❌

Reading view

Multi-agent Self-triage System with Medical Flowcharts

arXiv:2511.12439v1 Announce Type: new Abstract: Online health resources and large language models (LLMs) are increasingly used as a first point of contact for medical decision-making, yet their reliability in healthcare remains limited by low accuracy, lack of transparency, and susceptibility to unverified information. We introduce a proof-of-concept conversational self-triage system that guides LLMs with 100 clinically validated flowcharts from the American Medical Association, providing a structured and auditable framework for patient decision support. The system leverages a multi-agent framework consisting of a retrieval agent, a decision agent, and a chat agent to identify the most relevant flowchart, interpret patient responses, and deliver personalized, patient-friendly recommendations, respectively. Performance was evaluated at scale using synthetic datasets of simulated conversations. The system achieved 95.29% top-3 accuracy in flowchart retrieval (N=2,000) and 99.10% accuracy in flowchart navigation across varied conversational styles and conditions (N=37,200). By combining the flexibility of free-text interaction with the rigor of standardized clinical protocols, this approach demonstrates the feasibility of transparent, accurate, and generalizable AI-assisted self-triage, with potential to support informed patient decision-making while improving healthcare resource utilization.
  •  
  •  

Site-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.
  •  
  •  

Fair 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.

Continue to STAT+ to read the full story…

© 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

  •  

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

  •  

Human interpretable grammar encodes multicellular systems biology models to democratize virtual cell laboratories

We developed a plain text modeling language—a cell behavior hypothesis grammar—to easily build virtual cell models and connect them to data, helping scientists to unlock the hidden dynamics of tissues. We provide examples showing how to use them in virtual experiments exploring how cancer responds to the cells in its environment and how the brain forms layers in development.
  •  

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.
  •  

Circulating tumour DNA and circulating tumour cells in bladder cancer - from discovery to clinical implementation

Nat Rev Urol. 2025 Apr 15. doi: 10.1038/s41585-025-01023-9. Online ahead of print.

ABSTRACT

Liquid biopsies, indicating the sampling of body fluids rather than solid-tissue biopsies, have the potential to revolutionize cancer care through personalized, noninvasive disease detection and monitoring. Circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) are promising blood-based biomarkers in bladder cancer. Results from several studies have shown the clinical potential of ctDNA and CTCs in bladder cancer for prognostication, treatment-response monitoring, and early detection of minimal residual disease and disease recurrence. Following successful clinical trial evaluation, assessment of ctDNA and CTCs holds the potential to transform the therapeutic pathway for patients with bladder cancer - potentially in combination with the analysis of urinary tumour DNA - through tailored treatment guidance and optimized disease surveillance.

PMID:40234713 | DOI:10.1038/s41585-025-01023-9

  •  

Digital phenotyping from wearables using AI characterizes psychiatric disorders and identifies genetic associations

Complex disorders require precise strategies for their characterization. AI-based digital phenotypes from biosensors can be used to predict psychiatric disorders and identify GWAS loci.
  •  

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood

Am J Hum Genet. 2025 Jan 6:S0002-9297(24)00456-7. doi: 10.1016/j.ajhg.2024.12.014. Online ahead of print.

ABSTRACT

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. We show that haplotype-based calling methods can be used with WGS data to successfully identify mLOY events. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European (EUR) ancestry group compared to other ancestries. We identify multiple loci associated with mLOY susceptibility and show that subsets of human hematopoietic stem cells are enriched for the activity of mLOY susceptibility variants. Finally, we found that certain alleles on chromosome Y are more likely to be lost than others in detectable mLOY clones.

PMID:39809269 | DOI:10.1016/j.ajhg.2024.12.014

  •  

Liquid Biopsy for Spinal Tumors: On the Frontiers of Clinical Application

Global Spine J. 2025 Jan;15(1_suppl):16S-28S. doi: 10.1177/21925682231222012.

ABSTRACT

STUDY DESIGN: Narrative review.

OBJECTIVES: This article aims to provide a narrative review of the current state of research for liquid biopsy in spinal tumors and to discuss the potential application of liquid biopsy in the clinical management of patients with spinal tumors.

METHODS: A comprehensive review of the literature was performed using PubMed, Google Scholar, Medline, Embase and Cochrane databases, and the review was limited to articles of English language. All the relevant articles which were identified to be related to liquid biomarker study in spinal tumors, were studied in full text.

RESULTS: Liquid biopsy has revolutionized the field of precision medicine by guiding personalized clinical management of cancer patients based on the liquid biomarker status. In recent years, more research has been done to investigate its potential utilization in patients with tumors from the spine. Herein, we review the liquid biomarkers that have been proposed in different spine malignancies including chordoma, chondrosarcoma, Ewing sarcoma, osteosarcoma, astrocytoma and ependymoma. We also discuss the wide window of opportunity to utilize these liquid biomarkers in diagnosis, treatment response, monitoring, and detection of minimal residual disease in patients with spinal tumors.

CONCLUSIONS: Liquid biomarkers, especially blood-derived circulating tumor DNA, has a promising clinical utility as they are disease-specific, minimally invasive, and the procedure is repeatable. Prospective studies with larger populations are needed to fully establish its use in the setting of spinal tumors.

PMID:39801114 | PMC:PMC11726521 | DOI:10.1177/21925682231222012

  •  
❌