bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Blueprint for Creating Mentored, Collaborative Networks for Early-Career Physician-Scientists
Authors: Mueller Margaret G. , Andy Uduak , Brennaman Lisa , Dieter Alexis A. , Kirby Anna C. , Shepherd Jonathan , Gregory W. Thomas , Amundsen Cindy L. 
Published: December 2020

Objectives
The objective is to improve the high-quality collaborative research of early-career investigators, the American Urogynecologic Society/Pelvic Floor Disorders Foundation funded and developed the Junior Faculty Research Network (JFRN). The purpose of this report is to describe the process of development of the network, discuss barriers, acknowledge accomplishments, and provide a framework for future collaborations.

Methods
The development of the JFRN provided sponsorship and mentorship, supported collaboration, and created a network structure for early-career investigators. A request for applications was circulated, requiring a competitive submission process, and 6 physician-scientists were selected to participate in a multicenter trial whose initial focus was on the urinary microbiome and its interaction with sacral neuromodulation.

Results
The JFRN infrastructure consisted of early-career investigators, senior advisors, and research support staff. Study development and roll-out progressed over monthly conference calls. Initial barriers included the development of institutional participation agreements, logistics of funding disbursement, and coordination of support staff. In addition to the inaugural research project, the network continued to collaborate, and the initial grant provided pilot data for a National Institutes of Health-funded project.

Conclusions
The JFRN is a successful mentored collaborative of early-career investigators. The creation of this self-sustaining, independent research network may serve as a blueprint for other early-career physician-scientists to participate in productive multicenter research.
Rates of Sling Procedures and Revisions—A National Surgical Quality Improvement Program Database Study
Authors: Bretschneider C. Emi , Geynisman-Tan Julia , Mueller Margaret G. , Collins Sarah A. , Lewicky-Gaupp Christina , Kenton Kimberly 
Published: December 2020

Objective
The aim of this study was to describe trends in sling procedures and revisions, including fascial slings and midurethral slings (MUS) using a large, national database with respect to the 2011 U.S. Food and Drug Administration (FDA) mesh-related safety communication.

Methods
This was a cross-sectional cohort study using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database from 2010 to 2018, evaluating the prevalence of sling revision and fascial slings and their trends over time. Patients who underwent MUS, fascial slings, and sling revisions were identified by Current Procedural Terminology codes. Sling revisions and fascial slings were evaluated as a proportion of the total number of MUS performed per year. Three distinct periods were evaluated in relation to the 2011 FDA communication: 2010 to 2012, 2012 to 2015, and 2015 to 2018. Observed trends were assessed with Pearson correlation coefficients with a P value less than 0.05 considered significant.

Results
During the study period, 32,657 slings were captured: 32,389 MUS and 268 fascial slings. The rate of sling revisions was low (0.4% in 2010 to 1.2% in 2015). Between 2012 and 2015, the rate of sling revision increased significantly (R = 1, P = 0.002); following 2015, the rate of sling revisions decreased significantly over time (R = −0.96, P = 0.04). The rate of fascial slings between 2012 and 2015 increased significantly (R = 0.95, P = 0.047); however, the rate plateaued starting in 2015 (R = −0.49, −P = 0.51).

Conclusions
Our data suggest that MUS remain the preferred procedure for treatment of stress urinary incontinence despite the recent FDA communications with MUS representing 99% of sling procedures during the study period.
Chronic Histologic Changes Are Present Regardless of HLA Mismatches: Evidence from HLA-Identical Living Donor Kidney Transplants
Authors: D’Costa Matthew R. , Bentall Andrew , Denic Aleksandar , Schinstock Carrie A. , Merzkani Massini A. , Park Walter D. , Ryan Margaret S. , Alexander Mariam P. , Smith Byron H. , Gandhi Manish J. , Stegall Mark D. 
Published: December 2020

Background.
At 5 and 10 y after kidney transplantation, chronic histologic changes such as arteriolar hyalinosis and mesangial expansion are common; however, determining cause is difficult. We compared surveillance biopsies in living donor kidney transplants (LDKTx) from HLA-matched siblings (termed HLA-identical [HLA-ID]) with HLA non-ID to investigate which histologic changes were likely due to alloimmune injury and which were due to nonalloimmune injury.

Methods.
We performed a retrospective, cohort study comparing HLA-ID sibling LDKTx (n = 175) with HLA non-ID LDKTx (n = 175; matched for age, sex, and year of transplant ±2 y) performed at a single institution from March 1999 to November 2018.

Results.
Baseline characteristics and maintenance immunosuppression were similar. Mortality rates were similar, but in the HLA-ID group, 10-y death-censored graft survival was higher (93.8% versus 80.9% HLA non-ID LDKTx; P < 0.001), rejection rates were lower (after 1 y 9.6% versus 27.1%; P < 0.001), and Banff inflammation scores including glomerulitis and peritubular capillaritis were lower on surveillance biopsies at 1, 5, and 10 y. In contrast, chronic Banff scores (interstitial fibrosis, arteriolar hyalinosis, mesangial expansion, etc) were similar in prevalence and severity on surveillance biopsies at 1, 5, and 10 y.

Conclusions.
HLA-ID LDKTx have less inflammation and less transplant glomerulopathy, but most chronic histologic changes were similar to less well-matched LDKTx. We conclude that these types of chronic changes are not associated with HLA mismatches and may be due to nonimmunologic causes (hypertension, obesity, etc), suggesting that new management approaches to prevent these lesions may be needed.
Unconscious mental imagery
Authors: Nanay Bence 
Published: December 2020

Historically, mental imagery has been defined as an experiential state—as something necessarily conscious. But most behavioural or neuroimaging experiments on mental imagery—including the most famous ones—do not actually take the conscious experience of the subject into consideration. Further, recent research highlights that there are very few behavioural or neural differences between conscious and unconscious mental imagery. I argue that treating mental imagery as not necessarily conscious (as potentially unconscious) would bring much needed explanatory unification to mental imagery research. It would also help us to reassess some of the recent aphantasia findings inasmuch as at least some subjects with aphantasia would be best described as having unconscious mental imagery.This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
Exploring the neural basis of fear produced by mental imagery: imaginal exposure in individuals fearful of spiders
Authors: Hoppe Johanna M. , Holmes Emily A. , Agren Thomas 
Published: December 2020

Imaginal exposure, i.e. reducing fear using exposure to mental imagery, is a widely used psychological treatment technique for dysfunctional fears. Yet, little is known about its underlying neural mechanisms. The present study examines the neural basis of imaginal exposure using a novel experimental procedure consisting of repeated exposure to flashpoint mental imagery of phobic (spiders) and neutral (gloves) stimuli. Whether the 10 min long imaginal exposure procedure could reduce fear responses was examined one week later. Thirty participants fearful of spiders underwent the experimental procedure. Neural activity was assessed using functional magnetic resonance imaging (session 1). Subjective fear and skin conductance responses were measured throughout the study (sessions 1 and 2). Imaginal exposure evoked intense fear and heightened skin conductance responses, and indicated robust activation in several brain regions, including amygdala, midcingulate cortex and insula. Findings demonstrate that neural activity in fear-processing brain areas can be elicited solely by generating a mental image of a phobic stimulus, that is, in the absence of the percept. Relevant for treatment development, results reveal that a single 10 min session of brief exposures to flashpoint mental imagery can lead to lasting reductions in phobic fear at both the subjective and physiological levels.This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.
Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Authors: Horby Peter W , Roddick Alistair , Spata Enti , Staplin Natalie , Emberson Jonathan R , Pessoa-Amorim Guilherme , Peto Leon , Campbell Mark , Brightling Christopher , Prudon Ben , Chadwick David , Ustianowski Andrew , Ashish Abdul , Todd Stacy , Yates Bryan , Buttery Robert , Scott Stephen , Maseda Diego , Baillie J Kenneth , Buch Maya H , Chappell Lucy C , Day Jeremy N , Faust Saul N , Jaki Thomas , Jeffery Katie , Juszczak Edmund , Lim Wei Shen , Montgomery Alan , Mumford Andrew , Rowan Kathryn , Thwaites Guy , Mafham Marion , Haynes Richard , Landray Martin J ,   RECOVERY Collaborative Group
Published: December 2020

SUMMARYBackgroundAzithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We evaluated the efficacy and safety of azithromycin in hospitalised patients with COVID-19.MethodsIn this randomised, controlled, open-label, adaptive platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once daily by mouth or intravenously for 10 days or until discharge (or one of the other treatment arms). Patients were twice as likely to be randomised to usual care as to any of the active treatment groups. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).FindingsBetween 7 April and 27 November 2020, 2582 patients were randomly allocated to receive azithromycin and 5182 patients to receive usual care alone. Overall, 496 (19%) patients allocated to azithromycin and 997 (19%) patients allocated to usual care died within 28 days (rate ratio 1·00; 95% confidence interval [CI] 0·90-1·12; p=0·99). Consistent results were seen in all pre-specified subgroups of patients. There was no difference in duration of hospitalisation (median 12 days vs. 13 days) or the proportion of patients discharged from hospital alive within 28 days (60% vs. 59%; rate ratio 1·03; 95% CI 0·97-1·10; p=0·29). Among those not on invasive mechanical ventilation at baseline, there was no difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0·97; 95% CI 0·89-1·07; p=0·54).InterpretationIn patients hospitalised with COVID-19, azithromycin did not provide any clinical benefit. Azithromycin use in patients hospitalised with COVID-19 should be restricted to patients where there is a clear antimicrobial indication.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).
Analysing economic costs of invasive alien species with the invacost R package
Authors: Leroy Boris , Kramer Andrew M. , Vaissière Anne-Charlotte , Kourantidou Melina , Courchamp Franck , Diagne Christophe 
Published: December 2020

AbstractThe reported costs of invasive alien species from the global database InvaCost are heterogenous and cover different spatio-temporal scales. A standard procedure for aggregating invasive species cost estimates is necessary to ensure the repeatability and comparativeness of studies.We introduce here theinvacostR package, an open-source software designed to query and analyse the InvaCost database. We illustrate this package and its framework with cost data associated with invasive alien invertebrates.First, theinvacostpackage provides updates of this dynamic database directly in the analytical environment R. Second, it helps understand the heteregoneous nature of monetary cost data for invasive species, processes to harmonize the data, and the inherent biases associated with such data. Third, it readily provides complementary methods to investigate the costs of invasive species at different scales, all the while accounting for econometric statistical issues.This tool will be useful for scientists working on invasive alien species, by (i) facilitating access to and use of this multi-disciplinary data resource and (ii) providing a standard procedure which will facilitate reproducibility and comparability among studies, one of the major critics of this topic until now. It should facilitate further interdisciplinary works including economists and invasion ecology researchers.
Baby makes three: maternal, paternal, and zygotic genetic effects shape larval phenotypic evolution
Authors: Zakas Christina , Rockman Matthew V. 
Published: December 2020

ABSTRACTThe evolutionary potential of a population is shaped by the genetic architecture of its life-history traits. Early-life phenotypes are influenced by both maternal and offspring genotype, and efforts to understand life-history evolution therefore require consideration of the interactions between these separate but correlated genomes. We used a four-generation experimental pedigree to estimate the genetic architecture of early-life phenotypes in a species with dramatic variation in larval size and morphology. In the polychaete annelidStreblospio benedicti, females make either many small eggs that develop into complex larvae that feed in the plankton or few large eggs that develop into benthic juveniles without having to feed as larvae. By isolating the contributions of maternal, paternal, and zygotic genotype to larval traits, we determined that larval anatomical structures are governed by the offspring genotype at a small number of large-effect loci. Larval size is not shaped by the larva’s own genotype but instead depends on loci that act in the mother, and at two genomic locations, by loci that act in the father. The overall phenotype of each larva thus depends on three separate genomes, and a population’s response to selection on larval traits will reflect the interactions among them.
Allosteric conformational ensembles have unlimited capacity for integrating information
Authors: Biddle John W. , Martinez-Corral Rosa , Wong Felix , Gunawardena Jeremy 
Published: December 2020

ABSTRACTIntegration of binding information by macromolecular entities is fundamental to cellular functionality. Recent work has shown that such integration cannot be explained by pairwise cooperativities, in which binding is modulated by binding at another site. Higher-order cooperativities (HOCs), in which binding is collectively modulated by multiple other binding events, appears to be necessary but an appropriate mechanism has been lacking. We show here that HOCs arise through allostery, in which effective cooperativity emerges indirectly from an ensemble of dynamically-interchanging conformations. Conformational ensembles play important roles in many cellular processes but their integrative capabilities remain poorly understood. We show that sufficiently complex ensembles can implement any form of information integration achievable without energy expenditure, including all HOCs. Our results provide a rigorous biophysical foundation for analysing the integration of binding information through allostery. We discuss the implications for eukaryotic gene regulation, where complex conformational dynamics accompanies widespread information integration.
Cellular adaptation and the importance of the purine biosynthesis pathway during biofilm formation in Gram-positive pathogens
Authors: Gélinas Martin , Museau Léa , Milot Arielle , Beauregard Pascale B. 
Published: December 2020

AbstractBacterial biofilms are involved in chronic infections and confer 10 to 1000 times more resistance to antibiotics, leading to treatment failure and complications. When transitioning from a planktonic lifestyle to biofilms, certain Gram-positive bacteria are likely to modulate several cellular pathways including central carbon metabolism, primary biosynthesis pathways and production of secondary metabolites. These metabolic adaptations might play a crucial role in biofilm formation by Gram-positive pathogens such asStaphylococcus aureusandEnterococcus faecalis. Here, we performed a transcriptomic approach to identify cellular pathways that might be similarly regulated during biofilm formation in these bacteria. Different strains and biofilm-inducing media were used to identify a set of regulated genes that are common and independent of the environment or accessory genomes analysed. The gene set enrichment analysis of the transcriptome of four different strains of Gram-positive bacteria identified biosynthesis of secondary metabolites, biosynthesis of antibiotics and purine biosynthesis as three commonly upregulated pathways in biofilm. Our approach did not highlight downregulated pathways during biofilm formation that were common toS. aureusandE. faecalis. Of the three upregulated pathways, thede novoIMP biosynthesis pathway constitutes a promising target of cellular adaptation during biofilm formation. Gene deletions in this pathway, particularlypurN, purL, purQ, purHandpurMsignificantly impaired biofilm formation ofS. aureus.ImportanceBiofilms are often involved in nosocomial infections and can cause serious chronic infections if not treated properly. Current anti-biofilm strategies rely on antibiotic usage, but they have a limited impact because of the biofilm’s intrinsic resistance to drugs. Metabolism remodelling likely plays a central role during biofilm formation, but it is still unclear if these cellular adaptations are shared between strains and species. Using comparative transcriptomics of different strains ofStaphylococcus aureusandEnterococcus faecalis, we identified a core of commonly regulated genes during biofilm formation. Interestingly, we observed that thede novoIMP biosynthesis was systematically upregulated during biofilm formation. This pathway could constitute an interesting new anti-biofilm target to increase the host spectrum, drug efficiency and prevent resistance evolution. These results are also relevant to a better understanding of biofilm physiology.
Uncovering the Structure and Function of Microbial Communities Formed During Periodic Tilling of TNT and DNT Co-Contaminated Soils
Authors: Keshani-Langroodi Saeed , Lan Yemin , Stenuit Ben , Rosen Gail , Hughes Joseph B. , Alvarez-Cohen Lisa , Sales Christopher M. 
Published: December 2020

1.AbstractEnvironmental contamination by 2,4,6-trinitrotoluene (TNT), historically the most widely used secondary explosive, is a long-standing problem in former military conflict areas and at manufacturing and decommissioning plants. In field test plots at a former explosives manufacturing site, removal of TNT and dinitrotoluenes (DNTs) was observed following periods of tillage. Since tilling of soils has previously been shown to alter the microbial community, this study was aimed at understanding how the microbial community is altered in soils with historical contamination of nitro explosives from the former Barksdale TNT plant. Samples of untilled pristine soils, untilled TNT-contaminated soils and tilled TNT-contaminated soils were subjected to targeted amplicon sequencing of 16S ribosomal RNA genes in order to compare the structure of their bacterial communities. In addition, metagenomic data generated from the TNT tilled soil was used to understand the potential functions of the bacterial community relevant to nitroaromatic degradation. While the biodiversity dropped and theBurkholderialesorder became dominant in both tilled and untilled soil regardless of tillage, the bacterial community composition at finer taxonomic levels revealed a greater difference between the two treatments. Functional analysis of metagenome assembled genome (MAG) bins through systematic review of commonly proposed DNT and TNT biotransformation pathways suggested that both aerobic and anaerobic degradation pathways were present. A proposed pathway that considers both aerobic and anaerobic steps in the degradation of TNT in the scenario of the tilled contaminated soils is presented.2.ImportanceIn this study, TNT and DNT removal has been observed in field-scale experiments following periodic tilling of historically contaminated soils. The microbial community structures of uncontaminated pristine soils, untilled contaminated soils, and tilled contaminated soils were investigated using high-throughput sequencing platforms. In addition, shotgun metagenome libraries of samples from tilled contaminated soils were generated. The results indicated that a significant shift of the bacterial community at the family level between tilled and untilled contaminated soils, with tilled soils being dominated byAlcaligenaceaeand untilled soils byBurkholderiacea.In-depth metagenomic analysis of samples from tilled contaminated soils, indicate the presence of genes that encode for enzymes that potentially could lead to mineralization of TNT and DNT under mixed aerobic and anaerobic periods.
Association of Structural Variation with Cardiometabolic Traits in Finns
Authors: Chen Lei , Abel Haley J. , Das Indraniel , Larson David E. , Ganel Liron , Kanchi Krishna L. , Regier Allison A. , Young Erica P. , Kang Chul Joo , Scott Alexandra J , Chiang Colby , Wang Xinxin , Lu Shuangjia , Christ Ryan , Service Susan K. , Chiang Charleston W.K. , Havulinna Aki S. , Kuusisto Johanna , Boehnke Michael , Laakso Markku , Palotie Aarno , Ripatti Samuli , Freimer Nelson B. , Locke Adam E. , Stitziel Nathan O. , Hall Ira M. 
Published: December 2020

AbstractThe contribution of genome structural variation (SV) to quantitative traits associated with cardiometabolic diseases remains largely unknown. Here, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. We used sensitive methods to identify and genotype 129,166 high-confidence SVs from deep whole genome sequencing (WGS) data of 4,848 individuals. We tested the 64,572 common and low frequency SVs for association with 116 quantitative traits, and tested candidate associations using exome sequencing and array genotype data from an additional 15,205 individuals. We discovered 31 genome-wide significant associations at 15 loci, including two novel loci at which SVs have strong phenotypic effects: (1) a deletion of theALBgene promoter that is greatly enriched in the Finnish population and causes decreased serum albumin level in carriers (p=1.47×10−54), and is also associated with increased levels of total cholesterol (p=1.22×10−28) and 14 additional cholesterol-related traits, and (2) a multiallelic copy number variant (CNV) atPDPRthat is strongly associated with pyruvate (p=4.81×10−21) and alanine (p=6.14×10−12) levels and resides within a structurally complex genomic region that has accumulated many rearrangements over evolutionary time. We also confirmed six previously reported associations, including five led by stronger signals in single nucleotide variants (SNVs), and one linking recurrentHPgene deletion and cholesterol levels (p=6.24×10−10), which was also found to be strongly associated with increased glycoprotein level (p=3.53×10−35). Our study confirms that integrating SVs in trait-mapping studies will expand our knowledge of genetic factors underlying disease risk.