CMV serostatus is associated with improved survival and delayed toxicity onset following anti-PD-1 checkpoint blockade.

Cytomegalovirus (CMV) is a globally endemic latent herpes virus that profoundly impacts T cell immunity. We investigated the oncological consequences of CMV infection across 341 prospectively recruited patients receiving immune checkpoint blockade (ICB) for melanoma. CMV patients with metastatic melanoma (MM) have higher lymphocyte counts, reduced neutrophil to lymphocyte ratio and divergent CD8 T cell gene expression.

Global prevalence of long COVID and its most common symptoms among healthcare workers: a systematic review and meta-analysis.

Objectives: Long COVID, a condition where symptoms persist after the acute phase of COVID-19, is a significant concern for healthcare workers (HCWs) due to their higher risk of infection. However, there is limited knowledge regarding the prevalence, symptoms and clustering of long COVID in HCWs. We aimed to estimate the pooled prevalence and identify the most common symptoms of long COVID among HCWs who were infected with SARS-CoV-2 virus globally, and investigate any differences by geographical region and other factors.

A weakly-supervised follicle segmentation method in ultrasound images.

Accurate follicle segmentation in ultrasound images is crucial for monitoring follicle development, a key factor in fertility treatments. However, obtaining pixel-level annotations for fully supervised instance segmentation is often impractical due to time and workload constraints. This paper presents a weakly supervised instance segmentation method that leverages bounding boxes as approximate annotations, aiming to assist clinicians with automated tools for follicle development monitoring.

Profiling the resistome and virulome of Bacillus strains used for probiotic-based sanitation: a multicenter WGS analysis.

Background: Healthcare-associated infections (HAIs) caused by microbes that acquire antimicrobial resistance (AMR) represent an increasing threat to human health worldwide. The high use of chemical disinfectants aimed at reducing the presence of pathogens in the hospital environment can simultaneously favor the selection of resistant strains, potentially worsening AMR concerns. In the search for sustainable ways to control bioburden without affecting this aspect, probiotic-based sanitation (PBS) using Bacillus spp.

Determinants of the use of insecticide-treated nets and intermittent preventive treatment of malaria among pregnant women in Angola.

Background: The determinants of insecticide-treated nets (ITNs) use and uptake of three doses or more of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp 3+) among pregnant women can vary between regions and is not well studied in Angola.

Methods: This study analysed secondary data of a cluster-randomized controlled trial that evaluated the impact of the Maternal and Child Health Handbook (MCH-HB) on the continuum of care among pregnant women and mothers in Angola from 2019 to 2020. Those who received antenatal care (ANC) were analysed.

Systematic identification of disease-causing promoter and untranslated region variants in 8040 undiagnosed individuals with rare disease.

Background: Both promoters and untranslated regions (UTRs) have critical regulatory roles, yet variants in these regions are largely excluded from clinical genetic testing due to difficulty in interpreting pathogenicity. The extent to which these regions may harbour diagnoses for individuals with rare disease is currently unknown.

Methods: We present a framework for the identification and annotation of potentially deleterious proximal promoter and UTR variants in known dominant disease genes.

Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum.

Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses (n = 6,095-246,862).

MSP-tracker: A versatile vesicle tracking software tool used to reveal the spatial control of polarized secretion in Drosophila epithelial cells.

Understanding how specific secretory cargoes are targeted to distinct domains of the plasma membrane in epithelial cells requires analyzing the trafficking of post-Golgi vesicles to their sites of secretion. We used the RUSH (retention using selective hooks) system to synchronously release an apical cargo, Cadherin 99C (Cad99C), and a basolateral cargo, the ECM protein Nidogen, from the endoplasmic reticulum and followed their movements to the plasma membrane. We also developed an interactive vesicle tracking framework, MSP-tracker and viewer, that exploits developments in computer vision and deep learning to determine vesicle trajectories in a noisy environment without the need for extensive training data.

Omics Analyses Uncover Host Networks Defining Virus-Permissive and -Hostile Cellular States.

The capacity of host cells to sustain or restrict virus infection is influenced by their proteome. Understanding the compendium of proteins defining cellular permissiveness is key to many questions in fundamental virology. Here, we apply a multi-omic approach to determine the proteins that are associated with highly permissive, intermediate, and hostile cellular states.

Global, regional, and national burden of neglected tropical diseases and malaria in the general population, 1990-2021: Systematic analysis of the global burden of disease study 2021.

Background: Neglected Tropical Diseases (NTDs) and malaria present considerable health obstacles, particularly impacting the socio-economic progress in at-risk areas. We aimed to estimate the burden, trends, and inequalities of NTDs and malaria globally, regionally, and nationally from 1990 to 2021.

Methods: The study utilized data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, encompassing 204 countries and territories, spanning 21 global regions, including diverse populations across different Socio-Demographic Index (SDI) levels.

Genetic association studies in critically ill patients: a systematic review.

Background: Critical illness is complex, and genetic research holds the potential to uncover underlying disease mechanisms. However, existing research results have not been systematically summarized. This study aims to compile all genetic association studies in critically ill patients and assess their risks of bias.

Genetically distinct within-host subpopulations of hepatitis C virus persist after Direct-Acting Antiviral treatment failure.

Analysis of viral genetic data has previously revealed distinct within-host population structures in both untreated and interferon-treated chronic hepatitis C virus (HCV) infections. While multiple subpopulations persisted during the infection, each subpopulation was observed only intermittently. However, it was unknown whether similar patterns were also present after Direct-Acting Antiviral (DAA) treatment, where viral populations were often assumed to go through narrow bottlenecks.

The role of the enrolling clinician in emergency research conducted under an exception from informed consent.

The Exception from Informed Consent (EFIC) permits patient enrolment into therapeutic emergency research where obtaining informed consent is challenging. Yet this fails to resolve a core ethical conflict in the research and has generated controversy. This is because existing justification and practice has relied on applying EFIC per study-a wholesale permission to enroll irrespective of circumstance-instead of per patient.

Accessible, realistic genome simulation with selection using stdpopsim.

Selection is a fundamental evolutionary force that shapes patterns of genetic variation across species. However, simulations incorporating realistic selection along heterogeneous genomes in complex demographic histories are challenging, limiting our ability to benchmark statistical methods aimed at detecting selection and to explore theoretical predictions. stdpopsim is a community-maintained simulation library that already provides an extensive catalog of species-specific population genetic models.

Socio-economic status is a social construct with heritable components and genetic consequences.

In civilizations, individuals are born into or sorted into different levels of socio-economic status (SES). SES clusters in families and geographically, and is robustly associated with genetic effects. Here we first review the history of scientific research on the relationship between SES and heredity.

Amount and intensity of daily total physical activity, step count and risk of incident cancer in the UK Biobank.

Objectives: To investigate associations between daily physical activity, activity intensity and step counts with incident cancer risk.

Methods: Prospective analysis of UK Biobank participants who wore wrist-based accelerometers for 7 days, followed for cancer incidence (mean follow-up 5.8 years, SD 1.

Transformers and large language models are efficient feature extractors for electronic health record studies.

Background: Free-text data is abundant in electronic health records, but challenges in accurate and scalable information extraction mean less specific clinical codes are often used instead.

Methods: We evaluated the efficacy of feature extraction using modern natural language processing methods (NLP) and large language models (LLMs) on 938,150 hospital antibiotic prescriptions from Oxfordshire, UK. Specifically, we investigated inferring the type(s) of infection from a free-text "indication" field, where clinicians state the reason for prescribing antibiotics.

Molecular clock complexities of Clostridioides difficile.

Objectives: Reconstruct the phylogenetic status of a collection of historical Clostridioides difficile isolates and evaluate the congruence of their evolutionary trajectories with established molecular clock models.

Methods: Phylogenetic analysis was performed on Illumina sequence reads from previously analysed historic C. difficile isolates (1980-86; n = 75) demonstrating multiple antimicrobial resistances.

Epidemiological and phylogenetic analyses of public SARS-CoV-2 data from Malawi.

The COVID-19 pandemic has had varying impacts across different regions, necessitating localised data-driven responses. SARS-CoV-2 was first identified in a person in Wuhan, China, in December 2019 and spread globally within three months. While there were similarities in the pandemic's impact across regions, key differences motivated systematic quantitative analysis of diverse geographical data to inform responses.

Cancer inequalities in the United Kingdom and the data used to measure them: a scoping review.

Significant cancer inequalities may exist across the United Kingdom (UK). Data are required to delineate and quantify these inequalities. This scoping review was undertaken to map the research evidence on UK cancer inequalities and determine the current data available, and the data gaps, that, if filled, could inform a strategy to reduce them.

Selection of Plasmodium falciparum kelch13 mutations in Uganda in comparison with southeast Asia: a modelling study.

Background: Artemisinin partial resistance, mediated by mutations in the Plasmodium falciparum kelch13 gene (k13), rapidly spread in southeast Asia, undermining the antimalarial effectiveness of artemisinin-based combination therapies. k13 mutations have also arisen in Africa, but their rates of increase are not well characterised. We aimed to quantify the selection of k13 mutations in Africa and compare the selection with that in southeast Asia.

Prognosis of surgically resected clinical stage 1A non-small cell lung cancers manifesting as a subsolid nodule on computed tomography including pure ground glass nodules.

This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: To quantify the risk of tumour relapse/recurrence after a surgical resection of stage 1A non-small cell lung cancer (NSCLC) as manifested on computed tomography (CT) imaging as a subsolid nodule.

A novel gene linked to Imipenem resistance in E. coli isolate lacking known Imipenem-resistance genes.

Imipenem-resistant Escherichia coli strains represent a growing public health concern, posing a threat due to their resistance to last-resort antibiotics. Here, we present the discovery of the Imipenem-Linked Resistance Gene VIN (ILR-VIN) within E. coli isolates from Vietnam, revealing its absence in non-resistant E.