eLife

ObjectivesCervical cancer is a preventable disease, and a properly implemented screening programme can reduce its incidence and mortality and potentially save resources. This study aimed to evaluate the cost-effectiveness of options for potential transformation of the nationwide screening programme in the Czech Republic, especially considering recent changes in HPV DNA testing recommendations. MethodsA microsimulation model was developed to assess the cost-effectiveness and health benefits of a...

ObjectiveTo describe the Swedish 2020 switch to primary cervical screening using Human Papillomavirus (HPV) self-sampling at home and compare with cervical cancer incidence trends. MethodsStatistics on HPV self-sampling and cervical cancer incidence were obtained from comprehensive nationwide registries. ResultsHPV self-sampling was recommended in 2017 for non-attending women and was in 2020 recommended as a primary screening for all women aged 23-70 years of age. During 2016-2020 there were <...

ObjectiveThis study utilizes small-sample periodontitis data to exploratively investigate causal relationships between the oral microbiome and periodontitis in East Asian populations. We aimed to identify specific oral microbial taxa that may drive disease pathogenesis. Given the exploratory nature of the dataset, findings should be interpreted as hypothesis-generating. MethodsWe performed a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary stat...

Structured AbstractO_ST_ABSIntroductionC_ST_ABSCervical cancer screening is difficult to initiate and sustain during war due to disrupted health services, population displacement and limited clinical capacity. Evidence on whether human papillomavirus (HPV)-based screening using self-sampling can function as a screening pathway during armed conflict is unknown. This study evaluated the feasibility, acceptability and operational performance of HPV self-sampling for cervical cancer screening in a w...

There is no readily accessible, scalable cure for HIV infection. Trials of HIV-specific broadly neutralising antibodies (bNAbs) demonstrate inhibition of viral replication and reduction of the reservoir of latently-infected cells, potentially offering new strategies for HIV eradication. Animal and human studies suggest bNAbs have multiple activities, including a direct antiviral action and a secondary induction of T cell responses, the vaccinal effect. The RIO trial assessed HIV-specific cell-m...

Background. Although health mediation is widely studied in the U.S. through community health worker programs, evidence on their effectiveness in promoting cancer screening in Europe is limited. Since 2022, the "13 en Sante" program has implemented a multicomponent health mediation intervention -combining educational activities, outreach strategies, and navigation support- in socioeconomically disadvantaged neighbourhoods of Marseille, France. This study evaluates the effectiveness of this progra...

BackgroundBladder cancer imposes substantial clinical and economic burden, yet key natural-history quantities that determine the potential effectiveness of screening--such as the size of the screen-detectable preclinical reservoir and the preclinical sojourn time--are largely unobservable. The Cancer Intervention and Surveillance Modeling Network (CISNET) uses standardized stress tests to compare independently developed microsimulation models and to clarify how differences in model structure tra...

BackgroundPeople with Citrin Deficiency (CD), inactivated for both copies of SLC25A13, have lean metabolic dysfunction-associated steatotic liver disease (MASLD) and an aversion to sweets. The mouse model of CD, which inactivates Slc25a13 and Gpd2, has been shown to elevate hepatic glycerol-3-phosphate (G3P) and activate carbohydrate response element binding protein (ChREBP) thereby increasing lipogenic transcription, which could account for MASLD, and circulation of FGF21, which could account f...

BackgroundCervical cancer remains a significant global public health challenge, with the overwhelming majority of its burden borne by low- and middle-income countries. Globally, an estimated 660,000 new cases and 350,000 deaths occur each year, with more than 90% of cervical cancer-related mortality concentrated in resource-limited settings. In Africa, limited access to organized screening programs and early detection services continues to contribute to persistently high incidence and mortality ...

Mitochondrial dysfunction has long been associated with insulin resistance, yet the causal relationship in humans remains unresolved. Here, we leveraged individuals carrying the diabetogenic m.3243A>G mtDNA mutation as a human genetic model to probe the causal contribution of mitochondrial defects to insulin resistance and delineate the underlying molecular and bioenergetic mechanisms. In vivo metabolic phenotyping revealed selective skeletal muscle insulin resistance with preserved liver and ad...

BackgroundMetformin is the cornerstone therapy for type 2 diabetes, but gastrointestinal intolerance commonly limits dose escalation and long-term adherence. In the ProGasMet trial, multi-strain probiotic supplementation improved metformin tolerability. However, the underlying microbiome-metabolome mechanisms remain unclear. Methods and analysisWe performed an exploratory multi-omics analysis using Period 1 of a randomized, double-blind, placebo-controlled trial. Participants with metformin int...

BackgroundSubsequent primary malignancies following human papillomavirus (HPV)-related cancers represent an important survivorship concern. However, evidence remains limited regarding sociodemographic and clinical factors associated with registry-defined subsequent cancers among children, adolescents, and young adults in U.S. population-based cohorts. MethodsWe conducted a retrospective population-based analysis of 1,326 individuals diagnosed with HPV-related cancers using Surveillance, Epidemi...

Clonal hematopoiesis (CH), defined by the expansion of hematopoietic cells with somatic mutations in leukemogenic genes (CH of indeterminate potential (CHIP)) or with mosaic chromosomal alterations (mCAs), is associated with aging and adverse health outcomes in the general population. CHIP prevalence has been shown to be higher in People with HIV (PWH) than in controls. However, the full spectrum, prevalence, and clinical consequences of CH in PWH remain incompletely understood. Here, we provide...

ContextPolycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and frequent metabolic disturbances, including insulin resistance (IR), and is commonly accompanied by chronic low-grade inflammation. Complete blood count (CBC)-derived indices provide inexpensive markers reflecting systemic inflammatory and hematologic status; however, their relationships with androgen-related features in PCOS remain incompletely characterized. ObjectiveTo evaluate associations between androgen-relat...

BackgroundPlasmodium vivax is the predominant cause of malaria in South Asia. P. vivax cases have fallen over the past decade, but cross-border transmission remains a major challenge to elimination. Genetic data can generate valuable insights into transmission; however, until now, only low-resolution data have been available from Nepal, Bhutan and Bangladesh. We piloted high-resolution genotyping using a new microhaplotype (multiallelic) assay to monitor P. vivax transmission across borders. Me...

AimsThe distribution of abdominal adipose depots and their mechanistic links to type 2 diabetes remain incompletely understood. This study elucidated the relationship between type 2 diabetes presence and quantitative abdominal imaging traits, including hepatic steatosis, liver and spleen size, and adipose distribution, using unenhanced computed tomography (CT) scans from a large-scale, racially diverse, disease-focused medical biobank. Materials and MethodsDeep learning algorithms were applied ...

Cervical intraepithelial neoplasia grade 2 (CIN2) lesions show variable outcomes, and accurate prediction of regression remains a major clinical challenge. We developed an interpretable machine learning pipeline that integrates quantitative histological, clinical, and human papillomavirus (HPV) -genotyping data to predict lesion regression within one and two years. Using panoptic segmentation of routine hematoxylin and eosin (H&E) -stained biopsies, we extracted human-interpretable morphological...

Age-defined type 1 diabetes (T1D) endotypes, T1DE1 and T1DE2, are characterized by reproducible differences in pancreatic immunopathology and clinical course. In particular, these endotypes differ in the extent and composition of lymphocytic insulitis and in the extent of loss of insulin-producing {beta} cell mass, at diagnosis. However, blood-based biomarkers that may distinguish these endotypes and inform the underlying immune-islet biology axis at diagnosis remain limited. Here, we characteri...

BackgroundPlasmodium malariae, one of the five parasite species causing malaria in humans, though less widespread than P. falciparum, can result in prolonged and persistent infections. This research aims to monitor asymptomatic Plasmodium infections and characterize genetic diversity in the merozoite surface protein (msp-1) of P. malariae in Beninese population. Methods and findingsBlood samples collected from 484 asymptomatic participants in Southern Benin underwent analysis for all human Plas...

The use of semaglutide (SE), a glucagon-like peptide-1 receptor agonist (GLP-1RA) with glucose-lowering and weight-loss effects, has risen rapidly, particularly among women of reproductive age. While preclinical studies suggest benefits for ovarian function via the hypothalamic-pituitary-ovarian axis, its impact on the endometrial-embryo interface remains unclear. Here, we show that GLP-1R is dynamically expressed in fertile human endometrium, restricted to epithelial cells and markedly upregula...