bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Canadian COVID-19 Experiences Project: Design and Protocol
Authors: Hall Peter A. , Fong Geoffrey T. , Hitchman Sara C. , Quah Anne C.K. , Agar Thomas , Meng Gang , Ayaz Hasan , Dore Bruce P. , Sakib Mohammad N. , Hudson Anna , Boudreau Christian 
Published: December 2021

AbstractIntroductionVaccine hesitancy and inconsistent mitigation behavior performance have been significant challenges throughout the COVID-19 pandemic. In Canada, despite relatively high vaccine availability and uptake, willingness to accept booster shots and maintain mitigation behaviors in the post-acute phase of COVID-19 remain uncertain. The aim of the Canadian COVID-19 Experiences Project (CCEP) is two-fold: 1) to identify social-cognitive and neurocognitive correlates of vaccine hesitancy and mitigation behaviors, and 2) to identify optimal communication strategies to promote vaccination and mitigation behaviors into the post-acute phase of the pandemic.Methods and analysesThe CCEP is comprised of two components: a conventional population survey (Study 1) and a functionally interconnected laboratory study (Study 2). Study 1 will involve 3 waves of data collection. Wave 1, completed between 28 September and 21 October, 2021, recruited 1,958 vaccine-hesitant (49.8%) and fully vaccinated (50.2%) adults using quota sampling to ensure maximum statistical power. Measures included a variety of social cognitive (e.g., beliefs, intentions) and neurocognitive (e.g., delay discounting) measures, followed by an opportunity to view and rate a set of professionally produced COVID-19 public service announcement (PSA) videos for perceived efficacy. Study 2 employs the same survey items and PSAs but coupled with lab-based eye tracking and functional brain imaging to directly quantify neural indicators of attention capture and self-reflection in a smaller community sample. In the final phase of the project, subjective impressions and neural indicators of PSA efficacy will be compared and used to inform recommendations for construction of COVID-19 PSAs into the post-acute phase of the pandemic.Ethics and disseminationThe CCEP has received ethical review and approval by the University of Waterloo Office of Research Ethics. Findings will be disseminated through peer-reviewed publications and presentations at scientific meetings.
Considering variance in pollinator responses to stressors can reveal potential for resilience
Authors: Cabirol Amélie , Gómez-Moracho Tamara , Monchanin Coline , Pasquaretta Cristian , Lihoreau Mathieu 
Published: December 2021

AbstractEnvironmental stressors have sublethal consequences on animals, often affecting the mean of phenotypic traits in a population. However, potential effects on variance are poorly understood. Since phenotypic variance is the basis for adaptation, any influence of stressors may have important implications for population resilience.Here we explored this possibility in insect pollinators by analysing raw datasets from 24 studies (6,913 bees) in which individuals were first exposed to stressors and then tested for cognitive tasks.While all types of stressors decreased the mean cognitive performance of bees, their effect on variance was complex. Focusing on 15 pesticide studies, we found that the dose and the mode of exposure to stressors were critical. At low pesticide doses, cognitive variance decreased following chronic exposures but not for acute exposures. Acute exposure to low doses thus seems less damaging at the population level. In all cases however, the variance decreased with increasing doses.Policy implications. Current guidelines for the authorization of plant protection products on the European market prioritize acute over chronic toxicity assessments on non-target organisms. By overlooking the consequences of a chronic exposure, regulatory authorities may register new products that are harmful to bee populations. Our findings thus call for more research on stress-induced phenotypic variance and its incorporation to policy guidelines to help identify levels and modes of exposure animals can cope with.
mRNA-1273 vaccination protects against SARS-CoV-2 elicited lung inflammation in non-human primates
Authors: Waickman Adam T. , Victor Kaitlin , Newell Krista , Li Tao , Friberg Heather , Foulds Kathy , Roederer Mario , Bolton Diane L. , Currier Jeffrey R. , Seder Robert 
Published: December 2021

ABSTRACTVaccine-elicited SARS-CoV-2 antibody responses are an established correlate of protection against viral infection in humans and non-human primates. However, it is less clear that vaccine-induced immunity is able to limit infection-elicited inflammation in the lower respiratory tract. To assess this, we collected bronchoalveolar lavage fluid samples post-SARS-CoV-2 strain USA-WA1/2020 challenge from rhesus macaques vaccinated with mRNA-1273 in a dose-reduction study. Single-cell transcriptomic profiling revealed a broad cellular landscape 48 hours post-challenge with distinct inflammatory signatures that correlated with viral RNA burden in the lower respiratory tract. These inflammatory signatures included phagocyte-restricted expression of chemokines such asCXCL10(IP10) andCCL3(MIP-1A) and the broad expression of interferon-induced genes such asMX1, ISG15, andIFIT1. Induction of these inflammatory profiles was suppressed by prior mRNA-1273 vaccination in a dose-dependent manner, and negatively correlated with pre-challenge serum and lung antibody titers against SARS-CoV-2 spike. These observations were replicated and validated in a second independent macaque challenge study using the B.1.351/beta-variant of SARS-CoV-2. These data support a model wherein vaccine-elicited antibody responses restrict viral replication following SARS-CoV-2 exposure, including limiting viral dissemination to the lower respiratory tract and infection-mediated inflammation and pathogenesis.One Sentence SummarySingle cell RNA sequencing analysis demonstrates that mRNA-1273 vaccination limits the development of lower respiratory tract inflammation in SARS-CoV-2 challenged rhesus macaques
SIR model for assessing the impact of the advent of Omicron and mitigating measures on infection pressure and hospitalization needs
Authors: van Wees Jan-Diederik , van der Kuip Martijn , Osinga Sander , Keijser Bart , van Westerloo David , Hanegraaf Maurice , Pluymaekers Maarten , Leeuwenburgh Olwijn , Brunner Logan , van Furth Marceline Tutu 
Published: December 2021

ABSTRACTBackgroundOn 26 November 2021, the world health organization (WHO) designated the coronavirus SARS-CoV-2 B.1.1.529 a variant of concern, named Omicron (WHO, 2021a). As of December 16, Omicron has been detected in 89 countries (WHO, 2021b). The thread posed by Omicron is highly uncertain.Methods and findingsFor the analysis of the impact of Omicron on infection pressure and hospitalization needs we developed an open-source stochastic SIR (Susceptible-Infectious-Removed) fast-model for simulating the transmission in the transition stage from the prevailing variant (most often Delta) to Omicron. The model is capable to predict trajectories of infection pressure and hospitalization needs, considering (a) uncertainties for the (Omicron) parametrization, (b) pre-existing vaccination and/or partial immunity status of the population, and demographic specific aspects regarding reference hospitalization needs, (c) effects of mitigating measures including social distancing and accelerated vaccination (booster) campaigns.ConclusionsThe SIR model approach yields results in fair agreement with Omicron transmission characteristics observed in South Africa and prognosis results in Europe (UK and Netherlands). The equations underlying the SIR formulation allows to effectively explore the effect of Omicron parametrization on anticipated infection growth rates and hospitalization rates relative to the prevailing variant. The models are online available as open source on GitHub.One Sentence Summaryfast-model for the impact of Omicron
Cooccurrence of N501Y, P681R and other key mutations in SARS-CoV-2 Spike
Authors: Lee Carol , Mangalaganesh Shruthi , Wilson Laurence O.W. , Kuiper Michael J. , Drew Trevor W. , Vasan Seshadri S. 
Published: December 2021

AbstractAnalysis of circa 4.2 million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences on ‘Global Initiative on Sharing All Influenza Data (GISAID)’ shows the spike mutations ‘N501Y’ (common to Alpha, Beta, Gamma, Omicron variants) and ‘P681R’ (central to Delta variant’s spread) have cooccurred 3,678 times between 17 October 2020 and 1 November 2021. In contrast, the N501Y+P681H combination is present in Alpha and Omicron variants and circa 1.1 million entries. Two-thirds of the 3,678 cooccurrences were in France, Turkey or US (East Coast), and the rest across 62 other countries. 55.5% and 4.6% of the cooccurrences were Alpha’s Q.4 and Gamma’s P.1.8 sub-lineages acquiring P681R; 10.7% and 3.8% were Delta’s B.1.617.2 lineage and AY.33 sub-lineage acquiring N501Y; remaining 10.2% were in other variants. Despite the selective advantages individually conferred by N501Y and P681R, the N501Y+P681R combination counterintuitively didn’t outcompete other variants in every instance. Although a relief to worldwide public health efforts, in vitro and in vivo studies are urgently required in the absence of a strong in silico explanation for this phenomenon. This study demonstrates a pipeline to analyse combinations of key mutations from public domain information in a systematic manner and provide early warnings of spread.
The SARS-CoV-2 nucleocapsid protein preferentially binds long and structured RNAs
Authors: Tai Christen E. , Tayeb-Fligelman Einav , Griner Sarah , Salwinski Lukasz , Bowler Jeannette T. , Abskharon Romany , Cheng Xinyi , Seidler Paul M. , Jiang Yi Xiao , Eisenberg David S. , Guo Feng 
Published: December 2021

ABSTRACTThe SARS-CoV-2 nucleocapsid protein (NCAP) functions in viral RNA genome packaging, virion assembly, RNA synthesis and translation, and regulation of host immune response. RNA-binding is central to these processes. Little is known how NCAP selects its binding partners in the myriad of host and viral RNAs. To address this fundamental question, we employed electrophoresis mobility shift and competition assays to compare NCAP binding to RNAs that are of SARS-CoV-2 vs. non-SARS-CoV-2, long vs. short, and structured vs. unstructured. We found that although NCAP can bind all RNAs tested, it primarily binds structured RNAs, and their association suppresses strong interaction with single-stranded RNAs. NCAP prefers long RNAs, especially those containing multiple structures separated by single-stranded linkers that presumably offer conformational flexibility. Additionally, all three major regions of NCAP bind RNA, including the low complexity domain and dimerization domain that promote formation of NCAP oligomers, amyloid fibrils and liquid-liquid phase separation. Combining these observations, we propose that NCAP-NCAP interactions that mediate higher-order structures during packaging also drive recognition of the genomic RNA and call this mechanism recognition-by-packaging. This study provides a biochemical basis for understanding the complex NCAP-RNA interactions in the viral life cycle and a broad range of similar biological processes.HIGHLIGHTSNCAP primarily binds structured RNAs.NCAP prefers multiple RNA structures separated by single-stranded linkers.NCAP favors binding to long RNAs.
Identification of a novel proteomic Biomarker in Parkinson’s Disease: Discovery and Replication in Blood, brain and CSF
Authors: Winchester Laura , Lawton Michael , Barber Imelda , Ash Jessica , Liu Benjamine , Evetts Samuel , Hopkins-Jones Lucinda , Lewis Suppalak , Bresner Catherine , Vingill Siv , Malpartida Ana Belen , Williams Nigel , Gentlemen Steve , Wade-Martins Richard , Ryan Brent , Holgado-Nevado Alejo , Hu Michele , Ben-Shlomo Yoav , Grosset Donald , Lovestone Simon 
Published: December 2021

AbstractBiomarkers to aid diagnosis and delineate progression of Parkinson’s Disease (PD) are vital for targeting treatment in the early phases of disease. Here, we aim to discover a multi-protein panel representative of PD and make mechanistic inferences from protein expression profiles within the broader objective of finding novel biomarkers.We used aptamer-based technology (SomaLogic®) to measure proteins in 1,599 serum samples, 85 CSF samples and 37 brain tissue samples collected from two observational longitudinal cohorts (Oxford Parkinson’s Disease Centre and Tracking Parkinson’s) and the PD Brain Bank, respectively. Random forest machine learning was performed to discover new proteins related to disease status and generate multi-protein expression signatures with potential novel biomarkers. Differential regulation analysis and pathway analysis was performed to identify functional and mechanistic disease associations.The most consistent diagnostic classifier signature was tested across modalities (CSF AUC = 0.74, p-value = 0.0009; brain AUC = 0.75, p-value = 0.006; serum AUC = 0.66, p-value = 0.0002). In the validation dataset we showed that the same classifiers were significantly related to disease status (p-values < 0.001). Differential expression analysis and Weighted Gene Correlation Network Analysis (WGCNA) highlighted key proteins and pathways with known relationships to PD. Proteins from the complement and coagulation cascades suggest a disease relationship to immune response.The combined analytical approaches in a relatively large number of samples, across tissue types, with replication and validation, provides mechanistic insights into the disease as well as nominating a protein signature classifier that deserves further biomarker evaluation.
Can individuals with suboptimal antibody responses to conventional antiviral vaccines acquire adequate antibodies from SARS-CoV-2 mRNA vaccination?
Authors: Ogura Wataru , Ohtsuka Kouki , Matsuura Sachiko , Okuyama Takahiro , Matsushima Satsuki , Ymasaki Satoko , Miyagi Hiroyuki , Sekiguchi Kumiko , Ohnishi Hiroaki , Watanabe Takashi 
Published: December 2021

AbstractObjectiveIn Japan, healthcare workers (HCWs) are vaccinated against contagious viruses (measles, rubella, chickenpox, mumps, and hepatitis B) to prevent nosocomial infection; however, some do not produce sufficient antibodies (suboptimal responders). Whether suboptimal responders to live attenuated viruses or inactivated viruses vaccines can produce adequate antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines remains to be elucidated.MethodsIn this prospective cohort study, SARS-CoV-2 anti-spike antibodies were measured 11 times, from before the first BNT162b2 vaccination to 5 months after the second vaccination. Antibody titers of suboptimal and normal responders were compared. SARS-CoV-2 neutralizing antibody activity was measured twice in suboptimal responders, 1 week to 1 month, and 5 months after the second vaccination.PatientsThis study included 50 HCWs who received two doses of mRNA BNT162b2 vaccine 3 weeks apart.ResultsAfter vaccination, the SARS-CoV-2 anti-spike antibody was detectable in the samples from suboptimal and normal responders at each timepoint. The median SARS-CoV-2 anti-spike antibody titer was higher in suboptimal responders than in normal responders 1 week after receiving the second dose of BNT162b2 vaccine (3721.0 vs. 2251.5, P=0.029). Suboptimal responders had SARS-CoV-2 neutralizing antibody activity 1 week to 1 month, and 5 months after the second vaccination, which exceeded the positive threshold 5 months after the second vaccination.ConclusionAfter BNT162b2 vaccination, suboptimal responders acquired adequate SARS-CoV-2 anti-spike and SARS-CoV-2 neutralizing antibodies to prevent SARS-CoV-2. These results suggest that vaccination with mRNA vaccine against SARS-CoV-2 should also be recommended for suboptimal responders to conventional vaccines.
SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron
Authors: Keeton Roanne , Tincho Marius B. , Ngomti Amkele , Baguma Richard , Benede Ntombi , Suzuki Akiko , Khan Khadija , Cele Sandile , Bernstein Mallory , Karim Farina , Madzorera Sharon V. , Moyo-Gwete Thandeka , Mennen Mathilda , Skelem Sango , Adriaanse Marguerite , Mutithu Daniel , Aremu Olukayode , Stek Cari , Bruyn Elsa du , Van Der Mescht Mieke A. , de Beer Zelda , de Villiers Talita R. , Bodenstein Annie , van den Berg Gretha , Mendes Adriano , Strydom Amy , Venter Marietjie , Grifoni Alba , Weiskopf Daniela , Sette Alessandro , Wilkinson Robert J. , Bekker Linda-Gail , Gray Glenda , Ueckermann Veronica , Rossouw Theresa , Boswell Michael T. , Bihman Jinal , Moore Penny L. , Sigal Alex , Ntusi Ntobeko A. B. , Burgers Wendy A. , Riou Catherine 
Published: December 2021

SummaryThe SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron’s extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.
NATIONAL SCALE REAL-TIME SURVEILLANCE OF SARS-COV-2 VARIANTS DYNAMICS BY WASTEWATER MONITORING IN ISRAEL
Authors: Bar-Or Itay , Indenbaum Victoria , Weil Merav , Elul Michal , Levi Nofar , Aguvaev Irina , Cohen Zvi , Levy Virginia , Azar Roberto , Mannasse Batya , Shirazi Rachel , Bochris Efrat , Zuckerman Neta S. , Brown Alin Sela , Sofer Danit , Mor Orna , Mendelson Ella , Erster Oran 
Published: December 2021

ABSTRACTIn this report, we describe a national-scale monitoring of the SARS-COV-2 (SC-2) variant dynamics in Israel, using multiple-time sampling of twelve wastewater treatment plants. We used a combination of inclusive and selective quantitative PCR assays that specifically identify variants A19 or B.1.1.7 and tested each sample for the presence and relative viral RNA load of each variant. We show that between December-2020 and March-2021, a complete shift in the SC-2 variant circulation was observed, where the B.1.1.7 replaced the A19 in all examined test points. We further show that the normalized viral load (NVL) values and the average new cases per week reached a peak in January 2021, and then decreased gradually in almost all test points, in parallel with the progression of the national vaccination campaign, during February-March 2021. This study demonstrates the importance of monitoring SC-2 variant dynamics on a national scale through wastewater sampling. It also provides a proof-of-concept methodology for continuous surveillance by using a combination of inclusive and selective PCR tests, which is far more amendable for high throughput monitoring compared with sequencing. This approach may be useful for real-time dynamics surveillance of current and future variants, such as the Omicron (BA.1) variant.SynopsisThis study describes the continuous monitoring of the SARS CoV-2 variant B.1.1.7 circulation in wastewater in Israel using a positive/negative quantitative PCR assay.
Use of Baricitinib in Treatment of COVID-19: A Systematic Review
Authors: Sampath A , Banerjee A , Atal S , Jhaj R 
Published: December 2021

AbstractObjectivesTo assess the role of baricitinib alone or in combination with other therapies as a treatment for patients with COVID-19.MethodsSystematic literature search was conducted in the WHO COVID-19 Coronavirus disease database to find clinical studies on use of baricitinib for treatment of COVID-19 between December 1st 2019 and September 30th 2021. Two independent set of reviewers identified the eligible studies fulfilling the inclusion criteria, and relevant data was extracted and a qualitative synthesis of evidence performed. The risk of bias was evaluated with validated tools.ResultsA total of 267 articles were found to be eligible after primary screening of title and abstracts. Following assessment of full texts, 19 studies were finally included for this systematic review, out of which 16 are observational, and 3 are interventional studies. Collating the results from these observational and interventional studies, baricitinib used as add on to standard therapy, either alone or in combination with other drugs, was found to have favourable outcomes in moderate to severe hospitalised patients with COVID-19. Furthermore, ongoing trials indicate that drug is being extensively studied across the world for its safety and efficacy in COVID-19.ConclusionBaricitinib significantly improves clinical outcomes in hospitalized patients with COVID-19 pneumonia and further evidence may establish the drug as a standard treatment among such patients.
Phytoremediation of EMS InducedBrassica junceaHeavy Metal Hyperaccumulator Genotypes
Authors: Halder Shema , Anirban Apurba 
Published: December 2021

AbstractBuriganga, an economically important river of Dhaka, Bangladesh, is highly polluted by different toxic heavy metals. In this study, phytoremediation of EMS induced Indian mustard (Brassica junceaL) genotypes against three pollutantsviz. lead (Pb), chromium (Cr) and cadmium (Cd) of Buriganga riverbank soil was assessed in field condition. Among 1-, 2- and 3% EMS induced genotypes, better seed germination rate, germination speed and plant survival rate were observed in 1% EMS induced genotype, BE21. The highest concentration of Pb, Cr and Cd were also obtained in the leaf of BE21 genotype and therefore was considered as a super-hyperaccumulator genotype. Concentration of Pb in the next generation of this genotype was approximately two-fold higher in the root (91.53±6.59 mg/kg dry weight, DW); three-fold higher in the shoot (33.31±1.01 mg/kg DW) and leaf (28.35±3.61 mg/kg DW), and more in the fruit (5.59±0.93 mg/kg DW) than the control. Concentration of Cr was approximately two-fold in the root (57.02±3.24 mg/kg DW), shoot (18.51±1.36 mg/kg DW) and leaf (14.98±2.01 mg/kg DW), and more in the fruit (6.15±1.92 mg/kg DW) of BE21 genotype compared to the control. Cd concentration was more in the root (1.96±0.92 mg/kg DW), leaf (0.52±0.32 mg/kg DW) and fruit (0.19±0.02 mg/kg DW) and less in the shoot (0.19±0.01 mg/kg DW) of BE21 genotype than the control. Root, shoot, leaf and fruit of BE21 altogether accumulated 98-, 73- and 87% Pb, Cr and Cd, respectively and can thus be utilized to remove heavy metals of Buriganga River. As like root, shoot and leaf, fruit also accumulated heavy metals; hence those plants which are used in phytoremediation should not be used as food or fodder. To the best of our knowledge, this is the first report of developing EMS induced hyperaccumulator genotype ofB. junceafor phytoremediation of Buriganga riverbank soil of Bangladesh.