Medical Diagnosis

While Large Language Models (LLMs) have demonstrated potential in healthcare, they often struggle with the complex, non-linear reasoning required for accurate clinical diagnosis. Existing methods typically rely on static, linear mappings from symptoms to diagnoses, failing to capture the iterative, hypothesis-driven reasoning inherent in human clinicians. To bridge this gap, we introduce ClinicalAgents, a novel multi-agent framework designed to simulate the cognitive workflow of expert clinicians. Unlike rigid sequential chains, ClinicalAgents employs a dynamic orchestration mechanism modeled as a Monte Carlo Tree Search (MCTS) process. This allows an orchestrator to iteratively generate hypotheses, actively verify evidence, and trigger backtracking when critical information is missing. The foundation of this framework is a Dual-Memory architecture: a mutable working memory that maintains the evolving patient state for context-aware reasoning, and a static experience memory that retrieves clinical guidelines and historical cases via an active feedback loop. Extensive experiments demonstrate that ClinicalAgents achieves the best performance among evaluated baselines, significantly enhancing both diagnostic accuracy and explainability compared to strong single-agent and multi-agent baselines. Our code is released at https://github.com/ZhuohanGe/ClinicalAgents-Code.

While recent advancements in Large Language Models have significantly advanced dermatological diagnosis, monolithic LLMs frequently struggle with fine-grained, large-scale multi-class diagnostic tasks and rare skin disease diagnosis owing to training data sparsity, while also lacking the interpretability and traceability essential for clinical reasoning. Although multi-agent systems can offer more transparent and explainable diagnostics, existing frameworks are primarily concentrated on Visual Question Answering and conversational tasks, and their heavy reliance on static knowledge bases restricts adaptability in complex real-world clinical settings. Here, we present SkinGPT-X, a multimodal collaborative multi-agent system for dermatological diagnosis integrated with a self-evolving dermatological memory mechanism. By simulating the diagnostic workflow of dermatologists and enabling continuous memory evolution, SkinGPT-X delivers transparent and trustworthy diagnostics for the management of complex and rare dermatological cases. To validate the robustness of SkinGPT-X, we design a three-tier comparative experiment. First, we benchmark SkinGPT-X against four state-of-the-art LLMs across four public datasets, demonstrating its state-of-the-art performance with a +9.6% accuracy improvement on DDI31 and +13% weighted F1 gain on Dermnet over the state-of-the-art model. Second, we construct a large-scale multi-class dataset covering 498 distinct dermatological categories to evaluate its fine-grained classification capabilities. Finally, we curate the rare skin disease dataset, the first benchmark to address the scarcity of clinical rare skin diseases which contains 564 clinical samples with eight rare dermatological diseases. On this dataset, SkinGPT-X achieves a +9.8% accuracy improvement, a +7.1% weighted F1 improvement, a +10% Cohen's Kappa improvement.

Coronary artery disease, a leading cause of cardiovascular mortality worldwide, can be assessed non-invasively by coronary computed tomography angiography (CCTA). Although deep learning has advanced automated CCTA analysis, clinical translation remains constrained by the scarcity of expert-annotated data and by the spatial sparsity of coronary pathology, which occupies only a small fraction of each scan. Widely used label-free pretraining strategies, such as masked image modeling and contrastive learning, optimize for global anatomical reconstruction and tend to under-represent these tiny localized pathological features. Here we present CORA, an annotation-efficient model for comprehensive coronary artery disease assessment. Rather than reconstructing background anatomy, CORA learns from volumetric CCTA through a synthesis-driven self-supervised strategy: an anatomy-guided engine inserts diverse synthetic calcified and non-calcified lesions into unlabeled scans, reframing pretraining as an abnormality-detection task that biases representation learning toward clinically relevant disease features. We pretrained CORA on 10,138 unlabeled CCTA volumes and evaluated it across datasets from nine independent hospitals. Across plaque characterization, stenosis detection, and coronary artery segmentation, CORA consistently outperformed strong self-supervised pretraining baselines, with the largest gains on external multi-center data, indicating robust generalization under distributional shift. Coupling the imaging encoder with structured clinical variables further enabled near-term major adverse cardiac event (MACE) risk stratification. Our results show that pathology-centric, synthesis-driven pretraining is an effective and scalable strategy for annotation-efficient coronary artery disease assessment from CCTA.

For accurate glaucoma diagnosis and monitoring, reliable retinal layer segmentation in OCT images is essential. However, existing 2D segmentation methods often suffer from slice-to-slice inconsistencies due to the lack of contextual information across adjacent B-scans. 3D segmentation methods are better for capturing slice-to-slice context, but they require expensive computational resources. To address these limitations, we propose a 2.5D segmentation framework that incorporates a novel cross-slice feature fusion (CFF) module into a U-Net-like architecture. The CFF module fuses inter-slice features to effectively capture contextual information, enabling consistent boundary detection across slices and improved robustness in noisy regions. The framework was validated on both a clinical dataset and the publicly available DUKE DME dataset. Compared to other segmentation methods without the CFF module, the proposed method achieved an 8.56% reduction in mean absolute distance and a 13.92% reduction in root mean square error, demonstrating improved segmentation accuracy and robustness. Overall, the proposed 2.5D framework balances contextual awareness and computational efficiency, enabling anatomically reliable retinal layer delineation for automated glaucoma evaluation and potential clinical applications.

Alzheimer's disease (AD) diagnosis requires integrating neuroimaging with heterogeneous clinical evidence and reasoning under established criteria, yet most multimodal models remain opaque and weakly guideline-aligned. We present AD-Reasoning, a multimodal framework that couples structural MRI with six clinical modalities and a rule-based verifier to generate structured, NIA-AA-consistent diagnoses. AD-Reasoning combines modality-specific encoders, bidirectional cross-attention fusion, and reinforcement fine-tuning with verifiable rewards that enforce output format, guideline evidence coverage, and reasoning--decision consistency. We also release AD-MultiSense, a 10,378-visit multimodal QA dataset with guideline-validated rationales built from ADNI/AIBL. On AD-MultiSense, AD-Reasoning achieves state-of-the-art diagnostic accuracy and produces structured rationales that improve transparency over recent baselines, while providing transparent rationales.

The limited availability of dysarthric speech data makes cross-lingual detection an important but challenging problem. A key difficulty is that speech representations often encode language-dependent structure that can confound dysarthria detection. We propose a representation-level language shift (LS) that aligns source-language self-supervised speech representations with the target-language distribution using centroid-based vector adaptation estimated from healthy-control speech. We evaluate the approach on oral DDK recordings from Parkinson's disease speech datasets in Czech, German, and Spanish under both cross-lingual and multilingual settings. LS substantially improves sensitivity and F1 in cross-lingual settings, while yielding smaller but consistent gains in multilingual settings. Representation analysis further shows that LS reduces language identity in the embedding space, supporting the interpretation that LS removes language-dependent structure.

In this work, we propose Oph-Guid-RAG, a multimodal visual RAG system for ophthalmology clinical question answering and decision support. We treat each guideline page as an independent evidence unit and directly retrieve page images, preserving tables, flowcharts, and layout information. We further design a controllable retrieval framework with routing and filtering, which selectively introduces external evidence and reduces noise. The system integrates query decomposition, query rewriting, retrieval, reranking, and multimodal reasoning, and provides traceable outputs with guideline page references. We evaluate our method on HealthBench using a doctor-based scoring protocol. On the hard subset, our approach improves the overall score from 0.2969 to 0.3861 (+0.0892, +30.0%) compared to GPT-5.2, and achieves higher accuracy, improving from 0.5956 to 0.6576 (+0.0620, +10.4%). Compared to GPT-5.4, our method achieves a larger accuracy gain of +0.1289 (+24.4%). These results show that our method is more effective on challenging cases that require precise, evidence-based reasoning. Ablation studies further show that reranking, routing, and retrieval design are critical for stable performance, especially under difficult settings. Overall, we show how combining visionbased retrieval with controllable reasoning can improve evidence grounding and robustness in clinical AI applications,while pointing out that further work is needed to be more complete.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors, of which 15-25% develop metastatic disease with 5-year survival rates reported as low as 34%. PPGL may indicate hereditary syndromes requiring stricter, syndrome-specific treatment and surveillance, but clinicians often fail to recognize these associations in routine care. Clinical practice uses GAPP score for PPGL grading, but several limitations remain for PPGL diagnosis: (1) GAPP scoring demands a high workload for clinician because it requires the manual evaluation of six independent components; (2) key components such as cellularity and Ki-67 are often evaluated with subjective criteria; (3) several clinically relevant metastatic risk factors are not captured by GAPP, such as SDHB mutations, which have been associated with reported metastatic rates of 35-75%. Agent-driven diagnostic systems appear promising, but most lack traceable reasoning for decision-making and do not incorporate domain-specific knowledge such as PPGL genotype information. To address these limitations, we present PPGL-Swarm, an agentic PPGL diagnostic system that generates a comprehensive report, including automated GAPP scoring (with quantified cellularity and Ki-67), genotype risk alerts, and multimodal report with integrated evidence. The system provides an auditable reasoning trail by decomposing diagnosis into micro-tasks, each assigned to a specialized agent. The gene and table agents use knowledge enhancement to better interpret genotype and laboratory findings, and during training we use reinforcement learning to refine tool selection and task assignment.

Multimodal Large Language Models (MLLMs) have demonstrated remarkable potential in medical image analysis. However, their application in gastrointestinal endoscopy is currently hindered by two critical limitations: the misalignment between general model reasoning and standardized clinical cognitive pathways, and the lack of causal association between visual features and diagnostic outcomes. In this paper, we propose a novel Clinical-Cognitive-Aligned (CogAlign) framework to address these challenges. First, we endow the model with rigorous clinical analytical capabilities by constructing the hierarchical clinical cognition dataset and employing Supervised Fine-Tuning (SFT). Unlike conventional approaches, this strategy internalizes the hierarchical diagnostic logic of experts, ranging from anatomical localization and morphological evaluation to microvascular analysis, directly into the model. Second, to eliminate visual bias, we provide a theoretical analysis demonstrating that standard supervised tuning inevitably converges to spurious background correlations. Guided by this insight, we propose a counterfactual-driven reinforcement learning strategy to enforce causal rectification. By generating counterfactual normal samples via lesion masking and optimizing through clinical-cognition-centric rewards, we constrain the model to strictly ground its diagnosis in causal lesion features. Extensive experiments demonstrate that our approach achieves State-of-the-Art (SoTA) performance across multiple benchmarks, significantly enhancing diagnostic accuracy in complex clinical scenarios.

In clinical practice, crossmodal information including medical images and tabular data is essential for disease diagnosis. There exists a significant modality gap between these data types, which obstructs advancements in crossmodal diagnostic accuracy. Most existing crossmodal learning (CML) methods primarily focus on exploring relationships among high-level encoder outputs, leading to the neglect of local information in images. Additionally, these methods often overlook the extraction of task-relevant information. In this paper, we propose a novel coarse-to-fine crossmodal learning (CFCML) framework to progressively reduce the modality gap between multimodal images and tabular data, by thoroughly exploring inter-modal relationships. At the coarse stage, we explore the relationships between multi-granularity features from various image encoder stages and tabular information, facilitating a preliminary reduction of the modality gap. At the fine stage, we generate unimodal and crossmodal prototypes that incorporate class-aware information, and establish hierarchical anchor-based relationship mining (HRM) strategy to further diminish the modality gap and extract discriminative crossmodal information. This strategy utilize modality samples, unimodal prototypes, and crossmodal prototypes as anchors to develop contrastive learning approaches, effectively enhancing inter-class disparity while reducing intra-class disparity from multiple perspectives. Experimental results indicate that our method outperforms the state-of-the-art (SOTA) methods, achieving improvements of 1.53% and 0.91% in AUC metrics on the MEN and Derm7pt datasets, respectively. The code is available at https://github.com/IsDling/CFCML.

Recent vision-language models (VLMs) have shown strong generalization and multimodal reasoning abilities in natural domains. However, their application to medical diagnosis remains limited by the lack of comprehensive and structured datasets that capture real clinical workflows. To advance the development of VLMs for clinical applications, particularly in gastric cancer, we introduce Gastric-X, a large-scale multimodal benchmark for gastric cancer analysis providing 1.7K cases. Each case in Gastric-X includes paired resting and dynamic CT scans, endoscopic image, a set of structured biochemical indicators, expert-authored diagnostic notes, and bounding box annotations of tumor regions, reflecting realistic clinical conditions. We systematically examine the capability of recent VLMs on five core tasks: Visual Question Answering (VQA), report generation, cross-modal retrieval, disease classification, and lesion localization. These tasks simulate critical stages of clinical workflow, from visual understanding and reasoning to multimodal decision support. Through this evaluation, we aim not only to assess model performance but also to probe the nature of VLM understanding: Can current VLMs meaningfully correlate biochemical signals with spatial tumor features and textual reports? We envision Gastric-X as a step toward aligning machine intelligence with the cognitive and evidential reasoning processes of physicians, and as a resource to inspire the development of next-generation medical VLMs.

To characterize lobar and segmental airway volume differences between systemic lupus erythematosus (SLE) patients with interstitial lung disease (ILD) and those without ILD (non-ILD) using a deep learning-based approach on non-contrast chest high-resolution CT (HRCT). Methods: A retrospective analysis was conducted on 106 SLE patients (27 SLE-ILD, 79 SLE-non-ILD) who underwent HRCT. A customized deep learning framework based on the U-Net architecture was developed to automatically segment airway structures at the lobar and segmental levels via HRCT. Volumetric measurements of lung lobes and segments derived from the segmentations were statistically compared between the two groups using two-sample t-tests (significance threshold: p < 0.05). Results: At lobar level, significant airway volume enlargement in SLE-ILD patients was observed in the right upper lobe (p=0.009) and left upper lobe (p=0.039) compared to SLE-non-ILD. At the segmental level, significant differences were found in segments including R1 (p=0.016), R3 (p<0.001), and L3 (p=0.038), with the most marked changes in the upper lung zones, while lower zones showed non-significant trends. Conclusion: Our study demonstrates that an automated deep learning-based approach can effectively quantify airway volumes on HRCT scans and reveal significant, region-specific airway dilation in patients with SLE-ILD compared to those without ILD. The pattern of involvement, predominantly affecting the upper lobes and specific segments, highlights a distinct topographic phenotype of SLE-ILD and implicates airway structural alterations as a potential biomarker for disease presence. This AI-powered quantitative imaging biomarker holds promise for enhancing the early detection and monitoring of ILD in the SLE population, ultimately contributing to more personalized patient management.

3D intraoral scans (IOS) are increasingly adopted in routine dentistry due to abundant geometric evidence, and unified multi-disease diagnosis is desirable for clinical documentation and communication. While recent works introduce dental vision-language models (VLMs) to enable unified diagnosis and report generation on 2D images or multi-view images rendered from IOS, they do not fully leverage native 3D geometry. Such work is necessary and also challenging, due to: (i) heterogeneous scan forms and the complex IOS topology, (ii) multi-disease co-occurrence with class imbalance and fine-grained morphological ambiguity, (iii) limited paired 3D IOS-text data. Thus, we present IOSVLM, an end-to-end 3D VLM that represents scans as point clouds and follows a 3D encoder-projector-LLM design for unified diagnosis and generative visual question-answering (VQA), together with IOSVQA, a large-scale multi-source IOS diagnosis VQA dataset comprising 19,002 cases and 249,055 VQA pairs over 23 oral diseases and heterogeneous scan types. To address the distribution gap between color-free IOS data and color-dependent 3D pre-training, we propose a geometry-to-chromatic proxy that stabilizes fine-grained geometric perception and cross-modal alignment. A two-stage curriculum training strategy further enhances robustness. IOSVLM consistently outperforms strong baselines, achieving gains of at least +9.58% macro accuracy and +1.46% macro F1, indicating the effectiveness of direct 3D geometry modeling for IOS-based diagnosis.

This research paper outlines the development and implementation of a novel Clinical Decision Support System (CDSS) that integrates AI predictive modeling with medical knowledge bases. It utilizes the quantifiable information elements in lab results for inferring likely diagnoses a patient might have. Subsequently, suggesting investigations to confirm the likely diagnoses -- an assistive tool for physicians. The system fuses knowledge contained in a rule-base expert system with inferences of data driven predictors based on the features in labs. The data for 593,055 patients was collected from 547 primary care centers across the US to model our decision support system and derive Real-Word Evidence (RWE) to make it relevant for a large demographic of patients. Our Rule-Base comprises clinically validated rules, modeling 59 health conditions that can directly confirm one or more of diseases and assign ICD-10 codes to them. The Likely Diagnosis system uses multi-class classification, covering 37 ICD-10 codes, which are grouped together into 11 categories based on the labs that physicians prescribe to confirm the diagnosis. This research offers a novel system that assists a physician by utilizing medical profile of a patient and routine lab investigations to predict a group of likely diseases and then confirm them, coupled with providing explanations for inferences, thereby assisting physicians to reduce misdiagnosis of patients in clinical decision-making.

Modeling the complex interactions among functional subnetworks is crucial for the diagnosis of mental disorders and the identification of functional pathways. However, learning the interactions of the underlying subnetworks remains a significant challenge for existing Transformer-based methods due to the limited number of training samples. To address these challenges, we propose KD-Brain, a Prior-Informed Graph Learning framework for explicitly encoding prior knowledge to guide the learning process. Specifically, we design a Semantic-Conditioned Interaction mechanism that injects semantic priors into the attention query, explicitly navigating the subnetwork interactions based on their functional identities. Furthermore, we introduce a Pathology-Consistent Constraint, which regularizes the model optimization by aligning the learned interaction distributions with clinical priors. Additionally, KD-Brain leads to state-of-the-art performance on a wide range of disorder diagnosis tasks and identifies interpretable biomarkers consistent with psychiatric pathophysiology. Our code is available at https://anonymous.4open.science/r/KDBrain.

Knee osteoarthritis frequently exhibits discordance between structural damage observed in imaging and patient-reported symptoms such as pain. This mismatch complicates clinical interpretation and patient stratification and remains insufficiently modeled in existing decision support systems. We propose a discordance aware multimodal framework that combines machine learning prediction models with a tool grounded multi agent reasoning system. Using baseline data from the FNIH Osteoarthritis Biomarkers Consortium, we trained multimodal models to predict two progression tasks, joint space loss only progression versus non progression, and pain only progression versus non progression. The predictive system integrates three modality specific experts: a CatBoost tabular model using demographic, radiographic, MRI-derived scalar, and biomarker features; MRI image embeddings extracted using a ResNet18 backbone; and Xray embeddings derived from the same architecture. Expert predictions are fused using a stacking ensemble. Residual based models estimate expected pain from structural features, enabling the computation of a pain structure discordance score between observed and expected symptoms. A multi-agent reasoning layer interprets these signals to assign clinically interpretable OA phenotypes and generate phenotype specific management recommendations.

The automatic identification of cough segments in audio through the determination of start and end points is pivotal to building scalable screening tools in health technologies for pulmonary related diseases. We propose the application of two current pre-trained architectures to the task of cough activity detection. A dataset of recordings containing cough from patients symptomatic for tuberculosis (TB) who self-present at community-level care centres in South Africa and Uganda is employed. When automatic start and end points are determined using XLS-R, an average precision of 0.96 and an area under the receiver-operating characteristic of 0.99 are achieved for the test set. We show that best average precision is achieved by utilising only the first three layers of the network, which has the dual benefits of reduced computational and memory requirements, pivotal for smartphone-based applications. This XLS-R configuration is shown to outperform an audio spectrogram transformer (AST) as well as a logistic regression baseline by 9% and 27% absolute in test set average precision respectively. Furthermore, a downstream TB classification model trained using the coughs automatically isolated by XLS-R comfortably outperforms a model trained on the coughs isolated by AST, and is only narrowly outperformed by a classifier trained on the ground truth coughs. We conclude that the application of large pre-trained transformer models is an effective approach to identifying cough end-points and that the integration of such a model into a screening tool is feasible.

Clinical diagnosis is a complex cognitive process, grounded in dynamic cue acquisition and continuous expertise accumulation. Yet most current artificial intelligence (AI) systems are misaligned with this reality, treating diagnosis as single-pass retrospective prediction while lacking auditable mechanisms for governed improvement. We developed DxEvolve, a self-evolving diagnostic agent that bridges these gaps through an interactive deep clinical research workflow. The framework autonomously requisitions examinations and continually externalizes clinical experience from increasing encounter exposure as diagnostic cognition primitives. On the MIMIC-CDM benchmark, DxEvolve improved diagnostic accuracy by 11.2% on average over backbone models and reached 90.4% on a reader-study subset, comparable to the clinician reference (88.8%). DxEvolve improved accuracy on an independent external cohort by 10.2% (categories covered by the source cohort) and 17.1% (uncovered categories) compared to the competitive method. By transforming experience into a governable learning asset, DxEvolve supports an accountable pathway for the continual evolution of clinical AI.

We present PULSE, a medical reasoning agent that combines a domain-tuned large language model with scientific literature retrieval to support diagnostic decision-making in complex real-world cases. To evaluate its capabilities, we curated a benchmark of 82 authentic endocrinology case reports encompassing a broad spectrum of disease types and incidence levels. In controlled experiments, we compared PULSE's performance against physicians with varying levels of expertise-from residents to senior specialists-and examined how AI assistance influenced human diagnostic reasoning. PULSE attained expert-competitive accuracy, outperforming residents and junior specialists while matching senior specialist performance at both Top@1 and Top@4 thresholds. Unlike physicians, whose accuracy declined with disease rarity, PULSE maintained stable performance across incidence tiers. The agent also exhibited adaptive reasoning, increasing output length with case difficulty in a manner analogous to the longer deliberation observed among expert clinicians. When used collaboratively, PULSE enabled physicians to correct initial errors and broaden diagnostic hypotheses, but also introduced risks of automation bias. The study explores both serial and concurrent collaboration workflows, revealing that PULSE offers robust support across common and rare presentations. These findings underscore both the promise and the limitations of language model-based agents in clinical diagnosis, and offer a framework for evaluating their role in real-world decision-making.

Brain imaging classification is commonly approached from two perspectives: modeling the full image volume to capture global anatomical context, or constructing ROI-based graphs to encode localized and topological interactions. Although both representations have demonstrated independent efficacy, their relative contributions and potential complementarity remain insufficiently understood. Existing fusion approaches are typically task-specific and do not enable controlled evaluation of each representation under consistent training settings. To address this gap, we propose a unified cross-view contrastive framework for joint imaging-ROI representation learning. Our method learns subject-level global (imaging) and local (ROI-graph) embeddings and aligns them in a shared latent space using a bidirectional contrastive objective, encouraging representations from the same subject to converge while separating those from different subjects. This alignment produces comparable embeddings suitable for downstream fusion and enables systematic evaluation of imaging-only, ROI-only, and joint configurations within a unified training protocol. Extensive experiments on the ADHD-200 and ABIDE datasets demonstrate that joint learning consistently improves classification performance over either branch alone across multiple backbone choices. Moreover, interpretability analyses reveal that imaging-based and ROI-based branches emphasize distinct yet complementary discriminative patterns, explaining the observed performance gains. These findings provide principled evidence that explicitly integrating global volumetric and ROI-level representations is a promising direction for neuroimaging-based brain disorder classification. The source code is available at https://anonymous.4open.science/r/imaging-roi-contrastive-152C/.

Dynamic functional connectivity captures time-varying brain states for better neuropsychiatric diagnosis and spatio-temporal interpretability, i.e., identifying when discriminative disease signatures emerge and where they reside in the connectivity topology. Reliable interpretability faces major challenges: diagnostic signals are often subtle and sparsely distributed across both time and topology, while nuisance fluctuations and non-diagnostic connectivities are pervasive. To address these issues, we propose BrainSTR, a spatio-temporal contrastive learning framework for interpretable dynamic brain network modeling. BrainSTR learns state-consistent phase boundaries via a data-driven Adaptive Phase Partition module, identifies diagnostically critical phases with attention, and extracts disease-related connectivity within each phase using an Incremental Graph Structure Generator regularized by binarization, temporal smoothness, and sparsity. Then, we introduce a spatio-temporal supervised contrastive learning approach that leverages diagnosis-relevant spatio-temporal patterns to refine the similarity metric between samples and capture more discriminative spatio-temporal features, thereby constructing a well-structured semantic space for coherent and interpretable representations. Experiments on ASD, BD, and MDD validate the effectiveness of BrainSTR, and the discovered critical phases and subnetworks provide interpretable evidence consistent with prior neuroimaging findings. Our code: https://anonymous.4open.science/r/BrainSTR1.

Brain network analysis based on functional Magnetic Resonance Imaging (fMRI) is pivotal for diagnosing brain disorders. Existing approaches typically rely on predefined functional sub-networks to construct sub-network associations. However, we identified many cross-network interaction patterns with high Pearson correlations that this strict, prior-based organization fails to capture. To overcome this limitation, we propose the Brain Hierarchical Organization Learning (BrainHO) to learn inherently hierarchical brain network dependencies based on their intrinsic features rather than predefined sub-network labels. Specifically, we design a hierarchical attention mechanism that allows the model to aggregate nodes into a hierarchical organization, effectively capturing intricate connectivity patterns at the subgraph level. To ensure diverse, complementary, and stable organizations, we incorporate an orthogonality constraint loss, alongside a hierarchical consistency constraint strategy, to refine node-level features using high-level graph semantics. Extensive experiments on the publicly available ABIDE and REST-meta-MDD datasets demonstrate that BrainHO not only achieves state-of-the-art classification performance but also uncovers interpretable, clinically significant biomarkers by precisely localizing disease-related sub-networks.

Coronary Artery Disease (CAD) remains a leading cause of morbidity and mortality worldwide. Early detection is critical to recover patient outcomes and decrease healthcare costs. In recent years, machine learning (ML) advancements have shown significant potential in enhancing the accuracy of CAD diagnosis. This study investigates the application of ML algorithms to improve the detection of CAD by analyzing patient data, including clinical features, imaging, and biomarker profiles. Bi-directional Long Short-Term Memory (Bi-LSTM), Gated Recurrent Units (GRU), and a hybrid of Bi-LSTM+GRU were trained on large datasets to predict the presence of CAD. Results demonstrated that these ML models outperformed traditional diagnostic methods in sensitivity and specificity, offering a robust tool for clinicians to make more informed decisions. The experimental results show that the hybrid model achieved an accuracy of 97.07%. By integrating advanced data preprocessing techniques and feature selection, this study ensures optimal learning and model performance, setting a benchmark for the application of ML in CAD diagnosis. The integration of ML into CAD detection presents a promising avenue for personalized healthcare and could play a pivotal role in the future of cardiovascular disease management.

Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system whose molecular mechanisms remain incompletely understood. In this study, we developed an end-to-end machine learning pipeline to analyze transcriptomic data from peripheral blood mononuclear cells and cerebrospinal fluid, integrating both bulk microarray and single-cell RNA sequencing datasets (concentrating on CD4+ and B-cells). After rigorous preprocessing, batch correction, and gene declustering, XGBoost classifiers were trained to distinguish MS patients from healthy controls. Explainable AI tools, namely SHapley Additive exPlanations (SHAP), were employed to identify key genes driving classification, and results were compared with Differential Expression Analysis (DEA). SHAP-prioritized genes were further investigated through interaction networks and pathway enrichment analyses. The models achieved strong performance, particularly in CSF B-cells (AUC=0.94) and microarray (AUC=0.86). SHAP gene selection proved to be complementary to classical DEA. Gene clusters identified across multiple datasets highlighted immune activation, non-canonical immune checkpoints (ITK, CLEC2D, KLRG1, CEACAM1), ribosomal and translational programs, ubiquitin-proteasome regulation, lipid trafficking, and Epstein-Barr virus-related pathways. Our integrative and explainable framework reveals complementary insights beyond conventional analysis and provides novel mechanistic hypotheses and potential biomarkers for MS pathogenesis.

Diagnosing hepatic diseases accurately and interpretably is critical, yet it remains challenging in real-world clinical settings. Existing AI approaches for clinical diagnosis often lack transparency, structured reasoning, and deployability. Recent efforts have leveraged large language models (LLMs), retrieval-augmented generation (RAG), and multi-agent collaboration. However, these approaches typically retrieve evidence from a single source and fail to support iterative, role-specialized deliberation grounded in structured clinical data. To address this, we propose MedCoRAG (i.e., Medical Collaborative RAG), an end-to-end framework that generates diagnostic hypotheses from standardized abnormal findings and constructs a patient-specific evidence package by jointly retrieving and pruning UMLS knowledge graph paths and clinical guidelines. It then performs Multi-Agent Collaborative Reasoning: a Router Agent dynamically dispatches Specialist Agents based on case complexity; these agents iteratively reason over the evidence and trigger targeted re-retrievals when needed, while a Generalist Agent synthesizes all deliberations into a traceable consensus diagnosis that emulates multidisciplinary consultation. Experimental results on hepatic disease cases from MIMIC-IV show that MedCoRAG outperforms existing methods and closed-source models in both diagnostic performance and reasoning interpretability.

Functional Magnetic Resonance Imaging(fMRI) has now become a classic way for measuring brain activity, and recent trend is shifting toward utilizing fMRI brain data for AI-driven diagnosis. Given that the brain functions as not a discrete but interconnected whole, Graph-based architectures represented by Graph Convolutional Network(GCN) has emerged as a dominant framework for such task, since they are capable of treating ROIs as dynamically interconnected nodes and extracting relational architecture between them. Ironically, however, it is the very nature of GCN's architecture that acts as an obstacle to its performance. The mathematical foundation of GCN, effective for capturing global regularities, acts as a tradeoff; by smoothing features across the connected nodes repeatedly, traditional GCN tend to blur out the contrastive dynamics that might be crucial in identifying certain neurological disorders. In order to break through this structural bottleneck, we propose LUMINA, a Laplacian-Unifying Mechanism for Interpretable Neurodevelopmental Analysis. Our model is a Quad-Stream GCN that employs a bipolar RELU activation and a dual-spectrum graph Laplacian filtering mechanism, thereby capturing heterogeneous dynamics that were often blurred out in conventional GCN. By doing so, we can preserve the diverse range and characteristics of neural connections in each fMRI data. Through 5-fold cross validation on the ADHD200(N=144) and ABIDE(N=579) dataset, LUMINA demonstrates stable diagnostic performance in two of the most critical neurodevelopmental disorder in childhood, ADHD and ASD, outperforming existing models with an accuracy of 84.66% and 88.41% each.

Obstructive sleep apnea (OSA) is a sleep disorder that affects nearly one billion people globally and significantly elevates cardiovascular risk. Traditional diagnosis through polysomnography is resource-intensive and limits widespread access, creating a critical need for accurate and efficient alternatives. In this paper, we introduce KindSleep, a deep learning framework that integrates clinical knowledge with single-channel patient-specific oximetry signals and clinical data for precise OSA diagnosis. KindSleep first learns to identify clinically interpretable concepts, such as desaturation indices and respiratory disturbance events, directly from raw oximetry signals. It then fuses these AI-derived concepts with multimodal clinical data to estimate the Apnea-Hypopnea Index (AHI). We evaluate KindSleep on three large, independent datasets from the National Sleep Research Resource (SHHS, CFS, MrOS; total n = 9,815). KindSleep demonstrates excellent performance in estimating AHI scores (R2 = 0.917, ICC = 0.957) and consistently outperforms existing approaches in classifying OSA severity, achieving weighted F1-scores from 0.827 to 0.941 across diverse populations. By grounding its predictions in a layer of clinically meaningful concepts, KindSleep provides a more transparent and trustworthy diagnostic tool for sleep medicine practices.

Psychiatric consultation requires agents to elicit discriminative evidence, map uncertain narratives to diagnostic criteria, and decide when evidence suffices. Existing dialogue and retrieval-augmented systems condition policies on raw histories or appended passages, leaving observed evidence, missing checks, differentials, and support reliability entangled. We introduce MIND, a criteria-grounded evidence-state decision interface. At each turn, MIND constructs a typed state containing observed evidence, unresolved criterion checks, active differentials, criterion-linked supports, and reliability metadata. A training-split Psychiatric Reasoning Bank supplies gated supports, turning retrieval into state construction rather than prompt injection. The same state conditions action selection, process rewards, information-gain scoring, and trajectory rectification. Under EMR-grounded simulator protocols, MIND improves accuracy by 8.8 and 7.3 points over strong inference-only, RAG, and RL baselines, with gains transferring to public MDD-5k dialogues. Matched interventions attribute these gains to the shared state rather than prompt length, retrieval text, or formatting. MIND targets screening-level decision support, not autonomous diagnosis. Code is available at https://github.com/Lingxi-mental-health/MIND.Å

Clinical diagnosis is a gradual process of evidence integration, in which physicians move from symptoms and medical history to examinations, competing hypotheses, disease relations, and treatment decisions. Large language models have advanced medical text understanding and generation. Yet their clinical use remains limited by weak evidence grounding, opaque reasoning, and inconsistent links among differential diagnosis, final diagnosis, diagnostic basis, and treatment planning. We introduce MedCollab, a multi-agent framework for full-cycle clinical diagnosis and report generation. MedCollab coordinates specialist and examination agents according to patient records. It structures agent deliberation with an Issue-Based Information System (IBIS) protocol, so that each diagnostic position is supported by patient-specific evidence and medical knowledge. It also builds Hierarchical Disease Relation Chains (HDRC) to connect accepted hypotheses through progression, complication, and comorbidity relations. During multi-round deliberation, a verifier-guided consensus module evaluates evidence support, medical plausibility, and logical conflicts. It then adjusts agent contributions and filters unsupported reasoning. Experiments on ClinicalBench and MIMIC-IV show that MedCollab outperforms leading LLMs and medical multi-agent baselines in diagnostic accuracy, evidence consistency, and clinical reasoning quality. These results indicate that structured and auditable collaboration can produce more faithful and clinically coherent diagnostic reports.

Multimodal large language models (MLLMs) demonstrate considerable potential in clinical diagnostics, a domain that inherently requires synthesizing complex visual and textual data alongside consulting authoritative medical literature. However, existing benchmarks primarily evaluate MLLMs in end-to-end answering scenarios. This limits the ability to disentangle a model's foundational multimodal reasoning from its proficiency in evidence retrieval and application. We introduce the Clinical Understanding and Retrieval Evaluation (CURE) benchmark. Comprising $500$ multimodal clinical cases mapped to physician-cited reference literature, CURE evaluates reasoning and retrieval under controlled evidence settings to disentangle their respective contributions. We evaluate state-of-the-art MLLMs across distinct evidence-gathering paradigms in both closed-ended and open-ended diagnosis tasks. Evaluations reveal a stark dichotomy: while advanced models demonstrate clinical reasoning proficiency when supplied with physician reference evidence (achieving up to $73.4\%$ accuracy on differential diagnosis), their performance substantially declines (as low as $25.4\%$) when reliant on independent retrieval mechanisms. This disparity highlights the dual challenges of effectively integrating multimodal clinical evidence and retrieving precise supporting literature. CURE is publicly available at https://github.com/yanniangu/CURE.