bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracing genetic connections of ancient Hungarians to the 6-14thcentury populations of the Volga-Ural region
Authors: Szeifert Bea , Gerber Dániel , Csáky Veronika , Langó Péter , Stashenkov Dmitrii A. , Khokhlov Aleksandr A. , Sitdikov Ayrat G. , Gazimzyanov Ilgizar R. , Volkova Elizaveta V. , Matveeva Natalia P. , Zelenkov Alexander S. , Poshekhonova Olga E. , Sleptsova Anastasiia V. , Karacharov Konstantin G. , Ilyushina Viktoria V. , Konikov Boris A. , Sungatov Flarit A. , Kolonskikh Alexander G. , Botalov Sergei G. , Grudochko Ivan V. , Komar Oleksii , Egyed Balázs , Mende Balázs G. , Türk Attila , Szécsényi-Nagy Anna 
Published: February 2022

AbstractMost of the early Hungarian tribes originated from the Volga-Kama and South-Ural regions, where they were composed of a mixed population based on historical, philological, and archaeological data. We present here the uniparental genetic makeup of the medieval era of these regions that served as a melting pot for ethnic groups with different linguistic and historical backgrounds. Representing diverse cultural contexts, the new genetic data originates from ancient proto-Ob-Ugric people from Western Siberia (6th-13thcentury), the pre-Conquest period, and subsisting Hungarians from the Volga-Ural region (6th-14thcentury) and their neighbours. By examining the eastern archaeology traits of Hungarian prehistory, we also study their genetic composition and origin in an interdisciplinary framework.We analysed 110 deep-sequenced mitogenomes and 42 Y-chromosome haplotypes from 18 archaeological sites in Russia. The results support the studied groups’ genetic relationships regardless of geographical distances, suggesting large-scale mobility. We detected long-lasting genetic connections between the sites representing the Kushnarenkovo and Chiyalik cultures and the Carpathian Basin Hungarians and confirmed the Uralic transmission of several East-Eurasian uniparental lineages in their genepool. Based on phylogenetics, we demonstrate and model the connections and splits of the studied Volga-Ural and conqueror groups.Early Hungarians and their alliances conquered the Carpathian Basin around 890 AD. Re-analysis of the Hungarian conquerors’ maternal genepool reveals numerous surviving maternal relationships in both sexes; therefore, we conclude that men and women came to the Carpathian Basin together, and although they were subsequently genetically fused into the local population, certain eastern lineages survived for centuries.
Specific Peptides Predict Protein Classification
Authors: Horn David , Weingart Uri 
Published: February 2022

AbstractThe methodology of Specific Peptides (SP) has been introduced within the context of enzymes. It is based on an unsupervised machine leaning (ML) tool for motif extraction, followed by supervised annotation of the motifs. In the case of enzymes, the classifier is the Enzyme Classification (EC) number. Here we demonstrate that this method reaches precision of 96.5% and recall of 89.1% on presently available protein sequences. We also apply this method to two other protein families, GPCR and ZF, find their corresponding SPs, and provide the code for searching any protein sequence for its classification under any such family.
Lipid network and moiety analysis for revealing enzymatic dysregulation and mechanistic alterations from lipidomics data
Authors: Rose Tim D. , Köhler Nikolai , Falk Lisa , Klischat Lucie , Lazareva Olga E. , Pauling Josch K. 
Published: February 2022

AbstractLipidomics is of growing importance for clinical and biomedical research due to many associations between lipid metabolism and diseases. The discovery of these associations is facilitated by improved lipid identification and quantification. Sophisticated computational methods are advantageous for interpreting such large-scale data for understanding metabolic processes and their underlying (patho)mechanisms. To generate hypothesis about these mechanisms, the combination of metabolic networks and graph algorithms is a powerful option to pinpoint molecular disease drivers and their interactions. Here we present LINEX2(Lipid Network Explorer), a lipid network analysis framework that fuels biological interpretation of alterations in lipid compositions. By integrating lipid-metabolic reactions from public databases we generate dataset-specific lipid interaction networks. To aid interpretation of these networks we present an enrichment graph algorithm that infers changes in enzymatic activity in the context of their multispecificity from lipidomics data. Our inference method successfully recovered the MBOAT7 enzyme from knock-out data. Furthermore, we mechanistically interpret lipidomic alterations of adipocytes in obesity by leveraging network enrichment and lipid moieties. We address the general lack of lipidomics data mining options to elucidate potential disease mechanisms and make lipidomics more clinically relevant.Graphical AbstractLINEX2(Lipid Network Explorer) is a framework to visualize and analyze quantitative lipidomics data. The included algorithms offer new perspectives on the lipidome and can propose potential mechanisms of dysregulation.Using the Reactome and Rhea databases, a comprehensive set of lipid class reactions is included and utilized to map the lipidome on custom data-specific networks.With a novel network enrichment method, enzymatic dysregulation can be recovered from lipidomics data.We validate its usability on data with a central lipid enzymatic deficiency.LINEX2is the first tool capable of such analysis and includes complimentary analysis options for structural lipid analysis. It is freely available as a web service (https://exbio.wzw.tum.de/linex2).
A Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19
Authors: Shrimp Jonathan H. , Janiszewski John , Chen Catherine Z. , Xu Miao , Wilson Kelli M. , Kales Stephen C. , Sanderson Philip E. , Shinn Paul , Itkin Zina , Guo Hui , Shen Min , Klumpp-Thomas Carleen , Michael Samuel G. , Zheng Wei , Simeonov Anton , Hall Matthew D. 
Published: February 2022

AbstractSARS-CoV-2 is the causative viral pathogen driving the COVID-19 pandemic that prompted an immediate global response to the development of vaccines and antiviral therapeutics. For antiviral therapeutics, drug repurposing allowed for rapid movement of existing clinical candidates and therapies into human clinical trials to be tested as COVID-19 therapies. One effective antiviral treatment strategy used early in symptom onset is to prevent viral entry. SARS-CoV-2 enters ACE2-expressing cells when the receptor-binding domain of the spike protein on the surface of SARS-CoV-2 binds to ACE2 followed by cleavage at two cut sites on the spike protein. TMPRSS2 has a protease domain capable of cleaving the two cut sites; therefore, a molecule capable of inhibiting the protease activity of TMPRSS2 could be a valuable antiviral therapy. Initially, we used a fluorogenic high-throughput screening assay for the biochemical screening of 6030 compounds in NCATS annotated libraries. Then, we developed an orthogonal biochemical assay that uses mass spectrometry detection of product formation to ensure that hits from the primary screen are not assay artifacts from the fluorescent detection of product formation. Finally, we assessed the hits from the biochemical screening in a cell-based SARS-CoV-2 pseudotyped particle entry assay. Of the six molecules advanced for further studies, two are approved drugs in Japan (camostat and nafamostat), two have entered clinical trials (PCI-27483 and otamixaban), while the other two molecules are peptidomimetic inhibitors of TMPRSS2 taken from the literature that have not advanced into clinical trials (compounds 92 and 114). This work demonstrates a suite of assays for the discovery and development of new inhibitors of TMPRSS2.
SARS-CoV-2 variant of concern type and biological sex affect efficacy of molnupiravir in dwarf hamster model of severe COVID-19
Authors: Lieber Carolin M. , Cox Robert M , Sourimant Julien , Wolf Josef D. , Juergens Kate , Phung Quynh , Saindane Manohar T , Natchus Michael G , Painter George R , Sakamoto Kaori , Greninger Alexander L. , Plemper Richard K 
Published: February 2022

Summary ParagraphSARS-CoV-2 variants of concern (VOC) have triggered distinct infection waves in the coronavirus disease 2019 (COVID-19) pandemic, culminating in currently all-time high incidence rates of VOC omicron. Orally available direct-acting antivirals such as molnupiravir promise to improve disease management and limit SARS-CoV-2 spread. However, molnupiravir efficacy against VOC delta was questioned based on clinical trial results and its potency against omicron is unknown. This study evaluates molnupiravir against a panel of relevant VOC in three efficacy models: primary human airway epithelium organoids, the ferret model of upper respiratory disease, and a lethal Roborovski dwarf hamster efficacy model of severe COVID-19-like acute lung injury. All VOC were equally efficiently inhibited by molnupiravir in cultured cells and organoids. Treatment consistently reduced upper respiratory VOC shedding in ferrets and prevented viral transmission. Pathogenicity in the dwarf hamsters was VOC-dependent and highest for gamma, omicron, and delta with fulminant lung histopathology. Oral molnupiravir started 12 hours after infection resulted in complete survival of treated dwarf hamsters independent of challenge VOC. However, reduction in lung virus differed VOC-dependently, ranging from one (delta) to four (gamma) orders of magnitude compared to vehicle-treated animals. Dwarf hamsters infected with VOC omicron showed significant individual variation in response to treatment. Virus load reduction was significant in treated males, but not females. The dwarf hamster model recapitulates mixed efficacy of molnupiravir seen in human trials and alerts that therapeutic benefit of approved antivirals must be continuously reassessed in vivo as new VOC emerge.
Detection of SARS-CoV-2 Omicron variant (B.1.1.529) infection of white-tailed deer
Authors: Vandegrift Kurt J. , Yon Michele , Surendran-Nair Meera , Gontu Abhinay , Amirthalingam Saranya , Nissly Ruth H. , Levine Nicole , Stuber Tod , DeNicola Anthony J. , Boulanger Jason R. , Kotschwar Nathan , Aucoin Sarah Grimké , Simon Richard , Toal Katrina , Olsen Randall J. , Davis James J. , Bold Dashzeveg , Gaudreault Natasha N. , Richt Juergen A. , Musser James M. , Hudson Peter J. , Kapur Vivek , Kuchipudi Suresh V. 
Published: February 2022

AbstractWhite-tailed deer (Odocoileus virginianus) are highly susceptible to infection by SARS-CoV-2, with multiple reports of widespread spillover of virus from humans to free-living deer. While the recently emerged SARS-CoV-2 B.1.1.529 Omicron variant of concern (VoC) has been shown to be notably more transmissible amongst humans, its ability to cause infection and spillover to non-human animals remains a challenge of concern. We found that 19 of the 131 (14.5%; 95% CI: 0.10–0.22) white-tailed deer opportunistically sampled on Staten Island, New York, between December 12, 2021, and January 31, 2022, were positive for SARS-CoV-2 specific serum antibodies using a surrogate virus neutralization assay, indicating prior exposure. The results also revealed strong evidence of age-dependence in antibody prevalence. A significantly (χ2, p < 0.001) greater proportion of yearling deer possessed neutralizing antibodies as compared with fawns (OR=12.7; 95% CI 4–37.5). Importantly, SARS-CoV-2 nucleic acid was detected in nasal swabs from seven of 68 (10.29%; 95% CI: 0.0–0.20) of the sampled deer, and whole-genome sequencing identified the SARS-CoV-2 Omicron VoC (B.1.1.529) is circulating amongst the white-tailed deer on Staten Island. Phylogenetic analyses revealed the deer Omicron sequences clustered closely with other, recently reported Omicron sequences recovered from infected humans in New York City and elsewhere, consistent with human to deer spillover. Interestingly, one individual deer was positive for viral RNA and had a high level of neutralizing antibodies, suggesting either rapid serological conversion during an ongoing infection or a “breakthrough” infection in a previously exposed animal. Together, our findings show that the SARS-CoV-2 B.1.1.529 Omicron VoC can infect white-tailed deer and highlights an urgent need for comprehensive surveillance of susceptible animal species to identify ecological transmission networks and better assess the potential risks of spillback to humans.Key FindingsThese studies provide strong evidence of infection of free-living white-tailed deer with the SARS-CoV-2 B.1.1.529 Omicron variant of concern on Staten Island, New York, and highlight an urgent need for investigations on human-to-animal-to-human spillovers/spillbacks as well as on better defining the expanding host-range of SARS-CoV-2 in non-human animals and the environment.
Characteristics and Preparedness for COVID-19 Outbreaks of Australian Residential Aged Care Facilities: a Cross-sectional Survey
Authors: Gilbert Gwendolyn L , Smith Jenna , Cvejic Erin , Lilly Alan , McCaffery Kirsten 
Published: February 2022

ABSTRACTObjectiveTo provide an overview of Australian residential aged care facilities’ (RACFs’) COVID-19 outbreak preparedness and responses, 12 months after the pandemic began in early 2020.MethodsA cross-sectional survey of RACF managers was conducted as part of an overview of COVID-19 experience during 2020. Survey questions were based on findings of previous outbreak reviews.ResultsComparison with available data from the Australian Institute for Health and Welfare suggested that survey respondents (n=331) were a representative sample. Almost all RACFs had outbreak management plans, including provision for a surge workforce. However, anticipated staff replacements fell short of those often required during outbreaks. Staff of most (83%) RACFs had completed online infection control training, and a smaller proportion (73%) face-to-face training, by the time of the survey. Exploratory analyses to identify RACF characteristics associated with increased outbreak risk found a strong association with location in Victoria (adjusted risk ratio [aRR] 12.8) where most community transmission occurred during 2020. The only other association was an increased risk in facilities where all staff had not completed face-to-face infection control training (aRR 2.1). Respondents ranked leadership and management; planning and preparation; and infection control as the top three of seven critical lines of defence against COVID-19.ConclusionSurvey results suggest that, in early 2021, most Australian RACFs were better prepared for the ongoing risk of COVID-19 than in 2020. Continued implementation of the Aged Care Royal Commission’s recommendations is needed to ensure the aged care sector is prepared for future infectious disease emergencies.
Estimating the risk reduction of isolation on COVID-19 non-household transmission and severe/critical illness in non-immune individuals: September to November 2021
Authors: Prosser Aaron , Helfer Bartosz , Streiner David L. 
Published: February 2022

AbstractIn the fall 2021, immunity mandates/passports for COVID-19 started to be discussed and implemented globally. In addition to increasing vaccination levels, these interventions isolate non-immune individuals from various settings to reduce non-household transmission and severe/critical illness. This is based on the hypothesis that the non-immune are at high absolute risk of these outcomes. However, these absolute risks were not quantified in the literature such that the absolute risk reductions of isolation on these outcomes remain unknown. This study estimated these absolute risks from September to November 2021 prior to the emergence of Omicron (B.1.1.529) using known data on the risk of infection, transmission in non-household settings, and age-stratified severe/critical illness in non-immune individuals for the Delta (B.1.617.2) variant, focusing on the European Union, United Kingdom, United States, Canada, Australia, and Israel. This allowed us to quantify the absolute risk reductions of isolation on (1) non-household transmission from the non-immune and (2) severe/critical illness amongst the non-immune in these regions during this period. We observed that on any given day the absolute risk reductions of isolation were typically small for transmission in most types of non-household settings and severe/critical illness in most age-groups, especially those aged <40. During a wave or sustained higher infection risks, the risk reductions were modest only for transmission in intimate social gatherings and severe/critical illness in adults aged ≥50-60. The limitations of this study and the implications for the expected benefits of isolating non-immune individuals on reducing these outcomes are discussed.
Changes in the number of public health nurses employed in local governments in Japan during the Covid-19 pandemic: A cross-sectional study
Authors: Taira Kazuya , Hosokawa Rikuya , Shiomi Misa 
Published: February 2022

AbstractObjectivesThis study aims to clarify the recruitment of public health nurses in local governments in Japan during the Covid-19 pandemic.Study designA cross-sectional study.MethodsA cross-sectional study of 150 local governments that have public health centers in Japan was conducted. The survey period was November to December 2021. The survey items were the number of full-time and part-time public health nurses (PHNs), the number of PHNs who resigned or retired from the job, and the number of PHN recruitment examinations for each year from 2017 to 2021. For all variables, the mean, standard deviation, maximum, and minimum values for each type of municipality and year were calculated, and a one-way analysis of variance was performed.ResultsThe recovery rate was 54.0% (81/150). Although a statistically significant difference was not recorded in the change in employment status of PHNs from 2019 to 2020, during the year that COVID-19 infection began in Japan, the number of full-time PHNs increased by only 2.6 at the maximum, while the number of part-time PHNs was 5.2±8.3 to 10.8±9.6 (p = 0.61) for prefectures, from 13.6±13.1 to 21.5±34.8 (p = 0.23) for city, and from 16.8±26.8 to 52.3±132.5 (p = 0.70) for ward.ConclusionsThis study reveals that support for the increased workload due to COVID-19 is heavily dependent on part-time PHNs. Drastic change to the ideal way of the original countermeasure to Covid-19 in Japan or the supply of stronger human support to the public health center might be desired.
COVID-19 vaccines uptake: Public knowledge, awareness, perception and acceptance among adult Africans
Authors: Ahiakpa John K. , Cosmas Nanma T. , Anyiam Felix E. , Enalume Kingsley O. , Lawan Ibrahim , Gabriel Ijuptil B. , Oforka Chinonyelum L. , Dahir Hamze G. , Fausat Salisu T. , Nwobodo Maureen A. , Massawe Getrude P. , Obagha Adachukwu S. , Okeh Debra U. , Karikari Benjamin , Aderonke Samuel T. , Awoyemi Olushola M. , Aneyo Idowu A. , Doherty Funmilayo V. 
Published: February 2022

AbstractIntroductionThe willingness of Africa’s population to take the COVID-19 vaccines is critical to the efficiency of national immunisation programmes. This study surveys the views of adult African inhabitants toward vaccination and the possibility of participating or not participating in governments’ efforts to get citizens vaccinated.MethodA cross-sectional online survey of adult Africans was undertaken from December 2020 to March 2021. Responses were anonymised. The Pearson Chi-square test was performed to determine whether or not there were any variations in knowledge, awareness, perception and acceptance of the COVID-19 vaccines among the participants. Binomial logistic regression was used to evaluate the factors associated with willingness to accept COVID-19 vaccines and participate in immunisation programmes.ResultsThe results indicate that COVID-19 vaccines are more likely to be used by adult Africans over the age of 18 who are largely technologically savvy (55 percent) if the vaccine is made broadly available. A total of 33 percent of those who responded said they were unlikely to receive the vaccine, with another 15 percent stating they were undecided. Aside from that, we found that vaccine hesitancy was closely associated with socio-demographic characteristics such as age, gender, education and source of information. We also found that there were widespread conspiracies and myths about the COVID-19 vaccines.ConclusionMore than two-thirds of African adults who participated in the survey indicated they would not receive the COVID-19 vaccine, with majority of them expressing skepticisms about the vaccine’s efficacy. It is possible that many of the people who would not be vaccinated would have an impact on the implementation of a COVID-19 immunisation programme that is meant for all of society. Majority of the respondents were unwilling to pay for the COVID-19 vaccines when made available. An awareness campaign should be focused on promoting the benefits of vaccination at the individual and population levels, as well as on taking preemptive actions to debunk misconceptions about the vaccines before they become further widespread.
Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis
Authors: Ma Hong , Lin Yu-Hao , Dai Li-Zhen , Lin Chen-Shi , Huang Yanling , Liu Shu-Yuan 
Published: February 2022

ABSTRACTObjectiveTo compare the efficacy and safety between and within glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in overweight or obese adults with or without diabetes mellitus.MethodsPubMed, ISI Web of Science, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) database were comprehensively searched to identify randomised controlled trials (RCTs) of effects of GLP-1RAs and SGLT-2is in overweight or obese participants from inception to Jan 16, 2022. The efficacy outcomes were the changes of body weight, glucose level and blood pressure. The safety outcomes were serious adverse events and discontinuation due to adverse events. The mean differences (MDs), odds ratios (ORs), 95% credible intervals (95% CI), the surface under the cumulative ranking (SUCRA) were evaluated for each outcome by network meta-analysis.ResultsSixty-one RCTs were included in our analysis. Both GLP-1RAs and SGLT-2is conferred greater extents in body weight reduction, achieving at least 5% weight loss, HbA1c and fasting plasma glucose decrease compared with placebo. GLP-1RAs was superior to SGLT-2is in HbA1c reduction (MD: -0.39%, 95% CI: -0.70 to -0.08). GLP-1RAs had high risk of adverse events, while SGLT-2is were relatively safe. Based on intraclass comparison, semaglutide 2.4mg was among the most effective interventions in losing body weight (MD: -11.51kg, 95% CI: -12.83 to -10.21), decreasing HbA1c (MD: -1.49%, 95% CI: -2.07 to -0.92) and fasting plasma glucose (MD: -2.15mmol/L, 95% CI: -2.83 to -1.59), reducing systolic blood pressure (MD: -4.89mmHg, 95% CI: -6.04 to -3.71) and diastolic blood pressure (MD: -1.59mmHg, 95% CI: -2.37 to -0.86) with moderate certainty evidences, while it was associated with high risk of adverse events.ConclusionsSemaglutide 2.4mg showed greatest effects on losing body weight, controlling glycemic level and reducing blood pressure while it was associated with high risk of adverse events.ARTICLE SUMMARYStrengths and limitations of this study▸The RoB 2.0 and GRADE methods were used to assess the risk of bias and evaluate the confidence in effect estimates.▸Study selection, data extraction, quality of study and evidence assessment were conducted independently by two authors and audited by the third author.▸The network meta-analysis was mostly based on indirect comparisons due to limited reported comparisons in available literatures.▸The small number of randomised controlled trials available in some comparisons.