bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation and comparative analysis of antibodies that broadly neutralize sarbecoviruses
Authors: Liu Lihong , Iketani Sho , Guo Yicheng , Casner Ryan G. , Reddem Eswar R. , Nair Manoj S. , Yu Jian , Chan Jasper F-W. , Wang Maple , Cerutti Gabriele , Li Zhiteng , Castagna Candace D. , Corredor Laura , Chu Hin , Yuan Shuofeng , Poon Vincent Kwok-Man , Chan Chris Chun-Sing , Chen Zhiwei , Luo Yang , Cunningham Marcus , Chavez Alejandro , Yin Michael T. , Perlin David S. , Tsuji Moriya , Yuen Kwok-Yung , Kwong Peter D. , Sheng Zizhang , Huang Yaoxing , Shapiro Lawrence , Ho David D. 
Published: December 2021

AbstractThe devastation caused by SARS-CoV-2 has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses and thus its promise as an agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses, but also uncovered a new antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.One sentence summaryA monoclonal antibody that neutralizes or binds all sarbecoviruses tested and represents a reproducible antibody class.
Correlation between faecal microbial taxa and ulcerative colitis in different phases of disease activity in a north Indian cohort
Authors: Juyal Garima , Sood Ajit , Midha Vandana , Singh Arshdeep , Singh Dharmatma , Mahajan Ramit , Verma Vijay , Bhatnagar Rakesh , Joshi Mohan C 
Published: December 2021

AbstractBackground and AimsA link between gut microbiota and Ulcerative colitis (UC) has been established in several studies. However, only a few studies have examined specific changes in microbiota associated with different phases of disease activity in UC. In this study, we attempted to identify differentially abundant taxa between (i) UC patients and healthy controls and (ii) different phases of disease activity, in a genetically distinct north Indian (NI) population.Methods16S rRNA (V3–V4) sequencing of 105 patients with UC [newly diagnosed (n=14); patients in remission (n=36) and active disease (relapse, n=55)]; and 36 healthy controls was performed and analysed.ResultsLower gut microbial diversity; enrichment of lactate-producing bacteria namely Streptococcus, Bifidobacterium and Lactobacillus; and depletion of butyrate-producing bacteria (e.g., Lachnospiraceae and Ruminococcaceae), were observed among UC patients. Subgroup analysis revealed differential abundance of Escherichia-Shigella, Streptococcus, Enterococcus and Faecalibacterium in newly diagnosed UC patients. No discrete microbial features were observed between patients in remission and those with active disease. Co-occurrence network analysis revealed a mutualistic association between opportunistic pathogens and Bifidobacterium and Lactobacillus and antagonistic relationship with butyrate-producers.ConclusionThis first faecal microbiome study among NI UC cohort elucidated dysanaerobiosis; loss of short chain fatty acid producers and enrichment of inflammation associated microbes; population specific differential microbial genera; and a potential microbial signature for early dysbiosis.
Racial and ethnic disparities in COVID-19 vaccinations in the United States during the booster rollout
Authors: Faust Jeremy Samuel , Renton Benjamin , Essien Utibe R. , Gounder Céline R. , Lin Zhenqiu , Krumholz Harlan M. 
Published: December 2021

AbstractBackgroundWe sought to quantify whether there were statistically significant disparities along race and ethnicity lines during the early rollout of Covid-19 vaccine booster doses in the United States. We also studied whether such disparities replicated or widened disparities that had already been observed during the initial series rollout as of 2 months earlier (Janssen) or 6 months earlier (Pfizer-BioNTech or Moderna), which comprised the booster-eligible population.MethodsThis cross-sectional study of US adults (ages ≥18 years) used public data from US Centers for Disease Control and Prevention. The observed shares of vaccine doses for each race and ethnicity were compared to the expected shares, predicted based upon the compositions of the booster-eligible and initial series-eligible populations.ResultsAs of November 16, 2021, 123.5 million US adults were eligible for a booster dose of either the Pfizer-BioNTech, Moderna, or Janssen vaccines. Of these, 21.7 million had received a booster dose, among whom race and ethnicity information was available for 18.8 million booster recipients.A statistically significant higher share of Non-Hispanic White and Non-Hispanic Multiple/Other race individuals had received a booster vaccination than projected based on the composition of the booster-eligible population. A statistically significant lower share of Hispanic, Non-Hispanic American Indian/Alaskan Native, Non-Hispanic Asian, Non-Hispanic Black, and Non-Hispanic Native Hawaiian/Other Pacific Islander individuals had received a booster vaccination than expected based on the booster-eligible population. A secondary analysis of the booster-eligible population found that some of these disparities had already occurred at the time of the initial series. However, the booster campaign widened all of those disparities and added new disparities for Non-Hispanic American Indian/Alaskan Native and Non-Hispanic Native Hawaiian/Other Pacific Islander individuals.ConclusionDisparities in Covid-19 vaccine administration on race and ethnicity lines occurred during the initial series rollout in the US. However, these disparities were not merely replicated but widened by the early booster rollout.
The potential impact of Omicron and future variants of concern on SARS-CoV-2 transmission dynamics and public health burden: a modelling study
Authors: Le Rutte Epke A , Shattock Andrew J , Chitnis Nakul , Kelly Sherrie L , Penny Melissa A 
Published: December 2021

SummarySARS-CoV-2 variant Omicron (B.1.1.529) was classified as a variant of concern (VOC) on November 26, 2021. (1, 2) The infectivity, severity, and immune evasion properties of Omicron relative to the Delta variant would determine 1) the probability of dominant future transmission, and 2) the impact on disease burden. (3, 4) Here we apply individual-based transmission model OpenCOVID to identify thresholds for Omicron’s or any VOC’s potential future dominance, impact on health, and risk to health systems; and identify for which combinations of viral properties, current interventions would be sufficient to control transmission. We show that, with first-generation SARS-CoV-2 vaccines (5) and limited physical distancing in place, the threshold for Omicron’s future dominance was primarily be driven by its degree of infectivity. However, we identified that a VOC’s potential dominance will not necessarily lead to increased public health burden. Expanded vaccination, that includes a third-dose for adults and child vaccination strategies, was projected to have the biggest public health benefit for a highly infective, highly severe VOC with low immune evasion capacity. However, a highly immune evading variant that becomes dominant would likely require alternative measures for control, such as strengthened physical distancing measures, novel treatments, and second-generation vaccines. These findings provide quantitative guidance to decision-makers at a critical time while Omicron’s properties are being assessed and preparedness for new VOC’s is eminent. (6) We emphasize the importance of both genomic and population epidemiological surveillance.
Black chromatin is indispensable for accurate simulations of Drosophila melanogaster chromatin structure
Authors: Tuszynska Irina , Bednarz Pawel , Wilczynski Bartek 
Published: December 2021

AbstractThe interphase chromatin structure is extremely complex, precise and dynamic. Experimental methods can only show the frequency of interaction of the various parts of the chromatin. Therefore, it is extremely important to develop theoretical methods to predict the chromatin structure. In this publication, we describe the necessary factors for the effective modeling of the chromatin structure in Drosophila melanogaster. We also compared Monte Carlo with Molecular Dynamic methods. We showed that incorporating black, non-reactive chromatin is necessary for successfully prediction of chromatin structure, while the loop extrusion model or using Hi-C data as input are not essential for the basic structure reconstruction.Abstract Figure
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
Authors: Cameroni Elisabetta , Saliba Christian , Bowen John E. , Rosen Laura E. , Culap Katja , Pinto Dora , VanBlargan Laura A. , De Marco Anna , Zepeda Samantha K. , Iulio Julia di , Zatta Fabrizia , Kaiser Hannah , Noack Julia , Farhat Nisar , Czudnochowski Nadine , Havenar-Daughton Colin , Sprouse Kaitlin R. , Dillen Josh R. , Powell Abigail E. , Chen Alex , Maher Cyrus , Yin Li , Sun David , Soriaga Leah , Bassi Jessica , Silacci-Fregni Chiara , Gustafsson Claes , Franko Nicholas M. , Logue Jenni , Iqbal Najeeha Talat , Mazzitelli Ignacio , Geffner Jorge , Grifantini Renata , Chu Helen , Gori Andrea , Riva Agostino , Giannini Olivier , Ceschi Alessandro , Ferrari Paolo , Cippà Pietro , Franzetti-Pellanda Alessandra , Garzoni Christian , Halfmann Peter J. , Kawaoka Yoshihiro , Hebner Christy , Purcell Lisa A. , Piccoli Luca , Pizzuto Matteo Samuele , Walls Alexandra C. , Diamond Michael S. , Telenti Amalio , Virgin Herbert W. , Lanzavecchia Antonio , Veesler David , Snell Gyorgy , Corti Davide 
Published: December 2021

SUMMARYThe recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity relative to the Wuhan-Hu-1 RBD and acquires binding to mouse ACE2. Severe reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for vaccinated and convalescent individuals. Most (26 out of 29) receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only three mAbs, including the ACE2-mimicking S2K146 mAb1, retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs recognizing antigenic sites outside the RBM, including sotrovimab2, S2X2593 and S2H974, neutralized Omicron. The magnitude of Omicron-mediated immune evasion and the acquisition of binding to mouse ACE2 mark a major SARS-CoV-2 mutational shift. Broadly neutralizing sarbecovirus mAbs recognizing epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.
genomicSimulation: fast R functions for stochastic simulation of breeding programs
Authors: Villiers Kira , Dinglasan Eric , Hayes Ben J. , Voss-Fels Kai P. 
Published: December 2021

AbstractSimulation tools are key to designing and optimising breeding programs that are multi-year, high-effort endeavours. Tools that operate on real genotypes and integrate easily with other analysis software are needed to guide users to crossing decisions that best balance genetic gains and diversity to maintain gains in the future. This paper presents genomicSimulation, a fast and flexible tool for the stochastic simulation of crossing and selection on real genotypes. It is fully written in C for high execution speeds, has minimal dependencies, and is available as an R package for integration with R’s broad range of analysis and visualisation tools. Comparisons of a simulated recreation of a breeding program to the real data shows that the tool’s simulated offspring correctly show key population features, such as linkage disequilibrium patterns and genomic relationships. Both versions of genomicSimulation are freely available on GitHub: The R package version at https://github.com/vllrs/genomicSimulation/ and the C library version at https://github.com/vllrs/genomicSimulationC/
Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection
Authors: Shoham Shmuel , Bloch Evan M , Casadevall Arturo , Hanley Daniel , Lau Bryan , Gebo Kelly , Cachay Edward , Kassaye Seble G. , Paxton James H. , Gerber Jonathan , Levine Adam C , Currier Judith , Patel Bela , Allen Elizabeth S. , Anjan Shweta , Appel Lawrence , Baksh Sheriza , Blair Paul W. , Bowen Anthony , Broderick Patrick , Caputo Christopher A , Cluzet Valerie , Cordisco Marie Elena , Cruser Daniel , Ehrhardt Stephan , Forthal Donald , Fukuta Yuriko , Gawad Amy L. , Gniadek Thomas , Hammel Jean , Huaman Moises A. , Jabs Douglas A. , Jedlicka Anne , Karlen Nicky , Klein Sabra , Laeyendecker Oliver , Lane Karen , McBee Nichol , Meisenberg Barry , Merlo Christian , Mosnaim Giselle , Park Han-Sol , Pekosz Andrew , Petrini Joann , Rausch William , Shade David M. , Shapiro Janna R. , Singleton J. Robinson , Sutcliffe Catherine , Thomas David L. , Yarava Anusha , Zand Martin , Zenilman Jonathan M. , Tobian Aaron A.R. , Sullivan David 
Published: December 2021

ABSTRACTBACKGROUNDThe efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection.METHODSThis double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was development of SARS-CoV-2 infection.RESULTS180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for SARS-CoV-2 RT-PCR positivity at screening. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. There were 28 adverse events in CCP and 58 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs. 25.2 days; p=0.49) and COVID-19 (26.3 vs. 25.9 days; p=0.35) were similar for both groups.CONCLUSIONIn this trial, which enrolled persons with recent exposure to a person with confirmed COVID-19, high titer CCP as post-exposure prophylaxis appeared safe, but did not prevent SARS-CoV-2 infection.Trial RegistrationClinicaltrial.gov number NCT04323800.
Evaluating the impact and cost-effectiveness of scaling-up HCV treatment among people who inject drugs in Ukraine
Authors: Stone Jack , Walker Josephine G , Bivegete Sandra , Trickey Adam , Chasela Charles , Semchuk Nadiya , Sazonova Yana , Varetska Olga , Saliuk Tetiana , Altice Frederick L , Tsenilova Zhanna , Islam Zahedul , Marunko Dina , Wang Bangyuan , Voets Ancella , Chawla Revati , Vickerman Peter 
Published: December 2021

AbstractIntroductionPeople who inject drugs (PWID) in Ukraine have a high prevalence of hepatitis C virus (HCV). Since 2015, PWID have been receiving HCV treatment, but their impact and cost-effectiveness has not been estimated.MethodsWe developed a dynamic model of HIV and HCV transmission among PWID in Ukraine, incorporating ongoing HCV treatment (5,933 treatments) over 2015–2021; 46.1% among current PWID. We estimated the impact of these treatments and different treatment scenarios over 2021-2030: continuing recent treatment rates (2,394 PWID/year) with 42.5/100% among current PWID, or treating 5,000/10,000 current PWID/year. We also estimated the treatment rate required to decrease HCV incidence by 80% if preventative interventions are scaled-up or not. Required costs were collated from previous studies in Ukraine. We estimated the incremental cost-effectiveness ratio (ICER) of the HCV treatments undertaken in 2020 (1,059) by projecting the incremental costs and disability adjusted life years (DALYs) averted over 2020-2070 (3% discount rate) compared to a counterfactual scenario without treatment from 2020 onwards.ResultsOn average, 0.4% of infections among PWID were treated annually over 2015-2021, without which HCV incidence would have been 0.6% (95%CrI: 0.3-1.0%) higher in 2021. Continuing existing treatment rates could reduce HCV incidence by 10.2% (7.8-12.5%) or 16.4% (12.1-22.0%) by 2030 if 42.5% or 100% of treatments are given to current PWID, respectively. HCV incidence could reduce by 29.3% (20.7-44.7%) or 93.9% (54.3-99.9%) by 2030 if 5,000 or 10,000 PWID are treated annually. To reduce incidence by 80% by 2030, 19,275 (15,134-23,522) annual treatments are needed among current PWID, or 17,955 (14,052-21,954) if preventative interventions are scaled-up. The mean ICER was US$828.8/DALY averted; cost-effective at a willingness-to-pay threshold of US$3,096/DALY averted (1xGDP).ImplicationsExisting HCV treatment is cost-effective but has had little preventative impact due to few current PWID being treated. Further treatment expansion for current PWID could significantly reduce HCV incidence.
Proinflammatory Cytokine Levels in Sepsis and in Health and TNFα Association with Sepsis Mortality and patient characteristics: a Systematic Review and Meta-analysis
Authors: Gharamti Amal A. , Samara Omar , Monzon Anthony , Montalbano Gabrielle , Scherger Sias , DeSanto Kristen , Chastain Daniel B. , Sillau Stefan , Montoya Jose G. , Franco-Paredes Carlos , Henao-Martínez Andrés F. , Shapiro Leland 
Published: December 2021

AbstractBackgroundSepsis is a global health problem associated with significant morbidity and mortality. Detrimental sepsis effects are attributed to a “cytokine storm.” However, anti-cytokine therapies have failed to lower sepsis mortality. We aim to characterize levels of key cytokines in sepsis patients and healthy controls and relate TNFα levels to patient characteristics and outcomes.MethodsWe performed a systematic review and meta-analysis. Medline, Embase, Cochrane Library, and Web of Science Core Collection databases were searched from 1985 to May 2020 for studies in English. We included randomized controlled trials (RCTs), controlled trials, cohort studies, case series, and cross-sectional studies that reported mean levels of cytokines in the circulation thought to be relevant for sepsis pathogenesis. We also evaluated concentrations of these cytokines in healthy persons. Quality in Prognosis Studies tool was used to assess the methodological quality of included studies. We extracted summary data from published reports. Data analyses were performed using a random-effects model to estimate pooled odds ratios (OR) with 95% confidence intervals for cytokine levels and mortality. This systematic review is registered in PROSPERO (CRD42020179800).FindingsWe identified 3654 records, and 104 studies were included with a total of 3250 participants. The pooled estimated mean TNFα concentration in sepsis patients was 58.4 pg/ml (95% Confidence Interval or CI 39.8-85.8 pg/ml) and 5.5 pg/ml (95% CI 3.8-8.0 pg/ml) in healthy controls. Pooled estimate means for IL-1β and IFNγ in sepsis patients were 21.8 pg/ml and 63.3 pg/ml, respectively. Elevated TNFα concentrations associated with increased 28-day sepsis mortality (p=0.001). In subgroup analyses, TNFα levels did not relate to sepsis source, sepsis severity, or sequential organ failure assessment (SOFA) score.InterpretationTNFα concentration in sepsis is increased approximately 10-fold compared to healthy persons, and TNFα associated with sepsis mortality but not with sepsis severity. The concept that elevated cytokines cause sepsis should be revisited in the context of these data.FundingNone.
Oxoglutarate dehydrogenase coordinates myofibril growth by maintaining amino acid homeostasis
Authors: Morales Nicanor González , Marescal Océane , Szikora Szilárd , Erdelyi Miklos , Bíró Péter , Mesquita Tuana , Mihály József , Schöck Frieder 
Published: December 2021

AbstractMyofibrils are long intracellular cables specific to muscles, composed mainly of actin and myosin filaments. The actin and myosin filaments are organized into repeated units called sarcomeres, which form the myofibril cables. Muscle contraction is achieved by the simultaneous shortening of sarcomeres and for a highly coordinated contraction to occur all sarcomeres should have the same size. Muscles have evolved a variety of ways to ensure sarcomere homogeneity, one example being the controlled oligomerization of Zasp proteins that sets the diameter of the myofibril. To understand how Zasp proteins effect myofibril growth, we looked for Zasp-binding proteins at the Z-disc. We found that the E1 subunit of the oxoglutarate dehydrogenase complex is recruited to the Z-disc by Zasp52 and is required to sustain myofibril growth. By making specific mutants, we show that its enzymatic activity is important for myofibril growth, and that the other two subunits of the complex are also required for myofibril formation. Using super resolution microscopy, we revealed the overall organization of the complex at the Z-disc. Then, using metabolomic analysis, we uncovered an amino acid balance defect affecting protein synthesis, that we also confirmed by genetic tools. In summary, we show that Zasp controls the local amino acid pool responsible for myofibril growth by recruiting the OGDH complex to the Z-disc.
Regenerated crustacean limbs are precise replicas
Authors: Almazán Alba , Çevrim Çağrı , Musser Jacob M. , Averof Michalis , Paris Mathilde 
Published: December 2021

AbstractAnimals can regenerate complex organs, yet this frequently results in imprecise replicas of the original structure. In the crustacean Parhyale, embryonic and regenerating legs differ in gene expression dynamics but produce apparently similar mature structures. We examine the fidelity of Parhyale leg regeneration using complementary approaches to investigate microanatomy, sensory function, cellular composition and cell molecular profiles. We find that regeneration precisely replicates the complex microanatomy and spatial distribution of external sensory organs, and restores their sensory function. Single-nuclei sequencing shows that regenerated and uninjured legs are indistinguishable in terms of cell type composition and transcriptional profiles. This remarkable fidelity highlights the ability of organisms to achieve identical outcomes via distinct processes.