bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of pneumococcus during hospitalization for SARS-CoV-2
Authors: Watkins Anne E. , Glick Laura R. , Ott Isabel M. , Craft Samuel B. , Yolda-Carr Devyn , Harden Christina A. , Nakahata Maura , Farhadian Shelli F. , Grant Lindsay R. , Alexander-Parrish Ronika , Arguedas Adriano , Gessner Bradford D. , Weinberger Daniel M. , Wyllie Anne L. 
Published: July 2022

ABSTRACTBackgroundInfections with respiratory viruses (e.g., influenza, RSV) can increase the risk of severe pneumococcal infections. Likewise, pneumococcal co-infection is associated with poorer outcomes in viral respiratory infection. However, there are limited data describing the frequency of pneumococcus and SARS-CoV-2 co-infection and the role of co-infection in influencing COVID-19 severity.MethodsThe study included patients admitted to Yale-New Haven Hospital who were symptomatic for respiratory infection and tested positive for SARS-CoV-2 during March-August 2020. Patients were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and serotype-specific urine antigen detection (UAD) assays (to identify presumed lower respiratory tract pneumococcal disease).ResultsAmong 148 subjects, the median age was 65 years; 54.7% were male; 50.7% had an ICU stay; 64.9% received antibiotics; 14.9% died while admitted. Pneumococcal carriage was detected in 3/96 (3.1%) individuals tested by saliva RT-qPCR. Additionally, pneumococcus was detected in 14/127 (11.0%) individuals tested by UAD, and more commonly in severe than moderate COVID-19 (OR: 2.20; 95% CI: [0.72, 7.48]); however, the numbers were small with a high degree of uncertainty. None of the UAD-positive individuals died.ConclusionsPneumococcal LRTI, as detected by positive UAD, occurred in patients hospitalized with COVID-19. Moreover, pneumococcal LRTI was more common in those with more serious COVID-19 outcomes. Future studies should assess how pneumococcus and SARS-CoV-2 interact to influence COVID-19 severity in hospitalized patients.One Sentence SummaryPneumococcal lower respiratory tract infection, as detected by positive UAD, occurred in patients hospitalized with COVID-19 at rates similar to those reported prepandemic.
Predicting expression divergence and its evolutionary parameters between single-copy genes in two species
Authors: Piya Antara Anika , DeGiorgio Michael , Assis Raquel 
Published: July 2022

AbstractPredicting gene expression divergence and its evolutionary parameters is integral to understanding the emergence of new gene functions and associated traits. Whereas several sophisticated methods have been developed for these tasks, their applications are either limited to duplicate genes or require expression data from more than two species. Thus, here we present PiXi, the first machine learning framework for predicting expression divergence and its evolutionary parameters between single-copy genes in two species. In particular, PiXi models gene expression evolution as an Ornstein-Uhlenbeck process, and overlays this model with multi-layer neural network, random forest, and support vector machine architectures for making predictions. We show that PiXi has high power and accuracy in predicting gene expression divergence and its underlying parameters across a wide range of evolutionary scenarios, with the globally best performance achieved by a multi-layer neural network. Moreover, application of our best performing PiXi predictor to empirical data from single-copy genes residing at different loci in two species ofDrosophilareveals that expression divergence occurs in approximately 20% of these positionally relocated genes and is driven by a combination of neutral and selective forces. Further analysis shows that several of these genes are involved in the electron transport chain of the mitochondrial membrane, suggesting that new chromatin environments may impact energy production inDrosophila. Thus, by providing a toolkit for predicting expression divergence and its evolutionary parameters between single-copy genes in two species, PiXi can shed light on the origins of novel phenotypes across diverse biological processes and study systems.
Genetic score omics regression and multi-trait meta-analysis detect widespread cis-regulatory effects shaping bovine complex traits
Authors: Xiang Ruidong , Fang Lingzhao , Liu Shuli , Liu George E. , Tenesa Albert , Gao Yahui ,   CattleGTEx Consortium, Mason Brett A , Chamberlain Amanda J. , Goddard Michael E. 
Published: July 2022

AbstractTo complete the genome-to-phenome map, transcriptome-wide association studies (TWAS) are performed to correlate genetically predicted gene expression with observed phenotypic measurements. However, the relatively small training population assayed with gene expression could limit the accuracy of TWAS. We propose Genetic Score Omics Regression (GSOR) correlating observed gene expression with genetically predicted phenotype, i.e., genetic score. The score, calculated using variants near genes with assayed expression, provides a powerful association test between cis-effects on gene expression and the trait. In simulated and real data, GSOR outperforms TWAS in detecting causal/informative genes. Applying GSOR to transcriptomes of 16 tissue (N∼5000) and 37 traits in ∼120,000 cattle, multi-trait meta-analyses of omics-associations (MTAO) found that, on average, each significant gene expression and splicing mediates cis-genetic effects on 8∼10 traits. Supported by Mendelian Randomisation, MTAO prioritised genes/splicing show increased evolutionary constraints. Many newly discovered genes/splicing regions underlie previously thought single-gene loci to influence multiple traits.
Molecular characterization of the intact muscle spindle using a multi-omics approach
Authors: Bornstein Bavat , Heinemann-Yerushalmi Lia , Krief Sharon , Adler Ruth , Dassa Bareket , Leshkowitz Dena , Kim Minchul , Bewick Guy , Banks Robert W. , Zelzer Elazar 
Published: July 2022

ABSTRACTThe proprioceptive system is essential for the control of coordinated movement, posture and skeletal integrity. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. Despite its importance, the molecular composition of the muscle spindle is largely unknown. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development. Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease.
Principal and Independent Genomic Components of Brain Structure and Function
Authors: Oblong Lennart M. , Soheili-Nezhad Sourena , Trevisan Nicolò , Shi Yingjie , Beckmann Christian F. , Sprooten Emma 
Published: July 2022

AbstractIntroductionThe highly polygenic and pleiotropic nature of behavioural traits, psychiatric disorders, and structural and functional brain phenotypes complicate mechanistic interpretation of related genome-wide association study (GWAS) signals, such that the underlying causal biological processes remain obscure. We propose the novel method of genomic principal and independent component analysis (PCA, ICA) to decompose a large set of univariate GWAS statistics of multimodal brain traits into more interpretable latent genomic components. Here we introduce this new method and evaluate its various analytic parameters and reproducibility across independent samples.MethodsTwo releases of GWAS summary statistics from the UK biobank (UKB), with 11,086 and 22,138 participants respectively, were retrieved from the Oxford BIG-40 server. GWAS summary statistics were clumped resulting in n=165,364 single nucleotide polymorphisms (SNP) and m=2,240 imaging derived phenotypes (IDPs). Both genome-wide beta-values and their corresponding, standard-error scaled z-values were decomposed using multivariate exploratory linear optimised decomposition into independent components (MELODIC). We evaluated variance explained at multiple dimensions up to 200. We tested the reproducibility of output of dimensions 5, 10, 25, and 50 by computing Pearson’s correlation between component loadings, and Fisher Exact tests on overlap of the top SNP loadings across samples. Reproducibility statistics of the original raw and z-transformed univariate GWAS served as benchmarks. We also inspected the clustering of genomic components across neuroimaging modalities using t-SNE.ResultsThe first five PCs derived from z-transformed GWAS captured 31.9% of the variance across SNP effect sizes, while 200 PCs increased the variance explained to 79.6%. Reproducibility of 10-dimensional PCs and ICs showed the best balance between model complexity and robustness, and variance explained (PCs: |rz-max|=0.33, |rraw-max|=0.30; ICs: |rz-max|=0.23, |rraw-max|=0.19), with decreasing model stability and reproducibility at higher dimensions. Both genomic PC and IC reproducibilities improved substantially relative to mean univariate GWAS reproducibility up to a dimension of 10. Genomic components clustered along neuroimaging modalities.ConclusionOur results indicate that these novel methods of genomic ICA and PCA decompose genetic effects on IDPs from raw GWAS statistics with high reproducibility by taking advantage of the inherent pleiotropic patterns. These findings encourage further applications of genomic ICA and PCA as fully data-driven methods to effectively reduce the dimensionality, enhance the signal to noise ratio, and improve interpretability of high-dimensional multi-trait genome-wide analyses.
Audiovisual Integration in the Human Brain: A Coordinate-based Meta-analysis
Authors: Gao Chuanji , Green Jessica J. , Yang Xuan , Oh Sewon , Kim Jongwan , Shinkareva Svetlana V. 
Published: July 2022

AbstractPeople can seamlessly integrate a vast array of information from what we see and hear in the noisy and uncertain world. However, the neural underpinnings of audiovisual integration continue to be the topic of debate. Using strict inclusion criteria, we performed activation likelihood estimation meta-analysis on 121 neuroimaging experiments with a total of 2,092 participants. We found that audiovisual integration is linked with the coexistence of multiple integration sites including early cortical, subcortical, and higher association areas. Although activity was consistently found within the superior temporal cortex, different portions of this cortical region were identified depending on the analytical contrast used, complexity of the stimuli, and modality within which attention was directed. The context-dependent neural activity related to audiovisual integration suggests a flexible rather than fixed neural pathway for audiovisual integration. Together, our findings highlight a flexible multiple pathways model for audiovisual integration, with superior temporal cortex as the central node in these neural assemblies.
Mental health of pregnant women during the SARS-CoV-2 pandemic in France: evolution of self-perceived psychological state during the first lockdown, and anxiety frequency two months after the lockdown ended
Authors: Doncarli Alexandra , Araujo-Chaveron Lucia , Crenn-Hebert Catherine , Vacheron Marie-Noëlle , Léon Christophe , Khireddine Imane , Chin Francis , Benachi Alexandra , Tebeka Sarah , Regnault Nolwenn 
Published: July 2022

AbstractPrevious pandemics and related lockdowns have had a deleterious impact on pregnant women’s mental health. We studied the impact of the SARS-CoV-2/Covid-19 pandemic and France’s first lockdown on pregnant women’s mental health.A cross-sectional study was conducted in July 2020 using a web-questionnaire completed by 500 adult women who were pregnant during the first lockdown in France (March-May 2020). Questions focused on their self-perceived psychological state and affects they felt before and during the lockdown and anxiety symptomatology (HAD) two months after it ended. A robust variance Poisson regression model was used to estimate adjusted prevalence ratios (aPR) for anxiety and self-perceived psychological state evolution.One in five respondents (21.1%) reported psychological deterioration during lockdown. Associated determinants were: i) little or no social support (self-perceived) (aRP=1.77, 95%CI[1.18-2.66]), ii) increased workload (1.65, [1.02-2.66]), and iii) poor/moderate knowledge about SARS-CoV-2 transmission (1.60, [1.09-2.35]). Seven percent of women reporting psychological deterioration had access to professional psychological support during lockdown, while 19% did not despite wanting it. Women reported heightened powerlessness (60.3%), frustration (64%) and fear (59.2%) during lockdown.One in seven respondents (14.2%, 95%CI[10.9-18.2]) had anxiety symptoms. Determinants associated: i) at least one pregnancy-related pathology (aPR=1.82, 95%CI[1.15-2.88]), ii) overweightness or obesity (1.61, [1.07-2.43]), iii) one child under the age of six years in the household during the lockdown (3.26, [1.24-8.53]), iv) little or no social support (self-perceived) during the lockdown (1.66, [1.07-2.58]), v) friend or relatives diagnosed with Covid-19 or with symptoms of the disease (1.66; [1.06-2.60]), vi) no access to medication for psychological distress (2.86, [1.74-4.71]), and vii) unsuccessfully seeking exchanges with healthcare professionals about their pregnancy during the pandemic (1.66, [1.08-2.55]).Our results can guide prevention and support policies for pregnant women during pandemics, current or future, with or without lockdowns. Preventing perinatal mental health problems is essential to ensure a supportive environment for the child’s development.
Variation in maternal mortality in Sidama Regional State, southern Ethiopia: A population based cross sectional household survey
Authors: Kea Aschenaki Zerihun , Lindtjorn Bernt , Gebretsadik Achamyelesh , Hinderaker Sven Gudmund 
Published: July 2022

AbstractIntroductionMaternal mortality studies conducted at national level do not provide information needed for planning and monitoring health programs at lower administrative levels. The aim of this study was to measure maternal mortality, identify risk factors and district level variations in Sidama Regional State, southern Ethiopia.MethodsA cross sectional population-based survey was carried in households where a woman reported pregnancy and birth outcomes in the past five year. The study was conducted in the Sidama Regional State, southern Ethiopia, from July 2019 to May 2020. Multi-stage cluster sampling technique was employed. The outcome variable of the study was maternal mortality. Complex sample logistic regression analysis was applied to assess variables independently associated with maternal mortality.ResultsWe registered 10602 live births (LB) and 48 maternal deaths yielding the overall maternal mortality ratio (MMR) of 419; 95% CI: 260-577 per 100,000 LB. Aroresa districts had the highest MMR with 1142 (95% CI: 693-1591) per 100,000 LB. Leading causes of death were haemorrhage 21 (41%) and eclampsia 10 (27%). Thirty (59%) mothers died during labour or with 24 hours after delivery, 25 (47%) died at home and 17 (38%) at health facility. Mothers who did not have formal education had higher risk of maternal death (AOR: 4.3; 95% CI: 2.0 – 9.2). The risk of maternal death was higher in districts with low midwife to population ratio (AOR: 3.0; 95% CI: 1.2-7.9).ConclusionThe high maternal mortality with district level variations in Sidama region highlights the importance of improving obstetric care and employing targeted interventions in areas with high mortality rates. Due attention should be given to improving access to female education. Additional midwives has to be trained and deployed to improve maternal health services and consequently save the life of mothers.
mergem: merging and comparing genome-scale metabolic models using universal identifiers
Authors: Hari Archana , Lobo Daniel 
Published: July 2022

AbstractNumerous methods exist to produce and refine genome-scale metabolic models. However, due to the use of incompatible identifier systems for metabolites and reactions, computing and visualizing the metabolic differences and similarities of such models is a current challenge. Furthermore, there is a lack of automated tools that can combine the strengths of multiple reconstruction pipelines into a curated single comprehensive model by merging different drafts, which possibly use incompatible namespaces. Here we presentmergem, a novel method to compare and merge two or more metabolic models. Using a universal metabolic identifier mapping system constructed from multiple metabolic databases,mergemrobustly can compare models from different pipelines and merge their common elements.mergemis implemented as a command line tool, a Python package, and on the web-application Fluxer, which allows simulating and visually comparing multiple models with different interactive flux graphs. The ability to merge and compare diverse genome scale metabolic models can facilitate the curation of comprehensive reconstructions and the discovery of unique and common metabolic features among different organisms.
Vitamin C is an efficient natural product for prevention of SARS-CoV-2 infection by targeting ACE2 in both cell and in vivo mouse models
Authors: Zuo Yibo , Zheng Zhijin , Huang Yingkang , He Jiuyi , Zang Lichao , Ren Tengfei , Cao Xinhua , Miao Ying , Yuan Yukang , Liu Yanli , Ma Feng , Tian Sheng , Dai Jianfeng , Ding Qiang , Zheng Hui 
Published: July 2022

SUMMARYACE2 is a major receptor for cell entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2’s binding, how to efficiently and flexibly control ACE2 levels for prevention of SARS-CoV-2 infection has not been explored. Here, we revealed Vitamin C (VitC) administration as an effective strategy to prevent SARS-CoV-2 infection. VitC reduced ACE2 protein levels in a dose-dependent manner, while partial reduction of ACE2 can greatly restrict SARS-CoV-2 infection. Further studies uncovered that USP50 is a crucial regulator of ACE2 protein levels, and VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination at Lys788 and degradation of ACE2, without disrupting ACE2 transcriptional expression. Importantly, VitC administration reduced host ACE2 and largely blocked SARS-CoV-2 infection in mice. This study identified anin vivoACE2 balance controlled by both USP50 and an essential nutrient VitC, and revealed a critical role and application of VitC in daily protection from SARS-CoV-2 infection.HighlightsVitC reduces ACE2 protein levels in a dose-dependent mannerVitC and USP50 regulate K48-linked ubiquitination at Lys788 of ACE2VitC blocks the interaction between USP50 and ACE2VitC administration lowers host ACE2 and prevents SARS-CoV-2 infectionin vivoAbstract FigureThe deubiquitinase USP50 controls ACE2 protein stability and levels, while Vitamin C blocks the USP50-ACE2 interaction and therefore results in ACE2 degradation, offering a flexible and efficient approach to protection of the host from SARS-CoV-2 infection.
The SPARC complex defines RNAPII promoters in Trypanosoma brucei
Authors: Staneva Desislava P. , Bresson Stefan , Auchynnikava Tatsiana , Spanos Christos , Rappsilber Juri , Jeyaprakash A. Arockia , Tollervey David , Matthews Keith R. , Allshire Robin C. 
Published: July 2022

ABSTRACTKinetoplastids are a highly divergent lineage of eukaryotes with unusual mechanisms for regulating gene expression. We previously surveyed 65 putative chromatin factors in the kinetoplastid Trypanosoma brucei. Our analyses revealed that the predicted histone methyltransferase SET27 and the Chromodomain protein CRD1 are tightly concentrated at RNAPII transcription start regions (TSRs). Here we report that SET27 and CRD1, together with four previously uncharacterized constituents, form the SET27 promoter-associated regulatory complex (SPARC), which is specifically enriched at TSRs. SET27 loss leads to aberrant RNAPII recruitment to promoter sites, accumulation of polyadenylated transcripts upstream of normal transcription start sites, and conversion of some normally unidirectional promoters to bidirectional promoters. Transcriptome analysis in the absence of SET27 revealed upregulated mRNA expression in the vicinity of SPARC peaks within the main body of chromosomes in addition to derepression of genes encoding variant surface glycoproteins (VSGs) located in subtelomeric regions. These analyses uncover a novel chromatin-associated complex required to establish accurate promoter position and directionality.
Fate Bias and Transcriptional Memory of human B cells
Authors: Swift Michael , Horns Felix , Quake Stephen R. 
Published: July 2022

AbstractLineage tracking offers a direct approach to study cell fate determination. In this work we combined single cell transcriptomics and lineage tracing to better understand fate-choice in human B cells. Using the antibody sequence to trace cell lineage during in vitro differentiation, we identified intrinsic proliferative and cell fate biases of B cell subtypes. Clonal analysis revealed that IgM memory B cells were more proliferative than any other B cell subtype, and that cells from the same clone had highly concordant fates. We found that transcriptional memory within clones varies across genes, with strongest persistence in genes related to cell fate determination. Similar persistent transcriptional programs were observed in human plasma cells from bone marrow, suggesting that these programs maintain long-term cell fate in vivo. These results show that cell-intrinsic fate bias influences human B cell differentiation and reveal molecular programs underpinning cell fate determination in B cells.
A zebrafish model of COVID-19-associated cytokine storm syndrome reveals that the Spike protein signals via TLR2
Authors: Tyrkalska Sylwia D. , Martínez-López Alicia , Pedoto Annamaria , Candel Sergio , Cayuela María L. , Mulero Victoriano 
Published: July 2022

AbstractUnderstanding the mechanism of virulence of SARS-CoV-2 and host innate immune responses are essential to develop novel therapies. One of the most studied defense mechanisms against invading pathogens, including viruses, are Toll-like receptors (TLRs). Among them, TLR3, TLR7, TLR8 and TLR9 detect different forms of viral nucleic acids in endosomal compartments, whereas TLR2 and TLR4 recognize viral structural and nonstructural proteins outside the cell. Although many different TLRs have been shown to be involved in SARS-CoV-2 infection and detection of different structural proteins, most studies have been performed in vitro and the results obtained are rather contradictory. In this study, we report using the unique advantages of the zebrafish model for in vivo imaging and gene editing that the S1 domain of the Spike protein from the Wuhan strain (S1WT) induced hyperinflammation in zebrafish larvae via a Tlr2/Myd88 signaling pathway and independently of interleukin-1β production. In addition, S1WT also triggered emergency myelopoiesis, but in this case through a Tlr2/Myd88-independent signaling pathway. These results shed light on the mechanisms involved in the COVID-19-associated cytokine storm syndrome.