bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Lockdown Decrease the Protective Role of Ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths?
Authors: Moozhipurath Rahul Kalippurayil , Kraft Lennart 
Published: July 2020

AbstractBackgroundNations are imposing unprecedented measures at large-scale to contain the spread of COVID-19 pandemic. Recent studies indicate that measures such as lockdowns may have slowed down the growth of COVID-19. However, in addition to substantial economic and social costs, these measures also limit the exposure to Ultraviolet-B radiation (UVB). Emerging observational evidence indicate the protective role of UVB and vitamin D in reducing the severity and mortality of COVID-19 deaths. In this observational study, we empirically outline the independent protective roles of lockdown and UVB exposure as measured by ultraviolet index (UVI), whilst also examining whether the severity of lockdown is associated with a reduction in the protective role.MethodsWe apply a log-linear fixed-effects model to a panel dataset of 162 countries over a period of 108 days (n=6049). We use the cumulative number of COVID-19 deaths as the dependent variable and isolate the mitigating influence of lockdown severity on the association between UVI and growth-rates of COVID-19 deaths from time-constant country-specific and time-varying country-specific potentially confounding factors.FindingsAfter controlling for time-constant and time-varying factors, we find that a unit increase in UVI and lockdown severity are independently associated with 17% [-1.8 percentage points] and 77% [-7.9 percentage points] decline in COVID-19 deaths growth rate, indicating their respective protective roles. However, the widely utilized and least severe lockdown (recommendation to not leave the house) already fully mitigates the protective role of UVI by 95% [1.8 percentage points] indicating its downside.InterpretationWe find that lockdown severity and UVI are independently associated with a slowdown in the daily growth rates of cumulative COVID-19 deaths. However, we find consistent evidence that increase in lockdown severity is associated with a significant reduction in the protective role of UVI in reducing COVID-19 deaths. Our results suggest that lockdowns in conjunction with adequate exposure to UVB radiation might have provided even more substantial health benefits, than lockdowns alone. For example, we estimate that there would be 21% fewer deaths on average with sufficient UVB exposure while people were recommended not to leave their house. Therefore, our study outlines the importance of considering UVB exposure, especially while implementing lockdowns and may support policy decision making in countries imposing such measures.
Data From the COVID-19 Epidemic in Florida Suggest That Younger Cohorts Have Been Transmitting Their Infections to Less Socially Mobile Older Adults
Authors: Harris Jeffrey E. 
Published: July 2020

AbstractWe analyzed the daily incidence of newly reported COVID-19 cases among adults aged 20-39 years, 40-59 years, and 60 or more years in the sixteen most populous counties of the state of Florida from March 1 through June 27, 2020. In all 16 counties, an increase in reported COVID-19 case incidence was observed in all three age groups soon after the governor-ordered Full Phase 1 reopening went into effect. Trends in social mobility, but not trends in testing, track case incidence. Data on hospitalization do not support the hypothesis that the observed increase in case incidence was merely the result of liberalization of testing criteria. Parameter estimates from a parsimonious two-group heterogeneous SIR model strongly support the hypothesis that younger persons, having first acquired their infections through increasing social contact with their peers, then transmitted their infections to older, less socially mobile individuals. Without such cross-infection, an isolated epidemic among older people in Florida would be unsustainable.
Role of pharmacist during the COVID-19 pandemic: a scoping review
Authors: Visacri Marília Berlofa , Figueiredo Isabel Vitória , de Mendonça Lima Tácio 
Published: July 2020

AbstractBackgroundSince the start of the new Coronavirus (COVID-19) outbreak in December 2019, pharmacists worldwide are playing a key role adopting innovative strategies to minimize the adverse impact of the pandemic.ObjectivesTo identify and describe core services provided by the pharmacist during the COVID-19 pandemic.MethodsA literature search was performed in MEDLINE, Embase, Scopus, and LILACS for studies published between December 1st, 2019 and May 20th, 2020 without language restriction. Studies that reported services provided by pharmacists during the COVID-19 pandemic were included. Two independent authors performed study selection and data extraction with a consensus process. The pharmacist’s intervention identified in the included studies were described based on key domains in the DEPICT v.2.ResultsA total of 1,189 records were identified, of which 11 studies fully met the eligibility criteria. Most of them were conducted in the United States of America (n=4) and China (n=4). The most common type of publication were letters (n=4) describing the workplace of the pharmacist in hospitals (n=8). These findings showed the different roles of pharmacists during the COVID-19 pandemic, such as disease prevention and infection control, adequate storage and drug supply, patient care and support for healthcare professionals. Pharmacists’ interventions were mostly conducted for healthcare professionals and patients (n=7), through one-to-one contact (n=11), telephone (n=6) or video conference (n=5). The pharmacists’ main responsibility was to provide drug information for healthcare professionals (n=7) as well as patient counseling (n=8).ConclusionsA reasonable number of studies that described the role of the pharmacists during the COVID-19 pandemic were found. All studies reported actions taken by pharmacists, although without providing a satisfactory description. Thus, future research with more detailed description as well as an evaluation of the impact of pharmacist intervention is needed in order to guide future actions in this and-or other pandemic.
OmpK36 and TraN facilitate conjugal transfer of theKlebsiella pneumoniaecarbapenem resistance plasmid pKpQIL
Authors: Low Wen Wen , Wong Joshua LC , Peña Alejandro , Seddon Chloe M , Costa Tiago RD , Beis Konstantinos , Frankel Gad 
Published: July 2020

AbstractWe investigated the mechanism of conjugal transfer of the endemicKlebsiella pneumoniaecarbapenem resistance plasmid, pKpQIL. Transfer efficiency of this plasmid was found to be dependent on the expression of the major outer membrane porin, OmpK36, in recipient cells. We also found that conjugal uptake is reduced in recipients expressing an OmpK36 isoform associated with the globally pervasiveK. pneumoniaeST258 clade (OmpK36ST258). This reduction was attributed to a glycine-aspartate insertion in loop 3 of OmpK36ST258, which constricts the pore by 26%. Deletion offinO, which encodes an RNA-binding protein, derepressed transfer of pKpQIL and enabled visualisation of the conjugation pilus and OmpK36-dependent conjugation in real time. While deletion oftraNabolished pKpQIL conjugation, substitutingtraNin pKpQIL with its homologue from R100-1 circumvented OmpK36 dependency. These results suggest that OmpK36 in recipientK. pneumoniaeand the pKpQIL-encoded TraN in donor bacteria cooperate to facilitate plasmid transfer. This is the first report since 1998 to suggest a novel recipient cell receptor for IncF plasmid transfer and supports the idea that TraN mediates receptor specificity for plasmids belonging to this incompatibility group.
Single-cell sequencing of human iPSC-derived cerebellar organoids shows recapitulation of cerebellar development
Authors: Nayler Samuel , Agarwal Devika , Curion Fabiola , Bowden Rory , Becker Esther B.E. 
Published: July 2020

ABSTRACTCurrent protocols for producing cerebellar neurons from human pluripotent stem cells (hPSCs) are reliant on animal co-culture and mostly exist as monolayers, which have limited capability to recapitulate the complex arrangement of the brain. We developed a method to differentiate hPSCs into cerebellar organoids that display hallmarks of in vivo cerebellar development. Single-cell profiling followed by comparison to an atlas of the developing murine cerebellum revealed transcriptionally-discrete populations encompassing all major cerebellar cell types. Matrigel encapsulation altered organoid growth dynamics, resulting in differential regulation of cell cycle, migration and cell-death pathways. However, this was at the expense of reproducibility. Furthermore, we showed the contribution of basement membrane signalling to both cellular composition of the organoids and developmentally-relevant gene expression programmes. This model system has exciting implications for studying cerebellar development and disease most notably by providing xeno-free conditions, representing a more biologically relevant and therapeutically tractable culture setting.
Organic dust induced mitochondrial dysfunction could be targeted via cGAS-STING or mitochondrial NOX-2 inhibition
Authors: Massey Nyzil , Shrestha Denusha , Bhat Sanjana Mahadev , Kondru Naveen , Charli Adhithiya , Karriker Locke A. , Kanthasamy Anumantha G. , Charavaryamath Chandrashekhar 
Published: July 2020

ABSTRACTOrganic dust (OD) exposure in animal production industries poses serious respiratory and other health risks. OD consists of microbial products and particulate matter and OD exposure induced respiratory inflammation is under intense investigation. However, the effect of OD exposure on brain largely remains unknown. Recently, we have shown that OD exposure of brain microglial cells induces an inflammatory phenotype with the release of mitochondrial DNA (mt-DNA). Therefore, we tested a hypothesis that OD-exposure induced secreted mt-DNA signaling drives the inflammation. OD samples were collected from commercial swine operations and a filter sterilized OD extract (ODE) was prepared. Mouse (C57BL/6) microglial cell line was treated with medium or ODE (5%) for 48 hours along with either PBS or mitoapocynin (MA, 10 μM, NOX-2 inhibitor). Microglia treated with control or anti-STING siRNA were exposed to medium or ODE. Next, mouse (C57BL/6) pups were euthanized under an approved protocol, organotypic brain slice cultures (BSCs) were prepared and exposed to medium or ODE with or without MA treatment daily for five days. Culture supernatant, cell pellets and mt-free cytosolic fractions were processed to quantify mt-superoxide, mt-DNA, cytochrome C, TFAM, mitochondrial stress markers and mt-DNA induced signaling via cGAS-STING and TLR9. Data were analyzed using one-way ANOVA and post-hoc tests. A p value of ≤ 0.05 was considered significant. ODE exposure increased the mt-superoxide formation andMA treatment decreased the ODE-induced mt-DNA release into cytosol. ODE exposure increased the cytochrome C and TFAM levels. ODE increased MFN1/2 and PINK1 but not DRP1 and MA treatment decreased the MFN2 expression. MA treatment decreased the ODE-exposure induced mt-DNA signaling via cGAS-STING and TLR9. Anti-STING siRNA decreased the ODE-induced increase in IRF3, IFN-β and Iba1 expression. In BSCs, MA-treatment decreased the ODE induced TNF-α, IL-6 and MFN1. Taken together, OD exposure induced mt-DNA signaling could be curtailed through mitochondrial NOX-2 inhibition or STING suppression to reduce neuroinflammation.
Early data on the performance of a combined SARS-CoV-2 spike-nucleocapsid antibody lateral flow device compared to a nucleocapsid-only device
Authors: Linares Christian A. , Ryan Felicity , Moses Samuel E. 
Published: July 2020

AbstractThe authors have withdrawn their manuscript whilst they perform additional experiments to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Genetic architecture of host proteins interacting with SARS-CoV-2
Authors: Pietzner Maik , Wheeler Eleanor , Carrasco-Zanini Julia , Raffler Johannes , Kerrison Nicola D. , Oerton Erin , Auyeung Victoria P.W. , Luan Jian’an , Finan Chris , Casas Juan P. , Ostroff Rachel , Williams Steve A. , Kastenmüller Gabi , Ralser Markus , Gamazon Eric R. , Wareham Nicholas J. , Hingorani Aroon D. , Langenberg Claudia 
Published: July 2020

ABSTRACTStrategies to develop therapeutics for SARS-CoV-2 infection may be informed by experimental identification of viral-host protein interactions in cellular assays and measurement of host response proteins in COVID-19 patients. Identification of genetic variants that influence the level or activity of these proteins in the host could enable rapid ‘in silico’ assessment in human genetic studies of their causal relevance as molecular targets for new or repurposed drugs to treat COVID-19. We integrated large-scale genomic and aptamer-based plasma proteomic data from 10,708 individuals to characterize the genetic architecture of 179 host proteins reported to interact with SARS-CoV-2 proteins or to participate in the host response to COVID-19. We identified 220 host DNA sequence variants acting incis(MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links, evidence that putative viral interaction partners such as MARK3 affect immune response, and establish the first link between a recently reported variant for respiratory failure of COVID-19 patients at theABOlocus and hypercoagulation, i.e. maladaptive host response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and dynamic and detailed interrogation of results is facilitated through an interactive webserver (https://omicscience.org/apps/covidpgwas/).
A Glu-Glu-Tyr sequence in the cytoplasmic tail of the M2 protein renders IAV susceptible to restriction of HA-M2 association in primary human macrophages
Authors: Bedi Sukhmani , Haag Amanda , Ono Akira 
Published: July 2020

AbstractInfluenza A virus (IAV) assembly at the plasma membrane is orchestrated by at least five viral components including hemagglutinin (HA), neuraminidase (NA), matrix (M1), the ion channel M2, and viral ribonucleoprotein (vRNP) complexes although particle formation itself requires only HA and/or NA. While these five viral components are expressed efficiently in primary human monocyte-derived macrophages (MDM) upon IAV infection, this cell type does not support efficient HA-M2 association and IAV particle assembly at the plasma membrane. The defects in HA-M2 association and particle assembly are specific to MDM and not observed in a monocytic cell line differentiated into macrophage-like cells. Notably, both these defects can be reversed upon disruption of the actin cytoskeleton. In the current study, we sought to examine whether M2 contributes to particle assembly in MDM and to identify a viral determinant involved in the MDM-specific and actin-dependent suppression of IAV assembly. An analysis using correlative fluorescence and scanning electron microscopy showed that an M2-deficient virus fails to form budding structures at the cell surface even after F-actin is disrupted, indicating that M2 is essential for virus particle formation at the MDM surface. Notably, proximity ligation analysis revealed that single amino acid substitution in a Glu-Glu-Tyr sequence (residues 74-76) in the M2 cytoplasmic tail allows HA-M2 association to occur efficiently even in MDM with intact actin cytoskeleton. This phenotype did not correlate with known phenotypes of the M2 substitution mutants regarding M1 interaction or vRNP packaging in epithelial cells. Overall, our study identifies a viral determinant for susceptibility to cytoskeleton-dependent regulation in MDM and hence, sheds light on the molecular mechanism behind the MDM-specific restriction of IAV assembly.ImportanceNon-permissive cell types that are unable to support viral replication serve as important tools for identification of host factors that either block viral replication (restriction factors) or support viral replication in permissive cell types (co-factors). We previously identified the MDM as a cell type that is non-permissive to IAV assembly, likely due to a block in HA-M2 association. In the current study, we determined that the IAV M2 protein is necessary for virus particle formation in MDM but also renders the virus susceptible to the MDM-specific suppression of virus assembly. We identified a specific amino acid motif in the M2 cytoplasmic tail, disruption of which allows M2 to associate with HA even in MDM. Our findings strongly support the possibility that the MDM-specific defect in HA-M2 association is due to the presence of a restriction factor(s) in MDM, which likely interacts directly with the M2 cytoplasmic domain, rather than indirectly through other internal viral components, and thereby prevents M2 from associating with HA.
High-frequency stimulation of ventral CA1 neurons reduces amygdala activity and inhibits fear
Authors: Graham Jalina , D’Ambra Alexa , Jung Se Jung , Vishwakarma Nina , Venkatesh Rasika , Parigi Abhijna , Antzoulatos Evan G. , Fioravante Diasynou , Wiltgen Brian J. 
Published: July 2020

AbstractThe hippocampus can be divided into distinct segments that make unique contributions to learning and memory. The dorsal hippocampus supports cognitive processes like spatial learning and navigation while the ventral hippocampus regulates emotional behaviors related to fear, anxiety and reward. In the current study, we determined how pyramidal cells in ventral CA1 respond to spatial cues and aversive stimulation during a context fear conditioning task. We also examined the effects of high and low frequency stimulation of these neurons on defensive behaviors. Similar to previous work in the dorsal hippocampus, we found that cells in ventral CA1 expressed high-levels of c-Fos in response to a novel spatial environment. Surprisingly, however, the number of activated neurons did not increase when the environment was subsequently paired with footshock. This was true even in the subpopulation of ventral CA1 pyramidal cells that send direct projections to the amygdala. When these cells were stimulated at high-frequencies (20-Hz), we observed feedforward inhibition of basal amygdala neurons and impaired expression of context fear. In contrast, low-frequency stimulation (4-Hz) did not inhibit principal cells in the amygdala and produced a slight increase in fear generalization. Similar results have been reported in dorsal CA1. Therefore, despite the clear differences between the dorsal and ventral hippocampus, CA1 neurons in each segment appear to make similar contributions to context fear conditioning.
Identifying novel high-impact rare disease-causing mutations, genes and pathways in exomes of Ashkenazi Jewish inflammatory bowel disease patients
Authors: Wu Yiming , Gettler Kyle , Giri Mamta , Li Dalin , Bayrak Cigdem Sevim , Jain Aayushee , Maffucci Patrick , Sabic Ksenija , Vleck Tielman Van , Nadkarni Girish , Denson Lee A. , Ostrer Harry , Kugathasan Subra , Stenson Peter D. , Cooper David N. , Schumm L. Philip , Snapper Scott , Daly Mark J. , Haritunians Talin , Duerr Richard H. , Silverberg Mark S. , Rioux John D. , Brant Steven R. , McGovern Dermot , Cho Judy H. , Itan Yuval 
Published: July 2020

ABSTRACTInflammatory bowel disease (IBD) is a group of chronic diseases, affecting different parts of the gastrointestinal tract, that mainly comprises Crohn’s Disease (CD) and Ulcerative Colitis (UC). Most IBD genomic research to date has involved genome-wide association studies (GWAS) of common genetic variants, mostly in Europeans, resulting in the identification of over 200 risk loci. The incidence of IBD in Ashkenazi Jews (AJ) is particularly high compared to other population groups and rare protein-coding variants are significantly enriched in AJ. These variants are expected to have a larger phenotypic effect and are hypothesized to complement the missing heritability that cannot be fully addressed by GWAS in IBD. Therefore, we genetically identified 4,974 AJs IBD cases and controls from whole exome sequencing (WES) data from the NIDDK IBD Genetics Consortium (IBDGC). We selected credible rare variants with high predicted impact, aggregated them into genes, and performed gene burden and pathway enrichment analyses to identify 7 novel plausible IBD-causing genes:NCF1, CES1, ICAM1, INPP5D, ABCB1, IL33andTLR4. We further perform bulk and single-cell RNA sequencing, demonstrating the likely relatedness of the novel genes to IBD. Importantly, we demonstrate that the rare and high impact genetic architecture of AJ adult IBD displays a significant overlap with very early onset IBD (VEOIBD) genetics. At the variant level, we performed Phenome-wide association studies (PheWAS) in the UK Biobank to replicate risk sites in IBD and reveal shared risk sites with other diseases. Finally, we showed that a polygenic risk score (PRS) has high power to differentiate AJ IBD cases from controls when using rare and high impact variants.
Willingness to work in assisted living facilities: The Ghanaian nurses perspectives
Authors: Aboh Irene Korkoi 
Published: July 2020

AbstractObjectiveThis study explored nurses willingness to work in assisted living institutions for the aged.BackgroundAssisted living institutions are multifunctional facilities that provide clinical and ambulatory (day hospital) care for somatic and psychogeriatric elderly with multiple pathology, disability, and handicaps.MethodsThe study used a mixed-methods approach in which qualitative data was collected first before the quantitative data. Data was collected through focused group discussions (FGDs) and questionnaires from 248 respondents with age ranging from 20 to 58 years from October 2016 to January 2017 with 8 missing from the quantitative data. Four pertinent questions were sked both in the study. Sampling was convenient and purposive from 4 different health institutions in the metropolis. Data from the FGDs were digitally recorded and transcribed verbatim. Quantitative data was entered in SPSS version 23 and cleaned. Both sets of data were coded and analysed.ResultThe nurses appreciate the increase in the number of the aged in their communities; they think community members prepare towards their ageing by using their children as security, and the idea of assisted living was enthusiastically supported, but with the proviso that it would need to be ran by a private entrepreneur. Almost all the 240 respondents said that government should establish an institution for the aged and they would be willing to work in such an institution, if only it will run by a private entrepreneur.ConclusionThe nurses also think that families are now becoming more nuclear; that is why caring for the aged has become a problem, thus creating a need for assisted living facilities.