Open science and conflict of interest policies of medical and health sciences journals before and during the COVID-19 pandemic: A repeat cross-sectional study: Open science policies of medical journals.

Objectives: To audit the transparent and open science standards of health and medical sciences journal policies and explore the impact of the COVID-19 pandemic. Design: Repeat cross-sectional study. Setting: 19 journals listed in Google Scholar's Top Publications for health and medical sciences. Participants: Blood, Cell, Circulation, European Heart Journal, Gastroenterology, Journal of Clinical Oncology, Journal of the American College of Cardiology, Nature Genetics, Nature Medicine, Nature Neuroscience, Neuron, PLoS ONE, Proceedings of the National Academy of Sciences, Science Translational Medicine, The British Medical Journal, The Journal of the American Medical Association, The Lancet, The Lancet Oncology, and The New England Journal of Medicine. Main outcome measures: We used the Transparency and Openness Promotion (TOP) guideline and the International Committee of Medical Journal Editors (ICMJE) requirements for disclosing conflicts of interest (COIs) to evaluate journals standards. Results: TOP scores slightly improved during the COVID-19 pandemic, from a median of 5 (IQR: 2-12.5) out of a possible 24 points in February 2020 to 7 (IQR: 4-12) in May 2021, but overall, scores were very low at both time points. Journal policies scored highest for their adherence to data transparency and scored lowest for preregistration of study protocols and analysis plans and the submission of replication studies. Most journals fulfilled all ICMJE provisions for reporting COIs before (84%; n = 16) and during (95%; n = 18) the COVID-19 pandemic. Conclusions: The COVID-19 pandemic has highlighted the importance of practising open science. However, requirements for open science practices in audited policies were overall low, which may impede progress in health and medical research. As key stakeholders in disseminating research, journals should promote a research culture of greater transparency and more robust open science practices.

Physical activity for treatment of irritable bowel syndrome.

BACKGROUND: Current recommendations for people with irritable bowel syndrome (IBS) to partake in physical activity are based on low-level evidence, do not incorporate evidence from all available randomised controlled trials (RCTs) and provide little information regarding potential adverse effects. OBJECTIVES: To assess the benefits and harms of physical activity interventions in adults diagnosed with irritable bowel syndrome and to explore possible effect moderators including type, setting and nature of physical activity interventions. SEARCH METHODS: We searched nine electronic databases including CENTRAL, MEDLINE and Embase to 5 November 2021. We handsearched reference lists and sought unpublished studies through trial registries. SELECTION CRITERIA: We included RCTs involving adults (aged 18 years or older) diagnosed with IBS and conducted in any setting comparing a physical activity intervention with no intervention, usual care or wait-list control group or another physical activity intervention group and assessing a validated measure of symptoms, quality of life or bowel movement. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence. We pooled studies that evaluated similar outcomes using a random-effects meta-analysis, and synthesised data from other studies narratively. MAIN RESULTS: We included 11 RCTs with data for 622 participants. Most (10/11) were set in high- or middle- to high-income countries, with five involving supervised physical activity, three unsupervised activity and three a mix of supervised and unsupervised activity. No trial was at low risk of bias. Four trials specified a minimally important difference for at least one assessed outcome measure. Data for 10 trials were obtained from published journal articles, with data for one obtained from an unpublished Masters degree thesis. Irritable bowel syndrome symptoms Six RCTs assessed the effectiveness of a physical activity intervention compared with usual care on global symptoms of IBS. Meta-analysis of five studies showed an observed improvement in reported symptoms following physical activity (standardised mean difference (SMD) -0.93, 95% confidence interval (CI) -1.44 to -0.42; 185 participants). We rated the certainty of evidence for this outcome as very low due to unclear and high risk of bias, inconsistency and imprecision from sparse data. This means physical activity may improve IBS symptoms but the evidence is very uncertain. The results of the remaining study supported the meta-analysis but were at unclear risk of bias and sample size was small. Two studies assessed the effectiveness of a yoga intervention compared with a walking intervention on global IBS symptoms. Meta-analysis of these two studies found no conclusive evidence of an effect of yoga compared with walking on IBS symptoms (SMD -1.16, 95% CI -3.93 to 1.62; 124 participants). We rated the certainty of evidence as very low, meaning the evidence is very uncertain about the effect of yoga interventions compared with walking interventions on IBS symptoms. Two studies assessed the effectiveness of a physical activity intervention (yoga) compared with medication. One reported no observed difference in global IBS symptoms, though CIs were wide, suggesting uncertainty in the observed estimates and risk of bias was high (MD -1.20, 95% CI -2.65 to 0.25; 21 participants). We excluded IBS symptom data for the remaining study as it used a non-validated method. One study compared a yoga intervention with a dietary intervention and reported an observed improvement in symptoms with both interventions but neither intervention was superior to the other. Quality of life Five RCTs assessed the impact of physical activity on self-reported quality of life compared with usual care. Meta-analysis of data from four studies found no improvement in quality of life following a physical activity intervention (SMD 1.17, 95% CI -0.30 to 2.64; 134 participants; very low certainty due to risk of bias, inconsistency and imprecision). We rated the certainty of evidence as very low, meaning the evidence is very uncertain about the effect of physical activity interventions on quality-of-life outcomes in people with IBS. One study assessed the impact on quality of life of a yoga intervention compared with walking and observed an improvement in the yoga group (MD 53.45, 95% CI 38.85 to 68.05; 97 participants ).  One study reported no observed difference in quality of life between a yoga and a dietary intervention. Abdominal pain Two trials assessed the impact of physical activity compared with usual care on reported abdominal pain. Meta-analysis found no improvement in abdominal pain with physical activity compared with usual care (SMD 0.01, 95% CI -0.48 to 0.50; 64 participants). We rated the certainty of the evidence as very low due to risk of bias and imprecision, meaning the evidence is very uncertain about the effect of physical activity interventions on abdominal pain in people with IBS. One study assessing the impact of a yoga intervention compared with walking advice reported no observed differences between groups on abdominal pain. One study comparing a yoga intervention with a dietary intervention found neither intervention had a more beneficial impact than the other and both interventions did not conclusively reduce abdominal pain. There was insufficient evidence to adequately assess adverse effects associated with physical activity due to a lack of reporting in trials. One study reported a musculoskeletal injury in a yoga intervention group but this did not result in withdrawal from the study. AUTHORS' CONCLUSIONS: Findings from a small body of evidence suggest that physical activity comprising of yoga, treadmill exercise or support to increase physical activity may improve symptoms but not quality of life or abdominal pain in people diagnosed with IBS but we have little confidence in these conclusions due to the very low certainty of evidence. The numbers of reported adverse events were low and the certainty of these findings was very low for all comparisons, so no conclusions can be drawn. Discussions with patients considering physical activity as part of symptom management should address the uncertainty in the evidence to ensure fully informed decisions. If deemed sufficiently important to patients and healthcare providers, higher quality research is needed to enable more certain conclusions.

The solution structure of the human IgG2 subclass is distinct from those for human IgG1 and IgG4 providing an explanation for their discrete functions.

Human IgG2 antibody displays distinct therapeutically-useful properties compared with the IgG1, IgG3, and IgG4 antibody subclasses. IgG2 is the second most abundant IgG subclass, being able to bind human FcγRII/FcγRIII but not to FcγRI or complement C1q. Structural information on IgG2 is limited by the absence of a full-length crystal structure for this. To this end, we determined the solution structure of human myeloma IgG2 by atomistic X-ray and neutron-scattering modeling. Analytical ultracentrifugation disclosed that IgG2 is monomeric with a sedimentation coefficient (s20, w0) of 7.2 S. IgG2 dimer formation was ≤5% and independent of the buffer conditions. Small-angle X-ray scattering in a range of NaCl concentrations and in light and heavy water revealed that the X-ray radius of gyration (Rg ) is 5.2-5.4 nm, after allowing for radiation damage at higher concentrations, and that the neutron Rg value of 5.0 nm remained unchanged in all conditions. The X-ray and neutron distance distribution curves (P(r)) revealed two peaks, M1 and M2, that were unchanged in different buffers. The creation of >123,000 physically-realistic atomistic models by Monte Carlo simulations for joint X-ray and neutron-scattering curve fits, constrained by the requirement of correct disulfide bridges in the hinge, resulted in the determination of symmetric Y-shaped IgG2 structures. These molecular structures were distinct from those for asymmetric IgG1 and asymmetric and symmetric IgG4 and were attributable to the four hinge disulfides. Our IgG2 structures rationalize the existence of the human IgG1, IgG2, and IgG4 subclasses and explain the receptor-binding functions of IgG2.