bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal maternal distress during the COVID-19 pandemic and its effects on the infant brain
Authors: Manning Kathryn Y. , Long Xiangyu , Watts Dana , Tomfohr-Madsen Lianne , Giesbrecht Gerald F. , Lebel Catherine 
Published: October 2021

AbstractThe COVID-19 pandemic has caused elevated distress in pregnant individuals, which has the potential to impact the developing infant. In this study, we examined anxiety and depression symptoms during the pandemic in a large sample of pregnant individuals (n=8602). For a sub-sample of participants, their infants underwent magnetic resonance imaging (MRI) at 3-months of age to examine whether this prenatal maternal distress was associated with infant brain changes. We found significantly elevated prenatal maternal distress compared to pre-pandemic rates, with 47% and 33% of participants reporting clinically significant symptoms of anxiety and depression, respectively. Importantly, we identified social support as a protective factor for clinically elevated prenatal maternal distress. We found significant relationships between prenatal maternal distress and infant amygdala-prefrontal microstructural and functional connectivity and demonstrate for the first time that social support moderates this relationship. Our findings suggest a potentially long-lasting impact of the COVID-19 pandemic on children and show that social support acts as a protective factor not just for pregnant individuals, but also for their developing infants. These findings provide timely evidence to inform clinical practice and policy surrounding the care of pregnant individuals and highlight the importance of social support.
A framework for reconstructing SARS-CoV-2 transmission dynamics using excess mortality data
Authors: Ghafari Mahan , Watson Oliver J , Karlinsky Ariel , Ferretti Luca , Katzourakis Aris 
Published: October 2021

AbstractDetailed reconstruction of the SARS-CoV-2 transmission dynamics and assessment of its burden in several parts of the world has still remained largely unknown due to the scarcity of epidemiological analyses and limited testing capacities of different countries to identify cases and deaths attributable to COVID-19 [1-4]. Understanding the true burden of the Iranian COVID-19 epidemic is subject to similar challenges with limited clinical and epidemiological studies at the subnational level [5-9]. To address this, we develop a new quantitative framework that enables us to fully reconstruct the transmission dynamics across the country and assess the level of under-reporting in infections and deaths using province-level, age-stratified all-cause mortality data. We show that excess mortality aligns with seroprevalence estimates in each province and subsequently estimate that as of 2021-10-22, only 48% (95% confidence interval: 43-55%) of COVID-19 deaths in Iran have been reported. We find that in the most affected provinces such as East Azerbaijan, Qazvin, and Qom approximately 0.4% of the population have died of COVID-19 so far. We also find significant heterogeneity in the estimated attack rates across the country with 11 provinces reaching close to or higher than 100% attack rates. Despite a relatively young age structure in Iran, our analysis reveals that the infection fatality rate in most provinces is comparable to high-income countries with a larger percentage of older adults, suggesting that limited access to medical services, coupled with undercounting of COVID-19-related deaths, can have a significant impact on accurate estimation of COVID-19 fatalities. Our estimation of high attack rates in provinces with largely unmitigated epidemics whereby, on average, between 10% to 25% individuals have been infected with COVID-19 at least twice over the course of 20 months also suggests that, despite several waves of infection, herd immunity through natural infection has not been achieved in the population.
Postvaccination SARS-CoV-2 infection among healthcare workers – A Systematic Review and meta-analysis
Authors: Chandan Saurabh , Khan Shahab R. , Deliwala Smit , Mohan Babu P. , Ramai Daryl , Chandan Ojasvini C. , Facciorusso Antonio 
Published: October 2021

ABSTRACTINTRODUCTIONHealthcare workers (HCWs) remain on the front line of the battle against SARS-CoV-2 and COVID-19 infection, and are among the highest groups at risk of infection during this raging pandemic. We conducted a systematic review and meta-analysis to assess incidence of postvaccination SARS-CoV-2 infection among vaccinated HCWs.METHODSWe searched multiple databases from inception through August 2021 to identify studies that reported on incidence of postvaccination SARS-CoV-2 infection among HCWs. Meta-analysis was performed to determine pooled proportions of COVID-19 infection in partially and fully vaccinated individuals.RESULTSEighteen studies with 228,873 HCWs were included in the final analysis. Total number of partially vaccinated, fully vaccinated, and unvaccinated HCWs were 132,922, 155,673 and 17505, respectively. Overall pooled proportion of COVID-19 infections among partially/fully vaccinated and unvaccinated HCWs was 2.1% (95% CI 1.2-3.5). Among partially vaccinated, fully vaccinated and unvaccinated HCWs, pooled proportion of COVID-19 infections was 3.7% (95% CI 1.8-7.3), 1.3% (95% CI 0.6-2.9), and 10.1% (95% CI 4.5-19.5), respectively.DISCUSSIONOur analysis shows the risk of COVID-19 infection in both partially and fully vaccinated HCWs remains exceedingly low when compared to unvaccinated individuals. There remains an urgent need for all frontline HCWs to be vaccinated against SARS-CoV-2 infection.
Correlation of long-term care facility vaccination practices between seasons and resident types
Authors: O’Neill Emily T , Bosco Elliott , Persico Erin , Silva Joe B , Riester Melissa R , Moyo Patience , van Aalst Robertus , Loiacono Matt M , Chit Ayman , Gravenstein Stefan , Zullo Andrew R 
Published: October 2021

ABSTRACTObjectivesInfluenza vaccination varies widely across LTCFs due to staff behaviors, LTCF practices, and patient factors. It is unclear how seasonal LTCF vaccination varies between cohabitating but distinct short-stay and long-stay residents. Thus, we assessed the correlation of LTCF vaccination between these populations and across seasons.DesignNational retrospective cohort using Medicare and Minimum Data Set (MDS) data.Setting and ParticipantsU.S. LTCFs. Short-stay and long-stay Medicare-enrolled residents age ≥65 in U.S. LTCFs from a source population of residents during October 1st-March 31stin 2013-2014 (3,042,881 residents; 15,683 LTCFs) and 2014-2015 (3,143,174, residents; 15,667 LTCFs).MethodsMDS-assessed influenza vaccination was the outcome. Pearson correlation coefficients were estimated to assess seasonal correlations between short-stay and long-stay resident vaccination within LTCFs.ResultsThe median proportion of short-stay residents vaccinated across LTCFs was 70.4% (IQR, 50.0-82.7%) in 2013-2014 and 69.6% (IQR, 50.0-81.6%) in 2014-2015. The median proportion of long-stay residents vaccinated across LTCFs was 85.5% (IQR, 78.0-90.9%) in 2013-2014 and 84.6% (IQR, 76.6-90.3%) in 2014-2015. Within LTCFs, there was a moderate correlation between short-stay and long-stay vaccination in 2013-2014 (r=0.50, 95%CI: 0.49-0.51) and 2014-2015 (r=0.53, 95%CI: 0.51-0.54). Across seasons, there was a moderate correlation for LTCFs with short-stay residents (r=0.54, 95%CI: 0.53-0.55) and a strong correlation for those with long-stay residents (r=0.68, 95%CI: 0.67-0.69).Conclusion and ImplicationsIn LTCFs with inconsistent influenza vaccination across seasons or between populations, targeted vaccination protocols for all residents, regardless of stay type, may improve successful vaccination in this vulnerable patient population.Brief summaryIn LTCFs, influenza vaccination was moderately correlated across all residents, but varied across seasons. Inconsistent vaccination among cohabitating residents may increase infection risk in LTCFs.
Antigen receptor stimulation drives selection against pathogenic mtDNA variants that dysregulate lymphocyte responses
Authors: Zhang Jingdian , Koolmeister Camilla , Han Jinming , Filograna Roberta , Hanke Leo , Àdori Monika , Sheward Daniel J. , Teifel Sina , Liu Yong , Harris Robert A. , Murrell Ben , Mcinerney Gerald , Aoun Mike , Bäckdahl Liselotte , Holmdahl Rikard , Pekalski Marcin , Wedell Anna , Engvall Martin , Wredenberg Anna , Karlsson Hedestam Gunilla B. , Dopico Xaquin Castro , Rorbach Joanna 
Published: October 2021

AbstractPathogenic mitochondrial (mt)DNA molecules can exhibit heteroplasmy in single cells and cause a range of clinical phenotypes, although their contribution to immunity is poorly understood. Here, in mice carrying heteroplasmic C5024T in mt-tRNAAla– that impairs oxidative phosphorylation – we found a reduced mutation burden in peripheral T and B memory lymphocyte subsets, compared to their naïve counterparts. Furthermore, selection diluting the mutation was inducedin vitroby triggering T and B cell antigen receptors. While C5024T dysregulated naïve CD8+T cell respiration and metabolic remodeling post-activation, these phenotypes were partially ameliorated by selection. Analogous to mice, peripheral blood memory T and B lymphocyte subsets from human MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) patients – carrying heteroplasmic A3243G in mt-tRNALeu– displayed a reduced mutation burden, compared to naïve cells. In both humans and mice, mtDNA selection was observed in IgG+antigen-specific B cells after SARS-CoV-2 Spike vaccination, illustrating an on-going processin vivo. Taken together, these data illustrate purifying selection of pathogenic mtDNA variants during the oxidative phosphorylation checkpoints of the naïve-memory lymphocyte transition.HighlightsIn human MELAS patients (A3243G in mt-tRNALeu) and a related mouse model (C5024T in mt-tRNAAla), T and B memory subsets displayed a reduced mtDNA mutation burden compared to their naïve counterparts.Selection was observed in antigen-specific IgG+B cells after SARS-CoV-2 Spike protein vaccination.T and B cell antigen receptor stimulation triggered purifying selectionin vitro, facilitating mechanistic studies of mtDNA selection.Heteroplasmic pathogenic mutations in mtDNA dysregulated metabolic remodeling after lymphocyte activation and reduced macrophage OXPHOS capacity.
Serum but not mucosal antibody responses are associated with pre-existing SARS-CoV-2 spike cross-reactive CD4+T cells following BNT162b2 vaccination in the elderly
Authors: Meyer-Arndt Lil , Schwarz Tatjana , Loyal Lucie , Henze Larissa , Kruse Beate , Dingeldey Manuela , Gürcan Kübrah , Uyar-Aydin Zehra , Müller Marcel A. , Drosten Christian , Paul Friedemann , Sander Leif E. , Demuth Ilja , Lauster Roland , Giesecke-Thiel Claudia , Braun Julian , Corman Victor M. , Thiel Andreas 
Published: October 2021

AbstractAdvanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analysed human cellular, serological and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to BNT162b2 COVID-19 vaccine in old (69-92 years) and middle-aged (24-57 years) vaccinees compared to natural infection (COVID-19 convalescents, 21-55 years). Serological humoral responses to vaccination exceeded those of convalescents but salivary anti-spike subunit 1 (S1) IgA and neutralizing capacity were less durable in vaccinees. In old vaccinees, we observed that pre-existing spike-specific CD4+T cells are associated with efficient induction of anti-S1 IgG and neutralizing capacity in serum but not saliva. Our results suggest pre-existing SARS-CoV-2 cross-reactive CD4+T cells as predictor of an efficient COVID-19 vaccine-induced humoral immune response in old individuals.
Relationship between five Epigenetic Clocks, Telomere Length and Functional Capacity assessed in Older Adults: Cross-sectional and Longitudinal Analyses
Authors: Vetter Valentin Max , Kalies Christian Humberto , Sommerer Yasmine , Spira Dominik , Drewelies Johanna , Regitz-Zagrosek Vera , Bertram Lars , Gerstorf Denis , Demuth Ilja 
Published: October 2021

AbstractDNA methylation age acceleration (DNAmAA, derived from an epigenetic clock) and relative leukocyte telomere length (rLTL) are widely accepted biomarkers of aging. Nevertheless, it is still unclear which aspects of aging they represent best. Here we evaluated longitudinal associations between baseline rLTL and DNAmAA (estimated with 7-CpG clock) and functional assessments covering different domains of aging. Additionally, we made use of cross-sectional data on these assessments and examined their association with DNAmAA estimated by five different DNAm age measures.Two-wave longitudinal data was available for 1,083 participants of the Berlin Aging Study II (BASE-II) who were re-examined on average 7.4 years after baseline as part of the GendAge study. Functional outcomes were assessed with Fried’s frailty score, Tinetti mobility test, falls in the past 12 months (yes/no), Finger-floor distance, Mini Mental State Examination (MMSE), Center for Epidemiologic Studies Depression Scale (CES-D), Activities of Daily Living (ADL), Instrumented ADL (IADL) and Mini Nutritional Assessment (MNA).Overall, we found no evidence for an association between the molecular biomarkers measured at baseline, rLTL and DNAmAA (7-CpG clock), and functional assessments assessed at follow-up. Similarly, a cross-sectional analyses of follow-up data did also not show evidence for associations of the various DNAmAA measures (7-CpG clock, Horvath’s clock, Hannum’s clock PhenoAge, and GrimAge) with functional assessments.In conclusion, neither rLTL nor 7-CpG DNAmAA were able to predict impairment in the analyzed assessments over a ∼7 year time-course. Similarly, DNAmAA as estimated by five epigenetic clocks was not a good cross-sectional marker of health deterioration either.
Feasibility and acceptability of daily testing at school as an alternative to self-isolation following close contact with a confirmed case of COVID-19: A qualitative analysis
Authors: Denford Sarah , Towler Lauren , Ali Behiye , Treneman-Evans Georgiana , Bloomer Rachael , Peto Tim , Young Bernadette C , Yardley Lucy 
Published: October 2021

BackgroundDaily testing using a rapid Lateral Flow Device (LFD) has been suggested as an alternative to self-isolation. A randomised trial comparing daily contact testing (DCT) in schools with self-isolation found that SARS-CoV-2 transmission within school was comparable and low in both groups. However, if this approach is to be adopted widely, it is critical that we understand the perspective of those who will be delivering and receiving DCT. The aim of this qualitative process study embedded in the randomised controlled trial (RCT) was to improve understanding of a range of behavioural factors that could influence implementation.MethodsInterviews were conducted with 63 participants, including staff, students, and parents of students who had been identified as being in close contact with someone with COVID-19. The topic guide explored perceptions of daily testing, understanding of positive and negative test results, and adherence to guidance. Data were analysed using an inductive thematic approach.ResultsResults were organised under three main headings: (1) factors influencing daily testing (2) interpretation of test results (3) behaviour during testing period. Participants recognized that daily testing may allow students to remain in school, which was viewed as necessary for both education and social needs. Whilst some felt safer as a result of daily testing, others raised concerns about safety. Participants did not always understand how to interpret and respond to test results, and although participants reported high levels of adherence to the guidance, improved communications were desired.ConclusionDaily testing may be a feasible and acceptable alternative to self-isolation among close contacts of people who test positive. However, improved communications are needed to ensure that all students and parents have a good understanding of the rationale for testing, what test results mean, how test results should be acted on, and how likely students are to test positive following close contact. Support is needed for students and parents of students who have to self-isolate and for those who have concerns about the safety of daily testing.
Enhancing Tele-Simulation during OSCE: Incorporating Feedback from Standardized Patients
Authors: Sudhir Meghana 
Published: October 2021

AbstractBackgroundAs COVID-19 impacted universities across the globe for over one year, the organization of OSCEs also demanded change. The traditional OSCEs had to transition to Tele simulation OSCEs. As the pandemic continues, there is possibility that this approach may continue for some time, it is imminent to capture feedback from the simulated patients so that we can explore ways to improve in future.ObjectivesTo gather feedback from standardized patients doing Tele Simulation in OSCEs, To develop plans to improve Tele Simulation involving Standardized Patients based on the feedback gathered.MethodData were collected immediately after Tele simulation OSCE during debriefing from 18 Simulated Patients. This was followed up with an open-ended questionnaire and gathered additional information.ResultsThe feedback from SPs included their feelings when they were introduced to Tele simulation OSCE, Tele simulation versus Face to Face OSCE and areas of improvement.ConclusionTele simulation OSCE was a quick adaptation during COVID-19 pandemic. But the lessons learned, and the feedback received are pearls for future innovative approaches to assessments. It is encouraged to collect verbal and written feedback for the improvement of Tele simulation.
Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies
Authors: Perez-Cornago Aurora , Dunneram Yashvee , Watts Eleanor L. , Key Timothy J. , Travis Ruth C. 
Published: October 2021

AbstractIntroductionThe association of adiposity with prostate cancer specific mortality remains unclear. We examined how adiposity and its distribution relates to fatal prostate cancer by analysing data from UK Biobank, and conducting a dose-response meta-analysis to integrate existing prospective evidence. We also described the cross-sectional associations in UK Biobank of commonly used adiposity measurements with indices of adiposity estimated by imaging.Methods218,246 men from UK Biobank who were free from cancer at baseline were included and participants were followed-up via linkage to health administrative datasets. Body mass index (BMI), total body fat percentage (using bioimpedance), waist circumference (WC) and waist-to-hip ratio (WHR) were collected at recruitment. Risk of dying from prostate cancer (primary cause) by the different adiposity measurements was estimated using multivariable-adjusted Cox proportional hazards models. Results from this and other prospective cohort studies were combined in a dose-response meta-analysis.ResultsIn UK Biobank, 631 men died from prostate cancer over a mean follow-up of 11.5 years. The hazard ratios (HR) for prostate cancer death were 1.10 (95% confidence interval=1.00-1.21) per 5 kg/m2 higher BMI, 1.03 (0.96-1.11) per 5% increase in total body fat percentage, 1.09 (1.02-1.18) per 10 cm increase in WC, and 1.09 (1.02-1.16) per 0.05 increase in WHR. Our meta-analyses of prospective studies included 22,106 prostate cancer deaths for BMI, 642 for body fat percentage, 3,153 for WC and 1,611 for WHR, and the combined HRs for dying from prostate cancer for the increments above were 1.10 (1.08-1.13), 1.03 (0.96-1.11), 1.08 (1.04-1.12), and 1.07 (1.02-1.12), respectively. In up to 4,800 UK Biobank participants with magnetic resonance imaging and dual-energy X-ray absorptiometry, BMI and WC were strongly associated with imaging estimations of total and central adiposity (e.g. visceral fat, trunk fat), with associations marginally larger for WC. There might be ∼1000 fewer prostate cancer deaths per year in the UK if the mean BMI in men was reduced by 5 kg/m2.ConclusionOverall, we found that men with higher total and central adiposity had similarly higher risks of prostate cancer death, which may be biologically driven or due to differences in detection. In either case, these findings provide further reasons for men to maintain a healthy body weight.
Single-Molecule Detection of SARS-CoV-2 by Plasmonic Sensing of Isothermally Amplified Nucleic Acids
Authors: Ye Haihang , Nowak Chance , Liu Yaning , Li Yi , Zhang Tingting , Bleris Leonidas , Qin Zhenpeng 
Published: October 2021

AbstractSingle-molecule detection of pathogens such as SARS-CoV-2 is key to combat infectious diseases outbreak and pandemic. Currently colorimetric sensing with loop-mediated isothermal amplification (LAMP) provides simple readouts but suffers from intrinsic non-template amplification. Herein, we report that plasmonic sensing of LAMP amplicons via DNA hybridization allows highly specific and single-molecule detection of SARS-CoV-2 RNA. Our work has two important advances. First, we develop gold and silver alloy (Au-Ag) nanoshells as plasmonic sensors that have 4-times stronger extinction in the visible wavelengths and give 20-times lower detection limit for oligonucleotides than Au nanoparticles. Second, we demonstrate that the diagnostic method allows cutting the complex LAMP amplicons into short repeats that are amendable for hybridization with oligonucleotide-functionalized nanoshells. This additional sequence identification eliminates the contamination from non-template amplification. The detection method is a simple and single-molecule diagnostic platform for virus testing at its early representation.Table of Content