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Somatic evolution following cancer treatment in normal tissue
Nature, Published online: 10 December 2025; doi:10.1038/s41586-025-09792-4
High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.A Field Guide to Deploying AI Agents in Clinical Practice
Cognitive bias in LLM reasoning compromises interpretation of clinical oncology notes
Human Experts' Evaluation of Generative AI for Contextualizing STEAM Education in the Global South
Multi-agent Self-triage System with Medical Flowcharts
Equipping mathematical models for hospital dynamics using information theory
npj Digital Medicine, Published online: 12 November 2025; doi:10.1038/s41746-025-02013-2
Equipping mathematical models for hospital dynamics using information theorySite-specific DNA insertion into the human genome with engineered recombinases
Nature Biotechnology, Published online: 06 November 2025; doi:10.1038/s41587-025-02895-3
Engineered DNA recombinases efficiently and specifically insert genetic cargos without the use of landing pads.Improving dataset transparency in dermatologic Artificial Intelligence using a dataset nutrition label
npj Digital Medicine, Published online: 05 November 2025; doi:10.1038/s41746-025-02125-9
Biased and poorly documented dermatology datasets pose risks to the development of safe and generalizable artificial intelligence (AI) tools. We created a Dataset Nutrition Label (DNL) for multiple dermatology datasets to support transparent and responsible data use. The DNL offers a structured, digestible summary of key attributes, including metadata, limitations, and risks, enabling data users to better assess suitability and proactively address potential sources of bias in datasets.Evaluating clinical AI summaries with large language models as judges
npj Digital Medicine, Published online: 05 November 2025; doi:10.1038/s41746-025-02005-2
Evaluating clinical AI summaries with large language models as judgesFair human-centric image dataset for ethical AI benchmarking
Nature, Published online: 05 November 2025; doi:10.1038/s41586-025-09716-2
The Fair Human-Centric Image Benchmark (FHIBE, pronounced ‘Feebee’)—an image dataset that implements best practices for consent, privacy, compensation, safety, diversity and utility—can be used responsibly as a fairness evaluation dataset for many human-centric computer vision applications.STAT+: Moderna says key study of its CMV vaccine, expected to be its next big win, failed
Moderna said Wednesday afternoon that its experimental vaccine for cytomegalovirus, a cause of disability in newborns, failed in a Phase 3 trial, a significant setback for a company already facing pressure from Wall Street and the federal government.
The CMV vaccine had been the company’s lead program prior to the Covid-19 pandemic. Leadership had repeatedly said it could bring in between $2 billion and $5 billion in peak annual sales. Analysts polled by Visible Alpha forecast peak sales of $1.6 billion for the product.
“It’s obviously disappointing,” said Stephen Hoge, Moderna’s president, in an interview.
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© Ruby Wallau for STAT
Circulating tumor DNA in Non-Viral head and neck squamous cell Carcinoma: A systematic review and Meta-Analysis
Oral Oncol. 2025 Nov;170:107760. doi: 10.1016/j.oraloncology.2025.107760. Epub 2025 Oct 17.
ABSTRACT
Non-viral head and neck squamous cell carcinoma (HNSCC) has poor survival and high recurrence rates. Circulating tumor DNA (ctDNA) is a promising biomarker for understanding tumor biology, assessing treatment response, and monitoring disease progression. While extensively studied in virally mediated HNSCC, its role in non-viral HNSCC remains underexplored. This systematic review and meta-analysis consolidates evidence on the diagnostic, prognostic, and therapeutic value of ctDNA in non-viral HNSCC. A systematic search across Medline, PubMed, Embase, and the Cochrane Library identified 1,915 records, of which 47 were included. Data extraction followed PRISMA guidelines, with overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS), pooled as hazard ratios (HRs) with 95% confidence intervals (CIs) using a fixed-effect model. Among 3,574 patients, the most common tumor sites were the oral cavity (35 %) and oropharynx (22 %), with the majority presenting with stage IVA/IVB disease (29 %). Pre-treatment ctDNA detection rates ranged from 50 % to 100 % (median: 83 %), while post-treatment detection rates varied between 28 % and 100 % (median: 48 %). ctDNA detected recurrence in 80 % of patients, with a median lead time of 4.6 months. ctDNA detection was significantly associated with worse OS (HR 10.26, 95 % CI 3.58-29.40; P < 0.0001). Residual ctDNA was strongly correlated with worse PFS (HR 7.32, 95 % CI 4.17-12.86; P < 0.00001) and RFS (HR 7.33, 95 % CI 2.75-19.58; P < 0.0001). ctDNA holds potential for improving diagnostic accuracy, monitoring progression, and predicting survival outcomes in non-viral HNSCC. However, further large-scale studies and standardized guidelines are needed for validation and clinical implementation.
PMID:41108912 | DOI:10.1016/j.oraloncology.2025.107760
AI models that lie, cheat and plot murder: how dangerous are LLMs really?
Nature, Published online: 08 October 2025; doi:10.1038/d41586-025-03222-1
Tests of large language models reveal that they can behave in deceptive and potentially harmful ways. What does this mean for the future?Clinical validation of an AI-based blood testing device for diagnosis and prognosis of acute infection and sepsis
Nature Medicine, Published online: 30 September 2025; doi:10.1038/s41591-025-03933-y
In a prospective study enrolling 1,222 patients from 22 emergency departments, a device using a machine-learning-based signature of blood mRNAs demonstrated clinically acceptable performance to diagnose bacterial and viral infections and to predict the all-cause need for critical care interventions within 7 days, with benchmark to established biomarkers and risk scores.Integrative Spatial Omics for Systems-Level Mapping of Pathological Niches
bioRxiv [Preprint]. 2025 Sep 17:2025.09.12.675904. doi: 10.1101/2025.09.12.675904.
ABSTRACT
Spatial 'omics technologies are a powerful tool for mapping the relationship between cellular organization and molecular distributions in healthy and diseased tissue microenvironments. Here, we describe a novel multimodal pipeline that represents experimental and computational advances for spatiomolecular analysis of tissue samples across molecular classes. This adaptable method integrates matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) lipidomics, spatial transcriptomics (ST), multiplexed immunofluorescence microscopy (MxIF), and histopathological staining to uncover spatiomolecular profiles associated with unique cellular niches and pathological features. We demonstrate the power of this approach using two different complex human disease systems: Alzheimer's disease in human brain tissue and type 2 diabetes mellitus in the human pancreas. By identifying molecular markers associated with disease pathology in the pancreas and brain, we shed light on biologically significant pathways that are impacted in these two spatially complex diseases and highlight the powerful potential of accurate, high-resolution multimodal integration approaches.
PMID:41000710 | PMC:PMC12458195 | DOI:10.1101/2025.09.12.675904
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 modelHuman interpretable grammar encodes multicellular systems biology models to democratize virtual cell laboratories
Detection, quantitation, and genotyping of human papillomavirus circulating tumor DNA by droplet digital PCR
J Clin Microbiol. 2025 Aug 19:e0058525. doi: 10.1128/jcm.00585-25. Online ahead of print.
ABSTRACT
Human papillomavirus (HPV) is comprised of >200 genotypes and has an ~8 kb, circular, double-stranded DNA genome. Transmission of HPV occurs through skin-to-skin contact and infection of squamous epithelial cells of cutaneous and mucosal surfaces. HPV genotypes are categorized as low- or high-risk (hrHPV) based on oncogenic potential. There are approximately 14 types of hrHPV that can cause several types of cancer, including HPV-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC). Detection of HPV(+)OPSCC is traditionally accomplished using p16 immunohistochemistry (IHC) and HPV-specific testing, either DNA or RNA in situ hybridization (ISH) staining or DNA-based PCR of suspected tumor biopsy tissue. More recently, platelet-poor plasma (PPP) samples from patients with HPV(+)OPSCC have proven useful for detection and quantitation of fragments of HPV circulating tumor DNA (ctDNA). ctDNA has been shown to be useful in determining treatment response and monitoring for disease recurrence. In this study, a novel droplet digital PCR assay (ddPCR) was developed and validated for the detection and quantitation of ctDNA from 5 hrHPV genotypes in PPP. Analytical sensitivity ranged from 7.71 to 19.45 fragments of HPV ctDNA per milliliter of PPP across five hrHPV genotypes. In patients with confirmed primary or recurrent HPV(+)OPSCC or HPV(-)OPSCC, testing of corresponding PPP samples (n = 32) by ddPCR demonstrated 90.63% (29/32) overall agreement with p16/HPV-ISH biopsy results. Compared with reference ddPCR assays performed at outside laboratories, our ddPCR assay yielded 90% (9/10) overall agreement. This assay may provide clinicians with a tool for monitoring HPV ctDNA prior to, during, and after treatment of an HPV-associated cancer.
IMPORTANCE: At least 14 genotypes of human papillomavirus (HPV) have been identified to have high oncogenic potential. While molecular diagnostic testing for HPV is widely available for liquid cytologic cervical samples, testing is limited for other sample types, including liquid biopsy samples, such as platelet-poor plasma (PPP). With the rising incidence of HPV-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC), laboratory testing is an essential part of patient diagnosis, management, and surveillance. Here, we summarize the development and analytical performance validation of a multiplexed, droplet digital PCR (ddPCR) assay for the detection and quantitation of HPV circulating tumor DNA (ctDNA) in PPP. This assay may provide clinicians with a tool to address minimal residual disease for patients with an HPV-associated cancer.
PMID:40827899 | DOI:10.1128/jcm.00585-25
Complex genetic variation in nearly complete human genomes
Nature, Published online: 23 July 2025; doi:10.1038/s41586-025-09140-6
Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.