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Comparative Evaluation of a Medical Large Language Model in Answering Real-World Radiation Oncology Questions: Multicenter Observational Study
<b>These 99 'lab hacks' will make your scientific work easier</b>
Nature, Published online: 23 September 2025; doi:10.1038/d41586-025-02719-z
Nature asked contributors, editors and working researchers to share their best advice for scientists.Deciphering the Heterogeneity of Pancreatic Cancer: DNA Methylation-Based Cell Type Deconvolution Unveils Distinct Subgroups and Immune Landscapes
Epigenomes. 2025 Sep 5;9(3):34. doi: 10.3390/epigenomes9030034.
ABSTRACT
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous malignancy, characterized by low tumor cellularity, a dense stromal response, and intricate cellular and molecular interactions within the tumor microenvironment (TME). Although bulk omics technologies have enhanced our understanding of the molecular landscape of PDAC, the specific contributions of non-malignant immune and stromal components to tumor progression and therapeutic response remain poorly understood. Methods: We explored genome-wide DNA methylation and transcriptomic data from the Cancer Genome Atlas Pancreatic Adenocarcinoma cohort (TCGA-PAAD) to profile the immune composition of the TME and uncover gene co-expression networks. Bioinformatic analyses included DNA methylation profiling followed by hierarchical deconvolution, epigenetic age estimation, and a weighted gene co-expression network analysis (WGCNA). Results: The unsupervised clustering of methylation profiles identified two major tumor groups, with Group 2 (n = 98) exhibiting higher tumor purity and a greater frequency of KRAS mutations compared to Group 1 (n = 87) (p < 0.0001). The hierarchical deconvolution of DNA methylation data revealed three distinct TME subtypes, termed hypo-inflamed (immune-deserted), myeloid-enriched, and lymphoid-enriched (notably T-cell predominant). These immune clusters were further supported by co-expression modules identified via WGCNA, which were enriched in immune regulatory and signaling pathways. Conclusions: This integrative epigenomic-transcriptomic analysis offers a robust framework for stratifying PDAC patients based on the tumor immune microenvironment (TIME), providing valuable insights for biomarker discovery and the development of precision immunotherapies.
PMID:40981070 | PMC:PMC12452622 | DOI:10.3390/epigenomes9030034
Adaptive cancer therapy: can non-genetic factors become its achilles heel?
Oncogene, Published online: 22 September 2025; doi:10.1038/s41388-025-03582-y
Adaptive cancer therapy: can non-genetic factors become its achilles heel?Cancer in a drop: Liquid biopsy highlights from the American Society of Clinical Oncology (ASCO) 2025 annual congress
J Liq Biopsy. 2025 Aug 6;9:100320. doi: 10.1016/j.jlb.2025.100320. eCollection 2025 Sep.
ABSTRACT
Over the past decade, liquid biopsy has progressively expanded its role in oncology, supported by mounting evidence demonstrating an increasing number of clinical applications. At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, liquid biopsy emerged as a central theme across multiple sessions, with more than 700 abstracts, investigating the clinical utility of liquid biopsy across a wide range of tumor types and disease stages. Applications presented included cancer screening, minimal residual disease (MRD) detection, management of metastatic disease, and potential use for matching patients to clinical trials. This editorial, authored on the behalf of the Young Committee of the International Society of Liquid Biopsy (ISLB) highlights the result of selected studies, grouped by tumor type.
PMID:40980343 | PMC:PMC12447415 | DOI:10.1016/j.jlb.2025.100320
Circulating tumor DNA in patients with cancer: insights from clinical laboratory
Adv Lab Med. 2025 Jun 16;6(3):259-276. doi: 10.1515/almed-2025-0010. eCollection 2025 Sep.
ABSTRACT
Blood-based circulating tumor DNA (ctDNA) analysis has emerged as a highly relevant non-invasive method for molecular profiling of solid tumors, offering valuable information about the genetic landscape of cancer. Somatic mutation analysis of ctDNA is now used clinically to guide targeted therapies for advanced cancers. Recent advancements have also revealed its potential in early detection, prognosis, minimal residual disease assessment, and prediction/monitoring of therapeutic response. In recent years, significant progress has been made with the development of various PCR and NGS-based methods designed for assessing gene variants in ctDNA of patients with cancer. However, despite the transformative possibilities that ctDNA analysis presents, challenges persist. Standardization of preanalytical and analytical protocols, assay sensitivity, and the interpretation of results remain critical hurdles that need to be addressed for the widespread clinical implementation of ctDNA testing. In addition to somatic mutations, emerging studies on DNA methylation (epigenomics) and fragment size patterns (fragmentomics) in several types of biological fluids are yielding promising results as non-invasive biomarkers for effective cancer management. This review addresses the clinical applications of somatic gene variants in ctDNA, emphasizes their potential as cancer biomarkers, and highlights essential factors for successful implementation in clinical laboratories and cancer management.
PMID:40977813 | PMC:PMC12446922 | DOI:10.1515/almed-2025-0010
A statistical physics approach to integrating multi-omics data for disease-module detection
Cell Rep Methods. 2025 Sep 19:101183. doi: 10.1016/j.crmeth.2025.101183. Online ahead of print.
ABSTRACT
Genes associated with the same disease frequently engage in mutual biological interactions, e.g., perturbation within a specific neighborhood in the molecular interactome, often referred to as the disease module. This has propelled the advancement of network-based approaches toward elucidating the molecular bases of human diseases. Although many computational methods have been developed to integrate the molecular interactome and omics profiles to extract such context-dependent disease modules, approaches that leverage multi-omics for disease-module detection are still lacking. Here, we developed a statistical physics approach based on the random-field O(n) model (RFOnM) to fill this gap. We applied the RFOnM approach to integrate gene-expression data and genome-wide association studies or mRNA data and DNA methylation for several complex diseases with the human interactome. We found that the RFOnM approach outperforms existing single omics methods in most of the complex diseases considered in this study.
PMID:40975055 | DOI:10.1016/j.crmeth.2025.101183
Implementation of a Virtual Hospital in the Home Service for Patients With COVID-19 in Queensland, Australia: Mixed Methods Evaluation Using the RE-AIM Framework
Opinion: Four reasons why generative AI chatbots could lead to psychosis in vulnerable people
Three scholars discovered a strange mirror deep in the forest. It spoke to them in a soothing voice and answered all their questions warmly, knowledgeably, and eloquently.
The captivated scholars became obsessed, whispering one secret after another to the mirror. It replied with affection, promise, and meaning that kept them returning to it. They began ignoring one another, each convinced the mirror “understood” them best.


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From frameworks to finance: how sharing benefits from the use of digital sequence information can evolve to contribute to biodiversity conservation
Nature Biotechnology, Published online: 18 September 2025; doi:10.1038/s41587-025-02820-8
The COP16 decision established a multilateral mechanism for digital sequence information (DSI) benefit-sharing. This Comment brings together insights from academia and commercial DSI researchers to assess what has been accomplished so far, identify remaining challenges and describe elements under discussion to support collective goals.Diagnostic Performance of Computed Tomography–Based Artificial Intelligence for Early Recurrence of Cholangiocarcinoma: Systematic Review and Meta-Analysis
Large Language Models’ Clinical Decision-Making on When to Perform a Kidney Biopsy: Comparative Study
Navigating the Boundaries of Teleconsultation—Capabilities, Limitations, and Pathways for Improvement: Qualitative Study of the Experiences of Patients With Stroke
The arts for disease prevention and health promotion: a systematic review
Nature Medicine, Published online: 18 September 2025; doi:10.1038/s41591-025-03962-7
The arts, according to a systematic synthesis of data from 95 studies (across 26 countries), may support non-communicable disease prevention by providing opportunities for increased physical activity, and helping to address social forces that contribute to health inequities.Clinical implementation of an AI-based prediction model for decision support for patients undergoing colorectal cancer surgery
Nature Medicine, Published online: 18 September 2025; doi:10.1038/s41591-025-03942-x
A model developed with data from 19,403 patients with colorectal cancer for prediction of 1-year mortality is used as a decision support tool in a prospective cohort, showing promising results in reducing postoperative complications.Bridging Technology and Pretest Genetic Services: Quantitative Study of Chatbot Interaction Patterns, User Characteristics, and Genetic Testing Decisions
Delegation to artificial intelligence can increase dishonest behaviour
Nature, Published online: 17 September 2025; doi:10.1038/s41586-025-09505-x
People cheat more when they delegate tasks to artificial intelligence, and large language models are more likely than humans to comply with unethical instructions—a risk that can be minimized by introducing prohibitive, task-specific guardrails.Which diseases will you have in 20 years? This AI accurately predicts your risks
Nature, Published online: 17 September 2025; doi:10.1038/d41586-025-02993-x
A modified large language model called Delphi-2M analyses a person’s medical records and lifestyle to provide risk estimates for more than 1,000 diseases.