Daily Papers

The 7-point checklist (7PCL) is a widely used diagnostic tool in dermoscopy for identifying malignant melanoma by assigning point values to seven specific attributes. However, the traditional 7PCL is limited to distinguishing between malignant melanoma and melanocytic Nevi, and falls short in scenarios where multiple skin diseases with appearances similar to melanoma coexist. To address this limitation, we propose a novel diagnostic framework that integrates a clinical knowledge-based topological graph (CKTG) with a gradient diagnostic strategy featuring a data-driven weighting system (GD-DDW). The CKTG captures both the internal and external relationships among the 7PCL attributes, while the GD-DDW emulates dermatologists' diagnostic processes, prioritizing visual observation before making predictions. Additionally, we introduce a multimodal feature extraction approach leveraging a dual-attention mechanism to enhance feature extraction through cross-modal interaction and unimodal collaboration. This method incorporates meta-information to uncover interactions between clinical data and image features, ensuring more accurate and robust predictions. Our approach, evaluated on the EDRA dataset, achieved an average AUC of 88.6%, demonstrating superior performance in melanoma detection and feature prediction. This integrated system provides data-driven benchmarks for clinicians, significantly enhancing the precision of melanoma diagnosis.

While Large Language Models (LLMs) achieve expert-level performance on standard medical benchmarks through single-hop factual recall, they severely struggle with the complex, multi-hop diagnostic reasoning required in real-world clinical settings. A primary obstacle is "shortcut learning", where models exploit highly connected, generic hub nodes (e.g., "inflammation") in knowledge graphs to bypass authentic micro-pathological cascades. To address this, we introduce ShatterMed-QA, a bilingual benchmark of 10,558 multi-hop clinical questions designed to rigorously evaluate deep diagnostic reasoning. Our framework constructs a topology-regularized medical Knowledge Graph using a novel k-Shattering algorithm, which physically prunes generic hubs to explicitly sever logical shortcuts. We synthesize the evaluation vignettes by applying implicit bridge entity masking and topology-driven hard negative sampling, forcing models to navigate biologically plausible distractors without relying on superficial elimination. Comprehensive evaluations of 21 LLMs reveal massive performance degradation on our multi-hop tasks, particularly among domain-specific models. Crucially, restoring the masked evidence via Retrieval-Augmented Generation (RAG) triggers near-universal performance recovery, validating ShatterMed-QA's structural fidelity and proving its efficacy in diagnosing the fundamental reasoning deficits of current medical AI. Explore the dataset, interactive examples, and full leaderboards at our project website: https://shattermed-qa-web.vercel.app/

Medical tasks such as diagnosis and treatment planning require precise and complex reasoning, particularly in life-critical domains. Unlike mathematical reasoning, medical reasoning demands meticulous, verifiable thought processes to ensure reliability and accuracy. However, there is a notable lack of datasets that provide transparent, step-by-step reasoning to validate and enhance the medical reasoning ability of AI models. To bridge this gap, we introduce MedReason, a large-scale high-quality medical reasoning dataset designed to enable faithful and explainable medical problem-solving in large language models (LLMs). We utilize a structured medical knowledge graph (KG) to convert clinical QA pairs into logical chains of reasoning, or ``thinking paths'', which trace connections from question elements to answers via relevant KG entities. Each path is validated for consistency with clinical logic and evidence-based medicine. Our pipeline generates detailed reasoning for various medical questions from 7 medical datasets, resulting in a dataset of 32,682 question-answer pairs, each with detailed, step-by-step explanations. Experiments demonstrate that fine-tuning with our dataset consistently boosts medical problem-solving capabilities, achieving significant gains of up to 7.7% for DeepSeek-Ditill-8B. Our top-performing model, MedReason-8B, outperforms the Huatuo-o1-8B, a state-of-the-art medical reasoning model, by up to 4.2% on the clinical benchmark MedBullets. We also engage medical professionals from diverse specialties to assess our dataset's quality, ensuring MedReason offers accurate and coherent medical reasoning. Our data, models, and code will be publicly available.

Large language models (LLMs) have recently showcased remarkable capabilities, spanning a wide range of tasks and applications, including those in the medical domain. Models like GPT-4 excel in medical question answering but may face challenges in the lack of interpretability when handling complex tasks in real clinical settings. We thus introduce the diagnostic reasoning dataset for clinical notes (DiReCT), aiming at evaluating the reasoning ability and interpretability of LLMs compared to human doctors. It contains 511 clinical notes, each meticulously annotated by physicians, detailing the diagnostic reasoning process from observations in a clinical note to the final diagnosis. Additionally, a diagnostic knowledge graph is provided to offer essential knowledge for reasoning, which may not be covered in the training data of existing LLMs. Evaluations of leading LLMs on DiReCT bring out a significant gap between their reasoning ability and that of human doctors, highlighting the critical need for models that can reason effectively in real-world clinical scenarios.

Medical deep learning models depend heavily on domain-specific knowledge to perform well on knowledge-intensive clinical tasks. Prior work has primarily leveraged unimodal knowledge graphs, such as the Unified Medical Language System (UMLS), to enhance model performance. However, integrating multimodal medical knowledge graphs remains largely underexplored, mainly due to the lack of resources linking imaging data with clinical concepts. To address this gap, we propose MEDMKG, a Medical Multimodal Knowledge Graph that unifies visual and textual medical information through a multi-stage construction pipeline. MEDMKG fuses the rich multimodal data from MIMIC-CXR with the structured clinical knowledge from UMLS, utilizing both rule-based tools and large language models for accurate concept extraction and relationship modeling. To ensure graph quality and compactness, we introduce Neighbor-aware Filtering (NaF), a novel filtering algorithm tailored for multimodal knowledge graphs. We evaluate MEDMKG across three tasks under two experimental settings, benchmarking twenty-four baseline methods and four state-of-the-art vision-language backbones on six datasets. Results show that MEDMKG not only improves performance in downstream medical tasks but also offers a strong foundation for developing adaptive and robust strategies for multimodal knowledge integration in medical artificial intelligence.

The rapid expansion of medical literature presents growing challenges for structuring and integrating domain knowledge at scale. Knowledge Graphs (KGs) offer a promising solution by enabling efficient retrieval, automated reasoning, and knowledge discovery. However, current KG construction methods often rely on supervised pipelines with limited generalizability or naively aggregate outputs from Large Language Models (LLMs), treating biomedical corpora as static and ignoring the temporal dynamics and contextual uncertainty of evolving knowledge. To address these limitations, we introduce MedKGent, a LLM agent framework for constructing temporally evolving medical KGs. Leveraging over 10 million PubMed abstracts published between 1975 and 2023, we simulate the emergence of biomedical knowledge via a fine-grained daily time series. MedKGent incrementally builds the KG in a day-by-day manner using two specialized agents powered by the Qwen2.5-32B-Instruct model. The Extractor Agent identifies knowledge triples and assigns confidence scores via sampling-based estimation, which are used to filter low-confidence extractions and inform downstream processing. The Constructor Agent incrementally integrates the retained triples into a temporally evolving graph, guided by confidence scores and timestamps to reinforce recurring knowledge and resolve conflicts. The resulting KG contains 156,275 entities and 2,971,384 relational triples. Quality assessments by two SOTA LLMs and three domain experts demonstrate an accuracy approaching 90%, with strong inter-rater agreement. To evaluate downstream utility, we conduct RAG across seven medical question answering benchmarks using five leading LLMs, consistently observing significant improvements over non-augmented baselines. Case studies further demonstrate the KG's value in literature-based drug repurposing via confidence-aware causal inference.

Epilepsy diagnosis and treatment require evidence-intensive reasoning across heterogeneous clinical knowledge, including biosignal patterns, genetic mechanisms, pharmacogenomics, treatment strategies, and patient outcomes. In this work, we present EpiGraph, a large-scale epilepsy knowledge graph and benchmark for evaluating knowledge-augmented clinical reasoning. EpiGraph integrates 48,166 peer-reviewed papers and seven clinical resources into a heterogeneous graph containing 24,324 entities and 32,009 evidence-grounded triplets across five clinical layers. Built upon this graph, EpiBench defines five clinically motivated tasks spanning clinical decision-making, EEG report generation, pharmacogenomic precision medicine, treatment recommendation, and deep research planning. We evaluate six LLMs under both standard and Graph-RAG settings. Results show that integrating EpiGraph consistently improves performance across all tasks, with the largest gains observed in pharmacogenomic reasoning (+30--41\%). Our findings demonstrate that structured epilepsy knowledge substantially enhances evidence-grounded clinical reasoning and provides a practical benchmark framework for evaluating knowledge-augmented LLMs in real-world neurological settings. Our code is available at: https://github.com/LabRAI/EEG-KG.

Electronic Health Records (EHR) are high-dimensional data with implicit connections among thousands of medical concepts. These connections, for instance, the co-occurrence of diseases and lab-disease correlations can be informative when only a subset of these variables is documented by the clinician. A feasible approach to improving the representation learning of EHR data is to associate relevant medical concepts and utilize these connections. Existing medical ontologies can be the reference for EHR structures, but they place numerous constraints on the data source. Recent progress on graph neural networks (GNN) enables end-to-end learning of topological structures for non-grid or non-sequential data. However, there are problems to be addressed on how to learn the medical graph adaptively and how to understand the effect of the medical graph on representation learning. In this paper, we propose a variationally regularized encoder-decoder graph network that achieves more robustness in graph structure learning by regularizing node representations. Our model outperforms the existing graph and non-graph based methods in various EHR predictive tasks based on both public data and real-world clinical data. Besides the improvements in empirical experiment performances, we provide an interpretation of the effect of variational regularization compared to standard graph neural network, using singular value analysis.

Answering complex real-world questions often requires accurate retrieval from textual knowledge graphs (TKGs). The scarcity of annotated data, along with intricate topological structures, makes this task particularly challenging. As the nature of relational path information could enhance the inference ability of Large Language Models (LLMs), efficiently retrieving more complex relational path information from TKGs presents another key challenge. To tackle these challenges, we first develop a Dataset for LLMs Complex Reasoning over Textual Knowledge Graphs (RiTeK) with a broad topological structure coverage.We synthesize realistic user queries that integrate diverse topological structures, relational information, and complex textual descriptions. We conduct rigorous expert evaluation to validate the quality of our synthesized queries. And then, we introduce an enhanced Monte Carlo Tree Search (MCTS) method, Relational MCTS, to automatically extract relational path information from textual graphs for specific queries. Our dataset mainly covers the medical domain as the relation types and entity are complex and publicly available. Experimental results indicate that RiTeK poses significant challenges for current retrieval and LLM systems, while the proposed Relational MCTS method enhances LLM inference ability and achieves state-of-the-art performance on RiTeK.

Vision-Language Models (VLMs) are advancing computational pathology with superior visual understanding capabilities. However, current systems often reduce diagnosis to directly output conclusions without verifiable evidence-linked reasoning, which severely limits clinical trust and hinders expert error rectification. To address these barriers, we construct PathReasoner, the first large-scale dataset of whole-slide image (WSI) reasoning. Unlike previous work reliant on unverified distillation, we develop a rigorous knowledge-guided generation pipeline. By leveraging medical knowledge graphs, we explicitly align structured pathological findings and clinical reasoning with diagnoses, generating over 20K high-quality instructional samples. Based on the database, we propose PathReasoner-R1, which synergizes trajectory-masked supervised fine-tuning with reasoning-oriented reinforcement learning to instill structured chain-of-thought capabilities. To ensure medical rigor, we engineer a knowledge-aware multi-granular reward function incorporating an Entity Reward mechanism strictly aligned with knowledge graphs. This effectively guides the model to optimize for logical consistency rather than mere outcome matching, thereby enhancing robustness. Extensive experiments demonstrate that PathReasoner-R1 achieves state-of-the-art performance on both PathReasoner and public benchmarks across various image scales, equipping pathology models with transparent, clinically grounded reasoning capabilities. Dataset and code are available at https://github.com/cyclexfy/PathReasoner-R1.

Biomedical knowledge graphs (KGs) are widely used in the life sciences, yet many are derived from unstructured documents and therefore lack schema-level constrains, whereas graphs assembled from structured resources are difficult to harmonize into a unified representation. We present OptimusKG, a multimodal biomedical labeled property graph (LPG) built from structured and semi-structured resources to preserve factual, type-specific metadata across molecular, anatomical, clinical, and environmental domains. OptimusKG contains 190,531 nodes across 10 entity types, 21,813,816 edges across 26 relation types, and 67,249,863 property instances encoding 110,276,843 values across 150 distinct property keys, derived from 18 ontologies and controlled vocabularies. The graph enforces a top-level schema for nodes and edges and retains granular, type-specific properties, cross-references, and provenance across molecular, anatomical, clinical, and environmental domains. We assessed the validity of OptimusKG by evaluating whether graph relationships are supported by evidence from the scientific literature using a multimodal agent, PaperQA3. PaperQA3 identified supporting evidence for 70.0% of sampled edges, whereas 83.4% of sampled false edges received no supporting evidence. Edges without literature support were concentrated in associations derived from experimental and functional genomics resources, suggesting that OptimusKG captures biomedical knowledge that may precede synthesis in the scientific literature. OptimusKG is distributed as Apache Parquet files, providing a standardized resource for graph-based machine learning, knowledge-grounded retrieval with large language models, and biomedical discovery use cases such as hypothesis generation.

This paper explores the advancements and applications of large-scale models in the medical field, with a particular focus on Medical Large Models (MedLMs). These models, encompassing Large Language Models (LLMs), Vision Models, 3D Large Models, and Multimodal Models, are revolutionizing healthcare by enhancing disease prediction, diagnostic assistance, personalized treatment planning, and drug discovery. The integration of graph neural networks in medical knowledge graphs and drug discovery highlights the potential of Large Graph Models (LGMs) in understanding complex biomedical relationships. The study also emphasizes the transformative role of Vision-Language Models (VLMs) and 3D Large Models in medical image analysis, anatomical modeling, and prosthetic design. Despite the challenges, these technologies are setting new benchmarks in medical innovation, improving diagnostic accuracy, and paving the way for personalized healthcare solutions. This paper aims to provide a comprehensive overview of the current state and future directions of large models in medicine, underscoring their significance in advancing global health.

Knowledge Graph (KG) plays a crucial role in Medical Report Generation (MRG) because it reveals the relations among diseases and thus can be utilized to guide the generation process. However, constructing a comprehensive KG is labor-intensive and its applications on the MRG process are under-explored. In this study, we establish a complete KG on chest X-ray imaging that includes 137 types of diseases and abnormalities. Based on this KG, we find that the current MRG data sets exhibit a long-tailed problem in disease distribution. To mitigate this problem, we introduce a novel augmentation strategy that enhances the representation of disease types in the tail-end of the distribution. We further design a two-stage MRG approach, where a classifier is first trained to detect whether the input images exhibit any abnormalities. The classified images are then independently fed into two transformer-based generators, namely, ``disease-specific generator" and ``disease-free generator" to generate the corresponding reports. To enhance the clinical evaluation of whether the generated reports correctly describe the diseases appearing in the input image, we propose diverse sensitivity (DS), a new metric that checks whether generated diseases match ground truth and measures the diversity of all generated diseases. Results show that the proposed two-stage generation framework and augmentation strategies improve DS by a considerable margin, indicating a notable reduction in the long-tailed problem associated with under-represented diseases.

Automated clinical diagnosis remains a core challenge in medical AI, which usually requires models to integrate multi-modal data and reason across complex, case-specific contexts. Although recent methods have advanced medical report generation (MRG) and visual question answering (VQA) with medical vision-language models (VLMs), these methods, however, predominantly operate under a sample-isolated inference paradigm, as such processing cases independently without access to longitudinal electronic health records (EHRs) or structurally related patient examples. This paradigm limits reasoning to image-derived information alone, which ignores external complementary medical evidence for potentially more accurate diagnosis. To overcome this limitation, we propose HyperWalker, a Deep Diagnosis framework that reformulates clinical reasoning via dynamic hypergraphs and test-time training. First, we construct a dynamic hypergraph, termed iBrochure, to model the structural heterogeneity of EHR data and implicit high-order associations among multimodal clinical information. Within this hypergraph, a reinforcement learning agent, Walker, navigates to and identifies optimal diagnostic paths. To ensure comprehensive coverage of diverse clinical characteristics in test samples, we incorporate a linger mechanism, a multi-hop orthogonal retrieval strategy that iteratively selects clinically complementary neighborhood cases reflecting distinct clinical attributes. Experiments on MRG with MIMIC and medical VQA on EHRXQA demonstrate that HyperWalker achieves state-of-the-art performance. Code is available at: https://github.com/Bean-Young/HyperWalker

Biomedical knowledge is uniquely complex and structured, requiring distinct reasoning strategies compared to other scientific disciplines like physics or chemistry. Biomedical scientists do not rely on a single approach to reasoning; instead, they use various strategies, including rule-based, prototype-based, and case-based reasoning. This diversity calls for flexible approaches that accommodate multiple reasoning strategies while leveraging in-domain knowledge. We introduce KGARevion, a knowledge graph (KG) based agent designed to address the complexity of knowledge-intensive medical queries. Upon receiving a query, KGARevion generates relevant triplets by using the knowledge base of the LLM. These triplets are then verified against a grounded KG to filter out erroneous information and ensure that only accurate, relevant data contribute to the final answer. Unlike RAG-based models, this multi-step process ensures robustness in reasoning while adapting to different models of medical reasoning. Evaluations on four gold-standard medical QA datasets show that KGARevion improves accuracy by over 5.2%, outperforming 15 models in handling complex medical questions. To test its capabilities, we curated three new medical QA datasets with varying levels of semantic complexity, where KGARevion achieved a 10.4% improvement in accuracy.

Deep learning has enabled the development of highly robust foundation models for various pathological tasks across diverse diseases and patient cohorts. Among these models, vision-language pre-training, which leverages large-scale paired data to align pathology image and text embedding spaces, and provides a novel zero-shot paradigm for downstream tasks. However, existing models have been primarily data-driven and lack the incorporation of domain-specific knowledge, which limits their performance in cancer diagnosis, especially for rare tumor subtypes. To address this limitation, we establish a Knowledge-enhanced Pathology (KEEP) foundation model that harnesses disease knowledge to facilitate vision-language pre-training. Specifically, we first construct a disease knowledge graph (KG) that covers 11,454 human diseases with 139,143 disease attributes, including synonyms, definitions, and hypernym relations. We then systematically reorganize the millions of publicly available noisy pathology image-text pairs, into 143K well-structured semantic groups linked through the hierarchical relations of the disease KG. To derive more nuanced image and text representations, we propose a novel knowledge-enhanced vision-language pre-training approach that integrates disease knowledge into the alignment within hierarchical semantic groups instead of unstructured image-text pairs. Validated on 18 diverse benchmarks with more than 14,000 whole slide images (WSIs), KEEP achieves state-of-the-art performance in zero-shot cancer diagnostic tasks. Notably, for cancer detection, KEEP demonstrates an average sensitivity of 89.8% at a specificity of 95.0% across 7 cancer types. For cancer subtyping, KEEP achieves a median balanced accuracy of 0.456 in subtyping 30 rare brain cancers, indicating strong generalizability for diagnosing rare tumors.

Large Language Models (LLMs) have significantly advanced medical question-answering by leveraging extensive clinical data and medical literature. However, the rapid evolution of medical knowledge and the labor-intensive process of manually updating domain-specific resources pose challenges to the reliability of these systems. To address this, we introduce Agentic Medical Graph-RAG (AMG-RAG), a comprehensive framework that automates the construction and continuous updating of medical knowledge graphs, integrates reasoning, and retrieves current external evidence, such as PubMed and WikiSearch. By dynamically linking new findings and complex medical concepts, AMG-RAG not only improves accuracy but also enhances interpretability in medical queries. Evaluations on the MEDQA and MEDMCQA benchmarks demonstrate the effectiveness of AMG-RAG, achieving an F1 score of 74.1 percent on MEDQA and an accuracy of 66.34 percent on MEDMCQA, outperforming both comparable models and those 10 to 100 times larger. Notably, these improvements are achieved without increasing computational overhead, highlighting the critical role of automated knowledge graph generation and external evidence retrieval in delivering up-to-date, trustworthy medical insights.

Human knowledge provides a formal understanding of the world. Knowledge graphs that represent structural relations between entities have become an increasingly popular research direction towards cognition and human-level intelligence. In this survey, we provide a comprehensive review of knowledge graph covering overall research topics about 1) knowledge graph representation learning, 2) knowledge acquisition and completion, 3) temporal knowledge graph, and 4) knowledge-aware applications, and summarize recent breakthroughs and perspective directions to facilitate future research. We propose a full-view categorization and new taxonomies on these topics. Knowledge graph embedding is organized from four aspects of representation space, scoring function, encoding models, and auxiliary information. For knowledge acquisition, especially knowledge graph completion, embedding methods, path inference, and logical rule reasoning, are reviewed. We further explore several emerging topics, including meta relational learning, commonsense reasoning, and temporal knowledge graphs. To facilitate future research on knowledge graphs, we also provide a curated collection of datasets and open-source libraries on different tasks. In the end, we have a thorough outlook on several promising research directions.

Clinical diagnosis is a highly specialized discipline requiring both domain expertise and strict adherence to rigorous guidelines. While current AI-driven medical research predominantly focuses on knowledge graphs or natural text pretraining paradigms to incorporate medical knowledge, these approaches primarily rely on implicitly encoded knowledge within model parameters, neglecting task-specific knowledge required by diverse downstream tasks. To address this limitation, we propose Retrieval-Augmented Diagnosis (RAD), a novel framework that explicitly injects external knowledge into multimodal models directly on downstream tasks. Specifically, RAD operates through three key mechanisms: retrieval and refinement of disease-centered knowledge from multiple medical sources, a guideline-enhanced contrastive loss that constrains the latent distance between multi-modal features and guideline knowledge, and the dual transformer decoder that employs guidelines as queries to steer cross-modal fusion, aligning the models with clinical diagnostic workflows from guideline acquisition to feature extraction and decision-making. Moreover, recognizing the lack of quantitative evaluation of interpretability for multimodal diagnostic models, we introduce a set of criteria to assess the interpretability from both image and text perspectives. Extensive evaluations across four datasets with different anatomies demonstrate RAD's generalizability, achieving state-of-the-art performance. Furthermore, RAD enables the model to concentrate more precisely on abnormal regions and critical indicators, ensuring evidence-based, trustworthy diagnosis. Our code is available at https://github.com/tdlhl/RAD.

Knowledge graph embedding involves learning representations of entities -- the vertices of the graph -- and relations -- the edges of the graph -- such that the resulting representations encode the known factual information represented by the knowledge graph and can be used in the inference of new relations. We show that knowledge graph embedding is naturally expressed in the topological and categorical language of cellular sheaves: a knowledge graph embedding can be described as an approximate global section of an appropriate knowledge sheaf over the graph, with consistency constraints induced by the knowledge graph's schema. This approach provides a generalized framework for reasoning about knowledge graph embedding models and allows for the expression of a wide range of prior constraints on embeddings. Further, the resulting embeddings can be easily adapted for reasoning over composite relations without special training. We implement these ideas to highlight the benefits of the extensions inspired by this new perspective.

Recent advancements in Large Language Models (LLMs) have demonstrated significant promise in clinical diagnosis. However, current models struggle to emulate the iterative, diagnostic hypothesis-driven reasoning of real clinical scenarios. Specifically, current LLMs suffer from three critical limitations: (1) generating hallucinated medical content due to weak grounding in verified knowledge, (2) asking redundant or inefficient questions rather than discriminative ones that hinder diagnostic progress, and (3) losing coherence over multi-turn dialogues, leading to contradictory or inconsistent conclusions. To address these challenges, we propose MedKGI, a diagnostic framework grounded in clinical practices. MedKGI integrates a medical knowledge graph (KG) to constrain reasoning to validated medical ontologies, selects questions based on information gain to maximize diagnostic efficiency, and adopts an OSCE-format structured state to maintain consistent evidence tracking across turns. Experiments on clinical benchmarks show that MedKGI outperforms strong LLM baselines in both diagnostic accuracy and inquiry efficiency, improving dialogue efficiency by 30% on average while maintaining state-of-the-art accuracy.

Medical image classification requires not only high predictive performance but also interpretability to ensure clinical trust and adoption. Graph Neural Networks (GNNs) offer a powerful framework for modeling relational structures within datasets; however, standard GNNs often operate as black boxes, limiting transparency and usability, particularly in clinical settings. In this work, we present an interpretable graph-based learning framework named FireGNN that integrates trainable fuzzy rules into GNNs for medical image classification. These rules embed topological descriptors - node degree, clustering coefficient, and label agreement - using learnable thresholds and sharpness parameters to enable intrinsic symbolic reasoning. Additionally, we explore auxiliary self-supervised tasks (e.g., homophily prediction, similarity entropy) as a benchmark to evaluate the contribution of topological learning. Our fuzzy-rule-enhanced model achieves strong performance across five MedMNIST benchmarks and the synthetic dataset MorphoMNIST, while also generating interpretable rule-based explanations. To our knowledge, this is the first integration of trainable fuzzy rules within a GNN. Source Code: https://github.com/basiralab/FireGNN

Motivation: Biomedical knowledge graphs (KGs) are crucial for drug discovery and disease understanding, yet their completion and reasoning are challenging. Knowledge Embedding (KE) methods capture global semantics but struggle with dynamic structural integration, while Graph Neural Networks (GNNs) excel locally but often lack semantic understanding. Even ensemble approaches, including those leveraging language models, often fail to achieve a deep, adaptive, and synergistic co-evolution between semantic comprehension and structural learning. Addressing this critical gap in fostering continuous, reciprocal refinement between these two aspects in complex biomedical KGs is paramount. Results: We introduce BioGraphFusion, a novel framework for deeply synergistic semantic and structural learning. BioGraphFusion establishes a global semantic foundation via tensor decomposition, guiding an LSTM-driven mechanism to dynamically refine relation embeddings during graph propagation. This fosters adaptive interplay between semantic understanding and structural learning, further enhanced by query-guided subgraph construction and a hybrid scoring mechanism. Experiments across three key biomedical tasks demonstrate BioGraphFusion's superior performance over state-of-the-art KE, GNN, and ensemble models. A case study on Cutaneous Malignant Melanoma 1 (CMM1) highlights its ability to unveil biologically meaningful pathways. Availability and Implementation: Source code and all training data are freely available for download at https://github.com/Y-TARL/BioGraphFusion. Supplementary information: Supplementary data are available at Bioinformatics online.

Retrieval-augmented generation (RAG) is a well-suited technique for retrieving privacy-sensitive Electronic Health Records (EHR). It can serve as a key module of the healthcare copilot, helping reduce misdiagnosis for healthcare practitioners and patients. However, the diagnostic accuracy and specificity of existing heuristic-based RAG models used in the medical domain are inadequate, particularly for diseases with similar manifestations. This paper proposes MedRAG, a RAG model enhanced by knowledge graph (KG)-elicited reasoning for the medical domain that retrieves diagnosis and treatment recommendations based on manifestations. MedRAG systematically constructs a comprehensive four-tier hierarchical diagnostic KG encompassing critical diagnostic differences of various diseases. These differences are dynamically integrated with similar EHRs retrieved from an EHR database, and reasoned within a large language model. This process enables more accurate and specific decision support, while also proactively providing follow-up questions to enhance personalized medical decision-making. MedRAG is evaluated on both a public dataset DDXPlus and a private chronic pain diagnostic dataset (CPDD) collected from Tan Tock Seng Hospital, and its performance is compared against various existing RAG methods. Experimental results show that, leveraging the information integration and relational abilities of the KG, our MedRAG provides more specific diagnostic insights and outperforms state-of-the-art models in reducing misdiagnosis rates. Our code will be available at https://github.com/SNOWTEAM2023/MedRAG

Biomedical Knowledge Graphs (BKGs) integrate diverse datasets to elucidate complex relationships within the biomedical field. Effective link prediction on these graphs can uncover valuable connections, such as potential novel drug-disease relations. We introduce a novel multimodal approach that unifies embeddings from specialized Language Models (LMs) with Graph Contrastive Learning (GCL) to enhance intra-entity relationships while employing a Knowledge Graph Embedding (KGE) model to capture inter-entity relationships for effective link prediction. To address limitations in existing BKGs, we present PrimeKG++, an enriched knowledge graph incorporating multimodal data, including biological sequences and textual descriptions for each entity type. By combining semantic and relational information in a unified representation, our approach demonstrates strong generalizability, enabling accurate link predictions even for unseen nodes. Experimental results on PrimeKG++ and the DrugBank drug-target interaction dataset demonstrate the effectiveness and robustness of our method across diverse biomedical datasets. Our source code, pre-trained models, and data are publicly available at https://github.com/HySonLab/BioMedKG

Clinical case formulation organizes patient symptoms and psychosocial factors into causal models, often using the 5P framework. However, constructing such graphs from therapy transcripts is time consuming and varies across clinicians. We present InsightFlow, an LLM based approach that automatically generates 5P aligned causal graphs from patient-therapist dialogues. Using 46 psychotherapy intake transcripts annotated by clinical experts, we evaluate LLM generated graphs against human formulations using structural (NetSimile), semantic (embedding similarity), and expert rated clinical criteria. The generated graphs show structural similarity comparable to inter annotator agreement and high semantic alignment with human graphs. Expert evaluations rate the outputs as moderately complete, consistent, and clinically useful. While LLM graphs tend to form more interconnected structures compared to the chain like patterns of human graphs, overall complexity and content coverage are similar. These results suggest that LLMs can produce clinically meaningful case formulation graphs within the natural variability of expert practice. InsightFlow highlights the potential of automated causal modeling to augment clinical workflows, with future work needed to improve temporal reasoning and reduce redundancy.

Biomedical knowledge graphs (BioMedKGs) are essential infrastructures for biomedical and healthcare big data and artificial intelligence (AI), facilitating natural language processing, model development, and data exchange. For decades, these knowledge graphs have been developed via expert curation; however, this method can no longer keep up with today's AI development, and a transition to algorithmically generated BioMedKGs is necessary. In this work, we introduce the Biomedical Informatics Ontology System (BIOS), the first large-scale publicly available BioMedKG generated completely by machine learning algorithms. BIOS currently contains 4.1 million concepts, 7.4 million terms in two languages, and 7.3 million relation triplets. We present the methodology for developing BIOS, including the curation of raw biomedical terms, computational identification of synonymous terms and aggregation of these terms to create concept nodes, semantic type classification of the concepts, relation identification, and biomedical machine translation. We provide statistics on the current BIOS content and perform preliminary assessments of term quality, synonym grouping, and relation extraction. The results suggest that machine learning-based BioMedKG development is a viable alternative to traditional expert curation.

Clinical predictive models often rely on patients' electronic health records (EHR), but integrating medical knowledge to enhance predictions and decision-making is challenging. This is because personalized predictions require personalized knowledge graphs (KGs), which are difficult to generate from patient EHR data. To address this, we propose GraphCare, an open-world framework that uses external KGs to improve EHR-based predictions. Our method extracts knowledge from large language models (LLMs) and external biomedical KGs to build patient-specific KGs, which are then used to train our proposed Bi-attention AugmenTed (BAT) graph neural network (GNN) for healthcare predictions. On two public datasets, MIMIC-III and MIMIC-IV, GraphCare surpasses baselines in four vital healthcare prediction tasks: mortality, readmission, length of stay (LOS), and drug recommendation. On MIMIC-III, it boosts AUROC by 17.6\% and 6.6\% for mortality and readmission, and F1-score by 7.9\% and 10.8\% for LOS and drug recommendation, respectively. Notably, GraphCare demonstrates a substantial edge in scenarios with limited data availability. Our findings highlight the potential of using external KGs in healthcare prediction tasks and demonstrate the promise of GraphCare in generating personalized KGs for promoting personalized medicine.

Integrating Large Language Models (LLMs) in healthcare diagnosis demands systematic frameworks that can handle complex medical scenarios while maintaining specialized expertise. We present KG4Diagnosis, a novel hierarchical multi-agent framework that combines LLMs with automated knowledge graph construction, encompassing 362 common diseases across medical specialties. Our framework mirrors real-world medical systems through a two-tier architecture: a general practitioner (GP) agent for initial assessment and triage, coordinating with specialized agents for in-depth diagnosis in specific domains. The core innovation lies in our end-to-end knowledge graph generation methodology, incorporating: (1) semantic-driven entity and relation extraction optimized for medical terminology, (2) multi-dimensional decision relationship reconstruction from unstructured medical texts, and (3) human-guided reasoning for knowledge expansion. KG4Diagnosis serves as an extensible foundation for specialized medical diagnosis systems, with capabilities to incorporate new diseases and medical knowledge. The framework's modular design enables seamless integration of domain-specific enhancements, making it valuable for developing targeted medical diagnosis systems. We provide architectural guidelines and protocols to facilitate adoption across medical contexts.

The drug development pipeline for a new compound can last 10-20 years and cost over 10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on biomedical knowledge graph representations have recently yielded new drug repurposing hypotheses. In this study, we present a novel, disease-specific hypergraph representation learning technique to derive contextual embeddings of biological pathways of various lengths but that all start at any given drug and all end at the disease of interest. Further, we extend this method to multi-disease hypergraphs. To determine the repurposing potential of each of the 1,522 drugs, we derive drug-specific distributions of cosine similarity values and ultimately consider the median for ranking. Cosine similarity values are computed between (1) all biological pathways starting at the considered drug and ending at the disease of interest and (2) all biological pathways starting at drugs currently prescribed against that disease and ending at the disease of interest. We illustrate our approach with Alzheimer's disease (AD) and two of its risk factors: hypertension (HTN) and type 2 diabetes (T2D). We compare each drug's rank across four hypergraph settings (single- or multi-disease): AD only, AD + HTN, AD + T2D, and AD + HTN + T2D. Notably, our framework led to the identification of two promising drugs whose repurposing potential was significantly higher in hypergraphs combining two diseases: dapagliflozin (antidiabetic; moved up, from top 32% to top 7%, across all considered drugs) and debrisoquine (antihypertensive; moved up, from top 76% to top 23%). Our approach serves as a hypothesis generation tool, to be paired with a validation pipeline relying on laboratory experiments and semi-automated parsing of the biomedical literature.

Drug repurposing plays a critical role in accelerating treatment discovery, especially for complex and rare diseases. Biomedical knowledge graphs (KGs), which encode rich clinical associations, have been widely adopted to support this task. However, existing methods largely overlook common-sense biomedical concept knowledge in real-world labs, such as mechanistic priors indicating that certain drugs are fundamentally incompatible with specific treatments. To address this gap, we propose LLaDR, a Large Language Model-assisted framework for Drug Repurposing, which improves the representation of biomedical concepts within KGs. Specifically, we extract semantically enriched treatment-related textual representations of biomedical entities from large language models (LLMs) and use them to fine-tune knowledge graph embedding (KGE) models. By injecting treatment-relevant knowledge into KGE, LLaDR largely improves the representation of biomedical concepts, enhancing semantic understanding of under-studied or complex indications. Experiments based on benchmarks demonstrate that LLaDR achieves state-of-the-art performance across different scenarios, with case studies on Alzheimer's disease further confirming its robustness and effectiveness. Code is available at https://github.com/xiaomingaaa/LLaDR.

Accurately predicting the criticalness of ICU patients (such as in-ICU mortality risk) is vital for early intervention in critical care. However, conventional models often treat each patient in isolation and struggle to exploit the relational structure in Electronic Health Records (EHR). We propose a Similarity-Based Self-Construct Graph Model (SBSCGM) that dynamically builds a patient similarity graph from multi-modal EHR data, and a HybridGraphMedGNN architecture that operates on this graph to predict patient mortality and a continuous criticalness score. SBSCGM uses a hybrid similarity measure (combining feature-based and structural similarities) to connect patients with analogous clinical profiles in real-time. The HybridGraphMedGNN integrates Graph Convolutional Network (GCN), GraphSAGE, and Graph Attention Network (GAT) layers to learn robust patient representations, leveraging both local and global graph patterns. In experiments on 6,000 ICU stays from the MIMIC-III dataset, our model achieves state-of-the-art performance (AUC-ROC 0.94) outperforming baseline classifiers and single-type GNN models. We also demonstrate improved precision/recall and show that the attention mechanism provides interpretable insights into model predictions. Our framework offers a scalable and interpretable solution for critical care risk prediction, with potential to support clinicians in real-world ICU deployment.

Digital twin technology has is anticipated to transform healthcare, enabling personalized medicines and support, earlier diagnoses, simulated treatment outcomes, and optimized surgical plans. Digital twins are readily gaining traction in industries like manufacturing, supply chain logistics, and civil infrastructure. Not in patient care, however. The challenge of modeling complex diseases with multimodal patient data and the computational complexities of analyzing it have stifled digital twin adoption in the biomedical vertical. Yet, these major obstacles can potentially be handled by approaching these models in a different way. This paper proposes a novel framework for addressing the barriers to clinical twin modeling created by computational costs and modeling complexities. We propose structuring patient health data as a knowledge graph and using closed-form continuous-time liquid neural networks, for real-time analytics. By synthesizing multimodal patient data and leveraging the flexibility and efficiency of closed form continuous time networks and knowledge graph ontologies, our approach enables real time insights, personalized medicine, early diagnosis and intervention, and optimal surgical planning. This novel approach provides a comprehensive and adaptable view of patient health along with real-time analytics, paving the way for digital twin simulations and other anticipated benefits in healthcare.

Although the preservation of shape continuity and physiological anatomy is a natural assumption in the segmentation of medical images, it is often neglected by deep learning methods that mostly aim for the statistical modeling of input data as pixels rather than interconnected structures. In biological structures, however, organs are not separate entities; for example, in reality, a severed vessel is an indication of an underlying problem, but traditional segmentation models are not designed to strictly enforce the continuity of anatomy, potentially leading to inaccurate medical diagnoses. To address this issue, we propose a graph-based approach that enforces the continuity and connectivity of anatomical topology in medical images. Our method encodes the continuity of shapes as a graph constraint, ensuring that the network's predictions maintain this continuity. We evaluate our method on two public benchmarks on retinal vessel segmentation, showing significant improvements in connectivity metrics compared to traditional methods while getting better or on-par performance on segmentation metrics.

Large language models (LLMs) have demonstrated strong performance and rapid progress in a wide range of medical reasoning tasks. However, their sequential autoregressive decoding forces inherently parallel clinical reasoning, such as differential diagnosis, into a single linear reasoning path, limiting both efficiency and reliability for complex medical problems. To address this, we propose MedVerse, a reasoning framework for complex medical inference that reformulates medical reasoning as a parallelizable directed acyclic graph (DAG) process based on Petri net theory. The framework adopts a full-stack design across data, model architecture, and system execution. For data creation, we introduce the MedVerse Curator, an automated pipeline that synthesizes knowledge-grounded medical reasoning paths and transforms them into Petri net-structured representations. At the architectural level, we propose a topology-aware attention mechanism with adaptive position indices that supports parallel reasoning while preserving logical consistency. Systematically, we develop a customized inference engine that supports parallel execution without additional overhead. Empirical evaluations show that MedVerse improves strong general-purpose LLMs by up to 8.9%. Compared to specialized medical LLMs, MedVerse achieves comparable performance while delivering a 1.3x reduction in inference latency and a 1.7x increase in generation throughput, enabled by its parallel decoding capability.

Biomedical research is growing at such an exponential pace that scientists, researchers, and practitioners are no more able to cope with the amount of published literature in the domain. The knowledge presented in the literature needs to be systematized in such a way that claims and hypotheses can be easily found, accessed, and validated. Knowledge graphs can provide such a framework for semantic knowledge representation from literature. However, in order to build a knowledge graph, it is necessary to extract knowledge as relationships between biomedical entities and normalize both entities and relationship types. In this paper, we present and compare few rule-based and machine learning-based (Naive Bayes, Random Forests as examples of traditional machine learning methods and DistilBERT, PubMedBERT, T5 and SciFive-based models as examples of modern deep learning transformers) methods for scalable relationship extraction from biomedical literature, and for the integration into the knowledge graphs. We examine how resilient are these various methods to unbalanced and fairly small datasets. Our experiments show that transformer-based models handle well both small (due to pre-training on a large dataset) and unbalanced datasets. The best performing model was the PubMedBERT-based model fine-tuned on balanced data, with a reported F1-score of 0.92. DistilBERT-based model followed with F1-score of 0.89, performing faster and with lower resource requirements. BERT-based models performed better then T5-based generative models.

In Natural Language Processing (NLP), Machine Reading Comprehension (MRC) is the task of answering a question based on a given context. To handle questions in the medical domain, modern language models such as BioBERT, SciBERT and even ChatGPT are trained on vast amounts of in-domain medical corpora. However, in-domain pre-training is expensive in terms of time and resources. In this paper, we propose a resource-efficient approach for injecting domain knowledge into a model without relying on such domain-specific pre-training. Knowledge graphs are powerful resources for accessing medical information. Building on existing work, we introduce a method using Multi-Layer Perceptrons (MLPs) for aligning and integrating embeddings extracted from medical knowledge graphs with the embedding spaces of pre-trained language models (LMs). The aligned embeddings are fused with open-domain LMs BERT and RoBERTa that are fine-tuned for two MRC tasks, span detection (COVID-QA) and multiple-choice questions (PubMedQA). We compare our method to prior techniques that rely on a vocabulary overlap for embedding alignment and show how our method circumvents this requirement to deliver better performance. On both datasets, our method allows BERT/RoBERTa to either perform on par (occasionally exceeding) with stronger domain-specific models or show improvements in general over prior techniques. With the proposed approach, we signal an alternative method to in-domain pre-training to achieve domain proficiency.

Standard Retrieval-Augmented Generation (RAG) relies on chunk-based retrieval, whereas GraphRAG advances this approach by graph-based knowledge representation. However, existing graph-based RAG approaches are constrained by binary relations, as each edge in an ordinary graph connects only two entities, limiting their ability to represent the n-ary relations (n >= 2) in real-world knowledge. In this work, we propose HyperGraphRAG, a novel hypergraph-based RAG method that represents n-ary relational facts via hyperedges, and consists of knowledge hypergraph construction, retrieval, and generation. Experiments across medicine, agriculture, computer science, and law demonstrate that HyperGraphRAG outperforms both standard RAG and previous graph-based RAG methods in answer accuracy, retrieval efficiency, and generation quality.

Integrating heterogeneous biomedical data including imaging, omics, and clinical records supports accurate diagnosis and personalised care. Graph-based models fuse such non-Euclidean data by capturing spatial and relational structure, yet clinical uptake requires regulator-ready interpretability. We present the first technical survey of interpretable graph based models for multimodal biomedical data, covering 26 studies published between Jan 2019 and Sep 2024. Most target disease classification, notably cancer and rely on static graphs from simple similarity measures, while graph-native explainers are rare; post-hoc methods adapted from non-graph domains such as gradient saliency, and SHAP predominate. We group existing approaches into four interpretability families, outline trends such as graph-in-graph hierarchies, knowledge-graph edges, and dynamic topology learning, and perform a practical benchmark. Using an Alzheimer disease cohort, we compare Sensitivity Analysis, Gradient Saliency, SHAP and Graph Masking. SHAP and Sensitivity Analysis recover the broadest set of known AD pathways and Gene-Ontology terms, whereas Gradient Saliency and Graph Masking surface complementary metabolic and transport signatures. Permutation tests show all four beat random gene sets, but with distinct trade-offs: SHAP and Graph Masking offer deeper biology at higher compute cost, while Gradient Saliency and Sensitivity Analysis are quicker though coarser. We also provide a step-by-step flowchart covering graph construction, explainer choice and resource budgeting to help researchers balance transparency and performance. This review synthesises the state of interpretable graph learning for multimodal medicine, benchmarks leading techniques, and charts future directions, from advanced XAI tools to under-studied diseases, serving as a concise reference for method developers and translational scientists.

Recent years have witnessed the resurgence of knowledge engineering which is featured by the fast growth of knowledge graphs. However, most of existing knowledge graphs are represented with pure symbols, which hurts the machine's capability to understand the real world. The multi-modalization of knowledge graphs is an inevitable key step towards the realization of human-level machine intelligence. The results of this endeavor are Multi-modal Knowledge Graphs (MMKGs). In this survey on MMKGs constructed by texts and images, we first give definitions of MMKGs, followed with the preliminaries on multi-modal tasks and techniques. We then systematically review the challenges, progresses and opportunities on the construction and application of MMKGs respectively, with detailed analyses of the strength and weakness of different solutions. We finalize this survey with open research problems relevant to MMKGs.

Recent advances in learning multi-modal representation have witnessed the success in biomedical domains. While established techniques enable handling multi-modal information, the challenges are posed when extended to various clinical modalities and practical modalitymissing setting due to the inherent modality gaps. To tackle these, we propose an innovative Modality-prompted Heterogeneous Graph for Omnimodal Learning (GTP-4o), which embeds the numerous disparate clinical modalities into a unified representation, completes the deficient embedding of missing modality and reformulates the cross-modal learning with a graph-based aggregation. Specially, we establish a heterogeneous graph embedding to explicitly capture the diverse semantic properties on both the modality-specific features (nodes) and the cross-modal relations (edges). Then, we design a modality-prompted completion that enables completing the inadequate graph representation of missing modality through a graph prompting mechanism, which generates hallucination graphic topologies to steer the missing embedding towards the intact representation. Through the completed graph, we meticulously develop a knowledge-guided hierarchical cross-modal aggregation consisting of a global meta-path neighbouring to uncover the potential heterogeneous neighbors along the pathways driven by domain knowledge, and a local multi-relation aggregation module for the comprehensive cross-modal interaction across various heterogeneous relations. We assess the efficacy of our methodology on rigorous benchmarking experiments against prior state-of-the-arts. In a nutshell, GTP-4o presents an initial foray into the intriguing realm of embedding, relating and perceiving the heterogeneous patterns from various clinical modalities holistically via a graph theory. Project page: https://gtp-4-o.github.io/.

Scientific inquiry requires systems-level reasoning that integrates heterogeneous experimental data, cross-domain knowledge, and mechanistic evidence into coherent explanations. While Large Language Models (LLMs) offer inferential capabilities, they often depend on retrieval-augmented contexts that lack structural depth. Traditional Knowledge Graphs (KGs) attempt to bridge this gap, yet their pairwise constraints fail to capture the irreducible higher-order interactions that govern emergent physical behavior. To address this, we introduce a methodology for constructing hypergraph-based knowledge representations that faithfully encode multi-entity relationships. Applied to a corpus of ~1,100 manuscripts on biocomposite scaffolds, our framework constructs a global hypergraph of 161,172 nodes and 320,201 hyperedges, revealing a scale-free topology (power law exponent ~1.23) organized around highly connected conceptual hubs. This representation prevents the combinatorial explosion typical of pairwise expansions and explicitly preserves the co-occurrence context of scientific formulations. We further demonstrate that equipping agentic systems with hypergraph traversal tools, specifically using node-intersection constraints, enables them to bridge semantically distant concepts. By exploiting these higher-order pathways, the system successfully generates grounded mechanistic hypotheses for novel composite materials, such as linking cerium oxide to PCL scaffolds via chitosan intermediates. This work establishes a "teacherless" agentic reasoning system where hypergraph topology acts as a verifiable guardrail, accelerating scientific discovery by uncovering relationships obscured by traditional graph methods.

Embedding-based methods for reasoning in knowledge hypergraphs learn a representation for each entity and relation. Current methods do not capture the procedural rules underlying the relations in the graph. We propose a simple embedding-based model called ReAlE that performs link prediction in knowledge hypergraphs (generalized knowledge graphs) and can represent high-level abstractions in terms of relational algebra operations. We show theoretically that ReAlE is fully expressive and provide proofs and empirical evidence that it can represent a large subset of the primitive relational algebra operations, namely renaming, projection, set union, selection, and set difference. We also verify experimentally that ReAlE outperforms state-of-the-art models in knowledge hypergraph completion, and in representing each of these primitive relational algebra operations. For the latter experiment, we generate a synthetic knowledge hypergraph, for which we design an algorithm based on the Erdos-R'enyi model for generating random graphs.

We develop graph-based methods for semi-supervised learning based on label propagation on a data similarity graph. When data is abundant or arrive in a stream, the problems of computation and data storage arise for any graph-based method. We propose a fast approximate online algorithm that solves for the harmonic solution on an approximate graph. We show, both empirically and theoretically, that good behavior can be achieved by collapsing nearby points into a set of local representative points that minimize distortion. Moreover, we regularize the harmonic solution to achieve better stability properties. We also present graph-based methods for detecting conditional anomalies and apply them to the identification of unusual clinical actions in hospitals. Our hypothesis is that patient-management actions that are unusual with respect to the past patients may be due to errors and that it is worthwhile to raise an alert if such a condition is encountered. Conditional anomaly detection extends standard unconditional anomaly framework but also faces new problems known as fringe and isolated points. We devise novel nonparametric graph-based methods to tackle these problems. Our methods rely on graph connectivity analysis and soft harmonic solution. Finally, we conduct an extensive human evaluation study of our conditional anomaly methods by 15 experts in critical care.

Graph self-supervised learning (SSL) is now a go-to method for pre-training graph foundation models (GFMs). There is a wide variety of knowledge patterns embedded in the graph data, such as node properties and clusters, which are crucial to learning generalized representations for GFMs. However, existing surveys of GFMs have several shortcomings: they lack comprehensiveness regarding the most recent progress, have unclear categorization of self-supervised methods, and take a limited architecture-based perspective that is restricted to only certain types of graph models. As the ultimate goal of GFMs is to learn generalized graph knowledge, we provide a comprehensive survey of self-supervised GFMs from a novel knowledge-based perspective. We propose a knowledge-based taxonomy, which categorizes self-supervised graph models by the specific graph knowledge utilized. Our taxonomy consists of microscopic (nodes, links, etc.), mesoscopic (context, clusters, etc.), and macroscopic knowledge (global structure, manifolds, etc.). It covers a total of 9 knowledge categories and more than 25 pretext tasks for pre-training GFMs, as well as various downstream task generalization strategies. Such a knowledge-based taxonomy allows us to re-examine graph models based on new architectures more clearly, such as graph language models, as well as provide more in-depth insights for constructing GFMs.

Drug discovery is a complex and time-intensive process that requires identifying and validating new therapeutic candidates. Computational approaches using large-scale biomedical knowledge graphs (KGs) offer a promising solution to accelerate this process. However, extracting meaningful insights from large-scale KGs remains challenging due to the complexity of graph traversal. Existing subgraph-based methods are tailored to graph neural networks (GNNs), making them incompatible with other models, such as large language models (LLMs). We introduce K-Paths, a retrieval framework that extracts structured, diverse, and biologically meaningful paths from KGs. Integrating these paths enables LLMs and GNNs to effectively predict unobserved drug-drug and drug-disease interactions. Unlike traditional path-ranking approaches, K-Paths retrieves and transforms paths into a structured format that LLMs can directly process, facilitating explainable reasoning. K-Paths employs a diversity-aware adaptation of Yen's algorithm to retrieve the K shortest loopless paths between entities in an interaction query, prioritizing biologically relevant and diverse relationships. Our experiments on benchmark datasets show that K-Paths improves the zero-shot performance of Llama 8.1B's F1-score by 12.45 points on drug repurposing and 13.42 points on interaction severity prediction. We also show that Llama 70B achieves F1-score gains of 6.18 and 8.46 points, respectively. K-Paths also improves the supervised training efficiency of EmerGNN, a state-of-the-art GNN, by reducing KG size by 90% while maintaining strong predictive performance. Beyond its scalability and efficiency, K-Paths uniquely bridges the gap between KGs and LLMs, providing explainable rationales for predicted interactions. These capabilities show that K-Paths is a valuable tool for efficient data-driven drug discovery.

Multi-label text classification (MLTC) tasks in the medical domain often face the long-tail label distribution problem. Prior works have explored hierarchical label structures to find relevant information for few-shot classes, but mostly neglected to incorporate external knowledge from medical guidelines. This paper presents DKEC, Domain Knowledge Enhanced Classification for diagnosis prediction with two innovations: (1) automated construction of heterogeneous knowledge graphs from external sources to capture semantic relations among diverse medical entities, (2) incorporating the heterogeneous knowledge graphs in few-shot classification using a label-wise attention mechanism. We construct DKEC using three online medical knowledge sources and evaluate it on a real-world Emergency Medical Services (EMS) dataset and a public electronic health record (EHR) dataset. Results show that DKEC outperforms the state-of-the-art label-wise attention networks and transformer models of different sizes, particularly for the few-shot classes. More importantly, it helps the smaller language models achieve comparable performance to large language models.

Generating Natural Language Explanations (NLEs) for model predictions on medical images, particularly those depicting thoracic pathologies, remains a critical and challenging task. Existing methodologies often struggle due to general models' insufficient domain-specific medical knowledge and privacy concerns associated with retrieval-based augmentation techniques. To address these issues, we propose a novel Vision-Language framework augmented with a Knowledge Graph (KG)-based datastore, which enhances the model's understanding by incorporating additional domain-specific medical knowledge essential for generating accurate and informative NLEs. Our framework employs a KG-based retrieval mechanism that not only improves the precision of the generated explanations but also preserves data privacy by avoiding direct data retrieval. The KG datastore is designed as a plug-and-play module, allowing for seamless integration with various model architectures. We introduce and evaluate three distinct frameworks within this paradigm: KG-LLaVA, which integrates the pre-trained LLaVA model with KG-RAG; Med-XPT, a custom framework combining MedCLIP, a transformer-based projector, and GPT-2; and Bio-LLaVA, which adapts LLaVA by incorporating the Bio-ViT-L vision model. These frameworks are validated on the MIMIC-NLE dataset, where they achieve state-of-the-art results, underscoring the effectiveness of KG augmentation in generating high-quality NLEs for thoracic pathologies.

Clinical trials are crucial for drug development but are time consuming, expensive, and often burdensome on patients. More importantly, clinical trials face uncertain outcomes due to issues with efficacy, safety, or problems with patient recruitment. If we were better at predicting the results of clinical trials, we could avoid having to run trials that will inevitably fail more resources could be devoted to trials that are likely to succeed. In this paper, we propose Hierarchical INteraction Network (HINT) for more general, clinical trial outcome predictions for all diseases based on a comprehensive and diverse set of web data including molecule information of the drugs, target disease information, trial protocol and biomedical knowledge. HINT first encode these multi-modal data into latent embeddings, where an imputation module is designed to handle missing data. Next, these embeddings will be fed into the knowledge embedding module to generate knowledge embeddings that are pretrained using external knowledge on pharmaco-kinetic properties and trial risk from the web. Then the interaction graph module will connect all the embedding via domain knowledge to fully capture various trial components and their complex relations as well as their influences on trial outcomes. Finally, HINT learns a dynamic attentive graph neural network to predict trial outcome. Comprehensive experimental results show that HINT achieves strong predictive performance, obtaining 0.772, 0.607, 0.623, 0.703 on PR-AUC for Phase I, II, III, and indication outcome prediction, respectively. It also consistently outperforms the best baseline method by up to 12.4\% on PR-AUC.

Large language models have been extensively studied as neural knowledge bases for their knowledge access, editability, reasoning, and explainability. However, few works focus on the structural patterns of their knowledge. Motivated by this gap, we investigate these structural patterns from a graph perspective. We quantify the knowledge of LLMs at both the triplet and entity levels, and analyze how it relates to graph structural properties such as node degree. Furthermore, we uncover the knowledge homophily, where topologically close entities exhibit similar levels of knowledgeability, which further motivates us to develop graph machine learning models to estimate entity knowledge based on its local neighbors. This model further enables valuable knowledge checking by selecting triplets less known to LLMs. Empirical results show that using selected triplets for fine-tuning leads to superior performance.

Knowledge graphs (KGs) are increasingly used to support large lan guage model (LLM) reasoning, but standard triplet-based KGs treat each relation as globally valid. In many settings, whether a relation should count as evidence depends on the context. We therefore formulate triplet validity as a triplet-specific function of context and refer to this formulation as a Quantum Knowledge Graph (QKG). We instantiate QKG in medicine using a diabetes-centered PrimeKG subgraph, whose 68,651 context-sensitive relations are further annotated with patient-group-specific constraints. We evaluate it in a reasoner--validator pipeline for medical question answering on a KG-grounded subset of MedReason containing 2,788 questions. With Haiku-4.5 as both the Reasoner and the Validator, KG-backed validation significantly improves over a no-validator baseline (+0.61 pp), and QKG with context matching yields the largest gain, outperforming both KG validation without context matching (+0.79 pp) and the no-validator baseline (+1.40 pp; paired McNemar, all p<0.05). Under a stronger validator (Qwen-3.6-Plus), the raw QKG gain over the no-validator baseline grows from +1.40 pp to +5.96 pp; the context-matching gap is non-significant (p=0.73) on the raw set but becomes borderline significant (p=0.05) after adjustment for knowledge leakage and suspicious questions, consistent with a benchmark-gold ceiling rather than a QKG limitation. Taken together, the results support the view that the value of a KG in LLM-based clinical reasoning lies not merely in storing medically related facts, but in representing whether those facts are applicable to the specific patient context. For reproducibility and further research, we release the curated QKG datasets and source code.https://github.com/HKAI-Sci/QKG

A key component of deep learning (DL) for natural language processing (NLP) is word embeddings. Word embeddings that effectively capture the meaning and context of the word that they represent can significantly improve the performance of downstream DL models for various NLP tasks. Many existing word embeddings techniques capture the context of words based on word co-occurrence in documents and text; however, they often cannot capture broader domain-specific relationships between concepts that may be crucial for the NLP task at hand. In this paper, we propose a method to integrate external knowledge from medical terminology ontologies into the context captured by word embeddings. Specifically, we use a medical knowledge graph, such as the unified medical language system (UMLS), to find connections between clinical terms in cancer pathology reports. This approach aims to minimize the distance between connected clinical concepts. We evaluate the proposed approach using a Multitask Convolutional Neural Network (MT-CNN) to extract six cancer characteristics -- site, subsite, laterality, behavior, histology, and grade -- from a dataset of ~900K cancer pathology reports. The results show that the MT-CNN model which uses our domain informed embeddings outperforms the same MT-CNN using standard word2vec embeddings across all tasks, with an improvement in the overall micro- and macro-F1 scores by 4.97\%and 22.5\%, respectively.

Modern operating room is becoming increasingly complex, requiring innovative intra-operative support systems. While the focus of surgical data science has largely been on video analysis, integrating surgical computer vision with language capabilities is emerging as a necessity. Our work aims to advance Visual Question Answering (VQA) in the surgical context with scene graph knowledge, addressing two main challenges in the current surgical VQA systems: removing question-condition bias in the surgical VQA dataset and incorporating scene-aware reasoning in the surgical VQA model design. First, we propose a Surgical Scene Graph-based dataset, SSG-QA, generated by employing segmentation and detection models on publicly available datasets. We build surgical scene graphs using spatial and action information of instruments and anatomies. These graphs are fed into a question engine, generating diverse QA pairs. Our SSG-QA dataset provides a more complex, diverse, geometrically grounded, unbiased, and surgical action-oriented dataset compared to existing surgical VQA datasets. We then propose SSG-QA-Net, a novel surgical VQA model incorporating a lightweight Scene-embedded Interaction Module (SIM), which integrates geometric scene knowledge in the VQA model design by employing cross-attention between the textual and the scene features. Our comprehensive analysis of the SSG-QA dataset shows that SSG-QA-Net outperforms existing methods across different question types and complexities. We highlight that the primary limitation in the current surgical VQA systems is the lack of scene knowledge to answer complex queries. We present a novel surgical VQA dataset and model and show that results can be significantly improved by incorporating geometric scene features in the VQA model design. The source code and the dataset will be made publicly available at: https://github.com/CAMMA-public/SSG-QA

We introduce a novel graph-based Retrieval-Augmented Generation (RAG) framework specifically designed for the medical domain, called MedGraphRAG, aimed at enhancing Large Language Model (LLM) capabilities and generating evidence-based results, thereby improving safety and reliability when handling private medical data. Our comprehensive pipeline begins with a hybrid static-semantic approach to document chunking, significantly improving context capture over traditional methods. Extracted entities are used to create a three-tier hierarchical graph structure, linking entities to foundational medical knowledge sourced from medical papers and dictionaries. These entities are then interconnected to form meta-graphs, which are merged based on semantic similarities to develop a comprehensive global graph. This structure supports precise information retrieval and response generation. The retrieval process employs a U-retrieve method to balance global awareness and indexing efficiency of the LLM. Our approach is validated through a comprehensive ablation study comparing various methods for document chunking, graph construction, and information retrieval. The results not only demonstrate that our hierarchical graph construction method consistently outperforms state-of-the-art models on multiple medical Q\&A benchmarks, but also confirms that the responses generated include source documentation, significantly enhancing the reliability of medical LLMs in practical applications. Code will be at: https://github.com/MedicineToken/Medical-Graph-RAG/tree/main

Large Language Models~(LLMs) have demonstrated capabilities across various applications but face challenges such as hallucination, limited reasoning abilities, and factual inconsistencies, especially when tackling complex, domain-specific tasks like question answering~(QA). While Knowledge Graphs~(KGs) have been shown to help mitigate these issues, research on the integration of LLMs with background KGs remains limited. In particular, user accessibility and the flexibility of the underlying KG have not been thoroughly explored. We introduce AGENTiGraph (Adaptive Generative ENgine for Task-based Interaction and Graphical Representation), a platform for knowledge management through natural language interaction. It integrates knowledge extraction, integration, and real-time visualization. AGENTiGraph employs a multi-agent architecture to dynamically interpret user intents, manage tasks, and integrate new knowledge, ensuring adaptability to evolving user requirements and data contexts. Our approach demonstrates superior performance in knowledge graph interactions, particularly for complex domain-specific tasks. Experimental results on a dataset of 3,500 test cases show AGENTiGraph significantly outperforms state-of-the-art zero-shot baselines, achieving 95.12\% accuracy in task classification and 90.45\% success rate in task execution. User studies corroborate its effectiveness in real-world scenarios. To showcase versatility, we extended AGENTiGraph to legislation and healthcare domains, constructing specialized KGs capable of answering complex queries in legal and medical contexts.

Ontologies and knowledge graphs (KGs) are general-purpose computable representations of some domain, such as human anatomy, and are frequently a crucial part of modern information systems. Most of these structures change over time, incorporating new knowledge or information that was previously missing. Managing these changes is a challenge, both in terms of communicating changes to users, and providing mechanisms to make it easier for multiple stakeholders to contribute. To fill that need, we have created KGCL, the Knowledge Graph Change Language, a standard data model for describing changes to KGs and ontologies at a high level, and an accompanying human-readable controlled natural language. This language serves two purposes: a curator can use it to request desired changes, and it can also be used to describe changes that have already happened, corresponding to the concepts of "apply patch" and "diff" commonly used for managing changes in text documents and computer programs. Another key feature of KGCL is that descriptions are at a high enough level to be useful and understood by a variety of stakeholders--for example, ontology edits can be specified by commands like "add synonym 'arm' to 'forelimb'" or "move 'Parkinson disease' under 'neurodegenerative disease'". We have also built a suite of tools for managing ontology changes. These include an automated agent that integrates with and monitors GitHub ontology repositories and applies any requested changes, and a new component in the BioPortal ontology resource that allows users to make change requests directly from within the BioPortal user interface. Overall, the KGCL data model, its controlled natural language, and associated tooling allow for easier management and processing of changes associated with the development of ontologies and KGs.

In real world applications, knowledge graphs (KG) are widely used in various domains (e.g. medical applications and dialogue agents). However, for fact verification, KGs have not been adequately utilized as a knowledge source. KGs can be a valuable knowledge source in fact verification due to their reliability and broad applicability. A KG consists of nodes and edges which makes it clear how concepts are linked together, allowing machines to reason over chains of topics. However, there are many challenges in understanding how these machine-readable concepts map to information in text. To enable the community to better use KGs, we introduce a new dataset, FactKG: Fact Verification via Reasoning on Knowledge Graphs. It consists of 108k natural language claims with five types of reasoning: One-hop, Conjunction, Existence, Multi-hop, and Negation. Furthermore, FactKG contains various linguistic patterns, including colloquial style claims as well as written style claims to increase practicality. Lastly, we develop a baseline approach and analyze FactKG over these reasoning types. We believe FactKG can advance both reliability and practicality in KG-based fact verification.

Clinical diagnosis prediction models, when provided with a patient's medical history, aim to detect potential diseases early, facilitating timely intervention and improving prognostic outcomes. However, the inherent scarcity of patient data and large disease candidate space often pose challenges in developing satisfactory models for this intricate task. The exploration of leveraging Large Language Models (LLMs) for encapsulating clinical decision processes has been limited. We introduce MERA, a clinical diagnosis prediction model that bridges pertaining natural language knowledge with medical practice. We apply hierarchical contrastive learning on a disease candidate ranking list to alleviate the large decision space issue. With concept memorization through fine-tuning, we bridge the natural language clinical knowledge with medical codes. Experimental results on MIMIC-III and IV datasets show that MERA achieves the state-of-the-art diagnosis prediction performance and dramatically elevates the diagnosis prediction capabilities of generative LMs.

Knowledge graph embedding (KGE) is an increasingly popular technique that aims to represent entities and relations of knowledge graphs into low-dimensional semantic spaces for a wide spectrum of applications such as link prediction, knowledge reasoning and knowledge completion. In this paper, we provide a systematic review of existing KGE techniques based on representation spaces. Particularly, we build a fine-grained classification to categorise the models based on three mathematical perspectives of the representation spaces: (1) Algebraic perspective, (2) Geometric perspective, and (3) Analytical perspective. We introduce the rigorous definitions of fundamental mathematical spaces before diving into KGE models and their mathematical properties. We further discuss different KGE methods over the three categories, as well as summarise how spatial advantages work over different embedding needs. By collating the experimental results from downstream tasks, we also explore the advantages of mathematical space in different scenarios and the reasons behind them. We further state some promising research directions from a representation space perspective, with which we hope to inspire researchers to design their KGE models as well as their related applications with more consideration of their mathematical space properties.

Knowledge Graphs (KG) provide us with a structured, flexible, transparent, cross-system, and collaborative way of organizing our knowledge and data across various domains in society and industrial as well as scientific disciplines. KGs surpass any other form of representation in terms of effectiveness. However, Knowledge Graph Engineering (KGE) requires in-depth experiences of graph structures, web technologies, existing models and vocabularies, rule sets, logic, as well as best practices. It also demands a significant amount of work. Considering the advancements in large language models (LLMs) and their interfaces and applications in recent years, we have conducted comprehensive experiments with ChatGPT to explore its potential in supporting KGE. In this paper, we present a selection of these experiments and their results to demonstrate how ChatGPT can assist us in the development and management of KGs.

Knowledge Graphs (KGs) play a pivotal role in advancing various AI applications, with the semantic web community's exploration into multi-modal dimensions unlocking new avenues for innovation. In this survey, we carefully review over 300 articles, focusing on KG-aware research in two principal aspects: KG-driven Multi-Modal (KG4MM) learning, where KGs support multi-modal tasks, and Multi-Modal Knowledge Graph (MM4KG), which extends KG studies into the MMKG realm. We begin by defining KGs and MMKGs, then explore their construction progress. Our review includes two primary task categories: KG-aware multi-modal learning tasks, such as Image Classification and Visual Question Answering, and intrinsic MMKG tasks like Multi-modal Knowledge Graph Completion and Entity Alignment, highlighting specific research trajectories. For most of these tasks, we provide definitions, evaluation benchmarks, and additionally outline essential insights for conducting relevant research. Finally, we discuss current challenges and identify emerging trends, such as progress in Large Language Modeling and Multi-modal Pre-training strategies. This survey aims to serve as a comprehensive reference for researchers already involved in or considering delving into KG and multi-modal learning research, offering insights into the evolving landscape of MMKG research and supporting future work.

Persistent homology, a technique from computational topology, has recently shown strong empirical performance in the context of graph classification. Being able to capture long range graph properties via higher-order topological features, such as cycles of arbitrary length, in combination with multi-scale topological descriptors, has improved predictive performance for data sets with prominent topological structures, such as molecules. At the same time, the theoretical properties of persistent homology have not been formally assessed in this context. This paper intends to bridge the gap between computational topology and graph machine learning by providing a brief introduction to persistent homology in the context of graphs, as well as a theoretical discussion and empirical analysis of its expressivity for graph learning tasks.

Surgical intelligence has the potential to improve the safety and consistency of surgical care, yet most existing surgical AI frameworks remain task-specific and struggle to generalize across procedures and institutions. Although multimodal foundation models, particularly multimodal large language models, have demonstrated strong cross-task capabilities across various medical domains, their advancement in surgery remains constrained by the lack of large-scale, systematically curated multimodal data. To address this challenge, we introduce SurgΣ, a spectrum of large-scale multimodal data and foundation models for surgical intelligence. At the core of this framework lies SurgΣ-DB, a large-scale multimodal data foundation designed to support diverse surgical tasks. SurgΣ-DB consolidates heterogeneous surgical data sources (including open-source datasets, curated in-house clinical collections and web-source data) into a unified schema, aiming to improve label consistency and data standardization across heterogeneous datasets. SurgΣ-DB spans 6 clinical specialties and diverse surgical types, providing rich image- and video-level annotations across 18 practical surgical tasks covering understanding, reasoning, planning, and generation, at an unprecedented scale (over 5.98M conversations). Beyond conventional multimodal conversations, SurgΣ-DB incorporates hierarchical reasoning annotations, providing richer semantic cues to support deeper contextual understanding in complex surgical scenarios. We further provide empirical evidence through recently developed surgical foundation models built upon SurgΣ-DB, illustrating the practical benefits of large-scale multimodal annotations, unified semantic design, and structured reasoning annotations for improving cross-task generalization and interpretability.

In this study, we investigate the potential of Large Language Models to complement biomedical knowledge graphs in the training of semantic models for the biomedical and clinical domains. Drawing on the wealth of the UMLS knowledge graph and harnessing cutting-edge Large Language Models, we propose a new state-of-the-art approach for obtaining high-fidelity representations of biomedical concepts and sentences, consisting of three steps: an improved contrastive learning phase, a novel self-distillation phase, and a weight averaging phase. Through rigorous evaluations via the extensive BioLORD testing suite and diverse downstream tasks, we demonstrate consistent and substantial performance improvements over the previous state of the art (e.g. +2pts on MedSTS, +2.5pts on MedNLI-S, +6.1pts on EHR-Rel-B). Besides our new state-of-the-art biomedical model for English, we also distill and release a multilingual model compatible with 50+ languages and finetuned on 7 European languages. Many clinical pipelines can benefit from our latest models. Our new multilingual model enables a range of languages to benefit from our advancements in biomedical semantic representation learning, opening a new avenue for bioinformatics researchers around the world. As a result, we hope to see BioLORD-2023 becoming a precious tool for future biomedical applications.

This work introduces BioLORD, a new pre-training strategy for producing meaningful representations for clinical sentences and biomedical concepts. State-of-the-art methodologies operate by maximizing the similarity in representation of names referring to the same concept, and preventing collapse through contrastive learning. However, because biomedical names are not always self-explanatory, it sometimes results in non-semantic representations. BioLORD overcomes this issue by grounding its concept representations using definitions, as well as short descriptions derived from a multi-relational knowledge graph consisting of biomedical ontologies. Thanks to this grounding, our model produces more semantic concept representations that match more closely the hierarchical structure of ontologies. BioLORD establishes a new state of the art for text similarity on both clinical sentences (MedSTS) and biomedical concepts (MayoSRS).

Knowledge Graph Embedding (KGE) models are used to learn continuous representations of entities and relations. A key task in the literature is predicting missing links between entities. However, Knowledge Graphs are not just sets of links but also have semantics underlying their structure. Semantics is crucial in several downstream tasks, such as query answering or reasoning. We introduce the subgraph inference task, where a model has to generate likely and semantically valid subgraphs. We propose IntelliGraphs, a set of five new Knowledge Graph datasets. The IntelliGraphs datasets contain subgraphs with semantics expressed in logical rules for evaluating subgraph inference. We also present the dataset generator that produced the synthetic datasets. We designed four novel baseline models, which include three models based on traditional KGEs. We evaluate their expressiveness and show that these models cannot capture the semantics. We believe this benchmark will encourage the development of machine learning models that emphasize semantic understanding.

Clinical natural language processing requires methods that can address domain-specific challenges, such as complex medical terminology and clinical contexts. Recently, large language models (LLMs) have shown promise in this domain. Yet, their direct deployment can lead to privacy issues and are constrained by resources. To address this challenge, we delve into synthetic clinical text generation using LLMs for clinical NLP tasks. We propose an innovative, resource-efficient approach, ClinGen, which infuses knowledge into the process. Our model involves clinical knowledge extraction and context-informed LLM prompting. Both clinical topics and writing styles are drawn from external domain-specific knowledge graphs and LLMs to guide data generation. Our extensive empirical study across 7 clinical NLP tasks and 16 datasets reveals that ClinGen consistently enhances performance across various tasks, effectively aligning the distribution of real datasets and significantly enriching the diversity of generated training instances. We will publish our code and all the generated data in https://github.com/ritaranx/ClinGen.

While large language models show promise in medical applications, achieving expert-level clinical reasoning remains challenging due to the need for both accurate answers and transparent reasoning processes. To address this challenge, we introduce Fleming-R1, a model designed for verifiable medical reasoning through three complementary innovations. First, our Reasoning-Oriented Data Strategy (RODS) combines curated medical QA datasets with knowledge-graph-guided synthesis to improve coverage of underrepresented diseases, drugs, and multi-hop reasoning chains. Second, we employ Chain-of-Thought (CoT) cold start to distill high-quality reasoning trajectories from teacher models, establishing robust inference priors. Third, we implement a two-stage Reinforcement Learning from Verifiable Rewards (RLVR) framework using Group Relative Policy Optimization, which consolidates core reasoning skills while targeting persistent failure modes through adaptive hard-sample mining. Across diverse medical benchmarks, Fleming-R1 delivers substantial parameter-efficient improvements: the 7B variant surpasses much larger baselines, while the 32B model achieves near-parity with GPT-4o and consistently outperforms strong open-source alternatives. These results demonstrate that structured data design, reasoning-oriented initialization, and verifiable reinforcement learning can advance clinical reasoning beyond simple accuracy optimization. We release Fleming-R1 publicly to promote transparent, reproducible, and auditable progress in medical AI, enabling safer deployment in high-stakes clinical environments.

The exponential growth of scientific literature requires effective management and extraction of valuable insights. While existing scientific search engines excel at delivering search results based on relational databases, they often neglect the analysis of collaborations between scientific entities and the evolution of ideas, as well as the in-depth analysis of content within scientific publications. The representation of heterogeneous graphs and the effective measurement, analysis, and mining of such graphs pose significant challenges. To address these challenges, we present AceMap, an academic system designed for knowledge discovery through academic graph. We present advanced database construction techniques to build the comprehensive AceMap database with large-scale academic entities that contain rich visual, textual, and numerical information. AceMap also employs innovative visualization, quantification, and analysis methods to explore associations and logical relationships among academic entities. AceMap introduces large-scale academic network visualization techniques centered on nebular graphs, providing a comprehensive view of academic networks from multiple perspectives. In addition, AceMap proposes a unified metric based on structural entropy to quantitatively measure the knowledge content of different academic entities. Moreover, AceMap provides advanced analysis capabilities, including tracing the evolution of academic ideas through citation relationships and concept co-occurrence, and generating concise summaries informed by this evolutionary process. In addition, AceMap uses machine reading methods to generate potential new ideas at the intersection of different fields. Exploring the integration of large language models and knowledge graphs is a promising direction for future research in idea evolution. Please visit https://www.acemap.info for further exploration.

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.

Laboratory workflows in pharmaceutical and biomedical research encode substantial tacit knowledge -- expert judgment about failure conditions, decision branching logic, and contextual dependencies -- that remains inaccessible to protocol documents, sensor streams, and existing biomedical ontologies. We present a repeatable structured expert elicitation methodology and federated Semantic Knowledge Graph (SKG) architecture for capturing and querying this knowledge, demonstrated through deployment at the Biochemical and Cellular Pharmacology Department of Genentech. Knowledge is elicited via the Protocol Intelligence Co-pilot, a purpose-built AI interview agent that applies structured elicitation lenses to surface tacit procedural knowledge with expert-assigned confidence scores, producing graph representations across three tiers: program-level decision milestones, assay protocol knowledge, and physical execution infrastructure. Separately constructed subgraphs, exemplified by immunoassay (ELISA), quantitative mass spectrometry (LC-MS/PRM), and laboratory automation, are aligned through a shared upper ontology and queried as a single federated graph. Evaluation demonstrates seven query types structurally unavailable from any individual data source, including a cross-subgraph traversal that identifies automation-masked silent failures -- conditions where execution logs report success while scientific validity is compromised. Critically, the MASKED_BY graph relationship encodes a class of laboratory risk invisible to current informatics platforms -- the structural gap that prevents existing systems from reasoning about scientific validity. This architecture provides the semantic world model that AI laboratory agents currently lack: a queryable representation of where workflows fail silently, where human judgment is irreplaceable, and which execution assets mask rather than detect failure.

Medical visual question answering (VQA) aims to answer clinically relevant questions regarding input medical images. This technique has the potential to improve the efficiency of medical professionals while relieving the burden on the public health system, particularly in resource-poor countries. Existing medical VQA methods tend to encode medical images and learn the correspondence between visual features and questions without exploiting the spatial, semantic, or medical knowledge behind them. This is partially because of the small size of the current medical VQA dataset, which often includes simple questions. Therefore, we first collected a comprehensive and large-scale medical VQA dataset, focusing on chest X-ray images. The questions involved detailed relationships, such as disease names, locations, levels, and types in our dataset. Based on this dataset, we also propose a novel baseline method by constructing three different relationship graphs: spatial relationship, semantic relationship, and implicit relationship graphs on the image regions, questions, and semantic labels. The answer and graph reasoning paths are learned for different questions.

Large language models (LLMs) have recently demonstrated their potential in clinical applications, providing valuable medical knowledge and advice. For example, a large dialog LLM like ChatGPT has successfully passed part of the US medical licensing exam. However, LLMs currently have difficulty processing images, making it challenging to interpret information from medical images, which are rich in information that supports clinical decisions. On the other hand, computer-aided diagnosis (CAD) networks for medical images have seen significant success in the medical field by using advanced deep-learning algorithms to support clinical decision-making. This paper presents a method for integrating LLMs into medical-image CAD networks. The proposed framework uses LLMs to enhance the output of multiple CAD networks, such as diagnosis networks, lesion segmentation networks, and report generation networks, by summarizing and reorganizing the information presented in natural language text format. The goal is to merge the strengths of LLMs' medical domain knowledge and logical reasoning with the vision understanding capability of existing medical-image CAD models to create a more user-friendly and understandable system for patients compared to conventional CAD systems. In the future, LLM's medical knowledge can be also used to improve the performance of vision-based medical-image CAD models.

The exploitation of syntactic graphs (SyGs) as a word's context has been shown to be beneficial for distributional semantic models (DSMs), both at the level of individual word representations and in deriving phrasal representations via composition. However, notwithstanding the potential performance benefit, the syntactically-aware DSMs proposed to date have huge numbers of parameters (compared to conventional DSMs) and suffer from data sparsity. Furthermore, the encoding of the SyG links (i.e., the syntactic relations) has been largely limited to linear maps. The knowledge graphs' literature, on the other hand, has proposed light-weight models employing different geometric transformations (GTs) to encode edges in a knowledge graph (KG). Our work explores the possibility of adopting this family of models to encode SyGs. Furthermore, we investigate which GT better encodes syntactic relations, so that these representations can be used to enhance phrase-level composition via syntactic contextualisation.

Leveraging generative Artificial Intelligence (AI), we have transformed a dataset comprising 1,000 scientific papers into an ontological knowledge graph. Through an in-depth structural analysis, we have calculated node degrees, identified communities and connectivities, and evaluated clustering coefficients and betweenness centrality of pivotal nodes, uncovering fascinating knowledge architectures. The graph has an inherently scale-free nature, is highly connected, and can be used for graph reasoning by taking advantage of transitive and isomorphic properties that reveal unprecedented interdisciplinary relationships that can be used to answer queries, identify gaps in knowledge, propose never-before-seen material designs, and predict material behaviors. We compute deep node embeddings for combinatorial node similarity ranking for use in a path sampling strategy links dissimilar concepts that have previously not been related. One comparison revealed structural parallels between biological materials and Beethoven's 9th Symphony, highlighting shared patterns of complexity through isomorphic mapping. In another example, the algorithm proposed a hierarchical mycelium-based composite based on integrating path sampling with principles extracted from Kandinsky's 'Composition VII' painting. The resulting material integrates an innovative set of concepts that include a balance of chaos/order, adjustable porosity, mechanical strength, and complex patterned chemical functionalization. We uncover other isomorphisms across science, technology and art, revealing a nuanced ontology of immanence that reveal a context-dependent heterarchical interplay of constituents. Graph-based generative AI achieves a far higher degree of novelty, explorative capacity, and technical detail, than conventional approaches and establishes a widely useful framework for innovation by revealing hidden connections.

We introduce MentalBench, a benchmark for evaluating psychiatric diagnostic decision-making in large language models (LLMs). Existing mental health benchmarks largely rely on social media data, limiting their ability to assess DSM-grounded diagnostic judgments. At the core of MentalBench is MentalKG, a psychiatrist-built and validated knowledge graph encoding DSM-5 diagnostic criteria and differential diagnostic rules for 23 psychiatric disorders. Using MentalKG as a golden-standard logical backbone, we generate 24,750 synthetic clinical cases that systematically vary in information completeness and diagnostic complexity, enabling low-noise and interpretable evaluation. Our experiments show that while state-of-the-art LLMs perform well on structured queries probing DSM-5 knowledge, they struggle to calibrate confidence in diagnostic decision-making when distinguishing between clinically overlapping disorders. These findings reveal evaluation gaps not captured by existing benchmarks.

Foundation vision-language models are currently transforming computer vision, and are on the rise in medical imaging fueled by their very promising generalization capabilities. However, the initial attempts to transfer this new paradigm to medical imaging have shown less impressive performances than those observed in other domains, due to the significant domain shift and the complex, expert domain knowledge inherent to medical-imaging tasks. Motivated by the need for domain-expert foundation models, we present FLAIR, a pre-trained vision-language model for universal retinal fundus image understanding. To this end, we compiled 37 open-access, mostly categorical fundus imaging datasets from various sources, with up to 97 different target conditions and 284,660 images. We integrate the expert's domain knowledge in the form of descriptive textual prompts, during both pre-training and zero-shot inference, enhancing the less-informative categorical supervision of the data. Such a textual expert's knowledge, which we compiled from the relevant clinical literature and community standards, describes the fine-grained features of the pathologies as well as the hierarchies and dependencies between them. We report comprehensive evaluations, which illustrate the benefit of integrating expert knowledge and the strong generalization capabilities of FLAIR under difficult scenarios with domain shifts or unseen categories. When adapted with a lightweight linear probe, FLAIR outperforms fully-trained, dataset-focused models, more so in the few-shot regimes. Interestingly, FLAIR outperforms by a large margin more generalist, larger-scale image-language models, which emphasizes the potential of embedding experts' domain knowledge and the limitations of generalist models in medical imaging.

Knowledge graph (KG) embeddings learn low-dimensional representations of entities and relations to predict missing facts. KGs often exhibit hierarchical and logical patterns which must be preserved in the embedding space. For hierarchical data, hyperbolic embedding methods have shown promise for high-fidelity and parsimonious representations. However, existing hyperbolic embedding methods do not account for the rich logical patterns in KGs. In this work, we introduce a class of hyperbolic KG embedding models that simultaneously capture hierarchical and logical patterns. Our approach combines hyperbolic reflections and rotations with attention to model complex relational patterns. Experimental results on standard KG benchmarks show that our method improves over previous Euclidean- and hyperbolic-based efforts by up to 6.1% in mean reciprocal rank (MRR) in low dimensions. Furthermore, we observe that different geometric transformations capture different types of relations while attention-based transformations generalize to multiple relations. In high dimensions, our approach yields new state-of-the-art MRRs of 49.6% on WN18RR and 57.7% on YAGO3-10.

Understanding the intricate workflows of cataract surgery requires modeling complex interactions between surgical tools, anatomical structures, and procedural techniques. Existing datasets primarily address isolated aspects of surgical analysis, such as tool detection or phase segmentation, but lack comprehensive representations that capture the semantic relationships between entities over time. This paper introduces the Cataract Surgery Scene Graph (CAT-SG) dataset, the first to provide structured annotations of tool-tissue interactions, procedural variations, and temporal dependencies. By incorporating detailed semantic relations, CAT-SG offers a holistic view of surgical workflows, enabling more accurate recognition of surgical phases and techniques. Additionally, we present a novel scene graph generation model, CatSGG, which outperforms current methods in generating structured surgical representations. The CAT-SG dataset is designed to enhance AI-driven surgical training, real-time decision support, and workflow analysis, paving the way for more intelligent, context-aware systems in clinical practice.

Existing medical RAG systems mainly leverage knowledge from medical knowledge bases, neglecting the crucial role of experiential knowledge derived from similar patient cases -- a key component of human clinical reasoning. To bridge this gap, we propose DoctorRAG, a RAG framework that emulates doctor-like reasoning by integrating both explicit clinical knowledge and implicit case-based experience. DoctorRAG enhances retrieval precision by first allocating conceptual tags for queries and knowledge sources, together with a hybrid retrieval mechanism from both relevant knowledge and patient. In addition, a Med-TextGrad module using multi-agent textual gradients is integrated to ensure that the final output adheres to the retrieved knowledge and patient query. Comprehensive experiments on multilingual, multitask datasets demonstrate that DoctorRAG significantly outperforms strong baseline RAG models and gains improvements from iterative refinements. Our approach generates more accurate, relevant, and comprehensive responses, taking a step towards more doctor-like medical reasoning systems.

Large language models (LLMs), while exhibiting exceptional performance, suffer from hallucinations, especially on knowledge-intensive tasks. Existing works propose to augment LLMs with individual text units retrieved from external knowledge corpora to alleviate the issue. However, in many domains, texts are interconnected (e.g., academic papers in a bibliographic graph are linked by citations and co-authorships) which form a (text-attributed) graph. The knowledge in such graphs is encoded not only in single texts/nodes but also in their associated connections. To facilitate the research of augmenting LLMs with graphs, we manually construct a Graph Reasoning Benchmark dataset called GRBench, containing 1,740 questions that can be answered with the knowledge from 10 domain graphs. Then, we propose a simple and effective framework called Graph Chain-of-thought (Graph-CoT) to augment LLMs with graphs by encouraging LLMs to reason on the graph iteratively. Each Graph-CoT iteration consists of three sub-steps: LLM reasoning, LLM-graph interaction, and graph execution. We conduct systematic experiments with three LLM backbones on GRBench, where Graph-CoT outperforms the baselines consistently. The code is available at https://github.com/PeterGriffinJin/Graph-CoT.

Background. In the last decades, several life science resources have structured data using the same framework and made these accessible using the same query language to facilitate interoperability. Knowledge graphs have seen increased adoption in bioinformatics due to their advantages for representing data in a generic graph format. For example, yummydata.org catalogs more than 60 knowledge graphs accessible through SPARQL, a technical query language. Although SPARQL allows powerful, expressive queries, even across physically distributed knowledge graphs, formulating such queries is a challenge for most users. Therefore, to guide users in retrieving the relevant data, many of these resources provide representative examples. These examples can also be an important source of information for machine learning, if a sufficiently large number of examples are provided and published in a common, machine-readable and standardized format across different resources. Findings. We introduce a large collection of human-written natural language questions and their corresponding SPARQL queries over federated bioinformatics knowledge graphs (KGs) collected for several years across different research groups at the SIB Swiss Institute of Bioinformatics. The collection comprises more than 1000 example questions and queries, including 65 federated queries. We propose a methodology to uniformly represent the examples with minimal metadata, based on existing standards. Furthermore, we introduce an extensive set of open-source applications, including query graph visualizations and smart query editors, easily reusable by KG maintainers who adopt the proposed methodology. Conclusions. We encourage the community to adopt and extend the proposed methodology, towards richer KG metadata and improved Semantic Web services.

Large language models (LLMs) are increasingly envisioned as decision-support tools in clinical practice, yet safe clinical reasoning demands integrating heterogeneous knowledge bases -- trials, primary studies, regulatory documents, and cost data -- under strict accuracy constraints. Existing evaluations often rely on synthetic prompts, reduce the task to single-hop factoid queries, or conflate reasoning with open-ended generation, leaving their real-world utility unclear. To close this gap, we present MedBrowseComp, the first benchmark that systematically tests an agent's ability to reliably retrieve and synthesize multi-hop medical facts from live, domain-specific knowledge bases. MedBrowseComp contains more than 1,000 human-curated questions that mirror clinical scenarios where practitioners must reconcile fragmented or conflicting information to reach an up-to-date conclusion. Applying MedBrowseComp to frontier agentic systems reveals performance shortfalls as low as ten percent, exposing a critical gap between current LLM capabilities and the rigor demanded in clinical settings. MedBrowseComp therefore offers a clear testbed for reliable medical information seeking and sets concrete goals for future model and toolchain upgrades. You can visit our project page at: https://moreirap12.github.io/mbc-browse-app/

Current biomedical question answering (QA) systems often assume that medical knowledge applies uniformly, yet real-world clinical reasoning is inherently conditional: nearly every decision depends on patient-specific factors such as comorbidities and contraindications. Existing benchmarks do not evaluate such conditional reasoning, and retrieval-augmented or graph-based methods lack explicit mechanisms to ensure that retrieved knowledge is applicable to given context. To address this gap, we propose CondMedQA, the first benchmark for conditional biomedical QA, consisting of multi-hop questions whose answers vary with patient conditions. Furthermore, we propose Condition-Gated Reasoning (CGR), a novel framework that constructs condition-aware knowledge graphs and selectively activates or prunes reasoning paths based on query conditions. Our findings show that CGR more reliably selects condition-appropriate answers while matching or exceeding state-of-the-art performance on biomedical QA benchmarks, highlighting the importance of explicitly modeling conditionality for robust medical reasoning.

Medical Dialogue Generation serves a critical role in telemedicine by facilitating the dissemination of medical expertise to patients. Existing studies focus on incorporating textual representations, which have limited their ability to represent the semantics of text, such as ignoring important medical entities. To enhance the model's understanding of the textual semantics and the medical knowledge including entities and relations, we introduce the use of Abstract Meaning Representations (AMR) to construct graphical representations that delineate the roles of language constituents and medical entities within the dialogues. In this paper, We propose a novel framework that models dialogues between patients and healthcare professionals using AMR graphs, where the neural networks incorporate textual and graphical knowledge with a dual attention mechanism. Experimental results show that our framework outperforms strong baseline models in medical dialogue generation, demonstrating the effectiveness of AMR graphs in enhancing the representations of medical knowledge and logical relationships. Furthermore, to support future research in this domain, we provide the corresponding source code at https://github.com/Bernard-Yang/MedDiaAMR.

Knowledge graph reasoning (KGR), aiming to deduce new facts from existing facts based on mined logic rules underlying knowledge graphs (KGs), has become a fast-growing research direction. It has been proven to significantly benefit the usage of KGs in many AI applications, such as question answering, recommendation systems, and etc. According to the graph types, existing KGR models can be roughly divided into three categories, i.e., static models, temporal models, and multi-modal models. Early works in this domain mainly focus on static KGR, and recent works try to leverage the temporal and multi-modal information, which are more practical and closer to real-world. However, no survey papers and open-source repositories comprehensively summarize and discuss models in this important direction. To fill the gap, we conduct a first survey for knowledge graph reasoning tracing from static to temporal and then to multi-modal KGs. Concretely, the models are reviewed based on bi-level taxonomy, i.e., top-level (graph types) and base-level (techniques and scenarios). Besides, the performances, as well as datasets, are summarized and presented. Moreover, we point out the challenges and potential opportunities to enlighten the readers. The corresponding open-source repository is shared on GitHub https://github.com/LIANGKE23/Awesome-Knowledge-Graph-Reasoning.

We consider the hierarchical representation of documents as graphs and use geometric deep learning to classify them into different categories. While graph neural networks can efficiently handle the variable structure of hierarchical documents using the permutation invariant message passing operations, we show that we can gain extra performance improvements using our proposed selective graph pooling operation that arises from the fact that some parts of the hierarchy are invariable across different documents. We applied our model to classify clinical trial (CT) protocols into completed and terminated categories. We use bag-of-words based, as well as pre-trained transformer-based embeddings to featurize the graph nodes, achieving f1-scores around 0.85 on a publicly available large scale CT registry of around 360K protocols. We further demonstrate how the selective pooling can add insights into the CT termination status prediction. We make the source code and dataset splits accessible.

Objective: To transform heterogeneous clinical data from electronic health records into clinically meaningful constructed features using data driven method that rely, in part, on temporal relations among data. Materials and Methods: The clinically meaningful representations of medical concepts and patients are the key for health analytic applications. Most of existing approaches directly construct features mapped to raw data (e.g., ICD or CPT codes), or utilize some ontology mapping such as SNOMED codes. However, none of the existing approaches leverage EHR data directly for learning such concept representation. We propose a new way to represent heterogeneous medical concepts (e.g., diagnoses, medications and procedures) based on co-occurrence patterns in longitudinal electronic health records. The intuition behind the method is to map medical concepts that are co-occuring closely in time to similar concept vectors so that their distance will be small. We also derive a simple method to construct patient vectors from the related medical concept vectors. Results: For qualitative evaluation, we study similar medical concepts across diagnosis, medication and procedure. In quantitative evaluation, our proposed representation significantly improves the predictive modeling performance for onset of heart failure (HF), where classification methods (e.g. logistic regression, neural network, support vector machine and K-nearest neighbors) achieve up to 23% improvement in area under the ROC curve (AUC) using this proposed representation. Conclusion: We proposed an effective method for patient and medical concept representation learning. The resulting representation can map relevant concepts together and also improves predictive modeling performance.

The emergence of advanced reasoning capabilities in Large Language Models (LLMs) marks a transformative development in healthcare applications. Beyond merely expanding functional capabilities, these reasoning mechanisms enhance decision transparency and explainability-critical requirements in medical contexts. This survey examines the transformation of medical LLMs from basic information retrieval tools to sophisticated clinical reasoning systems capable of supporting complex healthcare decisions. We provide a thorough analysis of the enabling technological foundations, with a particular focus on specialized prompting techniques like Chain-of-Thought and recent breakthroughs in Reinforcement Learning exemplified by DeepSeek-R1. Our investigation evaluates purpose-built medical frameworks while also examining emerging paradigms such as multi-agent collaborative systems and innovative prompting architectures. The survey critically assesses current evaluation methodologies for medical validation and addresses persistent challenges in field interpretation limitations, bias mitigation strategies, patient safety frameworks, and integration of multimodal clinical data. Through this survey, we seek to establish a roadmap for developing reliable LLMs that can serve as effective partners in clinical practice and medical research.

Vision-Language Models (VLM) can support clinicians by analyzing medical images and engaging in natural language interactions to assist in diagnostic and treatment tasks. However, VLMs often exhibit "hallucinogenic" behavior, generating textual outputs not grounded in contextual multimodal information. This challenge is particularly pronounced in the medical domain, where we do not only require VLM outputs to be accurate in single interactions but also to be consistent with clinical reasoning and diagnostic pathways throughout multi-turn conversations. For this purpose, we propose a new alignment algorithm that uses symbolic representations of clinical reasoning to ground VLMs in medical knowledge. These representations are utilized to (i) generate GPT-4-guided visual instruction tuning data at scale, simulating clinician-VLM conversations with demonstrations of clinical reasoning, and (ii) create an automatic reward function that evaluates the clinical validity of VLM generations throughout clinician-VLM interactions. Our algorithm eliminates the need for human involvement in training data generation or reward model construction, reducing costs compared to standard reinforcement learning with human feedback (RLHF). We apply our alignment algorithm to develop Dr-LLaVA, a conversational VLM finetuned for analyzing bone marrow pathology slides, demonstrating strong performance in multi-turn medical conversations.

Current benchmarks for AI clinician systems, often based on multiple-choice exams or manual rubrics, fail to capture the depth, robustness, and safety required for real-world clinical practice. To address this, we introduce the GAPS framework, a multidimensional paradigm for evaluating Grounding (cognitive depth), Adequacy (answer completeness), Perturbation (robustness), and Safety. Critically, we developed a fully automated, guideline-anchored pipeline to construct a GAPS-aligned benchmark end-to-end, overcoming the scalability and subjectivity limitations of prior work. Our pipeline assembles an evidence neighborhood, creates dual graph and tree representations, and automatically generates questions across G-levels. Rubrics are synthesized by a DeepResearch agent that mimics GRADE-consistent, PICO-driven evidence review in a ReAct loop. Scoring is performed by an ensemble of large language model (LLM) judges. Validation confirmed our automated questions are high-quality and align with clinician judgment. Evaluating state-of-the-art models on the benchmark revealed key failure modes: performance degrades sharply with increased reasoning depth (G-axis), models struggle with answer completeness (A-axis), and they are highly vulnerable to adversarial perturbations (P-axis) as well as certain safety issues (S-axis). This automated, clinically-grounded approach provides a reproducible and scalable method for rigorously evaluating AI clinician systems and guiding their development toward safer, more reliable clinical practice.

Subgraph matching is vital in knowledge graph (KG) question answering, molecule design, scene graph, code and circuit search, etc. Neural methods have shown promising results for subgraph matching. Our study of recent systems suggests refactoring them into a unified design space for graph matching networks. Existing methods occupy only a few isolated patches in this space, which remains largely uncharted. We undertake the first comprehensive exploration of this space, featuring such axes as attention-based vs. soft permutation-based interaction between query and corpus graphs, aligning nodes vs. edges, and the form of the final scoring network that integrates neural representations of the graphs. Our extensive experiments reveal that judicious and hitherto-unexplored combinations of choices in this space lead to large performance benefits. Beyond better performance, our study uncovers valuable insights and establishes general design principles for neural graph representation and interaction, which may be of wider interest.

Text-rich Graph Knowledge Bases (TG-KBs) have become increasingly crucial for answering queries by providing textual and structural knowledge. However, current retrieval methods often retrieve these two types of knowledge in isolation without considering their mutual reinforcement and some hybrid methods even bypass structural retrieval entirely after neighboring aggregation. To fill in this gap, we propose a Mixture of Structural-and-Textual Retrieval (MoR) to retrieve these two types of knowledge via a Planning-Reasoning-Organizing framework. In the Planning stage, MoR generates textual planning graphs delineating the logic for answering queries. Following planning graphs, in the Reasoning stage, MoR interweaves structural traversal and textual matching to obtain candidates from TG-KBs. In the Organizing stage, MoR further reranks fetched candidates based on their structural trajectory. Extensive experiments demonstrate the superiority of MoR in harmonizing structural and textual retrieval with insights, including uneven retrieving performance across different query logics and the benefits of integrating structural trajectories for candidate reranking. Our code is available at https://github.com/Yoega/MoR.

Large language models (LLMs) show promise in medical diagnosis, but real-world deployment remains challenging due to high-stakes clinical decisions and imperfect reasoning reliability. As a result, careful inspection of model behavior is essential for assessing whether diagnostic reasoning is reliable and clinically grounded. However, debugging medical LLMs remains difficult. First, developers often lack sufficient medical domain expertise to interpret model errors in clinically meaningful terms. Second, models can fail across a large and diverse set of instances involving different input types, tasks, and reasoning steps, making it challenging for developers to prioritize which errors deserve focused inspection. Third, developers struggle to identify recurring error patterns across cases, as existing debugging practices are largely instance-centric and rely on manual inspection of isolated failures. To address these challenges, we present VeriLLMed, a visual analytics system that integrates external biomedical knowledge to audit and debug medical LLM diagnostic reasoning. VeriLLMed transforms model outputs into comparable reasoning paths, constructs knowledge graph-grounded reference paths, and identifies three recurring classes of diagnosis errors: relation errors, branch errors, and missing errors. Case studies and expert evaluation demonstrate that VeriLLMed helps developers identify clinically implausible reasoning and generate actionable insights that can inform the improvement of medical LLMs.

LLMs are bound to transform healthcare with advanced decision support and flexible chat assistants. However, LLMs are prone to generate inaccurate medical content. To ground LLMs in high-quality medical knowledge, LLMs have been equipped with external knowledge via RAG, where unstructured medical knowledge is split into small text chunks that can be selectively retrieved and integrated into the LLMs context. Yet, existing RAG pipelines rely on raw, unstructured medical text, which can be noisy, uncurated and difficult for LLMs to effectively leverage. Systematic approaches to organize medical knowledge to best surface it to LLMs are generally lacking. To address these challenges, we introduce MIRIAD, a large-scale, curated corpus of 5,821,948 medical QA pairs, each rephrased from and grounded in a passage from peer-reviewed medical literature using a semi-automated pipeline combining LLM generation, filtering, grounding, and human annotation. Unlike prior medical corpora, which rely on unstructured text, MIRIAD encapsulates web-scale medical knowledge in an operationalized query-response format, which enables more targeted retrieval. Experiments on challenging medical QA benchmarks show that augmenting LLMs with MIRIAD improves accuracy up to 6.7% compared to unstructured RAG baselines with the same source corpus and with the same amount of retrieved text. Moreover, MIRIAD improved the ability of LLMs to detect medical hallucinations by 22.5 to 37% (increase in F1 score). We further introduce MIRIAD-Atlas, an interactive map of MIRIAD spanning 56 medical disciplines, enabling clinical users to visually explore, search, and refine medical knowledge. MIRIAD promises to unlock a wealth of down-stream applications, including medical information retrievers, enhanced RAG applications, and knowledge-grounded chat interfaces, which ultimately enables more reliable LLM applications in healthcare.

The exponential growth of global academic output has confronted researchers and AI agents with an unprecedented ``information explosion,'' where fragmented and unstructured knowledge organization impedes deep interdisciplinary integration. Current academic retrieval tools predominantly rely on superficial keyword matching or vector-space semantic retrieval, which lack the topological reasoning capabilities required to navigate complex logical connections. Agentic deep-research-based frameworks are often prone to logical hallucinations and consuming high inference costs. To bridge this gap, in this report, we introduce SciAtlas, a large-scale, multi-disciplinary, heterogeneous academic resource knowledge graph designed as a panoramic scientific evolution network. By integrating over 43M papers from 26 disciplines, and a total of 157M entities and 3B triplets, SciAtlas provides a structured topological cognitive substrate that dismantles disciplinary barriers and furnishes AI agents with a global perspective. Furthermore, we develop a neuro-symbolic retrieval algorithm featuring tri-path collaborative recall and graph reranking, achieving a seamless transition from simple semantic matching to deterministic association discovery. We also present key application directions of SciAtlas, including literature review, automated research trend synthesis, idea positioning, and academic trajectory exploration, to demonstrate that SciAtlas can serve as an effective ``cognitive map'' to empower the full loop of automated scientific research while significantly reducing reasoning costs. We have released the interfaces for KG retrieval and various downstream tasks in our GitHub repo.

Temporal knowledge graphs represent temporal facts (s,p,o,tau) relating a subject s and an object o via a relation label p at time tau, where tau could be a time point or time interval. Temporal knowledge graphs may exhibit static temporal patterns at distinct points in time and dynamic temporal patterns between different timestamps. In order to learn a rich set of static and dynamic temporal patterns and apply them for inference, several embedding approaches have been suggested in the literature. However, as most of them resort to single underlying embedding spaces, their capability to model all kinds of temporal patterns was severely limited by having to adhere to the geometric property of their one embedding space. We lift this limitation by an embedding approach that maps temporal facts into a product space of several heterogeneous geometric subspaces with distinct geometric properties, i.e.\ Complex, Dual, and Split-complex spaces. In addition, we propose a temporal-geometric attention mechanism to integrate information from different geometric subspaces conveniently according to the captured relational and temporal information. Experimental results on standard temporal benchmark datasets favorably evaluate our approach against state-of-the-art models.

The application of large language models (LLMs) in clinical decision support faces significant challenges of "tunnel vision" and diagnostic hallucinations present in their processing unstructured electronic health records (EHRs). To address these challenges, we propose a novel chain-based clinical reasoning framework, called DxChain, which transforms the diagnostic workflow into an iterative process by mirroring a clinician's cognitive trajectory that consists of "Memory Anchoring", "Navigation" and "Verification" phases. DxChain introduces three key methodological innovations to elicit the potential of LLM: (i) a Profile-Then-Plan paradigm to mitigate cold-start hallucinations by establishing a panoramic patient baseline, (ii) a Medical Tree-of-Thoughts (Med-ToT) algorithm for strategic look ahead planning and resource aware navigation, and (iii) a Dialectical Diagnostic Verification procedure utilizing "Angel-Devil" adversarial debates to resolve complex evidence conflicts. Evaluated on two real world benchmarks, MIMIC-IV-Ext Cardiac Disease and MIMIC-IV-Ext CDM, DxChain achieves state-of-the-art performances in both diagnostic accuracy and logical consistency, offering a modular and reliable architecture for next-generation clinical AI. The code is at https://anonymous.4open.science/r/Dx-Chain.

The proliferation of Large Language Models (LLMs) presents transformative potential for healthcare, yet practical deployment is hindered by the absence of frameworks that assess real-world clinical utility. Existing benchmarks test static knowledge, failing to capture the dynamic, application-oriented capabilities required in clinical practice. To bridge this gap, we introduce a Medical LLM Benchmark MLB, a comprehensive benchmark evaluating LLMs on both foundational knowledge and scenario-based reasoning. MLB is structured around five core dimensions: Medical Knowledge (MedKQA), Safety and Ethics (MedSE), Medical Record Understanding (MedRU), Smart Services (SmartServ), and Smart Healthcare (SmartCare). The benchmark integrates 22 datasets (17 newly curated) from diverse Chinese clinical sources, covering 64 clinical specialties. Its design features a rigorous curation pipeline involving 300 licensed physicians. Besides, we provide a scalable evaluation methodology, centered on a specialized judge model trained via Supervised Fine-Tuning (SFT) on expert annotations. Our comprehensive evaluation of 10 leading models reveals a critical translational gap: while the top-ranked model, Kimi-K2-Instruct (77.3% accuracy overall), excels in structured tasks like information extraction (87.8% accuracy in MedRU), performance plummets in patient-facing scenarios (61.3% in SmartServ). Moreover, the exceptional safety score (90.6% in MedSE) of the much smaller Baichuan-M2-32B highlights that targeted training is equally critical. Our specialized judge model, trained via SFT on a 19k expert-annotated medical dataset, achieves 92.1% accuracy, an F1-score of 94.37%, and a Cohen's Kappa of 81.3% for human-AI consistency, validating a reproducible and expert-aligned evaluation protocol. MLB thus provides a rigorous framework to guide the development of clinically viable LLMs.

This work presents a unified knowledge protocol, called UKnow, which facilitates knowledge-based studies from the perspective of data. Particularly focusing on visual and linguistic modalities, we categorize data knowledge into five unit types, namely, in-image, in-text, cross-image, cross-text, and image-text, and set up an efficient pipeline to help construct the multimodal knowledge graph from any data collection. Thanks to the logical information naturally contained in knowledge graph, organizing datasets under UKnow format opens up more possibilities of data usage compared to the commonly used image-text pairs. Following UKnow protocol, we collect, from public international news, a large-scale multimodal knowledge graph dataset that consists of 1,388,568 nodes (with 571,791 vision-related ones) and 3,673,817 triplets. The dataset is also annotated with rich event tags, including 11 coarse labels and 9,185 fine labels. Experiments on four benchmarks demonstrate the potential of UKnow in supporting common-sense reasoning and boosting vision-language pre-training with a single dataset, benefiting from its unified form of knowledge organization. Code, dataset, and models will be made publicly available.

The integration of Artificial Intelligence (AI), especially Large Language Models (LLMs), into the clinical diagnosis process offers significant potential to improve the efficiency and accessibility of medical care. While LLMs have shown some promise in the medical domain, their application in clinical diagnosis remains underexplored, especially in real-world clinical practice, where highly sophisticated, patient-specific decisions need to be made. Current evaluations of LLMs in this field are often narrow in scope, focusing on specific diseases or specialties and employing simplified diagnostic tasks. To bridge this gap, we introduce CliBench, a novel benchmark developed from the MIMIC IV dataset, offering a comprehensive and realistic assessment of LLMs' capabilities in clinical diagnosis. This benchmark not only covers diagnoses from a diverse range of medical cases across various specialties but also incorporates tasks of clinical significance: treatment procedure identification, lab test ordering and medication prescriptions. Supported by structured output ontologies, CliBench enables a precise and multi-granular evaluation, offering an in-depth understanding of LLM's capability on diverse clinical tasks of desired granularity. We conduct a zero-shot evaluation of leading LLMs to assess their proficiency in clinical decision-making. Our preliminary results shed light on the potential and limitations of current LLMs in clinical settings, providing valuable insights for future advancements in LLM-powered healthcare.

In this work, we address the problem of grounding abnormalities in medical images, where the goal is to localize clinical findings based on textual descriptions. While generalist Vision-Language Models (VLMs) excel in natural grounding tasks, they often struggle in the medical domain due to rare, compositional, and domain-specific terms that are poorly aligned with visual patterns. Specialized medical VLMs address this challenge via large-scale domain pretraining, but at the cost of substantial annotation and computational resources. To overcome these limitations, we propose Knowledge to Sight (K2Sight), a framework that introduces structured semantic supervision by decomposing clinical concepts into interpretable visual attributes, such as shape, density, and anatomical location. These attributes are distilled from domain ontologies and encoded into concise instruction-style prompts, which guide region-text alignment during training. Unlike conventional report-level supervision, our approach explicitly bridges domain knowledge and spatial structure, enabling data-efficient training of compact models. We train compact models with 0.23B and 2B parameters using only 1.5\% of the data required by state-of-the-art medical VLMs. Despite their small size and limited training data, these models achieve performance on par with or better than 7B+ medical VLMs, with up to 9.82\% improvement in mAP_{50}. Code and models: https://lijunrio.github.io/K2Sight/{SOTAPink{https://lijunrio.github.io/K2Sight/}}.

With the development of large language models (LLMs), particularly with the introduction of the long reasoning chain technique, the reasoning ability of LLMs in complex problem-solving has been significantly enhanced. While acknowledging the power of long reasoning chains, we cannot help but wonder: Why do different reasoning chains perform differently in reasoning? What components of the reasoning chains play a key role? Existing studies mainly focus on evaluating reasoning chains from a functional perspective, with little attention paid to their structural mechanisms. To address this gap, this work is the first to analyze and evaluate the quality of the reasoning chain from a structural perspective. We apply persistent homology from Topological Data Analysis (TDA) to map reasoning steps into semantic space, extract topological features, and analyze structural changes. These changes reveal semantic coherence, logical redundancy, and identify logical breaks and gaps. By calculating homology groups, we assess connectivity and redundancy at various scales, using barcode and persistence diagrams to quantify stability and consistency. Our results show that the topological structural complexity of reasoning chains correlates positively with accuracy. More complex chains identify correct answers sooner, while successful reasoning exhibits simpler topologies, reducing redundancy and cycles, enhancing efficiency and interpretability. This work provides a new perspective on reasoning chain quality assessment and offers guidance for future optimization.

Generative Knowledge Graph Construction (KGC) refers to those methods that leverage the sequence-to-sequence framework for building knowledge graphs, which is flexible and can be adapted to widespread tasks. In this study, we summarize the recent compelling progress in generative knowledge graph construction. We present the advantages and weaknesses of each paradigm in terms of different generation targets and provide theoretical insight and empirical analysis. Based on the review, we suggest promising research directions for the future. Our contributions are threefold: (1) We present a detailed, complete taxonomy for the generative KGC methods; (2) We provide a theoretical and empirical analysis of the generative KGC methods; (3) We propose several research directions that can be developed in the future.

Electronic health records (EHR) contain narrative notes that provide extensive details on the medical condition and management of patients. Natural language processing (NLP) of clinical notes can use observed frequencies of clinical terms as predictive features for downstream applications such as clinical decision making and patient trajectory prediction. However, due to the vast number of highly similar and related clinical concepts, a more effective modeling strategy is to represent clinical terms as semantic embeddings via representation learning and use the low dimensional embeddings as feature vectors for predictive modeling. To achieve efficient representation, fine-tuning pretrained language models with biomedical knowledge graphs may generate better embeddings for biomedical terms than those from standard language models alone. These embeddings can effectively discriminate synonymous pairs of from those that are unrelated. However, they often fail to capture different degrees of similarity or relatedness for concepts that are hierarchical in nature. To overcome this limitation, we propose HiPrBERT, a novel biomedical term representation model trained on additionally complied data that contains hierarchical structures for various biomedical terms. We modify an existing contrastive loss function to extract information from these hierarchies. Our numerical experiments demonstrate that HiPrBERT effectively learns the pair-wise distance from hierarchical information, resulting in a substantially more informative embeddings for further biomedical applications

The emergence of groundbreaking large language models capable of performing complex reasoning tasks holds significant promise for addressing various scientific challenges, including those arising in complex clinical scenarios. To enable their safe and effective deployment in real-world healthcare settings, it is urgently necessary to benchmark the diagnostic capabilities of current models systematically. Given the limitations of existing medical benchmarks in evaluating advanced diagnostic reasoning, we present DiagnosisArena, a comprehensive and challenging benchmark designed to rigorously assess professional-level diagnostic competence. DiagnosisArena consists of 1,113 pairs of segmented patient cases and corresponding diagnoses, spanning 28 medical specialties, deriving from clinical case reports published in 10 top-tier medical journals. The benchmark is developed through a meticulous construction pipeline, involving multiple rounds of screening and review by both AI systems and human experts, with thorough checks conducted to prevent data leakage. Our study reveals that even the most advanced reasoning models, o3-mini, o1, and DeepSeek-R1, achieve only 45.82%, 31.09%, and 17.79% accuracy, respectively. This finding highlights a significant generalization bottleneck in current large language models when faced with clinical diagnostic reasoning challenges. Through DiagnosisArena, we aim to drive further advancements in AIs diagnostic reasoning capabilities, enabling more effective solutions for real-world clinical diagnostic challenges. We provide the benchmark and evaluation tools for further research and development https://github.com/SPIRAL-MED/DiagnosisArena.

To combat COVID-19, both clinicians and scientists need to digest vast amounts of relevant biomedical knowledge in scientific literature to understand the disease mechanism and related biological functions. We have developed a novel and comprehensive knowledge discovery framework, COVID-KG to extract fine-grained multimedia knowledge elements (entities and their visual chemical structures, relations, and events) from scientific literature. We then exploit the constructed multimedia knowledge graphs (KGs) for question answering and report generation, using drug repurposing as a case study. Our framework also provides detailed contextual sentences, subfigures, and knowledge subgraphs as evidence.

Rare diseases affect hundreds of millions worldwide, yet diagnosis often spans years. Convectional pipelines decouple noisy evidence extraction from downstream inferential diagnosis, and general/medical large language models (LLMs) face scarce real world electronic health records (EHRs), stale domain knowledge, and hallucinations. We assemble a large, domain specialized clinical corpus and a clinician validated reasoning set, and develop RareSeek R1 via staged instruction tuning, chain of thought learning, and graph grounded retrieval. Across multicenter EHR narratives and public benchmarks, RareSeek R1 attains state of the art accuracy, robust generalization, and stability under noisy or overlapping phenotypes. Augmented retrieval yields the largest gains when narratives pair with prioritized variants by resolving ambiguity and aligning candidates to mechanisms. Human studies show performance on par with experienced physicians and consistent gains in assistive use. Notably, transparent reasoning highlights decisive non phenotypic evidence (median 23.1%, such as imaging, interventions, functional tests) underpinning many correct diagnoses. This work advances a narrative first, knowledge integrated reasoning paradigm that shortens the diagnostic odyssey and enables auditable, clinically translatable decision support.

Recent developments in Large Language Model (LLM)-based agents have shown impressive capabilities spanning multiple domains, exemplified by deep research systems that demonstrate superior performance on complex information-seeking and synthesis tasks. While general-purpose deep research agents have shown impressive capabilities, they struggle significantly with medical domain challenges, as evidenced by leading proprietary systems achieving limited accuracy on complex medical benchmarks. The key limitations are: (1) the model lacks sufficient dense medical knowledge for clinical reasoning, and (2) the framework is constrained by the absence of specialized retrieval tools tailored for medical contexts.We present a medical deep research agent that addresses these challenges through two core innovations. First, we develop a novel data synthesis framework using medical knowledge graphs, extracting the longest chains from subgraphs around rare medical entities to generate complex multi-hop question-answer pairs. Second, we integrate a custom-built private medical retrieval engine alongside general-purpose tools, enabling accurate medical information synthesis. Our approach generates 2100+ diverse trajectories across 12 medical specialties, each averaging 4.2 tool interactions.Through a two-stage training paradigm combining supervised fine-tuning and online reinforcement learning with composite rewards, our MedResearcher-R1-32B model demonstrates exceptional performance, establishing new state-of-the-art results on medical benchmarks while maintaining competitive performance on general deep research tasks. Our work demonstrates that strategic domain-specific innovations in architecture, tool design, and training data construction can enable smaller open-source models to outperform much larger proprietary systems in specialized domains.

Reliable clinical decision support requires medical AI agents capable of safe, multi-step reasoning over structured electronic health records (EHRs). While large language models (LLMs) show promise in healthcare, existing benchmarks inadequately assess performance on action-based tasks involving threshold evaluation, temporal aggregation, and conditional logic. We introduce ART, an Action-based Reasoning clinical Task benchmark for medical AI agents, which mines real-world EHR data to create challenging tasks targeting known reasoning weaknesses. Through analysis of existing benchmarks, we identify three dominant error categories: retrieval failures, aggregation errors, and conditional logic misjudgments. Our four-stage pipeline -- scenario identification, task generation, quality audit, and evaluation -- produces diverse, clinically validated tasks grounded in real patient data. Evaluating GPT-4o-mini and Claude 3.5 Sonnet on 600 tasks shows near-perfect retrieval after prompt refinement, but substantial gaps in aggregation (28--64%) and threshold reasoning (32--38%). By exposing failure modes in action-oriented EHR reasoning, ART advances toward more reliable clinical agents, an essential step for AI systems that reduce cognitive load and administrative burden, supporting workforce capacity in high-demand care settings

We study the implications of the modeling choice to use a graph, instead of a hypergraph, to represent real-world interconnected systems whose constituent relationships are of higher order by nature. Such a modeling choice typically involves an underlying projection process that maps the original hypergraph onto a graph, and is common in graph-based analysis. While hypergraph projection can potentially lead to loss of higher-order relations, there exists very limited studies on the consequences of doing so, as well as its remediation. This work fills this gap by doing two things: (1) we develop analysis based on graph and set theory, showing two ubiquitous patterns of hyperedges that are root to structural information loss in all hypergraph projections; we also quantify the combinatorial impossibility of recovering the lost higher-order structures if no extra help is provided; (2) we still seek to recover the lost higher-order structures in hypergraph projection, and in light of (1)'s findings we propose to relax the problem into a learning-based setting. Under this setting, we develop a learning-based hypergraph reconstruction method based on an important statistic of hyperedge distributions that we find. Our reconstruction method is evaluated on 8 real-world datasets under different settings, and exhibits consistently good performance. We also demonstrate benefits of the reconstructed hypergraphs via use cases of protein rankings and link predictions.

Retrieval-augmented learning based on radiology reports has emerged as a promising direction to improve performance on long-tail medical imaging tasks, such as rare disease detection in chest X-rays. Most existing methods rely on comparing high-dimensional text embeddings from models like CLIP or CXR-BERT, which are often difficult to interpret, computationally expensive, and not well-aligned with the structured nature of medical knowledge. We propose a novel, ontology-driven alternative for comparing radiology report texts based on clinically grounded concepts from the Unified Medical Language System (UMLS). Our method extracts standardised medical entities from free-text reports using an enhanced pipeline built on RadGraph-XL and SapBERT. These entities are linked to UMLS concepts (CUIs), enabling a transparent, interpretable set-based representation of each report. We then define a task-adaptive similarity measure based on a modified and weighted version of the Tversky Index that accounts for synonymy, negation, and hierarchical relationships between medical entities. This allows efficient and semantically meaningful similarity comparisons between reports. We demonstrate that our approach outperforms state-of-the-art embedding-based retrieval methods in a radiograph classification task on MIMIC-CXR, particularly in long-tail settings. Additionally, we use our pipeline to generate ontology-backed disease labels for MIMIC-CXR, offering a valuable new resource for downstream learning tasks. Our work provides more explainable, reliable, and task-specific retrieval strategies in clinical AI systems, especially when interpretability and domain knowledge integration are essential. Our code is available at https://github.com/Felix-012/ontology-concept-distillation

Despite achieving high accuracy on medical benchmarks, LLMs exhibit the Einstellung Effect in clinical diagnosis--relying on statistical shortcuts rather than patient-specific evidence, causing misdiagnosis in atypical cases. Existing benchmarks fail to detect this critical failure mode. We introduce MedEinst, a counterfactual benchmark with 5,383 paired clinical cases across 49 diseases. Each pair contains a control case and a "trap" case with altered discriminative evidence that flips the diagnosis. We measure susceptibility via Bias Trap Rate--probability of misdiagnosing traps despite correctly diagnosing controls. Extensive Evaluation of 17 LLMs shows frontier models achieve high baseline accuracy but severe bias trap rates. Thus, we propose ECR-Agent, aligning LLM reasoning with Evidence-Based Medicine standard via two components: (1) Dynamic Causal Inference (DCI) performs structured reasoning through dual-pathway perception, dynamic causal graph reasoning across three levels (association, intervention, counterfactual), and evidence audit for final diagnosis; (2) Critic-Driven Graph and Memory Evolution (CGME) iteratively refines the system by storing validated reasoning paths in an exemplar base and consolidating disease-specific knowledge into evolving illness graphs. Source code is to be released.

Knowledge of the medical decision process, which can be modeled as medical decision trees (MDTs), is critical to build clinical decision support systems. However, the current MDT construction methods rely heavily on time-consuming and laborious manual annotation. In this work, we propose a novel task, Text2MDT, to explore the automatic extraction of MDTs from medical texts such as medical guidelines and textbooks. We normalize the form of the MDT and create an annotated Text-to-MDT dataset in Chinese with the participation of medical experts. We investigate two different methods for the Text2MDT tasks: (a) an end-to-end framework which only relies on a GPT style large language models (LLM) instruction tuning to generate all the node information and tree structures. (b) The pipeline framework which decomposes the Text2MDT task to three subtasks. Experiments on our Text2MDT dataset demonstrate that: (a) the end-to-end method basd on LLMs (7B parameters or larger) show promising results, and successfully outperform the pipeline methods. (b) The chain-of-thought (COT) prompting method Wei2022ChainOT can improve the performance of the fine-tuned LLMs on the Text2MDT test set. (c) the lightweight pipelined method based on encoder-based pretrained models can perform comparably with LLMs with model complexity two magnititudes smaller. Our Text2MDT dataset is open-sourced at https://tianchi.aliyun.com/dataset/95414, and the source codes are open-sourced at https://github.com/michael-wzhu/text2dt.

Large Language Models (LLMs) constitute a breakthrough state-of-the-art Artificial Intelligence (AI) technology which is rapidly evolving and promises to aid in medical diagnosis either by assisting doctors or by simulating a doctor's workflow in more advanced and complex implementations. In this technical paper, we outline Cognitive Network Evaluation Toolkit for Medical Domains (COGNET-MD), which constitutes a novel benchmark for LLM evaluation in the medical domain. Specifically, we propose a scoring-framework with increased difficulty to assess the ability of LLMs in interpreting medical text. The proposed framework is accompanied with a database of Multiple Choice Quizzes (MCQs). To ensure alignment with current medical trends and enhance safety, usefulness, and applicability, these MCQs have been constructed in collaboration with several associated medical experts in various medical domains and are characterized by varying degrees of difficulty. The current (first) version of the database includes the medical domains of Psychiatry, Dentistry, Pulmonology, Dermatology and Endocrinology, but it will be continuously extended and expanded to include additional medical domains.

Humans can develop internal world models that encode common sense knowledge, telling them how the world works and predicting the consequences of their actions. This concept has emerged as a promising direction for establishing general-purpose machine-learning models in recent preliminary works, e.g., for visual representation learning. In this paper, we present CheXWorld, the first effort towards a self-supervised world model for radiographic images. Specifically, our work develops a unified framework that simultaneously models three aspects of medical knowledge essential for qualified radiologists, including 1) local anatomical structures describing the fine-grained characteristics of local tissues (e.g., architectures, shapes, and textures); 2) global anatomical layouts describing the global organization of the human body (e.g., layouts of organs and skeletons); and 3) domain variations that encourage CheXWorld to model the transitions across different appearance domains of radiographs (e.g., varying clarity, contrast, and exposure caused by collecting radiographs from different hospitals, devices, or patients). Empirically, we design tailored qualitative and quantitative analyses, revealing that CheXWorld successfully captures these three dimensions of medical knowledge. Furthermore, transfer learning experiments across eight medical image classification and segmentation benchmarks showcase that CheXWorld significantly outperforms existing SSL methods and large-scale medical foundation models. Code & pre-trained models are available at https://github.com/LeapLabTHU/CheXWorld.

The opioid epidemic continues to ravage communities worldwide, straining healthcare systems, disrupting families, and demanding urgent computational solutions. To combat this lethal opioid crisis, graph learning methods have emerged as a promising paradigm for modeling complex drug-related phenomena. However, a significant gap remains: there is no comprehensive benchmark for systematically evaluating these methods across real-world opioid crisis scenarios. To bridge this gap, we introduce OPBench, the first comprehensive opioid benchmark comprising five datasets across three critical application domains: opioid overdose detection from healthcare claims, illicit drug trafficking detection from digital platforms, and drug misuse prediction from dietary patterns. Specifically, OPBench incorporates diverse graph structures, including heterogeneous graphs and hypergraphs, to preserve the rich and complex relational information among drug-related data. To address data scarcity, we collaborate with domain experts and authoritative institutions to curate and annotate datasets while adhering to privacy and ethical guidelines. Furthermore, we establish a unified evaluation framework with standardized protocols, predefined data splits, and reproducible baselines to facilitate fair and systematic comparison among graph learning methods. Through extensive experiments, we analyze the strengths and limitations of existing graph learning methods, thereby providing actionable insights for future research in combating the opioid crisis. Our source code and datasets are available at https://github.com/Tianyi-Billy-Ma/OPBench.

Knowledge Graphs (KGs) are valuable tools for representing relationships between entities in a structured format. Traditionally, these knowledge bases are queried to extract specific information. However, question-answering (QA) over such KGs poses a challenge due to the intrinsic complexity of natural language compared to the structured format and the size of these graphs. Despite these challenges, the structured nature of KGs can provide a solid foundation for grounding the outputs of Large Language Models (LLMs), offering organizations increased reliability and control. Recent advancements in LLMs have introduced reasoning methods at inference time to improve their performance and maximize their capabilities. In this work, we propose integrating these reasoning strategies with KGs to anchor every step or "thought" of the reasoning chains in KG data. Specifically, we evaluate both agentic and automated search methods across several reasoning strategies, including Chain-of-Thought (CoT), Tree-of-Thought (ToT), and Graph-of-Thought (GoT), using GRBench, a benchmark dataset for graph reasoning with domain-specific graphs. Our experiments demonstrate that this approach consistently outperforms baseline models, highlighting the benefits of grounding LLM reasoning processes in structured KG data.

Clinical dialogue represents a complex duality requiring both the empathetic fluency of natural conversation and the rigorous precision of evidence-based medicine. While Large Language Models possess unprecedented linguistic capabilities, their architectural reliance on reactive and stateless processing often favors probabilistic plausibility over factual veracity. This structural limitation has catalyzed a paradigm shift in medical AI from generative text prediction to agentic autonomy, where the model functions as a central reasoning engine capable of deliberate planning and persistent memory. Moving beyond existing reviews that primarily catalog downstream applications, this survey provides a first-principles analysis of the cognitive architecture underpinning this shift. We introduce a novel taxonomy structured along the orthogonal axes of knowledge source and agency objective to delineate the provenance of clinical knowledge against the system's operational scope. This framework facilitates a systematic analysis of the intrinsic trade-offs between creativity and reliability by categorizing methods into four archetypes: Latent Space Clinicians, Emergent Planners, Grounded Synthesizers, and Verifiable Workflow Automators. For each paradigm, we deconstruct the technical realization across the entire cognitive pipeline, encompassing strategic planning, memory management, action execution, collaboration, and evolution to reveal how distinct architectural choices balance the tension between autonomy and safety.

Constructing large-scaled medical knowledge graphs can significantly boost healthcare applications for medical surveillance, bring much attention from recent research. An essential step in constructing large-scale MKG is extracting information from medical reports. Recently, information extraction techniques have been proposed and show promising performance in biomedical information extraction. However, these methods only consider limited types of entity and relation due to the noisy biomedical text data with complex entity correlations. Thus, they fail to provide enough information for constructing MKGs and restrict the downstream applications. To address this issue, we propose Biomedical Information Extraction, a hybrid neural network to extract relations from biomedical text and unstructured medical reports. Our model utilizes a multi-head attention enhanced graph convolutional network to capture the complex relations and context information while resisting the noise from the data. We evaluate our model on two major biomedical relationship extraction tasks, chemical-disease relation and chemical-protein interaction, and a cross-hospital pan-cancer pathology report corpus. The results show that our method achieves superior performance than baselines. Furthermore, we evaluate the applicability of our method under a transfer learning setting and show that BioIE achieves promising performance in processing medical text from different formats and writing styles.