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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
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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Navigating the Boundaries of Teleconsultation—Capabilities, Limitations, and Pathways for Improvement: Qualitative Study of the Experiences of Patients With Stroke
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.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.Digital Health Technology Infrastructure Challenges to Support Health Equity in the United States: Scoping Review
Hugging Face Releases FinePDFs: a 3-Trillion-Token Dataset Built from PDFs

Hugging Face has unveiled FinePDFs, the largest publicly available corpus built entirely from PDFs. The dataset spans 475 million documents in 1,733 languages, totaling roughly 3 trillion tokens. At 3.65 terabytes in size, FinePDFs introduces a new dimension to open training datasets by tapping into a resource long considered too complex and expensive to process.
By Robert KrzaczyńskiPrognostic Value of Circulating Tumor DNA in HR+/HER2- Stage I-III Breast Cancer: A Systematic Review
Cancers (Basel). 2025 Aug 29;17(17):2831. doi: 10.3390/cancers17172831.
ABSTRACT
Background: Hormone receptor-positive (HR+), HER2-negative breast cancer accounts for the majority of breast cancer diagnoses. While outcomes have improved with neoadjuvant and adjuvant therapies, the risk of late recurrence persists, and there remains a critical need for reliable biomarkers to guide prognosis and post-treatment surveillance. Circulating tumor DNA (ctDNA), detectable via liquid biopsy, has emerged as a promising tool for monitoring minimal residual disease and predicting survival outcomes. This systematic review evaluates the association between ctDNA detection during neoadjuvant or adjuvant treatment and survival outcomes in early-stage HR+/HER2- breast cancer. Methods: This systematic review was conducted in accordance with PRISMA guidelines. A comprehensive literature search of Ovid MEDLINE and Embase was conducted to identify studies published through 3 May 2024 that evaluated ctDNA as a prognostic biomarker in stage I-III HR+/HER2- breast cancer. We included studies reporting recurrence-free survival, invasive disease-free survival, or overall survival and excluded non-original studies, conference abstracts, and non-English articles. Data extraction and qualitative synthesis were performed, and the risk of bias was qualitatively assessed across studies. No review protocol was registered. Results: Eleven studies comprising 1644 patients met the inclusion criteria. In the neoadjuvant setting, ctDNA positivity prior to treatment initiation was associated with inferior survival outcomes. In the adjuvant setting, detection of ctDNA during or after treatment was consistently linked to poorer recurrence-free and invasive disease-free survival. Across studies, ctDNA detection was a significant negative prognostic marker. Conclusions: This systematic review supports the prognostic value of ctDNA in HR+/HER2- early-stage breast cancer. Limitations include small sample sizes, observational study designs, and heterogeneity in ctDNA assays. Standardization of ctDNA testing methods and further prospective trials are needed to validate its clinical utility and explore its potential role in guiding therapeutic interventions.
PMID:40940926 | PMC:PMC12427406 | DOI:10.3390/cancers17172831
Interventions Based on Biofeedback Systems to Improve Workers’ Psychological Well-Being, Mental Health, and Safety: Systematic Literature Review
Fluctuating DNA methylation tracks cancer evolution at clinical scale
Nature, Published online: 10 September 2025; doi:10.1038/s41586-025-09374-4
Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.Google DeepMind Launches EmbeddingGemma, an Open Model for On-Device Embeddings

Google DeepMind has introduced EmbeddingGemma, a 308M parameter open embedding model designed to run efficiently on-device. The model aims to make applications like retrieval-augmented generation (RAG), semantic search, and text classification accessible without the need for a server or internet connection.
By Robert KrzaczyńskiSingle-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs of type 1 diabetes progression
Sci Adv. 2025 Sep 12;11(37):eady0080. doi: 10.1126/sciadv.ady0080. Epub 2025 Sep 10.
ABSTRACT
Cell type-specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here, we performed single-nucleus multiomics and spatial transcriptomics in up to 32 nondiabetic (ND), autoantibody-positive (AAB+), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine subtypes. β, Acinar, and other cell types, and related cellular niches, had altered abundance and gene activity in T1D progression, including distinct pathways altered in AAB+ compared to T1D. We identified epigenomic drivers of gene activity in T1D and AAB+ which, combined with genetic association, revealed causal pathways of T1D risk including antigen presentation in β cells. Last, single-cell and spatial profiles together revealed widespread changes in cell-cell signaling in T1D including signals affecting β cell regulation. Overall, these results revealed drivers of T1D in the pancreas, which form the basis for therapeutic targets for disease prevention.
PMID:40929272 | PMC:PMC12422192 | DOI:10.1126/sciadv.ady0080
The WHO global landscape of cancer clinical trials
Nature Medicine, Published online: 09 September 2025; doi:10.1038/s41591-025-03926-x
This Review of the WHO’s International Clinical Trials Registry Platform presents a snapshot of the global cancer trial landscape and provides critical empirical evidence to inform policy, practice and investment.Building the world’s first truly global medical foundation model
Nature Medicine, Published online: 08 September 2025; doi:10.1038/s41591-025-03859-5
Building the world’s first truly global medical foundation modelHugging Face Introduces AI Sheets, a No-Code Tool for Dataset Transformation

Hugging Face has released AI Sheets, an open-source application designed to let users build, transform, and enrich datasets using AI models through a spreadsheet-like interface. The tool, available both on the Hub and for local deployment, allows users to experiment with thousands of open models, including OpenAI’s gpt-oss, without requiring code.
By Robert KrzaczyńskiAntibody–bottlebrush prodrug conjugates for targeted cancer therapy
Nature Biotechnology, Published online: 09 September 2025; doi:10.1038/s41587-025-02772-z
Antibody–bottlebrush conjugates expand the options for drug cargos compared to antibody–drug conjugates.