Multimorbidity is strongly associated with mortality, but existing comorbidity indices often generalize poorly across populations because they depend on fixed disease lists and context-specific weights. We developed the large-language-model-based multimorbidity score (LLM-MMS), a prompt-based large-language-model-derived multimorbidity phenotype score, as a bio-inspired artificial intelligence score for human–machine clinical risk stratification and evaluated it for all-cause mortality prediction in 770,439 adults from 9 international longitudinal cohorts. Harmonized participant-level data were converted into standardized health narratives and processed without model fine-tuning. In the UK Biobank, LLM-MMS achieved strong discrimination, calibration, and prediction accuracy. Across 8 external cohorts, it maintained consistent performance, with C-indices of 0.67 to 0.86 and observed-to-expected ratios close to 1.00. This outperformed recalibrated conventional comorbidity indices in every cohort with absolute C-index gains of 0.12 to 0.21. Performance remained stable across sex and age subgroups, including adults younger than 60 years, and decision-curve analysis showed greater or comparable clinical net benefit in most cohorts. Proteomic and interpretability analyses supported the biological plausibility of LLM-MMS, linking high multimorbidity burden to inflammatory, metabolic, and tissue-damage pathways and identifying clinically coherent drivers of risk. These findings suggest that LLM-MMS offers a transportable and interpretable bio-inspired framework that integrates clinician-like multimodal reasoning with population-level validation for multimorbidity risk stratification across diverse populations.
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Open Access
Research Article
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Open Access
Review
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Lung cancer is associated with a heavy cancer-related burden in terms of patients’ physical and mental health worldwide. Two randomized controlled trials, the US-National Lung Screening Trial (NLST) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON), indicated that low-dose CT (LDCT) screening results in a statistically significant decrease in mortality in patients with lung cancer, LDCT has become the standard approach for lung cancer screening. However, many issues in lung cancer screening remain unresolved, such as the screening criteria, high false-positive rate, and radiation exposure. This review first summarizes recent studies on lung cancer screening from the US, Europe, and Asia, and discusses risk-based selection for screening and the related issues. Second, an overview of novel techniques for the differential diagnosis of pulmonary nodules, including artificial intelligence and molecular biomarker-based screening, is presented. Third, current explorations of strategies for suspected malignancy are summarized. Overall, this review aims to help clinicians understand recent progress in lung cancer screening and alleviate the burden of lung cancer.
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