bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the Effectiveness of Covid-19 Vaccines from SARS-CoV-2 Variants Neutralisation Data
Authors: Volkov Oleg , Borozdenkova Svetlana , Gray Alexander 
Published: September 2021

AbstractRapid and accurate prediction of Covid-19 vaccine effectiveness is crucial to response against SARS-CoV-2 variants of concern. Despite intensive research, several prediction tasks are not well supported, such as predicting effectiveness of partial vaccination, of vaccine boosters and in vaccinated subpopulations. This paper introduces a novel predictive framework to accommodate such tasks and improve prediction accuracy. It was developed for predicting the symptomatic effectiveness of the BNT162b2 (Comirnaty) and ChAdOx1 nCoV-19 (Vaxzevria) vaccines but could apply to other vaccines and effectiveness types. Direct prediction within the framework uses levels of vaccine-induced neutralising antibodies against SARS-CoV-2 variants to fit efficacy and effectiveness estimates from studies with a given vaccine. Indirect prediction uses a model fitted for one vaccine to predict the effectiveness of another. The directly predicted effectiveness of Comirnaty against the Delta variant was 44.8% (22, 69) after one and 84.6% (64, 97) after two doses, which is close to 45.6% and 85.5%, the average estimates from effectiveness studies with the vaccine. The corresponding direct predictions for Vaxzevria were 41.6% (18, 68) and 63.2% (37, 86); and the indirect predictions, from the model fitted to Comirnaty data, were 45.5% (23, 70) and 61.2% (37, 83). Both sets of predictions are comparable to the average estimates, 42.5% and 66.3%, from effectiveness studies with Vaxzevria. Further results are presented on age subgroups; prediction biases and their mitigation; and implications for vaccination policies.
Analysis of 6.4 million SARS-CoV-2 genomes identifies mutations associated with fitness
Authors: Obermeyer Fritz , Jankowiak Martin , Barkas Nikolaos , Schaffner Stephen F. , Pyle Jesse D. , Yurkovetskiy Lonya , Bosso Matteo , Park Daniel J. , Babadi Mehrtash , MacInnis Bronwyn L. , Luban Jeremy , Sabeti Pardis C. , Lemieux Jacob E. 
Published: September 2021

AbstractRepeated emergence of SARS-CoV-2 variants with increased fitness necessitates rapid detection and characterization of new lineages. To address this need, we developed PyR0, a hierarchical Bayesian multinomial logistic regression model that infers relative prevalence of all viral lineages across geographic regions, detects lineages increasing in prevalence, and identifies mutations relevant to fitness. Applying PyR0to all publicly available SARS-CoV-2 genomes, we identify numerous substitutions that increase fitness, including previously identified spike mutations and many non-spike mutations within the nucleocapsid and nonstructural proteins. PyR0forecasts growth of new lineages from their mutational profile, identifies viral lineages of concern as they emerge, and prioritizes mutations of biological and public health concern for functional characterization.One Sentence summaryA Bayesian hierarchical model of all SARS-CoV-2 viral genomes predicts lineage fitness and identifies associated mutations.
Genome-wide association study of REM sleep behavior disorder identifies novel loci with distinct polygenic and brain expression effects
Authors: Krohn Lynne , Heilbron Karl , Blauwendraat Cornelis , Reynolds Regina H. , Yu Eric , Senkevich Konstantin , Rudakou Uladzislau , Estiar Mehrdad A. , Gustavsson Emil K. , Brolin Kajsa , Ruskey Jennifer A. , Freeman Kathryn , Asayesh Farnaz , Chia Ruth , Arnulf Isabelle , Hu Michele T.M. , Montplaisir Jacques Y. , Gagnon Jean-François , Desautels Alex , Dauvilliers Yves , Gigli Gian Luigi , Valente Mariarosaria , Janes Francesco , Bernardini Andrea , Högl Birgit , Stefani Ambra , Ibrahim Abubaker , Sonka Karel , Kemlink David , Oertel Wolfgang , Janzen Annette , Plazzi Giuseppe , Biscarini Francesco , Antelmi Elena , Figorilli Michela , Puligheddu Monica , Mollenhauer Brit , Trenkwalder Claudia , Sixel-Döring Friederike , De Cock Valérie Cochen , Monaca Christelle Charley , Heidbreder Anna , Ferini-Strambi Luigi , Dijkstra Femke , Viaene Mineke , Abril Beatriz , Boeve Bradley F. ,   23andMe Research Team, Scholz Sonja W. , Ryten Mina , Bandres-Ciga Sara , Noyce Alastair , Cannon Paul , Pihlstrøm Lasse , Nalls Mike A. , Singleton Andrew B. , Rouleau Guy A. , Postuma Ronald B. , Gan-Or Ziv 
Published: September 2021

ABSTRACTRapid eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies. RBD also defines more severe forms of alpha-synucleinopathies. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we performed the first genome-wide association study of RBD, identifying five RBD risk loci. Expression analyses highlight SNCA-AS1 and SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Genetic risk score and other analyses provide further insights into RBD genetics, highlighting RBD as a unique subpopulation that will allow future early intervention.
SARS-CoV-2 variant exposures elicit antibody responses with differential cross-neutralization of established and emerging strains including Delta and Omicron
Authors: Laurie Matthew T , Liu Jamin , Sunshine Sara , Peng James , Black Douglas , Mitchell Anthea M , Mann Sabrina A , Pilarowski Genay , Zorn Kelsey C , Rubio Luis , Bravo Sara , Marquez Carina , Sabatino Joseph J , Mittl Kristen , Petersen Maya , Havlir Diane , DeRisi Joseph 
Published: September 2021

ABSTRACTThe wide spectrum of SARS-CoV-2 variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of the immune response to different spike protein versions. Here, we compare the neutralization of variants of concern, including B.1.617.2 (Delta) and B.1.1.529 (Omicron) in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure. We also observe that exposure to multiple spike variants increases the breadth of variant cross-neutralization. These findings contribute to understanding relationships between exposures and antibody responses and may inform booster vaccination strategies.SUMMARYThis study characterizes neutralization of eight different SARS-CoV-2 variants, including Delta and Omicron, with respect to nine different prior exposures, including vaccination, booster, and infections with Delta, Epsilon, and others. Different exposures were found to confer substantially differing neutralization specificity.
Impact of direct-acting antiviral treatment of hepatitis C on the quality of life of adults in Ukraine
Authors: Benade M , Rosen S , Antoniak S , Chasela C , Stopolianska Y , Barnard T , Gandhi MM , Ivanchuk I , Tretiakov V , Dible J , Minior T , Chew KW , van der Horst C , Tsenilova Z , Sanne I ,   for EQUIP Health
Published: September 2021

AbstractBackgroundDirect-acting antivirals (DAAs) are highly effective in achieving sustained virologic response among those with chronic hepatitis C virus (HCV) infection. Quality of life (QOL) benefits for an HCV-infected population with high numbers of people who inject drugs and people living with HIV (PLHIV) in Eastern Europe have not been explored. We estimated such benefits for Ukraine.MethodsUsing data from a demonstration study of 12-week DAA conducted in Kyiv, we compared self-reported QOL as captured with the MOS-SF20 at study entry and 12 weeks after treatment completion (week 24). We calculated domain scores for health perception, physical, role and social functioning, mental health and pain to at entry and week 24, stratified by HIV status.ResultsAmong the 857 patients included for the final analysis, health perception was the domain that showed the largest change, with an improvement of 85.7% between entry and week 24. The improvement was larger among those who were HIV negative (104.4%) compared to those living with HIV (69.9%). Other domains that showed significant and meaningful improvements were physical functioning, which improved from 80.5 (95% CI: 78.9-82.1) at study entry to 89.4 (88.1-90.7) at 24 weeks, role functioning (64.5 [62.3-66.8] to 86.5 [84.9-88.2], social functioning (74.2 [72.1-76.2] to 84.8 [83.2-86.5] and bodily pain (70.1 [68.2-72.0] to 89.8 [88.5-91.1]). Across all domains, QOL improvements among PLHIV were more modest than among HIV-negative participants.ConclusionQOL improved substantially across all domains between study entry and week 24. Changes over the study period were smaller among PLHIV.
‘Citizens’ Attitudes Under Covid19’: a cross-country panel survey of public opinion in 11 democracies
Authors: Brouard Sylvain , Foucault Martial , Michel Elie , Becher Michael , Vasilopoulos Pavlos , Bono Pierre-Henri , Sormani Nicolas 
Published: September 2021

AbstractThis article introduces data collected in the Citizens’ Attitudes Under Covid-19 Project (CAUCP), which surveyed public opinion throughout the Covid-19 pandemic in 11 countries between March to December 2020. In this paper, we present a unique cross-country panel survey of citizens’ attitudes and behaviors during a worldwide unprecedented health, governance, and economic crisis. This dataset allows to examine the behavioral and attitudinal consequences of crisis across time and contexts. In this paper, we describe the set-up of the CAUCP and the main features of the dataset and we present promising research prospects.
Investigating the biological and technical origins of unknown bases in the S region of the SARS-CoV-2 Delta variant genome sequences
Authors: Borcard Loïc , Gempeler Sonja , Terrazos Miani Miguel A. , Baumann Christian , Grädel Carole , Dijkman Ronald , Suter-Riniker Franziska , Leib Stephen L , Bittel Pascal , Neuenschwander Stefan , Ramette Alban 
Published: September 2021

AbstractWe are reporting on the observation of a large, under-sequenced region of the S gene of the SARS-CoV2 Delta variant genomes, identified in sequences originating from various sequencing centres worldwide (e.g. USA, India, England, Switzerland, France, Germany). This poorly sequenced region was identified from the early phases of the Delta variant spread and the phenomenon is still ongoing. As many commonly-used protocols rely on amplicon-based sequencing procedures, we investigated the likely origin of the issue. We established its biological origin as resulting from mutations in the viral genomes at primer binding sites. We designed and evaluated new PCR primers to circumvent this issue in order to complement the ARTIC v3 set, and validated their performance for the sequencing of circulating Delta variants.
The clinically extremely vulnerable to COVID: Identification and changes in healthcare while self-isolating (shielding) during the coronavirus pandemic
Authors: Butler Jessica E. , Nath Mintu , Blana Dimitra , Ball William P. , Beech Nicola , Black Corri , Osler Graham , Peytrignet Sebastien , Wilde Katie , Wozniak Artur , Sawhney Simon 
Published: September 2021

ABSTRACTBackgroundIn March 2020, the government of Scotland identified people deemed clinically extremely vulnerable to COVID due to their pre-existing health conditions. These people were advised to strictly self-isolate (shield) at the start of the pandemic, except for necessary healthcare. We examined who was identified as clinically extremely vulnerable, how their healthcare changed during isolation, and whether this process exacerbated healthcare inequalities.MethodsWe linked those on the shielding register in NHS Grampian, a health authority in Scotland, to healthcare records from 2015-2020. We described the source of identification, demographics, and clinical history of the cohort. We measured changes in out-patient, in-patient, and emergency healthcare during isolation in the shielding population and compared to the general non-shielding population.ResultsThe register included 16,092 people (3% of the population), clinically vulnerable primarily due to a respiratory disease, immunosuppression, or cancer. Among them, 42% were not identified by national healthcare record screening but added ad hoc, with these additions including more children and fewer economically-deprived.During isolation, all forms of healthcare use decreased (25%-46%), with larger decreases in scheduled care than in emergency care. However, people shielding had better maintained scheduled care compared to the non-shielding general population: out-patient visits decreased 35% vs 49%; in-patient visits decreased 46% vs 81%. Notably, there was substantial variation in whose scheduled care was maintained during isolation: younger people and those with cancer had significantly higher visit rates, but there was no difference between sexes or socioeconomic levels.ConclusionsHealthcare changed dramatically for the clinically extremely vulnerable population during the pandemic. The increased reliance on emergency care while isolating indicates that continuity of care for existing conditions was not optimal. However, compared to the general population, there was success in maintaining scheduled care, particularly in young people and those with cancer. We suggest that integrating demographic and primary care data would improve identification of the clinically vulnerable and could aid prioritising their care.
Effectiveness of the Single-Dose Ad26.COV2.S COVID Vaccine
Authors: Polinski Jennifer M. , Weckstein Andrew R. , Batech Michael , Kabelac Carly , Kamath Tripthi , Harvey Raymond , Jain Sid , Rassen Jeremy A. , Khan Najat , Schneeweiss Sebastian 
Published: September 2021

AbstractImportanceVaccination against the SARS-CoV-2 virus is critical to control the pandemic. Randomized trials demonstrated efficacy of the single-dose Ad26.COV2.S COVID vaccine but data on longer-term protection in clinical practice and effectiveness against variants are needed.ObjectiveTo assess the effectiveness of Ad26.COV2.S in preventing COVID infections and COVID-related hospitalizations in clinical practice, the longer-term stability of its protective effect and effectiveness against Delta variants.DesignCohort study of newly Ad26.COV2.S-vaccinated and unvaccinated individuals.SettingU.S. insurance claims data through July 2021.ParticipantsIndividuals 18 years and older newly vaccinated with Ad26.COV2.S and up to 10 unvaccinated individuals matched exactly by age, sex, date, location, comorbidity index plus 17 COVID-19 risk factors via propensity score (PS) matching.InterventionVaccination with Ad26.COV2.S versus no vaccination.Main outcomesWe estimated vaccine effectiveness (VE) for observed COVID-19 infection and COVID-19-related hospitalization, nationwide and stratified by age, immunocompromised status, calendar time, and states with high incidence of the Delta variant. We corrected VE estimates for under-recording of vaccinations in insurance data.ResultsAmong 390,517 vaccinated and 1,524,153 matched unvaccinated individuals, VE was 79% (95% CI, 77% to 80%) for COVID-19 and 81% (79% to 84%) for COVID-19-related hospitalizations. VE was stable over calendar time. Among states with high Delta variant incidence, VE during June/July 2021 was 78% (73% to 82%) for infections and 85% (73% to 91%) for hospitalizations. VE for COVID-19 was higher in individuals <50 years (83%; 81% to 85%) and lower in immunocompromised patients (64%; 57% to 70%). All estimates were corrected for under-recording; uncorrected VE was 69% (67% to 71%) and 73% (69% to 76%), for COVID-19 and COVID-19-related hospitalization, respectively.ConclusionsThese non-randomized data across U.S. clinical practices show high and stable vaccine effectiveness of Ad26.COV2.S over time before the Delta variant emerged to when the Delta variant was dominant.
MinoTour, real-time monitoring and analysis for Nanopore Sequencers
Authors: Munro Rory , Santos Roberto , Payne Alexander , Forey Teri , Osei Solomon , Holmes Nadine , Loose Matt 
Published: September 2021

AbstractSummaryMinoTour offers a LIMS system for Oxford Nanopore Technology (ONT) sequencers, with real-time metrics and analysis available permanently for review. Integration of unique real-time automated analysis can reduce the time required to answer biological questions, including mapping and classification of sequence whilst a run is in progress. Real-time sequence data requires new methods of analysis which do not wait for the completion of a run and MinoTour provides a framework to allow users to exploit these features.Availability and ImplementationSource code and documentation are available at https://github.com/LooseLab/minotourcli and https://github.com/LooseLab/minotourapp. Docker images are available from https://hub.docker.com/r/adoni5/, and can be installed using a preconfigured docker-compose script at https://github.com/LooseLab/minotour-docker. An example server is available at http://137.44.59.170.
Astrocytic cell adhesion genes linked to schizophrenia correlate with synaptic programs in neurons
Authors: Pietiläinen Olli , Trehan Aditi , Meyer Daniel , Mitchell Jana , Tegtmeyer Matthew , Valakh Vera , Gebre Hilena , Chen Theresa , Vartiainen Emilia , Farhi Samouil L. , Eggan Kevin , McCarroll Steven A. , Nehme Ralda 
Published: September 2021

AbstractThe maturation of neurons and the development of synapses – while emblematic of neurons – also rely on interactions with astrocytes and other glia. To study the role of glia-neuron interactions, we analyzed the transcriptomes of human pluripotent stem cell (hPSC)-derived neurons, from a total of 80 human donors, that were cultured with or without contact with glial cells. We found that the presence of astrocytes enhanced synaptic gene-expression programs in neurons. These changes in neuronal synaptic gene expression correlated with increased expression in the co-cultured glia of genes that encode synaptic cell adhesion molecules, and they were greatly enhanced in the glia in coculture. Both the neuronal and astrocyte gene-expression programs were enriched for genes that are linked to schizophrenia risk. Physical contact between the two cell types was required for the induction of synaptic programs in neurons. Our results suggest that astrocyte-expressed genes with synaptic functions are associated with stronger expression of synaptic genetic programs in neurons and suggest a potential role for astrocyte-neuron interactions in schizophrenia.
MKLP2 functions in early mitosis to ensure proper chromosome congression
Authors: Schrock Morgan S. , Scarberry Luke , Stromberg Benjamin R. , Sears Claire , Torres Adrian E. , Tallman David , Krupinski Lucas , Chakravarti Arnab , Summers Matthew K. 
Published: September 2021

AbstractMitotic kinesin-like protein 2 (MKLP2) is a motor protein with a well-established function in promoting cytokinesis. However, our results with siRNAs targeting MKLP2 and small molecule inhibitors of MKLP2 (MKLP2i) suggested a function earlier in mitosis, prior to anaphase. In this study we provide direct evidence that MKLP2 facilitates chromosome congression in prometaphase. We employed live imaging to observe HeLa cells with fluorescently tagged histones treated with MKLP2i and discovered a pronounced chromosome congression defect. We show that MKLP2 is essential for pole-based error correction as inhibited cells had a significant increase in unstable kinetochore-microtubule attachments due to impaired error correction of syntelic attachments. We propose that MKLP2 mediates kinetochore microtubule attachment stability by regulating Aurora Kinase activity and a downstream target, pHEC1 (Ser 55). Lastly, we show that MKLP2 inhibition results in aneuploidy, confirming that MKLP2 safeguards cells against chromosomal instability.SummarySchrock et al. demonstrate that the mitotic kinesin, MKLP2, is required for congression of chromosomes located near the spindle poles. They show that MKLP2 inhibition causes elevated active Aurora Kinase A, unstable microtubule kinetochore attachments, and impaired syntelic error correction.
Activation of the CaMKII-Sarm1-ASK1 MAP kinase pathway protects against axon degeneration caused by loss of mitochondria
Authors: Ding Chen , Wu Youjun , Dabas Hadas , Hammarlund Marc 
Published: September 2021

AbstractMitochondrial defects are tightly linked to axon degeneration, yet the underlying cellular mechanisms remain poorly understood. In C. elegans, PVQ axons that lack mitochondria degenerate spontaneously with age. Using an unbiased genetic screen, we found that cell-specific activation of CaMKII/UNC-43 suppresses axon degeneration due to loss of mitochondria. Unexpectedly, CaMKII/UNC-43 protects against degeneration through the conserved Sarm1/TIR-1-ASK1/NSY-1 MAPK pathway. In addition, we show that disrupting a trafficking complex composed of calsyntenin/CASY-1, Mint/LIN-10, and kinesin suppresses axon degeneration. Further analysis indicates that disruption of this trafficking complex activates the CaMKII-Sarm1-MAPK pathway through L-type voltage-gated calcium channels. Our findings identify CaMKII as a pivot point between mitochondrial defects and axon degeneration, describe how it is regulated in this context, and uncover a surprising neuroprotective role for the Sarm1-ASK1 pathway.
p57Kip2 regulates embryonic haematopoietic stem cell numbers by controlling the size of the sympathoadrenal progenitor pool
Authors: Kapeni Chrysa , Nitsche Leslie , Kilpatrick Alastair M. , Wilson Nicola K. , Xia Kankan , Mirshekar-Syahkal Bahar , Malouf Camille , Göttgens Berthold , Kirschner Kristina , Tomlinson Simon R. , Ottersbach Katrin 
Published: September 2021

ABSTRACTHaematopoietic stem cells (HSCs) are of major clinical importance, and finding methods for their in vitro generation is a prime research focus. We demonstrate that the cell cycle inhibitor p57Kip2/Cdkn1c limits HSC numbers by restricting the size of the sympathetic nervous system (SNS) and the amount of HSC-supportive catecholamines secreted by these cells, specifically in the aorta-gonads-mesonephros (AGM) region via β2-adrenergic receptor signalling. This regulation occurs at the SNS progenitor level and is in contrast to the cell-intrinsic function of p57Kip2 in maintaining adult HSCs. Using single-cell RNA-Seq we dissect the differentiation pathway of neural crest cells into SNS cells in the AGM and reveal that they are able to take an alternative differentiation pathway, giving rise to a subset of mesenchymal cells expressing HSC-supportive factors. Neural crest cells thus appear to contribute to the AGM HSC niche via two different mechanisms: SNS-mediated catecholamine secretion and HSC-supportive mesenchymal cell production.
Reciprocal differentiation via GABAergic components and ASD-related phenotypes in hES with 1q21.1 CNV
Authors: Nomura Yoshiko , Nomura Jun , Nishikawa Toru , Takumi Toru 
Published: September 2021

AbstractCopy number variations (CNVs) in the distal 1q21.1 region, both deletion (1q del) and duplication (1q dup), are associated with autism spectrum disorder, epilepsy and schizophrenia. Besides common phenotypes, 1q del and 1q dup manifest opposite clinical phenotypes—e.g., microcephaly in 1q del and macrocephaly in 1q dup. However, molecular and cellular mechanisms are still elusive. We generate isogenic human ES (hES) cell lines with reciprocal 1q21.1 CNVs using CRISPR/Cas9 system and differentiate them into 2-dimensional (2-D) neurons and 3-D cortical organoids. Our study recapitulates opposite organoid size and shows dosage-dependent differentiation changes i.e., more mature and GABAergic components in 1q del and more proliferative state in 1q dup. In contrast, both CNVs show hyperexcitability and altered expressions of glutamate system as common features. These results demonstrate that 1q21.1 CNVs dramatically affect cell fate in the early neurodevelopmental periods. This is the first isogenic model of hES CNVs and our findings provide new insights into the underlying mechanisms of neurodevelopmental disorders.