Medicine

eLife assessment

This study offers a useful advance by introducing a cord blood DNA methylation score for maternal smoking effects, with the inclusion of diverse cohorts. However, the overall strength of evidence is deemed incomplete, due to concerns regarding low exposure levels, low statistical power, potential overfitting, and the need for clearer descriptions of statistical methods. Building more directly from the existing evidence base, exploring differences between ancestries, and considering additional health outcomes would help to enhance the study.

eLife assessment

This valuable study highlights how the diversity of the malaria parasite population diminishes following the initiation of effective control interventions but quickly rebounds as control wanes. The data presented is solid and the work shows how genetic studies could be used to monitor changes in disease transmission.

eLife assessment

This valuable study presents findings characterising the genomic features of E. coli isolated from neonatal meningitis from seven countries, and documents bacterial persistence and reinfection in two case studies. The genomic analyses are solid, although the inclusion of a larger number of isolates from more diverse geographies would have strengthened the generalisability of findings. The work will be of interest to people involved in the management of neonatal meningitis patients, and those studying E. coli epidemiology, diversity, and pathogenesis.

eLife assessment

This fundamental study explores the relationship between guanine-quadruplex structures and pathogenicity islands in 89 bacterial strains representing a range of pathogens. Guanine-quadruplex structures were found to be non-randomly distributed within pathogenicity islands and conserved within the same strains. These compelling findings shed light on the molecular mechanisms of Guanine-quadruplex structure-pathogenicity island interactions and will be of interest to all microbiologists.

eLife assessment

This important work by Park et al. demonstrates an open-top two-photon light sheet microscopy (OT-TP-LSM) for lesser invasive evaluation of intraoperative 3D pathology. The authors provide convincing evidence for the effectiveness of this technique investigating various human cancer cells. This article will be of broad interest to biologists and, specifically, pathologists utilizing 3D optical microscopy.

eLife assessment

In this fundamental study, the authors analyzed associations between circulating immune cells and periodontitis. Convincing evidence identifies three immune cell types related to periodontitis, which substantially advances our understanding of periodontitis.

eLife assessment

This important study substantially advances our understanding of pediatric Crohn's disease, mapping the cellular make-up of this disease and how patients respond to treatment. The evidence supporting the conclusions is compelling, with thorough bioinformatic analyses, underpinned by rigorous methodology and data integration. The work will be of broad interest to pediatric clinicians, immunologists and bioinformaticians.

eLife assessment

This study presents a valuable inventory of immune responses to the BTN162b2 mRNA COVID-19 vaccination in 20 hemodialyses (HD) patients and controls at different time courses. The transcriptomic sequencing data were collected and analyzed using a solid and validated methodology. The data analysis and clinical predictors to predict anti-Spike IgG titers in HD can be a starting point for further studies characterizing the immune dysregulation seen in ESRD.

eLife assessment

This work is a valuable presentation of sharp-wave-ripple reactivation of hippocampal neural ensemble activity recorded as animals explored two different environments. It attempts to use the fact that the ensemble code remaps between the two mazes to identify the best replay-detection procedures for analyzing this type of data. The reviewers found the evidence for a prescriptive conclusion inadequate, while still appreciating the concept of comparing maze-identity discrimination with replay.

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Connelly and colleagues provide convincing genetic evidence that importation from mainland Tanzania is a major source of Plasmodium falciparum lineages currently circulating in Zanzibar. This study also reveals ongoing local malaria transmission and occasional near-clonal outbreaks in Zanzibar. Overall, the manuscript effectively highlights the role of human movements in maintaining residual malaria transmission in an area targeted for intensive control interventions over the past decades and provides clear and valuable information for epidemiologists and public health professionals.

eLife assessment

This study presents a valuable report on the first warm autopsy case of a metastatic prostate cancer patient and the follow-up genomic and epigenomic analysis. The evidence supporting the claims of the authors is solid, although inclusion of more discussion of the study limitation and elaboration of mechanistic link for TP53, CDK12, and CDKN1B mutations would have strengthened the study. The work will be of interest to medical biologists working on prostate cancer.

eLife assessment

This valuable study presents findings that suggest the need for postoperative type 2 diabetes screening and that this should be prioritized in colorectal cancer survivors with overweight/obesity regardless of the type of colorectal cancer treatment applied. The evidence supporting the claims of the authors is solid and the authors use a population-based cohort study including all Danish colorectal patients who had undergone colorectal cancer surgery between 2001-2018. The work will be of interest to medical biologists, endocrinologists and oncologists working on colorectal cancer.

eLife assessment

This study presents valuable new insights into a HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, and delineates the kidney cell types that express HIV genes and are injured in these HIV-transgenic mice. A series of compelling experiments demonstrated that PKR inhibition can ameliorate HIVAN with reversal of mitochondrial dysfunction (mainly confined to endothelial cells), a prominent feature shared in other kidney diseases. The data support that inhibition of PKR and mitochondrial dysfunction has potential clinical significance for HIVAN.

eLife assessment

This study presents valuable findings on the mechanism of glucocorticoid-induced osteonecrosis of the femoral head. The data were collected and analyzed using solid, validated methodology and can be used as a starting point for functional studies of development of glucocorticoid-induced osteonecrosis. This paper would be of interest to cell biologists and biophysicists working on potential pharmacological treatments for glucocorticoid-induced osteonecrosis.

eLife assessment

This study presents important findings linking structural and functional changes in frontotemporal dementia to underlying neurotransmitter systems. The evidence to support the claims is solid, however, relationships are relatively modest and there are limitations regarding the neurotransmitter data. This study will appeal to clinicians and neuroscientists who are interested in the potential effects of certain neurotransmitter systems on clinical features of frontotemporal dementia.

eLife assessment

This study provides valuable insights into understanding bone fragility in T2D patients through the use of human skeletal tissue, reinforcing previous pre-clinical studies or observational studies using serum samples that the Wnt signaling pathway may play a critical role in T2D-related bone impairment. The methods are solid, but a limited number of subjects and a small set of genes with lack of data in terms of cellular properties of skeletal tissue are viewed as weaknesses.

eLife assessment

This study presents an important finding that implicates a rhodopsin gene duplication in the progression of autosomal dominant retinitis pigmentosa in patients. The authors utilize a retinal organoid model to demonstrate a similar disease phenotype and suggest defects can be ameliorated by using photoregulin. The data supporting the conclusions are solid, but there are some concerns regarding the strength of the phenotype in retinal organoids. This work will be of broad interest to vision researchers.

eLife assessment

This study presents a valuable finding that erythrocyte precursors could re-gain EPO responsiveness after DFP chelation therapy. In addition, the authors investigated iron trafficking in erythroblasts using the MDS mouse model. However, the evidence supporting the claims of the authors is still inadequate. The work will be of interest to medical biologists working on hematology.

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.