Medicine

eLife assessment

This manuscript is a useful contribution to the field of complex trait genomics. The study does have some real strengths, such as focusing on cancer age-of-onset, developing methods for this unusual trait and using two cohorts. However, the significance of findings is difficult to evaluate without further comparisons and validations, leaving the work in its current form incomplete.

eLife assessment

Little is known about the role of the microbiome alterations in epithelial ovarian cancer. This important and rigorous study carefully examined the microbiome composition of 1001 samples from close to 200 ovarian cancer cases and controls, and presents compelling evidence that the fallopian tube microbiota are perturbed in ovarian cancer patients. These insights are expected to fuel further exploration into translational opportunities stemming from these findings.

eLife assessment

This study presents a valuable insight into a computational mechanism of pain perception. The evidence supporting the authors' claims is solid, although the inclusion of 1) more diverse candidate computational models, 2) more systematic analysis of the temporal regularity effects on the model fit, and 3) tests on clinical samples would have strengthened the study. The work will be of interest to pain researchers working on computational models and cognitive mechanisms of pain in a Bayesian framework.

eLife assessment

This study presents a valuable finding that serum androstenedione levels may provide a new biomarker for early detection and progression of glaucoma, although a single biomarker is unlikely to be singularly predictive due to the etiological heterogeneity of the disease. The strength of the evidence presented is solid, supported by multiple lines of evidence.

eLife assessment

This fundamental study substantially advances our understanding of the role of zinc in metabolism, specifically a newly established clinical link between mutations in the zinc transporter SLC39A5, elevated serum zinc levels, and a reduction in the risk of Type 2 Diabetes. The provided evidence is solid with state-of-the-art genetic analysis of large human cohorts followed by a comprehensive analysis of a mouse SLC39A5 knockout mutant, establishing that SLC39A5 plays a role in hepatic lipid handling through AMPK signaling, although the limited analysis of a pancreatic phenotype that has previously been described constitutes a weakness. This study will be of relevance to researchers interested in metabolism, fatty liver disease, and the biology of trace elements.

eLife assessment

This paper presents a valuable pipeline based on state-of-the-art analytical software that was used to study genetic pleiotropy between neuropsychiatric disorders. The presented evidence supporting the claims is solid, although the paper is lacking an appropriate comparison to previously published methods as well as a more detailed exploration of some of the findings. The created pipeline is made publicly available and can thus be used by researchers from diverse fields to study different combinations of diseases and traits.

eLife assessment

This study presents valuable findings that could be utilized for identifying women at risk for preeclampsia before the onset of the disease. The novel aspect of this study lies in the utilization of exosomes of two different sizes. The data are solid: the methods, data, and analysis broadly support the claims. This work will be of interest to medical researchers and clinicians who work on preeclampsia and women's health.

eLife assessment

This study presents valuable findings on genetic risk factors for type 1 diabetes and celiac disease using a large cohort from the Environmental Determinants of Diabetes in the Young (TEDDY) study. The evidence supporting the claims of the authors is solid, although the inclusion of the genetic effect of this locus on individuals with different genetic backgrounds would have strengthened the study. The work will be of interest to population geneticists working on diabetes and celiac disease.

eLife assessment

This study aims to explore the diabetes-bone paradox using the Mendelian Randomization approach. That diabetes itself is not the direct cause, but rather the complications or associated risk factors increase the risk of fracture, constitutes a valuable insight. Mendelian randomization to explain the relationship of two complex conditions is solid and conducted properly; however, the efforts to reconcile the discrepancies between the Mendelian Randomization analysis and observational studies are incomplete.

eLife assessment

This manuscript uses genetic mouse modeling to delve deeper into a rare human disease of aging. The targeted approaches employed lend greater pathophysiologic insight and makes this paper valuable to the field art large. Additionally, the approaches used are rigorous and solid in supporting their conclusions. Some minor weaknesses were noted along with suggestions to add greater clarity.

eLife assessment

This study addresses a pertinent and important topic related to prolonged delays in cervical cancer screening and the need to maintain routine and timely screening services in a large health maintenance network in Boston. The findings provide a solid, yet incomplete roadmap for implementing simple strategies to help patients return to essential health services.

eLife assessment

The authors establish a Drosophila model to assess the severity of disease-linked alleles of Uba5. Using both in vivo and in vitro experiments, this valuable study demonstrates the alleles fall into mild, intermediate, and severe classes, with convincing evidence to support their conclusion. This well-executed study establishes a model for further characterization of Uba5-related phenotypes in a powerful model system.

eLife assessment

This study presents a valuable deep learning-based model for predicting fracture within the next five years from just a standard distal radius and ulna scan obtained using high-resolution computed tomography images. The evidence supporting the conclusion that the model-predicted fracture prediction score can be used clinically to identify women at risk of fracture more effectively than with the current standard clinical approach is convincing. This work will be of interest to biomechanists and biomedical engineers working on osteoporosis.

eLife assessment

This study presents a valuable analysis of the effects of covariates, such as age, sex, socio-economic status, or biomarker levels, on the predictive accuracy of polygenic scores for body mass index; it also presents approaches for improving prediction accuracy by accounting for such covariates. While the analyses are solid, the study falls short of providing a cogent interpretation of key findings, which could be of great interest and utility. The work will be of interest to people using and developing methods for phenotypic prediction based on polygenic scores.

eLife assessment

This important work provides evidence regarding the impact of the COVID-19 pandemic on cervical cancer screening and precancer treatments in the USA. As there are few screening registries, the study provides solid evidence using a survey of health providers' impressions to assess whether cervical cancer screening services declined during the pandemic. The work will be of interest to public health professionals working in cancer prevention.

eLife assessment

This important manuscript, which describes the largest genetic association study to date, uses broadly compelling methods to address the genetic susceptibility to tuberculosis infection. A strength of the paper is that this multi-ancestry meta-analysis of genetic association studies than is more powerful than what has been done before. A weakness is that its main result is difficult to interpret due to the complexity of the genetic association signal.

eLife assessment

This important study brings together a clear application of the digital twin approach to make predictions using patient specific models with different genotypes. The data are compelling and go beyond the current state-of-the-art to support proof-of-principle evidence. Given the low subject numbers, further studies will be required going forward to support the veracity of the data and its translational utility.

eLife assessment

Overall, this is an important study that characterizes human oral lichen planus via single-cell analysis. Although the work is descriptive, it can represent an important resource for future studies and highlights potentially relevant biology. However, the claims are a bit overstated and some of the analyses that lead to interpretations remain incomplete.

eLife assessment

This US study presents findings from an online survey and in-person interviews of healthcare providers in areas associated with cervical screening provision during the post-acute phase of the pandemic. The findings are valuable as they provide insights into a range of areas, from healthcare characteristics to screening barriers and HPV self-sampling. The evidence supporting the claims of the authors is solid, although the inclusion of a nationally-representative sample of healthcare providers and a greater gender/ethnicity/racial mix of interviewees would have strengthened the study. The work will be of interest to public health scientists and a cancer prevention and control audience.

eLife assessment

This important paper describes a valuable systematic review and meta-analysis of mental health problems in polycystic ovary syndrome (PCOS) that drive the excess economic burden associated with this common endocrine disorder. Interestingly, the cost of the diagnostic evaluation is only a relatively minor part of the total costs, but mental health disorders were identified as a significant component of the economic burden. These solid findings could not have been anticipated intuitively and are of considerable value for public health prioritization of PCOS.