bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing dynamics of SARS-CoV2 B.1.617.2 (Delta variant) outbreak in the United Kingdom: Shifting of SARS-CoV2 infections from younger to elderly populations with increasing hospitalizations and mortality among elderly
Authors: Emani Venkata R. , Nakka Abirath S. , Goswami Kartik K. , Emani Shaila R. , Maddula Kailash R. , Reddy Nikhila K. , Reddy Nidhi K. , Nandanoor Dheeraj , Goswami Sanjeev , Reddy Raghunath 
Published: March 2022

AbstractBackgroundTo assess the comprehensive dynamics of outcomes during the SARS-CoV2 B.1.617.2 (Delta variant) compared to the Alpha variant outbreak in the United Kingdom.MethodsIn this observational study of the cases reported by Public Health England for confirmed (sequencing and genotyping), SARS-CoV2 cases Delta variant (n=592,692) and Alpha variant (n=150,934) were used. Outcomes were analyzed by age groups and compared with all reported weekly cases in the UK.ResultsThe Delta variant surge is associated with a significantly lower case fatality rate (0.43% vs 1.07; RR 0.39; 95% CI 0.37-0.42; P<0.0001); lower odds of hospitalization (2.1% vs 3.0%; RR 0.70; 95% CI 0.68-0.73; P<0.0001) than the Alpha variant. During the Delta variant surge there were significant increased cases (11.3% to 21.1%, RR 1.87; 95% CI 1.84-1.89; P<0.0001), hospitalizations (40.2% to 56.5%; RR 1.40, 95% CI 1.3-1.46; P<0.0001) among confirmed Delta variant cases in the ≥50 years age group during the August 3-September 12, 2021 period compared to earlier reported cases. There was also a significant increase in total weekly COVID-19 deaths noted among ≥70 years old age group (71.4% to 75.1%; RR 1.05; 95% CI 1.01-1.08; P=0.0028) during August 6-October 8, 2021 compared to June 4-July 30, 2021 period.ConclusionsThe Delta variant surge is associated with significantly lower mortality and hospitalizations than the Alpha variant. As the Delta variant surge progressed, ≥50 years old had a significant increased percentage of cases, hospitalizations and a significant increased COVID-19 deaths occurred among ≥70 years old age group.
Three separate spike antigen exposures by COVID-19 vaccination or SARS-CoV-2 infection elicit strong humoral immune responses in healthcare workers
Authors: Brehm Thomas Theo , Ullrich Felix , Thompson Michelle , Küchen Julia , Schwinge Dorothee , Spier Anthea , Huber Samuel , Knobloch Johannes K , Aepfelbacher Martin , Addo Marylyn M , Lohse Ansgar W , Lütgehetmann Marc , zur Wiesch Julian Schulze 
Published: March 2022

AbstractAs part of our ongoing prospective seroprevalence study, we assessed the SARS-CoV-2 infection and COVID-19 vaccination-induced immunity of 697 hospital workers at the University Medical Center Hamburg-Eppendorf between January 17 and 31, 2022. The overall prevalence of anti-NC-SARS-CoV-2 antibodies indicating prior infection was 9.8% (n=68) and thus lower than the seroprevalence in the general population in Hamburg. At the current study visit, 99.3% (n=692) had received at least one vaccine dose and 93.1% (n=649) had received at least three vaccine doses. All vaccinated individuals had detectable anti-S1-RBD-SARS-CoV-2 antibodies (median AU/ml [IQR]: 13’891 [8’505 – 23’543]), indicating strong protection against severe COVID-19. In addition, we show that individuals who received three COVID-19 vaccine doses (median AU/ml [IQR]: 13’856 [8’635 – 22’705]), and those who resolved a prior SARS-CoV-2 infection and received two COVID-19 vaccine doses (median AU/ml [IQR] 13’409 [6’934 – 25’000]) exhibited the strongest humoral immune responses. The low prevalence of anti-NC-SARS-CoV-2 antibodies indicates persistent effectiveness of established infection control interventions in preventing nosocomial SARS-CoV-2 transmission with the delta and omicron viral variants as predominant strains. Our study further indicates that three exposures to the viral spike protein by either SARS-CoV-2 infection or COVID-19 vaccination are necessary to elicit particularly strong humoral immune responses, which supports current vaccination recommendations.
Exploring potential causal genes for uterine leiomyomas: A summary data-based Mendelian randomization and FUMA analysis
Authors: Dai Yuxin , Liu Xudong , Zhu Yining , Mao Su , Yang Jingyun , Zhu Lan 
Published: March 2022

AbstractObjectiveTo explore potential causal genetic variants and genes underlying the pathogenesis of uterine leiomyomas (ULs).MethodsWe conducted the summary data-based Mendelian randomization (SMR) analysis and performed functional mapping and annotation using FUMA to examine genetic variants and genes that are potentially involved in the pathogenies of ULs.Both analyses used summarized data of a recent genome-wide association study (GWAS) on ULs, which has a total sample size of 244,324 (20,406 cases and 223,918 controls). For the SMR analysis, we performed separate analysis using CAGE and GTEx eQTL data.ResultsUsing the CAGE eQTL data, our SMR analysis identified 13 probes tagging 10 unique genes that were pleiotropically/potentially causally associated with ULs, with the top three probes being ILMN_1675156 (tagging CDC42, PSMR=8.03×10−9), ILMN_1705330 (tagging CDC42, PSMR=1.02×10−7) and ILMN_2343048 (tagging ABCB9, PSMR=9.37×10−7). Using GTEx eQTL data, our SMR analysis did not identify any significant genes after correction for multiple testing. FUMA analysis identified 106 independent SNPs, 24 genomic loci and 137 genes that are potentially involved in the pathogenesis of ULs, seven of which were also identified by the SMR analysis.ConclusionsWe identified many genetic variants, genes, and genomic loci that are potentially involved in the pathogenesis of ULs. More studies are needed to explore the exact underlying mechanisms in the etiology of ULs.
Increased variance in second electrode accuracy during deep brain stimulation and its relationship to pneumocephalus, brain shift, and clinical outcomes: a retrospective cohort study
Authors: Hart MG , Posa M , Buttery PC , Morris RC 
Published: March 2022

ABSTRACTIntroductionAccurate placement of deep brain stimulation electrodes within the intended target is believed to be a key variable related to outcomes. However, methods to verify electrode location are not universally established.Research QuestionThe aim of this study was to determine the feasibility of post-op lead localisation in clinical practice and its utility to audit our own DBS accuracy.Material and MethodsA retrospective cohort study was performed of a consecutive series of patients with Parkinson’s disease who underwent deep brain stimulation of either the globus pallidus internus (GPi) or subthalamic nucleus (STN) between 2016 and 2019. Image processing was performed using the Lead-DBS toolbox. Institutional ethical approval was granted as a review of service.ResultsIn total 38 participants met the inclusion criteria. Electrode localisation was completed in 79%. Clinical outcomes included improvement in UPDRS III of 46% and PDQ39 of 32%. Overall electrode accuracy was 0.22 +/- 0.4mm for all electrodes to the main nucleus with 9 (12%) outliers but only 3 (4%) electrodes out with 2mm from the intended target. Accuracy was worse for the second electrode implanted and in the GPi but was not affected by pneumocephalus or brain shift. Neither clinical outcomes nor the volume of activated tissue was affected by electrode accuracy.Discussion and ConclusionsA neuroimaging approach to electrode localisation allows qualitative appraisal of targeting accuracy and is feasible with routine clinical data. Such methods are complimentary to traditional co-ordinate approaches and lend themselves to developing large, collaborative, and quantitative projects.HIGHLIGHTSOverall electrode accuracy was 0.22 +/- 0.4mm with only 3 (4%) electrodes out with 2mm from the intended targetAccuracy was significantly worse in the GPi versus the STN and on the second side implantedInaccuracy occurred in the X (lateral) plane but was not related to pneumocephalus or brain shift
Risk Factor Stratification for Postoperative Delirium: A Retrospective Database Study
Authors: Vacas Susana , Grogan Tristan , Cheng Drew , Hofer Ira 
Published: March 2022

AbstractBackgroundPostoperative Delirium (POD) is a disturbing reality for patients and their families. Absence of easy-to-use and accurate risk scores prompted us to retrospectively extract data from the electronic health records (EHR) to identify clinical factors associated with POD. We seek to create a multivariate nomogram to predict the risk of POD based upon the most significant clinical factors.MethodsThe EHR of patients >18 years of age undergoing surgery and had POD assessment were reviewed. Patient characteristics and study variables were summarized between delirium groups. We constructed univariate logistic regression models for POD using each study variable to estimate odds ratios (OR) and constructed a multivariable logistic regression model with stepwise variable selection. In order to create a clinically useful/implementable tool we created a nomogram to predict risk of delirium.ResultsOverall, we found a rate of POD of 3.7% across our study population. The Model achieved an AUC of the ROC curve of 0.83 (95% CI 0.82-0.84). We found that age, increased ASA score (ASA 3-4 OR 2.81, CI1.49-5.28, p<0.001), depression (OR 1.28, CI1.12-1.47, p<0.001), postoperative benzodiazepine use (OR 3.52, CI3.06-4.06, p<0.001) and urgent cases (Urgent OR 3.51, CI2.92-4.21, p<0.001; Emergent OR 3.99, CI3.21-4.96, p<0.001; Critically Emergent OR 5.30, CI3.53-7.96, p<0.001) were associated with POD.ConclusionsWe were able to distinguish the contribution of individual risk factors to the development of POD. We created a clinically useful easy-to-use tool that has the potential to accurately identify those at high-risk of delirium, a first step to prevent POD.
New Microviridae isolated from Sulfitobacter reveals two cosmopolitan subfamilies of ssDNA phages infecting marine and terrestrial Alphaproteobacteria
Authors: Zucker Falk , Bischoff Vera , Olo Ndela Eric , Heyerhoff Benedikt , Poehlein Anja , Freese Heike M. , Roux Simon , Simon Meinhard , Enault Francois , Moraru Cristina 
Published: March 2022

AbstractThe Microviridae family represents one of the major clades of ssDNA phages. Their cultivated members are lytic and infect Proteobacteria, Bacteroidetes, and Chlamydiae. Prophages have been predicted in genomes from Bacteroidales, Hyphomicrobiales, and Enterobacteraceae and cluster within the “Alpavirinae”, “Amoyvirinae” and Gokushovirinae. We have isolated “Ascunsovirus oldenburgi” ICBM5, a novel phage distantly related to known Microviridae. It infects Sulfitobacter dubius SH24-1b and uses both a lytic and a carrier-state life strategy. Using ICBM5 proteins as a query, we uncovered in publicly available resources 65 new microviridae prophages and episomes in bacterial genomes and retrieved 47 environmental viral genomes (EVGs) from various viromes. Genome clustering based on protein content and phylogenetic analysis showed that ICBM5, together with Rhizobium phages, new prophages, episomes, and EVGs cluster within two new phylogenetic clades, here tentatively assigned the rank of subfamily and named “Tainavirinae” and “Occultatumvirinae”. They both infect Rhodobacterales. Occultatumviruses also infect Hyphomicrobiales, including nitrogen-fixing endosymbionts from cosmopolitan legumes. A biogeographical assessment showed that tainaviruses and occultatumviruses are spread worldwide, in terrestrial and marine environments. The new phage isolated here shed light onto new and diverse branches of the Microviridae tree, suggesting that much of the ssDNA phage diversity remains in the dark.
Control of NK cell tolerance in MHC class I-deficiency by regulated SHP-1 localization to the activating immune synapse
Authors: Schmied Laurent , Luu Thuy T. , Søndergaard Jonas N. , Meinke Stephan , Mohammad Dara K. , Singh Sunitha B. , Mayer Corinna , Casoni Giovanna P. , Chrobok Michael , Schlums Heinrich , Rota Giorgia , Truong Hieu M. , Westerberg Lisa S. , Guarda Greta , Alici Evren , Wagner Arnika K. , Kadri Nadir , Bryceson Yenan T. , Saeed Mezida B. , Höglund Petter 
Published: March 2022

ABSTRACTSignaling via inhibitory KIR/Ly49 receptors preserves natural killer (NK) cell self-tolerance but also conveys NK cell reactivity towards MHC class-I low target cells in an education process. Here, we demonstrate that mouse NK cell education by H-2Dd regulates transcription of several genes in Ly49A+ NK cells including Ptpn6, encoding the phosphatase SHP-1. SHP-1 was highly expressed in uneducated NK cells, in which knock-out of Ptpn6 increased responsiveness. Following NKp46 triggering of uneducated NK cells, a higher synaptic abundance of phosphorylated SHP-1 was found relative to educated NK cells, concomitant with reduced phosphorylation of several signaling molecules, including PLC-g2, SLP-76, ZAP70/Syk and ERK1/2. SHP-1 overlapped extensively with F-actin and SLP-76 in the uneducated activating synapse of Ly49A+ NK cells, whereas a greater association between Ly49A and SHP-1 was observed in educated NK cells. Thus, our results indicate that in addition to transcriptional regulation, a distinct SHP-1 patterning in NK cell activating synapses can determine their tolerance.
A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system inDrosophila
Authors: Oikawa Izumi , Kondo Shu , Hashimoto Kao , Yoshida Akiho , Hamajima Megumi , Tanimoto Hiromu , Furukubo-Tokunaga Katsuo , Honjo Ken 
Published: March 2022

AbstractNociception is a neural process that animals have developed to avoid potentially tissue-damaging stimuli. While nociception is triggered in the peripheral nervous system, its modulation by the central nervous system is a critical process in mammals, whose dysfunction has been extensively implicated in chronic pain pathogenesis. The peripheral mechanisms of nociception are largely conserved across the animal kingdom. However, it is unclear whether the brain-mediated modulation is also conserved in non-mammalian species. Here, we show thatDrosophilahas a descending inhibitory mechanism of nociception from the brain, mediated by the neuropeptide Drosulfakinin (DSK), a homolog of cholecystokinin (CCK) that plays an important role in the descending control of nociception in mammals. We found that mutants lackingdskor its receptors are hypersensitive to noxious heat. Through a combination of genetic, behavioral, histological, and Ca2+imaging analyses, we subsequently revealed neurons involved in DSK-mediated nociceptive regulation at a single-cell resolution and identified a DSKergic descending neuronal pathway that inhibits nociception. This study provides the first evidence for a descending modulatory mechanism of nociception from the brain in a non-mammalian species that is mediated by the evolutionarily conserved CCK system, raising the possibility that the descending inhibition is an ancient mechanism to regulate nociception.
ScrapPaper: A web scrapping method to extract journal information from PubMed and Google Scholar search result using Python
Authors: Rafsanjani Mohd Rifqi 
Published: March 2022

AbstractThis paper introduces a program called ScrapPaper, a simple Python script that use web-scraping method to extract journal information from PubMed and Google Scholar search results page. Currently the motivation behind the program development is trying to solve a problem to obtain scientific literatures information especially the title and link and save as a list for further use such as in meta-analysis and comparative study of literatures. ScrapPaper advantage that it is simple to use with no prior programming experience and get the results ready within minutes (depending on the total search result). Web-scrapping is a very powerful method to extract information from the web and ScrapPaper employ several server friendly approaches accessing both PubMed and Google Scholar site.Abstract Figure
Community diversity is associated with intra-species genetic diversity and gene loss in the human gut microbiome
Authors: Madi Naïma , Chen Daisy , Wolff Richard , Shapiro B. Jesse , Garud Nandita 
Published: March 2022

AbstractThe human gut microbiome contains a diversity of microbial species that varies in composition over time and across individuals. These species (and strains within species) can migrate across hosts and evolve by mutation and recombination within hosts. How the ecological process of community assembly interacts with intra-species diversity and evolutionary change is a longstanding question. Two contrasting hypotheses have been proposed based on ecological observations and theory: Diversity Begets Diversity (DBD), in which taxa tend to become more diverse in already diverse communities, and Ecological Controls (EC), in which higher community diversity impedes diversification within taxa. Previously, using 16S rRNA gene amplicon data across a range of environments, we showed a generally positive relationship between taxa diversity and community diversity at higher taxonomic levels, consistent with the predictions of DBD (Madi et al., 2020). However, this positive ‘diversity slope’ reaches a plateau at high levels of community diversity. Here we show that this general pattern holds at much finer genetic resolution, by analyzing intra-species strain and nucleotide variation in static and temporally sampled shotgun-sequenced fecal metagenomes from cohorts of healthy human hosts. We find that both intra-species polymorphism and strain number are positively correlated with community Shannon diversity. This trend is consistent with DBD, although we cannot exclude abiotic drivers of diversity. Shannon diversity is also predictive of increases in polymorphism over time scales up to ∼4-6 months, after which the diversity slope flattens and then becomes negative—consistent with DBD eventually giving way to EC. Also supporting a complex mixture of DBD and EC, the number of strains per focal species is positively associated with Shannon diversity but negatively associated with richness. Finally, we show that higher community diversity predicts gene loss in a focal species at a future time point. This observation is broadly consistent with the Black Queen Hypothesis, which posits that genes with functions provided by the community are less likely to be retained in a focal species’ genome. Together, our results show that a mixture of DBD, EC, and Black Queen may operate simultaneously in the human gut microbiome, adding to a growing body of evidence that these eco-evolutionary processes are key drivers of biodiversity and ecosystem function.
Mechanical Ventilation induced DNA Damage and P21 in an Acute Aging Model of Lung Injury
Authors: Kamga Gninzeko Franck J. , Tho Cindy K. , Valentine Michael S. , Wandling Emily N. , Heise Rebecca L. 
Published: March 2022

AbstractAcute respiratory distress syndrome (ARDS) is a form of acute lung injury which leads to a paucity of oxygen. To remedy ARDS, patients are put on mechanical ventilators; however, the stretch resulting from the mechanical ventilator can lead to ventilator-induced lung injury or VILI. VILI is exacerbated by age. The combined effects of ARDS and mechanical ventilation can result in a hostile environment which may lead to senescence (stable cell cycle arrest). The role of senescence in VILI is poorly understood. Senescence is characterized by increased cyclin-dependent kinase inhibitors P16 and P21; however, P21 has been shown to occur in early senescence. We hypothesized that mechanical ventilation would lead to DNA damage and senescence-like phenotype. Both in vivo and in vitro models of VILI were used to investigate senescence and its mechanism in VILI. Mechanical ventilation increased senescence-associated markers such as DNA damage marker characterized by ɣH2AX, P21, senescence-associated secretory phenotype IL6, and decreased proliferation. Moreover, mechanical ventilation led to increased apoptosis. Lung sections were stained for KRT8 proteins, markers of transiently differentiated alveolar type 2 (AT2) cells which were reported to be more prone to DNA damage. Age and mechanical ventilation increased KRT8 positive cells. Finally, we probed a potential mediator of the stretch induced senescence in vitro by inhibiting P38-MAPK, which can be activated by DNA damage response, leading to increased P21. Inhibiting P38 decreased in P21 but did not decrease ɣH2AXThese findings suggest that mechanical ventilation may lead to a senescence-like phenotype involving the P38-MAPK pathway.
Quantitative interactome proteomics identifies proteostasis network for GABAAreceptors
Authors: Wang Ya-Juan , Di Xiao-Jing , Mu Ting-Wei 
Published: March 2022

AbstractGamma-aminobutyric acid type A (GABAA) receptors, the primary inhibitory neurotransmitter-gated ion channels in the mammalian central nervous system, inhibit neuronal firing to preserve balanced neuronal activity. Maintenance of GABAAreceptor protein homeostasis (proteostasis) in the cell utilizing its interacting proteins is essential for the function of GABAAreceptors. However, how the proteostasis network orchestrates GABAAreceptor biogenesis in the endoplasmic reticulum (ER) is not well understood. To address this question systematically, we employed a proteomics-based approach to identify the interactomes of GABAAreceptors by carrying out a quantitative immunoprecipitation-tandem mass spectrometry (IP-MS/MS) analysis utilizing stable isotope labeling by amino acids in cell culture (SILAC). To enhance the coverage and reliability of the identified proteins, we performed comparative proteomics by using both wild type α1 subunit and a misfolding-prone α1 subunit carrying the A322D variant as the bait proteins. The wild type α1 interactome contains 125 proteins, the α1(A322D) interactome contains 105 proteins, and 54 proteins overlap within two interactomes. Bioinformatics analysis identified potential GABAAreceptor proteostasis network components, including chaperones, folding enzymes, trafficking factors, and degradation factors. Further, their potential involvement is modelled in the cellular folding, degradation and trafficking pathways for GABAAreceptors. In addition, we verified endogenous interactions between α1 subunit and their selected interactors by carrying out co-immunoprecipitation assay in mouse brain homogenates. This study paves the way for understanding the molecular mechanisms as well as fine-tuning of GABAAreceptor proteostasis to ameliorate related neurological diseases such as epilepsy.
Structure of the IL-27 quaternary receptor signaling complex
Authors: Caveney Nathanael A , Glassman Caleb R , Jude Kevin M , Tsutsumi Naotaka , Garcia K Christopher 
Published: March 2022

AbstractInterleukin 27 (IL-27) is a heterodimeric cytokine that functions to constrain T cell-mediated inflammation and plays an important role in immune homeostasis. Binding of IL-27 to cell surface receptors IL-27Rα and gp130 results in activation of receptor-associated Janus Kinases and nuclear translocation of STAT1 and STAT3 transcription factors. Despite the emerging therapeutic importance of this cytokine axis in cancer and autoimmunity, a molecular blueprint of the IL-27 receptor signaling complex, and its relation to other gp130/IL-12 family cytokines, is currently unclear. We used cryogenic-electron microscopy (cryo-EM) to determine the quaternary structure of IL-27 (p28/Ebi3) bound to receptor subunits, IL-27Rα and gp130. The resulting 3.47 Å resolution structure revealed a three-site assembly mechanism nucleated by the central p28 subunit of the cytokine. The overall topology and molecular details of this binding are reminiscent of IL-6 but distinct from related heterodimeric cytokines IL-12 and IL-23. These results indicate distinct receptor assembly mechanisms used by heterodimeric cytokines with important consequences for targeted agonism and antagonism of IL-27 signaling.