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Hua Xu

Publications and source records attributed to Hua Xu.

At least 19 recordsLinked to original sources

Evaluating Multi-Turn Multimodal Diagnostic Reasoning on Challenging Real-World Clinical Cases

Clinical diagnostic evaluation should not only assess whether models can provide correct diagnoses, but also reflect the realities of clinical practice, including progressive disclosure of multimodal information, dynamic updating of diagnostic hypotheses, and continuous refinement of clinical reasoning. However, existing evaluations of multimodal large language models (MLLMs) typically rely on single-turn or isolated tasks, making it difficult to fully capture the complexity of real-world clinical diagnosis. To bridge this gap, we developed ClinMM-Bench, the largest multi-turn multimodal clinical diagnostic evaluation benchmark to date. ClinMM-Bench contains 1,089 challenging real-world clinical cases and 3,760 medical images across eight specialties. We systematically evaluated 15 representative MLLMs using a two-level evaluation framework that assessed both diagnostic accuracy and diagnostic reasoning quality. Results showed that proprietary models achieved the highest overall diagnostic accuracy, but the proportion of completely correct diagnoses remained limited across all models. In terms of diagnostic reasoning quality, current models can identify plausible diagnostic directions but still have considerable limitations in generating reliable diagnostic reasoning. Error analysis further identified five representative failure modes: information synthesis failure, knowledge mapping error, perception error, premature closure, and visual hallucination.

cs.CL

Unsupervised Multimodal Intent Discovery via MLLM-Guided Concept Generation and Semantic Propagation

Unsupervised multimodal intent discovery aims to uncover latent intents from unlabeled multimodal dialogues, but remains challenging due to the lack of explicit semantic supervision. Existing methods often provide limited interpretability, as their refinement mainly relies on geometric similarity rather than high-level semantic guidance. To address these limitations, we propose MCSP, a fully unsupervised method that introduces semantic refinement based on concepts into multimodal intent discovery. To obtain reliable semantic evidence for intent discovery, we identify high-quality representative samples for each cluster and use them to support MLLM-guided contrastive reasoning against neighboring clusters, which produces interpretable high-level semantic concepts. Building on these concepts, we perform semantic propagation over a semantically weighted graph to align conceptual information with local structural consistency and generate reliable pseudo-labels for representation refinement. Extensive experiments on three challenging multimodal intent datasets show that MCSP consistently outperforms state-of-the-art methods while producing interpretable clusters grounded in semantic concepts.

cs.MM

MonteRET: AI Agent Enhancing Multimodal LLMs with Multi-granularity Knowledge Retrieval for Chest CT Report Generation

Automated chest CT report generation remains challenging because clinically faithful reporting requires both whole-volume understanding and accurate description of localized anatomical findings. Here we developed and retrospectively evaluated MonteRET, a region-aware retrieval-enhanced framework for generating chest CT findings sections. MonteRET integrates global CT features with region-level anatomical representations, retrieves clinically relevant knowledge using predicted medical conditions and region-level vision-language alignment, and refines initial reports through a knowledge-guided report rewriting agent. We trained our model on a public cohort with 24,128 CT scans from RadGenome-ChestCT. We evaluated MonteRET on the public RadGenome-ChestCT test set of 1,564 CT scans and an external cohort of 82 CT scans from NewYork-Presbyterian/Weill Cornell Medical Center. MonteRET improved report quality, semantic similarity, and clinical efficacy compared with a matched baseline and several state-of-the-art methods. Gains were most pronounced for recall, suggesting fewer omitted findings. Human expert evaluation by radiology residents also favored MonteRET.

cs.CV

A safety-oriented hypothetico-deductive framework for AI-assisted differential diagnosis

Diagnostic error is a major threat to patient safety, yet current large language model (LLM) systems often treat diagnosis as a one-shot prediction task, lacking safeguards against missed high-risk alternatives or rigorous verification of their reasoning. Here, we present AegisDx, a safety-oriented framework for hypothetico-deductive clinical reasoning. AegisDx coordinates specialized LLM components through role-specific contracts, structured intermediate outputs, evidence-retrieval interfaces, and verification gates to generate broad differential diagnoses, enforce explicit screening for dangerous "must-not-miss" conditions, verify reasoning against grounded medical evidence, and structure actionable next steps. We evaluated AegisDx across three layers. On literature-derived case reports from NEJM and JAMA, with GPT-oss-120B as the shared backbone, Top-3 diagnostic accuracy was 59.9% versus 52.1% for the standalone LLM on JAMA cases and 62.7% versus 51.4% on NEJM cases. On cases from Annals of Emergency Medicine, Top-3 accuracy was 85.7% versus 68.6%; against physician-consensus must-not-miss diagnosis sets, AegisDx captured at least one such condition among its top three diagnoses in 78.0% of cases versus 52.0%. In a blinded physician evaluation of 43 real-world emergency department notes from the Yale New Haven Health System compared against GPT-5, AegisDx improved the physician-rated composite safety score from 4.31 to 4.55 on a 5-point scale (adjusted p = 2.1x10^-4), with qualitative gains in must-not-miss identification and reasoning safety. Our findings suggest that engineering diagnostic AI as a safety-oriented reasoning framework, rather than optimizing raw predictive accuracy alone, can provide a safer, more transparent, and clinically meaningful layer of bedside decision support for acute care workflows.

cs.AI

MedPMC: A Systematic Framework for Scaling High-Fidelity Medical Multimodal Data for Foundation Models

Medicine is inherently multimodal, requiring clinicians to synthesize information across diverse data streams. Yet the development of multimodal foundation models is constrained by limited access to large-scale, high-quality clinical data. Although PubMed Central (PMC) offers a complementary source of expert-authored image-text data, existing PMC-derived resources remain limited in fidelity, reproducibility, and clinical validation. We introduce MedPMC, an automated, continuously updatable framework that transforms permissively licensed literature into high-fidelity infrastructure for medical multimodal models. Applied to 6.1 million PMC articles, MedPMC curated 11 million medical image-text pairs. Component evaluations showed strong performance for initial screening (F1 = 93.2), multi-panel figure detection (F1 = 96.5), figure separation (mAP = 89.8), caption separation and alignment (F1 = 81.4; ROUGE-L = 85.3), and medical figure classification (F1 = 96.5). Manual review by five annotators, three with medical training, found 95.3% of MedPMC images medically relevant, versus 19.7% in a prior PMC-derived dataset. Across 26 benchmarks spanning 11 specialties, a MedPMC-trained CLIP-style model improved average zero-shot AUC by 7.1 percentage points over the strongest architecture-matched biomedical CLIP baseline despite using fewer than half as many image-text pairs. As the vision encoder in a multimodal large language model, it improved medical visual question-answering by 1.9 and 16.9 percentage points across two benchmarks. In 10,524 Yale New Haven Health System dermatology photographs, it improved morphology-to-image retrieval Recall@5 by 11.7 percentage points. These findings show that high-fidelity literature curation strengthens medical multimodal foundation models across benchmark and clinical settings. We publicly release the framework, corpus, benchmarks, and pretrained models.

cs.CV

Teaching agentic AI to generalize expert diagnostic reasoning in rare diseases

Rare disease diagnosis depends on expert reasoning that is scarce and difficult to transfer. Large language models rank the correct disease first in only 35.4% of benchmark cases and often rely on learned phenotype-disease associations rather than reusable diagnostic reasoning strategies. We developed liteOdyssey through Policy Iteration with Human Feedback, a process in which model failures and expert corrections are iteratively consolidated into a clinician-gated, natural-language policy executed by a language model. Across 1,243 public benchmark cases spanning 722 rare diseases, liteOdyssey ranked the correct disease first in 59.3% of cases versus 26.5% without the policy, with comparable gains in cases involving diseases excluded from policy development. The same policy transferred across model families and sizes without retraining. Adaptation of the policy to the Undiagnosed Diseases Network (UDN) improved diagnostic accuracy among 515 UDN patients, with gains confirmed by blinded physician adjudication. These results show that expert reasoning can be externalized into an inspectable and revisable natural-language policy that generalizes across rare diseases, transfers across model backbones, and adapts to a real-world patient cohort.

cs.AI

Benchmarking AI Agents for Addressing Scientific Challenges Across Scales

AI agents are increasingly being developed to accelerate scientific discovery, yet their practical capabilities in real research settings remain poorly understood. Existing benchmarks for AI agents rarely capture the complexity, heterogeneity, and extended reasoning required by scientific work, whereas benchmarks for scientific tasks often reduce research to static, direct problems and provide limited support for interactive evaluation. Here, we introduce SciAgentArena, a systematic benchmark for evaluating AI agents in real-world scientific research scenarios drawn from emerging needs across multiple domains. SciAgentArena comprises approximately 200 tasks with stepwise verification and an interactive, agent-agnostic environment for assessing diverse AI agents. Using this benchmark, we find that current agents can contribute effectively to well-specified data-analysis workflows, particularly when the task structure and evaluation criteria are clear. However, their performance remains uneven across scientific contexts: agents struggle to generate genuinely novel insights, sustain self-directed exploration, and formulate robust solutions for open-ended research questions. We further characterize common failure modes across agents and identify opportunities for improving their reliability, autonomy, and scientific reasoning. Together, SciAgentArena provides a practical framework for measuring progress in AI agents for science and for guiding the design of future agents capable of addressing complex scientific challenges. Full codes, tasks, and datasets can be accessed via this link: https://sciagentarena.github.io/.

cs.AI

A PubMed-Scale Dataset of Structured Biomedical Abstracts

Structured abstracts are important for biomedical literature processing, by facilitating information retrieval, text mining, and knowledge synthesis. However, a vast portion of abstracts indexed in PubMed remain unstructured, presenting a significant bottleneck for downstream text-processing workflows and applications. To resolve this limitation, we introduce Structured PubMed, a comprehensive corpus of section-labeled biomedical abstracts compiled from the complete PubMed database, encompassing over 23.2 million research-article records. The corpus is divided into two distinct subsets: a collection of 5.9 million author-structured abstracts parsed from official XML files, and an automatically labeled collection of 17.2 million originally unstructured abstracts structured via a verbatim-extraction Large Language Model pipeline. Every record is harmonized under a unified five-section schema and mapped to its original PubMed identifier, publication type, and publication date. This dataset can be utilized to train sentence-classification models, benchmark text-segmentation architectures, and perform large-scale, section-specific information extraction at an unprecedented PubMed-wide scale.

cs.IR

A NISQ-Aware Hybrid Quantum-Classical Framework for Scalable Combinatorial Optimization

Scalable combinatorial optimization under resource-constrained quantum hardware remains a fundamental challenge in the Noisy Intermediate-Scale Quantum (NISQ) era, due to the mismatch between exponentially growing solution spaces and limited quantum computational capacity. In this work, we propose a NISQ-aware hybrid quantum-classical optimization framework that reformulates large-scale combinatorial optimization as a resource-bounded distribution evolution process. Instead of directly optimizing individual solutions, the proposed framework operates on a probabilistic representation of the solution space, enabling efficient exploration under hardware constraints. Specifically, large problem instances are decomposed into qubit-compatible subproblems via clustering-based decomposition, ensuring resource-bounded optimization. Within each subproblem, a quantum genetic algorithm evolves the solution distribution, while periodically embedded amplitude amplification acts as a controlled quantum enhancement mechanism that accelerates convergence without increasing circuit depth. A classical refinement stage ensures global solution consistency. Extensive experiments on benchmark and synthetic datasets demonstrate that the proposed framework consistently outperforms classical and quantum-inspired baselines, with performance gains that become more pronounced as problem scale increases. This scale-dependent behavior indicates that scalability is achieved through structured decomposition rather than increased quantum complexity. Noise simulations further confirm robustness under realistic NISQ conditions, and ablation studies validate that both quantum evolutionary search and amplitude amplification contribute significantly to performance improvements.

quant-ph

IRIS: time-structured manifold projections

High-dimensional biomedical data, such as cell-by-gene matrices, are increasingly generated temporally. However, Manifold Learning algorithms, like t-SNE and UMAP, cannot incorporate time-ordering in their layouts, obfuscating the dynamics of cell types or other classes. As a solution, we present IRIS, a new Manifold Learning algorithm that structures layouts both chronologically and by manifold topology. IRIS can visualize a wide range of dynamic biomedical data, including scRNA-seq, comparative metagenomics, and literature.

cs.LG

TRACE: Temporal Routing with Autoregressive Cross-channel Experts for EEG Representation Learning

Learning transferable representations for electroencephalography (EEG) remains challenging because EEG signals are inherently multi-channel and non-stationary. Channels observed at the same time provide coupled measurements of neural activity, while the relevant temporal dynamics vary across contexts. This structure is poorly matched by architectures that apply uniform computation across time or route each channel patch independently. To this end, we propose TRACE, an autoregressive EEG pre-training framework that predicts future EEG patches from causal context while performing temporally adaptive and cross-channel coherent computation. At each temporal step, TRACE derives an expert routing decision from the causal cross-channel history and applies it jointly to all channels at that step. This preserves instantaneous cross-channel coherence while allowing different temporal regimes to activate different computation. Since routing is defined over the available channel set and causal temporal context, TRACE is compatible with heterogeneous pre-training across corpora with different channel counts, montages, sequence lengths, and recording domains. Across eight downstream EEG benchmarks, TRACE is evaluated in both settings: when downstream domains are seen only as unlabeled pre-training data and when downstream datasets are completely unseen during pre-training. It obtains the best results on several benchmarks while remaining competitive on motor imagery and clinical event classification tasks, with ablations supporting the importance of cross-channel temporal routing.

cs.LG

A Versatile AI Agent for Rare Disease Diagnosis and Risk Gene Prioritization

Accurate and timely diagnosis is essential for effective treatment, particularly in the context of rare diseases. However, current diagnostic workflows often lead to prolonged assessment times and low accuracy. To address these limitations, we introduce Hygieia, a multi-modal AI agent system designed to support precision disease diagnosis by integrating diverse data sources, including phenotypic features, genetic profiles, and clinical records. Hygieia features a router-based and knowledge-enhanced framework that mitigates hallucination and tailors diagnostic strategies to different disease categories. Notably, it prioritizes risk-related genomic factors for rare diseases and provides confidence scores to assist clinical decision-making. We conducted a comprehensive evaluation demonstrating that Hygieia achieves state-of-the-art performance across multiple diagnostic benchmarks. In collaboration with clinical experts from Yale School of Medicine and Duke-NUS Medical School, we further validated its practical utility by showing (1) Hygieia's superior diagnostic performance compared to physicians with an improvement from 12%-60% and (2) its effectiveness in assisting clinicians with medical records for handling real-world cases. Our findings indicate that Hygieia not only enhances diagnostic accuracy and interpretability but also significantly reduces clinician workload, highlighting its potential as a valuable tool in clinical decision support systems.

cs.AI

Foundation Models to Unlock Real-World Evidence from Nationwide Medical Claims

Evidence derived from large-scale real-world data (RWD) is increasingly informing regulatory evaluation and healthcare decision-making. Administrative claims provide population-scale, longitudinal records of healthcare utilization, expenditure, and detailed coding of diagnoses, procedures, and medications, yet their potential as a substrate for healthcare foundation models remains largely unexplored. Here we present ReClaim, a generative transformer trained from scratch on 43.8 billion medical events from more than 200 million enrollees in the MarketScan claims data spanning 2008-2022. ReClaim models longitudinal trajectories across diagnoses, procedures, medications, and expenditure, and was scaled to 140 million, 700 million, and 1.7 billion parameters. Across over 1,000 disease-onset prediction tasks, ReClaim achieved a mean AUC of 75.6%, substantially outperforming disease-specific LightGBM (66.3%) and the transformer-based Delphi model (69.4%), with the largest gains for rare diseases. These advantages held across retrospective and prospective evaluations and in external validation on two independent datasets. Performance improved monotonically with scale, and post-training added 13.8 percentage points over pre-training alone. Beyond disease prediction, ReClaim captured financial outcomes and improved real-world evidence (RWE) analyses: for healthcare expenditure forecasting it increased explained variance from 0.28 to 0.37 relative to LightGBM, and in a target trial emulation it reduced systematic bias by 72% on average relative to Delphi. Together, these results establish administrative claims as a scalable substrate for healthcare foundation models and show that learned representations generalize across time periods and data sources, supporting disease surveillance, expenditure forecasting, and RWE generation.

cs.AI

Quantum-Enhanced Recurrent Neural Networks via Variational Quantum Gating for Battery State of Health Prediction

Accurate state-of-health (SOH) estimation for lithium-ion batteries remains a challenging problem due to complex electrochemical degradation mechanisms and long-range temporal dependencies. In this work, we propose a quantum-enhanced recurrent framework, termed QLSTM, in which variational quantum circuits are directly embedded into the gating mechanisms of long short-term memory networks. By replacing classical affine transformations with parameterized unitary operations, the proposed model introduces structured nonlinear transformations into the recurrent state-transition process. Extensive experiments on multiple benchmark battery datasets demonstrate that QLSTM consistently outperforms classical sequence models in both predictive accuracy and robustness, achieving significant reductions in mean absolute error (MAE), with improvements on the order of 20% compared with classical LSTM baselines. Ablation studies further confirm that these improvements arise primarily from quantum-enhanced gating rather than input-level transformations. Additional analyses on qubit scaling and noise robustness reveal that model performance is governed by a balance between expressive capacity and trainability. These results provide empirical evidence that embedding quantum computational primitives within recurrent architectures offers a structurally grounded approach to improving sequence modeling capability. The proposed framework establishes a new design paradigm for integrating quantum operators into temporal learning models, with potential applications in complex dynamical system prediction tasks.

quant-ph

Evolutionary Multimodal Reasoning via Hierarchical Semantic Representation for Intent Recognition

Multimodal intent recognition aims to infer human intents by jointly modeling various modalities, playing a pivotal role in real-world dialogue systems. However, current methods struggle to model hierarchical semantics underlying complex intents and lack the capacity for self-evolving reasoning over multimodal representations. To address these issues, we propose HIER, a novel method that integrates HIerarchical semantic representation with Evolutionary Reasoning based on Multimodal Large Language Model (MLLM). Inspired by human cognition, HIER introduces a structured reasoning paradigm that organizes multimodal semantics into three progressively abstracted levels. It starts with modality-specific tokens capturing localized semantic cues, which are then clustered via a label-guided strategy to form mid-level semantic concepts. To capture higher-order structure, inter-concept relations are selected using JS divergence scores to highlight salient dependencies across concepts. These hierarchical representations are then injected into MLLM via CoT-driven prompting, enabling step-wise reasoning. Besides, HIER utilizes a self-evolution mechanism that refines semantic representations through MLLM feedback, allowing dynamic adaptation during inference. Experiments on three challenging benchmarks show that HIER consistently outperforms state-of-the-art methods and MLLMs with 1-3% gains across all metrics. Code and more results are available at https://github.com/thuiar/HIER.

cs.MM

A Very Big Video Reasoning Suite

Rapid progress in video models has largely focused on visual quality, leaving their reasoning capabilities underexplored. Video reasoning grounds intelligence in spatiotemporally consistent visual environments that go beyond what text can naturally capture, enabling intuitive reasoning over spatiotemporal structure such as continuity, interaction, and causality. However, systematically studying video reasoning and its scaling behavior is hindered by the lack of large-scale training data. To address this gap, we introduce the Very Big Video Reasoning (VBVR) Dataset, an unprecedentedly large-scale resource spanning 200 curated reasoning tasks following a principled taxonomy and over one million video clips, approximately three orders of magnitude larger than existing datasets. We further present VBVR-Bench, a verifiable evaluation framework that moves beyond model-based judging by incorporating rule-based, human-aligned scorers, enabling reproducible and interpretable diagnosis of video reasoning capabilities. Leveraging the VBVR suite, we conduct one of the first large-scale scaling studies of video reasoning and observe early signs of emergent generalization to unseen reasoning tasks. Together, VBVR lays a foundation for the next stage of research in generalizable video reasoning. The data, benchmark toolkit, and models are publicly available at https://video-reason.com/?v=vbvr .

cs.CV

An artificial intelligence framework for end-to-end rare disease phenotyping from clinical notes using large language models

Phenotyping is fundamental to rare disease diagnosis, but manual curation of structured phenotypes from clinical notes is labor-intensive and difficult to scale. Existing artificial intelligence approaches typically optimize individual components of phenotyping but do not operationalize the full clinical workflow of extracting features from clinical text, standardizing them to Human Phenotype Ontology (HPO) terms, and prioritizing diagnostically informative HPO terms. We developed RARE-PHENIX, an end-to-end AI framework for rare disease phenotyping that integrates large language model-based phenotype extraction, ontology-grounded standardization to HPO terms, and supervised ranking of diagnostically informative phenotypes. We trained RARE-PHENIX using data from 2,671 patients across 11 Undiagnosed Diseases Network clinical sites, and externally validated it on 16,357 real-world clinical notes from Vanderbilt University Medical Center. Using clinician-curated HPO terms as the gold standard, RARE-PHENIX consistently outperformed a state-of-the-art deep learning baseline (PhenoBERT) across ontology-based similarity and precision-recall-F1 metrics in end-to-end evaluation (i.e., ontology-based similarity of 0.70 vs. 0.58). Ablation analyses demonstrated performance improvements with the addition of each module in RARE-PHENIX (extraction, standardization, and prioritization), supporting the value of modeling the full clinical phenotyping workflow. By modeling phenotyping as a clinically aligned workflow rather than a single extraction task, RARE-PHENIX provides structured, ranked phenotypes that are more concordant with clinician curation and has the potential to support human-in-the-loop rare disease diagnosis in real-world settings.

cs.AI

Confidence-Uncertainty Boundary Calibration for Bayesian Deep Learning in Medical Image Analysis

In critical decision support systems based on medical imaging, the reliability of AI-assisted decision-making is as relevant as predictive accuracy. Although deep learning models have demonstrated significant accuracy, they frequently suffer from miscalibration, manifested as overconfidence in erroneous predictions. To facilitate clinical acceptance, it is imperative that models quantify uncertainty in a manner that correlates with prediction correctness, allowing clinicians to identify unreliable outputs for further review. To address this necessity, this paper proposes a probabilistic optimization framework grounded in Bayesian deep learning. Specifically, the Confidence-Uncertainty Boundary Curve (CUBC) is first explored as an intermediate operational target. Grounded in this target, a novel Confidence-Uncertainty Boundary Loss (CUB-Loss) is proposed to regularize the alignment between prediction confidence and uncertainty estimates during training, imposing penalties on high-certainty errors and low-certainty correct predictions. Upon completion of training optimization, a Boundary Curve Calibration Error (BCCE) metric is further introduced to measure the degree of boundary alignment in the calibrated model. Building on this measurement, a Dual Temperature Scaling (DTS) strategy is devised to perform post-hoc refinement, further adjusting the posterior predictive distribution across different confidence-uncertainty regions. The proposed framework is validated on three distinct medical imaging tasks: automatic screening of pneumonia, diabetic retinopathy detection, and identification of skin lesions. Empirical results demonstrate that the proposed approach improves uncertainty calibration across diverse modalities, maintains robust performance in data-scarce scenarios, and remains effective on severely imbalanced datasets, underscoring its potential for real clinical deployment.

cs.CV