bluuebunny/crossref_metadata_2025_split huggingface dataset:
The functional polymorphisms linked with interleukin-1β gene expression are associated with bipolar disorder
Authors: Pu Xingfu , Li Jianghui , Ma Xiaoyuan , Yang Shunying , Wang Libo 
Published: March 2021

Background
Bipolar disorder (BD) is a severe psychiatric illness attributable to multifactorial risk components (e.g. environmental stimuli, neuroinflammation, etc.), and genetic variations affecting these risk components are considered pivotal predisposing factors. The interleukin-1β (IL-1β) gene and its protein product have been repeatedly highlighted in the pathogenesis of BD. As functional polymorphisms and haplotypes linked with IL-1β mRNA expression have been reported, whether they are correlated with the risk of developing BD remains to be tested.

Methods
To examine whether variations in the IL-1β gene locus confer genetic risk of BD, we recruited 930 BD patients and 912 healthy controls for the current study. All subjects were Han Chinese, and were age- and gender-matched. We tested seven functional single nucleotide polymorphisms (SNPs) spanning the IL-1β gene and one haplotype composed of three SNPs for their associations with risk of BD.

Results
We found that the functional SNPs in the promoter region of IL-1β gene were significantly associated with risk of BD. The haplotype analyses further supported the involvement of IL-1β promoter SNPs in BD. The BD risk SNPs in our study have been previously reported to predict higher IL-1β levels in the brain and peripheral blood, which is consistent with the clinical observation of elevated IL-1β levels in the lymphocytes or peripheral blood of patients with BD compared with healthy subjects.

Conclusion
Our results support the contention that IL-1β is likely a risk gene for BD, and further investigations on this gene may promote our understanding and clinical management of this illness.
Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study
Authors: Roy Sayak , Samajdar Shambo Samrat , Tripathi Santanu K , Mukherjee Shatavisa , Bhattacharjee Kingshuk 
Published: March 2021

AbstractIntroductionWith over 87,273,380 cases being reported and 1,899,440 deaths worldwide as of 9th January 2021, Coronavirus disease 2019 (COVID-19) has become the worst-hit pandemic till date. Every day clinicians are bombarded with many new treatment options that claim to be better than the others.Materials and methodsAfter screening the electronic database of COVID-19 patients retrospectively, 56 patients with mild COVID-19 infection matched the inclusion criteria and were divided into the four following groups - group having used Hydroxychloroquine (HCQ), group using doxycycline (DOX) + Ivermectin (IVR) combination, group receiving only azithromycin (AZ) and, group receiving only symptomatic treatment. The study’s primary objective was to see Clinical response of well-being (CRWB) reporting time after initiating treatment onset between the four different treatment arms.ResultsCRWB did not differ between the four groups receiving four different managements (p-value 0.846). There was significant correlation between blood levels of LDH (p-value 0.001), CRP (p-value 0.03) and D-dimer (p-value 0.04) with CRWB in IVR+DOX group and, between LDH (p-value 0.001), CRP (p-value 0.01) and age (p-value 0.035) with CRWB in the symptomatic management group.ConclusionMild COVID-19 infection in patients having low-risk to progress can be managed symptomatically without any specific drug intervention.
Optimization of magnetic bead-based nucleic acid extraction for SARS-CoV-2 testing using readily available reagents
Authors: Haile Simon , Nikiforuk Aidan M. , Pandoh Pawan K. , Twa David D. W. , Smailus Duane E. , Nguyen Jason , Pleasance Stephen , Wong Angus , Zhao Yongjun , Eisler Diane , Moksa Michelle , Cao Qi , Wong Marcus , Su Edmund , Krzywinski Martin , Nelson Jessica , Mungall Andrew J. , Tsang Frankie , Prentice Leah M. , Jassem Agatha , Manges Amee R. , Jones Steven J. M. , Coope Robin J. , Prystajecky Natalie , Marra Marco A. , Krajden Mel , Hirst Martin 
Published: March 2021

AbstractThe COVID-19 pandemic has highlighted the need for generic reagents and flexible systems in diagnostic testing. Magnetic bead-based nucleic acid extraction protocols using 96-well plates on open liquid handlers are readily amenable to meet this need. Here, one such approach is rigorously optimized to minimize cross-well contamination while maintaining sensitivity.Article SummaryA scalable, non-proprietary, magnetic bead-based automated nucleic acid extraction protocol optimised for minimum cross-well contamination
Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy
Authors: Elliott Maxwell L. , Caspi Avshalom , Houts Renate M. , Ambler Antony , Broadbent Jonathan M. , Hancox Robert J. , Harrington HonaLee , Hogan Sean , Keenan Ross , Knodt Annchen , Leung Joan H. , Melzer Tracy R. , Purdy Suzanne C. , Ramrakha Sandhya , Richmond-Rakerd Leah S. , Righarts Antoinette , Sugden Karen , Thomson W. Murray , Thorne Peter R. , Williams Benjamin S. , Wilson Graham , Hariri Ahmad R. , Poulton Richie , Moffitt Terrie E. 
Published: March 2021

ABSTRACTAll humans age, but some age faster than others. Variation in biological aging can be measured in midlife, but the implications of this variation are poorly understood. We tested associations between biological aging and indicators of future frailty risk in the Dunedin cohort of 1037 infants born the same year and followed to age 45. Participants’ Pace of Aging was quantified by tracking declining function in 19 biomarkers indexing the cardiovascular, metabolic, renal, hepatic, immune, dental, and pulmonary systems across ages 26, 32, 38, and 45 years, in 2019. Participants with faster Pace of Aging had more cognitive difficulties, signs of advanced brain aging, diminished sensory-motor functions, older appearance, and more pessimistic perceptions of aging. People who are aging more rapidly than same-age peers in midlife may prematurely need supports to sustain independence that are usually reserved for older adults. Chronological age does not adequately identify need for such supports.
High-resolution epigenome analysis in nasal samples derived from children with respiratory viral infections reveals striking changes upon SARS-CoV-2 infection
Authors: Winkley Konner , Koseva Boryana , Banerjee Dithi , Cheung Warren , Selvarangan Rangaraj , Pastinen Tomi , Grundberg Elin 
Published: March 2021

AbstractBackgroundDNA methylation patterns of the human genome can be modified by environmental stimuli and provide dense information on gene regulatory circuitries. We studied genome-wide DNA methylation in nasal samples from infants (<6 months) applying whole-genome bisulfite sequencing (WGBS) to characterize epigenome response to 10 different respiratory viral infections including SARS-CoV-2.ResultsWe identified virus-specific differentially methylated regions (vDMR) with human metapneumovirus (hMPV) and SARS-CoV-2 followed by Influenza B (Flu B) causing the weakest vs. strongest epigenome response with 496 vs. 78541 and 14361 vDMR, respectively. We found a strong replication rate of FluB (52%) and SARS-CoV-2 (42%) vDMR in independent samples indicating robust epigenome perturbation upon infection. Among the FluB and SARS-CoV-2 vDMRs, around 70% were hypomethylated and significantly enriched among epithelial cell-specific regulatory elements whereas the hypermethylated vDMRs for these viruses mapped more frequently to immune cell regulatory elements, especially those of the myeloid lineage. The hypermethylated vDMRs were also enriched among genes and genetic loci in monocyte activation pathways and monocyte count. Finally, we perform single-cell RNA-sequencing characterization of nasal mucosa in response to these two viruses to functionally analyze the epigenome perturbations. Which supports the trends we identified in methylation data and highlights and important role for monocytes.ConclusionsAll together, we find evidence indicating genetic predisposition to innate immune response upon a respiratory viral infection. Our genome-wide monitoring of infant viral response provides first catalogue of associated host regulatory elements. Assessing epigenetic variation in individual patients may reveal evidence for viral triggers of childhood disease.
Evaluating the impacts of tiered restrictions introduced in England, during October and December 2020 on COVID-19 cases: A synthetic control study
Authors: Zhang Xingna , Owen Gwilym , Green Mark , Buchan Iain , Barr Ben 
Published: March 2021

AbstractBackgroundIn 2020, a second wave of COVID-19 cases unevenly affected places in England leading to the introduction of a tiered system of controls with different geographical areas subject to different levels of restrictions. Whilst previous research has examined the impact of national lockdowns on transmission, there has been limited research examining the marginal effect of differences in localised restrictions or how these effects vary between socioeconomic contexts. We therefore examined how Tier 3 restrictions in England implemented between October-December 2020, which included additional restrictions on the hospitality sector and people meeting outdoors affected COVID-19 case rates, compared to Tier 2 restrictions, and how these effects varied by level of deprivation.MethodsWe used data on weekly reported COVID-19 cases for 7201 neighbourhoods in England and adjusted these for changing case-detection rates to provide an estimate of weekly SARS-CoV-2 infections in each neighbourhood. We identified those areas that entered Tier 3 restrictions at two time points in October and December, and constructed a synthetic control group of similar places that had entered Tier 2 restrictions, using calibration weights to match them on a wide range of covariates that may influence transmission. We then compared the change in weekly infections between those entering Tier 3 to the synthetic control group to estimate the proportional reduction of cases resulting from Tier 3 restrictions compared to Tier 2 restrictions, over a 4-week period. We further used interaction analysis to estimate whether this effect differed based on the level of socioeconomic deprivation in each neighbourhood and whether effects were modified by the prevalence of a new more infectious variant of SARS-CoV-2 (B.1.1.7) in each area.ResultsThe introduction of Tier 3 restrictions in October and December was associated with a 14% (95% CI 10% to 19%) and 20% (95% CI 13% to 29%) reduction in infections respectively, compared to the rates expected if only Tier 2 restrictions had been in place in those areas. We found that effects were similar across levels of deprivation and limited evidence that Tier 3 restrictions had a greater effect in areas where the new more infectious variant was more prevalent.InterpretationAdditional restrictions on hospitality and meeting outdoors introduced in Tier 3 areas in England had a moderate effect on transmission and these restrictions did not appear to increase inequalities, having a similar impact across areas with differing levels of socioeconomic deprivation. Where transmission risks vary between geographical areas a tiered approach of local restrictions on outdoor mixing and hospitality can contribute to control of SARS-CoV-2 and is unlikely to increases inequalities in transmission.
Vaccine confidence and timeliness of childhood immunisation by health information source, maternal, socioeconomic, and geographic characteristics in Albania
Authors: Mayerová Daniela , Abbas Kaja 
Published: March 2021

AbstractBackgroundAlbania is facing decreasing childhood immunisation coverage and timeliness despite a growing economy and universal health insurance. Our aim is to estimate vaccine confidence and timeliness of childhood immunisation by health information source, maternal, socioeconomic, and geographic characteristics in Albania.MethodsWe used the 2017-2018 Albania Demographic and Health Survey to analyse vaccine confidence, measured via the proxy of vaccine timeliness, among 2,156 mothers of under-5-year-old children using simple and multivariable logistic regression.Results77.9% [74.2, 81.2] of mothers had confidence in vaccines. Immunisation delay was reported by 21.5% [18.3, 25.3] of mothers, but a majority (65.7%) were caused by the infant’s sickness at the time of vaccination, while a minority (8.7%) due to mothers’ concerns about vaccine safety and side effects. Among 1.7% of mothers who ever refused vaccination of their children, the main concerns were about vaccine safety (35.9%) and adverse events (42.7%). Factors associated with lower vaccine confidence were using the Internet/social media as the main health information source compared to other sources (AOR=0.66 [0.47, 0.94], p=0.020), mother’s work outside the home (AOR=0.65 [0.47, 0.91], p=0.013), lack of maternal education (AOR=0.14 [0.03, 0.67], p=0.014), and living in AL02-Qender (AOR=0.38 [0.23, 0.63]) and AL03-Jug regions (AOR=0.36 [0.24, 0.53]) in comparison to AL01-Veri region (p<0.0001).ConclusionsReinforcement of scientific evidence-based online communication about childhood immunisation and monitoring anti-vaccination movements on the Internet/social media would be beneficial in improving vaccine confidence and timeliness in Albania, together with traditional ways of promoting vaccination by healthcare professionals who enjoy confidence as trusted sources of information.
An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status
Authors: Lumley Sheila F , Rodger Gillian , Constantinides Bede , Sanderson Nicholas , Chau Kevin K , Street Teresa L , O’Donnell Denise , Howarth Alison , Hatch Stephanie B , Marsden Brian D , Cox Stuart , James Tim , Warren Fiona , Peck Liam J , Ritter Thomas G , de Toledo Zoe , Warren Laura , Axten David , Cornall Richard J , Jones E Yvonne , Stuart David I , Screaton Gavin , Ebner Daniel , Hoosdally Sarah , Chand Meera ,   Oxford University Hospitals Staff Testing Group, Crook Derrick W , O’Donnell Anne-Marie , Conlon Christopher P , Pouwels Koen B , Walker A Sarah , Peto Tim EA , Hopkins Susan , Walker Timothy M , Stoesser Nicole E , Matthews Philippa C , Jeffery Katie , Eyre David W 
Published: March 2021

AbstractBackgroundNatural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity.MethodsIn a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomatic PCR-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after one versus two vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing.Results13,109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses) and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and two vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95%CI <0.01-0.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [0.02-0.38]) and 85% (0.15 [0.08-0.26]) respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [0.21-0.52]) and any PCR-positive result by 64% (0.36 [0.26-0.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7.ConclusionNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.SummaryNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provided ≥ 85% protection against symptomatic and asymptomatic SARS-CoV-2 infection in healthcare workers, including against the B.1.1.7 variant. Single dose vaccination reduced symptomatic infection by 67%.
Leg-heel chest compression as an alternative for medical professionals in times of COVID-19
Authors: Ott Matthias , Krohn Alexander , Bilfield Laurence H. , Dengler F. , Jaki C. , Echterdiek F. , Schilling T , Heymer J. 
Published: March 2021

AbstractObjectiveTo evaluate leg-heel chest compression without previous training as an alternative for medical professionals and its effects on distance to potential aerosol spread during chest compression.Methods20 medical professionals performed standard manual chest compression followed by leg-heel chest compression after a brief instruction on a manikin. We compared percentage of correct chest compression position, percentage of full chest recoil, percentage of correct compression depth, average compression depth, percentage of correct compression rate and average compression rate between both methods. In a second approach, potential aerosol spread during chest compression was visualized.ResultsThere was no significant difference between manual and leg-heel compression. The distance to potential aerosol spread could have been increased by leg-heel method.ConclusionUnder special circumstances like COVID-19-pandemic, leg-heel chest compression may be an effective alternative without previous training compared to manual chest compression while markedly increasing the distance to the patient.
COVID-19 mRNA Vaccination in Lactation: Assessment of adverse events and vaccine related antibodies in mother-infant dyads
Authors: Golan Yarden , Prahl Mary , Cassidy Arianna G. , Gay Caryl , Wu Alan H.B. , Jigmeddagva Unurzul , Lin Christine Y. , Gonzalez Veronica J. , Basilio Emilia , Warrier Lakshmi , Buarpung Sirirak , Li Lin , Murtha Amy P. , Asiodu Ifeyinwa V. , Ahituv Nadav , Flaherman Valerie J. , Gaw Stephanie L. 
Published: March 2021

AbstractBackgroundData regarding adverse events observed in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines.MethodsFrom a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers’ 2nd dose).ResultsNo severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period. PEGylated proteins, were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation.ConclusionsCOVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported.
Evaluation of anti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 patients in outbreak on a cruise ship
Authors: Kaku Norihito , Nishimura Fumitaka , Shigeishi Yui , Tachiki Rina , Sakai Hironori , Sasaki Daisuke , Ota Kenji , Sakamoto Kei , Kosai Kosuke , Hasegawa Hiroo , Izumikawa Koichi , Ariyoshi Koya , Mukae Hiroshi , Yasuda Jiro , Morita Kouichi , Kohno Shigeru , Yanagihara Katsunori 
Published: March 2021

AbstractBackgroundA few studies on antibody testing have focused on asymptomatic or mild coronavirus disease 2019 (COVID-19) patients with low initial anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses. Anti-SARS-CoV-2 antibody-testing performance was evaluated using blood samples from asymptomatic or mild COVID-19 patients.MethodsBlood samples were collected from 143 COVID-19 patients during an outbreak on a cruise ship 3 weeks after diagnosis. Simultaneously, a second SARS-CoV-2 genetic test was performed. Samples stored before the COVID-19 pandemic were also used to evaluate the lateral flow immunochromatographic assay (LFA) and electrochemiluminescence immunoassay (ECLIA). Titers of anti-SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured using the enzyme-linked immunosorbent assay to compare false-negative- with positive-result samples.ResultsSensitivity, specificity, positive-predictive, and negative-predictive values of LFA-detected IgM antibodies were 0.231, 1.000, 1.000, and 0.613, respectively; those of LFA-detected IgG antibodies were 0.483, 0.989, 0.972, and 0.601, respectively; and those of ECLIA-detected total antibodies were 0.783, 1.000, 1.000, and 0.848, respectively. IgM-, IgG-, and total-antibody positivity rates in the patients with negative results from the second genetic testing were 22.9%, 47.6%, and 72.4%, respectively. All antibody titers, especially those of the IgG antibody against nucleocapsid protein, were significantly lower in blood samples with false-negative results than in those with positive results.ConclusionsThese findings suggest that anti-SARS-CoV-2 antibody testing has lower performance in asymptomatic or mild COVID-19 patients than required in the guidelines, and situations in which it is useful are limited.Key pointsAnti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 patients is lower than the required clinical sensitivity, although it may be useful in patients at 3–4 weeks after symptom onset but with negative SARS-CoV-2 genetic test results.