bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 excess death rate in Eastern European countries associated with weaker regulation implementation and lower vaccination coverage
Authors: Ylli Alban , Burazeri Genc , Wu Yan Yan , Sentell Tetine 
Published: February 2022

AbstractAimThe objective of this analysis was to assess the association of excess COVID-19 mortality with regulation enforcement and vaccination rate in selected countries.MethodsThis analysis included 50 countries pertinent to the WHO European Region, in addition to USA and Canada. Excess mortality and vaccination data were retrieved from “Our World In Data” database, while regulation implementation was measured from a well-respected, standardized measure. Outpatient visits were also included in the analysis. Multiple linear regression was used to assess the independent association between excess mortality and each covariate.ResultsExcess mortality increased by 4.1/100 000 for every percent decrease in vaccination rate and with 6/100 000 for every decreased unit in the regulatory implementation score a country achieved in the Rule of Law Index.ConclusionDegree of regulation enforcement, likely including public health measure enforcement, may be an important factor in controlling COVID-19’s deleterious health impacts.
Inflammatory monocytes promote pyogranuloma formation to counteract Yersinia blockade of host defense
Authors: Sorobetea Daniel , Matsuda Rina , Peterson Stefan T. , Grayczyk James P. , Rao Indira , Krespan Elise , Lanza Matthew , Assenmacher Charles-Antoine , Beiting Daniel , Radaelli Enrico , Brodsky Igor 
Published: February 2022

AbstractGranulomas are organized immune cell aggregates that form in response to chronic infection or antigen persistence. Yersinia pseudotuberculosis (Yp) blocks innate inflammatory signaling and phagocytosis, inducing formation of neutrophil-rich pyogranulomas within lymphoid tissues. Here, we uncover that Yp triggers pyogranuloma formation within the murine intestinal mucosa, a site not known to contain such structures. Mice lacking circulating monocytes fail to form defined pyogranulomas, have defects in neutrophil activation, and succumb to Yp infection. Yersinia lacking the virulence factors that block phagocytosis did not induce pyogranulomas, indicating that intestinal pyogranulomas form in response to Yp disruption of phagocytosis. Notably, mutation of a single anti-phagocytic virulence factor, YopH, restored pyogranuloma formation and control of Yp infection in monocyte-deficient mice, demonstrating that monocytes override YopH-dependent blockade of innate immune defense. This work reveals an unappreciated site of Yersinia intestinal invasion, and defines host and pathogen drivers of intestinal granuloma formation.
Designing a novel monitoring approach for the effects of space travel on astronauts’ health
Authors: Sakharkar Anurag , Yang Jian 
Published: February 2022

AbstractSpace exploration and extraterrestrial civilization have fascinated humankind since the earliest days of human history. However, it was only until last century that humankind finally began taking significant steps towards these goals by sending astronauts into space, landing on the moon, and building the International Space Station. However, space voyage is very challenging and dangerous, and astronauts are under constant space radiation and microgravity. It has been shown that astronauts are at a high risk of developing a broad range of diseases/disorders. Thus, it is critical to develop a rapid and effective assay to monitor astronauts’ health in space. In this study, gene expression and correlation patterns were analyzed for 10 astronauts (8 male and 2 female) using the publicly available microarray dataset E-GEOD-74708. We identified 218 differentially expressed genes between In-flight and Pre-flight and noticed that space travel decreased genome regulation and gene correlations across the entire genome, as well as individual signaling pathways. Furthermore, we rationally designed a rapid assay of 32 genes which could be used to monitor astronauts’ health during space travel. Further studies, including microgravity experiments, are warranted to optimize and validate the proposed assay.
Validating saliva as a biological sample for cost-effective, rapid and routine screening for SARS-CoV-2
Authors: Ansil B.R. , George Carolin Elizabeth , Chandrasingh Sindhulina , Viswanathan Ashwin , Thattai Mukund , Raghu Padinjat , Devadiga Santhosha , Harikumar Arun Geetha , Harsha Pulleri Kandi , Nair Indu , Ramakrishnan Uma , Mayor Satyajit 
Published: February 2022

AbstractPurposeCompared to nasopharyngeal/oropharyngeal swabs, non-invasive saliva samples have enormous potential for scalability and routine population screening of SARS-CoV-2. In this study, we are investigating the efficacy of saliva samples relative to nasopharyngeal/oropharyngeal swabs for use as a direct source for the RT-PCR based SARS-CoV-2 detection.MethodsPaired nasopharyngeal/oropharyngeal swabs and saliva samples were collected from suspected positive SARS-CoV-2 patients and tested using RT-PCR. Generalised linear models were used to investigate factors that explain result agreement. Further, we used simulations to evaluate the effectiveness of saliva-based screening in restricting the spread of infection in a large campus such as an educational institution.ResultsWe observed 75.4% overall result agreement. Prospective positive samples stored for three or more days showed a drastic reduction in the probability of result agreement. We observed 83% result agreement and 74.5% test sensitivity in samples processed and tested within two days of collection. Our simulations suggest that a test with 75% sensitivity, but high daily capacity can be very effective in limiting the size of infection clusters in a workspace. Guided by these results, we successfully implemented a saliva-based screening in the Bangalore Life Sciences Cluster (BLiSC) campus.ConclusionThese results suggest that saliva may be a viable sample source for SARS-CoV-2 surveillance if samples are processed immediately. We strongly recommend the implementation of saliva-based screening strategies for large workplaces and in schools, as well as for population-level screening and routine surveillance as we learn to live with the SARS-CoV-2 virus.
Incidence and associated factors of elderly mortality following hip fracture in Brazil: a systematic review and meta-analysis
Authors: Peterle Viviane Cristina Uliana , Garbi Novaes Maria Rita Carvalho , Bezerra Junior Paulo Emiliano , Gomides Reis Ana Paula Monteiro , Geber Júnior João Carlos , de Souza Amanda Cristina , Alves Amanda Ribeiro , Silva de Albuquerque Natalia Mariana Diogenes , Mosquéra Júlia Milhomem , Peixoto Henry Maia 
Published: February 2022

AbstractIntroductionHip fractures are an important health problem worldwide, and several factors are associated with the mortality. This study aimed to investigate the factors associated with hip fractures in the elderly, based on studies on the population residing in Brazil, and the relationship of fractures with mortality.MethodProspective and retrospective primary observational studies including hospitalized men and/or women aged 60 or older presenting hip fracture due to bone fragility were selected on the Databases. Independent researchers conducted the study selection process and data extraction. A meta-analysis was performed to determine the hospital mortality rate at 90 days, six months, and one year. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the included studies, and the meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).ResultTwenty-five studies totalizing 3,949 patients were included in the systematic review. The population was mainly composed of women (2,680/67.86%). Most patients were in the age group of 70 to 80 years old. Meta-analysis findings: 1) hospital mortality (19 studies, n = 3,175), 10.22% (95% CI 7.27–14.17%; I2 88%); 2) 90-day mortality (3 studies, n = 543), 9.74% (95% CI 3.44–24.62%; I2 90%); 3) six-month mortality (3 studies, n = 205), 24.78% (95% CI 17.07–34.51%; I2 51%); 4) one-year mortality (13 studies, n = 2,790), 21.88% (95% CI 17.5–26.99%; I2 88%). The factors most related to mortality in the studies were: 1) demographic: Older age, male sex; 2) Attributed to clinical conditions: high scoring in preoperative risk scores, comorbidities, neurological/cognitive disorders, functional status; and 3) hospital factors: preoperative period and infections.ConclusionThis review identified variables, including functional status and cognitive changes, related to hip fracture mortality. Knowing these predictors allows for early intervention and planning to adapt health systems to the growing demands of the elderly population.
Ruminococcus bromii enables the growth of proximal Bacteroides thetaiotaomicron by releasing glucose during starch degradation
Authors: Rangarajan Aathmaja Anandhi , Chia Hannah E. , Azaldegui Christopher A. , Olszewski Monica H. , Koropatkin Nicole M. , Biteen Julie S. 
Published: February 2022

AbstractComplex carbohydrates shape the gut microbiota and the collective fermentation of resistant starch by gut microbes positively affects human health through enhanced butyrate production. The keystone species Ruminococcus bromii (Rb) is a specialist in degrading resistant starch; its degradation products are used by other bacteria including Bacteroides thetaiotaomicron (Bt). We analyzed the metabolic and spatial relationships between Rb and Bt during potato starch degradation and found that Bt utilizes glucose that is released from Rb upon degradation of resistant potato starch and soluble potato amylopectin. Additionally, we found that Rb produces a halo of glucose around it when grown on solid media containing potato amylopectin and that Bt cells deficient for growth on potato amylopectin (Δsus Bt) can grow within the halo. Furthermore, when these Δsus Bt cells grow within this glucose halo, they have an elongated cell morphology. This long-cell phenotype depends on the glucose concentration in the solid media: longer Bt cells are formed at higher glucose concentrations. Together, our results indicate that starch degradation by Rb cross-feeds other bacteria in the surrounding region by releasing glucose. Our results also elucidate the adaptive morphology of Bt cells under different nutrient and physiological conditions.Impact StatementDietary intake of complex carbohydrates including resistant starch benefits human health by supporting the growth of keystone species that increase the microbiome diversity via cross-feeding. For instance, Ruminococcus bromii (Rb) is a specialist in degrading resistant starch, and the byproducts of this degradation process are used by bacterial species. In this study, we show that Bacteroides thetaiotaomicron (Bt) cross-feeds on the glucose released during potato starch degradation by Rb. We also show that proximity to Rb cells that are releasing sugars is important for the growth of the cross-fed Bt in solid media. Additionally, we find a longer phenotype for Bt cells grown on solid media in high glucose conditions, indicating that, like other bacteria, human gut bacteria undergo significant nutrient-dependent morphological adaptations.
Machine learning-based approach KEVOLVE efficiently identifies SARS-CoV-2 variant-specific genomic signatures
Authors: Lebatteux Dylan , Soudeyns Hugo , Boucoiran Isabelle , Gantt Soren , Diallo Abdoulaye Baniré 
Published: February 2022

AbstractMachine learning was shown to be effective at identifying distinctive genomic signatures among viral sequences. These signatures are defined as pervasive motifs in the viral genome that allow discrimination between species or variants. In the context of SARS-CoV-2, the identification of these signatures can assist in taxonomic and phylogenetic studies, improve in the recognition and definition of emerging variants, and aid in the characterization of functional properties of polymorphic gene products. In this paper, we assess KEVOLVE, an approach based on a genetic algorithm with a machine-learning kernel, to identify multiple genomic signatures based on minimal sets ofk-mers. In a comparative study, in which we analyzed large SARS-CoV-2 genome dataset, KEVOLVE was more effective at identifying variant-discriminative signatures than several gold-standard statistical tools. Subsequently, these signatures were characterized using a new extension of KEVOLVE (KANALYZER) to highlight variations of the discriminative signatures among different classes of variants, their genomic location, and the mutations involved. The majority of identified signatures were associated with known mutations among the different variants, in terms of functional and pathological impact based on available literature. Here we showed that KEVOLVE is a robust machine learning approach to identify discriminative signatures among SARS-CoV-2 variants, which are frequently also biologically relevant, while bypassing multiple sequence alignments. The source code of the method and additional resources are available at:https://github.com/bioinfoUQAM/KEVOLVE.
Omicron BA.2 specifically evades broad sarbecovirus neutralizing antibodies
Authors: Cao Yunlong , Yisimayi Ayijiang , Jian Fanchong , Xiao Tianhe , Song Weiliang , Wang Jing , Du Shuo , Zhang Zhiying , Liu Pulan , Hao Xiaohua , Li Qianqian , Chen Xiaosu , Wang Lei , Wang Peng , An Ran , Wang Yao , Wang Jing , Yang Peng , Sun Haiyan , Zhao Lijuan , Zhang Wen , Zhao Dong , Zheng Jiang , Yu Lingling , Li Can , Zhang Na , Wang Rui , Niu Xiao , Yang Sijie , Song Xuetao , Zheng Linlin , Li Zhiqiang , Gu Qingqing , Shao Fei , Huang Weijin , Wang Youchun , Shen Zhongyang , Wang Xiangxi , Jin Ronghua , Xiao Junyu , Xie Xiaoliang Sunney 
Published: February 2022

AbstractOmicron sub-lineage BA.2 has rapidly surged globally, accounting for over 60% of recent SARS-CoV-2 infections. Newly acquired RBD mutations and high transmission advantage over BA.1 urge the investigation of BA.2’s immune evasion capability. Here, we show that BA.2 causes strong neutralization resistance, comparable to BA.1, in vaccinated individuals’ plasma. However, BA.2 displays more severe antibody evasion in BA.1 convalescents, and most prominently, in vaccinated SARS convalescents’ plasma, suggesting a substantial antigenicity difference between BA.2 and BA.1. To specify, we determined the escaping mutation profiles1,2 of 714 SARS-CoV-2 RBD neutralizing antibodies, including 241 broad sarbecovirus neutralizing antibodies isolated from SARS convalescents, and measured their neutralization efficacy against BA.1, BA.1.1, BA.2. Importantly, BA.2 specifically induces large-scale escape of BA.1/BA.1.1-effective broad sarbecovirus neutralizing antibodies via novel mutations T376A, D405N, and R408S. These sites were highly conserved across sarbecoviruses, suggesting that Omicron BA.2 arose from immune pressure selection instead of zoonotic spillover. Moreover, BA.2 reduces the efficacy of S309 (Sotrovimab)3,4 and broad sarbecovirus neutralizing antibodies targeting the similar epitope region, including BD55-5840. Structural comparisons of BD55-5840 in complexes with BA.1 and BA.2 spike suggest that BA.2 could hinder antibody binding through S371F-induced N343-glycan displacement. Intriguingly, the absence of G446S mutation in BA.2 enabled a proportion of 440-449 linear epitope targeting antibodies to retain neutralizing efficacy, including COV2-2130 (Cilgavimab)5. Together, we showed that BA.2 exhibits distinct antigenicity compared to BA.1 and provided a comprehensive profile of SARS-CoV-2 antibody escaping mutations. Our study offers critical insights into the humoral immune evading mechanism of current and future variants.
DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes
Authors: Mondal Sudipta , Kinatukara Priyadarshan , Singh Shubham , Shambhavi Sakshi , Patil Gajanan S. , Dubey Noopur , Singh Salam Herojeet , Pal Biswajit , Chandra Shekar P , Kamat Siddhesh S. , Sankaranarayanan Rajan 
Published: February 2022

AbstractChain-length specific subsets of diacylglycerol (DAG) lipids are proposed to regulate differential physiological responses ranging from signal transduction to modulation of the membrane properties. However, the mechanism or molecular players regulating the subsets of DAG species remains unknown. Here, we uncover the role of a conserved eukaryotic protein family, DISCO-interacting protein 2 (DIP2) as a homeostatic regulator of a chemically distinct subset of DAGs using yeast, fly and mouse models. Genetic and chemical screens along with lipidomics analysis in yeast reveal that DIP2 prevents the toxic accumulation of specific DAGs in the logarithmic growth phase, which otherwise leads to endoplasmic reticulum stress. We also show that the fatty acyl-AMP ligase-like domains of DIP2 are essential for the redirection of the flux of DAG subspecies to storage lipid, triacylglycerols. Such modulation of selective DAG abundance by DIP2 is found to be crucial for optimal vacuole-membrane fusion and consequently osmoadaptation in yeast. Thus, the study illuminates an unprecedented DAG metabolism route and provides new insights on how cell fine-tunes DAG subspecies for cellular homeostasis and environmental adaptation.
Atypical and distinct microtubule radial symmetries in the centriole and the axoneme ofLecudina tuzetae
Authors: Bezler Alexandra , Woglar Alexander , Schneider Fabian , Douma Friso , Bürgy Léo , Busso Coralie , Gönczy Pierre 
Published: February 2022

AbstractThe centriole is a minute cylindrical organelle present in a wide range of eukaryotic species. Most centrioles have a signature 9-fold radial symmetry of microtubules that is imparted onto the axoneme of the cilia and flagella they template, with 9 centriolar microtubule doublets growing into 9 axonemal microtubule doublets. There are exceptions to the 9-fold symmetrical arrangement of axonemal microtubules, with lower or higher fold symmetries in some species. In the few cases where this has been examined, such alterations in axonemal symmetries are grounded in likewise alterations in centriolar symmetries. Here, we examine the question of microtubule number continuity between centriole and axoneme in flagellated gametes of the gregarineLecudina tuzetae, which have been reported to exhibit a 6-fold radial symmetry of axonemal microtubules. We used time-lapse differential interference microscopy to identify the stage at which flagellated gametes are present. Thereafter, using electron microscopy and ultrastructure-expansion microscopy coupled to STimulated Emission Depletion (STED) super-resolution imaging, we uncover that a 6- or 5-fold radial symmetry in the axoneme is accompanied by an 8-fold radial symmetry in the centriole. We conclude that there can be plasticity in the transition between centriolar and axonemal microtubules.
Comparative assessment of quantification methods for tumor tissue phosphoproteomics
Authors: Zhang Yang , Dreyer Benjamin , Govorukhina Natalia , Heberle Alexander M. , Končarević Saša , Krisp Christoph , Opitz Christiane A. , Pfänder Pauline , Bischoff Rainer , Schlüter Hartmut , Kwiatkowski Marcel , Thedieck Kathrin , Horvatovich Peter L. 
Published: February 2022

AbstractWith increasing sensitivity and accuracy in mass spectrometry, the tumor phosphoproteome is getting into reach. However, the selection of quantitation techniques best-suited to the biomedical question and diagnostic requirements remains a trial and error decision as no study has directly compared their performance for tumor tissue phosphoproteomics. We compared label-free quantification (LFQ), spike-in-SILAC (stable isotope labeling by amino acids in cell culture) and TMT isobaric tandem mass tags technology for quantitative phosphosite profiling in tumor tissue. TMT offered the lowest accuracy and the highest precision and robustness towards different phosphosite abundances and matrices. Spike-in-SILAC offered the best compromise between these features but suffered from a low phosphosite coverage. LFQ offered the lowest precision but the highest number of identifications. Both spike-in-SILAC and LFQ presented susceptibility to matrix effects. Match between run (MBR)-based analysis enhanced the phosphosite coverage across technical replicates in LFQ and spike-in-SILAC but further reduced the precision and robustness of quantification. The choice of quantitative methodology is critical for both study design such as sample size in sample groups and quantified phosphosites, and comparison of published cancer phosphoproteomes. Using ovarian cancer tissue as an example, our study builds a resource for the design and analysis of quantitative phosphoproteomic studies in cancer research and diagnostics.
Imputation of 3D genome structure by genetic-epigenetic interaction modeling in mice
Authors: Kuffler Lauren , Skelly Daniel A. , Czechanski Anne , Fortin Haley J. , Munger Steven C. , Baker Christopher L. , Reinholdt Laura G. , Carter Gregory W. 
Published: February 2022

AbstractGene expression is known to be affected by interactions between local genetic variation and DNA accessibility, with the latter organized into three-dimensional chromatin structures.Analyses of these interactions has previously been limited, obscuring their regulatory context, and the extent to which they occur throughout the genome. Here we undertake a genome-scale analysis of these interactions in a genetically diverse population to systematically identify global genetic-epigenetic interaction, and reveal constraints imposed by chromatin structure. We establish the extent and structure of genotype-by-epigenotype interaction using embryonic stem cells derived from Diversity Outbred mice. This mouse population segregates millions of variants from eight inbred founders, enabling precision genetic mapping with extensive genotypic and phenotypic diversity. With 176 samples profiled for genotype, gene expression, and open chromatin, we used regression modeling to infer genetic-epigenetic interactions on a genome-wide scale. Our results demonstrate that statistical interactions between genetic variants and chromatin accessibility are common throughout the genome. We found that these interactions occur within the local area of the affected gene, and that this locality corresponds to topologically associated domains (TADs). The likelihood of interaction was most strongly defined by the three-dimensional (3D) domain structure rather than linear DNA sequence. We show that stable 3D genome structure is an effective tool to guide searches for regulatory elements and, conversely, that regulatory elements in genetically diverse populations provide a means to infer 3D genome structure. We confirmed this finding with CTCF ChIP-seq that revealed strain-specific binding in the inbred founder mice. In stem cells, open chromatin participating in the most significant regression models demonstrated an enrichment for developmental genes and the TAD-forming CTCF binding complex, providing an opportunity for statistical inference of shifting TAD boundaries operating during early development. These findings provide evidence that genetic and epigenetic factors operate within the context of three- dimensional chromatin structure.Graphical Abstract