bluuebunny/crossref_metadata_2025_split huggingface dataset:
RISK OF HOSPITALISATION WITH COVID-19 AMONG TEACHERS COMPARED TO HEALTHCARE WORKERS AND OTHER WORKING-AGE ADULTS. A NATIONWIDE CASE-CONTROL STUDY
Authors: Lynda Fenton , Ciara Gribben , David Caldwell , Sam Colville , Jen Bishop , Martin Reid , Jane White , Campbell Marion , Hutchinson S , Robertson C , Helen M Colhoun , Rachael Wood , Paul M McKeigue , David A McAllister 
Published: February 2021

AbstractObjectiveTo determine the risk of hospitalisation with COVID-19 and severe COVID-19 among teachers and their household members, overall and compared to healthcare workers and the general working-age population.DesignPopulation-based nested case-control study.SettingsScotland, March 2020 to January 2021. Before and after schools re-opened in early August 2020.ParticipantsAll cases of COVID-19 in Scotland in adults ages 21 to 65 (n = 83,817) and a random sample of controls matched on age, sex and general practice (n = 841,708).ExposureIndividuals identified as actively teaching in a Scottish school by the General Teaching Council for Scotland, and household members of such individuals identified via the Unique Property Reference Number.ComparatorIndividuals identified as healthcare workers in Scotland, their household members, and the remaining “general population” of working-age adults.Main outcomesThe primary outcome was hospitalisation with COVID-19 defined in anyone testing positive with COVID-19 in hospital, admitted to hospital within 28 days of a positive test, and/or diagnosed with COVID-19 on discharge from hospital. Severe COVID-19 was defined as individuals admitted to intensive care or dying within 28 days of a positive test or assigned COVID-19 as a cause of death.ResultsMost teachers were young (mean age 42), female (80%) and had no underlying conditions (84%). The cumulative incidence (risk) of hospitalisation with COVID-19 was below 1% for all of the working age adults. In the period after school re-opening, compared to the general population, in conditional logistic regression models adjusting for age, sex, general practice, deprivation, underlying conditions and number of adults in the household, the relative risk in teachers (among 18,479 cases and controls) for hospitalisation was rate ratio (RR) 0.97 (95%CI 0.72-1.29) and for severe COVID-19 was RR 0.27 (95%CI 0.09-0.77). Equivalent rate ratios for household members of teachers were 0.97 (95%CI 0.74-1.27) and 0.67 (95%CI 0.36-1.24), and for healthcare workers were 1.82 (95%CI 1.55-2.14) and 1.76 (95%CI 1.22-2.56), respectively.ConclusionCompared to working-age adults who are otherwise similar, teachers and their household members are not at increased risk of hospitalisation with COVID-19 and are at lower risk of severe COVID-19. These findings are broadly reassuring for adults engaged in face to face teaching.
Mendelian randomization analysis identified genes potentially pleiotropically associated with periodontitis
Authors: Wang Feng , Liu Di , Zhuang Yong , Feng Bowen , Lu Wenjin , Yang Jingyun , Zhuang Guanghui 
Published: February 2021

AbstractObjectiveTo prioritize genes that were pleiotropically or potentially causally associated with periodontitis.MethodsWe applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for periodontitis and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with periodontitis. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analysis were done for participants of European and East Asian ancestries, separately.ResultsWe identified multiple genes showing pleiotropic association with periodontitis in participants of European ancestry and participants of East Asian ancestry.PDCD2(corresponding probe: ILMN_1758915) was the top hit showing pleotropic association with periodontitis in participants of European ancestry, andBX093763(corresponding probe: ILMN_1899903) and AC104135.3 (corresponding probe: ENSG00000204792.2) were the top hits in participants of East Asian ancestry using CAGE eQTL data and GTEx eQTL data, respectively.ConclusionWe identified multiple genes that may be involved in the pathogenesis of periodontitis in participants of European ancestry and participants of East Asian ancestry. Our findings provided important leads to a better understanding of the mechanisms underlying periodontitis and revealed potential therapeutic targets for the effective treatment of periodontitis.
Emergence of an early SARS-CoV-2 epidemic in the United States
Authors: Zeller Mark , Gangavarapu Karthik , Anderson Catelyn , Smither Allison R. , Vanchiere John A. , Rose Rebecca , Snyder Daniel J. , Dudas Gytis , Watts Alexander , Matteson Nathaniel L. , Robles-Sikisaka Refugio , Marshall Maximilian , Feehan Amy K. , Sabino-Santos Gilberto , Bell-Kareem Antoinette R. , Hughes Laura D. , Alkuzweny Manar , Snarski Patricia , Garcia-Diaz Julia , Scott Rona S. , Melnik Lilia I. , Klitting Raphaëlle , McGraw Michelle , Belda-Ferre Pedro , DeHoff Peter , Sathe Shashank , Marotz Clarisse , Grubaugh Nathan , Nolan David J. , Drouin Arnaud C. , Genemaras Kaylynn J. , Chao Karissa , Topol Sarah , Spencer Emily , Nicholson Laura , Aigner Stefan , Yeo Gene W. , Farnaes Lauge , Hobbs Charlotte A. , Laurent Louise C. , Knight Rob , Hodcroft Emma B. , Khan Kamran , Fusco Dahlene N. , Cooper Vaughn S. , Lemey Phillipe , Gardner Lauren , Lamers Susanna L. , Kamil Jeremy P. , Garry Robert F. , Suchard Marc A. , Andersen Kristian G. 
Published: February 2021

AbstractThe emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the annual Mardi Gras festival, which went ahead without precautions. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large, crowded events may have accelerated early transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana initially had limited sequence diversity compared to other U.S. states, and that one successful introduction of SARS-CoV-2 led to almost all of the early SARS-CoV-2 transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras and that the festival dramatically accelerated transmission, eventually leading to secondary localized COVID-19 epidemics throughout the Southern U.S.. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate COVID-19 epidemics on a local and regional scale.
Lesion site and therapy time predict responses to a therapy for anomia after stroke: a prognostic model development study
Authors: Hope Thomas M.H. , Nardo Davide , Holland Rachel , Ondobaka Sasha , Akkad Haya , Price Cathy J. , Leff Alexander P. , Crinion Jenny 
Published: February 2021

AbstractBACKGROUNDStroke is a leading cause of disability, and language impairments (aphasia) after stroke are both common and particularly feared. Most stroke survivors with aphasia exhibit anomia (difficulties with naming common objects), but while many therapeutic interventions for anomia have been proposed, treatment effects are typically much larger in some patients than others. Here, we asked whether that variation might be more systematic, and even predictable, than previously thought.METHODS18 patients, each at least 6 months after left hemisphere stroke, engaged in a computerised treatment for their anomia over a 6 week period. Using only: (a) the patients’ initial accuracy when naming (to-be) trained items; (b) the hours of therapy that they devoted to the therapy; and (c) whole-brain lesion location data, derived from structural MRI; we developed Partial Least Squares regression models to predict the patients’ improvements on treated items, and tested them in cross-validation.RESULTSSomewhat surprisingly, the best model included only lesion location data and the hours of therapy undertaken. In cross-validation, this model significantly out-performed the null model, in which the prediction for each patient was simply the mean treatment effect of the group. This model also made promisingly accurate predictions in absolute terms: the correlation between empirical and predicted treatment response was 0.62 (95%CI: 0.27, 0.95).DISCUSSIONOur results indicate that individuals’ variation in response to anomia treatment are, at least somewhat, systematic and predictable, from the interaction between where and how much lesion damage they have suffered, and the time they devoted to the therapy.
Transsynaptic N-cadherin adhesion complexes control presynaptic vesicle and bulk endocytosis at physiological temperature
Authors: Dagar Sushma , Gottmann Kurt 
Published: February 2021

AbstractAt mammalian glutamatergic synapses, most basic elements of synaptic transmission have been shown to be modulated by specific transsynaptic adhesion complexes. However, although crucial for synapse homeostasis, a physiological regulation of synaptic vesicle endocytosis by adhesion molecules has not been firmly established. The homophilic adhesion protein N-cadherin is localized at the peri-active zone, where the highly temperature dependent endocytosis of vesicles occurs. Here, we demonstrate an important modulatory role of N-cadherin in endocytosis at near physiological temperature by synaptophysin-pHluorin imaging. Different modes of endocytosis including bulk endocytosis were dependent on N-cadherin expression and function. N-cadherin modulation was mediated by actin filaments, because actin polymerization rescued the knockout induced endocytosis defect. Using super-resolution imaging, we found a strong recruitment of N-cadherin to glutamatergic synapses upon massive vesicle release, which might in turn enhance vesicle endocytosis. This provides a novel, adhesion protein mediated mechanism for efficient coupling of exo- and endocytosis.
Network Propagation-based Prioritization of Long Tail Genes in 17 Cancer Types
Authors: Mohsen Hussein , Gunasekharan Vignesh , Qing Tao , Seay Montrell , Surovtseva Yulia , Negahban Sahand , Szallasi Zoltan , Pusztai Lajos , Gerstein Mark B. 
Published: February 2021

AbstractIntroductionThe diversity of genomic alterations in cancer pose challenges to fully understanding the etiologies of the disease. Recent interest in infrequent mutations, in genes that reside in the “long tail” of the mutational distribution, uncovered new genes with significant implication in cancer development. The study of these genes often requires integrative approaches with multiple types of biological data. Network propagation methods have demonstrated high efficacy in uncovering genomic patterns underlying cancer using biological interaction networks. Yet, the majority of these analyses have focused their assessment on detecting known cancer genes or identifying altered subnetworks. In this paper, we introduce a network propagation approach that entirely focuses on long tail genes with potential functional impact on cancer development.ResultsWe identify sets of often overlooked, rarely to moderately mutated genes whose biological interactions significantly propel their mutation-frequency-based rank upwards during propagation in 17 cancer types. We call these sets “upward mobility genes” (UMGs, 28-83 genes per cancer type) and hypothesize that their significant rank improvement indicates functional importance. We report new cancer-pathway associations based on UMGs that were not previously identified using driver genes alone, validate UMGs’ role in cancer cell survivalin vitro—alone and compared to other network methods—using extensive genome-wide RNAi and CRISPR data repositories, and further conductin vitrofunctional screenings resulting the validation of 8 previously unreported genes.ConclusionOur analysis extends the spectrum of cancer relevant genes and identifies novel potential therapeutic targets.
The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia
Authors: Cheung Wai W , Zheng Ronghao , Hao Sheng , Wang Zhen , Gonzalez Alex , Zhou Ping , Hoffman Hal M , Mak Robert H 
Published: February 2021

ABSTRACTCytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis inIl1β−/−/CKD,Il6−/−/CKD andTnfα−/−/CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized inIl1β−/−/CKD mice but were only partially rescued inIl6−/−/CKD andTnfα−/−/CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg.kg.day, IP) or saline for 6 weeks and compared with WT/sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.
Cell Type Hierarchy Reconstruction via Reconciliation of Multi-resolution Cluster Tree
Authors: Peng Minshi , Wamsley Brie , Elkins Andrew , Geschwind Daniel M , Wei Yuting , Roeder Kathryn 
Published: February 2021

AbstractA wealth of clustering algorithms are available for Single-cell RNA sequencing (scRNA-seq), but it remains challenging to compare and characterize the features across different scales of resolution. To resolve this challenge Multi-resolution Reconciled Tree (MRtree), builds a hierarchical tree structure based on multi-resolution partitions that is highly flexible and can be coupled with most scRNA-seq clustering algorithms. MRtree out-performs bottom-up or divisive hierarchical clustering approaches because it inherits the robustness and versatility of a flat clustering approach, while maintaining the hierarchical structure of cells. Application to fetal brain cells yields insight into subtypes of cells that can be reliably estimated.
High coverage whole genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios
Authors: Byrska-Bishop Marta , Evani Uday S. , Zhao Xuefang , Basile Anna O. , Abel Haley J. , Regier Allison A. , Corvelo André , Clarke Wayne E. , Musunuri Rajeeva , Nagulapalli Kshithija , Fairley Susan , Runnels Alexi , Winterkorn Lara , Lowy Ernesto ,   The Human Genome Structural Variation Consortium, Flicek Paul , Germer Soren , Brand Harrison , Hall Ira M. , Talkowski Michael E. , Narzisi Giuseppe , Zody Michael C. 
Published: February 2021

SUMMARYThe 1000 Genomes Project (1kGP) is the largest fully open resource of whole genome sequencing (WGS) data consented for public distribution of raw sequence data without access or use restrictions. The final release of the 1kGP included 2,504 unrelated samples from 26 populations and was based primarily on low coverage WGS. Here, we present a new,high coverage3,202-sample WGS 1kGP resource, sequenced to a targeted depth of 30X using the Illumina NovaSeq 6000 system, which now includes 602 complete trios. We performed SNV/INDEL calling against the GRCh38 reference using GATK’s HaplotypeCaller, and generated a comprehensive set of SVs by integrating multiple analytic methods through a sophisticated machine learning model. We make all the data generated as part of this project publicly available and we envision it to become the new de facto public resource for the worldwide genomics and genetics community.
Genome-wide Detection of Cytosine Methylations in Plant from Nanopore sequencing data using Deep Learning
Authors: Ni Peng , Huang Neng , Nie Fan , Zhang Jun , Zhang Zhi , Wu Bo , Bai Lu , Liu Wende , Xiao Chuan-Le , Luo Feng , Wang Jianxin 
Published: February 2021

AbstractMethylation states of DNA bases can be detected from native Nanopore reads directly. At present, there are many computational methods that can detect 5mCs in CpG contexts accurately by Nanopore sequencing. However, there is currently a lack of methods to detect 5mCs in non-CpG contexts. In this study, we propose a computational pipeline which can detect 5mC sites in both CpG and non-CpG contexts of plant genomes by using Nanopore sequencing. And we sequenced two model plants Arabidopsis thaliana (A. thaliana) and Oryza sativa (O. sativa) by using Nanopore sequencing and bisulfite sequencing. The results of our proposed pipeline in the two plants achieved high correlations with bisulfite sequencing: above 0.98, 0.96, 0.85 for CpG, CHG, and CHH (H indicates A, C or T) motif, respectively. Our proposed pipeline also achieved high performance on Brassica nigra (B. nigra). Experiments also showed that our proposed pipeline can achieve high performance even with low coverage of reads. Moreover, by using Nanopore sequencing, our proposed pipeline is capable of profiling methylation of more cytosines than bisulfite sequencing.
Paip2 associates with PABPC1 on mRNA, and may facilitate PABPC1 dissociation from mRNA upon deadenylation
Authors: Xie Jingwei , Wei Xiaoyu , Kozlov Guennadi , Chen Yu , Menade Marie 
Published: February 2021

AbstractPoly(A) binding protein cytoplasmic 1 (PABPC1) is an essential translational initiation factor. PABPC1 recognizes proteins through conserved PABPC1-interacting motifs 1 and 2 (PAM1 and PAM2). PABPC1-interacting protein-2 (Paip2) interacts with PABPC1 and modulates its activities. Here, we report that the formation of Paip2/PABPC1 complex protects it from proteasome independent degradation. We also show that PAM2 is critical for Paip2/PABPC1 interactionin vivo, in agreement with the observation that Paip2 requires PAM2 to interact with PABPC1 on mRNA. Lastly, we propose a role for Paip2 in displacing PABPC1 at the final stage of mRNA deadenylation when the poly(A) tail is partly degraded.
Genome wide mapping of DNA lesions by Repair Assisted Damage Detection sequencing – RADD-Seq
Authors: Gilat Noa , Fridman Dena , Sharim Hila , Margalit Sapir , Gassman Natalie R. , Michaeli Yael , Ebenstein Yuval 
Published: February 2021

AbstractMapping DNA damage and its repair has immense potential in understanding environmental exposures, their genotoxicity, and their impact on human health. Monitoring changes in genomic stability also aids in the diagnosis of numerous DNA-related diseases, like cancer, and assists in monitoring their progression and prognosis. However, genome-wide maps of DNA damage distribution are challenging to produce. Here we describe the localization of DNA damage and repair loci by Repair Assisted Damage Detection sequencing – RADD-Seq. Based on the enrichment of damage lesions coupled with a pull-down assay and followed by next generation sequencing, this method is easy to perform and can produce compelling results with minimal coverage. RADD-seq enables the localization of both DNA damage and repair sites for a wide range of single-strand damage types. Using this technique, we created a genome-wide map of oxidative DNA damage loci before and after repair. Oxidative lesions were heterogeneously distributed along the human genome, with less damage occurring in tight chromatin regions. Furthermore, we showed repair is prioritized for highly expressed, essential genes and in open chromatin regions. RADD-seq sheds light on cellular repair mechanisms and capable of identifying genomic hotspots prone to mutation.
Initial real world evidence for lower viral load of individuals who have been vaccinated by BNT162b2
Authors: Petter Ella , Mor Orna , Zuckerman Neta , Oz-Levi Danit , Younger Asaf , Aran Dvir , Erlich Yaniv 
Published: February 2021

AbstractOne of the key questions regarding COVID19 vaccines is whether they can reduce viral shedding. To date, Israel vaccinated substantial parts of the adult population, which enables extracting real world signals. The vaccination rollout started on Dec 20th 2020, utilized mainly the BNT162b2 vaccine, and focused on individuals who are 60 years or older. By now, more than 75% of the individuals of this age group have been at least 14 days after the first dose, compared to 25% of the individuals between ages 40-60 years old. Here, we traced the Ct value distribution of 16,297 positive qPCR tests in our lab between Dec 1st to Jan 31st that came from these two age groups. As we do not have access to the vaccine status of each test, our hypothesis was that if vaccines reduce viral load, we should see a difference in the Ct values between these two age groups in late January but not before. Consistent with this hypothesis, until Jan 15th, we did not find any statistically significant differences in the average Ct value between the groups. In stark contrast, our results in the last two weeks of January show a significant weakening in the average Ct value of 60+ individuals to the 40-60 group. To further corroborate these results, we also used a series nested linear models to explain the Ct values of the positive tests. This analysis favored a model that included an interaction between age and the late January time period, consistent with the effect of vaccination. We then used demographic data and the daily vaccination rates to estimate the effect of vaccination on viral load reduction. Our estimate suggests that vaccination reduces the viral load by 1.6x to 20x in individuals who are positive for SARS-CoV-2. This estimate might improve after more individuals receive the second dose. Taken together, our findings indicate vaccination is not only important for individual’s protection but can reduce transmission.