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Predicting Neuromodulation Outcome for Parkinson's Disease with Generative Virtual Brain Model

arXiv:2603.29176v1 Announce Type: new Abstract: Parkinson's disease (PD) affects over ten million people worldwide. Although temporal interference (TI) and deep brain stimulation (DBS) are promising therapies, inter-individual variability limits empirical treatment selection, increasing non-negligible surgical risk and cost. Previous explorations either resort to limited statistical biomarkers that are insufficient to characterize variability, or employ AI-driven methods which is prone to overfitting and opacity. We bridge this gap with a pretraining-finetuning framework to predict outcomes directly from resting-state fMRI. Critically, a generative virtual brain foundation model, pretrained on a collective dataset (2707 subjects, 5621 sessions) to capture universal disorder patterns, was finetuned on PD cohorts receiving TI (n=51) or DBS (n=55) to yield individualized virtual brains with high fidelity to empirical functional connectivity (r=0.935). By constructing counterfactual estimations between pathological and healthy neural states within these personalized models, we predicted clinical responses (TI: AUPR=0.853; DBS: AUPR=0.915), substantially outperforming baselines. External and prospective validations (n=14, n=11) highlight the feasibility of clinical translation. Moreover, our framework provides state-dependent regional patterns linked to response, offering hypothesis-generating mechanistic insights.

Multi-omics analysis reveals AR as a potential prognostic factor and immune-related therapeutic target in gastric cancer

Biochem Biophys Rep. 2026 Mar 16;46:102537. doi: 10.1016/j.bbrep.2026.102537. eCollection 2026 Jun.

ABSTRACT

BACKGROUND: Although studies have shown that the androgen receptor (AR) is associated with tumor progression and malignant regulation, its role in the tumor immune microenvironment and predictive value for prognosis and immunotherapy response in various cancer types have not been systematically analyzed.

METHODS: In this paper, multi-omics techniques was used to analyze AR comprehensively.

RESULTS: A comprehensive pan-cancer analysis revealed that the AR was expressed in a variety of tumors, especially as a risk factor for poor prognosis in gastric cancer. In addition, gene set enrichment analysis showed that the AR promotes cell proliferation and tumor cell invasion and regulates anti-tumor response. Immune score, immune cell infiltration, and anticancer immune cycle analysis showed that high AR levels were correlated with low infiltration of CD4+ T cells and NKT cells, high infiltration of Th2 cells and MDSCs, negatively correlated with antigen-presenting molecules, and positively correlated with various immune-negative regulatory molecules. Single-cell sequencing highlighted the heterogeneous expression of ARs in different cell types, particularly in epithelial cells, where high AR levels were associated with the enhanced activity of tumor-promoting pathways.

CONCLUSIONS: In conclusion, this study highlights the potential of the AR as a novel biomarker for gastric cancer prognosis and immunotherapy efficacy, expanding its applicability in the development of new antitumor drugs.

PMID:41890218 | PMC:PMC13014673 | DOI:10.1016/j.bbrep.2026.102537

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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