bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of IgG antibodies to SARS-CoV-2 in Wuhan – implications for the ability to produce long-lasting protective antibodies against SARS-CoV-2
Authors: Liu Tao , Wu Sanyun , Tao Huangheng , Zeng Guang , Zhou Fuling , Guo Fangjian , Wang Xinghuan 
Published: June 2020

AbstractBackgroundIt is to be determined whether people infected with SARS-CoV-2 will develop long-term immunity against SARS-CoV-2 and retain long-lasting protective antibodies after the infection is resolved. This study was to explore to explore the outcomes of IgG antibodies to SARS-CoV-2 in four groups of individuals in Wuhan, China.MethodsWe included the following four groups of individuals who received both COVID-19 IgM/IgG tests and RT-PCR tests for SARS-CoV-2 from February 29, 2020 to April 29, 2020: 1470 hospitalized patients with COVID-19 from Leishenshan Hospital, Zhongnan Hospital of Wuhan University, and Wuhan No. 7 Hospital, 3832 healthcare providers without COVID-19 diagnosis, 19555 general workers, and 1616 other patients to be admitted to the hospital (N=26473). COVID-19 patients who received IgM/IgG tests <21 days after symptom onset were excluded.ResultsIgG prevalence was 89.8% (95% CI 88.2-91.3%) in COVID-19 patients, 4.0% (95% CI 3.4-4.7%) in healthcare providers, 4.6 (95% CI 4.3-4.9 %) in general workers, and 1.0% in other patients (p all <0.001 for comparisons with COVID-19 patients). IgG prevalence increased significantly by age among healthcare workers and general workers. Prevalence of IgM antibodies to SARS-CoV-2 was 31.4% in COVID-19 patients, 1.5% in healthcare providers, 1.3% in general workers, and 0.2% in other patients.ConclusionsVery few healthcare providers had IgG antibodies to SARS-CoV-2, though a significant proportion of them had been infected with the virus. After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.Primary Funding SourcesPart of the study was supported by National Key Research and Development Program of China (2020YFC0845500). The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors.Role of the Funder/SponsorThe sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication.Data and code availability statementData and analyses codes are available from the corresponding authors on request. All request for raw and analyzed data and materials will be reviewed by the corresponding authors to verify whether the request is subject to any intellectual property or confidentiality obligations. Access will be granted after a signed data access agreement is attained.
Double COVID-19 Confirmed Case Fatality Rate in Countries with High Elderly Female Vitamin D Deficiency Prevalence
Authors: Bäcker Alex , Mageswaran Myron 
Published: June 2020

AbstractA number of clues point to a possible role of vitamin D in fighting COVID-19: a reduction in case growth speed with solar zenith angle, higher fatality rate in black people, lower fatality rate in populations that spend more time outdoors. Yet a direct demonstration that vitamin D deficiency is associated with COVID-19 fatalities has remained elusive. We show here in a comparison of 32 countries that countries with high prevalence of vitamin D deficiency among elderly females show a confirmed case fatality rate twice as high as those with low prevalence. We then show that this effect cannot be explained by differences in life expectancy between countries. A mechanistic role for vitamin D in the severity of COVID-19 is proposed.One Sentence SummaryVitamin D deficiency among elderly females is associated with countrywide COVID-19 confirmed case fatality rates up to twice as high as those of countries with low vitamin D deficiency prevalence.
Associations of joint swelling, joint stiffness, and joint pain with physical activity in first-degree relatives of patients with rheumatoid arthritis
Authors: Hughes-Austin Jan M. , Ix Joachim H. , Ward Samuel R. , Weisman Michael H. , O’Dell James R. , Mikuls Ted R. , Buckner Jane H. , Gregersen Peter K. , Keating Richard M. , Demoruelle M. Kristen , Deane Kevin D. , Holers V. Michael , Norris Jill M. 
Published: June 2020

ABSTRACTBackgroundPhysical activity (PA) in pre-clinical rheumatoid arthritis (RA) is associated with lower RA risk and disease severity. Yet, PA in RA patients is less than in counterparts without RA, which can be attributed partly to symptoms of inflammatory arthritis. Therefore, we investigated whether joint swelling, stiffness, or pain were associated with PA in first-degree relatives (FDRs) of RA patients, a population at higher risk for future RA.MethodsWe evaluated associations of joint stiffness, joint swelling, and joint pain with PA time in 268 FDRs with ≥2 visits over an average 1.2 years. Clinicians confirmed joint swelling. Participants self-reported joint stiffness and/or pain. PA during a typical 24-hour day was quantified via questionnaire, weighted to reflect metabolic expenditure, where 24 hours was the minimum PA time. Linear mixed models evaluated associations between symptoms and change in PA over time, adjusting for age, sex, race, body mass index, smoking, and RA-related autoantibodies.ResultsAverage weighted PA time was 37±7 hours. In cross-sectional analysis, PA time was 1.3±0.9 hours higher in FDRs reporting joint pain (p=0.15); and 0.8±1.6 and 0.4±1 hours lower in FDRs with joint swelling (p=0.60) and stiffness (p=0.69), respectively. Longitudinally, adjusting for baseline PA time, baseline symptoms were not significantly associated with changes in PA time. However, on average over time, joint stiffness and pain were associated with lower PA time (pinteraction=0.0002, pinteraction=0.002), and joint swelling was associated with higher PA time (pinteraction<0.0001)ConclusionBaseline symptoms did not predict future PA time, but on average over time, joint symptoms influenced PA time.
A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy
Authors: Miao Xiaoniu , Luo Yi , Huang Xi , Lee Suki M. Y. , Yuan Zhijun , Tang Yongzhou , Chen Liandi , Wang Chao , Jiang Wenchao , Gao Wei , Song Xuedong , Yan Yao , Pang Tuling , Zou Yuefeng , Fu Weihui , Wan Liping , Gilbert-Jaramillo Javier , Knight Michael , Tan Tiong Kit , Rijal Pramila , Townsend Alain , Sun Joanne , Liu Xiaolin , James William , Tsun Andy , Xu Yingda 
Published: June 2020

AbstractIn the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provides a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain (NTD) of the viral S glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain (RBD) of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic virus infection in a standard assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.
Engineering of extracellular vesicles for display of protein biotherapeutics
Authors: Gupta Dhanu , Wiklander Oscar P.B , Görgens André , Conceição Mariana , Corso Giulia , Liang Xiuming , Seow Yiqi , Balsu Sriram , Felldin Ulrika , Bostancioglu Beklem , Fiona Lee Yi Xin , Hean Justin , Mäger Imre , Roberts Thomas C. , Gustafsson Manuela , Mohammad Dara K , Sork Helena , Bäcklund Alexandra , Edvard Smith C.I. , Wood Matthew J.A. , Vandenbroucke Roosmarijn , Nordin Joel Z. , Andaloussi Samir EL 
Published: June 2020

AbstractExtracellular vesicles (EVs) have recently emerged as a highly promising cell-free bio-therapeutics. While a range of engineering strategies have been developed to functionalize the EV surface, current approaches fail to address the limitations associated with endogenous surface display, pertaining to the heterogeneous display of commonly used EV-loading moieties among different EV subpopulations. Here we present a novel engineering platform to display multiple protein therapeutics simultaneously on the EV surface. As proof-of-concept, we screened multiple endogenous display strategies for decorating the EV surface with cytokine binding domains derived from tumor necrosis factor receptor 1 (TNFR1) and interleukin 6 signal transducer (IL6ST), which can act as decoys for the pro-inflammatory cytokines TNFα and IL6, respectively. Combining synthetic biology and systematic screening of loading moieties, resulted in a three-component system which increased the display and decoy activity of TNFR1 and IL6ST, respectively. Further, this system allowed for combinatorial functionalization of two different receptors on the same EV surface. These cytokine decoy EVs significantly ameliorated disease phenotypes in three different inflammatory mouse models for systemic inflammation, neuroinflammation, and intestinal inflammation. Importantly, significantly improvedin vitroandin vivoefficacy of these engineered EVs was observed when compared directly to clinically approved biologics targeting the IL6 and TNFα pathways.
Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis
Authors: Herrera Natalia G. , Morano Nicholas C. , Celikgil Alev , Georgiev George I. , Malonis Ryan J. , Lee James H. , Tong Karen , Vergnolle Olivia , Massimi Aldo B. , Yen Laura Y. , Noble Alex J. , Kopylov Mykhailo , Bonanno Jeffrey B. , Garrett-Thomson Sarah C. , Hayes David B. , Bortz Robert H. , Wirchnianski Ariel S. , Florez Catalina , Laudermilch Ethan , Haslwanter Denise , Fels J. Maximilian , Dieterle M. Eugenia , Jangra Rohit K. , Barnhill Jason , Mengotto Amanda , Kimmel Duncan , Daily Johanna P. , Pirofski Liise-anne , Chandran Kartik , Brenowitz Michael , Garforth Scott J. , Eng Edward T. , Lai Jonathan R. , Almo Steven C. 
Published: June 2020

ABSTRACTCoronavirus disease 2019 (COVID-19) is a global health crisis caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and there is a critical need to produce large quantities of high-quality SARS-CoV-2 Spike (S) protein for use in both clinical and basic science settings. To address this need, we have evaluated the expression and purification of two previously reported S protein constructs in Expi293F™and ExpiCHO-S™cells, two different cell lines selected for increased expression of secreted glycoproteins. We show that ExpiCHO-S™cells produce enhanced yields of both SARS-CoV-2 S proteins. Biochemical, biophysical, and structural (cryo-EM) characterization of the SARS-CoV-2 S proteins produced in both cell lines demonstrate that the reported purification strategy yields high quality S protein (non-aggregated, uniform material with appropriate biochemical and biophysical properties). Importantly, we show that multiple preparations of these two recombinant S proteins from either cell line exhibit identical behavior in two different serology assays. We also evaluate the specificity of S protein-mediated host cell binding by examining interactions with proposed binding partners in the human secretome. In addition, the antigenicity of these proteins is demonstrated by standard ELISAs, and in a flexible protein microarray format. Collectively, we establish an array of metrics for ensuring the production of high-quality S protein to support clinical, biological, biochemical, structural and mechanistic studies to combat the global pandemic caused by SARS-CoV-2.
The adaptive function of sexual reproduction: resampling the genotype pool
Authors: Hickey Donal A. , Golding G. Brian 
Published: June 2020

AbstractRecombination allows a finite population to resample the genotype pool, i.e., the universe of all possible genotypic combinations. This is important in populations that contain abundant genetic variation because, in such populations, the number of potential genotypes is much larger than the number of individuals in the population. Here, we show how recombination, in combination with natural selection, enables an evolving sexual population to replace existing genotypes with new, higher-fitness genotypic combinations. In contrast to this, an asexual population is limited to selection among existing genotypes. Since it has been shown that most eukaryotic species are genetically polymorphic, our model can explain the ubiquity of sex among such species. The model also indicates that classic population genetics theory is applicable to ecological studies of natural selection acting on standing genetic variation.
Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney
Authors: Muto Yoshiharu , Wilson Parker C. , Wu Haojia , Waikar Sushrut S. , Humphreys Benjamin D. 
Published: June 2020

AbstractThe integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding of cell heterogeneity. We performed single nucleus ATAC (snATAC-seq) and RNA (snRNA-seq) sequencing to generate paired, cell-type-specific chromatin accessibility and transcriptional profiles of the adult human kidney. We demonstrate that snATAC-seq is comparable to snRNA-seq in the assignment of cell identity and can further refine our understanding of functional heterogeneity in the nephron. The majority of differentially accessible chromatin regions are localized to promoters and a significant proportion are closely-associated with differentially expressed genes. Cell-type-specific enrichment of transcription factor binding motifs implicates the activation of NFκB that promotesVCAM1expression and drives transition between a subpopulation of proximal tubule epithelial cells. These datasets can be visualized at this resource:http://humphreyslab.com/SingleCell/. Our multi-omics approach improves the ability to detect unique cell states within the kidney and redefines cellular heterogeneity in the proximal tubule and thick ascending limb.
An efficient root transformation system for recalcitrantVicia sativa
Authors: Nguyen Vy , Searle Iain R. 
Published: June 2020

AbstractCommon vetch (Vicia sativa) is a multi-purpose legume widely used in pasture and crop rotation systems. Vetch seeds have desirable nutritional characteristics and are often used to feed ruminant animals. Although transcriptomes are available for vetch, problems with genetic transformation and plant regeneration hinder functional gene studies in this legume species. Therefore, the aim of this study was to develop an efficient and rapid hairy root transformation system for common vetch to facilitate functional gene analysis. We infected the hypocotyls of five-day oldin vitroorin vivo,soil grown, seedlings withAgrobacterium rhizogenesand produced transformed hairy roots 28 days later at 24% and 43% efficiency, respectively. Seventy-nine percent of the hairy roots from thein vitroplants showed stable expression of a co-transformed marker β-glucuronidase (GUS). In summary, transgenic hairy roots were obtained within 28 days, and are sufficient to facilitate functional gene analysis in common vetch.
Autumn larval cold tolerance does not predict the northern range limit of a widespread butterfly species
Authors: Tremblay Philippe , MacMillan Heath A. , Kharouba Heather M. 
Published: June 2020

AbstractClimate change is driving range shifts, and a lack of cold tolerance is hypothesized to constrain insect range expansion at poleward latitudes. However, few, if any, studies have tested this hypothesis during autumn when organisms are subjected to sporadic low temperature exposure but may not have become cold tolerant yet. In this study, we integrated organismal thermal tolerance measures into species distribution models for larvae of the Giant Swallowtail butterfly,Papilio cresphontes, living at the northern edge of its actively expanding range. Cold hardiness of field-collected larvae was determined using three common metrics of cold-induced physiological thresholds: the supercooling point (SCP), critical thermal minimum (CTmin), and survival following cold exposure.P. cresphonteslarvae in autumn have a CTminof 2.14°C, and were determined to be tolerant of chilling. These larvae have a SCP of −6.6°C and can survive prolonged exposure to −2°C. They generally die, however, at temperatures below their SCP (−8°C), suggesting they are chill tolerant or modestly freeze avoidant. Using this information, we examined the importance of low temperatures at a broad scale, by comparing species distribution models ofP. cresphontesbased only on environmental data derived from other sources to models that also included the cold tolerance parameters generated experimentally. Our modelling revealed that growing degree-days and precipitation best predicted the distribution ofP. cresphontes, while the cold tolerance variables did not explain much variation in habitat suitability. As such, the modelling results were consistent with our experimental results: low temperatures in autumn are unlikely to limit the distribution ofP. cresphontes. Further investigation into the ecological relevance of the physiological thresholds determined here will help determine how climate limits the distribution ofP. cresphontes. Understanding the factors that limit species distributions is key to predicting how climate change will drive species range shifts.
LDBlockShow: a fast and convenient tool for visualizing linkage disequilibrium and haplotype blocks based on variant call format files
Authors: Dong Shan-Shan , He Wei-Ming , Ji Jing-Jing , Zhang Chi , Guo Yan , Yang Tie-Lin 
Published: June 2020

AbstractThe triangular correlation heatmap aiming to visualize the linkage disequilibrium (LD) pattern and haplotype block structure of SNPs is ubiquitous component of population-based genetic studies. However, current tools suffered from the problem of time and memory consuming, and direct calculation from variant call format (VCF) files is not supported. Here we developed LDBlockShow, an open source software, for visualizing LD and haplotype blocks from VCF files. It is time and memory saving. In a test dataset with 100 SNPs from 60,000 subjects, it was at least 429.03 times faster and used only 0.04% – 20.00% of physical memory as compared to other tools. In addition, it could generate figures that simultaneously display additional statistical context (e.g., associationPvalues) and genomic region annotations. It can also compress the SVG files with large number of SNPs and support subgroup analysis. This fast and convenient tool would facilitate the visualization of LD and haplotype blocks for geneticists.
Risk of death by age and gender from CoVID-19 in Peru, March-May, 2020
Authors: Munayco Cesar , Chowell Gerardo , Tariq Amna , Undurraga Eduardo A. , Mizumoto Kenji 
Published: June 2020

AbstractPeru implemented strict social distancing measures during the early phase of the epidemic and is now experiencing one of the largest CoVID-19 epidemics in Latin America. Estimates of disease severity are an essential indicator to inform policy decisions about the intensity and duration of interventions needed to mitigate the outbreak. Here we derive delay-adjusted case fatality rates (aCFR) of CoVID-19 in a middle-income country in South America.We used government-reported time series of CoVID-19 cases and deaths stratified by age group and gender.Our estimates as of May 25, 2020, of the aCFR for men and women are 10.8% (95%CrI: 10.5–11.1%) and 6.5% (95%CrI: 6.2–6.8%), respectively, and an overall aCFR of 9.1% (95%CrI: 8.9–9.3%). Our results show that senior individuals are the most severely affected by CoVID-19, particularly men, with aCFR of almost 60% for those aged 80-years. We found that men have a significantly higher cumulative morbidity ratio than women across most age groups (proportion test, p-value< 0.001), with the exception of those aged 0–9 years.The COVID-19 epidemic is imposing a large mortality burden in Peru. Senior individuals, especially those who are older than 70 years of age, are being disproportionately affected by the COVID-19 pandemic.
Development and validation of a tool to appraise guidelines on SARS-CoV-2 infection prevention strategies in healthcare workers
Authors: Subramaniam Ashwin , Reddy Mallikarjuna , Zubarev Alexander , Kadam Umesh , Lim Zhengjie , Anstey Chris , Bihari Shailesh , HAji Jumana , Karunanithi Subhathra , Ramanathan Kollengode , Luo Jinghang , Mara Neil , Mitra Saikat , Rajamani Arvind , Rubulotta Francesca , Svensk Erik , Shekar Kiran 
Published: June 2020

AbstractBackgroundClinical guidelines on infection prevention strategies in healthcare workers (HCWs) play an important role in protecting them during the SARS-CoV-2 pandemic. Poorly constructed guidelines that are not comprehensive and are ambiguous may compromise HCWs’ safety. We aimed to develop and validate a tool to appraise guidelines on infection prevention strategies in HCWs.MethodsA 3-stage, web-based, Delphi consensus-building process among a panel of diverse HCWs and healthcare managers was utilised. We validated the tool by appraising 40 international, specialty-specific and procedure-specific guidelines along with national guidelines from countries with a wide range of gross national income.ResultsOverall consensus (≥75%) was reached at the end of three rounds for all six domains included in the tool. The chosen domains allowed appraisal of guidelines in relation to general characteristics (domain-1), recommendations on engineering (domain-2) and administrative aspects (domain 4-6) of infection prevention, as well as personal protection equipment (PPE) use (domain-3). The appraisal tool performed well across all domains and inter-rater agreement was excellent. All included guidelines performed relatively better in domains 1-3 compared with domains 4-6 and this was more evident in guidelines originating from lower income countries.ConclusionThe guideline appraisal tool was robust and easy to use. Recommendations on engineering aspects of infection prevention, administrative measures that promote optimal PPE use and HCW wellbeing were generally lacking in assessed guidelines. This tool may enable health systems to adopt high quality HCW infection prevention guidelines during SARS-CoV-2 pandemic and may also provide a framework for future guideline development.FundingNo funding received.Key SummaryWe developed and validated a guideline-appraisal tool by appraising 40 different guidelines from countries with varying GNI. This tool may help healthcare systems to adopt high-quality HCW infection-prevention guidelines during COVID-19 pandemic and may also provide a guideline development framework.