bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 testing and COVID-19 related primary care use among people with citizenship, permanent residency, and temporary immigration status in British Columbia: Cross-sectional analysis of population-based administrative data
Authors: Wiedmeyer M , Goldenberg S , Peterson S , Wanigaratne S , Machado S , Tayyar E , Braschel M , Carrillo R , Sierra-Heredia C , Tuyisenge G , Lavergne MR 
Published: November 2021

AbstractBackgroundHaving temporary immigration status affords limited rights, workplace protections, and access to services. There is not yet research data on impacts of the COVID-19 pandemic for people with temporary immigration status in Canada.MethodsWe use linked administrative data to describe SARS-CoV-2 testing, positive tests, and COVID-19 primary care service use in British Columbia from January 1, 2020, to July 31, 2021, stratified by immigration status (Citizen, Permanent Resident, Temporary Resident). We plot the rate of people tested and the rate of people confirmed positive for COVID-19 by week from April 19, 2020, to July 31, 2021, across immigration groups.Results4.9% of people with temporary immigration status had a positive test for SARS-CoV-2 over this period, compared to 4.0% among people with permanent residency and 2.1% among people who hold Canadian citizenship. This pattern is persistent by sex/gender, age group, neighborhood income quintile, health authority, and in both metropolitan and small urban settings. At the same time we observe lower access to testing and COVID-19 related primary care among people with temporary status.InterpretationPeople with temporary immigration status in BC experience higher SARS-CoV-2 test positivity; alarmingly, this was coupled with lower access to testing and primary care. Interwoven immigration, health and occupational policies place people with temporary status in circumstances of precarity and higher health risk. Extending permanent residency status to all immigrants residing in Canada and decoupling access to health care from immigration status could reduce precarity due to temporary immigration status.
SARS-COV-2 Delta variant displays moderate resistance to neutralizing antibodies and spike protein properties of higher soluble ACE2 sensitivity, enhanced cleavage and fusogenic activity
Authors: Neerukonda Sabari Nath , Vassell Russell , Lusvarghi Sabrina , Wang Richard , Echegaray Fernando , Bentley Lisa , Eakin Ann E. , Erlandson Karl J. , Katzelnick Leah C. , Weiss Carol D. , Wang Wei 
Published: November 2021

AbstractThe SARS-CoV-2 B.1.617 lineage variants, Kappa (B.1.617.1) and Delta (B.1.617.2, AY) emerged during the second wave of infections in India, but the Delta variants have become dominant worldwide and continue to evolve. The spike proteins of B.1.617.1, B.1.617.2, and AY.1 variants have several substitutions in the receptor binding domain (RBD), including L452R+E484Q, L452R+T478K, and K417N+L452R+T478K, respectively, that could potentially reduce effectiveness of therapeutic antibodies and current vaccines. Here we compared B.1.617 variants, and their single and double RBD substitutions for resistance to neutralization by convalescent sera, mRNA vaccine-elicited sera, and therapeutic neutralizing antibodies using a pseudovirus neutralization assay. Pseudoviruses with the B.1.617.1, B.1.617.2, and AY.1 spike showed a modest 1.5 to 4.4-fold reduction in neutralization titer by convalescent sera and vaccine-elicited sera. In comparison, similar modest reductions were also observed for pseudoviruses with C.37, P.1, R.1, and B.1.526 spikes, but seven- and sixteen-fold reduction for vaccine-elicited and convalescent sera, respectively, was seen for pseudoviruses with the B.1.351 spike. Four of twenty-three therapeutic neutralizing antibodies showed either complete or partial loss of neutralization against B.1.617.2 pseudoviruses due to the L452R substitution, whereas six of twenty-three therapeutic neutralizing antibodies showed either complete or partial loss of neutralization against B.1.617.1 pseudoviruses due to either the E484Q or L452R substitution. Against AY.1 pseudoviruses, the L452R and K417N substitutions accounted for the loss of neutralization by four antibodies and one antibody, respectively, whereas one antibody lost potency that could not be fully accounted for by a single RBD substitution. The modest resistance of B.1.617 variants to vaccine-elicited sera suggest that current mRNA-based vaccines will likely remain effective in protecting against B.1.617 variants, but the therapeutic antibodies need to be carefully selected based on their resistance profiles. Finally, the spike proteins of B.1.617 variants are more efficiently cleaved due to the P681R substitution, and the spike of Delta variants exhibited greater sensitivity to soluble ACE2 neutralization, as well as fusogenic activity, which may contribute to enhanced spread of Delta variants.
Safety Assessment of BNT162b2 Vaccine in Adolescents Aged 12-15 Years
Authors: Patel Jayendrakumar , Bhavsar Bhavesh , Parikh Shalin , Ladani Nikunj 
Published: November 2021

ABSTRACTPresent evidence of the safety of BNT162b2 Vaccine in adolescents of 12 to 15 years relies only on 2260 subjects involved in phase 3 study. Therefore, clinical and post-clinical safety assessment of BNT162b2 Vaccine in Age Group of 12 to 15 Years is urgently needed to make an accurate judgment for mass vaccination. A rapid systemic review was conducted to determine safety profile of BNT162b2 Vaccine in Age Group of 12 to 15 Years following the PRISMA guidelines. Published literature before August 15, 2021 were searched in PubMed, Scopus, Web of Science, Embase, the Cochrane library and MedRxiv, using the defined search words. 135 records found from 6 databases, of which 4 studies (2 studies from NEJM and 2 MMWR), total subject who received at least one dose of vaccine: 64969, were included in this systemic review per the inclusion criteria. The major events reported in clinical phase and post-authorisation observational studies are pain at injection site (local), fatigue (systemic), headache (systemic), chill (systemic), diarrhoea (systemic) and joint pain (systemic). Post-authorisation observational study (n = 62,709) reported about 50% lower major systemic events, specifically, fatigue, headache, chill, diarrhoea and join pain and about 25% lower major local event, specifically, pain at injection site, than phase 3 clinical study (n = 1,131). Our study suggest that higher adherence rate (>97 percent received second dose) in clinical phase 3 and significantly lower incident of major local and systemic events in post-authorisation observational study indicating that BNT162b2 vaccine has highly favourable safety profile.
Adaptive trends of sequence compositional complexity over pandemic time in the SARS-CoV-2 coronavirus
Authors: Oliver José L. , Bernaola-Galván Pedro , Perfectti Francisco , Gómez-Martín Cristina , Castiglione Silvia , Raia Pasquale , Verdú Miguel , Moya Andrés 
Published: November 2021

AbstractDuring the spread of the COVID-19 pandemic, the SARS-CoV-2 coronavirus underwent mutation and recombination events that altered its genome compositional structure, thus providing an unprecedented opportunity to search for adaptive evolutionary trends in real-time. The mutation rate in coronavirus is known to be lower than expected for neutral evolution, thus suggesting a role for natural selection. We summarize the compositional heterogeneity of each viral genome by computing its Sequence Compositional Complexity (SCC). To study the full range of SCC diversity, random samples of high-quality coronavirus genomes covering pandemic time span were analyzed. We then search for evolutionary trends that could inform on the adaptive process of the virus to its human host by computing the phylogenetic ridge regression of SCC against time (i.e., the collection date of each viral isolate). In early samples, we find no statistical support for any trend in SCC, although the viral genome appears to evolve faster than Brownian Motion (BM) expectation. However, in samples taken after the emergence of high fitness variants, and despite the brief time span elapsed, a driven decreasing trend for SCC, and an increasing one for its absolute evolutionary rate, are detected, pointing to a role for selection in the evolution of SCC in coronavirus genomes. We conclude that the higher fitness of variant genomes leads to adaptive trends of SCC over pandemic time in the coronavirus.
Internet-based health survey on loneliness and sleep-related problems among the working-age population in Japan during COVID-19
Authors: Tesen Hirofumi , Konno Yusuke , Tateishi Seiichiro , Hino Ayako , Tsuji Mayumi , Ogami Akira , Nagata Masako , Muramatsu Keiji , Yoshimura Reiji , Fujino Yoshihisa ,   for the CORoNaWork Project
Published: November 2021

ABSTRACTBackgroundThe coronavirus disease 2019 (COVID-19) pandemic has been linked to a rise in loneliness. Loneliness is associated with sleep-related problems, which in turn can be a risk factor for various psychiatric disorders. However, it is unclear whether loneliness is linked to sleep-related problems during the pandemic. Here, we studied the association between loneliness and sleep-related problems during the COVID-19 pandemic in Japan.MethodsA total of 33,302 individuals who indicated they were employed were surveyed online. The survey responses of 27,036 participants were analyzed. Odds ratios (ORs) were estimated using univariate and multiple logistic regression analyses.ResultsOf those analyzed, 2,750 (10.2%) experienced feelings of loneliness. Further, sleep-related problems were significantly more common among those who felt lonely both in the short term (more than 3 days) and the long term (more than 3 months). The OR was much weaker after adjusting for factors related to interpersonal connections, such as family and friendships, than after adjusting for factors related to socioeconomic status.ConclusionsLoneliness may be a risk factor for sleep-related problems in the COVID-19 pandemic. Having connections with family and friends may have a moderating effect on the occurrence of sleep-related problems.
Favipiravir In Adults with Moderate to Severe COVID-19: A Phase 3 Multicentre, Randomized, Double-Blinded, Placebo-Controlled Trial
Authors: Shenoy Srinivas , Munjal Sagar , Youha Sarah Al , Alghounaim Mohammad , Almazeedi Sulaiman , Alshamali Yousef , Kaszynski Richard H , Al-Sabah Salman ,   Kuwait Clinical Trial Group
Published: November 2021

ABSTRACTAimTo assess the efficacy and safety of favipiravir in adults with moderate to severe coronavirus disease 2019 (COVID-19).MethodsIn this randomized, double-blind, multicenter, phase 3 trial, adults (21-80 years) with real-time reverse transcriptase polymerase chain reaction (rRT-PCR) confirmed SARS-CoV-2 infection and presenting with moderate to severe COVID-19 and requiring hospitalization were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2-10: 800 mg BID) (FPV) plus standard supportive care (SoC) versus placebo plus SoC (placebo). The primary endpoint was time to resolution of hypoxia.ResultsIn total, 353 patients were randomized to receive either FPV or placebo (175 and 178 in the FPV and placebo groups, respectively). Overall, 76% of the patients (240/315, 78% in FPV vs. 75% in placebo group) reached resolution of hypoxia on or before day 28. The median time to resolution of hypoxia was 7 days in the FPV group and 8 days in the placebo group. Treatment effect was not significant [Hazard ratio (HR) (95% CI): 0.991 (0.767, 1.280) (p=0.94)].Patients in the lower NEWS-2 clinical risk subgroup were more likely to achieve shorter time to resolution of hypoxia with the median time to resolution of hypoxia of 6 days in FPV and 7 days in placebo group [HR (95% CI): 1.21 (0.847, 1.731) (p=0.29)]; shorter time to hospital discharge with a median time to discharge of 8 and 10 days in the FPV and placebo group, respectively [HR (95% CI): 1.47 (1.081, 1.997) (p=0.014)]; and shorter time to improvement by 1-point improvement over baseline in WHO 10-point clinical status score with the median time to improvement by 1-point from baseline of 6 and 7 days in the FPV and placebo group, respectively [HR (95% CI): 1.16 (0.830, 1.624) (p=0.38)] than higher NEWS-2 clinical risk subgroup.Treatment emergent adverse event (TEAEs) were experienced by 62/334 (19%) patients [35/168 (21%) patients in FPV and 27/166 (16%) in placebo group]. Hyperuricaemia/increased blood uric acid was reported in 9 (3%)/2 (1%) patients [8 (5%)/1(1%) patients in FPV and 1 (1%)/1(1%) in placebo group], which were of mild intensity and transient. Overall, 36 serious adverse events (SAEs) were reported, 20 in FPV and 16 in placebo group.ConclusionThe trial did not find favipiravir to be effective in moderate to severe, hospitalized COVID-19 patients; favourable clinical trends were observed in patients with lower NEWS-2 risk when early administration of favipiravir could be achieved.
Third dose vaccine With BNT162b2 and its response on Long COVID after Breakthrough infections
Authors: Hoque Ashraful , Rahman Md Marufur , Imam Hossain , Nahar Nurun , Hasan Chowdhury Forhad Uddin 
Published: November 2021

AbstractBackgroundBreakthrough events are not rare after emerging of Delta variant. On the other hand, long COVID is an unsolved issue where sufferers suffer a lot. Some study has shown that COVID-19 vaccine has improved some clinical and libratory parameters in long COVID. But what will be the possible measures against long COVID after the breakthrough event is still a burning question.MethodWe have observed the third dose by BNT162b2 in a small group(n=20) who were diagnosed as long COVID after breakthrough infections, in Sheikh Hasina National Institute of Burn & Plastic Surgery Institute, Dhaka, Bangladesh. CRP(C-reactive protein) and Anti S1 RBD IgG responses were measured.ResultAll 20 participants in the study received both dosage of “ChAdOx1-nCoV-19” in between February 2021 to April 2021 and had breakthrough infection in the same or following month which led to long COVID syndrome. They all received a third dose of “BNT162b2”. A before and after 3rddose (14 days after) CRP from participants serum was measured. A Wilcoxon matched paired signed rank test revealed significant (P value <0.05) reduction of inflammatory marker (CRP) after receiving the 3rdvaccine dose. Pre and post 3rddose quantitative anti S1-RBD IgG response was measured and compared that revealed significant boosting effect that clearly correlates with the CRP response.ConclusionCoverage of vaccines all over the world is still not expected level to control this pandemic. WHO has not recommended the use of a third/booster dose of COVID vaccines. Though our results show some sort of hope for the long COVID in breakthrough events after getting the third dose more study is needed to conclude this issue.
No Evidence that Ongoing HIV-Specific Immune Responses Contribute to Persistent Inflammation and Immune Activation in Persons on Long-Term ART
Authors: Ward Adam R. , Thomas Allison S. , Stevenson Eva M. , Huang Szu-Han , Keating Sheila M. , Gandhi Rajesh T. , McMahon Deborah K. , Bosch Ronald J. , Macatangay Bernard J. , Cyktor Joshua C. , Eron Joseph J. , Mellors John W. , Jones R. Brad ,   for the ACTG A5321 Team
Published: November 2021

AbstractBackgroundPeople with HIV (PWH) have persistently elevated levels of inflammation and immune activation despite suppressive antiretroviral therapy (ART), with specific biomarkers showing associations with non-AIDS-defining morbidities and mortality. We investigated the potential role of the HIV-specific adaptive immune response, which also persists under ART, in driving levels of these clinically relevant biomarkers.MethodsHIV-specific T-cell responses and antibody concentrations were measured at study entry in the ACTG A5321 cohort, following a median of 7 years of suppressive ART. HIV persistence measures including cell-associated (CA)-DNA, CA-RNA, and plasma HIV RNA (single-copy assay) were also assessed. Plasma inflammatory biomarkers and T-cell activation and cycling were measured at a pre-ART time point and at study entry.ResultsNeither the magnitudes of HIV-specific T-cell responses nor HIV antibody levels were correlated with levels of the inflammatory or immune activation biomarkers, including hs-CRP, IL-6, neopterin, sCD14, sCD163, %CD38+HLA-DR+ CD8+ and CD4+ cells, and %Ki67+ CD8+ and CD4+ cells – including after adjustment for pre-ART biomarker level. Magnitudes of T-cell responses to HIV-Pol were correlated with TNF-α levels, but this was confounded by several factors. Plasma HIV RNA levels were correlated with CD8+ T-cell activation (r = 0.25, p = 0.027), but other HIV persistence parameters were not associated with these biomarkers. In mediation analysis, relationships between HIV persistence parameters and inflammatory biomarkers were not influenced by either HIV-specific T-cell responses or antibody levels.ConclusionsAdaptive HIV-specific immune responses do not appear to contribute to the elevated inflammatory and immune activation profile associated with morbidity and mortality under long-term ART.SummaryHIV-specific T-cell and antibody responses persist over years of suppressive ART, but there is no evidence that these ongoing immune responses contribute to elevated levels of inflammation and immune activation in people living with HIV on long-term ART.
Predicting Relative Protein Abundance via Sequence-Based Information
Authors: Parkes Gregory M. , Ewing Robert M. , Niranjan Mahesan 
Published: November 2021

ABSTRACTUnderstanding the complex interactions between transcriptome and proteome is essential in uncovering cellular mechanisms both in health and disease contexts. The limited correlations between corresponding transcript and protein abundance suggest that regulatory processes tightly govern information flow surrounding transcription and translation, and beyond. In this study we adopt an approach which expands the feature scope that models the human proteome: we develop machine learning models that incorporate sequence-derived features (SDFs), sometimes in conjunction with corresponding mRNA levels. We develop a large resource of sequence-derived features which cover a significant proportion of the H. sapiens proteome, demonstrate which of these features are significant in prediction on multiple cell lines, and suggest insights into which biological processes can be explained using these features. We reveal that (a) SDFs are significantly better at protein abundance prediction across multiple cell lines both in steady-state and dynamic contexts, (b) that SDFs can cover the domain of translation with relative efficiency but struggle with cell-line specific pathways and (c) provide a resource which can be plugged into many subsequent protein-centric analyses.
A full-length infectious cDNA clone of a dsRNA totivirus-like virus
Authors: Wang Han , Okamoto Kenta 
Published: November 2021

AbstractTotivirus-like viruses are icosahedral non-enveloped double-stranded (ds)RNA viruses belonging to a group recently discovered and provisionally assigned in the Totiviridae family. Unlike fungal and protozoan Totiviridae viruses, these totivirus-like viruses infect a diverse spectrum of metazoan hosts and currently have enormous impacts on fisheries and agriculture. We developed the first totivirus-like virus Omono River virus (OmRV) infectious full-length DNA clone and produce the infectious particles using an RNA-transcript-based method. Unlike the parent wild-type particles from nature, the reverse-genetically-generated OmRV particles had an indistinguishable cytopathic effect, infectivity, and morphology. The established system is one of the few systems that have been reported for generating a non-segmented dsRNA virus DNA clone.
Accelerating in-silico saturation mutagenesis using compressed sensing
Authors: Schreiber Jacob , Nair Surag , Balsubramani Akshay , Kundaje Anshul 
Published: November 2021

AbstractIn-silico saturation mutagenesis (ISM) is a popular approach in computational genomics for calculating feature attributions on biological sequences that proceeds by systematically perturbing each position in a sequence and recording the difference in model output. However, this method can be slow because systematically perturbing each position requires performing a number of forward passes proportional to the length of the sequence being examined. In this work, we propose a modification of ISM that leverages the principles of compressed sensing to require only a constant number of forward passes, regardless of sequence length, when applied to models that contain operations with a limited receptive field, such as convolutions. Our method, named Yuzu, can reduce the time that ISM spends in convolution operations by several orders of magnitude and, consequently, Yuzu can speed up ISM on several commonly used architectures in genomics by over an order of magnitude. Notably, we found that Yuzu provides speedups that increase with the complexity of the convolution operation and the length of the sequence being analyzed, suggesting that Yuzu provides large benefits in realistic settings. We have made this tool available at https://github.com/kundajelab/yuzu.
Sexual Dimorphic Metabolic and Cognitive Responses of C57BL/6 Mice to Fisetin or Dasatinib and Quercetin Cocktail Oral Treatment
Authors: Fang Yimin , Medina David , Stockwell Robert , McFadden Sam , Quinn Kathleen , Peck Mackenzie R. , Bartke Andrzej , Hascup Kevin N. , Hascup Erin R. 
Published: November 2021

AbstractSenolytic treatment in aged mice clears senescent cell burden leading to functional improvements. However, less is known regarding the effects of these compounds when administered prior to significant senescent cell accumulation. From 4-13 months of age, C57BL/6 male and female mice received monthly oral dosing of either 100 mg/kg Fisetin or a 5 mg/kg Dasatinib (D) plus 50 mg/kg Quercetin (Q) cocktail. During treatment, several aspects of healthy aging were assayed including glucose metabolism using an insulin and glucose tolerance test, cognitive performance using Morris water maze and novel object recognition, and energy metabolism using indirect calorimetry. Afterwards, mice were euthanized for plasma and tissue specific markers of senescence-associated secretory phenotype (SASP) and white adipose tissue accumulation (WAT). Sexually dimorphic treatment effects were observed. Fisetin treated male mice had reduced SASP, enhanced glucose and energy metabolism, improved cognitive performance, and increased mRNA expression of adiponectin receptor 1 and glucose transporter 4. D+Q treatment had minimal effects in male C57BL/6 mice, but was detrimental to females causing increased SASP expression along with accumulation of WAT depots. Reduced energy metabolism and cognitive performance were also noted. Fisetin treatment had no effect in female C57BL/6 mice potentially due to a slower rate of biological aging. In summary, the senolytic treatment in young adulthood, has beneficial, negligible, or detrimental effects in C57BL/6 mice dependent upon sex and treatment. These observations should serve as a note of caution in this rapidly evolving and expanding field of investigation.Graphical AbstractMale and female C57BL/6 mice were treated with once monthly oral doses of either Dasatinib (D) + Quercetin (Q) or Fisetin from 4-13 months of age. Females treated with D+Q had increased adiposity and SASP markers (red spheres) along with decreased metabolism (blue flame) and cognitive performance. Males treated with Fisetin had reduced SASP markers (blue spheres) as well as improved metabolism (red flame) and cognition. No effects were observed in females treated with Fisetin or males treated with D+Q.