bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination
Authors: Tscherne Alina , Schwarz Jan Hendrik , Rohde Cornelius , Kupke Alexandra , Kalodimou Georgia , Limpinsel Leonard , Okba Nisreen M.A. , Bošnjak Berislav , Sandrock Inga , Halwe Sandro , Sauerhering Lucie , Brosinski Katrin , Liangliang Nan , Duell Elke , Jany Sylvia , Freudenstein Astrid , Schmidt Jörg , Werner Anke , Sera Michelle Gellhorn , Klüver Michael , Guggemos Wolfgang , Seilmaier Michael , Wendtner Clemens-Martin , Förster Reinhold , Haagmans Bart L. , Becker Stephan , Sutter Gerd , Volz Asisa 
Published: January 2021

AbstractThe severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on vaccinia virus MVA against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here, we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust synthesis of S antigen, make it a suitable candidate vaccine for industrial scale production. Vaccinated mice produced S antigen-specific CD8+ T cells and serum antibodies binding to S glycoprotein that neutralized SARS-CoV-2. Prime-boost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.Significance StatementThe highly attenuated vaccinia virus MVA is licensed as smallpox vaccine, and as vector it is a component of the approved Adenovirus-MVA-based prime-boost vaccine against Ebola virus disease. Here we provide results from testing the COVID-19 candidate vaccine MVA-SARS-2-S, a poxvirus-based vector vaccine that proceeded to clinical evaluation. When administered by intramuscular inoculation, MVA-SARS-2-S expresses and safely delivers the full-length SARS-CoV-2 spike (S) protein, inducing balanced SARS-CoV-2-specific cellular and humoral immunity, and protective efficacy in vaccinated mice. Substantial clinical experience has already been gained with MVA vectors using homologous and heterologous prime-boost applications, including the immunization of children and immunocompromised individuals. Thus, MVA-SARS-2-S represents an important resource for developing further optimized COVID-19 vaccines.
Serologic Surveillance and Phylogenetic Analysis of SARS-CoV-2 Infection in Hospital Health Care Workers
Authors: Sikkens Jonne J. , Buis David T.P. , Peters Edgar J.G. , Dekker Mireille , Schinkel Michiel , Reijnders Tom. D.Y. , Schuurman Alex. R. , Brabander Justin de , Lavell Ayesha H.A. , Maas Jaap. J. , Koopsen Jelle , Han Alvin X. , Russell Colin A. , Schinkel Janke , Jonges Marcel , Matamoros Sebastien P.F. , Jurriaans Suzanne , van Mansfeld Rosa , Wiersinga W. Joost , Smulders Yvo M. , de Jong Menno D. , Bomers Marije K. 
Published: January 2021

AbstractBACKGROUNDIt is unclear how, when and where health care workers (HCW) working in hospitals are infected with SARS-CoV-2.METHODSProspective cohort study comprising 4-weekly measurement of SARS-CoV-2 specific antibodies and questionnaires from March to June 2020. We compared SARS-CoV-2 incidence between HCW working in Covid-19 patient care, HCW working in non-Covid-19 patient care and HCW not in patient care. Phylogenetic analyses of SARS-CoV-2 samples from patients and HCW were performed to identify potential transmission clusters.RESULTSWe included 801 HCW: 439 in the Covid-19 patient care group, 164 in the non-Covid-19 patient care group and 198 in the no patient care group. SARS-CoV-2 incidence was highest in HCW working in Covid-19 patient care (13.2%), as compared with HCW in non-Covid-19 patient care (6.7%, hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.2 to 4.3) and in HCW not working in patient care (3.6%, HR 3.9, 95% CI 1.8 to 8.6). Within the group of HCW caring for Covid-19 patients, SARS-CoV-2 cumulative incidence was highest in HCW working on Covid-19 wards (25.7%), as compared with HCW working on intensive care units (7.1%, HR 3.6, 95% CI 1.9 to 6.9), and HCW working in the emergency room (8.0%, HR 3.3, 95% CI 1.5 to 7.1). Phylogenetic analyses on Covid-19 wards identified multiple potential HCW-to-HCW transmission clusters while no patient-to-HCW transmission clusters were identified.CONCLUSIONSHCW working on Covid-19 wards are at increased risk for nosocomial SARS-CoV-2 infection, with an important role for HCW-to-HCW transmission.(Funded by the Netherlands Organization for Health Research and Development ZonMw & the Corona Research Fund Amsterdam UMC; Netherlands Trial Register number NL8645)
Effects of surgical masks on droplet and aerosol dispersion under various oxygen delivery modalities
Authors: Takazono Takahiro , Yamamoto Kazuko , Okamoto Ryuta , Tashiro Masato , Morimoto Shimpei , Hosogaya Naoki , Miyazaki Taiga , Yanagihara Katsunori , Izumikawa Koichi , Mukae Hiroshi 
Published: January 2021

ABSTRACTRationaleAerosol dispersion under various oxygen delivery modalities, including high flow nasal cannula, is a critical concern for healthcare workers who treat acute hypoxemic respiratory failure during the coronavirus disease 2019 pandemic. Effects of surgical masks on droplet and aerosol dispersion under oxygen delivery modalities are not yet clarified.ObjectivesTo visualize and quantify dispersion particles under various oxygen delivery modalities and examine the protective effect of surgical masks on particle dispersion.MethodsThree and five healthy men were enrolled for video recording and quantification of particles, respectively. Various oxygen delivery modalities including high flow nasal cannula were used in this study. Particle dispersions during rest breathing, speaking, and coughing were recorded and automatically counted in each condition and were evaluated with or without surgical masks.Measurements and Main ResultsCoughing led to the maximum amount and distance of particle dispersion, regardless of modalities. Droplet dispersion was not visually increased by oxygen delivery modalities compared to breathing at room air. With surgical masks over the nasal cannula or high-flow nasal cannula, droplet dispersion was barely visible. Oxygen modalities did not increase the particle dispersion counts regardless of breathing pattens. Wearing surgical masks significantly decreased particle dispersion in all modalities while speaking and coughing, regardless of particle sizes, and reduction rates were approximately 95 and 80-90 % for larger (> 5 μm) and smaller (> 0.5 μm) particles, respectively.ConclusionsSurgical mask over high flow nasal canula may be safely used for acute hypoxemic respiratory failure including coronavirus disease 2019 patients.Subject Category List4.13 Ventilation: Non-Invasive/Long-Term/Weaning*This article has an online data supplement, which is accessible from this issue’s table of content online at www.atsjournals.org.
Reverse causal effect of atrial fibrillation on 17 site-specific cancer risk: A Mendelian randomization study
Authors: Park Sehoon , Lee Soojin , Kim Yaerim , Cho Semin , Kim Kwangsoo , Kim Yong Chul , Han Seung Seok , Lee Hajeong , Lee Jung Pyo , Joo Kwon Wook , Lim Chun Soo , Kim Yon Su , Kim Dong Ki 
Published: January 2021

AbstractBackgroundBidirectional association between atrial fibrillation (AF) and cancer was reported by observational investigations. Additional study is warranted to investigate the causal effects of AF on risk of cancer.MethodsThis study was a summary-level Mendelian randomization (MR) analysis. Genetic instrument for AF was developed from a genome-wide association study (GWAS) meta-analysis for AF including 537,409 European ancestry individuals including 55,144 AF cases. The outcome data for risk of 17 site-specific cancer from a previous GWAS meta-analysis of the UK Biobank (48,961/359,825 case/controls) and Genetic Epidemiology Research on Adult Health and Aging (16,001/50,525 case/controls) cohorts including European ancestry individuals was investigated. Inverse variance weighted method was the main MR method, supported by pleiotropy-robust sensitivity analysis including MR-Egger regression and penalized weighted median method.ResultsThe causal estimates indicated that AF was causally linked to higher risk of cancers of lung, breast, cervix, endometrium, and melanoma. MR-Egger test for directional pleiotropy indicated absence of a pleiotropy in the identified causal estimates and MR-Egger regression and median-based methods provided similarly significant findings. On the other hand, the genetic predisposition of AF was significantly associated with lower risk of esophagus/gastric cancer, but possibility of a directional pleiotropy remained in the association.ConclusionsAF is a causal factor for certain types of cancer. Appropriate cancer screening should be suggested in clinical guidelines for AF patients. Future trial is necessary to confirm whether appropriate management of AF may reduce the risk of cancer which is a major cause of deaths in AF patients.
Identification of Fluoxetine as a direct NLRP3 inhibitor to treat atrophic macular degeneration
Authors: Ambati Meenakshi , Apicella Ivana , Narendran Siddharth , Wang Shao-bin , Leung Hannah , Pereira Felipe , Varshney Akhil , Baker Kirstie L. , Marion Kenneth M. , Shadmehr Mehrdad , Stains Cliff I. , Sadda Srinivas R. , Taylor Ethan W. , Sutton S. Scott , Werner Brian C. , Magagnoli Joseph , Gelfand Bradley D. 
Published: January 2021

AbstractThe atrophic form of age-related macular degeneration (dry AMD) affects nearly 200 million people worldwide. There is no FDA-approved therapy for this disease, which is the leading cause of irreversible blindness among people over 50 years of age. Vision loss in dry AMD results from degeneration of the retinal pigmented epithelium (RPE). RPE cell death is driven in part by accumulation ofAluRNAs, which are noncoding transcripts of a human retrotransposon.AluRNA induces RPE degeneration by activating the NLRP3-ASC inflammasome. We report that fluoxetine, an FDA-approved drug for treating clinical depression, binds NLRP3 in silico, in vitro, and in vivo, and that it inhibits activation of the NLRP3-ASC inflammasome in RPE cells and macrophages, two critical cell types in dry AMD. We also demonstrate that fluoxetine, unlike several other anti-depressant drugs, reducesAluRNA-induced RPE degeneration in mice. Finally, by analyzing two health insurance databases comprising more than 100 million Americans, we report a reduced hazard of developing dry AMD among patients with depression who were treated with fluoxetine. Collectively, these studies triangulate to link fluoxetine as a potential drug repurposing candidate for a major unmet medical need that causes blindness in millions of people in the United States and across the world.Significance StatementDry age-related macular degeneration (AMD) affects the vision of millions of people worldwide. There is currently no FDA-approved treatment for dry AMD. The inflammasome components NLRP3 and ASC have been implicated in the pathogenesis of dry AMD. We report that fluoxetine, which is approved for the treatment of clinical depression, directly binds the NLRP3 protein and prevents the assembly and activation of the NLRP3-ASC inflammasome. As a result, it also blocks the degeneration of retinal pigmented epithelium (RPE) cells in an animal model of dry AMD. Furthermore, we demonstrate through an analysis of health insurance databases that use of this FDA-approved anti-depressant drug is associated with reduced incidence of dry AMD. These studies identify that fluoxetine is a potential repurposing candidate for AMD, a prevalent cause of blindness.
Regulation of NMDA receptor trafficking and gating by activity-dependent CaMKIIα phosphorylation of the GluN2A subunit
Authors: Yong Xuan Ling Hilary , Zhang Lingrui , Yang Liming , Chen Xiumin , Yu Xiaojun , Chandra Mintu , Livingstone Emma , Tan Jing Zhi Anson , Widagdo Jocelyn , Vieira Marta M. , Roche Katherine W. , Lynch Joseph W. , Keramidas Angelo , Collins Brett M. , Anggono Victor 
Published: January 2021

AbstractNMDAR-dependent Ca2+influx underpins multiple forms of synaptic plasticity. In the adult forebrain, the majority of synaptic NMDAR currents are mediated by GluN2A-containing NMDARs. These receptors are rapidly inserted into synapses during LTP; however, the underlying molecular mechanisms remain poorly understood. Here we show that GluN2A is phosphorylated at Ser-1459 by CaMKIIα in response to glycine stimulation that mimics LTP in primary neurons. Phosphorylation of Ser-1459 promotes GluN2A interaction with the SNX27-retromer complex, therefore enhancing the endosomal recycling of NMDARs. Loss of SNX27 or CaMKIIα function blocks the glycine-induced increase in GluN2A-NMDARs on the neuronal membrane. Interestingly, mutations of Ser-1459, including the rare S1459G human epilepsy variant, prolong decay times of NMDAR-mediated synaptic currents in heterosynapses by increasing the active duration of channel openings. Taken together, these findings not only identify a critical role of Ser-1459 phosphorylation in regulating the function of NMDARs, but also explain how the S1459G epilepsy variant dysregulates NMDAR function.
Experimental corticosterone manipulation increases mature feather corticosterone content: implications for inferring avian stress history from feather analyses
Authors: Aharon-Rotman Yaara , Buttemer William A. , Koren Lee , Wynne-Edwards Katherine 
Published: January 2021

AbstractFeathers incorporate plasma corticosterone (CORT) during their development and, because feathers lack blood supply at maturity, the CORT content of feathers (CORTf) is presumed to represent an integrated average of plasma CORT levels during feather growth. We tested this assumption by quantifying CORTf in feathers of house sparrows (Passer domesticus) that were plucked before and after being implanted with either a corticosterone-filled, metyrapone-filled, or empty (sham) silastic capsule. Two of the seven flight feathers collected from each bird were fully grown when birds received implants. We found that CORTf of all seven feathers corresponded with treatment type, and with plasma CORT levels of non-moulting reference sparrows also given these implants. We also found that CORTf of the two mature feathers of each bird were 4 to 10-fold higher than values measured in new feathers. Given the avascular nature of mature feathers, and the fact that we did not wash the feathers prior to analysis, the most plausible explanation for our results is that CORT was externally deposited on feathers after implant. This outcome emphasises the need for follow-up studies to identify the external sources of CORT that may affect the CORTf of feathers. We hope this study will stimulate discussions and further much needed studies on the mechanism of CORT deposition in feathers and open exciting opportunities for application of such methods in ecological research, such as measuring multiple time scales in such a non-invasive manner.
Characterizing scaling laws in gut microbial dynamics from time series data: caution is warranted
Authors: Wang Xu-Wen , Liu Yang-Yu 
Published: January 2021

AbstractMany studies have revealed that both host and environmental factors can impact the gut microbial compositions, implying that the gut microbiota is considerably dynamic1–5. In their Article, Ji et al.6performed comprehensive analysis of multiple high-resolution time series data of human and mouse gut microbiota. They found that both human and mouse gut microbiota dynamics can be characterized by several robust scaling laws describing short- and long-term changes in gut microbiota abundances, distributions of species residence and return times, and the correlation between the mean and the temporal variance of species abundances. They claimed that those scaling laws characterize both short- and long-term dynamics of gut microbiota. However, we are concerned that their interpretation is quite misleading, because all the scaling laws can be reproduced by the shuffled time series with completely randomized time stamps of the microbiome samples.
YHP: Y-chromosome Haplogroup Predictor for predicting male lineages based on Y-STRs
Authors: Song Mengyuan , Song Feng , Zhao Chenxi , Hou Yiping 
Published: January 2021

AbstractHuman Y chromosome reflects the evolutionary process of males. Male lineage tracing by Y chromosome is of great use in evolutionary, forensic, and anthropological studies when male samples exist or especially when the biological sample is a mixture of male and female individuals. Identifying the male lineage based on the specific distribution of Y haplogroups narrows down the investigation scope. Integrating previously published datasets with genotypes of Y chromosome short tandem repeats (Y-STRs) and high-resolution haplogroups (122 haplogroups in total), we developed YHP (Y Haplogroup Predictor), an open-access and userfriendly software package to predict haplogroups, compare the similarity, and conduct mismatch analysis of samples with Y-STR profiles. The software is available at Github (https://github.com/cissy123/YHP-Y-Haplogroup-Predictor-).Author SummaryFamilial searching has been used in forensic, anthropologic, and personalized scenarios. Software packages have been developed to assist in male familial searching, such as predicting Y-SNP haplogroups by Y-STRs. However, these software packages, in general, achieve this goal with a rough resolution. In this study, we developed a software package to conduct high-resolution haplogroup inference to help familial searching and at the same time reduce the cost, since it does not require tiresome Y-SNP sequencing.
Spatial Congruence Analysis (SCAN): An objective method for detecting biogeographical patterns based on species’ range congruences
Authors: Gatto Cassiano A F R , Cohn-Haft Mario 
Published: January 2021

AbstractSimilar species ranges may represent outcomes of common biological processes and so form the basis for biogeographical concepts such as areas of endemism and ecoregions. Nevertheless, spatial range congruence is rarely quantified, much less incorporated in bioregionalization methods as an explicit parameter. Furthermore, most available methods suffer from limitations related to the loss, or the excess of range information, or scale bias associated with the use of grids, and the incapacity to recognize independent overlapped patterns or gradients of range distributions. Here, we propose an analytical method, Spatial Congruence Analysis (SCAN), to identify biogeographically meaningful groups of species, called biogeographic elements. Such elements are based on direct and indirect spatial relationships among species’ ranges and vary depending on an explicit measure of range congruence controlled as a numerical parameter in the analysis. A one-layered network connects species (vertices) using pairwise spatial congruence estimates (edges). This network is then analyzed for each species, separately, by an algorithm that accesses the entire web of spatial relationships to the reference species. The method was applied to two datasets: a simulated gradient of ranges and real distributions of birds. The gradient results showed that SCAN can describe gradients of distribution with a high level of detail, without confounding transition zones with true biogeographical units, a frequent pitfall of other methods. The bird dataset showed that only a small portion of range overlaps is biogeographically meaningful, and that there is a large variation in types of patterns that can be found with real distributions. Distinct reference species may converge on similar or identical groups of spatially related species, may lead to recognition of nested species groups, or may even generate similar spatial patterns with no species in common. The biological significance or causal processes of these patterns should be investigated a posteriori. Patterns can vary from simple ones, composed by few highly congruent species, to complex, with numerous alternative component species and spatial configurations, depending on particular parameter settings as determined by the investigator. This approach eliminates or reduces limitations of other methods and permits pattern description without hidden assumptions about processes, and so should make a valuable contribution to the biogeographer’s toolbox.“If there is any basic unit of biogeography, it is the geographic range of a species.” - Brown, Stevens & Kaufman [1].“[spatial] congruence […] should be optimized, while realizing that this criterion will most likely never be fully met” - HP Linder [2].
Fecal microbial transplant abates tolerance to methylone-induced hyperthermia
Authors: Goldsmith Robert , Aburahma Amal , Pachhain Sudhan , Choudhury Sayantan Roy , Phuntumart Vipa , Larsen Ray , Sprague Jon E. 
Published: January 2021

AbstractThe microbiome-gut-brain axis has been implicated in multiple bodily systems and pathologies, and intentional manipulation of the gut-microbiome has yielded clinically significant results. Here, we examined the effects of bi-directional fecal microbial transplants (FMT) between methylone-induced hyperthermic tolerant (MHT) and methylone-naïve (MN) rats. Rats treated with methylone once per week developed tolerance to methylone-induced hyperthermia by the fourth week. Once tolerant, daily bi-directional FMT between the two groups were performed for seven days prior to the next methylone treatment. The FMT abated the developed tolerance in the MHT group. When treated with methylone for the first time following FMT, recipient MN rats displayed significant tolerance to hyperthermia despite it being their initial drug treatment. Post-FMT, MHT rats displayed elevations in norepinephrine and expression ofUCP1,UCP3andTGR5in brown adipose tissue, with reductions in expression ofTGR5andUCP3in skeletal muscle. The pre- and post-FMT methylone tolerance phenotypes of transplant recipients are concurrent with changes in the relative abundance of several Classes ofProteobacteria, most evident forGammaproteobacterandAlphaproteobacter.MHT recipients demonstrated a marked increase in the relative proportion of theFirmicutesClassErysipelotrichia. These findings suggest that transplantation of gut-microbiomes can confer phenotypic responses to a drug.