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Grounded by Experience: Generative Healthcare Prediction Augmented with Hierarchical Agentic Retrieval

arXiv:2511.13293v1 Announce Type: new Abstract: Accurate healthcare prediction is critical for improving patient outcomes and reducing operational costs. Bolstered by growing reasoning capabilities, large language models (LLMs) offer a promising path to enhance healthcare predictions by drawing on their rich parametric knowledge. However, LLMs are prone to factual inaccuracies due to limitations in the reliability and coverage of their embedded knowledge. While retrieval-augmented generation (RAG) frameworks, such as GraphRAG and its variants, have been proposed to mitigate these issues by incorporating external knowledge, they face two key challenges in the healthcare scenario: (1) identifying the clinical necessity to activate the retrieval mechanism, and (2) achieving synergy between the retriever and the generator to craft contextually appropriate retrievals. To address these challenges, we propose GHAR, a \underline{g}enerative \underline{h}ierarchical \underline{a}gentic \underline{R}AG framework that simultaneously resolves when to retrieve and how to optimize the collaboration between submodules in healthcare. Specifically, for the first challenge, we design a dual-agent architecture comprising Agent-Top and Agent-Low. Agent-Top acts as the primary physician, iteratively deciding whether to rely on parametric knowledge or to initiate retrieval, while Agent-Low acts as the consulting service, summarising all task-relevant knowledge once retrieval was triggered. To tackle the second challenge, we innovatively unify the optimization of both agents within a formal Markov Decision Process, designing diverse rewards to align their shared goal of accurate prediction while preserving their distinct roles. Extensive experiments on three benchmark datasets across three popular tasks demonstrate our superiority over state-of-the-art baselines, highlighting the potential of hierarchical agentic RAG in advancing healthcare systems.

SciAgent: A Unified Multi-Agent System for Generalistic Scientific Reasoning

arXiv:2511.08151v2 Announce Type: replace Abstract: Recent advances in large language models have enabled AI systems to achieve expert-level performance on domain-specific scientific tasks, yet these systems remain narrow and handcrafted. We introduce SciAgent, a unified multi-agent system designed for generalistic scientific reasoning-the ability to adapt reasoning strategies across disciplines and difficulty levels. SciAgent organizes problem solving as a hierarchical process: a Coordinator Agent interprets each problem's domain and complexity, dynamically orchestrating specialized Worker Systems, each composed of interacting reasoning Sub-agents for symbolic deduction, conceptual modeling, numerical computation, and verification. These agents collaboratively assemble and refine reasoning pipelines tailored to each task. Across mathematics and physics Olympiads (IMO, IMC, IPhO, CPhO), SciAgent consistently attains or surpasses human gold-medalist performance, demonstrating both domain generality and reasoning adaptability. Additionally, SciAgent has been tested on the International Chemistry Olympiad (IChO) and selected problems from the Humanity's Last Exam (HLE) benchmark, further confirming the system's ability to generalize across diverse scientific domains. This work establishes SciAgent as a concrete step toward generalistic scientific intelligence-AI systems capable of coherent, cross-disciplinary reasoning at expert levels.

The dual immunomodulatory role of B cells in tumorigenesis: mechanisms, microenvironment crosstalk, and therapeutic implications

Front Immunol. 2025 Oct 30;16:1649812. doi: 10.3389/fimmu.2025.1649812. eCollection 2025.

ABSTRACT

B lymphocytes exhibit a multifaceted and context-dependent role in tumor biology, acting as both promoters and suppressors of malignancy through dynamic interactions within the tumor microenvironment (TME). This review synthesizes current evidence on the dual functions of B cells in tumor immunity, highlighting their capacity to orchestrate antitumor responses via antigen presentation, antibody-dependent cytotoxicity, and tertiary lymphoid structure (TLS)-mediated T cell activation, while paradoxically driving immunosuppression through regulatory B cells (Bregs), pro-angiogenic signaling, and immune checkpoint modulation. Key mechanisms include TLS formation, which enhances cytotoxic T cell priming and correlates with improved immunotherapy outcomes, and Breg-mediated secretion of IL-10/TGF-β, which fosters T cell exhaustion and myeloid-derived suppressor cell recruitment. Tumor-type specificity is evident: TLS-rich malignancies like melanoma and Non-Small Cell Lung Cancer (NSCLC) show B cell-driven immune activation, whereas pancreatic and hepatocellular carcinomas demonstrate B cell functional plasticity influenced by metabolic and epigenetic reprogramming. Therapeutically, B cell-targeted strategies-including CD20 antibodies, CAR-T cells, and B cell epitope vaccines-demonstrate efficacy in hematologic and solid tumors, yet face challenges due to subset heterogeneity and sex-specific response disparities. Emerging approaches combine immune checkpoint inhibitors (ICBs) with TLS-inducing agents or exploit B cell-derived biomarkers for personalized therapy. Future directions emphasize deciphering B cell metabolic-niche crosstalk, optimizing combinatorial regimens, and leveraging spatial multiomics to resolve functional heterogeneity. By bridging mechanistic insights with clinical translation, this work underscores B cells as pivotal regulators of tumor immunity and advocates for precision strategies to harness their antitumor potential while mitigating pro-tumor plasticity.

PMID:41246318 | PMC:PMC12611826 | DOI:10.3389/fimmu.2025.1649812

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