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Hierarchical Retrieval with Out-Of-Vocabulary Queries: A Case Study on SNOMED CT

arXiv:2511.16698v1 Announce Type: cross Abstract: SNOMED CT is a biomedical ontology with a hierarchical representation of large-scale concepts. Knowledge retrieval in SNOMED CT is critical for its application, but often proves challenging due to language ambiguity, synonyms, polysemies and so on. This problem is exacerbated when the queries are out-of-vocabulary (OOV), i.e., having no equivalent matchings in the ontology. In this work, we focus on the problem of hierarchical concept retrieval from SNOMED CT with OOV queries, and propose an approach based on language model-based ontology embeddings. For evaluation, we construct OOV queries annotated against SNOMED CT concepts, testing the retrieval of the most direct subsumers and their less relevant ancestors. We find that our method outperforms the baselines including SBERT and two lexical matching methods. While evaluated against SNOMED CT, the approach is generalisable and can be extended to other ontologies. We release code, tools, and evaluation datasets at https://github.com/jonathondilworth/HR-OOV.
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From Passive to Proactive: A Multi-Agent System with Dynamic Task Orchestration for Intelligent Medical Pre-Consultation

arXiv:2511.01445v1 Announce Type: new Abstract: Global healthcare systems face critical challenges from increasing patient volumes and limited consultation times, with primary care visits averaging under 5 minutes in many countries. While pre-consultation processes encompassing triage and structured history-taking offer potential solutions, they remain limited by passive interaction paradigms and context management challenges in existing AI systems. This study introduces a hierarchical multi-agent framework that transforms passive medical AI systems into proactive inquiry agents through autonomous task orchestration. We developed an eight-agent architecture with centralized control mechanisms that decomposes pre-consultation into four primary tasks: Triage ($T_1$), History of Present Illness collection ($T_2$), Past History collection ($T_3$), and Chief Complaint generation ($T_4$), with $T_1$--$T_3$ further divided into 13 domain-specific subtasks. Evaluated on 1,372 validated electronic health records from a Chinese medical platform across multiple foundation models (GPT-OSS 20B, Qwen3-8B, Phi4-14B), the framework achieved 87.0% accuracy for primary department triage and 80.5% for secondary department classification, with task completion rates reaching 98.2% using agent-driven scheduling versus 93.1% with sequential processing. Clinical quality scores from 18 physicians averaged 4.56 for Chief Complaints, 4.48 for History of Present Illness, and 4.69 for Past History on a 5-point scale, with consultations completed within 12.7 rounds for $T_2$ and 16.9 rounds for $T_3$. The model-agnostic architecture maintained high performance across different foundation models while preserving data privacy through local deployment, demonstrating the potential for autonomous AI systems to enhance pre-consultation efficiency and quality in clinical settings.
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An eyecare foundation model for clinical assistance: a randomized controlled trial

Nature Medicine, Published online: 28 August 2025; doi:10.1038/s41591-025-03900-7

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.
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Targeting spermine metabolism to overcome immunotherapy resistance in pancreatic cancer

Nat Commun. 2025 Aug 22;16(1):7827. doi: 10.1038/s41467-025-63146-2.

ABSTRACT

While dysregulation of polyamine metabolism is frequently observed in cancer, it is unknown how polyamines alter the tumor microenvironment (TME) and contribute to therapeutic resistance. Analysis of polyamines in the plasma of pancreatic cancer patients reveals that spermine levels are significantly elevated and correlate with poor prognosis. Using a multi-omics approach, we identify Serpinb9 as a vulnerability in spermine metabolism in pancreatic cancer. Serpinb9, a serine protease inhibitor, directly interacts with spermine synthase (SMS), impeding its lysosome-mediated degradation and thereby augmenting spermine production and secretion. Mechanistically, the accumulation of spermine in the TME alters the metabolic landscape of immune cells, promoting CD8+ T cell dysfunction and pro-tumor polarization of macrophages, thus creating an immunosuppressive microenvironment. Small peptides that disrupt the Serpinb9-SMS interaction significantly enhance the efficacy of immune checkpoint blockade therapy. Together, our findings suggest that targeting spermine metabolism is a promising strategy to improve pancreatic cancer immunotherapy.

PMID:40846845 | PMC:PMC12373741 | DOI:10.1038/s41467-025-63146-2

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Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses

Cell Metab. 2025 Jan 28:S1550-4131(24)00495-9. doi: 10.1016/j.cmet.2024.12.013. Online ahead of print.

ABSTRACT

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but remains effective in only a subset of patients. Emerging evidence suggests that the gut microbiome and its metabolites critically influence ICB efficacy. In this study, we performed a multi-omics analysis of fecal microbiomes and metabolomes from 165 patients undergoing anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy, identifying microbial and metabolic entities associated with treatment response. Integration of data from four public metagenomic datasets (n = 568) uncovered cross-cohort microbial and metabolic signatures, validated in an independent cohort (n = 138). An integrated predictive model incorporating these features demonstrated robust performance. Notably, we characterized five response-associated enterotypes, each linked to specific bacterial taxa and metabolites. Among these, the metabolite phenylacetylglutamine (PAGln) was negatively correlated with response and shown to attenuate anti-PD-1 efficacy in vivo. This study sheds light on the interplay among the gut microbiome, the gut metabolome, and immunotherapy response, identifying potential biomarkers to improve treatment outcomes.

PMID:39909032 | DOI:10.1016/j.cmet.2024.12.013

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