Foundation Models for Electronic Health Records (FEMRs) are pretrained on large-scale structured patient data, enabling them to convert longitudinal patient trajectories into generalizable representations for diverse clinical prediction tasks. Despite their effectiveness, FEMRs remain black-box models, raising concerns about bias, interpretability, and clinical trust. To address this, we propose the first token-level explainability approach for FEMRs. We train a Transformer-based surrogate model on input-output pairs from the FEMR across two prediction tasks, approximating its behavior while preserving temporal dynamics. We identify the most influential tokens, providing insights into how FEMRs leverage different aspects of patient history for predictions. To evaluate clinical relevance, we introduce a novel clinical alignment metric that quantifies the correspondence between the surrogate model’s key tokens and clinically validated features. Our results demonstrate that the surrogate closely approximates FEMR predictions and that token-level explanations align well with clinical knowledge, offering a practical framework for interpretable and trustworthy clinical AI.
论文检索
输入标题、作者或关键词，从 15,207 篇学术成果中精准定位
Multimodal medical imaging benefits from the global context modeling of transformers, yet most existing models fuse modalities implicitly by channel concatenation, leaving cross-modal interaction unstructured or relying on costly multi-stream cross-attention. We propose Modality-Aware Token Interaction (MATI), an architecturally lightweight and backbone-agnostic module that structures multimodal interaction within a single token stream by partitioning embedding channels into modality-aligned subspaces. MATI performs modality-preserving intra-subspace self-attention and gated global mixing for controlled inter-subspace exchange. We instantiate MATI in UNETR and introduce two architectures: ModaUNETR^S refines selected skip-token representations, and ModaUNETR^E injects MATI into the transformer encoder to progressively shape the token hierarchy. Experiments on the BraTS 2020 benchmark employ five-fold cross-validation and report segmentation and efficiency metrics on the official training and validation sets. Both models consistently improve over UNETR across all tumor subregions, with larger gains for tumor core and whole tumor, and ModaUNETR^E further improves upon ModaUNETR^S. An ablation study confirms monotonic gains from structured interaction. Compared with heavier transformers, the proposed models achieve a favorable accuracy-efficiency trade-off without modality-specific encoders or quadratic cross-attention, supporting structured multimodal interaction as a first-class architectural principle. Implementation of MATI and its instantiations is available at https://github.com/S3l11/MATI.
While Large Language Models (LLMs) offer promise in scientific discovery, leveraging LLMs to drive biomedical research requires the scientific discovery process to be performed in combination with cutting-edge biomedical research and rigorous mechanistic causal chains. As such, both current Retrieval-augmented generation methods lacking causal reasoning capabilities, and the static traditional knowledge graphs failing to reflect evolving scientific knowledge, present obstacles to utilizing LLMs as scientific discovery tools. In response to these ongoing challenges, we present THGAgents. THGAgents utilize collaborative and dynamically updating agents to build a Traceable Causal Knowledge Graph, which serves as the foundation for the evidence-based knowledge structure. Crucially, we employ an LLM-driven heuristic search algorithm to traverse the complex network, balancing both novelty and rigor to deduce strict, evidence-based mechanistic causal chains. Additionally, THGAgents utilize a generator-critic loop to support hypothesis refinement. In experimental benchmarks across both cancer systems and neuroscience, THGAgents achieved up to a 0.80 hit rate in predicting validated scientific discoveries, providing an almost 9.5% increase in hypothesis quality scores versus current state-of-the-art systems, and decreasing the mechanistic hallucination rate to 1.12%. Our code is available at https://github.com/yangCode-res/THGAgents/.
Deploying diabetic retinopathy (DR) screening models in primary care requires edge-efficient systems that remain accurate, safe, and reliable under domain shift. Multi-teacher knowledge distillation (KD) is a natural compression strategy, but existing approaches largely assume that all teachers provide equally trustworthy supervision. In our setting, this assumption fails: a strong CNN teacher (EfficientNet-B3, 0.876 QWK) and a weaker Transformer teacher (Swin-Base, 0.830 QWK) are complementary, yet the Transformer's logits can still mislead the student. We therefore propose OrthKD, a selective-trust distillation framework that transfers full supervision from the strong CNN, uses feature-only distillation from the weak ViT, and enforces orthogonality between teacher-specific student projections to encourage complementary rather than redundant evidence. This design preserves local lesion precision, injects global structural context, and improves robustness to distribution shift. On 132,049 retinal images, a 5.4M-parameter MobileNetV3 student reaches 0.885 QWK on EyePACS and improves zero-shot Messidor-2 performance from 0.507 to 0.728 QWK, while also achieving strong referral AUC and calibration. These results show that selectively distilling heterogeneous teachers can enable practical DR screening on resource-constrained devices.
Temporal constraints are an intrinsic component of most clinical guidelines. Several approaches to computerized clinical guidelines (CIGs) offer temporal reasoning facilities to support the execution of a CIG for a specific patient, mostly based on bounds on differences and on the Simple Temporal Problem framework. However, in scheduling activities (e.g., within a hospital), it is necessary to consider multiple executions of CIGs for different patients, which can also be (partly) related to each other. In this work we extend current temporal reasoning techniques to apply to such a context. We propose a new temporal constraint model, prove its properties, and exploit them to provide efficient management of patients' temporal constraints, and to support efficient query answering. We also propose an experimental evaluation, demonstrating the step forward with respect to current approaches. Notably, our approach is general, and can apply to all temporal reasoning problems having the same topology of the "multiple CIG execution" problem.
Federated Learning with LoRA fine-tuning offers an efficient and privacy-aware solution for institutions to collaboratively leverage their large datasets to train VLLMs. However, participating institutions often possess heterogeneous computational resources, resulting in imbalanced LoRA ranks, which pose a major challenge for effective collaboration. In addition, real-world applications in domains such as healthcare and transportation frequently suffer from missing modalities due to user mistakes or device failures, which significantly degrade global model performance in federated settings. To the best of our knowledge, no prior work has addressed these two challenges simultaneously in federated VLLMs. To tackle these issues, we propose FediLoRA, a lightweight federated LoRA aggregation framework that effectively mitigates the impact of missing modalities in heterogeneous environment. FediLoRA is explicitly motivated by the observation that simple averaging and structured editing can jointly benefit both global and personalized models. Our approach achieves strong performance across multiple general-domain and medical-domain benchmark datasets. Additional experiments on healthcare data further demonstrate that FediLoRA is well-suited for practical, real-world deployment scenarios. Our code is released at https://github.com/gotobcn8/FediLoRA.
We present SynCABEL (Synthetic Contextualized Augmentation for Biomedical Entity Linking), a framework that addresses a central bottleneck in supervised biomedical entity linking (BEL): the scarcity of expert-annotated training data. SynCABEL leverages large language models to generate context-rich synthetic training examples for all candidate concepts in a target knowledge base, providing broad supervision without manual annotation. We demonstrate that SynCABEL, when combined with decoder-only models and guided inference establish new state-of-the-art results across three widely used multilingual benchmarks: MedMentions for English, QUAERO for French, and SPACCC for Spanish. Evaluating data efficiency, we show that SynCABEL reaches the performance of full human supervision using up to 60% less annotated data, substantially reducing reliance on labor-intensive and costly expert labeling. Finally, acknowledging that standard evaluation based on exact code matching often underestimates clinically valid predictions due to ontology redundancy, we introduce an LLM-as-a-judge protocol. This analysis reveals that SynCABEL significantly improves the rate of clinically valid predictions. Our synthetic datasets, models, and code are released to support reproducibility and future research. • HuggingFace Datasets & Models • GitHub Repository
Large Language Models (LLMs) are extensively used at biomedical text processing but often fail to capture the complex, functional relationships encoded in expert knowledge graphs like the Human Phenotype Ontology (HPO). This "semantic gap'" limits their utility in precision medicine tasks such as rare disease diagnosis, where distinguishing overlapping clinical presentations requires understanding underlying pathophysiological connections rather than just surface-level textual similarity. In this work, we propose a Neuro-Symbolic Alignment Framework that bridges this separation by integrating literature-mined specialized phenotypical descriptions with the ontological structure used as reference. Specifically, we augment phenotype representations with automatically selected text fragments from massive corpus of descriptions mined from scientific literature (PubMed), overcoming the typical data scarcity of standard ontology definitions. We define a new embedding adaptation procedure whose fine-tuning approach is guided by a novel "Disease-Overlap" similarity measure, which prioritizes clinical co-occurrence of phenotypes over taxonomic distance, and optimizes the embedding space using AnglE Loss to mitigate gradient saturation. Extensive evaluations show that our approach significantly outperforms state-of-the-art baselines, including SapBERT, on both intrinsic semantic correlation and practical downstream tasks, including synthetic patient disease ranking and solving real cases stored in Phenopacket, where our model achieves x4 top-1 accuracy than the previous best model.
Extracting multi-step explanations from knowledge graphs poses a combinatorial challenge requiring both heuristic guidance (as candidates proliferate with depth) and credit assignment (as path quality emerges over extended sequences). Frontier LLMs, strong on knowledge/reasoning benchmarks, offer a compelling source of such heuristics, yet their knowledge comes sans guarantees and compositional performance degrades as chains lengthen. We thus present TESSERA, a 3-part neuro-symbolic framework that uses LLMs in a circumscribed role: for local discriminative judgement rather than autonomous multi-step generation; the knowledge graph then defines the hypothesis space enforcing hard structural constraints, and MCTS coordinates the long-horizon search with principled credit assignment via backpropagation. LLMs perform dual roles as a prior policy biasing exploration and a comparative state evaluator supplying reward signals. Evaluation on drug mechanism elucidation across two complementary knowledge graphs demonstrates fidelity to curated biology while surfacing coherent alternative mechanisms, with ablations confirming discriminative contribution from both LLM components. Beyond its current application, our framework offers a general paradigm for compositional reasoning over structured knowledge.
As a vital task in healthcare, combinatorial medication recommendation aims to generate drug combinations tailored to patient health status. Precisely capturing the rich semantic information within clinical narratives is crucial for achieving this goal. However, existing approaches primarily rely on isolated identifiers (i.e. patient IDs, drug codes), failing to leverage the inherent semantic associations between patient conditions and medication descriptions. To fill this gap, we propose the Dual-Channel Semantics-Enhanced Network (DCSENet), a novel dual-channel framework that explicitly incorporates context-rich clinical narratives knowledge. DCSENet fine-tunes domain-adapted pre-trained language models (LMs) to capture semantic correlations between patient status and medication narratives. A transformer-based dual-channel decoder decodes the semantic information at the disease-level and the patient-level respectively. The disease-level channel focuses on the natural text semantic associations between diseases and drugs, while the patient-channel provides personalized features. To mitigate the prohibitive computational overhead of the LMs in clinical deployment, we introduce an attention-map-based knowledge distillation mechanism that efficiently transfers semantic knowledge from the LMs into an identifier-based (ID-based) target model. Extensive experiments on MIMIC-Ⅲ and MIMIC-Ⅳ datasets demonstrate that DCSENet outperforms existing state-of-the-art methods in recommendation accuracy while maintaining a low computational cost.
Self-supervised pre-training has become a key paradigm for reducing annotation costs in 3D medical imaging, yet many recent approaches rely on complex objectives or incur substantial computational overhead. We propose a simple and efficient self-supervised pre-training framework for 3D medical images based on a two-fold patch-wise perturbation strategy. The method applies Bernoulli patch masking and discrete rotations, and trains a shared encoder with a three-head objective for reconstruction, perturbation localization, and rotation prediction. This design encourages spatially aware and transferable representations while remaining computationally lightweight. Experiments across diverse segmentation and classification benchmarks, including modality-shift scenarios, demonstrate consistent improvements over general self-supervised baselines and competitive or superior performance compared to recent medical self-supervised methods, while requiring substantially less memory, computation, and training time than the state-of-the-art pre-training pipelines.
Drug repositioning has emerged as an attractive drug development strategy with deep learning-based computational methods showing great potential in predicting Drug-Disease Associations (DDAs). However, dominant computational paradigms typically rely on Random Negative Sampling (RNS) and static embedding fusion, leading to two fundamental limitations. First, RNS treats unobserved pairs uniformly, resulting in coarse decision boundaries that fail to distinguish true associations from ambiguous candidates. Second, static fusion applies a monolithic combination of heterogeneous features, failing to adapt to the sample-specific dominance of different biological mechanisms. To address these issues, we propose DIAM, which establishes a mechanism-adaptive paradigm by explicitly decoupling structural and molecular signals. Specifically, DIAM introduces a Dual-Stream Biological Mechanism Decoupling module to construct global structural propagation and local molecular interaction views explicitly. Leveraging these views, we design a biological plausibility score to guide the hard negative sampling, enforcing finer-grained decision boundaries. Furthermore, an Adaptive Residual Gating (ARG) is devised to perform instance-aware modulation, dynamically weighing the contribution of global and local views for each specific pair. Extensive experiments on three benchmark datasets demonstrate that DIAM outperforms seven state-of-the-art methods. A case study on Alzheimer's disease further validates the model's effectiveness in identifying potential candidate drugs for practical application.
Spatio-temporal epidemic forecasting is critical for public health management, yet existing methods often struggle with insensitivity to weak epidemic signals, over-simplified spatial relations, and unstable parameter estimation. To address these challenges, we propose the Spatio-Temporal priOr-aware Epidemic Predictor (STOEP), a novel hybrid framework that integrates implicit spatio-temporal priors and explicit expert priors. STOEP consists of three key components: (1) Case-aware Adjacency Learning (CAL), which dynamically adjusts mobility-based regional dependencies using historical infection patterns; (2) Space-informed Parameter Estimating (SPE), which employs learnable spatial priors to amplify weak epidemic signals; and (3) Filter-based Mechanistic Forecasting (FMF), which uses an expert-guided adaptive thresholding strategy to regularize epidemic parameters. Extensive experiments on real-world COVID-19 and influenza datasets demonstrate that STOEP outperforms the best baseline by 11.1% in RMSE. The system has been deployed at a provincial CDC in China to facilitate downstream applications.
Self-supervised learning (SSL) is now a standard way to pretrain medical image models, but performance is still mostly judged by downstream accuracy. For safety-critical screening tasks such as diabetic retinopathy grading, this is not enough: a model must also know when its predictions are unreliable and defer uncertain cases for clinical review. In this work, we examine how the length of SSL pretraining influences confidence calibration and confidence-based abstention. We evaluate multiple SSL checkpoints under a fixed fine-tuning protocol and assess calibrated confidence, coverage, selective accuracy, and selective macro-F1. Across datasets and data regimes, SSL pretraining improves selective prediction compared to training from scratch. Unlike prior SSL studies that primarily evaluate downstream accuracy or AUROC, we analyze how SSL pretraining duration influences calibration and selective prediction behavior under confidence-based abstention. However, once accuracy saturates, selective performance can still change markedly across checkpoints, and longer pretraining does not consistently improve reliability. These results underscore the importance of abstention-aware evaluation and suggest that pretraining length should be treated as an important reliability-related design choice rather than only a computational detail. Code is available at https://github.com/29 muskaan712/ijcai-knowing-when-not-to-predict.
Identifying novel hypotheses is essential to scientific research, yet this process risks being overwhelmed by the sheer volume and complexity of available information. Existing automated methods often struggle to generate novel and evidence-grounded hypotheses, lack robust iterative refinement and rarely undergo rigorous temporal evaluation for future discovery potential. To address this, we propose BIODISCO, a multi-agent framework that draws upon language model-based reasoning and a dual-mode evidence system (biomedical knowledge graphs and automated literature retrieval) for grounded novelty, integrates an internal scoring and feedback loop for iterative refinement, and validates performance through pioneering temporal and human evaluations and a Bradley-Terry paired comparison model for statistical assessment. Evaluations suggest improved novelty and significance relative to ablated configurations and a generalist biomedical agent. Designed for flexibility and modularity, BIODISCO allows seamless integration of custom language models or knowledge graphs, and can be run with just a few lines of code.
Physiological signals are widely used for health assessment in clinical and daily-life settings. Established physiological signals collected for inpatient and clinical use are often impractical for patients' daily home use due to their complexity and resource demands. In contrast, wearable signals enable continuous monitoring in everyday life, but many have limited reliability and are not widely understood or accepted in clinical practices. To leverage complementary strengths of clinical and wearable physiological signals, we propose PhysioGMC, a Generalizable Multi-modal Coordination framework for Physiological signals that explicitly accounts for their strong inter-subject variability. PhysioGMC incorporates both clinical and wearable modalities into the training process to improve cross-subject performance when only a single wearable modality is available at deployment. The framework introduces a cross-modal contrastive learning module comprising two contrastive losses to jointly learn label-relevant, subject-agnostic representations across modalities. The self-supervised contrastive loss aligns latent features across modalities, while the supervised contrastive loss encourages learning label-discriminative features that are invariant to subject identity. Experiments on cardiovascular health monitoring and sleep staging tasks demonstrate that PhysioGMC consistently outperforms existing methods, achieving superior cross-subject performance at test time using only wearable modalities, such as photoplethysmography (PPG).
Predicting drug-disease associations (DDAs) plays a crucial role in drug development and disease treatment. However, existing researches predominantly focus on single DDAs prediction task, often overlooking the intricate relationships among different tasks, which can further improve the performance of methods for DDAs prediction. To address this limitation, a multi-task prediction framework, capable of simultaneously predicting drug-disease, drug-protein, and disease-protein associations, is proposed, named MTP-DDA. The framework constructs three distinct graphs to reflect different relationships between biological entities. Then, based on these graphs, two sub-views and one main-view are constructed. For sub-view, corruption strategy is adopted to generate corrupted view, and Graph Convolutional Network (GCN) is employed to extract features from both the original view and its corrupted version, with contrastive learning applied to enhance feature representations. For main-view, GCN and Node2Vec are utilized to extract low-order and high-order node features respectively, and an attention mechanism is utilized for feature fusion. Finally, the node features from three views above are integrated, and the dot product operation is applied to the node features of association pairs to derive association scores, thereby enabling multi-task association prediction. Under 10-fold cross-validation, the proposed framework outperforms current methods on public datasets, demonstrating its effectiveness and robustness.
Recent advances in vision-language models (VLMs) have shown remarkable performance in medical image classification tasks. However, applying VLMs to fetal cardiac ultrasound (FCU) remains challenging due to compound distribution shifts, including covariate shifts caused by cross-center heterogeneity and semantic shifts arising from clinically non-standard views. To address this issue, we propose Dual-Level Contrastive Learning (DLCL), the first prompt-based VLM framework for out-of-distribution (OOD) detection in FCU, to the best of our knowledge. DLCL explicitly shapes the vision-language representation space through complementary local-level and global-level contrastive objectives. Specifically, local contrastive learning aligns instance-level features to mitigate covariate shifts, whereas global contrastive learning regularizes global prototypes to address semantic shifts. We conduct extensive experiments on a private multi-center FCU dataset and the public ISIC-OOD dataset to validate the proposed approach. On the challenging FCU task, DLCL achieves an AUROC of 89.61% and a harmonic mean of 80.35%, significantly outperforming state-of-the-art methods.
Retrieving real time information is a fundamental capability for agents with search capabilities in real world applications. However, existing benchmarks are predominantly static and therefore fail to capture the temporal dynamics of information and the continuously evolving nature of real world knowledge. To address this limitation, we propose RT-QA, a dynamic evaluation framework that leverages executable code workflows to retrieve current answers at evaluation time. Specifically, we construct an agent based pipeline that autonomously generates code for web crawling and DOM based answer extraction to produce real time ground truth. To ensure robust evaluation over time, the pipeline further incorporates a repair mechanism to adapt to changes in web page structures. RT-QA spans 12 domains, such as Finance and Sports, with 320 Chinese questions categorized into three difficulty levels. Extensive evaluations of advanced models, such as GPT-5.2 and GLM-4.7, reveal significant limitations in real time adaptability: even the best models achieve only 46% accuracy. Our analysis highlights two primary failure modes: (1) Lazy Retrieval, where agents rely on search snippets instead of deeply scanning specific websites for information, accounting for 20% of failures; and (2) Temporal Confusion, a cognitive error where agents retrieve a historical date, for example an event in 2024, and fail to anchor again to the current time, 2026, for subsequent reasoning. These findings suggest that future agents require not just better retrieval strategies, but robust temporal state management.
In multi-turn interactions, large language models (LLMs) often exhibit a persistent influence from prior turns, even after an explicit topic switch. This behavior, which we term semantic inertia, can cause responses to deviate from the expected output distribution for an independent task, undermining task isolation and reliability. This paper introduces a rigorous experimental framework to systematically characterize the nature, form, and dynamics of semantic inertia. We propose an operational definition and a causal-contrastive method that isolates semantic carryover from confounding factors like context length. Through a series of experiments on five leading LLMs, we (i) confirm the existence of semantic inertia and identify its boundary conditions; (ii) model its decay over the course of generation, revealing a characteristic timescale and a heavy-tailed distribution; (iii) decompose its effects on three distinct channels—factual accuracy, structural integrity, and stylistic expression; and (iv) probe its controllability using prompt-based interventions. Our key findings show that inertia is not a simple length effect but an intrinsic dynamic, strongest in the initial part of a generation and decaying over a timescale of approximately 100-200 tokens. Its impact is most pronounced as a stylistic residue, while its effect on factual correctness is weaker and highly dependent on the task and domain switch. Crucially, we find that prompt-level ``reset'' instructions are unreliable and often counter-productive, while conflicting constraints consistently amplify, rather than resolve, output deviation. These results suggest that governing semantic inertia requires system-level state management mechanisms rather than relying on prompt engineering alone.