus groups with front-line staff (n = 35), observations of patient portal sign-up procedures and clinic work, review of marketing materials and portal use data, and a brief survey (n = 45).
Results:Our findings demonstrate that the health systems devoted considerable effort to enlisting staff support for portal adoption and integrating portal-related work into clinic routines. Although all health systems had achieved, or were close to achieving, MU benchmarks, patients faced numerous barriers to portal use and our participants were uncertain how to achieve and sustain “meaningful use” as defined by and for their patients.
Discussion:Health systems’ efforts to achieve MU certification united clinic staff under a shared ethos of improved quality of care. However, MU’s assumptions about patients’ demand for electronic access to health information and ability to make use of it directed clinics’ attention to enrollment and message routing rather than to the relevance and usability of a tool that is minimally adaptable to the safety net context.
Conclusion:We found a mismatch between MU-based metrics of patient engagement and the priorities and needs of safety net patient populations.
Crossing the health IT chasm: considerations and policy recommendations to overcome current challenges and enable value-based care
Authors: Adler-Milstein Julia , Embi Peter J , Middleton Blackford , Sarkar Indra Neil , Smith Jeff 
Published: February 2017

Abstract
While great progress has been made in digitizing the US health care system, today’s health information technology (IT) infrastructure remains largely a collection of systems that are not designed to support a transition to value-based care. In addition, the pursuit of value-based care, in which we deliver better care with better outcomes at lower cost, places new demands on the health care system that our IT infrastructure needs to be able to support. Provider organizations pursuing new models of health care delivery and payment are finding that their electronic systems lack the capabilities needed to succeed. The result is a chasm between the current health IT ecosystem and the health IT ecosystem that is desperately needed.
In this paper, we identify a set of focal goals and associated near-term achievable actions that are critical to pursue in order to enable the health IT ecosystem to meet the acute needs of modern health care delivery. These ideas emerged from discussions that occurred during the 2015 American Medical Informatics Association Policy Invitational Meeting. To illustrate the chasm and motivate our recommendations, we created a vignette from the multistakeholder perspectives of a patient, his provider, and researchers/innovators. It describes an idealized scenario in which each stakeholder’s needs are supported by an integrated health IT environment. We identify the gaps preventing such a reality today and present associated policy recommendations that serve as a blueprint for critical actions that would enable us to cross the current health IT chasm by leveraging systems and information to routinely deliver high-value care.
Selling Pain to the Saturated Self
Authors: Scott Rebecca , Cayla Julien , Cova Bernard 
Published: February 2017

Abstract
How can we comprehend people who pay for an experience marketed as painful? On one hand, consumers spend billions of dollars every year to alleviate different kinds of pain. On the other hand, millions of individuals participate in extremely painful leisure pursuits. In trying to understand this conundrum, we ethnographically study a popular adventure challenge where participants subject themselves to electric shocks, fire, and freezing water. Through sensory intensification, pain brings the body into sharp focus, allowing individuals to rediscover their corporeality. In addition, painful extraordinary experiences operate as regenerative escapes from the self. By flooding the consciousness with gnawing unpleasantness, pain provides a temporary relief from the burdens of self-awareness. Finally, when leaving marks and wounds, pain helps consumers create the story of a fulfilled life. In a context of decreased physicality, market operators play a major role in selling pain to the saturated selves of knowledge workers, who use pain as a way to simultaneously escape reflexivity and craft their life narrative.
Acquisition of radioresistance by IL-6 treatment is caused by suppression of oxidative stress derived from mitochondria after γ-irradiation
Authors: Tamari Yuki , Kashino Genro , Mori Hiromu 
Published: February 2017

Abstract
Interleukin (IL)-6 is a multifunctional cytokine and is one of the radiation-induced bystander factors. This study aimed to clarify the mechanism of acquisition of radioresistance through the control of reactive oxygen species (ROS) by IL-6. We used a rat glioma cell line (C6) as tumor cells and a rat astrocyte cell line (RNB) as non-tumor cells. Our results showed that the surviving fraction of C6 cells after 6 Gy irradiation was increased by the addition of IL-6, but that this was not the case in RNB cells. In addition, the number of 53BP1 foci in C6 cells at 30 min after γ-irradiation were decreased by IL-6. Levels of ROS in whole C6 cells, and superoxide in the mitochondria of C6 cells immediately after γ-irradiation, were reduced by IL-6, but this was not observed in RNB cells. The mitochondrial membrane potential detected by JC-1 in C6 and RNB cells was inhibited by IL-6 alone. Therefore, it was concluded that IL-6 leads specifically to radioresistance in tumor cells by inhibition of increases in ROS after γ-irradiation.