bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lenvatinib Plus Pembrolizumab for Advanced Endometrial Cancer
Authors: Makker Vicky , Colombo Nicoletta , Herráez Antonio Casado , Santin Alessandro D. , Colomba Emeline , Miller David S. , Fujiwara Keiichi , Pignata Sandro , Baron-Hay Sally , Ray-Coquard Isabelle , Shapira-Frommer Ronnie , Ushijima Kimio , Sakata Jun , Yonemori Kan , Kim Yong Man , Guerra Eva M. , Sanli Ulus A. , McCormack Mary M. , Smith Alan D. , Keefe Stephen , Bird Steven , Dutta Lea , Orlowski Robert J. , Lorusso Domenica 
Published: May 2022

(Abstracted from N Engl J Med 2022;386:437–448)
Little consensus exists on optimal treatment for advanced or recurrent endometrial cancer after disease progression with platinum-based chemotherapy. Lenvatinib is a multitargeted tyrosine kinase inhibitor that as a single agent has demonstrated limited efficacy as second-line treatment of recurrent endometrial carcinoma.
Mechanism of Spindle Pole Organization and Instability in Human Oocytes
Authors: So Chun , Menelaou Katerina , Uraji Julia , Harasimov Katarina , Steyer Anna M. , Seres K. Bianka , Bucevičius Jonas , Lukinavičius Gražvydas , Möbius Wiebke , Sibold Claus , Tandler-Schneider Andreas , Eckel Heike , Moltrecht Rüdiger , Blayney Martyn , Elder Kay , Schuh Melina 
Published: May 2022

(Abstracted from Science 2022;375:eabj3944)
Approximately 25% to 50% of human eggs are aneuploid, with even higher rates among older women. Aneuploidy is a leading cause of abnormal embryonic development resulting in miscarriage and genetic disorders.
Impact of a 1-Year Pediatric Emergency Medicine Training Program for International Medical Graduates
Authors: Cardenas Sandra , Scolnik Dennis , Jarvis D. Anna , Thull-Freedman Jennifer 
Published: May 2022

Objectives
The Hospital for Sick Children in Toronto has offered a 1-year subspecialty residency training program in pediatric emergency medicine (PEM) to Canadian and internationally trained pediatricians and emergency physicians since 1993. The program is intended to support clinical service delivery while simultaneously offering a unique educational opportunity to Canadian and international physicians who desire 1 year of clinically focused training. We describe the experiences and career outcomes of participants who completed this program.

Methods
Two surveys were sent to the 68 individuals who completed the clinical fellowship program from its inception in 1993 until 2014. A blinded survey focused on the fellowship experience and subsequent career activities. A nonblinded survey subsequently determined whether participants had served as a medical director or training program director.

Results
Sixty of the 68 participants (88%) completed the blinded survey. Ninety-one percent were in practice in emergency medicine. Twenty-five percent of the participants were living in Canada, compared with 17% before completing the program. This net migration of 8% was not significant (P = 0.26). Thirty-six of the 50 participants (72%) who applied from outside Canada responded to the nonanonymous survey; 18 (50%) had served as an emergency department medical director, and 18 (50%) reported serving as a PEM training program director.

Conclusions
Many participants attained leadership positions in PEM in countries outside of North America and/or participated in training program development. There was no significant change in the proportion of participants living in North America at the time of application compared with the time of survey completion.
Monthly excess mortality across counties in the United States during the Covid-19 pandemic, March 2020 to February 2022
Authors: Paglino Eugenio , Lundberg Dielle J. , Zhou Zhenwei , Wasserman Joe A. , Raquib Rafeya , Luck Anneliese N. , Hempstead Katherine , Bor Jacob , Preston Samuel H. , Elo Irma T. , Stokes Andrew C. 
Published: May 2022

ABSTRACTExcess mortality is the difference between expected and observed mortality in a given period and has emerged as a leading measure of the overall impact of the Covid-19 pandemic that is not biased by differences in testing or cause-of-death assignment. Spatially and temporally granular estimates of excess mortality are needed to understand which areas have been most impacted by the pandemic, evaluate exacerbating and mitigating factors, and inform response efforts, including allocating resources to affected communities. We estimated all-cause excess mortality for the United States from March 2020 through February 2022 by county and month using a Bayesian hierarchical model trained on data from 2015 to 2019. An estimated 1,159,580 excess deaths occurred during the first two years of the pandemic (first: 620,872; second: 538,708). Overall, excess mortality decreased in large metropolitan counties, but increased in nonmetro counties, between the first and second years of the pandemic. Despite the initial concentration of mortality in large metropolitan Northeast counties, beginning in February 2021, nonmetro South counties had the highest cumulative relative excess mortality. These results highlight the need for investments in rural health as the pandemic’s disproportionate impact on rural areas continues to grow.
Ex vivo to in vivo model of malignant peripheral nerve sheath tumors for precision oncology
Authors: Bhatia Himanshi , Larsson Alex T. , Calizo Ana , Pollard Kai , Zhang Xiaochun , Conniff Eric , Tibbitts Justin F. , Osum Sara H. , Williams Kyle B. , Crampton Ali L. , Jubenville Tyler , Schefer Daniel , Yang Kuangying , Lyu Yang , Bade Jessica , Pino James C. , Gosline Sara J.C. , Pratilas Christine A. , Largaespada David A. , Wood David K. , Hirbe Angela C. 
Published: May 2022

AbstractMalignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1-MPNST), but can occur sporadically. Through a multi-institution collaboration, we have developed 13 NF1-associated MPNST patient-derived xenografts (PDX). Genomic analysis of the PDX-tumor pairs identified somatic mutations in NF1 (61%), SUZ12 (61%), EED (15%), and TP53 (15%), and chromosome 8 (Chr8) gain (77%), consistent with published data. Pre-clinical models that capture this molecular heterogeneity are needed to identify and prioritize effective drug candidates for clinical translation. Here, we describe the successful development of a medium-throughput ex vivo 3D microtissue model with several advantages over 2D cell line growth, which can be utilized to predict drug response in vivo. Herein, we present proof-of-principle of this PDX-to-microtissue system, using four genomically representative MPNST and three drugs. This work highlights the development of a novel ex vivo to in vivo preclinical platform in MPNST that successfully captures the genomic diversity observed in patients and represents a resource to identify future therapeutic strategies.
Mortality during inpatient admissions for Takotsubo cardiomyopathy: can mortality be predicted with a scoring system?
Authors: Loomba Rohit S. 
Published: May 2022

AbstractIntroductionThis study aims to identify which comorbidities and demographic characteristics increase the inpatient mortality rate of patients with TCM and to establish a simple scoring system to help identify those at high risk for mortality.MethodsA retrospective cross-sectional study using the Nationwide Inpatient Sample was conducted. Admissions with and without inpatient mortality were then compared. Univariate analyses were conducted to compare admission characteristics with and without inpatient mortality. A logistic regression analysis was conducted with inpatient mortality as the dependent variability and various admission characteristics as the independent variables in order to develop a model to predict inpatient mortality. The model was then used to calculate a score, the TCM mortality score, for each admission. A receiver operator curve analysis was conducted to determine the sensitivity, specificity, negative predictive value, and positive predictive value of the TCM mortality score in prediction of inpatient mortality.ResultsA total of 19,454 admissions were included in the final analyses. Inpatient mortality was greater in patients that were older, males, Hispanics or Asian Pacific Islanders, and those with Medicare/Medicaid. In regards to comorbidities, inpatient mortality was greater in those with heart failure, arrhythmia, and acute kidney injury. Those with mortality were also more likely to have had an intra-aortic balloon pump or having had to be placed on extracorporeal membrane oxygenation. A mortality score was found to be 4.4 in the mortality group as compared to 1.6 for those in the non-mortality group.ConclusionInpatient mortality with Takotsubo cardiomyopathy is approximately 4.0% and those presenting with certain demographic characteristics and comorbidities are at an increased risk for mortality. A simple scoring system can help identify those at high risk for mortality.
PathGPS: Discover shared genetic architecture using biobank data
Authors: Gao Zijun , Hastie Trevor , Zhao Qingyuan 
Published: May 2022

AbstractThe increasing availability and scale of Genome Wide Association Studies (GWAS) bring new horizons for understanding biological mechanisms. PathGPS is an exploratory method that discovers genetic architecture using GWAS summary data. It can separate genetic components from unobserved environmental factors and extract clusters of genes and traits associated with the same biological pathways. When applying to a metabolomics dataset and the UK Biobank, PathGPS confirms several known gene-trait clusters and suggest many new hypotheses for future investigations.
SARS-CoV-2 outbreaks in secondary school settings in the Netherlands during fall 2020; silent circulation
Authors: Jonker Lotte , Linde Kimberly J , de Hoog Marieke LA , Sprado Robin , Huisman Robin C , Molenkamp Richard , Oude Munnink Bas B , Dohmen Wietske , Heederik Dick JJ , Eggink Dirk , Welkers Matthijs RA , Vennema Harry , Fraaij Pieter LA , Koopmans Marion PG , Wouters Inge M , Bruijning-Verhagen Patricia CJL 
Published: May 2022

AbstractBackgroundIn fall 2020 when schools in the Netherlands operated under a limited set of COVID-19 measures, we conducted outbreaks studies in four secondary schools to gain insight in the level of school transmission and the role of SARS-CoV-2 transmission via air and surfaces.MethodsOutbreak studies were performed between 11 November and 15 December 2020 when the wild-type variant of SARS-CoV-2 was dominant. Clusters of SARS-CoV-2 infections within schools were identified through a prospective school surveillance study. All school contacts of cluster cases, irrespective of symptoms, were invited for PCR testing twice within 48 hrs and 4-7 days later. Combined NTS and saliva samples were collected at each time point along with data on recent exposure and symptoms. Surface and active air samples were collected in the school environment. All samples were PCR-tested and sequenced when possible.ResultsOut of 263 sampled school contacts, 24 tested SARS-CoV-2 positive (secondary attack rate 9.1%), of which 62% remained asymptomatic and 42% had a weakly positive test result. Phylogenetic analysis on 12 subjects from 2 schools indicated a cluster of 8 and 2 secondary cases, respectively, but also other distinct strains within outbreaks. Of 51 collected air and 53 surface samples, none were SARS-CoV-2 positive.ConclusionOur study confirmed within school SARS-CoV-2 transmission and substantial silent circulation, but also multiple introductions in some cases. Absence of air or surface contamination suggests environmental contamination is not widespread during school outbreaks.
H3AGWAS : A portable workflow for Genome Wide Association Studies
Authors: Brandenburg Jean-Tristan , Clark Lindsay , Botha Gerrit , Panji Sumir , Baichoo Shakuntala , Fields Christopher , Hazelhurst Scott 
Published: May 2022

AbstractBackgroundGenome-wide association studies (GWAS) are a powerful method to detect associations between variants and phenotypes. A GWAS requires several complex computations with large data sets, and many steps may need to be repeated with varying parameters. Manual running of these analyses can be tedious, error-prone and hard to reproduce.ResultsThe H3AGWAS workflow from the Pan-African Bioinformatics Network for H3Africa is a powerful, scalable and portable workflow implementing pre-association analysis, implementation of various association testing methods and postassociation analysis of results.ConclusionsThe workflow is scalable — laptop to cluster to cloud (e.g., SLURM, AWS Batch, Azure). All required software is containerised and can run under Docker on Singularity.
GraphPred: An approach to predict multiple DNA motifs from ATAC-seq data using graph neural network and coexisting probability
Authors: Zhang Shuangquan , Yang Lili , Wu Xiaotian , Sheng Nan , Fu Yuan , Ma Anjun , Wang Yan 
Published: May 2022

AbstractAssay for Transposase-Accessible Chromatin sequencing (ATAC-seq) utilizes hyperactive Tn5 transposase to cut open chromatin and reveal chromatin accessibility at a genome-wide level. ATAC-seq can reveal more kinds of transcription factor binding regions than Chromatin immunoprecipitation sequencing (ChIP-seq) and DNase I hypersensitive sites sequencing (DNase-seq). Transcription factor binding sites (TFBSs) prediction is a crucial step to reveal the functions of TFs from the high throughput sequencing data. TFBSs of the same TF tend to be conserved in the sequence level, which is named motif. Several deep learning models based on the convolutional neural networks are used to find motifs from ATAC-seq data. However, these methods didn’t take into account that multiple TFs bind to a given sequence and the probability that a fragment of a given sequence is a TFBS. To find binding sites of multiple TFs, we developed a novel GNN model named GraphPred for TFBSs prediction and finding multiple motifs using the coexisting probability of k-mers. In the light of the experiment results, GraphPred can find more and higher quality motifs from 88 ATAC-seq datasets than comparison tools. Meanwhile, GraphPred achieved an area of eight metrics radar (AEMR) score of 2.31.
Taxonbridge: an R package to create custom taxonomies based on the NCBI and GBIF taxonomies
Authors: Veldsman Werner P. , Campli Giulia , Dind Sagane , de Laval Valentine Rech , Drage Harriet B. , Waterhouse Robert M. , Robinson-Rechavi Marc 
Published: May 2022

ABSTRACTSummaryBiological taxonomies establish conventions by which researchers can catalogue and systematically compare their work using nomenclature such as species binomial names and reference identifiers. The ideal taxonomy is unambiguous and exhaustive; however, no such single taxonomy exists, partly due to continuous changes and contributions made to existing taxonomies. The degree to which a taxonomy is useful furthermore depends on context provided by such variables as the taxonomic neighbourhood of a species (e.g., selecting arthropod or vertebrate species) or the geological time frame of the study (e.g., selecting extinct versus extant species). Collating the most relevant taxonomic information from multiple taxonomies is hampered by arbitrarily defined identifiers, ambiguity in scientific names, as well as duplicated and erroneous entries. The goal of taxonbridge is to provide tools for merging the Global Biodiversity Information Facility (GBIF) Backbone Taxonomy and the United States National Center for Biotechnology Information (NCBI) Taxonomy in order to create consistent, deduplicated and disambiguated custom taxonomies that reference both extant and extinct species.AvailabilityTaxonbridge is available as a package in the Comprehensive R Archive Network (CRAN) repository: https://CRAN.R-project.org/package=taxonbridge.Contactwernerpieter.veldsman@unil.ch
Robust associations between white matter microstructure and general intelligence
Authors: Stammen Christina , Fraenz Christoph , Grazioplene Rachael G. , Schlüter Caroline , Merhof Viola , Johnson Wendy , Güntürkün Onur , DeYoung Colin G. , Genç Erhan 
Published: May 2022

AbstractEarly research on the neural correlates of human intelligence was almost exclusively focused on gray matter properties. The advent of diffusion-weighted imaging led to an exponential growth of white matter brain imaging studies. However, this line of research has yielded mixed observations, especially about the relations between general intelligence and white matter microstructure. We used a multi-center approach to identify white matter regions that show replicable structure-function associations, employing data from four independent samples comprising over 2000 healthy participants. We used tract-based spatial statistics to examine associations between g factor scores and white matter microstructure and identified 188 voxels which exhibited positive associations between g factor scores and fractional anisotropy in all four data sets. Replicable voxels formed three clusters: one located around the forceps minor, crossing with extensions of the anterior thalamic radiation, the cingulum-cingulate gyrus, and the inferior fronto-occipital fasciculus in the left hemisphere, one located around the left-hemispheric superior longitudinal fasciculus, and one located around the left-hemispheric cingulum-cingulate gyrus, crossing with extensions of the anterior thalamic radiation and the inferior fronto-occipital fasciculus. Our results indicate that individual differences in general intelligence are robustly associated with white matter organization in specific fiber bundles.
Abrupt transitions and its indicators in mutualistic meta-networks: effects of network topology, size of metacommunities and species dispersal
Authors: Baruah Gaurav 
Published: May 2022

AbstractGradual changes in the environment could cause dynamical ecological networks to abruptly shift from one state to an alternative state. When this happens ecosystem functions and services provided by ecological networks get disrupted. We, however, know very little about how the topology of such interaction networks can play a role in the transition of ecological networks at spatial scales. In the event of such unwanted transitions, little is known about how statistical metrics used to inform such impending transitions, measured at the species-level or at the community-level could relate to network architecture and the scale of spatial interactions such as the size of the metacommunity. Here, using hundred and one empirical plant-pollinator networks in a spatial setting, I evaluated the impact of network topology and spatial scale of species interactions on abrupt transitions, and on statistical metrics used as predictors to forecast such abrupt transitions. Using generalized Lotka-Volterra equations in a meta-network framework, I show that species dispersal rate and the size of the metacommunity can impact when an abrupt transition can occur. In addition, forecasting such unwanted abrupt transitions of meta-networks using statistical metrics of instability was also consequently dependent on the topology of the network, species dispersal rate, and the size of the metacommunity. The results indicated that the plant-pollinator meta-networks that could exhibit stronger statistical signals before collapse than others were dependent on their network architecture and on the spatial scale of species interactions.
Gestational day 12 moderate prenatal alcohol exposure produces sex-specific social impairments and attenuates prelimbic excitability and amygdala-cortex modulation of adult social behavior
Authors: Przybysz Kathryn R. , Spodnick Mary B. , Johnson Julia M. , Varlinskaya Elena I. , Diaz Marvin R. 
Published: May 2022

AbstractLifelong social impairments are common in individuals with prenatal alcohol exposure (PAE), and preclinical studies have identified gestational day (G)12 as a vulnerable timepoint for producing social deficits following binge-level PAE. While moderate (m)PAE also produces social impairments, the long-term neuroadaptations underlying them are poorly understood. Activity of the projection from the basolateral amygdala to the prelimbic cortex (BLA→PL) leads to social avoidance, and the PL alone is implicated in negative social behaviors, making each of these potential candidates for the neuroadaptations underlying mPAE-induced social impairments. To examine this, we first established that G12 mPAE produced sex-specific social impairments lasting into adulthood. We then chemogenetically inhibited the BLA→PL using Clozapine N-Oxide (CNO) during adult social testing. This revealed that CNO reduced social investigation in control males, but had no effect on mPAE males or females of either exposure, indicating that mPAE attenuated the role of this projection in regulating male social behavior and highlighting one potential mechanism by which mPAE affects male social behavior more severely. Using whole-cell electrophysiology, we also examined mPAE-induced changes to PL pyramidal cell physiology and determined that mPAE reduced the excitability of these cells, likely due to increased suppression by inhibitory interneurons. Overall, this work identified two mPAE-induced neuroadaptations that last into adulthood and which may underlie the sexspecific vulnerability to mPAE-induced social impairments. Future research is necessary to expand upon how these circuits modulate both normal and pathological social behavior, and to identify sex-specific mechanisms leading to differential vulnerability in males and females.
The role of geology in creating stream climate-change refugia along climate gradients
Authors: Ishiyama Nobuo , Sueyoshi Masanao , Jorge García Molinos , Iwasaki Kenta , Negishi N Junjiro , Koizumi Itsuro , Nagayama Shigeya , Nagasaka Akiko , Nagasaka Yu , Nakamura Futoshi 
Published: May 2022

AbstractIdentifying climate-change refugia is a key adaptation strategy for reducing global warming impacts. Knowledge of the effects of underlying geology on thermal regime along climate gradients and the ecological responses to the geology-controlled thermal regime is essential to plan appropriate climate adaptation strategies. The dominance of volcanic rocks in the watershed is used as a landscape-scale surrogate for cold groundwater inputs to clarify the importance of underlying geology. Using statistical models, we explored the relationship between watershed geology and the mean summer water temperature of mountain streams along climate gradients in the Japanese archipelago. Summer water temperature was explained by the interaction between the watershed geology and climate in addition to independent effects. The cooling effect associated with volcanic rocks was more pronounced in streams with less summer precipitation or lower air temperatures. We also examined the function of volcanic streams as cold refugia under contemporary and future climatic conditions. Community composition analyses revealed that volcanic streams hosted distinct stream communities composed of more cold-water species compared with non-volcanic streams. Scenario analyses revealed a geology-related pattern of thermal habitat loss for cold-water species. Non-volcanic streams rapidly declined in thermally suitable habitats for lotic sculpins even under the lowest emission scenario (RCP 2.6). In contrast, most volcanic streams will be sustained below the thermal threshold, especially for low and mid-level emission scenarios (RCP 2.6, 4.5). However, the distinct stream community in volcanic streams and geology-dependent habitat loss for lotic sculpins was not uniform and was more pronounced in areas with less summer precipitation or lower air temperatures. Although further studies are needed to understand underlying mechanisms of the interplay of watershed geology and climate, findings highlight that watershed geology, climate variability, and their interaction should be considered simultaneously for effective management of climate-change refugia in mountain streams.