Medicine

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.

eLife assessment

This manuscript addresses an important question, that in countries endemic for P vivax the need to administer a primaquine (PQ) course adequate to prevent relapse in G6PD deficient persons poses a real dilemma. On one hand PQ will cause haemolysis; on the other hand, without PQ the chance of relapse is very high. As a result, out of fear of severe haemolysis, PQ has been under-used. This manuscript is convincing that regimen (1) can be used successfully to deliver within 3 weeks, under hospital conditions, the dose of PQ required to prevent P vivax relapse.

eLife assessment

This important study tested the hypothesis that liver-derived but not serum-derived antibodies that are cross-reactive to E.coli and to host proteins can play a role in the hepatic damage found in severe alcoholic hepatitis (SAH). Using a solid methodology that includes state-of-the-art microscopy, proteome arrays, and gene ontology assays, it provides strong evidence that liver-derived IgG and IgA with cytotoxic properties and reactivity to both gut-derived E.coli and autoantigens accumulated in hepatocytes of SAH patients but not of healthy controls. The study would benefit from a broader analysis of gut microbiota proteome and further characterization of B cells infiltrating the liver tissue including their numbers/field and their origin (infiltrating versus resident cells). The work opens new avenues of understanding for the pathogenesis of severe alcoholic hepatitis and is of great interest to researchers and clinicians in the field.

eLife assessment

In this valuable study, patients homozygous for both minor frequency alleles of the APOL1 gene are shown to be at significant risk for progression into sepsis after infection. The study has enrolled a significant number of subjects and provides solid results. The study addresses to infectious diseases and critical care experts and one major weakness is the lack of inclusion of non-Black patients.

eLife assessment:

Autosomal dominant optic atrophy (DOA) in humans is associated with mutations in OPA1, a mitochondrial dynamin like GTPase. This study uses Drosophila as a model to recapitulate some aspects of the disease phenotype, and it supports and extends previously published data to provide valuable findings that have theoretical or practical implications in the field of rare retinal diseases. The approaches used are solid and allow to investigate differences between mutations that are supposed to be loss-of-function or acting as dominant negative with consequences in the optic system or in a version of DOA, in which other tissues are also affected. However, the main claims are only partially supported and additional information in the materials and methods and several figure legends is needed to complete the study.

eLife assessment

This study provides solid evidence for differences in habit-learning in obsessive-compulsive disorder versus controls. Contrary to previous studies that employed a single laboratory session to study habit-learning, here a smartphone app delivered motor-sequence tasks daily for a month. These results have important implications for our understanding of goal-directed versus habit learning in obsessive-compulsive disorder.

eLife assessment

This valuable paper uses representative samples of micro-census data from Botswana to describe migration rates over four points in time, from 1981 to 2011. The authors use compelling descriptive data to present migration characteristics where roughly 10% of the population moved in the past year - with equal numbers of men and women, and with migration between districts more common than within districts. Preliminary data indicated migration patterns could have supported HIV diffusion, this can be a starting point for more in-depth analyses. The work will be of interest to those studying human movement and its impact on diseases.

eLife assessment

The manuscript by Brunetti et al. represents an important contribution where SARS-CoV-2 infection of T-helper cells is implicated and found to be mediated by CD4. The work progressed through a computationally driven hypothesis, by analyzing the interaction partners of SARS-CoV-2 spike glycoprotein (as initially modelled through similar SARS-CoV-1), followed by experimental validations, and further computational and experimental insights on the mechanism of binding. The study identifies the interaction between spike RBD domain and N Terminal domain of CD4 molecule as the specific viral attachment strategy. The evidence supporting the claims of the authors is solid, the results look significant and the data is clear and enough for understanding the manuscript. It also provides a potential usefulness of their approach in future work in understanding how viruses mediate infection of T cells. The work will be of interest to medical biologists working on SARS-CoV-2.

eLife assessment

This study presents a useful inventory of the joint effects of genetic and environmental factors on psychotic-like experiences and identifies cognitive ability as a potential underlying mediating pathway. The data were analyzed using a solid and validated methodology based on a large, multi-center dataset. The claim that these findings are of relevance to psychosis risk and have implications for policy changes is partially supported by the results.

eLife assessment

This small-sized clinical trial comparing nebulized dornase-alfa to the best available care in patients hospitalized with COVID-19 pneumonia is valuable, but in its present form the paper is incomplete.

eLife assessment

This paper presents an important effort to develop an open source software framework for monitoring trends and variations in healthcare over time in England. They demonstrate a compelling example of how this system can track key health care indicators over the course of the COVID-19 pandemic. The paper will likely be mainly of interest to stakeholders in England, but could inspire the creation of similar systems in other countries.

eLife assessment

This is an important study that uncovers a new molecular pathway that links traditional monoaminergic antidepressants with regulation of glutamate neurotransmission. The data provided for the model are convincing and demonstrate the pathway in human plasma and brain, mouse brain, and cultured cells, using the relative strengths of each system. The work will be of interest to psychiatrists studying depression as well as basic neurobiologists interested in monoamine signaling in the brain.

eLife assessment

These valuable findings presented by Wu et al. advance our understanding in novel cell signaling regulators of hepatic metabolism. The evidence supporting these conclusions are solid, utilizing in vivo and in vitro gain and loss of function studies. These work will be of interest to biologists working in the field of hepatic steatosis.

eLife assessment

The creation of a single-cell atlas of normal and degenerative human anterior cruciate ligament (ACL) tissues using a single-cell RNA sequencing method is an important approach to understanding the pathological mechanisms of ACL degeneration. The data of this study showed the existence of fibroblasts, endothelial cells, pericytes, and immune cells in healthy ACL, and their ratios altered in the degenerative ACL, mainly exhibited as an increase in fibroblasts and immune cells. The data analysis suggests that alterations of spatial transcriptome and changes in gene expression and signaling pathways may contribute to ACL degeneration.

eLife assessment

This paper is important because of its integration of movement and contextual information to control a virtual arm for individuals with upper-limb differences. The provided evidence convincingly demonstrates the approach's feasibility for manipulating a single object shape in different orientations within a virtual environment. However, additional improvements are needed for this proof-of-concept neuro-model to fulfil practical requirements.

eLife assessment

The findings of this article provide valuable information on the changes of cell clusters induced by chronic periodontitis. The observation of a new fibroblast subpopulation, named AG fibroblasts, is interesting, and the strength of evidence presented is solid.

eLife assessment

This important work employed global proteomic and phosphorylation site analysis to examine adipose tissue and skeletal muscle samples collected at baseline from a sample of 10 women, including those with and without PCOS, both before and after 5 weeks of electrical stimulation treatment. This work significantly enhances our knowledge by demonstrating that women with PCOS who exhibit protein hyperandrogenicity have elevated extramyocellular lipid levels and a decreased number of oxidative insulin-sensitive type I muscle fibers. The convincing evidence supporting these conclusions makes this research of broad interest not only to scientists but also to clinicians.

eLife assessment

This study presents valuable findings on the risk factors of avascular osteonecrosis in patients with Gaucher disease. The evidence supporting the claims of the authors is convincing. The work will interest clinicians who treat patients with inborn errors of metabolism.

eLife assessment

The findings of this study yield important new insights into the relationship between the number of close friends and mental health, cognition, and brain structure. Due to the large sample sizes, the evidence is solid but would have been improved if both of the analyzed datasets contained more closely matched measures. This work advances our understanding of how the friendship network relates to young adolescents' mental well-being and cognitive functioning and their underlying neural mechanisms.

eLife assessment

This study presents useful structural and functional connectivity profiles of patients receiving deep brain stimulation in the posterior hypothalamus for severe and refractory aggressive behavior. The inclusion of data from multiple centers is compelling. However, the imaging analysis is incomplete and the interpretation of the findings is not solid.