bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional impact of cancer-associated cohesin variants on gene expression and cellular identity
Authors: Rittenhouse Natalie L , Carico Zachary M , Liu Ying Frances , Stefan Holden C , Arruda Nicole L , Zhou Junjie , Dowen Jill M 
Published: February 2021

Abstract
Cohesin is a ring-shaped protein complex that controls dynamic chromosome structure. Cohesin activity is important for a variety of biological processes, including formation of DNA loops that regulate gene expression. The precise mechanisms by which cohesin shapes local chromosome structure and gene expression are not fully understood. Recurrent mutations in cohesin complex members have been reported in various cancers, though it is not clear whether many cohesin sequence variants have phenotypes and contribute to disease. Here, we utilized CRISPR/Cas9 genome editing to introduce a variety of cohesin sequence variants into murine embryonic stem cells and investigate their molecular and cellular consequences. Some of the cohesin variants tested caused changes to transcription, including altered expression of gene encoding lineage-specifying developmental regulators. Altered gene expression was also observed at insulated neighborhoods, where cohesin-mediated DNA loops constrain potential interactions between genes and enhancers. Furthermore, some cohesin variants altered the proliferation rate and differentiation potential of murine embryonic stem cells. This study provides a functional comparison of cohesin variants found in cancer within an isogenic system, revealing the relative roles of various cohesin perturbations on gene expression and maintenance of cellular identity.
Age of Peak Performance Differs by Functional Task in Mice Tracked Over 2 Years
Authors: Tavoian Dallin , Lozier Nicholas R , de Lacalle Sonsoles 
Published: February 2021

Abstract
Mouse models are often used to validate novel interventions prior to human testing, although biological differences between mice and humans limit the translatability of outcomes. A common assumption in animal research is that maximal physical performance will be present at a young age, and that differences in task performance between young and old can be attributed to the aging process. However, this may not be true for all physical function tasks, and leaving out intermediate time points could drastically alter data interpretation. Here, we document age-related changes in forelimb and hindlimb grip strength, balance and coordination, and body composition in mice (n = 43) collected at multiple time points between 4 and 24 months of age. Maximal forelimb grip strength was recorded at 4 months of age, but maximal hindlimb grip strength was recorded at 15 months of age. Balance performance was stable from 4 to 15 months of age, declining significantly at 18 months. Both lean and fat mass peaked at 18 months before declining steadily. We conclude that the inclusion of intermediate time points is essential for the accurate evaluation of physical function status in mice, particularly in the context of translating intervention outcomes into strategies to be tested in humans.
Longitudinal Master Track and Field Performance Decline Rates Are Lower and Performance Is Better Compared to Athletes Competing Only Once
Authors: Hoog Antink Christoph , Braczynski Anne K , Kleerekoper Anthony , Degens Hans , Ganse Bergita 
Published: February 2021

Abstract
In master athletics research, cross-sectional data are easier to obtain than longitudinal data. While cross-sectional data give the age-related performance decline for a population, longitudinal data show individual trajectories. It is not known whether athletes who repeatedly compete have (a) a better performance and (b) a slower age-related decline in performance than that obtained from cross-sectional data from athletes competing only once. To investigate this, we analyzed 33 254 results of 14 118 male athletes from 8 disciplines in the database of “Swedish Veteran Athletics.” For each discipline and for the pooled data of all disciplines, quadratic models of the evolution of performance over time were analyzed by ANCOVA/ANOCOVA using MATLAB. The performance was higher in athletes with 2 or more data points compared to those with only n = 1 (p &lt; .001), with further increases in performance with an increasing number of data points per athlete. The estimated performance decline was lower in people with 2 or more results (sprint, 10 km, jumps; p &lt; .001). In conclusion, we showed that longitudinal data are associated with higher performance and lower performance decline rates.
Advance Care Planning Practices in the Nursing Home Setting: A Secondary Analysis
Authors: Laging Bridget L , Nay Rhonda , Bauer Michael , Laging Rohan , Walker Katie , Kenny Amanda 
Published: February 2021

AbstractBackground and ObjectivesAdvance care planning is intended to support residents’ preferences regarding health decisions, even when they can no longer participate. Little is known about the power discourses influencing how residents, family members, and health care workers engage in advance care planning and how advance care directives are used if a conflict arises. A large critical ethnographic study was conducted exploring decision making when a resident’s health deteriorates in the nursing home setting. Advance care planning practices were not the focus of the original study, but the richness of the data warranted further exploration. A new research question was developed to inform a secondary analysis: How does advance care planning influence the relationship between resident values and clinical expertise when determining a direction of care at the time of a resident deterioration?Research Design and MethodsA secondary analysis of data from an ethnographic study involving 184 h of participatory observation, 40 semistructured interviews and advance care planning policies, and document review undertaken in two nursing homes in Melbourne, Australia.ResultsAdvance care planning may result in inaccurate documentation of residents’ preferences and devalue clinical decision making and communication with residents and family members at the time of deterioration.Discussion and ImplicationsAdvance care planning may contribute toward a reductionist approach to decision making. There is an urgent need for the development of evidence-based policy and legislation to support residents, families, and health care workers to make appropriate decisions, including withholding invasive treatment when a resident deteriorates.
HTSlib: C library for reading/writing high-throughput sequencing data
Authors: Bonfield James K , Marshall John , Danecek Petr , Li Heng , Ohan Valeriu , Whitwham Andrew , Keane Thomas , Davies Robert M 
Published: February 2021

Abstract

Background
Since the original publication of the VCF and SAM formats, an explosion of software tools have been created to process these data files. To facilitate this a library was produced out of the original SAMtools implementation, with a focus on performance and robustness. The file formats themselves have become international standards under the jurisdiction of the Global Alliance for Genomics and Health.

Findings
We present a software library for providing programmatic access to sequencing alignment and variant formats. It was born out of the widely used SAMtools and BCFtools applications. Considerable improvements have been made to the original code plus many new features including newer access protocols, the addition of the CRAM file format, better indexing and iterators, and better use of threading.

Conclusion
Since the original Samtools release, performance has been considerably improved, with a BAM read-write loop running 5 times faster and BAM to SAM conversion 13 times faster (both using 16 threads, compared to Samtools 0.1.19). Widespread adoption has seen HTSlib downloaded &gt;1 million times from GitHub and conda. The C library has been used directly by an estimated 900 GitHub projects and has been incorporated into Perl, Python, Rust, and R, significantly expanding the number of uses via other languages. HTSlib is open source and is freely available from htslib.org under MIT/BSD license.
Novel mutations in the WFS1 gene are associated with Wolfram syndrome and systemic inflammation
Authors: Panfili Eleonora , Mondanelli Giada , Orabona Ciriana , Belladonna Maria L , Gargaro Marco , Fallarino Francesca , Orecchini Elena , Prontera Paolo , Proietti Elisa , Frontino Giulio , Tirelli Eva , Iacono Alberta , Vacca Carmine , Puccetti Paolo , Grohmann Ursula , Esposito Susanna , Pallotta Maria T 
Published: February 2021

Abstract
Mutations in the WFS1 gene, encoding wolframin (WFS1), cause endoplasmic reticulum (ER) stress and are associated with a rare autosomal-recessive disorder known as Wolfram syndrome (WS). WS is clinically characterized by childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus and neurological signs. We identified two novel WFS1 mutations in a patient with WS, namely, c.316-1G &gt; A (in intron 3) and c.757A &gt; T (in exon 7). Both mutations, located in the N-terminal region of the protein, were predicted to generate a truncated and inactive form of WFS1. We found that although the WFS1 protein was not expressed in peripheral blood mononuclear cells (PBMCs) of the proband, no constitutive ER stress activation could be detected in those cells. In contrast, WS proband’s PBMCs produced very high levels of proinflammatory cytokines (i.e. TNF-α, IL-1β, and IL-6) in the absence of any stimulus. WFS1 silencing in PBMCs from control subjects by means of small RNA interference also induced a pronounced proinflammatory cytokine profile. The same cytokines were also significantly higher in sera from the WS patient as compared to matched healthy controls. Moreover, the chronic inflammatory state was associated with a dominance of proinflammatory T helper 17 (Th17)-type cells over regulatory T (Treg) lymphocytes in the WS PBMCs. The identification of a state of systemic chronic inflammation associated with WFS1 deficiency may pave the way to innovative and personalized therapeutic interventions in WS.
Prospective evaluation of a breast-cancer risk model integrating classical risk factors and polygenic risk in 15 cohorts from six countries
Authors: Hurson Amber N , Pal Choudhury Parichoy , Gao Chi , Hüsing Anika , Eriksson Mikael , Shi Min , Jones Michael E , Evans D Gareth R , Milne Roger L , Gaudet Mia M , Vachon Celine M , Chasman Daniel I , Easton Douglas F , Schmidt Marjanka K , Kraft Peter , Garcia-Closas Montserrat , Chatterjee Nilanjan ,   for the B-CAST Risk Modelling Group
Published: February 2021

AbstractBackgroundRigorous evaluation of the calibration and discrimination of breast-cancer risk-prediction models in prospective cohorts is critical for applications under clinical guidelines. We comprehensively evaluated an integrated model incorporating classical risk factors and a 313-variant polygenic risk score (PRS) to predict breast-cancer risk.MethodsFifteen prospective cohorts from six countries with 239 340 women (7646 incident breast-cancer cases) of European ancestry aged 19–75 years were included. Calibration of 5-year risk was assessed by comparing expected and observed proportions of cases overall and within risk categories. Risk stratification for women of European ancestry aged 50–70 years in those countries was evaluated by the proportion of women and future cases crossing clinically relevant risk thresholds.ResultsAmong women &lt;50 years old, the median (range) expected-to-observed ratio for the integrated model across 15 cohorts was 0.9 (0.7–1.0) overall and 0.9 (0.7–1.4) at the highest-risk decile; among women ≥50 years old, these were 1.0 (0.7–1.3) and 1.2 (0.7–1.6), respectively. The proportion of women identified above a 3% 5-year risk threshold (used for recommending risk-reducing medications in the USA) ranged from 7.0% in Germany (∼841 000 of 12 million) to 17.7% in the USA (∼5.3 of 30 million). At this threshold, 14.7% of US women were reclassified by adding the PRS to classical risk factors, with identification of 12.2% of additional future cases.ConclusionIntegrating a 313-variant PRS with classical risk factors can improve the identification of European-ancestry women at elevated risk who could benefit from targeted risk-reducing strategies under current clinical guidelines.
Risk aversion and strategic voting
Authors: Martin Danielle 
Published: February 2021

Abstract
Numerous studies investigate how personality traits and individual characteristics influence vote choice. However, the effect of risk attitudes on the proclivity to cast a strategic vote has not been tested yet. This article tests whether the likelihood of defecting from one’s preferred party is influenced by attitudes towards risk. I argue that the utility stemming from expressing a preference by opting for the favored party is a sure thing, whereas the utility stemming from an instrumental choice depends on some probabilities, and consequently that strategic voting is riskier than sincere voting. Using survey data from the United Kingdom and Canada, I find that risk-averse voters are less likely to vote strategically than risk-acceptant ones.
Empowering physicians with health information technology: An empirical investigation in Chinese hospitals
Authors: Chen Yang , Aljafari Ruba , Xiao Bo , Venkatesh Viswanath 
Published: February 2021

AbstractObjectiveFew studies examine physicians’ use of different features of health information technology (HIT) in relation to their psychological empowerment and stress, especially in China, where many hospitals are being pushed to share digitized medical information. Further, there are mixed findings about the impact of HIT on stress, with some studies suggesting that HIT increases stress and others suggesting no effect. Hence, there is a need for a nuanced view of HITs to incorporate different features, regions, and outcomes. This work seeks to extend the existing body of knowledge on HIT by assessing the effects of basic (data-related) and advanced (clinical) HIT features on physician empowerment, stress, and ultimately, job satisfaction in Chinese hospitals.Materials and MethodsWe surveyed 367 physicians at 5 class 3 hospitals (ie, regional hospitals that provide specialist medical and healthcare services and carry out high levels of teaching and scientific research tasks) in 5 provinces in China. We specified and estimated a structural equation model using partial least squares.ResultsPhysicians who used advanced features experienced improvement in all dimensions of physician empowerment and significant reduction in stress. Physicians who used basic technology, however, experienced improvement in fewer dimensions of physician empowerment and no significant change in stress. Except for efficacy, all dimensions of physician empowerment and stress predicted job satisfaction.ConclusionsHealthcare professionals should assess the purpose of HIT features and expect different effects on intermediate and ultimate outcomes. The nuanced view of HIT features and processes leading to outcomes sheds light on their differential effects and resolves inconsistencies in prior findings on HIT effects.
Molecular Characterization and Transcriptional Expression Analysis of ABC Transporter H Subfamily Genes in the Oriental Fruit Fly
Authors: He Wang , Wei Dan-Dan , Xu Hui-Qian , Yang Yang , Miao Ze-Qing , Wang Lei , Wang Jin-Jun 
Published: February 2021

Abstract
The oriental fruit fly, Bactrocera dorsalis Hendel (Diptera: Tephretidae), is a serious pest of fruits and vegetables and has developed high levels of insecticide resistance. ATP-binding cassette transporter genes (ABC transporters) are involved in mediating the energy-driven transport of many substances across membranes and are closely associated with development and insecticide detoxification. In this study, three ABC transporters in the H subfamily were identified, and the possible roles of these genes in B. dorsalis are discussed. Bioinformatics analysis revealed that those genes are conserved, typical of half-transporters. The expression profiles of BdABCH genes (BdABCHs) in the developmental stages, tissues, and following insecticide exposure, extreme temperature, warm- and cold-acclimated strain, starvation, and desiccation stress were determined by quantitative real-time PCR. Expression of BdABCHs can be detected in various tissues and in different developmental stages. They were most highly expressed in the hindgut and in newly emerged adults. The mRNA levels of BdABCHs in males (including most tissues and body segments) were higher than in females. The expression of BdABCH1 was significantly upregulated 3.8-fold in the cold-acclimated strain, and was significantly upregulated by 1.9-, 3.8- and 4.1-fold in the 0°C, starvation, and desiccation treatments, respectively. Treatment with malathion and avermectin at LD20 and LD30 concentrations produced no obvious changes in the levels of BdABCHs. BdABCHs may be involved in the transport of related hormones during eclosion, as well as water and inorganic salts. BdABCH1 also demonstrated that it is related to the ability to cope with adverse environments.
CharacterizingEscherichia coli’s transcriptional response to different styrene exposure modes reveals novel toxicity and tolerance insights
Authors: Machas Michael , Kurgan Gavin , Abed Omar A , Shapiro Alyssa , Wang Xuan , Nielsen David 
Published: February 2021

AbstractThe global transcriptional response of Escherichia coli to styrene and potential influence of exposure source was determined by performing RNA sequencing (RNA-seq) analysis on both styrene-producing and styrene-exposed cells. In both cases, styrene exposure appears to cause both cell envelope and DNA damage, to which cells respond by down-regulating key genes/pathways involved in DNA replication, protein production, and cell wall biogenesis. Among the most significantly up-regulated genes were those involved with phage shock protein response (e.g. pspABCDE/G), general stress regulators (e.g. marA, rpoH), and membrane-altering genes (notably, bhsA, ompR, ldtC), whereas efflux transporters were, surprisingly, unaffected. Subsequent studies with styrene addition demonstrate how strains lacking ompR [involved in controlling outer membrane (OM) composition/osmoregulation] or any of tolQ, tolA, or tolR (involved in OM constriction) each displayed over 40% reduced growth relative to wild-type. Conversely, despite reducing basal fitness, overexpression of plsX (involved in phospholipid biosynthesis) led to 70% greater growth when styrene exposed. These collective differences point to the likely importance of OM properties in controlling native styrene tolerance. Overall, the collective behaviours suggest that, regardless of source, prolonged exposure to inhibitory styrene levels causes cells to shift from‘growth mode’ to ‘survival mode’, redistributing cellular resources to fuel native tolerance mechanisms.
DeImplementing Ineffective and Low-Value Clinical Practices: Research and Practice Opportunities in Community Oncology Settings
Authors: Norton Wynne E , McCaskill-Stevens Worta , Chambers David A , Stella Philip J , Brawley Otis W , Kramer Barnett S 
Published: February 2021

Abstract
Patients, practitioners, and policy makers are increasingly concerned about the delivery of ineffective or low-value clinical practices in cancer care settings. Research is needed on how to effectively deimplement these types of practices from cancer care. In this commentary, we spotlight the National Cancer Institute Community Oncology Research Program (NCORP), a national network of community oncology practices, and elaborate on how it is an ideal infrastructure for conducting rigorous, real-world research on deimplementation. We describe key multilevel issues that affect deimplementation and also serve as a guidepost for developing strategies to drive deimplementation. We describe optimal study designs for testing deimplementation strategies and elaborate on how and why the NCORP network is uniquely positioned to conduct rigorous and impactful deimplementation trials. The number and diversity of affiliated community oncology care sites, coupled with the overall objective of improving cancer care delivery, make the NCORP an opportune infrastructure for advancing deimplementation research while simultaneously improving the care of millions of cancer patients nationwide.
Capture–Recapture Estimation of Characteristics of U.S. Local Food Farms Using a Web-Scraped List Frame
Authors: Hyman Michael , Sartore Luca , Young Linda J 
Published: February 2021

Abstract
The emerging sectors of agriculture, such as organics, urban, and local food, tend to be dominated by farms that are smaller, more transient, more diverse, and more dispersed than the traditional farms in the rural areas of the United States. As a consequence, a list frame of all farms within one of these sectors is difficult to construct and, even with the best of efforts, is incomplete. The United States Department of Agriculture’s (USDA’s) National Agricultural Statistics Service (NASS) maintains a list frame of all known and potential U.S. farms and uses this list frame as the sampling frame for most of its surveys. Traditionally, NASS has used its area frame to assess undercoverage. However, getting a good measure of the incompleteness of the NASS list frame using an area frame is cost prohibitive for farms in these emerging sectors that tend to be located within and near urban areas. In 2016, NASS conducted the Local Food Marketing Practices (LFMP) survey. Independent samples were drawn from (1) the NASS list frame and (2) a web-scraped list of local food farms. Using these two samples and capture–recapture methods, the total number and sales of local food operations at the United States, regional, and state levels were estimated. To our knowledge, the LFMP survey is the first survey in which a web-scraped list frame has been used to assess undercoverage in a capture–recapture setting to produce official statistics. In this article, the methods are presented, and the challenges encountered are reviewed. Best practices and open research questions for conducting surveys using web-scraped list frames and capture–recapture methods are discussed.
Allelopathy in rice: a story of momilactones, kin recognition, and weed management
Authors: Serra Serra Núria , Shanmuganathan Reshi , Becker Claude 
Published: February 2021

Abstract
In the struggle to secure nutrient access and to outperform competitors, some plant species have evolved a biochemical arsenal with which they inhibit the growth or development of neighbouring plants. This process, known as allelopathy, exists in many of today’s major crops, including rice. Rice synthesizes momilactones, diterpenoids that are released into the rhizosphere and inhibit the growth of numerous plant species. While the allelopathic potential of rice was recognized decades ago, many questions remain unresolved regarding the biosynthesis, exudation, and biological activity of momilactones. Here, we review current knowledge on momilactones, their role in allelopathy, and their potential to serve as a basis for sustainable weed management. We emphasize the gaps in our current understanding of when and how momilactones are produced and of how they act in plant cells, and outline what we consider the next steps in momilactone and rice allelopathy research.