PLoS Medicine最新文献

Glucagon-like peptide-1 (GLP-1)-based medications, such as semaglutide and tirzepatide, have transformed obesity care. However, rising use brings concerns about side effects, long-term outcomes, and unregulated products. Ensuring safe access requires oversight, monitoring, and coordinated clinical care.

Background: Approximately 20% of patients with stage II colorectal cancer (CRC) experience tumor relapse despite standard surgical treatment. Histopathological analysis holds promise for postsurgical risk stratification and guiding adjuvant chemotherapy (ACT) decisions. The aim of this study was to use deep learning to extract explainable tissue biomarkers from whole-slide images.

Methods and findings: In this retrospective cohort study, we developed and validated SurvFinder, an interpretable deep learning framework designed to autonomously identify tissue-based risk biomarkers from hematoxylin and eosin (H&E)-stained slides. The framework aims to support individualized risk stratification and explore associations with treatment outcomes. The present study included 6,950 H&E slides from 1,604 patients with stage II CRC across four independent cohorts in China. Patients were enrolled from 2012 to 2018 and followed for a minimum of 24 months. The primary outcome of the study was relapse-free survival (RFS). Our analyses identified tertiary lymphoid structures (TLSs) as critical prognostic features in stage II CRC. The multi-view integration of TLS characteristics by SurvFinder consistently demonstrated superior predictive and prognostic accuracy across four multicenter datasets (AUROC with 95% confidence interval [CI]: 0.827 [0.789,0.864], 0.805 [0.749,0.860], 0.805 [0.748,0.861], and 0.712 [0.621,0.804]), surpassing traditional clinical prognostic parameters (hazard ratio [HR]: 8.23, 95% CI: 5.43-12.47; p < 0.001). Using explainable AI (XAI) methods, we ensured model transparency and identified key TLS features-such as their location at the tumor periphery and their maturity state-as significant factors influencing prognosis and the efficacy of adjuvant therapy. The retrospective design without prospective validation and real-world clinical deployment is the main limitation of this study.

Conclusions: Together, these results highlight the potential utility of deep learning-based histopathological analysis for automated risk stratification in stage II CRC. In particular, our findings support the relevance of TLSs as a histological biomarker with potential implications for personalizing ACT decisions.

Background: Klebsiella pneumoniae causes ~20% of sepsis in neonates, with ~40% crude mortality. A vaccine administered to pregnant women, protecting against ≥70% of K. pneumoniae infections, could avert ~400,000 cases and ~80,000 deaths annually, mostly in Africa and South Asia. Vaccine formulations targeting the capsular polysaccharide (K) or lipopolysaccharide (O) antigens are in development. Global K. pneumoniae populations display extensive K and O diversity, necessitating a polyvalent vaccine targeted to the serotypes associated with neonatal disease in relevant geographical regions. We investigated the prevalence of K and O types associated with neonatal sepsis in Africa and South Asia to inform maternal vaccine design.

Methods and findings: We analysed 1,930 K. pneumoniae neonate blood isolates from 13 surveillance studies across 35 sites in 13 countries. We used pathogen whole-genome sequencing to predict K and O serotypes and adjust for local transmission clusters, and Bayesian hierarchical meta-analysis to estimate K and O prevalence overall and per region, treating site as a random effect. Eighty-seven K loci were identified. KL2, KL102, KL25, KL15, and KL62 accounted for 49% of isolates. We estimate that 20 K loci, combining the eight most prevalent per region, could cover 72.9% of all infections (95% credible interval: [69.4%, 76.5%]) and ≥70% in each of Eastern, Western, and Southern Africa and South Asia. Preliminary findings from three sites suggested sufficient temporal stability of K loci to maintain 20-valent K vaccine coverage over 5-10 years, but more longitudinal data are needed to support this prediction. O types were far less diverse (n = 14 types). We estimate the top-5 (O1⍺β,2⍺, O1⍺β,2β, O2⍺, O2β, and O4) would cover 86.2% [82.6, 89.9%] of total infections (76%-92% per region), while the top-10 would cover ~99% of infections in all four regions. The main limitations of our study are the reliance on genome sequences to predict K and O serotypes (as serological typing is not available) and a lack of longitudinal data to explore stability of antigen prevalence over time.

Conclusions: Neonatal sepsis is associated with diverse K and O types, with substantial geographic and temporal variation even after adjusting for localised transmission clusters. Despite this, a single 20-valent K vaccine could theoretically cover ≥70% of infections in all target regions. Locally-targeted vaccines could achieve higher coverage with lower valency, but are less feasible. In principle, very high coverage could be achieved with lower valency O-based vaccines, however, the protective efficacy against disease of antibodies targeting the O antigen remains uncertain. Further research is needed on cross-reactivity, antigen exposure, and stability of antigens over time, to better inform vaccine development.

Background: Governments in several countries have introduced a minimum unit price (MUP) for alcohol. Evaluation studies suggest this has reduced alcohol-related harm, but MUPs must increase with inflation to remain effective. This paper estimates the impact of the impact of the Scottish Government's decision to increase its MUP from £0.50 to £0.65 in September 2024 and, alternative options where the MUP changes to between £0.40 and £0.80. It examines impacts on alcohol consumption, spending, and related health outcomes, how impacts vary across the population with regard to deprivation, and how drinkers move between lighter and heavier alcohol consumption groups.

Methods and findings: Policy appraisal using the Sheffield Tobacco and Alcohol Policy Model, a dynamic microsimulation model that combines data on alcohol purchasing and consumption for 10 beverage types and 800 subgroups comprising adults in the Scottish population with price elasticities and an epidemiological model. Deprivation is measured using quintiles of the Scottish Index of Multiple Deprivation. Drinker group is categorised as moderate (<14 units/week, 1 UK unit = 8 g ethanol), hazardous (>14 to ≤35/ ≤50 units/week for women/men), and harmful (>35/50 units/week for women/men). The policy appraisal estimates that, compared to retaining Scotland's MUP at £0.50, increasing the MUP to £0.65 leads to an estimated 12.0% decrease in alcohol consumption, 2.1% decrease in alcohol spending, 3,385 fewer deaths overall, and 2,578 fewer deaths wholly attributable to alcohol over 20 years. Estimated effects are largest in the quintile of the population living in the most deprived areas. Increasing the MUP to £0.65 is also estimated to reduce the proportion of drinkers consuming at harmful levels by 29.4% and the proportion consuming at hazardous levels by 8.0%. Key limitations of the study include relying on data on alcohol consumption and spending collected before the COVID-19 pandemic, synthesising consumption and spending data from separate datasets, and assuming no supply-side responses (e.g., price changes above the MUP threshold).

Conclusions: Increasing the threshold of an established MUP can lead to additional reductions in alcohol consumption, related harm, and health inequalities. Benefits accrue particularly to the most deprived and heaviest drinkers.

Proton pump inhibitors revolutionized acid-related disorder therapy, yet widespread overuse has raised concerns about long-term safety. A recent study in PLOS Medicine presents new evidence assessing whether links between their prolonged use and upper gastrointestinal cancer are causal.

Mental health problems are known to run in families, but it is not clear to what extent this reflects nature or nurture. By disentangling these influences, a recent PLOS Medicine article sheds light on how mental health problems are transmitted across generations.