bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variations in clot phenotype following injury: The MA-R ratio and fragile clots
Authors: Harrington James , Zarzaur Ben L. , Fox Erin E. , Wade Charles E. , Holcomb John B. , Savage Stephanie A. 
Published: October 2021

INTRODUCTION
Trauma-induced coagulopathy is a continuum ranging from hypercoagulable to hypercoagulable phenotypes. In single-center studies, the maximum amplitude (MA) to r-time (R) (MA-R) ratio has identified a phenotype of injured patients with high mortality risk. The purpose of this study was to determine the relationship between MA-R and mortality using multicenter data and to investigate fibrinogen consumption in the development of this specific coagulopathy phenotype.

METHODS
Using the Pragmatic Randomized Optimal Platelet and Plasma Ratios data set, patients were divided into blunt and penetrating injury cohorts. MA was divided by R time from admission thromboelastogram to calculate MA-R. MA-R was used to assess odds of early and late mortality using multivariable models. Multivariable models were used to assess thrombogram values in both cohorts. Refinement of the MA-R cut point was performed with Youden index. Repeat multivariable analysis was performed with a binary CRITICAL and NORMAL MA-R.

RESULTS
In initial analysis, MA-R quartiles were not associated with mortality in the penetrating cohort. In the blunt cohort, there was an association between low MA-R and early and late mortality. A refined cut point of 11 was identified (CRITICAL: MA-R, ≤11; NORMAL: MA-R, >11). CRITICAL MA-R was associated with mortality in both penetrating and blunt subgroups. In further injury subgroup analysis, CRITICAL patients had significantly decreased fibrinogen levels in the blunt subgroup only. In both blunt and penetrating injury, there was no difference in time to initiation of thrombin burst (lagtime). However, both endogenous thrombin potential and peak thrombin levels were significantly lower in CRITICAL patients.

CONCLUSIONS
MA-R identifies a trauma-induced coagulopathy phenotype characterized in blunt injury by impaired thrombin generation that is associated with early and late mortality. The endotheliopathy and tissue factor release likely plays a role in the cascade of impaired thrombin burst, possible early fibrinogen consumption and the weaker clot identified by MA-R.

LEVEL OF EVIDENCE
Therapeutic/care management, level II.
Performance assessment of a new indirect rapid diagnostic test for plague detection in humans and other mammalian hosts
Authors: Bezerra Matheus Filgueira , dos Santos Wagner José Tenório , Rocha Igor Vasconcelos , Nadaes Natalia Rocha , Dantas-Torres Filipe , Silva Sales Kamila Gaudêncio da , de Melo Neto Osvaldo Pompilio , da Silva Marise Sobreira Bezerra , Silva Edimilson Domingos , de Almeida Alzira Maria Paiva , de Souza Reis Christian Robson 
Published: October 2021

ABSTRACTPlague is a flea-borne zoonosis that affects a wide range of mammals and still causes outbreaks in human populations yearly across several countries. While crucial for proper treatment, early diagnosis is still a major challenge in low- and middle-income countries due to poor access to laboratory infrastructure in rural areas. To tackle this issue, we developed and evaluated a new F1-based rapid diagnostic test (RDT) as an alternative method for plague diagnosis in humans and other mammals in the field. In this study, 187 serum samples from humans, dogs, rodents and rabbits were retrospectively assessed using the Plague RDT method. To calculate its performance rates, results were confronted to those obtained by hemagglutination (HA) and ELISA, considered as the reference standards. Remarkably, the results from RDT were in full agreement with those from the ELISA and HA assays, resulting in 100% (CI 95% = 95.5-100%) of sensitivity and 100% (CI 95% = 96.6-100%) of specificity. Accordingly, the Cohen’s Kappa test coefficient was 1.00 (almost perfect agreement). Moreover, the RDT showed no cross-reaction when tested with sera from individuals positive to other pathogens, such as Yersinia pseudotuberculosis, Yersinia enterocolitica, Anaplasma platys, Erliquia canis and Leishmania infantum. Although preliminary, this study brings consistent proof-of-concept results with high performance rates of the Plague RDT when compared to other methods well-established in the plague routine serodiagnosis. Although further human and animal population-based studies will be necessary to validate these findings, the data presented here show that the Plague RDT is highly sensitive and specific, polyvalent to several mammal species and simple to use in field surveillance or point-of-care situations with instant results.
Association of Body Anthropometry and Obstructive Sleep Apnea in Children: Impact of Hispanic Ethnicity
Authors: Bhattacharjee Emily B , Sun Xiaoying , Malhotra Atul , Tantisira Kelan G , Landeo-Gutierrez Jeremy S , Jain Sonia , Bhattacharjee Rakesh 
Published: October 2021

AbstractObjectivesObesity is a risk factor for obstructive sleep apnea (OSA) in children. Childhood obesity rates vary amongst different ethnic groups. Here we explore the interaction of Hispanic ethnicity and obesity on OSA risk.MethodsRetrospective cross-sectional analysis of consecutive children undergoing polysomnography and anthropometry using bioelectrical impedance from 2017-2020. Demographics obtained from the medical chart. Children who had also undergone cardiometabolic testing were identified to assess the relationship of cardiometabolic markers with OSA and anthropometry.ResultsData from 1217 children revealed Hispanic children were more likely to have moderate-severe OSA (36.0%) compared to Non-Hispanic children (26.5%), p<0.001. Hispanic children had greater BMI, BMI percentile and percent body fat, p<0.0001. In children that underwent cardiometabolic testing, Hispanic children had significantly greater serum ALT levels. Following adjustment of age and sex, Hispanic ethnicity was not found to moderate the association of anthropometry with OSA, anthropometry with cardiometabolic markers, and OSA with cardiometabolic markers.ConclusionsOSA is more likely in Hispanic children; this relationship is likely driven by obesity status rather than ethnicity. Among children undergoing cardiometabolic testing, Hispanic children were observed to have greater ALT concentrations however ethnicity did not impact the association of anthropometry and ALT or other cardiometabolic markers.
Predictors of SARS-CoV-2 infection following high-risk exposure
Authors: Andrejko Kristin L. , Pry Jake , Myers Jennifer F. , Openshaw John , Watt James , Birkett Nozomi , DeGuzman Jennifer L. , Li Sophia S. , Barbaduomo Camilla M. , Fang Anna T. , Tran Vivian H. , Javadi Mahsa H. , Frost Paulina M. , Dong Zheng N. , Jain Seema , Lewnard Joseph A. 
Published: October 2021

ABSTRACTBackgroundNon-pharmaceutical interventions (NPIs) are recommended for COVID-19 mitigation. However, the effectiveness of NPIs in preventing SARS-CoV-2 transmission remains poorly quantified.MethodsWe conducted a test-negative design case-control study enrolling cases (testing positive for SARS-CoV-2) and controls (testing negative) with molecular SARS-CoV-2 diagnostic test results reported to California Department of Public Health between 24 February-26 September, 2021. We used conditional logistic regression to assess predictors of case status among participants who reported contact with an individual known or suspected to have been infected with SARS-CoV-2 (“high-risk exposure”) within ≤14 days of testing.Results643 of 1280 cases (50.2%) and 204 of 1263 controls (16.2%) reported high-risk exposures ≤14 days before testing. Adjusted odds of case status were 2.94-fold (95% confidence interval: 1.66-5.25) higher when high-risk exposures occurred with household members (vs. other contacts), 2.06-fold (1.03-4.21) higher when exposures occurred indoors (vs. not indoors), and 2.58-fold (1.50-4.49) higher when exposures lasted ≥3 hours (vs. shorter durations) among unvaccinated and partially-vaccinated individuals; excess risk associated with such exposures was mitigated among fully-vaccinated individuals. Mask usage by participants or their contacts during high-risk exposures reduced adjusted odds of case status by 48% (8-72%). Adjusted odds of case status were 68% (32-84%) and 77% (59-87%) lower for partially- and fully-vaccinated participants, respectively, than for unvaccinated participants. Benefits of mask usage were greatest when exposures lasted ≥3 hours, occurred indoors, or involved non-household contacts.ConclusionsNPIs reduced the likelihood of SARS-CoV-2 infection following high-risk exposure. Vaccine effectiveness was substantial for partially and fully vaccinated persons.KEY POINTSSARS-CoV-2 infection risk was greatest for unvaccinated participants when exposures to known or suspected cases occurred indoors or lasted ≥3 hours.Face mask usage when participants were exposed to a known or suspect case reduced odds of infection by 48%.
Generation time of the Alpha and Delta SARS-CoV-2 variants
Authors: Hart WS , Miller E , Andrews NJ , Waight P , Maini PK , Funk S , Thompson RN 
Published: October 2021

SummaryBackgroundIn May 2021, the Delta SARS-CoV-2 variant became dominant in the UK. This variant is associated with increased transmissibility compared to the Alpha variant that was previously dominant. To understand ongoing transmission and interventions, a key question is whether the Delta variant generation time (the time between infections in infector- infectee pairs) is typically shorter–i.e., transmissions are happening more quickly–or whether infected individuals simply generate more infections.MethodsWe analysed transmission data from a UK Health Security Agency household study. By fitting a mathematical transmission model to the data, we estimated the generation times for the Alpha and Delta variants.ResultsThe mean intrinsic generation time (the generation time if there had been a constant supply of susceptibles throughout infection) was shorter for the Delta variant (4·6 days, 95% CrI 4·0-5·4 days) than the Alpha variant (5·5 days, 95% CrI 4·6-6·4 days), although within uncertainty ranges. However, there was a larger difference in the realised mean household generation time between the Delta (3·2 days, 95% CrI 2·4-4·2 days) and Alpha (4·5 days, 95% CrI 3·7-5·4 days) variants. This is because higher transmissibility led to faster susceptible depletion in households, in addition to the reduced intrinsic generation time.ConclusionsThe Delta variant transmits more quickly than previously circulating variants. This has implications for interventions such as contact tracing, testing and isolation, which are less effective if the virus is transmitted quickly. Epidemiological models of interventions should be updated to include the shorter generation time of the Delta variant.
Reduced context updating but intact visual priors in autism
Authors: Randeniya R. , Vilares I. , Mattingley J. B. , Garrido M. I. 
Published: October 2021

AbstractA general consensus persists that sensory-perceptual differences in autism, such as hypersensitivities to light or sound, result from an overreliance on new (rather than prior) sensory observations. However, conflicting Bayesian accounts of autism remain unresolved as to whether such alterations are caused by more precise sensory observations (precise likelihood model) or by forming a less precise model of the sensory context (hypo-priors model). We used a decision-under-uncertainty paradigm that manipulated uncertainty in both likelihoods and priors. Contrary to model predictions we found no differences in reliance on likelihood in autistic group (AS) compared to neurotypicals (NT) and found no differences in subjective prior variance between groups. However, we found reduced context adjustment in the AS group compared to NT. Further, the AS group showed heightened variability in their relative weighting of sensory information (vs. prior) on a trial-by-trial basis. When participants were aligned on a continuum of autistic traits, we found no associations with likelihood reliance or prior variance but found an increased likelihood precision with autistic traits. These findings together provide empirical evidence for intact priors, precise likelihood, reduced context updating and heightened variability during sensory learning in autism.
Variations in cell-surface ACE2 levels alter direct binding of SARS-CoV-2 Spike protein and viral infectivity: Implications for measuring Spike protein interactions with animal ACE2 orthologs
Authors: Kazemi Soheila , López-Muñoz Alberto Domingo , Hollý Jaroslav , Jin Ling , Yewdell Jonathan W. , Dolan Brian P. 
Published: October 2021

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19, the most severe pandemic in a century. The virus gains access to host cells when the viral Spike protein (S-protein) binds to the host cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Studies have attempted to understand SARS-CoV-2 S-protein interaction with vertebrate orthologs of ACE2 by expressing ACE2 orthologs in mammalian cells and measuring viral infection or S-protein binding. Often these cells only transiently express ACE2 proteins and levels of ACE2 at the cell surface are not quantified. Here, we describe a cell-based assay that uses stably transfected cells expressing ACE2 proteins in a bi-cistronic vector with an easy to quantify reporter protein to normalize ACE2 expression. We found that both binding of the S-protein receptor-binding domain (RBD) and infection with a SARS-CoV-2 pseudovirus is proportional to the amount of human ACE2 expressed at the cell surface, which can be inferred by quantifying the level of reporter protein, Thy1.1. We also compared different ACE2 orthologs which were expressed in stably transfected cells expressing equivalent levels of Thy1.1. When ranked for either viral infectivity or RBD binding, mouse ACE2 had a weak to undetectable affinity for S-protein while human ACE2 was the highest level detected and feline ACE2 had an intermediate phenotype. The generation of stably transfected cells whose ACE2 level can be normalized for cross-ortholog comparisons allows us to create a reusable cellular library useful for measuring emerging SARS-CoV-2 variant’s ability to potentially infect different animals.ImportanceSARS-CoV-2 is a zoonotic virus responsible for the worst global pandemic in a century. An understanding of how the virus can infect other vertebrate species is important for controlling viral spread and understanding the natural history of the virus. Here we describe a method to generate cells stably expressing equivalent levels of different ACE2 orthologs, the receptor for SARS-CoV-2, on the surface of a human cell line. We find that both binding of the viral Spike protein receptor binding domain (RBD) and infection of cells with a SARS-CoV-2 pseudovirus are proportional to ACE2 levels at the cell surface. Adaptation of this method will allow for the creation of a library of stable transfected cells expressing equivalent levels of different vertebrate ACE2 orthologs which can be repeatedly used for identifying vertebrate species which may be susceptible to infection with SARS-CoV-2 and its many variants.
Hippocampal spatio-temporal cognitive maps adaptively guide reward generalization
Authors: Garvert Mona M. , Saanum Tankred , Schulz Eric , Schuck Nicolas W. , Doeller Christian F. 
Published: October 2021

ABSTRACTThe brain forms cognitive maps of relational knowledge, an organizing principle thought to underlie our ability to generalize and make inferences. However, how can a relevant map be selected in situations where a stimulus is embedded in multiple relational structures? Here, we find that both spatial and temporal cognitive maps influence generalization in a choice task, where spatial location determines reward magnitude. Mirroring behavior, the hippocampus not only builds a map of spatial relationships but also encodes temporal distances. As the task progresses, participants’ choices become more influenced by spatial relationships, reflected in a strengthening of the spatial and a weakening of the temporal map. This change is driven by orbitofrontal cortex, which represents the evidence that an observed outcome is generated from the spatial rather than the temporal map and updates hippocampal representations accordingly. Taken together, this demonstrates how hippocampal cognitive maps are used and updated flexibly for inference.
Disruption of Epithelial Integrity Drives Mesendoderm Differentiation in Human Induced Pluripotent Stem Cells by Enabling BMP and ACTIVIN Sensing
Authors: Rattier Diane , Legier Thomas , Vannier Thomas , Maina Flavio , Dono Rosanna 
Published: October 2021

ABSTRACTThe processes of primitive streak formation and fate specification in the mammalian epiblast rely on complex interactions between morphogens and tissue organization. Little is known about how these instructive cues functionally interact to regulate gastrulation. We interrogated the interplay between tissue organization and morphogens by using human induced pluripotent stem cells (hiPSCs) down-regulated for the morphogen regulator GLYPICAN-4, in which defects in tight junctions result in areas of disrupted epithelial integrity. Remarkably, this phenotype does not affect hiPSC stemness, but impacts on cell fate acquisition processes. Strikingly, cells within disrupted areas become competent to perceive BMP4 and ACTIVIN A/NODAL gastrulation signals and thus, differentiate into mesendoderm. Yet, disruption of epithelial integrity prolongs temporal activation of BMP4 and ACTIVIN A/NODAL downstream effectors and correlates with enhanced hiPSC endoderm/mesoderm differentiation potential. Altogether, our results disclose epithelial cell integrity as a key determinant of TGF-β activity and highlight a new mechanism guiding morphogen sensing and spatial cell fate change within an epithelium.
Coordinated DNA and Histone Dynamics Drive Accurate Histone H2A.Z Exchange
Authors: Poyton Matthew F. , Feng Xinyu A. , Ranjan Anand , Lei Qin , Wang Feng , Zarb Jasmin S. , Louder Robert K. , Park Giho , Jo Myung Hyun , Ye Joseph , Liu Sheng , Ha Taekjip , Wu Carl 
Published: October 2021

AbstractNucleosomal histone H2A is exchanged for its variant H2A.Z by the SWR1 chromatin remodeler, but the mechanism and timing of histone exchange remain unclear. Here, we quantify DNA and histone dynamics during histone exchange in real-time using a three-color single-molecule FRET assay. We show that SWR1 operates with timed precision to unwrap DNA with large displacement from one face of the nucleosome, remove H2A-H2B from the same face, and rewrap DNA, all within 2.3 seconds. Such productive DNA unwrapping requires full SWR1 activation and differs from unproductive, smaller-scale DNA unwrapping caused by SWR1 binding alone. On an asymmetrically positioned nucleosome, SWR1 intrinsically senses long-linker DNA to preferentially exchange H2A.Z on the distal face as observed in vivo. The displaced H2A-H2B dimer remains briefly associated with the SWR1-nucleosome complex and is dissociated by histone chaperones. These findings reveal how SWR1 coordinates DNA unwrapping with histone dynamics to rapidly and accurately place H2A.Z at physiological sites on chromatin.One-Sentence SummaryMulticolor single-molecule FRET reveals how SWR1 unwraps DNA to exchange nucleosomal H2A-H2B for H2A.Z-H2B.
A Goldilocks Principle for the Gut Microbiome: Taxonomic Resolution Matters for Microbiome-Based Classification of Colorectal Cancer
Authors: Armour Courtney R. , Topçuoğlu Begüm D. , Garretto Andrea , Schloss Patrick D. 
Published: October 2021

AbstractColorectal cancer is a common and deadly disease in the United States accounting for over 50,000 deaths in 2020. This progressive disease is highly preventable with early detection and treatment, but many people do not comply with the recommended screening guidelines. The gut microbiome has emerged as a promising target for non-invasive detection of colorectal cancer. Most microbiome-based classification efforts utilize taxonomic abundance data from operational taxonomic units (OTUs) or amplicon sequence variants (ASVs) with the goal of increasing taxonomic resolution. However, it is unknown which taxonomic resolution is optimal for microbiome-based classification of colorectal cancer. To address this question, we used a reproducible machine learning framework to quantify classification performance of models based on data annotated to phylum, class, order, family, genus, OTU, and ASV levels. We found that model performance increased with increasing taxonomic resolution, up to the family level where performance was equal (p > 0.05) among family (mean AUC: 0.689), genus (mean AUC: 0.690), and OTU (mean AUC: 0.693) levels before decreasing at the ASV level (p < 0.05, mean AUC: 0.676). These results demonstrate a trade-off between taxonomic resolution and prediction performance, where coarse taxonomic resolution (e.g. phylum) is not distinct enough but fine resolution (e.g. ASV) is to individualized to accurately classify samples. Similar to the story of Goldilocks and the three bears, mid-range resolution (i.e. family, genus, and OTU) is just right for optimal prediction of colorectal cancer from microbiome data.ImportanceDespite being highly preventable, colorectal cancer remains a leading cause of cancer related death in the United States. Low-cost, non-invasive detection methods could greatly improve our ability to identify and treat early stages of disease. The microbiome has shown promise as a resource for detection of colorectal cancer. Research on the gut microbiome tends to focus on improving our ability to profile species and strain level taxonomic resolution. However, we found that finer resolution impedes the ability to predict colorectal cancer based on the gut microbiome. These results highlight the need for consideration of the appropriate taxonomic resolution for microbiome analyses and that finer resolution is not always more informative.
The role of social ties in accelerating career progress of senior executives and directors in Poland
Authors: Mielcarz Paweł , Osiichuk Dmytro 
Published: October 2021

Purpose
This study aims to elucidate the role of social ties in facilitating the career progress of senior officers within public companies in an emerging market.

Design/methodology/approach
The authors followed the career track of 2,151 senior officers serving on management and supervisory boards of Polish public companies. The authors used multivariate econometric modeling to investigate the factors shaping their career progress.

Findings
The authors document an increasing impact of officers’ social networks on the likelihood of assuming multiple consecutive senior positions. It takes progressively less time for incumbent senior officers to find a subsequent/concomitant board position with a network of social ties from prior workplaces facilitating career progress and prior experience being negatively associated with multiple positions. Officers’ social ties at the senior level are also shown to be positively associated with total compensation and with the likelihood of cross-industry career transition in both executive and supervisory roles.

Originality/value
Social network appears to play a more salient role in accelerating careers of supervisory board members even though executives also benefit therefrom. Finally, the network of social ties with former or incumbent supervisory board members exercises a more pronounced positive impact on career progress than ties with former or incumbent executives.