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...

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...

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 ...

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...

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...

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...

Prediabetes and type 2 diabetes (T2D) are metabolic disorders characterized by insulin resistance and {beta}-cell dysfunction. To understand the molecular mechanisms driving the transition from prediabetes to T2D, we performed a longitudinal proteogenomic analysis on 458 participants from the Prediabetes Lifestyle Intervention Study (PLIS). We identified 185 plasma proteins to be differentially expressed between conditions, 36 of which predict future T2D-onset. Integrating genetic data from 321 ...

BackgroundThe NHS-Galleri trial reported a substantial reduction in Stage IV cancer diagnoses and a four-fold increase in cancer detection rates, but did not meet its primary endpoint of reducing combined Stage III+IV diagnoses in a prespecified group of 12 cancers. We hypothesize that stage slip-- progression of cancers from Stage I/II to Stage III during diagnostic workup--is the primary mechanism behind this statistical masking. MethodsWe developed a Monte Carlo simulation of 142,000 partici...

The daily cortisol cycle is a critical indicator of hypothalamic-pituitary-adrenal (HPA) axis function. The current analytical approaches produce several outputs difficult to integrate into simple statistical models, clinical workflows, and ML/AI pipelines requiring single-value inputs. We developed the Cortisol Sine Score (CSS), a model-free scalar metric that quantifies daily cortisol exposure by computing a weighted sum of cortisol measurements across the day, using sine-transformed time-of-d...

ContextPolycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder associated with reproductive dysfunction and long-term cardiometabolic risk. Traditional phenotype classifications based on diagnostic criteria may not fully capture the multidimensional biological variability underlying endocrine and metabolic risk profiles, particularly in young women. ObjectiveTo identify data-driven endocrine-metabolic phenotypes in young women with PCOS and evaluate their association with establi...

Uric acid (UA) is traditionally regarded as a metabolic risk marker; however, its dynamic behavior during glucose-lowering therapy remains incompletely understood. We compared UA responses to a modified traditional Japanese diet (MJDD) and the DPP-4 inhibitor alogliptin in patients with early-stage type 2 diabetes mellitus (T2DM). In this prospective observational study, drug-naive patients received MJDD (n=58) or alogliptin (n=52) monotherapy for 3 months. Changes ({Delta}) in serum UA were ana...

BackgroundPlatelet count and C-reactive protein (CRP) are blood tests commonly used in primary care as part of diagnostic work up for symptomatic patients. Abnormal results of these tests can indicate an undetected cancer; however, it is not known whether the association between an abnormal test result and cancer risk varies by patient ethnicity. MethodsThis cohort study used routinely collected primary and secondary health care records in England with linkage to national cancer registry data. ...

Diet is an essential factor influencing biological aging, yet few exsiting dietary indices were specifically developed to target biological aging. We developed a data-driven food-based Empirical Dietary Index for Slower Epigenetic Aging (EDISEA) in the US Health and Retirement Study (HRS, n=7,398), which predicted deceleration of GrimAge, an established DNA methylation-based epigenetic clock. Participants in the highest versus lowest EDISEA quintile had 4.65-year deceleration in GrimAge (P value...

Obesity-driven type 2 diabetes (T2D) is characterized by pathological alterations in visceral white adipose tissue (vWAT). While microRNAs (miRNAs) are key post-transcriptional regulators, comprehensive human vWAT profiling across metabolic states remains limited. This study characterized vWAT miRNA expression in lean, obese, and obese+T2D individuals to identify regulatory networks associated with metabolic failure. Deep miRNA sequencing was performed on vWAT samples from a discovery cohort, fo...

Obesity and metabolic dysfunction are among the strongest risk factors for poor brain and mental health, yet the neural mechanisms linking metabolism, brain, and behaviour remains poorly understood. Here, we provide the first evidence for two distinct large-scale brain network configurations--one associated with metabolic health and another with obesity-- identified using resting-state fMRI data and metabolic phenotypes from a large community cohort (N = 564). While obesity was linked to enhance...

Background & AimsPerihilar cholangiocarcinoma is an aggressive malignancy with clinical heterogeneity and poor long-term outcomes after resection. Current prognostic assessment relies mainly on anatomical staging and pathological features, which incompletely capture the entire postoperative risk. We aimed to determine whether integrative analysis of clinical, surgical, pathological and tumor genomic data could improve time-resolved, individualized recurrence-risk prediction after curative-intent...

The gut microbiome composition varies across human populations, but its characteristics and determinants in a multi-ethnic setting remain incompletely understood. Singapore, a multicultural city-state, provides a context in which culturally diverse groups share a broadly similar built environment. Using the Health for Life in Singapore (HELIOS) cohort, we profiled the gut microbiome of ethnic Chinese, Indian, and Malay participants (n=861) who resided in the country. Despite substantial overlap ...

The gut microbiome has been linked to breast cancer, largely through microbial functions involved in estrogen metabolism (the "estrobolome"); however, specific microbial targets remain poorly defined in human studies. Here, we profiled the gut microbiome using whole-metagenome shotgun sequencing, and plasma and stool metabolites were quantified using targeted metabolomics, in a study of 70 postmenopausal female cases with treatment-naive ER-positive breast cancer and 70 controls. Reduced species...

BackgroundHelicobacter pylori infection accounts for 98% of gastric cancer (GC) cases in Japan. Since 2013, the nationwide expansion of H. pylori eradication therapy to chronic gastritis patients has created a unique opportunity to evaluate its population-level impact on GC primary prevention. However, short-term reductions in GC deaths are difficult to interpret given the long natural history of gastric carcinogenesis. This study aimed to assess the early impact of population-level eradication ...

IntroductionBRCA1/2 alterations are increasingly recognized as biologically and clinically relevant features in prostate cancer, yet the prognostic and therapeutic significance of zygosity status remains uncertain. Understanding differences between monoallelic and biallelic inactivation may refine risk stratification and guide therapeutic decision-making. Materials and MethodsA retrospective, desk-based observational analysis was performed using publicly accessible datasets from TCGA-PRAD (prim...