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Hypoxia-related and immune phenotype-related fusion model for non-invasive prognostication of hepatocellular carcinoma treated by TACE: a multicentre study

Gut. 2026 Mar 30:gutjnl-2025-337938. doi: 10.1136/gutjnl-2025-337938. Online ahead of print.

ABSTRACT

BACKGROUND: Survival outcomes after transarterial chemoembolisation (TACE) vary in hepatocellular carcinoma (HCC) patients, and existing prognostic scores and imaging models often lack generalisability and biological interpretability.

OBJECTIVE: To develop and validate a multimodal prognostication model for HCC that allows for a precise assessment of survival outcomes of HCC patients receiving TACE therapy.

DESIGN: This study enrolled 1448 HCC patients, including a TACE cohort (n=1349), a biomarker subset from a randomised trial (n=41), a single-cell RNA sequencing cohort and The Cancer Genome Atlas (TCGA) HCC cohort (n=50). Pre-treatment contrast-enhanced CT images were used to construct deep learning and conventional radiomic models. The early-fusion and late-fusion models (LFMs) were compared, and a clinical-radiologic model (CRM) was formed by integrating the better-performing LFM with clinical variables. Using TCGA data and single-cell transcriptomic profiles, the differences between high-score and low-score groups in tumour immune microenvironment, cellular functional states and key signalling pathways were investigated.

RESULTS: The CRM effectively stratified patients' survival across multiple independent cohorts and achieved more granular risk stratification than the existing clinical models. Multi-omic analyses revealed that in the LFM high-score group, myelocytomatosis oncogene was activated, epithelial-mesenchymal transition enhanced, glycolysis upregulated and hypoxia pathway activated. Single-cell transcriptomic data confirmed that virtually all cell types in high-risk patients scored high in hypoxia, and cytotoxic T cells had a reduced cytotoxic activity.

CONCLUSION: The CRM model can non-invasively predict the prognosis of HCC patients treated by TACE therapy.

PMID:41856522 | DOI:10.1136/gutjnl-2025-337938

Towards AI Search Paradigm

arXiv:2506.17188v2 Announce Type: replace-cross Abstract: In this paper, we introduce the AI Search Paradigm, a comprehensive blueprint for next-generation search systems capable of emulating human information processing and decision-making. The paradigm employs a modular architecture of four LLM-powered agents (Master, Planner, Executor and Writer) that dynamically adapt to the full spectrum of information needs, from simple factual queries to complex multi-stage reasoning tasks. These agents collaborate dynamically through coordinated workflows to evaluate query complexity, decompose problems into executable plans, and orchestrate tool usage, task execution, and content synthesis. We systematically present key methodologies for realizing this paradigm, including task planning and tool integration, execution strategies, aligned and robust retrieval-augmented generation, and efficient LLM inference, spanning both algorithmic techniques and infrastructure-level optimizations. By providing an in-depth guide to these foundational components, this work aims to inform the development of trustworthy, adaptive, and scalable AI search systems.

Beyond Static Snapshots: Dynamic Modeling and Forecasting of Group-Level Value Evolution with Large Language Models

arXiv:2602.14043v1 Announce Type: cross Abstract: Social simulation is critical for mining complex social dynamics and supporting data-driven decision making. LLM-based methods have emerged as powerful tools for this task by leveraging human-like social questionnaire responses to model group behaviors. Existing LLM-based approaches predominantly focus on group-level values at discrete time points, treating them as static snapshots rather than dynamic processes. However, group-level values are not fixed but shaped by long-term social changes. Modeling their dynamics is thus crucial for accurate social evolution prediction--a key challenge in both data mining and social science. This problem remains underexplored due to limited longitudinal data, group heterogeneity, and intricate historical event impacts. To bridge this gap, we propose a novel framework for group-level dynamic social simulation by integrating historical value trajectories into LLM-based human response modeling. We select China and the U.S. as representative contexts, conducting stratified simulations across four core sociodemographic dimensions (gender, age, education, income). Using the World Values Survey, we construct a multi-wave, group-level longitudinal dataset to capture historical value evolution, and then propose the first event-based prediction method for this task, unifying social events, current value states, and group attributes into a single framework. Evaluations across five LLM families show substantial gains: a maximum 30.88\% improvement on seen questions and 33.97\% on unseen questions over the Vanilla baseline. We further find notable cross-group heterogeneity: U.S. groups are more volatile than Chinese groups, and younger groups in both countries are more sensitive to external changes. These findings advance LLM-based social simulation and provide new insights for social scientists to understand and predict social value changes.

An Agentic System for Rare Disease Diagnosis with Traceable Reasoning

arXiv:2506.20430v3 Announce Type: replace-cross Abstract: Rare diseases affect over 300 million individuals worldwide, yet timely and accurate diagnosis remains an urgent challenge. Patients often endure a prolonged diagnostic odyssey exceeding five years, marked by repeated referrals, misdiagnoses, and unnecessary interventions, leading to delayed treatment and substantial emotional and economic burdens. Here we present DeepRare, a multi-agent system for rare disease differential diagnosis decision support powered by large language models, integrating over 40 specialized tools and up-to-date knowledge sources. DeepRare processes heterogeneous clinical inputs, including free-text descriptions, structured Human Phenotype Ontology terms, and genetic testing results, to generate ranked diagnostic hypotheses with transparent reasoning linked to verifiable medical evidence. Evaluated across nine datasets from literature, case reports and clinical centres across Asia, North America and Europe spanning 14 medical specialties, DeepRare demonstrates exceptional performance on 3,134 diseases. In human-phenotype-ontology-based tasks, it achieves an average Recall@1 of 57.18%, outperforming the next-best method by 23.79%; in multi-modal tests, it reaches 69.1% compared with Exomiser's 55.9% on 168 cases. Expert review achieved 95.4% agreement on its reasoning chains, confirming their validity and traceability. Our work not only advances rare disease diagnosis but also demonstrates how the latest powerful large-language-model-driven agentic systems can reshape current clinical workflows.
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