IJCAI 2026 Papers

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.

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.

Recent breakthroughs in Vision-Language Models (VLMs) have shown strong potential in medical analysis, but they remain limited in the brain lesion image domain, especially when pathological regions occupy a small portion of the image. This is because VLMs tend to put excessive attention on background regions that are visually similar to target regions. Based on the findings, we propose SAM-GPT, a novel framework that leverages segmentation-derived spatial priors to support VLM-based lesion classification. It first uses an enhanced segmentation model to localize pathological regions for diagnostic tasks, and then converts lesion attributes (e.g., size, pixel range, lesion location) into linguistic guidance for a vision–language model. To improve small lesion recognition, we incorporate a new Hilbert scanning method into Mamba that improves both local spatial continuity and global spatial modeling. Experiments on benchmark datasets show that our model achieves an average Dice coefficient of 72.80% on the brain lesion segmentation task and an accuracy of 80.56% on the brain disease classification task, demonstrating the effectiveness of the proposed framework. The code is available at https://github.com/1JF-Wang/sam-gpt.

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.

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.

Clinical prediction increasingly relies on multi-modal inputs, where reliability and efficiency are crucial for real-world deployment. However, mainstream fusion and MoE gating typically treat all available modalities as uniformly beneficial and allow noisy or weakly informative modalities to perturb routing, leading to instability, routing collapse, and miscalibrated confidence under missingness and shift. We propose QA-MoE, a Quality-Aware and stable multimodal Mixture-of-Experts that decouples reliability estimation from routing to enable robust, sparse, and interpretable fusion. QA-MoE adopts a modular architecture where each modality is initially encoded into a shared embedding space. To deal with structurally missing data, we employ a completion pathway that maintains a consistent interface. Unlike standard approaches, QA-MoE separates reliability estimation from the routing process. We propose an Evidential Quality Scorer to measure epistemic uncertainty, which then guides a Stability-Enhanced Subset Selector to filter out noisy modalities on the fly. Additionally, we include a Ternary Expert Aggregation mechanism acting as a specialized branch to stabilize predictions when data missingness is severe. Evaluations on clinical benchmarks (ADNI for Alzheimer’s staging and MIMIC-IV for Length-of-Stay) demonstrate that QA-MoE outperforms strong multimodal baselines, improving reliability while cutting down unnecessary computation. This indicates that QA-MoE offers a robust solution for multimodal decision support, especially in clinical settings prone to noise and missing data.

Contemporary glioma diagnosis integrates molecular features with histopathology to guide clinical decision-making. However, in clinical settings, divergent imaging protocols result in incomplete MRI sequences, leading to two primary challenges: forcing existing frameworks to discard a large portion of clinical data during training and consequently limiting their clinical applicability. To address these limitations, we propose GMENet, a Generative Mixture of Experts Network for multi-center glioma diagnosis with incomplete imaging sequences. Firstly, we design a Cross-attention-based Gated Generation Module that synthesizes missing sequence features from available sequences via cross-attention and dynamic gating mechanisms, incorporating a cycle-consistency loss to preserve semantic integrity. Secondly, we introduce a Dynamically Weighted Experts Fusion Module that performs mixture-of-experts interaction and confidence-aware fusion over original and synthesized dual-sequence features for multi-task prediction. We evaluate GMENet on a multi-center cohort of 1,241 subjects from four in-house datasets and two public repositories. Experiments show that GMENet expands clinically usable training data by 97%, relative to complete-sequence-only data. Furthermore, it consistently outperforms state-of-the-art methods trained on complete data, demonstrating improved robustness under cross-center distribution shifts. Code is available at: https://github.com/spf-sd/GMENet.

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.

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

Non-pharmaceutical interventions (NPIs), such as diagnostic testing and quarantine, are crucial for controlling infectious disease outbreaks but are often constrained by limited resources, particularly in the early outbreak stages. In real-world public health settings, resources must be allocated across multiple outbreak clusters that emerge asynchronously, vary in size and risk, and compete for a shared resource budget. We define a cluster as a group of close contacts generated by a single infected index case. Thus, decisions must be made under uncertainty and heterogeneous demands while respecting operational constraints. We formulate this problem as a constrained restless multi-armed bandit and propose a hierarchical reinforcement learning framework. A global controller learns a continuous action cost multiplier that adjusts global resource demand, while a generalized local policy estimates the marginal value of allocating resources to individuals within each cluster. We evaluate the proposed framework in a realistic agent-based simulator of SARS-CoV-2 with dynamically arriving clusters. Across a wide range of system scales and testing budgets, our method consistently outperforms RMAB-inspired and heuristic baselines, improving outbreak control effectiveness by 20--30%. Experiments on up to 40 concurrently active clusters further demonstrate that the hierarchical framework is highly scalable and enables faster decision-making than the RMAB-inspired method.

Large vision-language models (VLMs) demonstrate strong performance in medical image understanding, but frequently generate clinically plausible yet incorrect statements, raising significant safety concerns. Existing medical hallucination benchmarks primarily focus on 2D imaging with one-shot diagnostic questions, offering limited insight into whether predictions are grounded in correct localization and abnormality identification, allowing critical reasoning errors to remain hidden behind seemingly correct diagnoses. We introduce Med-StepBench, the first large-scale benchmark for step-wise hallucination detection in 3D oncological PET/CT, comprising over 12,000 images and more than 1,000,000 image–statement pairs across volumetric and multi-view 2D data, which decomposes clinical reasoning into four expert-designed diagnostic stages. Using clinician-verified annotations, we perform the first step-level evaluation of general-purpose and medical VLMs, revealing systematic failure modes obscured by aggregate accuracy metrics. Furthermore, we show that current VLMs are highly susceptible to adversarial yet clinically plausible intermediate explanations, which significantly amplify hallucinations despite contradictory visual evidence. Together, our findings highlight fundamental limitations in grounding multi-step clinical reasoning and establish Med-StepBench as a rigorous benchmark for developing safer and more reliable medical VLMs.

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.

Contrastive vision–language pretraining models such as CLIP align images and text in a shared embedding space but do not explicitly model or evaluate the hierarchical semantics common in medical image interpretation. We propose HCE-CLIP (Hierarchical Conditional Energy CLIP), a vision–language pretraining framework that formulates medical image–text alignment as a hierarchical label-conditional energy modeling problem. HCE-CLIP encodes an image series using transformer-based aggregation and aligns it with free-text reports and structured label state prompts across multiple semantic levels. At each level, conditional energy functions favor clinically consistent label states while suppressing contradictory alternatives, enabling uncertainty-aware inference. To assess semantic coherence, we introduce a hierarchical contradiction-based metric that quantifies logical inconsistencies between fine-grained disease predictions and higher-level clinical summaries. Experiments on MIMIC-CXR and other public benchmarks show that HCE-CLIP outperforms existing medical vision–language pretraining methods in seen-label, zero-shot and linear-probe settings, while producing substantially fewer hierarchical contradictions.

Speech activity recognition in MEG-based non-invasive BCI systems provides a reliable speech gate that can trigger downstream decoders only when speech-related neural activity is present. Such a gate can help users interact with assistive devices in continuous settings. While MEG provides excellent temporal resolution, many MEG speech activity classifiers do not fully exploit available spatial information. We describe a hybrid MEG speech/non-speech classifier that combines a geometry-aware covariance branch with temporal neural streams. We compute shrinkage covariance matrices (SPD) and map them to a Riemannian tangent space around a reference mean; a logistic regression classifier operates on these features. A limited sensor array defines the region-of-interest component, while the final system adds a residual temporal fusion layer over aligned probability streams. The final decision rule, including fusion weights, thresholds, and sequence-level post-processing, is selected on validation only and then applied unchanged to frozen test. On a large within-subject MEG corpus, the final system achieved validation macro-F1 of 0.8972 and frozen-test macro-F1 of 0.8914. This provides a compute-efficient research prototype for MEG-based speech gating.

Predicting single-cell gene responses to chemical perturbations is vital for personalized therapy, yet existing deep learning models face significant hurdles. Standard regression-based approaches suffer from "mean prediction bias," failing to capture cellular heterogeneity, while current Flow Matching (FM) methods struggle with the extreme sparsity of single-cell data and the dimensionality mismatches inherent in transformer-based generation. To address these challenges, we introduce sc2Flow, a dual-stage framework that unifies discrete and continuous flow matching. sc2Flow first predicts the binary mask of expressed genes and subsequently models their quantitative levels using a scalable Transformer. This decoupling effectively resolves dimensionality conflicts and eliminates parameter redundancy. Extensive benchmarks on Sci-Plex3 and other datasets demonstrate that sc2Flow significantly outperforms state-of-the-art baselines on distribution matching, successfully mitigating mean bias to preserve critical biological heterogeneity.

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.

Mechanical ventilation (MV) is essential in intensive care units (ICUs), yet conventional protocols lack personalization and risk harmful over- or under-ventilation. Offline reinforcement learning (ORL) enables policy optimization from retrospective clinical data without unsafe online interaction, but existing methods are highly sensitive to distributional shift and out-of-distribution (OOD) actions, limiting their reliability in complex clinical settings. To address these challenges, We propose UBER-CQL (Uncertainty-Balanced Exploration and Robust Conservative Q-Learning), a robust ORL algorithm for safe decision-making under dataset shift. UBER-CQL integrates heteroscedastic Bayesian neural networks with conservative Q-learning to model posterior Q-value uncertainty, which is used to adaptively penalize unreliable high-risk actions while maintaining performance within the data support. We further design numerically stable objectives for conservative Bayesian value estimation. Experiments on in-distribution and OOD subsets of MIMIC-III and eICU demonstrate that UBER-CQL outperforms state-of-the-art ORL and clinician baselines, producing safer and more effective MV strategies.

Fluorescence molecular tomography (FMT) serves as a pivotal modality for preclinical tumor screening. While single-view FMT offers distinct advantages in data acquisition efficiency and cost-effectiveness, the scarcity of projection views severely exacerbates photon scattering-induced depth ambiguity, rendering 3D volumetric recovery a highly ill-posed inverse problem. To address these challenges, we propose a physics-inspired spectral topology aware reconstruction network (STAR-Net). Specifically, STAR-Net establishes a synergistic framework: initially, a frequency domain decoupling strategy is introduced to simulate the physical characteristics of diffuse light fields; building on this, a differentiable inverse spectral gating (DISG) mechanism is utilized to explicitly impose low-pass spectral regularization for precise depth recovery; and further, a dual-domain synergistic module is integrated to dynamically fuse spatial and frequency features, achieving high-fidelity detail preservation. Extensive experiments on the Digimouse benchmark demonstrate that the proposed STAR-Net achieves the highest dice coefficient under single-view conditions, validating that explicit spectral topology modeling is a powerful paradigm for mitigating depth ambiguity.

Electroencephalogram (EEG) signals are vital for automated seizure detection, but their inherent noise makes robust representation learning challenging. Existing graph construction methods, whether correlation-based or learning-based, often generate redundant or irrelevant edges due to the noisy nature of EEG data. This significantly impairs the quality of graph representations and limits downstream task performance. Motivated by the remarkable reasoning and contextual understanding capabilities of large language models (LLMs), we explore the idea of using LLMs as graph edge refiners. Specifically, we propose a two-stage framework: we first verify that LLM-based edge refinement can effectively identify and remove redundant connections, leading to significant improvements in seizure detection accuracy and more meaningful graph structures. Building on this insight, we further develop a robust solution where the initial graph is constructed using a transformer-based edge predictor and multilayer perceptron, assigning probability scores to potential edges and applying a threshold to determine their existence. The LLM then acts as an edge set refiner, making informed decisions based on both textual and statistical features of node pairs to validate the remaining connections. Extensive experiments on TUSZ dataset demonstrate that our LLM-refined graph learning framework not only enhances task performance but also yields cleaner and more interpretable graph representations.