bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contemporary burden of atrial fibrillation in mechanical thrombectomy stroke patients in the United States
Authors: Otite Fadar Oliver , Patel Smit D. , Hoffman Haydn , Aneni Ehimen , Anikpezie Nnabuchi , Akano Emmanuel Oladele , Wee Claribel , Burke Devin , Albright Karen , Beutler Timothy , Latorre Julius Gene , Singla Amit , Morris Nicholas , Chaturvedi Seemant , Khandelwal Priyank 
Published: February 2024

AbstractBackgroundHow the prevalence of atrial fibrillation (AF) differs between various demographic subgroups of acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT) in the United States (US) is unknown. Data on whether AF prevalence in MT admissions changed over the last decade are sparse.MethodsWe conducted a serial cross-sectional study using all primary AIS discharges in the 2010-2020 National Inpatient Sample. Discharges with MT codes were identified (n=155,277) and the proportion with AF in various age, sex and racial subgroups were computed. We used multivariable-adjusted negative binomial regression to compare AF prevalence between demographic subgroups and Joinpoint regression to evaluate trends over time. Multivariable-adjusted generalized linear models were used to evaluate the association of AF with in-hospital outcomes.ResultsAcross the study period, 45.0% of AIS discharges with MT had AF but marked disparity existed by age, sex and race. After multivariable adjustment, AF prevalence was 4% higher in women vs. men (prevalence rate ratio [PRR] 1.04, 95%CI 1.01-1.07), was lower in Black vs White (PRR 0.80, 95%CI 0.77-0.84) but higher in Asian compared to White discharges (PRR 1.11, 95%CI 1.05-1.18). Prevalence increased with age (PRR for ≥80 years vs 18-39 years: 5.23, 95%CI 4.28-6.39). Following joinpoint regression, prevalence increased by 3.2% (95%CI 1.3 to 5.2%) annually across the period 2010-2015 but declined by -2.2% (95%CI -2.9% to -1.4%) from 2015-2020. AF was associated with 27% lower odds of in-hospital mortality (Odds ratio 0.72, 95%CI 0.62-0.84) and 31% greater odds of routine home discharge (Odds ratio, 95%CI 1.17 to 1.47) compared to no AF.ConclusionAF prevalence in MT patients in the US is approximately twice that of the general AIS population but marked disparity exists by age, sex and race. AF Prevalence in MT increased from 2010-2015 but declined in the period 2015-2020.Clinical PerspectiveWhat is new?Approximately 45% of mechanical thrombectomy acute ischemic stroke hospitalizations have comorbid atrial fibrillation (AF) and this proportion increases with age with 70% of patients >=80 years having AF.In contrast to all AIS patients, in the subset of AF patients undergoing MT, AF is associated with reduced in-hospital mortality and better odds of routine home discharge.What are the clinical implications?Given the post-stroke CHA2DS2-VASc score of at least 2, almost half of all MT patients in the US may be potential candidates for therapeutic anticoagulation.
Phasing Diploid Genome Assembly Graphs with Single-Cell Strand Sequencing
Authors: Henglin Mir , Ghareghani Maryam , Harvey William , Porubsky David , Koren Sergey , Eichler Evan E. , Ebert Peter , Marschall Tobias 
Published: February 2024

AbstractHaplotype information is crucial for biomedical and population genetics research. However, current strategies to producede-novohaplotype-resolved assemblies often require either difficult-to-acquire parental data or an intermediate haplotype-collapsed assembly. Here, we present Graphasing, a workflow which synthesizes the global phase signal of Strand-seq with assembly graph topology to produce chromosome-scalede-novohaplotypes for diploid genomes. Graphasing readily integrates with any assembly workflow that both outputs an assembly graph and has a haplotype assembly mode. Graphasing performs comparably to trio-phasing in contiguity, phasing accuracy, and assembly quality, outperforms Hi-C in phasing accuracy, and generates human assemblies with over 18 chromosome-spanning haplotypes.
A critical reexamination of recovered SARS-CoV-2 sequencing data
Authors: Débarre F. , Hensel Z. 
Published: February 2024

AbstractSARS-CoV-2 genomes collected at the onset of the Covid-19 pandemic are valuable because they could help understand how the virus entered the human population. In 2021, Jesse Bloom reported on the recovery of a dataset of raw sequencing reads that had been removed from the NCBI SRA database at the request of the data generators, a scientific team at Wuhan University (Wanget al., 2020b). Bloom concluded that the data deletion had obfuscated the origin of SARS-CoV-2 and suggested that deletion may have been requested to comply with a government order; further, he questioned reported sample collection dates on and after January 30, 2020. Here, we show that sample collection dates were published in 2020 by Wanget al. together with the sequencing reads, and match the dates given by the authors in 2021. Collection dates of January 30, 2020 were manually removed by Bloom during his analysis of the data. We examine mutations in these sequences and confirm that they are entirely consistent with the previously known genetic diversity of SARS-CoV-2 of late January 2020. Finally, we explain how an apparent phylogenetic rooting paradox described by Bloom was resolved by subsequent analysis. Our reanalysis demonstrates that there was no basis to question the sample collection dates published by Wanget al..Note for bioRxiv readersThe automatically generated Full Text version of our manuscript is missing footnotes; they are available in the PDF version.
The polysaccharide capsule ofAcinetobacter baumanniiaffects bacterial adhesion and natural transformation
Authors: Whiteway Clemence , de Pillecyn Victor , Maure Alexandra , Breine Anke , Valcek Adam , Buylaere Juliette Van , Van der Henst Charles 
Published: February 2024

AbstractAcinetobacter baumanniiis an important threat worldwide due to its ability to acquire antibiotic resistance and survive harsh conditions. The polysaccharide capsule represents a major virulence and resistance asset. How the capsular polysaccharides barrier impacts bacterial adhesion remains to be investigated inA. baumannii.We characterized capsule mutants of the commonly used AB5075 strain. We assessed how these different capsule mutants adhere to biotic (bacterial and eukaryotic cells) and abiotic surfaces (polystyrene). We confirmed our observations using modern and relevant clinical isolates characterized by different capsule types and capsulation levels. Strains with low capsulation levels systematically depicted increased adhesion compared to capsulated strains, and mucoid isolates showed minimal adhesion. These results show capsule production inA. baumanniiaffects adhesion to various surfaces. We also determined that the presence/absence ofA. baumanniicapsule influences its natural transformability. This illustrates the importance of the trade-off of capsule production inA. baumannii.
Gender/Sex Disparities in the COVID-19 Cascade from Testing to Mortality: An Intersectional Analysis of Swiss Surveillance Data
Authors: Auderset Diane , Amiguet Michaël , Clair Carole , Pittet Valérie , Riou Julien , Schwarz Joëlle , Mueller Yolanda 
Published: February 2024

ABSTRACTObjectivesThis study investigates gender and sex disparities in COVID-19 epidemiology in the Canton of Vaud, Switzerland, focusing on the interplay with socioeconomic position (SEP) and age.MethodsWe analyzed COVID-19 surveillance data from March 2020 to June 2021, using an intersectional approach. Negative binomial regression models assessed disparities between women and men, across SEP quintiles and age groups, in testing, positivity, hospitalizations, ICU admissions, and mortality (Incidence Rate Ratios [IRR], with 95% Confidence Intervals [CI]).ResultsWomen had higher testing and positivity rates than men, while men experienced more hospitalizations, ICU admissions, and deaths. The higher positivity in women under 50 was mitigated when accounting for their higher testing rates. Within SEP quintiles, gender/sex differences in testing and positivity were not significant. In the lowest quintile, women’s mortality risk was 68% lower (Q1: IRR 0.32, CI 0.20-0.52), with decreasing disparities with increasing SEP quintiles (Q5: IRR 0.66, CI 0.41-1.06).ConclusionOur findings underscore the complex epidemiological patterns of COVID-19, shaped by the interactions of gender/sex, SEP, and age, highlighting the need for intersectional perspectives in both epidemiological research and public health strategy development.
Immunological Drivers and Potential Novel Drug Targets for Major Psychiatric, Neurodevelopmental, and Neurodegenerative Conditions
Authors: Dardani Christina , Robinson Jamie W. , Jones Hannah J. , Rai Dheeraj , Stergiakouli Evie , Grove Jakob , Gardner Renee , McIntosh Andrew M. , Havdahl Alexandra , Hemani Gibran , Smith George Davey , Richardson Tom G. , Gaunt Tom R. , Khandaker Golam M. 
Published: February 2024

AbstractImmune dysfunction is implicated in the aetiology of psychiatric, neurodevelopmental, and neurodegenerative conditions, but the issue of causality remains unclear impeding attempts to develop new interventions. We have tested evidence for causality for 735 immune response-related biomarkers on 7 neuropsychiatric conditions, using cutting-edge genomic causal inference methods (Mendelian randomization and genetic colocalization) applied to genomic data on protein and gene expression across blood and brain. We provide robust evidence of causality for 21 biomarkers, including two previously unreported (LATS1, andFCN1), confirming a role of both brain specific and systemic immune response in the pathogenesis of several neuropsychiatric conditions especially schizophrenia, Alzheimer’s disease, depression, and bipolar disorder. Furthermore, 18 of the identified biomarkers are therapeutically tractable, includingACE,TNFRSF17, andCD40,with drugs approved or in advanced clinical trials, offering an opportunity for repurposing existing drugs for neuropsychiatric indications.
Spatial and Temporal Distribution of Visceral Leishmaniasis in Karamoja Region, Uganda: Analysis of surveillance data, 2015–2022
Authors: Wanyana Mercy Wendy , Migisha Richard , King Patrick , Kwesiga Benon , Kadobera Daniel , Bulage Lilian , Ario Alex Riolexus 
Published: February 2024

AbstractBackgroundUganda targets to control leishmaniasis and eliminate visceral leishmaniasis as a public health problem by 2030, with 85% of the cases detected, 95% treated, and visceral leishmaniasis eliminated (<1% case fatality rate [CFR]). However, little is documented on the country’s progress towards achieving these targets. We examined the temporal trends and spatial distribution of leishmaniasis in the endemic Karamoja Region of Uganda, 2015–2022.MethodsWe analysed aggregate secondary data on clinically diagnosed leishmaniasis laboratory-confirmed cases, visceral leishmaniasis cases, hospital admissions, and deaths from the District Health Information System 2. We used population-based calculations to determine the annual prevalence of leishmaniasis and quarterly prevalence of visceral leishmaniasis per 1,000,000 persons, while the prevalence of leishmaniasis admissions and CFRs were calculated per 100 cases. We used the Mann-Kendall test to assess the significance of the trend.ResultsOverall, 4,008 cases of clinically diagnosed leishmaniasis were reported, and of these, 11% were laboratory-confirmed. The average annual prevalence of leishmaniasis was 4 per 1,000,000 population. From 2020 to 2022, there was an increasing trend in quarterly prevalence of visceral leishmaniasis (Kendall’s score=36, p=0.016), averaging 3 cases per 1,000,000 population. Leishmaniasis admissions increased annually to 55 per 100 cases (Kendall’s score=23, p=0.006). The average annual CFR was 5%, with no deaths reported in 2018, 2019, and 2021. Amudat District had the highest prevalence rates of leishmaniasis (477 per 1,000,000 population) and visceral leishmaniasis (139 per 100,000 population).ConclusionThe increasing trend of visceral leishmaniasis, and CFR >1% threaten the goal of controlling leishmaniasis as a public health problem by 2030. Gaps in case detection may further prevent the achievement of targets. Strengthening existing interventions, such as vector control and rapid diagnostic kits for early detection and treatment, may be crucial to sustain progress toward elimination targets.
The far extracellular CUB domain of the adhesion GPCR ADGRG6/GPR126 is a key regulator of receptor signaling
Authors: Dintzner Ethan , Bandekar Sumit J. , Leon Katherine , Cechova Kristina , Vafabakhsh Reza , Araç Demet 
Published: February 2024

AbstractAdhesion G Protein–coupled receptors (aGPCRs) transduce extracellular adhesion signals into cytoplasmic signaling pathways. ADGRG6/GPR126 is an aGPCR critical for axon myelination, heart development and ear development; and is associated with developmental diseases and cancers. ADGRG6 has a large, alternatively-spliced, five-domain extracellular region (ECR) that samples different conformations and regulates receptor signaling. However, the molecular details of how the ECR regulates signaling are unclear. Herein, we studied the conformational dynamics of the conserved CUB domain which is located at the distal N-terminus of the ECR and is deleted in an alternatively-spliced isoform (ΔCUB). We showed that theΔCUB isoform has decreased signaling. Molecular dynamics simulations suggest that the CUB domain is involved in interdomain contacts to maintain a compact ECR conformation. A cancer-associated CUB domain mutant, C94Y, drastically perturbs the ECR conformation and results in elevated signaling, whereas another CUB mutant, Y96A, located near a conserved Ca2+-binding site, decreases signaling. Our results suggest an ECR-mediated mechanism for ADGRG6 regulation in which the CUB domain instructs conformational changes within the ECR to regulate receptor signaling.
Structural characterization and dynamics of AdhE ultrastructures fromClostridium thermocellum:A containment strategy for toxic intermediates
Authors: Ziegler Samantha J. , Knott Brandon C. , Gruber Josephine N. , Hengge Neal N. , Xu Qi , Olson Daniel G. , Romero Eduardo E. , Joubert Lydia M. , Bomble Yannick J. 
Published: February 2024

AbstractClostridium thermocellum, a cellulolytic thermophilic anaerobe, is considered by many to be a prime candidate for the realization of consolidated bioprocessing (CBP) and is known as an industry standard for biofuel production.C. thermocellumis among the best biomass degraders identified to date in nature and produces ethanol as one of its main products. Many studies have helped increase ethanol titers in this microbe, however ethanol production usingC. thermocellumis still not economically viable. Therefore, a better understanding of its ethanol synthesis pathway is required. The main pathway for ethanol production inC. thermocelluminvolves the bifunctional aldehyde-alcohol dehydrogenase (AdhE). To better understand the function of theC. thermocellumAdhE, we used cryo-electron microscopy (cryo-EM) to obtain a 3.28 Å structure of the AdhE complex. This high-resolution structure, in combination with molecular dynamics simulations, provides insight into the substrate channeling of the toxic intermediate acetaldehyde, indicates the potential role ofC. thermocellumAdhE to regulate activity and cofactor pools, and establishes a basis for future engineering studies. The containment strategy found in this enzyme offers a template that could be replicated in other systems where toxic intermediates need to be sequestered to increase the production of valuable biochemicals.
Ultrastructure expansion microscopy (U-ExM) of mouse and human kidneys for analysis of subcellular structures
Authors: Langner Ewa , Puapatanakul Pongpratch , Pudlowski Rachel , Alsabbagh Dema Yaseen , Miner Jeffrey H. , Horani Amjad , Dutcher Susan K. , Brody Steven L. , Wang Jennifer T. , Suleiman Hani Y. , Mahjoub Moe R. 
Published: February 2024

AbstractUltrastructure expansion microscopy (U-ExM) involves the physical magnification of specimens embedded in hydrogels, which allows for super-resolution imaging of subcellular structures using a conventional diffraction-limited microscope. Methods for expansion microscopy exist for several organisms, organs, and cell types, and used to analyze cellular organelles and substructures in nanoscale resolution. Here, we describe a simple step-by-step U-ExM protocol for the expansion, immunostaining, imaging, and analysis of cytoskeletal and organellar structures in kidney tissue. We detail the critical modified steps to optimize isotropic kidney tissue expansion, and preservation of the renal cell structures of interest. We demonstrate the utility of the approach using several markers of renal cell types, centrioles, cilia, the extracellular matrix, and other cytoskeletal elements. Finally, we show that the approach works well on mouse and human kidney samples that were preserved using different fixation and storage conditions. Overall, this protocol provides a simple and cost-effective approach to analyze both pre-clinical and clinical renal samples in high detail, using conventional lab supplies and standard widefield or confocal microscopy.
Proteomic analysis uncovers clusterin-mediated disruption of actin-based contractile machinery in the trabecular meshwork to lower intraocular pressure
Authors: Soundararajan Avinash , Wang Ting , Pattabiraman Padmanabhan P 
Published: February 2024

AbstractGlaucoma, a major cause of blindness, is characterized by elevated intraocular pressure (IOP) due to improper drainage of aqueous humor via the trabecular meshwork (TM) outflow pathway. Our recent work identified that loss of clusterin resulted in elevated IOP. This study delves deeper to elucidate the role of clusterin in IOP regulation. Employing anex vivohuman anterior segment perfusion model, we established that constitutive expression and secretion as well as exogenous addition of clusterin can significantly lower IOP. Interestingly, clusterin significantly lowered transforming growth factor β2 (TGFβ2)-induced IOP elevation. This effect was linked to the suppression of extracellular matrix (ECM) deposition and, highlighting the crucial role of clusterin in maintaining ECM equilibrium. A comprehensive global proteomic approach revealed the broad impact of clusterin on TM cell structure and function by identifying alterations in protein expression related to cytoskeletal organization, protein processing, and cellular mechanics, following clusterin induction. These findings underscore the beneficial modulation of TM cell structure and functionality by clusterin. Specifically, clusterin influences the actin-cytoskeleton and focal adhesion dynamics, which are instrumental in cell contractility and adhesion processes. Additionally, it suppresses the activity of proteins critical in TGFβ2, G-protein, and JAK-STAT signaling pathways, which are vital for the regulation of ocular pressure. By delineating these targeted effects of clusterin within the TM outflow pathway, our findings pave the way for novel treatment strategies aimed at mitigating the progression of ocular hypertension and glaucoma through targeted molecular interventions.
Resistance to Naïve and Formative Pluripotency Conversion in RSeT Human Embryonic Stem Cells
Authors: Chen Kevin G. , Johnson Kory R. , Park Kyeyoon , Maric Dragan , Yang Forest , Liu Wen Fang , Fann Yang C. , Mallon Barbara S. , Robey Pamela G. 
Published: February 2024

ABSTRACTOne of the most important properties of human embryonic stem cells (hESCs) is related to their primed and naïve pluripotent states. Our previous meta-analysis indicates the existence of heterogeneous pluripotent states derived from diverse naïve protocols. In this study, we have characterized a commercial medium (RSeT)-based pluripotent state under various growth conditions. Notably, RSeT hESCs can circumvent hypoxic growth conditions as required by naïve hESCs, in which some RSeT cells (e.g., H1 cells) exhibit much lower single cell plating efficiency, having altered or much retarded cell growth under both normoxia and hypoxia. Evidently, hPSCs lack many transcriptomic hallmarks of naïve and formative pluripotency (a phase between naive and primed states). Integrative transcriptome analysis suggests our primed and RSeT hESCs are close to the early stage of post-implantation embryos, similar to the previously reported primary hESCs and early hESC cultures. Moreover, RSeT hESCs did not express naïve surface markers such as CD75, SUSD2, and CD130 at a significant level. Biochemically, RSeT hESCs exhibit a differential dependency of FGF2 and co-independency of both Janus kinase (JAK) and TGFβ signaling in a cell-line-specific manner. Thus, RSeT hESCs represent a previously unrecognized pluripotent state downstream of formative pluripotency. Our data suggest that human naïve pluripotent potentials may be restricted in RSeT medium. Hence, this study provides new insights into pluripotent state transitionsin vitro.
The gaming concession system in Macao: reform or retain?
Authors: Wang Changbin , Yan Libo 
Published: February 2024

Purpose This study aims to examine the problems of the concession system that Macao has long-term adopted to regulate its gaming industry and discuss alternatives.Design/methodology/approach Theoretical reflection was used to provide qualitatively different insights about governmental supervision of the gaming industry.Findings Two options for reform are proposed: (1) replace the concession system with a licensing system that does not restrict the number of concessionaires or the period of concession or (2) adopt a modified form of the concession system that changes the number of concessionaires, period of concessions and methods for selecting concessionaires.Practical implications This study’s results have implications for the Macao government and other gaming jurisdictions in Asia.Originality/value This study provides a comprehensive examination of the concession system for governmental supervision of the gaming industry.
Aligning academic career management in the evolving landscape of Cambodian public universities
Authors: Hum Chan , Choi Tae-Hee , Lo Sing-Kai , Sok Say , Yu Wai Mui Christina 
Published: February 2024

PurposeThis study examines the management practices and alignment features needed to develop academic staff’s careers, mainly focusing on teaching competencies in the evolving landscape of Cambodian public universities.Design/methodology/approachA multiple-case research design was adopted to collect data from interviews with 11 academic leaders and focus-group discussions (FGDs) with 13 academic teachers at two public universities in provincial Cambodia. A thematic approach was performed to code and analyse data to address the research questions.FindingsThis study found that the management of academic careers in the selected universities was hybrid, deregulating state control to relative institutional autonomy for contracted employees but rather centralised management for civil servants. However, weak institutional leadership and negligence in formulating comprehensive institutional guidelines for strategic human resource management (HRM) have caused misalignments of management practices to develop academic careers in the studied contexts.Research limitations/implicationsThis case study limits its findings to two universities in provincial Cambodia. Nevertheless, this study adds to the scarce literature on the research topic in Cambodian public universities and opens a path for cross-institutional and national comparative studies on similar foci.Originality/valueThis is a ground-breaking study set in the evolving space of Cambodian public higher education, where attention to the research area remains limited.