bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding COVID-19 testing pathways in English care homes to identify the role of point-of-care testing: an interview-based process mapping study
Authors: Micocci Massimo , Gordon Adam L , Allen A. Joy , Hicks Timothy , Kierkegaard Patrick , McLister Anna , Walne Simon , Buckle Peter 
Published: November 2020

AbstractIntroductionCare home residents are at high risk of dying from COVID-19. Regular testing producing rapid and reliable results is important in this population because infections spread quickly and presentations are often atypical or asymptomatic. This study evaluated current testing pathways in care homes to explore the role of point-of-care tests (POCTs).MethodsTen staff from eight care homes, purposively sampled to reflect care organisational attributes that influence outbreak severity, underwent a semi-structured remote videoconference interview. Transcripts were analysed using process mapping tools and framework analysis focussing on perceptions about, gaps within, and needs arising from, current pathways.ResultsFour main steps were identified in testing: infection prevention, preparatory steps, swabbing procedure, and management of residents. Infection prevention was particularly challenging for mobile residents with cognitive impairment. Swabbing and preparatory steps were resource-intensive, requiring additional staff resource. Swabbing required flexibility and staff who were familiar to the resident. Frequent approaches to residents were needed to ensure they would participate at a suitable time. After-test management varied between sites. Several homes reported deviating from government guidance to take more cautious approaches, which they perceived to be more robust.ConclusionSwab-based testing is organisationally complex and resource-intensive in care homes. It needs to be flexible to meet the needs of residents and provide care homes with rapid information to support care decisions. POCT could help address gaps but the complexity of the setting means that each technology must be evaluated in context before widespread adoption in care homes.Key-pointsTesting for COVID-19 in care homes is complex and requires reconfiguration of staffing and environment.Isolation and testing procedures are challenged when providing person-centred care to people with dementia.Point-of-care testing results could give care homes greater flexibility to test in person-centred ways.There was evidence that care home staff interpret testing guidance, rather than follow it verbatim.Each POCT must be evaluated in the context of care homes to understand its effect on care home processes.
Vascular Thrombosis in COVID-19: A Potential Association with Antiphospholipid Antibodies
Authors: Kallapur Aneesh S , Yen Eric Y , Singh Ram Raj 
Published: November 2020

ABSTRACTBackgroundVascular thrombosis is common in patients with coronavirus disease 2019 (COVID-19). Etiologies underlying this complication are unclear.PurposeTo determine the prevalence of antiphospholipid (aPL), including lupus anticoagulant, anti-cardiolipin and anti-β2-glycoprotein-1 antibodies, and its possible association with thrombotic manifestations of COVID-19.Data SourcesWe searched MEDLINE indexed journals on September 24, 2020 using the tool LitCovid and the pre-print server medRxIV.Study SelectionOriginal investigations (cross-sectional studies, cohort studies, case series, and research letters) on COVID-19 and thrombosis were included.Data ExtractionData were independently extracted, and compiled into spreadsheets based on the PRISMA principles.Data SynthesisHospitalized patients with COVID-19 showed a higher prevalence of lupus anticoagulant compared to non-COVID-19 patients. Temporally, lupus anticoagulant was generally positive early in the course of illness, whereas anti-cardiolipin and anti-β2-glycoprotein-1 antibodies appeared to emerge later in the disease. Some patients who were aPL-negative at an early time-point after disease onset became aPL-positive at a later time-point. Lupus anticoagulant was independently associated with thrombosis in 60 COVID-19 patients in New York had who had 32 thrombotic events (8 arterial and 24 venous). In 88 patients in Wuhan, who had more than 20 each of arterial and venous thrombotic events, medium/high positivity for multiple aPL was significantly associated with arterial thrombosis. However, the association of aPL with thrombosis was not evident in reports that had an overall lower number of or predominantly venous thrombotic events. Analysis of pooled patients revealed that aPL were significantly more frequent in COVID-19 patients with stroke than stroke patients in the general population. Furthermore, injection of IgG aPL fractions from COVID-19 patients into mice accelerated venous thrombosis.LimitationLimited data and paucity of prospective studies.ConclusionThe aPL are prevalent in patients with COVID-19 and their presence is associated with thrombosis. Importantly, these antibodies may be a key mechanism of thrombosis in COVID-19. Follow-up studies are required to understand the relationship between aPL and the spectrum of vascular thrombosis during and after infection with SARS-CoV-2.Primary Funding SourceNone.
The CCR5-delta32 variant might explain part of the association between COVID-19 and the chemokine-receptor gene cluster
Authors: Gómez Juan , Cuesta-Llavona Elías , Albaiceta Guillermo M. , García-Clemente Marta , López-Larrea Carlos , Amado-Rodríguez Laura , López-Alonso Inés , Hermida Tamara , EnrÍquez Ana I. , Gil Helena , Alonso Belén , Iglesias Sara , Suarez-Alvarez Beatriz , Alvarez Victoria , Coto Eliecer 
Published: November 2020

AbstractA polymorphism in the LZTFL1 gene located in the chemokine-receptor gene cluster (chromosome 3p) has been associated with the risk of developing COVID-19. The chemokine receptor-5 (CCR5) maps to this region, and the common 32 bp deletion variant (Δ32) has been associated with the extent of inflammatory disease and the outcome in several viral diseases. Several studies have also suggested that the pharmacological targeting of CCR5 could reduce the impact of SARS-CoV-2 infection and the severity of COVID-19. We sought to investigate whether this polymorphism was associated with the risk of moderate-severe COVID-19.We genotyped 294 patients who required hospitalization due to COVID-19 (85 were severe cases) and 460 controls. We found a significantly lower frequency of CCR5-Δ32 among the COVID-19 patients (0.10 vs 0.18 in controls; p=0.002, OR=0.48, 95%CI=0.29-0.76). The difference was mainly due to the reduced frequency of CCR5-Δ32 carriers in the severe, significantly lower than in the non-severe patients (p=0.036). Of note, we did not find deletion-homozygotes among the patients compared to 1% among controls. We also confirmed the association between a LZTFL1 variant and COVID-19. Our study points to CCR5 as a promising target for treatment of COVID-19, but requires validation in additional large cohorts. In confirmed by others, the genetic analysis of CCR5-variants (such as Δ32) might help to identify patients with a higher susceptibility to severe COVID-19.
Sharing ventilators in the Covid-19 pandemics. A bench study
Authors: Guérin Claude , Cour Martin , Stevic Neven , Degivry Florian , L’Her Erwan , Louis Bruno , Argaud Laurent 
Published: November 2020

AbstractCOVID-19 pandemics sets the healthcare system to a shortage of ventilators. We aimed at assessing tidal volume (VT) delivery and air recirculation during expiration when one ventilator is divided into 2 patients. The study was performed in a research laboratory in a medical ICU of a University hospital. An ICU-dedicated (V500) and a lower-level ventilator (Elisée 350) were attached to two test-lungs (QuickLung) through a dedicated flow-splitter. A 50 mL/cmH2O Compliance (C) and 5 cmH2O/L/s Resistance (R) were set in both A and B lungs (step1), C50R20 in A / C20R20 in B (step 2), C20R20 in A / C10R20 in B (step 3), and C50R20 in A / C20R5 in B (step 4). Each ventilator was set in volume and pressure control mode to deliver 0.8L VT. We assessed VT from a pneumotachograph placed immediately before each lung, rebreathed volume, and expiratory resistance (circuit and valve). Values are median (1st-3rd quartiles) and compared between ventilators by non-parametric tests. Between Elisée 350 and V500 in volume control VT in A/B patients were 0.381/0.387 vs. 0.412/0.433L in step 1, 0.501/0.270 vs. 0.492/0.370L in step 2, 0.509/0.237 vs. 0.496/0.332L in step 3, and 0.496/0.281 vs. 0.480/0.329L in step 4. In pressure control the corresponding values were 0.373/0.336 vs. 0.430/0.414L, 0.416/0.185/0.322/0.234L, 0.193/0.108 vs. 0.176/0.092L and 0.422/0.201 vs. 0.481/0.329L, respectively (P<0.001 between ventilators at each step for each volume). Rebreathed air volume ranged between 0.7 to 37.8 ml and negatively correlated with expiratory resistance in steps 2 and 3. The lower-level ventilator performed closely to the ICU-dedicated ventilator. Due to dependence of VT to C pressure control should be used to maintain adequate VT at least in one patient when C and/or R changes abruptly and monitoring of VT should be done carefully. Increasing expiratory resistance should reduce rebreathed volume.
Encoding of facial features by single neurons in the human amygdala and hippocampus
Authors: Cao Runnan , Li Xin , Brandmeir Nicholas J. , Wang Shuo 
Published: November 2020

AbstractThe human amygdala and hippocampus play a key role in face processing. However, it has been unknown how the neurons in the human amygdala and hippocampus encode facial feature information and directs eye movements to salient facial features such as the eyes and mouth. In this study, we identified a population of neurons that differentiated fixations on the eyes vs. mouth. The response of these feature-selective neurons was not dependent on fixation order, and eye-preferring and mouth-preferring neurons were not of different neuronal types. We found another population of neurons that differentiated saccades to the eyes vs. mouth. Population decoding confirmed our results and further revealed the temporal dynamics of face feature coding. Interestingly, we found that the amygdala and hippocampus played a different role in encoding face features. Lastly, we revealed two functional roles of feature-selective neurons that they encoded the salient region for face recognition and they encoded perceived social trait judgment. Together, we revealed and characterized a new class of neurons that encoded facial features. These neurons may play an important role in social perception and recognition of faces.
Heritable environments: bias due to conditioning on a collider in models with polygenic scores
Authors: Akimova Evelina T. , Breen Richard , Brazel David M. , Mills Melinda C. 
Published: November 2020

AbstractThe application of polygenic scores has transformed our ability to investigate whether and how genetic and environmental factors jointly contribute to the variation of complex traits. Modelling the complex interplay between genes and environment, however, raises serious methodological challenges. Here we illustrate the largely unrecognised impact of gene-environment dependencies on the identification of the effects of genes and their variation across environments. We show that controlling for heritable covariates in regression models that include polygenic scores as independent variables introduces endogenous selection bias when one or more of these covariates depends on unmeasured factors that also affect the outcome. This results in the problem of conditioning on a collider, which in turn leads to spurious associations and effect sizes. Using graphical and simulation methods we demonstrate that the degree of bias depends on the strength of the gene-covariate correlation and of hidden heterogeneity linking covariates with outcomes, regardless of whether the main analytic focus is mediation, confounding, or gene × covariate (commonly gene × environment) interactions. We offer potential solutions, highlighting the importance of causal inference. We also urge further caution when fitting and interpreting models with polygenic scores and non-exogenous environments or phenotypes and demonstrate how spurious associations are likely to arise, advancing our understanding of such results.
Cortical representation of pain by stable dedicated neurons and dynamic ensembles
Authors: Acuña Mario A. , Kasanetz Fernando , De Luna Paolo , Nevian Thomas 
Published: November 2020

AbstractThe perception of pain arises from distributed brain activity triggered by noxious stimuli. However, which patterns of activity make nociception distinct from other salient sensory experiences is still unknown. Usingin vivochronic two-photon calcium imaging in slightly anaesthetized mice, we identified a nociception-specific representation in the anterior cingulate cortex (ACC), that is attained by a core of neurons that code for a generalized concept of the pain experience. The overall ensemble activity allowed for an efficient discrimination of the sensory space, despite a drift in single-neuron sensory tuning over time. Following sciatic nerve lesion, the representation of nociceptive stimuli was impaired as a consequence of innocuous stimuli expanded into the nociception-specific ensemble, leading to a dysfunctional discrimination of sensory events in the ACC. Thus, the hallmark of chronic pain at the cortical neuronal network level is an impairment of pattern separation and classification identifying a circuit mechanism for altered pain processing in the brain.
The meadow jumping mouse genome and transcriptome suggest mechanisms of hibernation
Authors: Cong Qian , Brem Ethan A. , Zhang Jing , Alföldi Jessica , Johnson Jeremy , Karlsson Elinor K. , Lindblad-Toh Kerstin , Malaney Jason L. , Israelsen William J. 
Published: November 2020

ABSTRACTHibernating mammals exhibit medically relevant phenotypes, but the genetic basis of hibernation remains poorly understood. Using the meadow jumping mouse (Zapus hudsonius), we investigated the genetic underpinnings of hibernation by uniting experimental and comparative genomic approaches. We assembled aZ. hudsoniusgenome and identified widespread expression changes during hibernation in genes important for circadian rhythm, membrane fluidity, and cell cycle arrest. Tissue-specific gene expression changes during torpor encompassed Wnt signaling in the brain and structural and transport functions in the kidney brush border. Using genomes from the closely relatedZapus oregonus(previously classified asZ. princeps) and leveraging a panel of hibernating and non-hibernating rodents, we found selective pressure on genes involved in feeding behavior, metabolism, and cell biological processes potentially important for function at low body temperature. Leptin stands out with elevated conservation in hibernating rodents, implying a role for this metabolic hormone in triggering fattening and hibernation. These findings illustrate that mammalian hibernation requires adaptation at all levels of organismal form and function and lay the groundwork for future study of hibernation phenotypes.
Properties of genes encoding transfer RNAs as integration sites for genomic islands and prophages inKlebsiella pneumoniae
Authors: Berríos-Pastén Camilo , Acevedo Rodolfo , Arros Patricio , Varas Macarena A. , Wyres Kelly L. , Lam Margaret M. C. , Holt Kathryn E. , Lagos Rosalba , Marcoleta Andrés E. 
Published: November 2020

ABSTRACTThe evolution of traits including antibiotic resistance, virulence, and increased fitness inKlebsiella pneumoniaeand related species has been linked to the acquisition of mobile genetic elements through horizontal transfer. Among them, genomic islands (GIs) preferentially integrating at genes encoding tRNAs and the tmRNA (t(m)DNAs) would be significant in promoting chromosomal diversity. Here, we studied the whole set of t(m)DNAs present in 66Klebsiellachromosomes, investigating their usage as integration sites and the properties of the integrated GIs. A total of 5,624 t(m)DNAs were classified based on their sequence conservation, genomic context, and prevalence. 161 different GIs and prophages were found at these sites, hosting 3,540 gene families including various related to virulence and drug resistance. Phylogenetic analyses supported the acquisition of several of these elements through horizontal gene transfer, likely mediated by a highly diverse set of encoded integrases targeting specific t(m)DNAs and sublocations inside them. Only a subset of the t(m)DNAs had integrated GIs and even identical tDNA copies showed dissimilar usage frequencies, suggesting that the genomic context would influence the integration site selection. This usage bias, likely towards avoiding disruption of polycistronic transcriptional units, would be conserved across Gammaproteobacteria. The systematic comparison of the t(m)DNAs across different strains allowed us to discover an unprecedented number ofK. pneumoniaeGIs and prophages and to raise important questions and clues regarding the fundamental properties of t(m)DNAs as targets for the integration of mobile genetic elements and drivers of bacterial genome evolution and pathogen emergence.
Successive waves in pandemic infections: physical diffusion theory and data comparisons
Authors: Duffey Romney B 
Published: November 2020

AbstractWe establish the principal that the prediction, timing and magnitude of second and more distinct waves of infection can be based on the well - known physics and assumptions of classical diffusion theory. This model is fundamentally different from the commonly used SEIR and R0 fitting methods. Driven by data, we seek a working approximation for the observed orders of magnitude for the timing and rate of second and more waves. The dynamic results and characteristics are compared to the data and enable predictions of timescales and maximum expected rates where diffusive effects dominate.The important point is this simple physical model allows understanding of the dominant processes, provides prediction estimates, and is based the solutions derived from existing, consistent and well-known physical principles. The medical system and health policy implications of such inexorable diffusive spread are that any NPI and other countermeasures deployed for and after the rapid first peak must recognize that large residual infection waves will then likely occur.
Novel incursion of a highly pathogenic avian influenza subtype H5N8 virus in the Netherlands, October 2020
Authors: Beerens Nancy , Heutink Rene , Harders Frank , Roose Marit , Pritz-Verschuren Sylvia B.E. , Germeraad Evelien A. , Engelsma Marc 
Published: November 2020

AbstractThe HPAI H5N8 virus detected in mute swans in the Netherlands in October 2020 shares a common ancestor with clade 2.3.4.4b viruses last detected in Egypt in 2018-2019 and has a similar genetic composition. The virus is not directly related to European H5N8 viruses detected in first half of 2020.
HIV-1 and microglia: EcoHIV and HIV-1 transgenic rats
Authors: Li Hailong , McLaurin Kristen A. , Illenberger Jessica M. , Mactutus Charles F. , Booze Rosemarie M. 
Published: November 2020

ABSTRACTThe persistence of HIV-1 viral reservoirs in the brain, despite treatment with combination antiretroviral therapy (cART), remains a critical roadblock for the development of a novel cure strategy for HIV-1. To enhance our understanding of viral reservoirs, two complementary studies were conducted to 1) evaluate the HIV-1 mRNA neuroanatomical distribution pattern and major cell type expressing HIV-1 mRNA in the HIV-1 transgenic (Tg) rat (i.e., under conditions of latent infection), and 2) to validate our findings by developing and critically testing a novel biological system to model active HIV-1 infection in the rat. First, a restricted, region-specific HIV-1 mRNA distribution pattern was observed in the HIV-1 Tg rat. Microglia were the predominant cell type expressing HIV-1 mRNA in the HIV-1 Tg rat. Second, we developed and critically tested a novel biological system to model key aspects of HIV-1 by infusing F344/N control rats with chimeric HIV (EcoHIV).In vitro,primary cultured microglia were treated with EcoHIV revealing prominent expression within 24 hours of infection.In vivo,EcoHIV expression was observed seven days after stereotaxic injections. Following EcoHIV infection, microglia were the major cell type expressing HIV-1 mRNA, results which are consistent with observations in the HIV-1 Tg rat. Within eight weeks of infection, EcoHIV rats exhibited neurocognitive impairments, synaptic dysfunction, which may result from activation of the NogoA-NgR3/PirB-RhoA signaling pathway, and neuroinflammation. Collectively, these studies enhance our understanding of HIV-1 viral reservoirs in the brain and offer a novel biological system to model HIV-associated neurocognitive disorders and associated comorbidities (i.e., drug abuse) in rats.
The foot fault scoring system to assess walking adaptability in rats and mice: a reliability study
Authors: Martins Lucas Athaydes , Schiavo Aniuska , Xavier Léder Leal , Mestriner Régis Gemerasca 
Published: November 2020

ABSTRACTThe foot fault scoring system of the ladder rung walking test is used to assess walking adaptability in rodents. However, the reliability of the ladder rung walking test foot fault score has not been properly investigated. This study was designed to address this issue.Two independent and blinded raters analyzed 20 rat and 20 mice videos. Each video was analyzed twice by the same rater (80 analyses per rater). The intraclass correlation coefficient (ICC) and the Kappa coefficient were employed to check the accuracy of agreement and reliability in the intra- and inter-rater analyses of the ladder rung walking test outcomes. Excellent intra- and inter-rater agreement was found for the forelimb, hindlimb and both limbs combined in rats and mice. The agreement level was also excellent for total crossing time, total time stopped and number of stops during the walking path. Rating individual scores in the foot fault score system (0 to 6) ranged from satisfactory to excellent, in terms of the intraclass correlation indexes. Moreover, we showed experienced and inexperienced raters can obtain reliable results if supervised training is provided. We conclude the ladder rung walking test is a reliable and useful tool to study walking adaptability in rodents and can help researchers address walking-related neurobiological questions.