bluuebunny/crossref_metadata_2025_split huggingface dataset:
gwasrapidd: an R package to query, download and wrangle GWAS catalog data
Authors: Magno Ramiro , Maia Ana-Teresa 
Published: August 2019

Abstract

Motivation
The National Human Genome Research Institute Catalog of Published Genome-Wide Association Studies (GWAS) Catalog has collected, curated and made available data from over 7100 studies. The recently developed GWAS Catalog representational state transfer (REST) application programming interface (API) is the only method allowing programmatic access to this resource.

Results
Here, we describe gwasrapidd, an R package that provides the first client interface to the GWAS Catalog REST API, representing an important software counterpart to the server-side component. gwasrapidd enables users to quickly retrieve, filter and integrate data with comprehensive bioinformatics analysis tools, which is particularly critical for those looking into functional characterization of risk loci.

Availability and implementation
gwasrapidd is freely available under an MIT License, and can be accessed from https://github.com/ramiromagno/gwasrapidd.

Supplementary information
Supplementary data are available at Bioinformatics online.
DNA Rchitect: an R based visualizer for network analysis of chromatin interaction data
Authors: Ramirez R N , Bedirian K , Gray S M , Diallo A 
Published: August 2019

Abstract

Motivation
Visualization of multiple genomic data generally requires the use of public or commercially hosted browsers. Flexible visualization of chromatin interaction data as genomic features and network components offer informative insights to gene expression. An open source application for visualizing HiC and chromatin conformation-based data as 2D-arcs accompanied by interactive network analyses is valuable.

Results
DNA Rchitect is a new tool created to visualize HiC and chromatin conformation-based contacts at high (Kb) and low (Mb) genomic resolutions. The user can upload their pre-filtered HiC experiment in bedpe format to the DNA Rchitect web app that we have hosted or to a version they themselves have deployed. Using DNA Rchitect, the uploaded data allows the user to visualize different interactions of their sample, perform simple network analyses, while also offering visualization of other genomic data types. The user can then download their results for additional network functionality offered in network based programs such as Cytoscape.

Availability and implementation
DNA Rchitect is freely available both as a web application written primarily in R available at http://shiny.immgen.org/DNARchitect/ and as an open source released under an MIT license at: https://github.com/alosdiallo/DNA_Rchitect.
VirtualCytometry: a webserver for evaluating immune cell differentiation using single-cell RNA sequencing data
Authors: Kim Kyungsoo , Yang Sunmo , Ha Sang-Jun , Lee Insuk 
Published: August 2019

Abstract

Motivation
The immune system has diverse types of cells that are differentiated or activated via various signaling pathways and transcriptional regulation upon challenging conditions. Immunophenotyping by flow and mass cytometry are the major approaches for identifying key signaling molecules and transcription factors directing the transition between the functional states of immune cells. However, few proteins can be evaluated by flow cytometry in a single experiment, preventing researchers from obtaining a comprehensive picture of the molecular programs involved in immune cell differentiation. Recent advances in single-cell RNA sequencing (scRNA-seq) have enabled unbiased genome-wide quantification of gene expression in individual cells on a large scale, providing a new and versatile analytical pipeline for studying immune cell differentiation.

Results
We present VirtualCytometry, a web-based computational pipeline for evaluating immune cell differentiation by exploiting cell-to-cell variation in gene expression with scRNA-seq data. Differentiating cells often show a continuous spectrum of cellular states rather than distinct populations. VirtualCytometry enables the identification of cellular subsets for different functional states of differentiation based on the expression of marker genes. Case studies have highlighted the usefulness of this subset analysis strategy for discovering signaling molecules and transcription factors for human T-cell exhaustion, a state of T-cell dysfunction, in tumor and mouse dendritic cells activated by pathogens. With more than 226 scRNA-seq datasets precompiled from public repositories covering diverse mouse and human immune cell types in normal and disease tissues, VirtualCytometry is a useful resource for the molecular dissection of immune cell differentiation.

Availability and implementation
www.grnpedia.org/cytometry
ArtiFuse—computational validation of fusion gene detection tools without relying on simulated reads
Authors: Sorn Patrick , Holtsträter Christoph , Löwer Martin , Sahin Ugur , Weber David 
Published: August 2019

Abstract

Motivation
Gene fusions are an important class of transcriptional variants that can influence cancer development and can be predicted from RNA sequencing (RNA-seq) data by multiple existing tools. However, the real-world performance of these tools is unclear due to the lack of known positive and negative events, especially with regard to fusion genes in individual samples. Often simulated reads are used, but these cannot account for all technical biases in RNA-seq data generated from real samples.

Results
Here, we present ArtiFuse, a novel approach that simulates fusion genes by sequence modification to the genomic reference, and therefore, can be applied to any RNA-seq dataset without the need for any simulated reads. We demonstrate our approach on eight RNA-seq datasets for three fusion gene prediction tools: average recall values peak for all three tools between 0.4 and 0.56 for high-quality and high-coverage datasets. As ArtiFuse affords total control over involved genes and breakpoint position, we also assessed performance with regard to gene-related properties, showing a drop-in recall value for low-expressed genes in high-coverage samples and genes with co-expressed paralogues. Overall tool performance assessed from ArtiFusions is lower compared to previously reported estimates on simulated reads. Due to the use of real RNA-seq datasets, we believe that ArtiFuse provides a more realistic benchmark that can be used to develop more accurate fusion gene prediction tools for application in clinical settings.

Availability and implementation
ArtiFuse is implemented in Python. The source code and documentation are available at https://github.com/TRON-Bioinformatics/ArtiFusion.

Supplementary information
Supplementary data are available at Bioinformatics online.
The Elimination of Neglected Tropical Diseases: A Case Study Exemplifying How Foreign Assistance Funding Can Be Catalytic in Reducing the Burden of Major Global Health Conditions
Authors: Wainwright Emily , Evans Darin , Rotondo Lisa , Pou Bolivar , Yevstigneyeva Violetta , Zoerhoff Kathryn L , Ottesen Eric A , Reithinger Richard 
Published: August 2019

Abstract
In 2006, following direct advocacy and published rationale, the US Agency for International Development (USAID) established a neglected tropical diseases (NTDs) program to support the scale-up of integrated platforms to target the elimination and control of 5 NTDs—lymphatic filariasis, trachoma, onchocerciasis, schistosomiasis, and soil-transmitted helminthiasis.
By 2017, more than 2.3 billion NTD treatments had been delivered to at-risk populations in 25 countries, leveraging $19 billion in donated drugs—approximately $26 dollars in donated medicine per $1 spent by USAID. As a result, most of the supported countries are on track to achieve their elimination goals (for lymphatic filariasis and trachoma) by 2020 or 2021 and their control goals soon thereafter.
Though “small” when compared to other global health initiatives, this investment proved to be catalytic, and indeed highlights how foreign assistance funding can be transformative, in reducing the burden of major global health conditions such as NTDs.
Meeting Challenges of Late Life Disability Proactively
Authors: Kahana Eva , Kahana Jeffrey S , Kahana Boaz , Ermoshkina Polina 
Published: August 2019

AbstractDiscussions of disability in the gerontological and the disability studies literatures have seldom considered unique perspectives and needs of older adults. Disability has often been stigmatized and viewed as antithetical to successful aging. We call for expansion of prevailing paradigms of disability to address the resilience and continuing human potential of older adults living with disabilities. In addition to recognizing the environmental context of disability, we propose greater attention to adaptive potential of disabled older adults. We discuss 6 types of proactive adaptations that can contribute to empowerment, meaning, enhanced quality of life and psychological well-being among persons living with late-life onset disabilities. These include: (a) helping others, (b) planning for future care, (c) marshaling intergenerational support, (d) self-advocacy for responsive health care, (e) making environmental modifications to improve safety and comfort of the home, and (f) finding strength in spiritual pursuits. Enacting proactive adaptations can contribute to resilience in facing late life impairments and functional limitations. Such efforts can complement utilization of services and obtaining accommodations. Maintaining life satisfaction among older adults living with disabilities also involves focus on transcendent personal goals and acceptance of an altered self. We note how a more integrative view of medical and social dimensions of disability, infused with concepts of human agency, contributes to rapprochement between alternative disciplinary orientations to late life disability. Without negating society’s important responsibilities for accommodating to needs of older adults living with disability, we reaffirm their potential for greater control and self-determination through proactive adaptations.
Animal welfare and ecology in the contested ethics of rodent control in Cape Town
Authors: Nattrass Nicoli , Stephens Jed , Loubser Jorich Johann 
Published: August 2019

AbstractThere is growing concern globally about the inhumane treatment of ‘pest’ animals, including rodents, and about the ecological consequences of rodenticides, notably the poisoning of non-target wildlife like raptors and scavengers. Recent contestation between Environmental Health (EH) officials in Khayelitsha, Cape Town’s largest African township, and the National Council for Societies for the Prevention of Cruelty to Animals (NSPCA) illustrates the tension that can arise between innovative ecologically-focused strategies and existing legislation and animal protection practices. In 2013/14 EH officials introduced a job-creation project to trap and drown rats, describing it as ‘humane’ because it avoided poison thereby posing no danger to wildlife such as owls. The NSPCA, however, halted the project, arguing that drowning was both inhumane and illegal. Death by poison is also inhumane but the South Africa’s Animals Protection Act (1962) allows it (and trapping and hunting) to be used against ‘pests’/‘vermin’. The NSPCA, which has never challenged the Act for allowing the inhumane treatment of these animals, used it to trump local preferences. A representative survey from Khayelitsha showed that there was some support for an NSPCA-like position (14% thought that drowning was cruel and that workers should not be allowed to trap and drown rats) but that the majority (70%) indicated that they were both concerned about the poisoning of non-target animals and supported the continuation of the trapping and drowning project. This was not a contestation over whether animals should be protected, but over how to do this, and which animals to include.
Heat stress increases the use of cytosolic pyruvate for isoprene biosynthesis
Authors: Yáñez-Serrano Ana Maria , Mahlau Lucas , Fasbender Lukas , Byron Joseph , Williams Jonathan , Kreuzwieser Jürgen , Werner Christiane 
Published: August 2019

Abstract
The increasing occurrence of heatwaves has intensified temperature stress on terrestrial vegetation. Here, we investigate how two contrasting isoprene-emitting tropical species, Ficus benjamina and Pachira aquatica, cope with heat stress and assess the role of internal plant carbon sources for isoprene biosynthesis in relation to thermotolerance. To our knowledge, this is the first study to report isoprene emissions from P. aquatica. We exposed plants to two levels of heat stress and determined the temperature response curves for isoprene and photosynthesis. To assess the use of internal C sources in isoprene biosynthesis, plants were fed with 13C position-labelled pyruvate. F. benjamina was more heat tolerant with higher constitutive isoprene emissions and stronger acclimation to higher temperatures than P. aquatica, which showed higher induced isoprene emissions at elevated temperatures. Under heat stress, both isoprene emissions and the proportion of cytosolic pyruvate allocated into isoprene synthesis increased. This represents a mechanism that P. aquatica, and to a lesser extent F. benjamina, has adopted as an immediate response to sudden increase in heat stress. However, in the long run under prolonged heat, the species with constitutive emissions (F. benjamina) was better adapted, indicating that plants that invest more carbon into protective emissions of biogenic volatile organic compounds tend to suffer less from heat stress.
Reconstructing complex lineage trees from scRNA-seq data using MERLoT
Authors: Parra R Gonzalo , Papadopoulos Nikolaos , Ahumada-Arranz Laura , Kholtei Jakob El , Mottelson Noah , Horokhovsky Yehor , Treutlein Barbara , Soeding Johannes 
Published: August 2019

Abstract
Advances in single-cell transcriptomics techniques are revolutionizing studies of cellular differentiation and heterogeneity. It has become possible to track the trajectory of thousands of genes across the cellular lineage trees that represent the temporal emergence of cell types during dynamic processes. However, reconstruction of cellular lineage trees with more than a few cell fates has proved challenging. We present MERLoT (https://github.com/soedinglab/merlot), a flexible and user-friendly tool to reconstruct complex lineage trees from single-cell transcriptomics data. It can impute temporal gene expression profiles along the reconstructed tree. We show MERLoT’s capabilities on various real cases and hundreds of simulated datasets.
The role of cancer-associated autoantibodies as biomarkers in paraneoplastic myositis syndrome
Authors: Lu Xin , Peng Qinglin , Wang Guochun 
Published: August 2019

Purpose of review
The aim of this study is to provide a comprehensive overview of the current insight about the clinical utility of cancer-associated autoantibodies (CAAs) as biomarkers in paraneoplastic myositis syndrome (PMS). In addition, the possible mechanisms of the relationship between malignancy and myositis onset are discussed.

Recent findings
It has become increasingly clear that a subgroup of the myositis-specific autoantibodies could be considered as CAAs because they are closely related to the PMS. Increased risk of cancer was found in patients with antitranscriptional intermediary factor 1-γ (TIF1-γ), antinuclear matrix protein-2 (NXP-2), anti3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) or antismall ubiquitin-like modifier 1-activating enzyme (SAE) antibodies. However, the diagnosing sensitivity and specificity of these CAAs for PMS are different among different cohort studies. Abnormally expressed or mutated autoantigen genes in tumor could possibly induce cross immunity against self-proteins and subsequently lead to the development of PMS.

Summary
Anti-TIF1-γ, anti-NXP-2, anti-HMGCR and anti-SAE antibodies may act as CAAs in PMS. It is necessary to closely screen and monitor for cancer in patients with CAAs. The recent studies of the relationship between CAAs and PMS provided important new insights into the disease mechanisms.
Ventilation Rates and Pediatric In-Hospital Cardiac Arrest Survival Outcomes*
Authors: Sutton Robert M. , Reeder Ron W. , Landis William P. , Meert Kathleen L. , Yates Andrew R. , Morgan Ryan W. , Berger John T. , Newth Christopher J. , Carcillo Joseph A. , McQuillen Patrick S. , Harrison Rick E. , Moler Frank W. , Pollack Murray M. , Carpenter Todd C. , Notterman Daniel A. , Holubkov Richard , Dean J. Michael , Nadkarni Vinay M. , Berg Robert A. 
Published: August 2019

Objectives:
The objective of this study was to associate ventilation rates during in-hospital cardiopulmonary resuscitation with 1) arterial blood pressure during cardiopulmonary resuscitation and 2) survival outcomes.

Design:
Prospective, multicenter observational study.

Setting:
Pediatric and pediatric cardiac ICUs of the Collaborative Pediatric Critical Care Research Network.

Patients:
Intubated children (≥ 37 wk gestation and < 19 yr old) who received at least 1 minute of cardiopulmonary resuscitation.

Interventions:
None.

Measurements and Main Results:
Arterial blood pressure and ventilation rate (breaths/min) were manually extracted from arterial line and capnogram waveforms. Guideline rate was defined as 10 ± 2 breaths/min; high ventilation rate as greater than or equal to 30 breaths/min in children less than 1 year old, and greater than or equal to 25 breaths/min in older children. The primary outcome was survival to hospital discharge. Regression models using Firth penalized likelihood assessed the association between ventilation rates and outcomes. Ventilation rates were available for 52 events (47 patients). More than half of patients (30/47; 64%) were less than 1 year old. Eighteen patients (38%) survived to discharge. Median event-level average ventilation rate was 29.8 breaths/min (interquartile range, 23.8–35.7). No event-level average ventilation rate was within guidelines; 30 events (58%) had high ventilation rates. The only significant association between ventilation rate and arterial blood pressure occurred in children 1 year old or older and was present for systolic blood pressure only (–17.8 mm Hg/10 breaths/min; 95% CI, –27.6 to –8.1; p < 0.01). High ventilation rates were associated with a higher odds of survival to discharge (odds ratio, 4.73; p = 0.029). This association was stable after individually controlling for location (adjusted odds ratio, 5.97; p = 0.022), initial rhythm (adjusted odds ratio, 3.87; p = 0.066), and time of day (adjusted odds ratio, 4.12; p = 0.049).

Conclusions:
In this multicenter cohort, ventilation rates exceeding guidelines were common. Among the range of rates delivered, higher rates were associated with improved survival to hospital discharge.
Accelerated Versus Standard Corneal Cross-Linking for Progressive Keratoconus: A Meta-Analysis of Randomized Controlled Trials
Authors: Kobashi Hidenaga , Tsubota Kazuo 
Published: August 2019

Purpose:
To compare the clinical results of accelerated corneal collagen cross-linking (ACXL) to standard corneal collagen cross-linking (SCXL) in progressive keratoconus by summarizing randomized controlled trials using a meta-analysis.

Methods:
Trials meeting the selection criteria were quality appraised, and data were extracted by 2 independent authors. A comprehensive search was performed using the Cochrane methodology to evaluate the clinical outcomes of ACXL and SCXL for treating progressive keratoconus. Estimates were evaluated by weighted mean difference (WMD) and 95% confidence interval (CI) for absolute changes of the outcomes during 12-month observation periods. Postoperative demarcation line depth was also compared.

Results:
We identified 6 randomized controlled trials that met the eligibility criteria for this meta-analysis. SCXL resulted in a significantly better outcome in postoperative changes in best spectacle-corrected visual acuity (WMD = −0.02; 95% CI, −0.03 to −0.01; P < 0.0001); however, the small differences may not be clinically significant. ACXL provided a significantly better improvement of cylindrical refraction after the 1-year follow-up (WMD = 0.15; 95% CI, 0.05–0.26; P = 0.005). Demarcation line depth at 1 month after SCXL was deeper than that after ACXL (WMD = −102.25; 95% CI, −157.16 to −47.35; P = 0.0003). No differences in the changes in maximum keratometry, central corneal thickness, uncorrected visual acuity, spherical equivalent refraction, corneal biomechanical properties, and corneal endothelial cell density were found among both groups.

Conclusions:
An ACXL shows a comparable efficacy and safety profile at the 1-year follow-up, but it has less impact on improving best spectacle-corrected visual acuity when compared with the Dresden protocol. Overall, both methods similarly stop the disease progression.
Smoke screen: The teen vaping epidemic uncovers a new concerning addiction
Authors: Huey Sally W. , Granitto Margaret H. 
Published: August 2019

ABSTRACT
The use of nicotine products among adolescents is now designated as a national epidemic by the United States Surgeon General. The largest one-year increase ever recorded for substance use in the adolescent population should sound the alarm for Nurse Practitioners (NPs) practicing in family health and pediatrics. Vaping, or the use of e-cigarettes or electronic nicotine delivery systems (ENDS), has been purported by the vaping industry as a less harmful alternative for tobacco users in their attempt to quit smoking. In adolescents, vaping represents a dangerous and highly addictive health behavior. Initiatives on both the state and federal levels have begun to address marketing and access to young users. However, the active involvement of NPs on the front line of primary care will be necessary to combat this imposing threat. The protection of our young patients from nicotine addiction and the education of patients and families about the potential dangers of e-cigarettes are imperative to prevent harm. This article addresses concerns related to e-cigarette use in the adolescent population and the important role NPs can play in promoting their health and well-being.
Thyroid disease and the metabolic syndrome
Authors: Mehran Ladan , Amouzegar Atieh , Azizi Fereidoun 
Published: August 2019

Purpose of review
To summarize recent developments in the association of thyroid function with metabolic syndrome (MetS).

Recent findings
Although thyroid hormones even within low normal range are associated with various metabolic abnormalities, the risk of MetS remains a controversial issue. Hyperthyroid state might be associated only with insulin resistance and dysglycemia. Autoimmune thyroid diseases may be a potential risk factor for metabolic abnormalities even in those with low normal thyroid function.

Summary
The interrelation between thyroid stimulating hormone, free T3, freeT4 and metabolic parameters is complex and might be affected by age, sex, BMI, insulin resistance, smoking, iodine intake and inflammatory markers.