bluuebunny/crossref_metadata_2025_split huggingface dataset:
Puerto Rico Health System Resilience After Hurricane Maria: Implications for Disaster Preparedness in the COVID-19 Era
Authors: Rios Christopher C. , Ling Emilia J , Rivera-Gutierrez Ralph , Sanchez Juan Gonzalez , Bruce Janine , Barry Michele , de Jesus Perez Vinicio 
Published: September 2020

AbstractBackgroundEvery year, Puerto Rico faces a hurricane season fraught with potentially catastrophic structural, emotional and health consequences. In 2017, Puerto Rico was hit by Hurricane Maria, the largest natural disaster to ever affect the island. Several studies have estimated the excess morbidity and mortality following Hurricane Maria in Puerto Rico, yet no study has comprehensively examined the underlying health system weaknesses contributing to the deleterious health outcomes.MethodsA qualitative case study was conducted to assess the ability of the UPR health system to provide patient care in response to Hurricane Maria. An established five key resilience framework and inductive analysis was used to identify factors that affected health system resilience. Thirteen Emergency Medicine Physicians, Family Medicine Physicians, and Hospital Administrators in a University of Puerto Rico (UPR) Community Hospital were interviewed as part of our study.ResultsOf the five key resiliency components, three domains were notably weak with respect to UPR’s resiliency. Prior to the Hurricane, key personnel at the UPR hospital wereunawareof the limited capacity of back-up generators at hospitals and were ill-prepared to transfer ICU patients to appropriate hospitals. Post Hurricane, the hospital facedself-regulationchallenges when triaging the provision of Hurricane-related emergency services with delivering core health services, in particular for patients with chronic conditions. Finally, during and after the Hurricane,integrationof patient care coordination between the UPR hospital ambulances, neighboring hospitals, and national and state government was suboptimal. The two remaining resiliency factors, addressingdiverseneeds and systemadaptivenessin a time of crisis, were seen as strengths.ConclusionsHurricane Maria exposed weaknesses in the Puerto Rican health system, notably the lack of awareness about the limited capacity of backup generators, poor patient care coordination, and interruption of medical care for patients with chronic conditions. As in other countries, the current COVID epidemic is taxing the capacity of the Puerto Rico health system, which could increase the likelihood of another health system collapse should another hurricane hit the island. Therefore, a resilience framework is a useful tool to help health systems identify areas of improvement in preparation for possible natural disasters.
Genome-wide association studies reveal novel locus with sex-/therapy-specific fracture risk effects in childhood cancer survivors
Authors: Im Cindy , Li Nan , Moon Wonjong , Liu Qi , Morton Lindsay M. , Leisenring Wendy M. , Howell Rebecca M. , Chow Eric J. , Sklar Charles A. , Wilson Carmen L. , Wang Zhaoming , Sapkota Yadav , Chemaitilly Wassim , Ness Kirsten K. , Hudson Melissa M. , Robison Leslie L. , Bhatia Smita , Armstrong Gregory T. , Yasui Yutaka 
Published: September 2020

ABSTRACTSurvivors of childhood cancer treated with radiation therapy (RT) and osteotoxic chemotherapies are at increased risk for fractures. However, research focusing on how genetic and clinical susceptibility factors jointly contribute to fracture risk among long-term (≥5 years) survivors of childhood cancer has been limited. To address this gap, we conducted genome-wide association studies of fracture risk in 2,453 participants from the Childhood Cancer Survivor Study (CCSS) using Cox regression models and prioritized sex- and treatment-stratified genetic associations. Replication analyses were conducted in an independent survivor sample from the St. Jude Lifetime Cohort Study (SJLIFE). We identified a genome-wide significant (P<5⨯10−8) fracture risk locus, 16p13.3 (HAGHL), among female CCSS survivors (N=1,289) with strong evidence of sex-specific effects (Psex-heterogeneity<7⨯10−6). We found rs1406815 showed the strongest association with fracture risk after replication (HRmeta-analysis per risk allele=1.43, P=8.2⨯10−9; N=1,935 women). While the association between rs1406815 and fracture risk was weak among female survivors who did not receive radiation therapy (RT) (HRCCSS=1.22, P=0.11), the association strength increased with greater RT doses to the head or neck (HRCCSS=1.88, P=2.4⨯10−10 in those with any head/neck RT; HRCCSS=3.79, P=9.1⨯10−7 in those treated with >36 Gray). In silico bioinformatics analyses suggest these fracture risk alleles regulate HAGHL gene expression and related bone resorption pathways, and are plausibly moderated by head/neck RT. Genetic risk profiles integrating this locus may help identify young female survivors who would benefit from targeted interventions to reduce fracture risk.
Analyzing How Changes in the Health Status of Healthcare Workers Affects Epidemic Outcomes
Authors: Phadke I. , McKee A. , Conway J.M. , Shea K. 
Published: September 2020

AbstractDuring a disease outbreak, healthcare workers (HCWs) are essential to treat infected individuals. However, these HCWs are themselves susceptible to contracting the disease. As more HCWs get infected, fewer are available to provide care for others, and the overall quality of care available to infected individuals declines. This depletion of HCWs may contribute to the epidemic’s severity. To examine this issue, we explicitly model declining quality of care in four differential equation-based SIR-type models with vaccination. We assume that vaccination, recovery, and survival rates are affected by quality of care delivered. We show that explicitly modelling healthcare workers and accounting for declining quality of care significantly alters model-predicted disease outcomes, specifically case counts and mortality. Models neglecting the decline of quality of care resulting from infection of HCWs may significantly under-estimate cases and mortality. These models may be useful to inform health policy that may differ for healthcare workers and the general population. Models accounting for declining quality of care may therefore improve the management interventions considered to mitigate the effects of a future outbreak.
Validation of the Brazilian Portuguese version of the Copenhagen Burnout Inventory (CBI) in healthcare professionals
Authors: Moser Carolina M. , Tietbohl-Santos Bárbara , Arenas Daniel Luccas , Xavier Aurora , Ornell Felipe , Borges Rogerio Boff , Hauck Simone 
Published: September 2020

ABSTRACTThe objective of this study was the validation of the Brazilian Portuguese version of The Copenhagen Burnout Inventory (CBI). The study sample consisted of 1.256 Brazilian health professionals. Data were collected during one month (May-2020 to June-2020) through an online self-administered questionnaire, including the CBI and the Patient Health Questionnaire 9 (PHQ-9) to evaluate depressive symptoms. All consistency measures showed values > 0.90. The split-half correlation values with Spearman-Brown reliability were higher than 0.8. The parallel analysis suggested two factors: the items of CBI’s personal burnout (PB) and work-related burnout (WB) sub-dimensions that were associated with factor 1 (personal and work-related fatigue and exhaustion) and the items of CBI’s client-related burnout (CB) sub-dimension were associated with factor 2 (exhaustion that emerges while working with people). The correlation between the PHQ-9 score and factor 1 was 0.76 (0.73; 0.79) and with factor 2, 0.49 (0.43; 0.55). Our study provides a valid and reliable Brazilian Portuguese version of CBI, encouraging the expansion of the burnout research field in our country.
Monitoring SARS-CoV-2 circulation and diversity through community wastewater sequencing
Authors: Izquierdo-Lara Ray , Elsinga Goffe , Heijnen Leo , Oude Munnink Bas B. , Schapendonk Claudia M. E. , Nieuwenhuijse David , Kon Matthijs , Lu Lu , Aarestrup Frank M. , Lycett Samantha , Medema Gertjan , Koopmans Marion P.G. , de Graaf Miranda 
Published: September 2020

ABSTRACTThe current SARS-CoV-2 pandemic has rapidly become a major global health problem for which public health surveillance is crucial to monitor virus spread. Given the presence of viral RNA in feces in around 40% of infected persons, wastewater-based epidemiology has been proposed as an addition to disease-based surveillance to assess the spread of the virus at the community level. Here we have explored the possibility of using next-generation sequencing (NGS) of sewage samples to evaluate the diversity of SARS-CoV-2 at the community level from routine wastewater testing, and compared these results with the virus diversity in patients from the Netherlands and Belgium. Phylogenetic analysis revealed the presence of viruses belonging to the most prevalent clades (19A, 20A and 20B) in both countries. Clades 19B and 20C were not identified, while they were present in clinical samples during the same period. Low frequency variant (LFV) analysis showed that some known LFVs can be associated with particular clusters within a clade, different to those of their consensus sequences, suggesting the presence of at least 2 clades within a single sewage sample. Additionally, combining genome consensus and LFV analyses we found a total of 57 unique mutations in the SARS-CoV-2 genome which have not been described before. In conclusion, this work illustrates how NGS analysis of wastewater can be used to approximate the diversity of SARS-CoV-2 viruses circulating in a community.
Norwich COVID-19 Testing Initiative: feasibility project evaluation
Authors: Gillam T Berger , Cole J , Gharbi K , Hitchcock M , Edwards D , Brabbs T , Lipscombe J , Davidson R , Rushworth S , Steel N 
Published: September 2020

AbstractBackgroundThere is a high prevalence of COVID-19 in university-age students, who are returning to university campuses. There is little evidence regarding the feasibility of universal, asymptomatic testing to control outbreaks in this population. This study aimed to pilot mass COVID-19 testing on a university research park, to assess the feasibility and acceptability of scaling up to all staff and students.MethodsThis was a cross-sectional feasibility study on a university research park in the East of England. Staff and students (5,625) on the research park were eligible to participate. Polymerase chain reaction (PCR) testing was offered to all participants. Participants were offered 4 swabs, which they self-administered over a two-week period. Outcome measures included: uptake; drop-out rate; positivity rates; participant acceptability measures; laboratory processing measures.Results798/1053 (76%) of those who registered provided at least one swab and of these, 687 (86%) provided all four. 681/687 (99%) had all negative results. 6 participants had one inconclusive result. There were no positive results. 458/798 (57%) participants responded to a post-testing questionnaire. 446/458 (97.5%) of those who responded agreed that they would be interested in repeat testing in the future.ConclusionsRepeated self-testing is feasible and acceptable to a university population.
A Highly Conserved 310-Helix Within the Kinesin Motor Domain is Critical for Kinesin Function and Human Health
Authors: Lam Aileen J. , Rao Lu , Anazawa Yuzu , Okada Kyoko , Chiba Kyoko , Niwa Shinsuke , Gennerich Arne , Nowakowski Dan W. , McKenney Richard J. 
Published: September 2020

AbstractKIF1A, a kinesin-3 family member, plays critical roles as a long-distance cargo-transporter within neurons. Over 100 known KIF1A mutations in humans result inKIF1AAssociated Neurological Disease (KAND), developmental and degenerative neurological conditions for which there is no cure. A de novo missense mutation, P305L, was recently identified in several children diagnosed with KAND, but the underlying molecular basis for the disease phenotype is unknown. Interestingly, this residue is highly conserved in kinesin-family proteins, and together with adjacent conserved residues also implicated in KAND, forms an unusual 310-helical element immediately C-terminal to loop-12 (L12, also known as the K-loop in KIF1A) in the conserved kinesin motor core. In KIF1A, the disordered K-loop contains a highly charged insertion of lysines that is thought to endow the motor with a high microtubule-association rate. Here, we characterize the molecular defects of the P305L mutation in KIF1A using genetic, biochemical, and single-molecule approaches. We find the mutation negatively impacts the velocity, run-length, and force generation of the motor. However, a much more dramatic effect is observed on the microtubule-association rate of the motor, revealing that the presence of an intact K-loop is not sufficient for its function. We hypothesize that an elusive K-loop conformation, mediated by formation of a highly conserved adjacent 310-helix that is modulated via P305, is critically important for the kinesin-microtubule interaction. Importantly, we find that the function of this proline is conserved in the canonical kinesin, KIF5, revealing a fundamental principle of the kinesin motor mechanism.
Aerobic exercise improves hippocampal blood flow for hypertensiveAPOE4carriers
Authors: Kaufman Carolyn S. , Honea Robyn A. , Pleen Joseph , Lepping Rebecca J. , Watts Amber , Morris Jill K , Billinger Sandra A. , Burns Jeffrey M. , Vidoni Eric D. 
Published: September 2020

ABSTRACTBackgroundEvidence increasingly suggests cerebrovascular dysfunction plays an early and important role in the pathogenesis of Alzheimer’s disease (AD). Studies have shown the strongest known genetic risk factor for sporadic AD,Apolipoprotein E4(APOE4), may act synergistically with vascular risk factors to promote dementia development. Aerobic exercise may attenuate cognitive decline at least partially through improvements in cerebral blood flow. Therefore, exercise interventions that improve vascular health may be particularly beneficial forAPOE4carriers.ObjectivesTo test the hypothesis that exercise would more effectively increase hippocampal blood flow (HBF) in hypertensiveAPOE4carriers than non-carriers, we performed an analysis of arterial spin labeling MRI data (ASL-MRI) from a randomized controlled trial (secondary outcome). Additionally, we tested the hypothesis that changes in systolic blood pressure (ΔSBP) would be more negatively associated with ΔHBF forAPOE4carriers than non-carriers.MethodsWe assigned cognitively normal adults (65–87 years) to a 52-week aerobic exercise intervention or education only. Genotyping was performed by Taqman SNP allelic discrimination assay. ASL-MRI measured HBF before and after the 52-week intervention. We selected participants with hypertension at enrollment (n = 44), defined as SBP ≥ 130mmHg or diastolic blood pressure (DBP) ≥ 80mmHg.ResultsA two-way ANCOVA showed a significant interaction betweenAPOE4carrier status and treatment group on change in HBF (ΔHBF) over the 52 weeks, controlling for age and sex (p= 0.040). ForAPOE4carriers, ΔHBF was significantly (p= 0.006) higher for participants who underwent the exercise intervention (4.09 mL/100g/min) than for the control group (−2.08 mL/100g/min). There was no difference in ΔHBF between the control (−0.32 mL/100g/min) and exercise (−0.54 mL/100g/min) intervention groups forAPOE4non-carriers (p = 0.918). Additionally, a multiple linear regression showed a significant interaction between ΔSBP andAPOE4carrier status on ΔHBF (p= 0.035), with a reduction in SBP associated with an increase in HBF forAPOE4carriers only.ConclusionsAerobic exercise significantly improved HBF for hypertensiveAPOE4carriers only. Additionally, onlyAPOE4carriers exhibited an inverse relationship between ΔSBP and ΔHBF. This suggests exercise interventions, particularly those that lower SBP, may be beneficial for individuals at highest genetic risk of AD.
Identifying gaps in COVID-19 health equity data reporting in Canada using a scorecard approach
Authors: Blair Alexandra , Warsame Kahiye , Naik Harsh , Byrne Walter , Parnia Abtin , Siddiqi Arjumand 
Published: September 2020

AbstractObjectiveTo assess thealth equity-oriented COVID-19 data reporting across Canadian provinces and territories, using a scorecard approach.MethodA scan was performed of provincial and territorial reporting of five data elements (cumulative totals of tests, cases, hospitalizations, deaths and population size) across three units of aggregation (province or territory-level, health regions, and local areas) (15 “overall” indicators), and for two vulnerable settings (long term care and detention facilities) and six social markers (age, sex, immigration status, race/ethnicity, essential worker status, and income) (120 “equity-related” indicators). Per indicator, one point was awarded if case-delimited data were released, 0.7 points if only summary statistics were reported, and 0 if neither was provided. Results were presented using a scorecard approach.ResultsOverall, information on cases and deaths was more complete than for tests, hospitalizations and population size denominators needed for rate estimation. Information provided on jurisdictions and their regions, overall, tended to be more available (average score of 53%, “B”) than for equity-related indicators (average score of 21%, “D”). Only British Columbia and Alberta provided case-delimited data, and only Alberta provided information for local areas. No jurisdiction reported on outcomes according to patients’ individual-level immigration status, race, or income. Only Ontario and Quebec provided detailed information for long-term care settings and detention facilities.ConclusionSocially stratified reporting for COVID-19 outcomes is sparse in Canada. However, several “best practices” in health equity-oriented reporting were observed and set a relevant precedent for all jurisdictions to follow for this pandemic and future ones.
Endometrial epithelial ARID1A is critical for uterine gland function in early pregnancy establishment
Authors: Marquardt Ryan M. , Kim Tae Hoon , Yoo Jung-Yoon , Teasley Hanna E. , Fazleabas Asgerally T. , Young Steven L. , Lessey Bruce A. , Arora Ripla , Jeong Jae-Wook 
Published: September 2020

AbstractThough endometriosis and infertility are clearly associated, the pathophysiological mechanism remains unclear. Previous work has linked endometrial ARID1A loss to endometriosis-related endometrial non-receptivity. Here, we show in mice that ARID1A binds and regulates transcription of theFoxa2gene required for endometrial gland function. Uterine specific deletion ofArid1acompromises gland development and diminishesFoxa2andLifexpression. Deletion ofArid1awith Ltf-iCre in the adult mouse endometrial epithelium preserves gland development while still compromising gland function. Mice lacking endometrial epithelialArid1aare severely sub-fertile due to defects in implantation, decidualization, and endometrial receptivity from disruption of the LIF-STAT3-EGR1 pathway. FOXA2 is also reduced in the endometrium of women with endometriosis in correlation with diminished ARID1A, and both ARID1A and FOXA2 are reduced in non-human primates induced with endometriosis. Our findings describe a role for ARID1A in the endometrial epithelium supporting early pregnancy establishment through the maintenance of gland function.
Unsupervised tensor decomposition-based method to extract candidate transcription factors as histone modification bookmarks in post-mitotic transcriptional reactivation
Authors: Taguchi Y-h. , Turki Turki 
Published: September 2020

AbstractThe histone group added to a gene sequence must be removed during mitosis to halt transcription during the DNA replication stage of the cell cycle. However, the detailed mechanism of this transcription regulation remains unclear. In particular, it is not realistic to reconstruct all appropriate histone modifications throughout the genome from scratch after mitosis. Thus, it is reasonable to assume that there might be a type of “bookmark” that retains the positions of histone modifications, which can be readily restored after mitosis. We developed a novel computational approach comprising tensor decomposition (TD)-based unsupervised feature extraction (FE) to identify transcription factors (TFs) that bind to genes associated with reactivated histone modifications as candidate histone bookmarks. To the best of our knowledge, this is the first application of TD-based unsupervised FE to the cell division context and phases pertaining to the cell cycle in general. The candidate TFs identified with this approach were functionally related to cell division, suggesting the suitability of this method and the potential of the identified TFs as bookmarks for histone modification during mitosis.
A Joint Deep Learning Model for Simultaneous Batch Effect Correction, Denoising and Clustering in Single-Cell Transcriptomics
Authors: Lakkis Justin , Wang David , Zhang Yuanchao , Hu Gang , Wang Kui , Pan Huize , Ungar Lyle , Reilly Muredach P. , Li Xiangjie , Li Mingyao 
Published: September 2020

AbstractRecent development of single-cell RNA-seq (scRNA-seq) technologies has led to enormous biological discoveries. As the scale of scRNA-seq studies increases, a major challenge in analysis is batch effect, which is inevitable in studies involving human tissues. Most existing methods remove batch effect in a low-dimensional embedding space. Although useful for clustering, batch effect is still present in the gene expression space, leaving downstream gene-level analysis susceptible to batch effect. Recent studies have shown that batch effect correction in the gene expression space is much harder than in the embedding space. Popular methods such as Seurat3.0 rely on the mutual nearest neighbor (MNN) approach to remove batch effect in the gene expression space, but MNN can only analyze two batches at a time and it becomes computationally infeasible when the number of batches is large. Here we present CarDEC, a joint deep learning model that simultaneously clusters and denoises scRNA-seq data, while correcting batch effect both in the embedding and the gene expression space. Comprehensive evaluations spanning different species and tissues showed that CarDEC consistently outperforms scVI, DCA, and MNN. With CarDEC denoising, those non-highly variable genes offer as much signal for clustering as the highly variable genes, suggesting that CarDEC substantially boosted information content in scRNA-seq. We also showed that trajectory analysis using CarDEC’s denoised and batch corrected expression as input revealed marker genes and transcription factors that are otherwise obscured in the presence of batch effect. CarDEC is computationally fast, making it a desirable tool for large-scale scRNA-seq studies.
COVID-19 CG: Tracking SARS-CoV-2 mutations by locations and dates of interest
Authors: Chen Albert Tian , Altschuler Kevin , Zhan Shing Hei , Chan Yujia Alina , Deverman Benjamin E. 
Published: September 2020

AbstractCOVID-19 CG is an open resource for tracking SARS-CoV-2 single-nucleotide variations (SNVs) and lineages while filtering by location, date, gene, and mutation of interest. COVID-19 CG provides significant time, labor, and cost-saving utility to diverse projects on SARS-CoV-2 transmission, evolution, emergence, immune interactions, diagnostics, therapeutics, vaccines, and intervention tracking. Here, we describe case studies in which users can interrogate (1) SNVs in the SARS-CoV-2 Spike receptor binding domain (RBD) across different geographic regions to inform the design and testing of therapeutics, (2) SNVs that may impact the sensitivity of commonly used diagnostic primers, and (3) the recent emergence of a dominant lineage harboring an S477N RBD mutation in Australia. To accelerate COVID-19 research and public health efforts, COVID-19 CG will be continually upgraded with new features for users to quickly and reliably pinpoint mutations as the virus evolves throughout the pandemic and in response to therapeutic and public health interventions.