bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitigating the Adverse Effects of 12-Hour Shifts
Authors: Keys Yolanda 
Published: September 2020

OBJECTIVE
The purpose of this study was to explore perspectives of nurse leaders regarding strategies to mitigate the job demands of 12-hour shift work and learn their views regarding the role of breaks in offsetting the cognitive and physical demands of acute care nurses working 12-hour shifts.

BACKGROUND
The strain of long shifts can result in adverse outcomes for nurses, organizations, and patients.

METHODS
A modified, 3-round, e-Delphi solicited input from nurse leaders. First, qualitative information about support and resources to mitigate the adverse effects of 12-hour shifts was collected, and then 2 subsequent rounds used consensus identification and item ranking to develop recommendations.

RESULTS
Findings reinforce that job demands of 12-hour shifts can be mitigated via staffing practices, quiet break spaces, and the opportunity to work with familiar patients.

CONCLUSIONS
Recommendations from this work may enhance patient safety, positive organizational outcomes, and a resilient and sustainable nursing workforce.
Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial)
Authors: Agarwal Anup , Mukherjee Aparna , Kumar Gunjan , Chatterjee Pranab , Bhatnagar Tarun , Malhotra Pankaj ,   PLACID Trial Collaborators
Published: September 2020

AbstractObjectivesConvalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19.DesignOpen-label, parallel-arm, phase II, multicentre, randomized controlled trial.SettingThirty-nine public and private hospitals across India.ParticipantsHospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air).InterventionParticipants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm.Main Outcome MeasureComposite of progression to severe disease (PaO2/FiO2< 100) or all-cause mortality at 28 days post-enrolment.ResultsBetween 22ndApril to 14thJuly 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: −0.61 to 1.83].InterpretationCP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.Trial registrationThe trial was registered with Clinical Trial Registry of India (CTRI); CTRI/2020/04/024775.
Modelling the transmission of infectious diseases inside hospital bays: implications for Covid-19
Authors: Martos David Moreno , Parcell Benjamin J. , Eftimie Raluca 
Published: September 2020

AbstractHealthcare associated transmission of viral infections is a major problem that has significant economic costs and can lead to loss of life. Infections with the highly contagious SARS-CoV-2 virus have been shown to have a high prevalence in hospitals around the world. The spread of this virus might be impacted by the density of patients inside hospital bays. To investigate this aspect, in this study we consider a mathematical modelling and computational approach to describe the spread of SARS-CoV-2 among hospitalised patients. We focus on 4-bed bays and 6-bed bays, which are commonly used to accommodate various non-Covid-19 patients in many hospitals across UK. We use this mathematical model to investigate the spread of SARS-CoV-2 infections among patients in non-Covid bays, in the context of various scenarios: changes in the number of contacts with infected patients and staff, having symptomatic vs. asymptomatic patients, removing infected individuals from these hospital bays once they are known to be infected, and the role of periodic testing of hospitalised patients. Our results show that 4-bed bays reduce the spread of SARS-CoV-2 compared to 6-bed bays. Moreover, we show that the position of a new (not infected) patient in specific beds in a 6-bed bay might also slow the spread of the disease. Finally, we propose that regular SARS-CoV-2 testing of hospitalised patients would allow appropriate placement of infected patients in specific (Covid-only) hospital bays.
Activin/Follistatin-axis deregulation is independently associated with COVID-19 in-hospital mortality
Authors: Synolaki Evgenia , Papadopoulos Vasileios , Divolis Georgios , Gavriilidis Efstratios , Loli Georgia , Gavriil Arianna , Tsigalou Christina , Tsahouridou Olga , Sertaridou Eleni , Rafailidis Petros , Pasternack Arja , Boumpas Dimitrios , Germanidis Georgios , Ritvos Olli , Metallidis Simeon , Skendros Panagiotis , Sideras Paschalis 
Published: September 2020

AbstractRationaleActivins are inflammatory and tissue-repair-related members of the TGFβ-superfamily that have been implicated in the pathogenesis of several immuno-inflammatory disorders including sepsis/acute respiratory distress syndrome (ARDS). We hypothesized that they might be of particular relevance to COVID-19 pathophysiology.ObjectivesTo assess the involvement of the Activin-Follistatin-axis in COVID-19 pathophysiology.MethodsLevels of Activins -A, -B and their physiological inhibitor Follistatin, were retrospectively analyzed in 314 serum samples from 117 COVID-19 patients derived from two independent centers and compared with common demographic, clinical and laboratory parameters. Optimal-scaling with ridge-regression was used to screen variables and establish a prediction model.Main ResultsThe Activin/Follistatin-axis was significantly deregulated during the course of COVID-19 and was independently associated with severity and in-hospital mortality. FACT-CLINYCoD, a novel disease scoring system, adding one point for each of Follistatin >6235 pg/ml, Activin-A >591 pg/ml, Activin-B >249 pg/ml, CRP >10.3 mg/dL, LDH >427 U/L, Intensive Care Unit (ICU) admission, Neutrophil/Lymphocyte-Ratio >5.6, Years of Age >61, Comorbidities >1 and D-dimers >1097 ng/ml, efficiently predicted and monitored fatal outcome independently of multiplicity and timing of sampling (AUC: 0.951±0.032, p<10-6). Validation in 35 samples derived from a third hospital indicated comparable AUC (0.958±0.086, p=0.032).ConclusionThis study unravels the link between Activin/Folistatin-axis and COVID-19 mortality and introduces FACT-CLINYCoD, a novel pathophysiology-based tool that copes with the dynamic and heterogeneous nature of COCVID-19, predicts disease outcome and supports clinical decision making. Prospective large-scale validation of this calculator, as well as investigation of the mechanisms linking Activin/Folistatin-axis to COVID-19 pathogenesis is warranted.
Dietary suppression of MHC-II expression in intestinal stem cells enhances intestinal tumorigenesis
Authors: Beyaz Semir , Roper Jatin , Bauer-Rowe Khristian E. , Xifaras Michael E. , Ergin Ilgin , Dohnalova Lenka , Biton Moshe , Shekar Karthik , Mou Haiwei , Eskiocak Onur , Özata Deniz M. , Papciak Katherine , Chung Charlie , Almeqdadi Mohammed , Fein Miriam , Valle-Encinas Eider , Erdemir Aysegul , Dogum Karoline , Garipcan Aybuke , Meyer Hannah , Fox James G. , Elinav Eran , Kucukural Alper , Kumar Pawan , McAleer Jeremy , Thaiss Christoph A. , Regev Aviv , Orkin Stuart H. , Yilmaz Ömer H. 
Published: September 2020

AbstractLittle is known about how interactions between diet, immune recognition, and intestinal stem cells (ISCs) impact the early steps of intestinal tumorigenesis. Here, we show that a high fat diet (HFD) reduces the expression of the major histocompatibility complex II (MHC-II) genes in ISCs. This decline in ISC MHC-II expression in a HFD correlates with an altered intestinal microbiome composition and is recapitulated in antibiotic treated and germ-free mice on a control diet. Mechanistically, pattern recognition receptor and IFNg signaling regulate MHC-II expression in ISCs. Although MHC-II expression on ISCs is dispensable for stem cell function in organoid culturesin vitro, upon loss of the tumor suppressor geneApcin a HFD, MHC-II- ISCs harbor greaterin vivotumor-initiating capacity than their MHC-II+ counterparts, thus implicating a role for epithelial MHC-II in suppressing tumorigenesis. Finally, ISC-specific genetic ablation of MHC-II in engineeredApc-mediated intestinal tumor models increases tumor burden in a cell autonomous manner. These findings highlight how a HFD alters the immune recognition properties of ISCs through the regulation of MHC-II expression in a manner that could contribute to intestinal tumorigenesis.
Metastatic Lymph Node Station Number Predicts Survival in Small Cell Lung Cancer
Authors: Zhang Han , Jiang Cong , Jing Kaiqi , Zhang Jing , Chen Yan , Zhu Yuming , Jiang Gening , Zhang Peng 
Published: September 2020

AbstractPurposeAs for pathologic N category, various regrouping strategies have been raised in non-small cell lung cancer (NSCLC) but little was done in small cell lung cancer(SCLC). On the basis of the suggestions discussed in NSCLC, we proposed a novel, metastatic lymph node station number (MNSN) - based pathologic N parameter and compared its efficacy in predicting survival with pN in SCLC.MethodsWe retrospectively analyzed the patients operated and pathologically diagnosed as SCLC in our hospital between 2009 and 2019. Kaplan–Meier method and Cox regression analysis were used to compare survival between groups defined by pN and MNSN.ResultsFrom 2009 to 2019, 566 patients received surgery for SCLC and 530 of them were eligible for subsequent analysis, with a median follow-up time of 21 months. The 5-year overall survival (OS) rates were 58.8%, 38.6%, 27.9% for pN0, pN1, pN2 stages and were 58.8%, 36.8%, 22.1%, 0% for MNSN0, 1-2, 3-5, 6-7 groups, respectively. Analyses of overall and recurrence-free survival (RFS) revealed that pN1 could not be distinguished from pN2 (OS, p = 0.099; RFS, p = 0.254), but the groups in MNSN were well separated from each other (OS, p< 0.001, p = 0.001, p = 0.063; RFS, p< 0.001, p = 0.026, p = 0.01, compared with the former group). When adjusted for sex, age, smoking, tumor purity and T stage, MNSN groups were independent hazard factors for OS and RFS.ConclusionsBased on our cohort study, the MNSN-based N parameter might be a better indicator to predict survival than pN in SCLC and worth considering in the definition of N category in the future.
Unequal Lives: A Sociodemographic Analysis of Covid19 Transmission and Mortality in India
Authors: Dibyachintan Soham , Nandy Priyanka , Das Kalyan , Vinjanampathy Sai , Mitra Mithun K. 
Published: September 2020

AbstractThe hierarchy of social structures shape, in very particular and measurable ways, the differential impact that a disease has on different parts of society. In this study, we use district-level disease data to perform an ecological analysis of Covid19 outcomes in India vis a vis the local socioeconomic gradient. Average doubling times and case fatality ratios have been quantified as measures of transmission and mortality, respectively, and association analysis performed with twenty variables of socioeconomic vulnerability. Persistent patterns are observed between disease outcome and social inequality, linking poor living conditions to a faster spread, an elderly populace to a slower spread, and both a college education and the presence of medical facilities to low fatality rates.
Metagenomics Strain Resolution on Assembly Graphs
Authors: Quince Christopher , Nurk Sergey , Raguideau Sebastien , James Robert , Soyer Orkun S. , Summers J. Kimberly , Limasset Antoine , Eren A. Murat , Chikhi Rayan , Darling Aaron E. 
Published: September 2020

AbstractWe introduce a novel bioinformatics pipeline, STrain Resolution ON assembly Graphs (STRONG), which identifies strainsde novo, when multiple metagenome samples from the same community are available. STRONG performs coassembly, followed by binning into metagenome assembled genomes (MAGs), but uniquely it stores the coassembly graph prior to simplification of variants. This enables the subgraphs for individual single-copy core genes (SCGs) in each MAG to be extracted. It can then thread back reads from the samples to compute per sample coverages for the unitigs in these graphs. These graphs and their unitig coverages are then used in a Bayesian algorithm, BayesPaths, that determines the number of strains present, their sequences or haplotypes on the SCGs and their abundances in each of the samples.Our approach both avoids the ambiguities of read mapping and allows more of the information on co-occurrence of variants in reads to be utilised than if variants were treated independently, whilst at the same time exploiting the correlation of variants across samples that occurs when they are linked in the same strain. We compare STRONG to the current state of the art on synthetic communities and demonstrate that we can recover more strains, more accurately, and with a realistic estimate of uncertainty deriving from the variational Bayesian algorithm employed for the strain resolution. On a real anaerobic digestor time series we obtained strain-resolved SCGs for over 300 MAGs that for abundant community members match those observed from long Nanopore reads.
Soil stabilisatizion for DNA metabarcoding of plants and fungi. Implications for sampling at remote locations or via third-parties
Authors: Clasen Lina A , Detheridge Andrew P , Scullion John , Griffith Gareth W 
Published: September 2020

AbstractStorage of soil samples prior to metagenomic analysis presents a problem. If field sites are remote or if samples are collected by third parties, transport to analytical laboratories may take several days or even weeks. The bulk of such samples and requirement for later homogenisation precludes the convenient use of a stabilisation buffer, so samples are usually cooled or frozen during transit. There has been limited testing of the most appropriate storage methods for later study of soil organisms by eDNA approaches. Here we tested a range of storage methods on two contrasting soils, comparing these methods to the control of freezing at −80°C followed by freeze-drying. To our knowledge this is the first study to examine the effect of storage conditions on eukaryote DNA in soil, including both viable organisms (fungi) and DNA contained within dying/dead tissues (plants). For fungi, the best storage regimes (closest to the control) were storage a 4°C (for up to 14 d) or active air-drying at room temperature. The worst treatments involved initial freezing followed by thawing which led to significant later spoilage. The key spoilage organisms were identified asMetarhizium carneumandMortierellaspp., with a general increase in saprotrophic fungi and reduced abundances of mycorrhizal/biotrophic fungi. Plant data showed a similar pattern but with greater variability in community structure especially in the freeze-thaw treatments, probably due to stochastic variation in substrates for fungal decomposition, algal proliferation and some seed germination. In the absence of freeze drying facilities, samples should be shipped refrigerated but not frozen if there is any risk of thawing.
Mutational Analysis of SARS-CoV-2 Genome in African Population
Authors: Omotoso Olabode E. , Babalola Ayoade D. , Matareek Amira 
Published: September 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly infectious and pathogenic virus has claimed lot of lives globally since its outbreak in December 2019 posing dire threat on public health, global economy, social and human interaction. At moderate rate, mutations in the SARS-CoV-2 genome are evolving which might have contributed to viral genome variability, transmission, replication efficiency and virulence in different regions of the world. The present study elucidated the mutational landscape in SARS-CoV-2 genome among the African population, which may have contributed to the virulence, pathogenicity and transmission observed in the region. Multiple sequence alignment of the SARS-CoV-2 genome (356 viral protein sequences) was performed using ClustalX version 2.1 and phylogenetic tree was built using Molecular Evolutionary Genetics Analysis (MEGA) X software. ORF1ab polyprotein, spike glycoprotein, ORF3, ORF8 and nucleocapsid phosphoprotein were observed as mutational hotspots in the African population and may be of keen interest in the adaptability of SARS-CoV-2 to the human host. While, there is conservation in the envelope protein, membrane glycoprotein, ORF6, ORF7a, ORF7b and ORF10. The accumulation of moderate mutations (though slowly) in the SARS-CoV-2 genome as revealed in our study, could be a promising strategy to develop drugs or vaccines with respect to the viral conserved domains and host cellular proteins and/or receptors involved in viral invasion and replication to avoid a new viral wave due to drug resistance and vaccine evasion.
Development of a method for revertable CRISPR/Cas9-based mutagenesis in cell culture
Authors: Walsh Jonathon , Eggenschwiler Jonathan 
Published: September 2020

AbstractCRISPR/Cas9 mutagenesis is a revolutionary tool for genetics in organismal and cell culture systems. One notable caveat with this system is the potential for phenotype-inducing off-target/background mutations. There has been considerable success in modifying the methodology to minimize these potential confounds. Here we have developed a tool to functionally demonstrate that a targeted mutation of interest is responsible for the phenotype observed. This approach creates revertable mutations in cell culture systems using CRISPR/Cas9-induced homology-directed repair (HDR) to insert a LoxP-flanked transcriptional stop sequence into an early intron of a target gene. This method has the potential to be used in multiplexed and inducible scenarios to restore gene function within a given experiment.
Unique Genotypic Features of HIV-1 C Gp41 Membrane Proximal External Region Variants during Pregnancy Relate to Mother-to-child Transmission via Breastfeeding
Authors: Yin Li , Chang Kai-Fen , Nakamura Kyle J. , Kuhn Louise , Aldrovandi Grace M. , Goodenow Maureen M. 
Published: September 2020

ABSTRACTMother-to-child transmission (MTCT) through breastfeeding remains a major source of pediatric HIV-1 infection worldwide. To characterize plasma HIV-1 subtype C populations from infected mothers during pregnancy that related to subsequent breast milk transmission, an exploratory study was designed to apply next generation sequencing and a custom bioinformatics pipeline for HIV-1 gp41 extending from heptad repeat region 2 (HR2) through the membrane proximal external region (MPER) and the membrane spanning domain (MSD). Viral populations during pregnancy from women who transmitted by breastfeeding, compared to those who did not, displayed greater biodiversity, more frequent amino acid polymorphisms, lower hydropathy index and greater positive charge. Viral characteristics were restricted to MPER, failed to extend into flanking HR2 or MSD regions, and were unrelated to predicted neutralization resistance. Findings provide novel parameters to evaluate an association between maternal MPER variants present during gestation and lactogenesis with subsequent transmission outcomes by breastfeeding.IMPORTANCEHIV-1 transmission through breastfeeding accounts for 39% of MTCT and continues as a major route of pediatric infection in developing countries where access to interventions for interrupting transmission is limited. Identifying women who are likely to transmit during breastfeeding would focus therapies during the breastfeeding period to reduce MTCT. Findings from our pilot study identify novel characteristics of gestational viral MPER quasispecies related to transmission outcomes and raise the possibility for predicting MTCT by breastfeeding based on identifying mothers with high-risk viral populations.
Targeted manipulation of abundant and rare taxa in theDaphnia magnamicrobiota with antibiotics impacts host fitness differentially
Authors: Cooper Reilly O. , Vavra Janna M. , Cressler Clayton E. 
Published: September 2020

AbstractHost-associated microbes contribute to host fitness, but it is unclear whether these contributions are from rare keystone taxa, numerically abundant taxa, or interactions among community members. Experimental perturbation of the microbiota can highlight functionally important taxa; however, this approach is primarily applied in systems with complex communities where the perturbation affects hundreds of taxa, making it difficult to pinpoint contributions of key community members. Here, we use the ecological model organismDaphnia magnato examine the importance of rare and abundant taxa by perturbing its relatively simple microbiota with targeted antibiotics. We used sublethal antibiotic doses to target either rare or abundant members across two temperatures, then measured key host life history metrics and shifts in microbial community composition. We find that removal of abundant taxa had greater impacts on host fitness than did removal of rare taxa and that the abundances of non-target taxa were impacted by antibiotic treatment, suggesting no rare keystone taxa exist in theDaphnia magnamicrobiota but microbe-microbe interactions may play a role in host fitness. We also find that microbial community composition was impacted by antibiotics differently across temperatures, indicating ecological context shapes within-host microbial responses and effects on host fitness.ImportanceUnderstanding the contributions of rare and abundant taxa to host fitness is an outstanding question in host microbial ecology. In this study, we use the model zooplanktonDaphnia magnaand its relatively simple cohort of bacterial taxa to disentangle the roles of distinct taxa on host life history metrics, using a suite of antibiotics to selectively reduce the abundance of functionally important taxa. We also examine how environmental context shapes the importance of these bacterial taxa on host fitness.