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Human humoral immune responses to SARS-CoV-2 vaccines exhibit substantial inter-individual variability and have been linked to vaccine efficacy. To elucidate the underlying mechanism behind this variability, we conducted a genome-wide association study (GWAS) on the anti-spike IgG serostatus of UK Biobank participants who were previously uninfected by SARS-CoV-2 and had received either the first dose (n = 54,066) or the second dose (n = 46,232) of COVID-19 vaccines. Our analysis revealed significant genome-wide associations between the IgG antibody serostatus following the initial vaccine and human leukocyte antigen (HLA) class II alleles. Specifically, the HLA-DRB1∗13:02 allele (MAF = 4.0%, OR = 0.75, p = 2.34e-16) demonstrated the most statistically significant protective effect against IgG seronegativity. This protective effect was driven by an alteration from arginine (Arg) to glutamic acid (Glu) at position 71 on HLA-DRβ1 (p = 1.88e-25), leading to a change in the electrostatic potential of pocket 4 of the peptide binding groove. Notably, the impact of HLA alleles on IgG responses was cell type specific, and we observed a shared genetic predisposition between IgG status and susceptibility/severity of COVID-19. These results were replicated within independent cohorts where IgG serostatus was assayed by two different antibody serology tests. Our findings provide insights into the biological mechanism underlying individual variation in responses to COVID-19 vaccines and highlight the need to consider the influence of constitutive genetics when designing vaccination strategies for optimizing protection and control of infectious disease across diverse populations.

Background: Data sharing improves the value, synthesis, and integrity of research, but rates are low. Data sharing might be improved if data sharing policies were prominent and actionable at every stage of research. We aimed to systematically describe the epidemiology of data sharing policies across the health research lifecycle. Methods: This was a cross‐sectional analysis of the data sharing policies of the largest health research funders, all national ethics committees, all clinical trial registries, the highest‐impact medical journals, and all medical research data repositories. Stakeholders' official websites, online reports, and other records were reviewed up to May 2022. The strength and characteristics of their data sharing policies were assessed, including their policies on data sharing intention statements (a.k.a. data accessibility statements) and on data sharing specifically for coronavirus disease studies. Data were manually extracted in duplicate, and policies were descriptively analysed by their stakeholder and characteristics. Results: Nine hundred and thirty‐five eligible stakeholders were identified: 110 funders, 124 ethics committees, 18 trial registries, 273 journals, and 410 data repositories. Data sharing was required by 41% (45/110) of funders, no ethics committees or trial registries, 19% (52/273) of journals and 6% (24/410) of data repositories. Among funder types, a higher proportion of private (63%, 35/55) and philanthropic (67%, 4/6) funders required data sharing than public funders (12%, 6/49). Conclusion: Data sharing requirements, and even recommendations, were insufficient across health research. Where data sharing was required or recommended, there was limited guidance on implementation. We describe multiple pathways to improve the implementation of data sharing. Public funders and ethics committees are two stakeholders with particularly important untapped opportunities. [ABSTRACT FROM AUTHOR]

Maintaining normal thyroid function is crucial in pregnancy, yet thyroid dysfunction and the presence of thyroid peroxidase antibodies (TPOAb) affect 0.5% to 18% of pregnant women. Here, we conducted a genome-wide association study (GWAS) of eight thyroid traits, including two thyroid-related hormones, four thyroid dysfunctions, and two thyroid autoimmunity measurements among 85,421 Chinese pregnant women to investigate the genetic basis of thyroid function during pregnancy. Our study identified 176 genetic loci, including 125 previously unknown genome-wide associations. Joint epidemiological and Mendelian randomization analyses revealed significant associations between the gestational thyroid phenotypes and gestational complications, birth outcomes, and later-age health outcomes. Specifically, genetically elevated thyroid-stimulating hormone (TSH) levels during pregnancy correlated with lower glycemic levels, reduced blood pressure, and longer gestational duration. Additionally, TPOAb and thyroid functions during pregnancy share genetic correlations with later-age thyroid and cardiac disorders. These findings provide insights into the genetic determinants of thyroid traits during pregnancy, which may lead to new therapeutics, early pre-diagnosis and preventive strategies starting from early adulthood. Normal maternal thyroid function holds significant relevance for pregnancy outcomes and long-term health. Here, the authors detect genetic associations with thyroid related traits in pregnant women. [ABSTRACT FROM AUTHOR]

Aim: This case series aimed to evaluate the effectiveness of the autologous circular cortical lamina‐anchoring (CCA) technique for horizontal bone augmentation in the maxillary aesthetic region. Materials and methods: A total of 25 patients with 28 implants underwent horizontal bone augmentation using CCA followed by implant placement and crown delivery. The primary outcome measures were alveolar ridge width (ARW) and buccal bone thickness (BBT), whereas the secondary outcome measures included marginal bone loss (MBL), mid‐facial mucosal margin loss (MML), clinical assessment of peri‐implant and aesthetic parameters, patient‐reported outcome measures (PROMs), and implant survival rates. Results: All 25 patients with 28 implants completed the treatment, no dropouts occurred. After CCA, the mean ARW at 1, 2, and 4 mm below the alveolar crest significantly increased from 2.38 ± 0.48, 2.85 ± 0.51, and 3.21 ± 0.53 mm to 6.80 ± 0.48, 6.99 ± 0.50, and 8.08 ± 0.52 mm, respectively. At the 3‐year follow‐up, the mean BBT0, BBT2, and BBT4 slightly decreased from 2.51 ± 0.26, 2.63 ± 0.31, and 2.75 ± 0.29 mm to 2.43 ± 0.27, 2.51 ± 0.30, and 2.64 ± 0.28 mm, respectively. Although the overall MBL was <0.15 mm, the results were statistically significant. The mean MML at the 3‐year follow‐up was 0.02 mm. All implant sites showed acceptable peri‐implant and aesthetic outcomes. Incisions healed without complications, and no significant differences in PROMs observed at any time point. The 3‐year follow‐up showed a 100% implant survival rate. Conclusion: The autologous CCA technique is a useful method for increasing ARW and maintaining BBT in the maxillary aesthetic region. [ABSTRACT FROM AUTHOR]

Objective: Anterior uveitis is a common extra‐articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease‐modifying drugs in AxSpA. Methods: We conducted a systematic review and meta‐analysis to identify phase II/III double‐blinded randomized controlled trials of anti–tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti–interleukin‐17 (anti–IL‐17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient‐exposure years (PEY) were calculated using the per‐protocol approach. Incidence rate (IR) of AU/100 person‐years were calculated by treatment group using the random effects approach. Network meta‐analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias‐2 tool. Results: Forty‐four trials were included: 17 anti‐TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti–IL‐17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti‐TNF mAb: 4.1, 95% confidence interval (CI) 0–8.5; etanercept: 5.4, 95% CI 0–16.0; anti–IL‐17: 2.8, 95% CI 1.6–4.1; JAKi: 1.5, 95% CI 0.0–3.0; and placebo: 10.8, 95% CI 7.4–14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti‐TNF mAb: 0.32, 95% CI 0.10–1.04; etanercept 0.42, 95% CI 0.08–2.38; anti–IL‐17: 0.43, 95% CI 0.19–0.98; and JAKi: 0.32, 95% CI 0.06–1.67. Comparisons between anti‐TNF mAb, anti–IL‐17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti‐TNF mAbs were associated with the lowest risk followed by JAKi, anti–IL‐17, and etanercept. All treatments were ranked superior to placebo. Conclusion: Anti‐TNF mAbs, JAKi, and anti–IL‐17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments. [ABSTRACT FROM AUTHOR]

Objectives To evaluate trust-level performance in time to initiation of DMARD therapy in patients with early inflammatory arthritis (EIA), with identification of the change in performance trajectories over time and investigation of trust characteristics associated with this change. Methods We included 130 trusts from the UK contributing to the National Early Inflammatory Arthritis Audit (NEIAA) from 2018 to 2020. The primary outcome was days from referral to initiation of DMARD therapy in patients with EIA. Latent class growth mixture models were applied to identify distinct groups of trusts with similar trajectories of performance change over time. We used mixed effects linear and multinomial logistic regression models to evaluate the association between delay in treatment and trust-level characteristics. Results The mean time to DMARD initiation was 53 days (s. d. 18), with an average 0.3-day decrease with each month over time. Four latent trajectories were identified in our cohort, with >77% of individual trusts showing ongoing improvements in decreasing treatment waiting times. Prior to separating by latent class, time to DMARD initiation was shorter in trusts with higher rheumatology staffing, a local EIA treatment pathway and those with access to musculoskeletal ultrasound. Trusts with more nurses in the rheumatology department were less likely to be in the worst performance group [odds ratio 0.69 (95% CI 0.49, 0.93)]. Conclusion In this cohort study, we observed a reduction in treatment waiting time over time. Trusts with better staffed and improved EIA clinical structure are likely to initiate definitive treatment earlier in patients with EIA. [ABSTRACT FROM AUTHOR]