Nature Medicine, Published online: 11 September 2025; doi:10.1038/s41591-025-03936-9
In an irrevocably changed landscape, reform of the global health system needs to answer key questions on functions, what should be delivered in different contexts and at different levels, and how the system should operate.
Chest. 2025 Sep;168(3):581-583. doi: 10.1016/j.chest.2025.04.023.
NO ABSTRACT
PMID:40935546 | DOI:10.1016/j.chest.2025.04.023
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.
Nature, Published online: 10 September 2025; doi:10.1038/d41586-025-02911-1
Representatives of four medical research centres have told Nature they have waived normal ethical review because ‘synthetic’ data do not contain real or traceable patient information.
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 Krzaczyński
Nature, Published online: 09 September 2025; doi:10.1038/d41586-025-02810-5
The academic community has looked at how artificial-intelligence tools help researchers to write papers, but not how they distort the literature scientists choose to cite.
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
Stem Cell Rev Rep. 2025 Sep 11. doi: 10.1007/s12015-025-10973-x. Online ahead of print.
ABSTRACT
The emergence of organoid models has significantly bridged the gap between traditional cell cultures/animal models and authentic human disease states, particularly for genetic disorders, where their inherent genetic fidelity enables more biologically relevant research directions and enhances translational validity. This review systematically analyzes established organoid models of genetic diseases across organs (e.g., brain, eye, kidney, lung, and heart), highlighting their pivotal roles in identifying novel pathogenic genes, elucidating disease mechanisms, and advancing therapeutic strategies such as drug screening platforms, gene-editing therapies, and organ transplantation strategies. Furthermore, we critically address current limitations-including challenges in recapitulating complex pathologies and scaling production-while underscoring their potential for personalized medicine through multi-omics integration and bioengineering innovations. Although the scope of "genetic diseases" is broad, this synthesis focuses on disorders with well-defined inheritance patterns, such as monogenic disorders, copy number variations (CNVs), and aneuploidies. Despite covering only a subset of these conditions, this review aims to provide researchers with a comprehensive overview of the field, emphasizing how organoid-based approaches could accelerate both mechanistic discoveries and clinical translation in genetic disease research.
PMID:40931310 | DOI:10.1007/s12015-025-10973-x
J Liq Biopsy. 2025 Aug 9;9:100323. doi: 10.1016/j.jlb.2025.100323. eCollection 2025 Sep.
ABSTRACT
Liquid biopsy, specifically circulating tumor DNA (ctDNA) analysis, has emerged as a transformative tool in precision oncology, providing real-time, minimally invasive characterizations of the tumor and tumor dynamics. While tissue biopsy is a critical tool for baseline diagnosis of malignancy, it is often limited by sampling constraints and an inability to capture tumor heterogeneity. In this study, we explored the clinical utility of serial ctDNA testing in guiding therapeutic decisions across a cohort of 30 patients with diverse solid tumors. Our real-world analysis demonstrates that ctDNA profiling meaningfully influenced treatment escalation, de-escalation, disease monitoring, and early relapse prediction. Cases where ctDNA positivity indicated minimal residual disease prompted timely escalation of therapy, while ctDNA clearance allowed safe treatment de-intensification, minimizing toxicity without compromising outcomes. Longitudinal ctDNA monitoring provided a dynamic, non-invasive method for assessing treatment response and detecting recurrence months before radiological progression. Our study highlights the potential of integrating liquid biopsy into routine clinical practice to enable dynamic treatment monitoring, early detection of therapeutic resistance, and more informed, personalized decision-making across various cancer types.
PMID:40919127 | PMC:PMC12409318 | DOI:10.1016/j.jlb.2025.100323
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.
Nature Medicine, Published online: 08 September 2025; doi:10.1038/s41591-025-03859-5
Building the world’s first truly global medical foundation model
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 Krzaczyński
“My watch saved my life.”
Liam — not his real name — is a 75-year-old retired teacher in Boston. Two years ago, his son-in-law gave him an Apple Watch. Soon after, it began flagging something strange: possible atrial fibrillation.
© Adobe
DOVER, N.H. — Not long after he woke from surgery in June, Bill Stewart made a pact with his newest organ. He wasn’t sure how long the thing would last. The doctors had been up-front from the get-go: It could be three months or six, one year or four. Still, the uncertainty hit him as he started getting back preliminary lab results, which were okay but left room for improvement. “My pig kidney and I had a little conversation while I was laying there. I just basically said, ‘I’m going to do everything I can to make sure that you stay healthy, and I appreciate you doing everything you can to keep me upright and breathing,” Stewart said.
It’s been almost three months, and Stewart is home, back to work, and has even been able to go e-biking on a lakeside trail with his wife, blessedly untethered to the grueling schedules of dialysis for the first time in years, all thanks to a gene-edited Yucatan miniature pig named Lavender.
Stewart is the most recent recipient of a pig kidney — but chances are, he won’t hold that distinction for long. On Monday, eGenesis, a Cambridge-based biotechnology company, announced that it had been cleared by the Food and Drug Administration to begin a trial of kidneys from donor pigs that have been CRISPR’d to make their organs more human-friendly. Now, Massachusetts researchers will be performing more surgeries like Stewart’s to see whether these animal parts could serve as a lifeline for people with end-stage renal disease.
Continue to STAT+ to read the full story…
© Cheryl Senter for STAT
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.
Int J Biol Macromol. 2025 Sep 5;327(Pt 2):147473. doi: 10.1016/j.ijbiomac.2025.147473. Online ahead of print.
ABSTRACT
Osteosarcoma (OS), the most prevalent primary bone malignancy in adolescents, is characterized by aggressive progression and early metastasis. However, the epigenetic drivers of its metastatic heterogeneity remain poorly understood. Herein, we integrated bulk DNA methylation profiling and single-cell RNA sequencing (scRNA-seq) to elucidate the epigenetic mechanisms driving OS metastatic heterogeneity. Consensus clustering identified two methylation subtypes (K = 2) with distinct survival outcomes, where hypermethylated (MSO-high) tumors exhibited poor prognosis. Weighted gene co-expression network analysis (WGCNA) revealed methylation-associated modules enriched in metabolic and immune pathways, pinpointing key genes such as CAMK1G and SLC11A1. Single-cell profiling uncovered MSO-high myeloid cells associated with inflammatory and oxidative phosphorylation pathways, while MSO-high OS cells displayed transdifferentiation toward fibroblasts via pseudotime trajectories, remodeling the extracellular matrix (ECM) to facilitate lung metastasis. Conversely, MSO-low tumors activated HLA-B-mediated neutrophil-CD8+ T cell interactions, promoting lymphatic metastasis via CXCR4/CXCL12 signaling. Furthermore, functional validation using the DNA demethylating agent decitabine demonstrated reduced fibroblastic transdifferentiation and suppressed invasive capacity in MSO-high osteosarcoma cells, supporting the therapeutic potential of targeting methylation dysregulation. These findings establish a model where DNA methylation dictates metastatic phenotypes through differential tumor-stromal crosstalk, providing novel targets for epigenetic therapy to disrupt fibrotic-immune networks and metastatic colonization.
PMID:40915448 | DOI:10.1016/j.ijbiomac.2025.147473
bioRxiv [Preprint]. 2025 Aug 25:2025.08.21.671519. doi: 10.1101/2025.08.21.671519.
ABSTRACT
Lung cancer is the most common cause of cancer-related death worldwide. Recent advancements in targeted therapies and immunotherapies have achieved remarkable success. However, patient responses to treatments with lung cancer vary substantially. The mutation status of driver genes can direct personalized treatment, but their prognostic value and treatment efficacy are limited. In this study, we developed a statistical framework named Genomic Aberration-Derived Signature for Patient Stratification (GASPS) to characterize the transcriptomic deregulation of driver genomic aberrations and stratify patients. By applying GASPS to The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) data, we developed gene signatures for 38 driver genomic aberrations, including gene mutations, amplifications, and deletions. These signatures were applied to independent lung cancer transcriptomic datasets containing a total of 2,226 patient samples. Our results indicated that these driver gene signatures are much more prognostic than their corresponding genomic mutations. Interestingly, the two EGFR-related signatures characterizing EGFR mutation and amplification, respectively, exhibited contrasting associations with prognosis, treatment response, and immune infiltration in the tumor microenvironment. Moreover, the STK11 mutation signature, rather than the mutation status, was found to be predictive of the response and long-term benefit of patients treated with immune checkpoint blockade therapy in lung cancer. This framework is readily applicable to most cancer types using existing data to improve prognostic risk assessment and treatment efficacy by guiding personalized therapies.
PMID:40909579 | PMC:PMC12407784 | DOI:10.1101/2025.08.21.671519
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