Propagating construction-time knowledge quality into medical question answering: A framework grounded in clinical guidelines

Large language models have facilitated knowledge graph (KG) construction from clinical guidelines, but extracted triples vary in structural validity and evidential support. Meanwhile, graph-augmented question answering (QA) systems typically optimize query relevance during retrieval, with limited reuse of quality information produced during KG construction. This creates a disconnect between construction-time quality control and inference-time evidence use. We investigate whether construction-time triple quality can serve as a persistent signal for downstream evidence selection and presentation. We propose a quality-aware framework that models structural conformance (SchemaConf) and evidential support (EvidScore) as complementary dimensions and fuses them into a per-triple quality signal, Q(t). Rather than using quality solely for filtering, the framework retains Q(t) and derived quality tiers as graph attributes and propagates them into quality-weighted subgraph retrieval and tier-conditioned evidence prompting, while preserving passage-level provenance. Experiments on Chinese diabetes clinical guidelines show that the utility of the quality signal is distribution dependent. Under cross-version and cross-model shift, the fused Q(t) provides stronger triple-quality discrimination than either component alone (AUC 0.748 vs. 0.703 for EvidScore and 0.645 for SchemaConf). In guideline-grounded QA, propagating construction-time quality reduces required-knowledge omission from 16.3% to 5.3% and conflicting outputs from 16.3% to 2.7%, with an evidence-grounded precision of 81.6% and near-zero invalid citations. Blinded clinician ratings favor the full framework over no retrieval (4.68 vs. 4.21 on a five-point scale) and approach the oracle condition (4.80), while cross-generator experiments show consistent trends.

Neurosymbolic Alignment for Physiologically-Safe Clinical Language Models

Clinical LLMs can generate recommendations that are factually plausible yet physiologically unsafe. We investigate whether safety alignment can be improved by grounding preference optimization in structured physiological knowledge rather than text-only supervision. Methods: We propose Neurosymbolic Alignment, a training-time framework that couples a 7B clinical LLM with an HGNN-based Physiological World Model over an 847K-node biomedical knowledge graph. Candidate responses are scored using homeostatic constraints, multi-hop path plausibility, and drug-interaction penalties, and the resulting rankings drive iterative on-policy ORPO updates. Evaluation is performed on the Clinical Safety Benchmark (CSB), a 2,500-scenario benchmark for physiological constraint violations in generative clinical reasoning. Results: Relative to ORPO, the proposed method improves CSS from 69.5% to 90.8% (+21.3 pp), reduces physician-evaluated HR from 14.1% to 5.1% on the blinded subset, and improves DID from 72.8% to 91.6%. These gains are corroborated by an HGNN-independent Rule-Engine Safety Score (RSS: 86.4%, +21.2 pp over ORPO; r=0.97 concordance with CSS). The method also exceeds GPT-4 (5-shot) on all safety metrics despite a 10x parameter disadvantage, and outperforms an inference-time self-correction pipeline (SFT+SelfCorrect) by 11.4 pp CSS. Under synthetic EHR-style noise, 84.2% CSS is retained. Ablation analysis shows that HGNN scoring (-16.2 pp) and iterative training (-11.5 pp) are the dominant contributors. PhysioScore calibration against 200 clinician labels yielded ECE = 0.038 and kappa = 0.91. Conclusion: Training-time physiological grounding produces measurable and independently verifiable safety improvements in open-weight clinical LLMs under controlled evaluation. External validation on real clinical data is required to determine whether these gains transfer to deployment settings

Graph-Supervised Hierarchical Clinical Alignment for Radiology Report Generation with Large Language Models

Radiology report generation (RRG) has recently benefited from large language models, which substantially improve report fluency. However, clinically faithful generation remains challenging because current supervision is still imposed mostly at the report level. This creates a granularity mismatch: radiology reports are composed of disease-grounded findings, while existing methods are trained mainly with whole-report objectives. To address this problem, we propose Graph-Supervised Hierarchical Clinical Alignment, which reformulates image-report supervision as a hierarchical clinical alignment problem. Our method structures this alignment as a disease-conditioned process, where supervision is decomposed into two levels: Disease-Centric Alignment for fine-grained disease-specific correspondence, and Global Clinical Semantic Alignment for report-level semantic coherence. A clinical knowledge graph is used as a training-time-only structural prior that defines disease-specific supervision units and their clinical relationships, introducing no additional overhead at inference. Because standard contrastive alignment could produce false negatives when studies share overlapping pathologies, we combine instance-conditioned discriminative matching with disease-conditioned soft regularization, enabling fine-grained yet clinically consistent cross-modal representations. Experiments on MIMIC-CXR, IU-Xray, and COV-CTR show that our method consistently improves performance on both conventional and clinical metrics. Notably, our 3B model surpasses several prior systems with larger 7B/13B backbones, suggesting that improving supervision structure, rather than increasing model size, can be more effective for RRG.

A knowledge-guided agentic framework for mitigating patient-context ambiguity in health queries

Patients often submit short, underspecified queries to healthcare chatbots that lack the patient-specific information needed to determine an appropriate response. Although these queries may be linguistically clear, they can support multiple plausible answers depending on undisclosed factors such as symptoms, diagnoses, medications, allergies, or dietary restrictions. A language model answering such a query directly may therefore rely on unsupported assumptions about the patient. We introduce a knowledge-guided agentic framework for mitigating patient-context ambiguity before final response generation. The framework operates between the patient and an otherwise unchanged downstream language model. It interprets the initial query, uses a task-specific knowledge graph to construct a set of plausible hypotheses, identifies the missing patient-context variables needed to distinguish among them, and asks targeted follow-up questions. The original query and the acquired context are then combined into a clarified prompt for the downstream model. We evaluated the framework across five language models using two controlled ambiguity-mitigation benchmarks: diagnosis retrieval from 1,034 symptom queries with clinically relevant evidence systematically masked, and dietary-safety classification from 487 queries with decisive health context omitted. The framework was compared with direct answering of the underspecified query and with rephrasing the same query without acquiring new patient information. In diagnosis retrieval, it increased overall exact Top-1 accuracy by at least 57.1 percentage points and selective exact Recall@5 by at least 77.7 percentage points across the five evaluated models compared with direct prompting. In dietary-safety classification, it improved accuracy across all five models and achieved the highest Matthews correlation coefficient for four...

Authoring and Management of Transparent Research Integrity Assessments of Randomised Clinical Trial Publications Using LLM-assisted Tools and Provenance Knowledge Graphs

Systematic reviews of Randomised Controlled Trials (RCTs) are routinely used as evidence for clinical care guidelines. Such evidence has to meet high research integrity standards to prevent low quality or false research outputs influencing the clinical care. However, assessing research integrity of published RCTs is a complex process requiring manual effort, and potentially resulting in diverse opinions of the human assessors. This paper describes INSPECT-AI, an LLM-based interactive tool that assists human reviewers with research integrity assessments of published RCTs based on the community approved INSPECT-SR framework, and the Research Integrity Provenance and Evidence ontology (RIPE-O) for documenting the provenance of the assessment process. In addition, we present the Research Integrity Provenance and Evidence knowledge graph (RIPE-KG), an initial set of 140 expert research integrity assessments of 95 RCT publications generated by INSPECT-AI and described using RIPE-O.

PatTree: a novel approach for automated creation of multimodal, graph-based patient representations for medical classification tasks

Access to holistic, multimodal data improves the performance of Artificial Intelligence (AI) in medical classification tasks compared to utilizing single modalities or data sources. However, the inherent heterogeneity and complexity of clinical real-world data pose significant challenges to structured data analysis and AI application. This heterogeneity includes missing values, multiple time points, diverse modalities, and inconsistent formats and semantics. Data harmonization prior to data integration tackles this challenge but remains resource-intensive and error-prone, limiting the scalability and reproducibility of holistic, AI-driven decision support on clinical real-world data. We therefore propose PatTree, a graph-based, holistic representation of patients that can be derived from real-world clinical data through the automated structuring of multimodal clinical data. PatTree enables early-stage data integration without relying on pre-standardized inputs. While representing heterogeneous clinical data within a unified knowledge graph, PatTree preserves the semantic relationships between data elements across modalities and data sources, facilitating interoperability and machine-interpretable data access. Using a subset of the ADNI-1 cohort (n = 763), we demonstrate that classification of patients is directly feasible on PatTree reaching state-of-the-art classification performance. In the three-class classification task distinguishing Alzheimer's disease, mild cognitive impairment, and cognitively normal individuals, we achieve a balanced accuracy of 98.5% and an F$_1$ score of 0.987 on the held-out test set. Our results show that assumption-free, automated structuring of multimodal medical data can serve as a scalable foundation for clinical AI pipelines bypassing tedious data preparation and standardization.

LUNG-KGMM: Knowledge-Guided Multimodal Learning for Lung Cancer Incidence Prediction

Early identification of lung cancer risk is critical for timely intervention, yet existing prediction models are limited by their reliance on single data modalities and their inability to leverage structured clinical knowledge. We propose LUNG-KGMM, a knowledge-guided multimodal framework that integrates longitudinal electronic health records, radiology reports, chest radiograph representations, and guideline-derived knowledge for 1-to-6-year incident lung cancer prediction. To address modality heterogeneity and potential data leakage, we develop a leakage-sanitized report processing pipeline and a horizon-masked cumulative training objective that handles incomplete follow-up. We further introduce a knowledge-graph representation of clinical guidance that encodes report-triggered finding-attribute-action relations as an auditable knowledge stream. We build a multimodal development cohort from the publicly available MIMIC databases and construct a real-world validation cohort from the Xiamen Medical Big Data Platform. Extensive experiments on the MIMIC cohort demonstrate that LUNG-KGMM achieves superior performance over state-of-the-art methods, and validation on the Xiamen cohort further characterizes its cross-cohort portability and the need for local adaptation. The MIMIC development cohort is publicly accessible; the Xiamen cohort is governed by local data privacy regulations.

LingShu: A Large-Scale Symptom-Centric Contextualized Knowledge Graph Bridging Traditional Chinese Medicine and Modern Biomedicine

Biomedical knowledge graphs (KGs) are pivotal for knowledge organization, yet traditional binary relations often struggle to represent the conditional nature of biomedical knowledge. Symptoms provide a shared phenotypic layer for linking Traditional Chinese Medicine (TCM), which relies on symptom patterns for syndrome differentiation and treatment selection, with modern biomedicine, which connects clinical manifestations to diseases and molecular mechanisms. We present LingShu, a large-scale symptom-centric contextualized knowledge graph designed to bridge TCM and modern biomedicine. The exported version of LingShu analyzed in this study comprises 17.33 million atom-level entity records and 39.47 million relation records, including 17.19 million semantic triples and 22.29 million contextualized quadruples. LingShu integrates multi-source data, including clinical electronic medical records, authoritative TCM texts, biomedical ontologies, and curated knowledge bases, through a pipeline combining natural language processing, terminology normalization, and human-in-the-loop verification. A key innovation of LingShu is its hybrid data model: it maintains 64 typed triple relation patterns to ensure broad connectivity, while incorporating 35 contextual quadruple relation patterns to capture conditional medical associations. This dual-structure approach explicitly encodes conditional knowledge, providing a granular representation of the contexts associated with medical relations. These contextualized relations cover syndrome-dependent herb efficacy, disease-contextualized drug effects, population-specific clinical associations, and mechanism-related therapeutic responses. Furthermore, we developed a web platform (http://www.tcmkg.com/) that integrates graph visualization, graph-based reasoning, and an evidence-grounded knowledge question-answering agent.

MedJudgeRAG: Option-Wise Evidence Judgment with Dynamic Knowledge Graphs for Medical MCQA

In medical multiple-choice question answering (MCQA), Retrieval-Augmented Generation (RAG) can supplement the domain knowledge of language models (LMs). However, since vanilla RAG indiscriminately utilizes retrieved documents, it can degrade LM performance. To address this, we propose MedJudgeRAG. Our framework represents retrieved documents as a dynamic knowledge graph (KG) composed of entities and relations. For each option, the model judges an evidence verdict from the retrieved documents and the KG. Based on the verdict combination, the model determines a knowledge utilization strategy to reason toward the final answer. These capabilities are trained via supervised fine-tuning using structured reasoning traces generated by a teacher LM. The training employs a weighted cross-entropy loss that differentially weights the KG and reasoning segments. Experiments on two medical MCQA benchmarks demonstrate that MedJudgeRAG consistently outperforms both vanilla RAG and parametric baselines. Furthermore, ablation analysis reveals that the dynamic KG is more effective as graph-conditioned supervision at training time than as an explicit output at inference time. Our code is available at https://github.com/hyu-amllab/medjudgerag, and the generated reasoning traces are released at https://huggingface.co/datasets/youarethewon/medjudgerag.

Agent-Guided Relational Concept Discovery: Toward Interpretable Surgical Margin Assessment

Deep learning models can effectively use Rapid Evaporative Ionization Mass Spectrometry (REIMS) data for surgical margin assessment. However, their clinical adoption remains challenging due to limited generalization to operating room conditions. This difficulty arises because models are typically trained on labeled spectra collected from resected tissue samples, while they must operate on noisy, unlabeled data acquired directly during surgery. In addition, the black-box nature of deep learning models makes it difficult to understand and systematically improve their behavior. Concept-based learning offers a promising way to address these challenges by mapping raw measurements to human-understandable concepts. However, supervised concept-based approaches rely on concept annotations, which are difficult to obtain in complex mass spectrometry workflows. We propose Agent-Guided Concept Discovery, a framework that learns meaningful concepts directly from data without requiring predefined concept labels. During training, a reasoning agent refines semantic descriptions of the learned concepts and adaptively adjusts their weight based on diagnostic relevance. These concepts are further grounded using a biochemical knowledge graph to ensure consistency with known metabolic relationships. Across Skin and Breast Cancer datasets, our model improves balanced accuracy and sensitivity over the baseline. In a representative intraoperative case, it shows fewer false positives, indicating better generalization to surgical conditions.

NeuroGRIP: Retrieval-Augmented Graph Refinement for Knowledge-Grounded EEG Seizure Diagnosis

Seizure diagnosis from EEG signals is a critical yet persistently challenging task, due to the complicated neural dynamics and the spurious connections in inter-channel modeling. While spatial-temporal graph neural networks (STGNNs) have advanced EEG brain network representation learning, the resulting graph structures suffer from low clinical plausibility and limited interpretability due to their purely data-driven nature. To this end, we introduce NeuroGRIP, a retrieval-augmented graph refinement framework that incorporates external medical knowledge to calibrate noisy EEG graphs. We first construct a large-scale, domain-specific knowledge base derived from authoritative clinical guidelines. Leveraging large language models, we extract structured biomedical entities and relations to form a textual knowledge graph (KG), which serves as external knowledge source of clinical priors. Our framework performs alignment-aware query construction by projecting STGNN-generated EEG node embeddings into the semantic space of KG. Semantic queries are then executed via FAISS-based similarity search over knowledge triplets to retrieve relation evidence. Each predicted edge is assigned a confidence score based on retrieved similarity, relation type, and source reliability, enabling us to prune medically implausible edges from the originally predicted graph. Extensive experiments on TUSZ and CHB-MIT demonstrate that NeuroGRIP not only improves seizure detection accuracy but also enhances interpretability by grounding each prediction in clinically validated knowledge. This work provides the first unified framework that tightly couples brain dynamics with external medical expertise via retrieval-augmented reasoning, paving the way for knowledge-enhanced, explainable clinical diagnosis. The code is available at: https://github.com/LincanLi-X/NeuroGRIP.

Predicting Therapeutic Outcome via Aligning Patient-Specific Knowledge Graph and Gene-Level Perturbation Representations

Accurate prediction of patient-specific therapeutic response from pre-treatment transcriptomes is hindered by the scarcity of matched clinical response labels and post-treatment molecular profiles. Preclinical transfer-learning models can simulate drug-induced expression changes but are often hard to interpret and unstable, whereas knowledge-graph methods provide mechanistic context yet remain static and fail to capture drug-induced transcriptomic perturbation dynamics. We propose PREDIKTOR, a patient-centered multi-view framework that aligns a personalized network view with a transferable transcriptomic perturbation view to predict clinical drug response. For each patient, we construct an individualized gene regulatory network from tumor expression using DysRegNet and augment it with drug-target links from DrugBank; a graph neural encoder yields a drug-centric, mechanistically grounded embedding. In parallel, a frozen condition-specific gene-gene attention model pretrained on LINCS L1000 generates a simulated post-perturbation transcriptomic profile for the same patient-drug pair. We align the two views in a shared latent space via a CLIP-style contrastive objective with drug-context hard negatives, then concatenate the representations for end-to-end response classification. On TCGA, PREDIKTOR consistently outperforms state-of-the-art baselines under patient-, drug-, and tissue-split evaluations, and transfers zero-shot to the I-SPY2 trial, improving AUROC by 5.6% over competing methods. The aligned embeddings yield stable gene and pathway attributions that recover known mechanisms, supporting actionable and interpretable precision oncology.

CoFEND: A Cross-Modal Fusion End-to-End Network for Cold-Start Drug-Drug Interaction Prediction

Cold-start drug-drug interaction (DDI) prediction for new drugs is critical for minimizing unexpected adverse drug reactions. The key challenge is to capture similarity between new and known drugs. However, such similarity is closely associated with complex relationships and mechanisms among drugs, enzymes, transporters, molecular structures, and other biomedical entities. Existing methods have three limitations in capturing such similarity: (1) only partial relationships and mechanisms are considered, which overlooks cross-modal information and yields incomplete or biased similarity modeling; (2) similarity computation between new and known drugs is conducted separately across modalities and performed offline for cold-start DDI prediction, leading to misalignment between similarity computation and DDI prediction; and (3) existing interpretability analyses are typically single-modality and focus primarily on key determinants of the perpetrator drug, while the underlying causes of susceptibility for the victim drug are seldom investigated. To address these issues, this paper proposes a novel Cross-Modal-Fused End-to-End Learning Network (CMF-ELN) with three components. First, diverse multimodal information is leveraged to construct four types of drug-centered knowledge graphs, enabling comprehensive similarity modeling under reconstruction-based supervision. Second, a four-channel graph autoencoder is designed to fuse cross-modal similarity within an end-to-end learning framework. Finally, a two-stage interpretability scheme is devised to precisely localize key factors for both perpetrator and victim drugs. Extensive experiments on two real datasets demonstrate that CMF-ELN achieves significantly higher prediction accuracy and more comprehensive interpretability of mechanisms than its peers.

MKGR: Multimodal Knowledge-Graph Representation Learning for Cold-Start Protein-Protein Interaction Prediction

Accurate protein-protein interaction (PPI) prediction is central to functional genomics, disease mechanism discovery, and drug development. A difficult setting arises when candidate interactions include proteins that have no observed PPI edges during training, where models relying on network topology alone often lose useful context. This paper presents \method, a multimodal representation framework for cold-start PPI prediction. \method\ combines region-aware protein sequence encoding with four protein-centered biomedical knowledge graphs, including protein-drug, protein-disease, protein-miRNA, and protein-lncRNA associations. The sequence branch extracts contextual representations from structurally informed sequence regions, while graph attention encoders learn modality-specific protein embeddings from sparse biomedical associations. A bridge reconstruction objective regularizes graph learning by recovering shared protein-entity associations, and a pair-level gating module adaptively integrates sequence and graph evidence for each candidate protein pair. Experiments on two benchmark datasets under novel-old and novel-novel cold-start settings show that \method\ consistently outperforms competitive sequence, network, and knowledge-graph baselines across ACC, F1, AUC, AUPR, and MCC.

Cross-Domain Feature Expansion for Tabular Medical Data via Knowledge Graphs Injection

Acquiring comprehensive cross-domain biomedical profiles is often costly and time-consuming, resulting in severe data scarcity in medical research. To address this challenge, we propose MedKGTab, a knowledge-injected framework specifically engineered for cross-domain feature expansion in tabular medical data. MedKGTab seeks to infer uncollected biomedical features from available ones by exploiting their inherent statistical dependencies and established medical correlations. By employing a row-column dual-attention mechanism, MedKGTab operates directly on raw structured tabular data, inherently capturing exact numerical distributions without the structural loss caused by tokenization. Crucially, MedKGTab integrates data-driven statistical priors with the SPOKE biomedical knowledge graph, achieving an optimal synergy between the data and knowledge channels. Within this synergy, the representations derived from the data channel are modulated by the injected biomedical knowledge, ensuring the final generated data are grounded in empirical medical research. Experimental results demonstrate that MedKGTab achieves high data fidelity and realistic data representation in cross-domain feature expansion. It outperforms both SOTA medical large models (e.g., Baichuan M3-plus) and specialized tabular models designed for medical data generation. Furthermore, MedKGTab consistently delivers superior performance across various data generation scenarios, whether inferring missing features within the same dataset or generalizing across different medical cohorts.

DysLexLens: A Low-Resource LLM Framework for Analysing Dyslexic Learners Insights from Online Forums

Dyslexic learners increasingly use artificial intelligence (AI) tools to support reading, writing, organisation, and study-related tasks. However, their lived experiences with these tools remain largely underexamined. This paper proposes DysLexLens, a low-resource LLM framework, designed to analyse dyslexic learners experience with AI through online forum discussions. DysLexLens is designed as an end-to-end, evidence-traceable architecture which transforms noisy social media posts into a dictionary-driven corpora, provides knowledge-graph (KG)-based question reasoning, generates verifiable query responses, and enables response evaluation through quantitative and human-grounded assessment. DysLexLens has four key features. First, it employs a dictionary-driven filtering method to construct a more focused Reddit corpus on dyslexia and AI, filtering out noisy and weakly related posts to improve the relevance of data collected from low-resource forum contexts. Second, it integrates LLM-assisted semantic analysis with KG-based query reasoning to uncover meaningful patterns. Third, it has quantitative evaluation metrics (RAGAS and Query Robustness) to measure LLM-generated response performance. Fourth, it provides structured qualitative validation guidelines for assessing response quality, with a specific focus on hallucination and evidence alignment. We demonstrate the effectiveness of DysLexLens using dyslexia-related Reddit forum data and 30 questions. The results show its potential generalisability to other low-resource forum data contexts. DysLexLens, sample data, questions and evaluation results are available at Github to support reproducibility.

Knowledge-augmented Agentic AI for Mental Health Medication Information Seeking

Patients increasingly seek medication information online, yet safety knowledge for psychiatric drugs is split between regulatory adverse-event records, which are authoritative but abstract, and patient narratives, which are experience-near but unvalidated. Integrating them without conflating evidence and anecdote is especially consequential in psychiatry, where poorly contextualised information can amplify fear, nocebo responses, and non-adherence. Here we develop a provenance-aware, knowledge-graph-based multi-agent framework unifying 466,525 Reddit posts, 60,782 WebMD reviews, and twenty years of U.S. FDA Adverse Event Reporting System records for nine antidepressants. A large-language-model entity-recognition pipeline benchmarked against physician annotations reached highest F1 scores of 0.969 for medications and 0.973 for conditions. The two community platforms were far more concordant with each other (overlap up to a Jaccard similarity of 0.905) than with regulatory reports, indicating that patient-generated data form a partly independent safety signal. For sertraline, many adverse events appeared in community sources hundreds of days before the corresponding FDA date. A Neo4j knowledge graph grounded in ATC-N, ICD-10, and MedDRA vocabularies preserves provenance, keeping every claim traceable and regulatory facts distinct from patient experience. These results establish source-aware integration as a route to more auditable psychiatric medication information, with usefulness and patient benefit to be tested prospectively.

KG-TRACE: A Neuro-Symbolic Framework for Mechanistic Grounding in Antimicrobial Resistance Prediction

While WGS-based AMR prediction has reached high accuracy, existing models lack a mechanism to ground neural attributions in established biological pathways. We present KG-TRACE, a novel neuro-symbolic framework that integrates the WHO mutation knowledge graph (KG) as a structured biological constraint on a neural genomic model. Unlike existing methods that learn statistical patterns in isolation, KG-TRACE fuses genomic features and RotatE-based KG embeddings through a learned epistemic trust gate, dynamically weighting neural evidence against symbolic biological knowledge. Evaluated on the CRyPTIC M. tuberculosis cohort, KG-TRACE achieves an AUROC of 0.9760 for isoniazid, achieving competitive accuracy while its primary value lies in symbolic grounding, not predictive uplift. More importantly, we introduce the Biological Grounding Ratio (BGR), a dataset-level metric that quantifies alignment between neural attributions and established biology. Our framework achieves a 92.5% symbolic coverage of isoniazid-resistant predictions and effectively identifies MDR co-occurrence artifacts by issuing laboratory follow-up flags for 'UNCERTAIN' cases. We demonstrate that neuro-symbolic grounding provides a verifiable audit trail for clinicians, bridging the gap between predictive accuracy and clinical trust.

TTFT-Aware Graph Chain-of-Thought:Distance-Indexed Neural A* for Low-Hallucination Multi-Hop Medical Reasoning

Hallucinations and opaque reasoning remain unacceptable failure modes for clinical LLMs. We present a production-grade GraphRAG stack that constrains answers to verifiable graph chain-of-thought paths in a heterogeneous, ~700K-node medical knowledge graph powering a fertility assistant. The core idea is targeted navigation: a directed Pruned Landmark Labeling (PLL) oracle provides exact distances for sub-millisecond feasibility checks and simple-path enumeration, while a lightweight AStarNet heuristic operates strictly within the PLL corridor to prioritize clinically plausible expansions. We score and pack a small, diverse set of paths (CUI/semantic-type overlap, length prior, provenance priors) to condition generation, yielding compact prompts and improved Time to First Token (TTFT). On fertility-focused queries, the hybrid (PLL+AStarNet) establishes a better latency/recall Pareto frontier than text-only RAG and single-component baselines, lowers TTFT, and reduces clinician-audited hallucinations while preserving explanation clarity. The result is a practical recipe for explainable, low-hallucination multi-hop medical reasoning ready for real-world deployment.

VISTA Architect: A graph database-oriented health AI system demonstrated in multidisciplinary tumor boards

We introduce VISTA Architect, a database-oriented AI architecture for integrating large language models (LLMs) with longitudinal electronic health records (EHRs). At ingestion, it transforms complex clinical documentation into a persistent, provenance-linked knowledge graph, eliminating repeated reprocessing of raw records at query time. The architecture has two layers: a source-faithful MEDS Graph preserving granular EHR structure with full provenance, and a clinically abstracted Timeline Object Architecture (TOA) that uses graph-guided LLM extraction to synthesize a concise timeline of deduplicated, temporally coherent clinical events. This addresses key limitations of direct long-context prompting and retrieval-augmented generation (RAG), which often miss temporal relationships and incur high cost and latency from repeated raw-text processing. By precomputing clinical synthesis once, downstream queries access an organized patient state and traverse to source documentation only when detailed verification is needed. We demonstrate the system in multidisciplinary thoracic oncology tumor boards at Stanford Medicine, where precise reconstruction of patient histories is critical. Across 1,180 patients, VISTA Architect achieved 96.4% accuracy (mean 9.75/10) on 15 tumor board-salient variables (17,700 evaluations; 95% CI 96.1-96.7%), surpassing a matched BM25 RAG baseline and recent benchmarks for LLM-based clinical extraction. An agentic interface reduced preparation for a 30-patient held-out cohort to about 2.2 minutes without sacrificing accuracy. While configured here for thoracic oncology, the modular design adapts to other specialties through customizable event definitions, episode structures, and agentic tools; validation beyond thoracic oncology remains future work.

MedHal-Loc: Are "Explainable-by-Architecture" Medical Hallucination Detectors Faithful Localizers? A Localization Benchmark

Detecting hallucinations in clinical text is increasingly framed as an explainability problem: systems should not merely flag an unreliable response but point to the offending span. Architectures built around knowledge-graph (KG) triple decomposition are marketed for exactly this auditability, yet their localization ability is typically assumed rather than measured. We introduce MedHal-Loc, a benchmark and metric for localization faithfulness -- whether a detector's top-ranked error unit actually overlaps the erroneous span. The controlled subset comprises 300 PubMedQA-derived statements with single, span-level errors injected across four localizable types (entity substitution, relation error, mechanism misattribution, invention), yielding gold spans by construction; a complementary natural subset documents that real hallucinations are dominated by diffuse conclusion-flips that resist span localization (a human expert accepted 1/18 candidate spans). Evaluating four fine-grained paradigms, we find that NLI-per-clause, consistency-per-sentence, and the dedicated span detector FAVA all localize well above chance, whereas an elaborate KG-triple pipeline localizes no better than chance (+3.3pp, n.s.), bottlenecked by ~59% entity-extraction coverage -- despite competitive detection F1 (0.609). Detection competence does not imply faithful localization; architectural explainability must be validated, not presumed.

Weaving Multi-Source Evidence for Biomedical Reasoning: The BioMedHop Benchmark and BioWeave Framework

Biomedical question answering (QA) increasingly requires reasoning over interacting entities, where supporting evidence is scattered across biomedical knowledge graphs, literature documents, and web-accessible resources. However, existing biomedical QA benchmarks mainly focus on exam-style knowledge, literature comprehension, or short-range multi-hop inference, leaving source-conditioned graph reasoning and evidence topology construction underexplored. To fill this gap, we introduce BioMedHop, a multi-source graph-grounded benchmark for evaluating biomedical reasoning over structured evidence topologies. BioMedHop contains 10,045 instances across KG, document, web, and hybrid evidence settings, covering shared-neighbor matching, intersection reasoning, path-based reasoning, and counting, with option-based, open-ended, and numeric count renderings. To support this benchmark, we further propose BioWeave, a source-aware reasoning framework that retrieves biomedical KG paths, gathers supporting clues from documents and web sources, assembles them into a unified evidence graph, and verifies answers through entity-level evidence support. Comprehensive experiments show that BioWeave achieves the best overall performance among compared methods on BioMedHop, outperforming the strong hybrid baseline ToG-2 by 10.5% in the overall average. Moreover, BioWeave consistently improves different LLM backbones and enables smaller models, such as Qwen3-4B, to achieve reasoning performance comparable to GPT-4-Turbo.

DeepRoot: A KG-Coordinated Multi-Agent System for Therapeutic Reasoning over Historical Medical Texts

Historical medical archives and traditional medicines hold immense potential for drug discovery and remain a primary source for current drug development. However, pre-ontological prose and idiosyncratic taxonomies prevent the standardization and medical modernization of the data for use in current biomedical pipelines. Furthermore, no existing LLM agent system, whether tool-calling, retrieval-augmented, or agentic deep-research, can convert such text into verifiable drug-discovery leads at scale. We close this gap with DeepRoot, a multi-agent LLM system that jointly builds and utilizes a verified knowledge graph, showing that grounding and reasoning -- often conflated -- are separable axes the system can compose for therapeutic reasoning. Applied to the Shen Nong Ben Cao Jing, DeepRoot recovers $10$ of $21$ held-out compound-disease treatment pairs at R@$20$ ($47.6\%$ vs $4.8\%$ for a raw corpus LLM and $\sim\!2.4\%$ random) and dominates an LLM-as-judge audit for reasoning quality over baseline LLMs and LLMs with direct tool-call access to the same APIs DeepRoot itself queries. Tool-using LLMs hallucinate evidence on $87\%$ of claims, versus 7-10% for DeepRoot. Graph-only inference hallucinates $0\%$ but ranks lowest on reasoning coherence; DeepRoot KG+LLM is the only condition to win on both axes, pointing toward a route for systematic mining and repurposing of historical medical knowledge.

Lung-R1: A Knowledge Graph-Guided LLM for Pulmonary Diagnostic Reasoning

Diagnosing pulmonary diseases requires integrating heterogeneous evidence amid phenotypic variability and cross-disease overlap. Although large language models (LLMs) have shown progress on pulmonary knowledge question answering (QA) and information-processing tasks, reliable pulmonary diagnosis requires patient-specific, relation-aware reasoning over electronic medical record (EMR) evidence rather than isolated knowledge recall. We define this gap between pulmonary knowledge and case-level diagnostic reasoning as the Pulmonary Knowledge-to-Diagnosis Gap. To address it, we introduce LungKG, the first structured pulmonary knowledge graph for diagnostic knowledge organization and record-grounded reasoning. LungKG contains 59,038 nodes and 164,308 edges across 15 entity types and 112 relation types, serving as both a reusable pulmonary knowledge resource and the foundation for LungKG-guided model adaptation. Built on LungKG, we propose Lung-R1, a LungKG-guided pulmonary LLM trained through KG-constrained reasoning-chain construction and KG-guided reinforcement learning. In a 20-system evaluation, Lung-R1-14B achieves state-of-the-art performance across Choice, Pulmonary-QA, and EMR Diagnosis, reaching an EMR Diagnosis score of 4.3583 and surpassing the strongest non-Lung-R1 baseline by 0.1476 points. These results demonstrate the value of LungKG-guided training for EMR-based pulmonary diagnosis.

XMedFusion: A Knowledge-Guided Multimodal Perception and Reasoning Framework for Autonomous Medical Systems

Autonomous medical and robotic systems increasingly rely on intelligent perception and reasoning capabilities to interpret visual data and support clinical decision making. Radiology report generation represents a critical component of such automated diagnostic workflows, yet existing end-to-end multimodal models often suffer from weak visual grounding, resulting in unreliable interpretations and omission of subtle clinical findings. This paper presents XMedFusion, a modular AI framework designed as an intelligent perception and reasoning module for autonomous medical systems. The proposed framework decomposes visual information into coordinated functional components that emulate expert-driven analysis, including a visual perception agent that extracts image-grounded evidence, a knowledge graph construction agent that structures clinically relevant findings, and a retrieval-guided drafting process that ensures a consistent reporting structure. A synthesis agent iteratively integrates visual and structured evidence through reasoning-driven verification to produce reliable and interpretable diagnostic outputs. Experimental evaluation on a public chest radiograph dataset demonstrates significant improvements over baseline vision-language models, achieving gains from 0.0493 to 0.3359 in BLEU-1, 0.0863 to 0.2440 in ROUGE-L, and 0.0829 to 0.1708 in METEOR, along with substantial improvements in semantic evaluation metrics such as Consistency (2.38 to 7.80) and Accuracy (2.34 to 6.93). The results highlight the effectiveness of structured multi-agent perception and reasoning for enhancing robustness, transparency, and automation in intelligent medical imaging systems, enabling integration into autonomous healthcare and robotic diagnostic workflows.

Correlation Is Not Enough: Embedding Human Metadata for Individual Causal Discovery

Ask a pretrained biomedical language model whether "cortisol 28 ug/dL" and "stock-market volatility" are related, and it returns a cosine similarity of 0.83 on a scale where 1.0 means identical. The two share no mechanism. This is not a corner case: every off-the-shelf biomedical encoder we tested (BioBERT, PubMedBERT, BioM-ELECTRA) scores unrelated cross-domain pairs between 0.76 and 0.92 when the answer should be near zero. Accuracy on cross-domain discrimination is 0%. Retrieval systems survive this, because a language model downstream filters the noise. A Large Behavioural Model (LBM), a foundation model whose subject is a person rather than a sentence, does not: it reasons over a graph of a user's life and treats embedding proximity as evidence that two events are causally linked. False proximity writes a false causal edge, and everything downstream inherits the error. Here, embedding geometry is not a tuning knob; it is correctness. We report the fix. A contrastive pass over 72,034 pairs raises PubMedBERT BIOSSES correlation from 0.633 to 0.828 and within-vs-across-domain separation from 1.05x to 1.63x. A second pass, BODHI, mines hard negatives from edges absent in a biomedical knowledge graph and lifts separation to 2.30x and the discrimination gap to +0.392, at a 4.5% BIOSSES cost. On an Intel Xeon 6737P with AMX, OpenVINO cuts single-query latency from 1367 ms to 10 ms (133x) and reaches 555 sentences/sec. One finding contradicts standard advice: FP16 beats INT8 on this silicon at every serving batch size, and we explain why. The same model on a no-AMX Ice Lake instance runs 13-27x slower. We release the benchmark suite, training corpora, the BODHI generator, and the OpenVINO scripts.

A Multimodal Agentic Pathology Co-pilot via Evidence Grounded Reasoning

Pathology is the cornerstone of modern medicine, where accurate decision-making relies heavily on evidence-based practices. While artificial intelligence (AI) has the potential to transform clinical workflows, the intersection of AI and evidence-based medicine remains under-explored, with primitive attempts restricted to text-only general medicine. In this work, we present PathPocket, a multimodal AI agentic co-pilot designed specifically for evidence grounded pathology. We construct the most comprehensive pathology evidence corpus to date, encompassing approximately 110,472 public and authorized documents structured across a rigorous hierarchy of evidence from clinical guideline to expert opinion. From this meticulously graded foundation, we build a large-scale multimodal pathology hypergraph containing over 4.55 million entities and 7.10 million relations. Serving as a robust knowledge engine, this hypergraph provides traceable evidence for a collaborative multi-agent reasoning framework integrating input understanding, evidence retrieval, filtering, and diagnosis generation. This enables PathPocket to seamlessly resolve a wide spectrum of clinical tasks, ranging from text-only queries to complex multimodal diagnostics involving region-of-interest (ROI) and gigapixel whole-slide images (WSIs). We rigorously evaluate the system on a multidimensional benchmark of over 200,000 real-world cases, where it significantly outperforms existing state-of-the-arts. Crucially, extensive user studies demonstrate that PathPocket substantially improves the diagnostic accuracy and confidence of pathologists. By directly grounding pathology interpretations in verifiable literature, PathPocket offers a practical and scalable solution for the future of evidence grounded computational pathology.

Pharmacogenomic Knowledge Graph Augmentation for Graph Neural Network-Based Drug-Drug Interaction Prediction

Graph neural networks (GNNs) applied to drug-drug interaction (DDI) prediction rely exclusively on molecular structure encoded as SMILES-derived graphs. Prior work in this series demonstrated that model performance is bounded by the structural information content of training labels -- an Information Ceiling -- that architectural refinements alone cannot overcome. The present study investigates whether pharmacogenomic prior knowledge from the PharmGKB database partially closes this ceiling by providing metabolic pathway context that is independent of, and complementary to, molecular structure. Cytochrome P450 (CYP) enzyme substrate, inhibitor, and inducer annotations for four clinically relevant isoforms (CYP2D6, CYP3A4, CYP2C19, CYP2C9) are extracted and incorporated as a 12-dimensional feature vector concatenated to the molecular embedding prior to interaction prediction. Experiments are conducted under both pair-level and drug-level data splits to quantify generalization to unseen drugs. Results indicate that knowledge graph (KG) augmentation substantially improves DDI type classification under pair-level split conditions (F1-macro: 0.532 vs. 0.241 baseline), while binary interaction detection and drug-level generalization remain bounded by the Information Ceiling (AUC inflation: 0.224 vs. 0.250 baseline). Mechanistic validation on strictly held-out compounds confirms that augmentation preferentially improves CYP2C9-mediated interaction prediction, with probabilities increasing from 0.033-0.117 (baseline) to 0.560-0.586 (KG-augmented). An extension to single-molecule toxicity prediction on the Tox21 benchmark confirms that the effect is contingent on pharmacogenomic annotation coverage. These findings motivate the multimodal framework proposed for the subsequent study in this series.

Evidence-Based Intelligent Diagnostic and Therapeutic Visualization System with Large Language Models: Multi-Turn Interaction and Multimodal Treatment Plan Generation

Aim: Existing AI-assisted traditional Chinese medicine diagnostic tools suffer from opaque reasoning processes, passive interaction, and limited treatment plan presentation. This study proposes a knowledge-enhanced visual diagnostic system to improve the transparency and interpretability of syndrome differentiation and treatment. Methods: The system is built upon a Neo4j knowledge graph comprising 241 syndromes, 1,263 symptoms, and 2,485 relations. It incorporates a four-stage symptom matching pipeline (exact, semantic, fuzzy, and large language model verification), an information gain-driven proactive questioning strategy optimized with genetic algorithms, and a multimodal treatment presentation integrating artificial intelligence-generated illustrations, three-dimensional meridian-acupoint models, and evidence-based literature. Results: Knowledge graph constraints reduced non-standard outputs by 32%. Case studies validated the effectiveness of the interactive workflow across patient self-assessment, clinician-assisted diagnosis, and traditional Chinese medicine education. Automated paired-comparison evaluation across 30 cases further demonstrated significant improvements in diagnostic trust (Cohen's d = 1.82, p < 0.001), reduced cognitive load (improvements in four of five dimensions), and higher credibility of evidence-based references (4.21 vs. 2.95). Conclusions: The proposed system enhances the transparency of traditional Chinese medicine diagnostic reasoning and the interpretability of treatment plans through knowledge graph-driven visualization and multimodal interaction, offering a practical solution for trustworthy artificial intelligence-assisted traditional Chinese medicine applications.

Trajectory-Aware Clinical Risk Prediction via Severity-Grounded Knowledge Graphs and Retrieval-Augmented Generation

While Electronic Health Records (EHRs) offer a wealth of clinical data, effectively augmenting a patient's records with heterogeneous external knowledge to predict the patient's clinical risk remains a significant challenge. Existing methods fail to capture disease severity, treatment responses, and nuanced clinical progression, due to data sparsity and the underutilization of unstructured clinical notes. To address these challenges, we propose TRACER (a trajectory-aware and clinically grounded prediction framework) that (1) constructs a medical knowledge graph enriched with severity information from medical literature, (2) retrieves clinically relevant, severity-weighted paths of a patient's progression from the knowledge graph, (3) extracts clinically relevant events from unstructured clinical notes, and (4) augments patient context with similar peer cases. Experiments on the MIMIC-III and MIMIC-IV datasets demonstrate large gains over state-of-the-art baselines, with up to 28.5% increase in Macro F1 score for the mortality prediction task, and 19.7% increase for the readmission prediction task.