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
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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.
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.
Physiological signals such as EEG, ECG, and PPG are widely used in clinical monitoring. Recent self-supervised learning (SSL) methods offer an attractive way to leverage unlabeled recordings, yet they still fall short in practice. In particular, current SSL methods struggle across heterogeneous datasets, often distorting clinically meaningful structures or learning shortcuts from temporal and cross-channel redundancy. Consequently, existing SSL methods often deliver limited performance under linear probing, a lightweight adaptation setting that better matches real-world medical scenarios. Moreover, most Transformer-based SSL models encode a flattened spatiotemporal token sequence, incurring high computation and memory cost, and are typically developed within a single modality. To address these limitations, we present SPOTR (Spatio-temporal Pooling One-Token Reconstruction), a compress-reconstruct pretraining framework that introduces a single-token global bottleneck for physiological signals. SPOTR compresses each waveform into a single-token representation and reconstructs the signal conditioned only on this representation. Meanwhile, SPOTR introduces an efficient spatio-temporal compaction module to reduce computation and memory cost. Pretrained on 20 datasets spanning EEG, iEEG, ECG, and PPG, SPOTR consistently outperforms the strongest baseline under linear probing, improving average AUC by 18.49%, 21.71%, 17.86%, and 4.64%, respectively. Compared with a representative general-purpose time-series foundation model, SPOTR achieves around 78% lower latency and 52% lower peak GPU memory on average. The code and supplementary material can be found at https://github.com/5GYYYYY/SPOTR.
Automatic radiology report generation (RRG) aims to simulate the workflow of radiologists, assisting them in clinical diagnosis. However, existing methods often fall short in utilizing all information relevant to the examination, as is typically done in clinical practice. Although some works attempt to incorporate multi-view images and historical data, these additional inputs may sometimes lead to avoidable diagnostic errors on the contrary. To address these challenges, we introduce a decision-making stage after report generation for the first time and propose a Posterior Diagnostic Decision framework (PDD-RRG) to integrate potentially conflicting diagnoses. Specifically, we create various subsets of input data and utilize an existing RRG model to generate reports from different perspectives. Then the Bayesian posterior probability and the learned thresholds for each clinical observation are calculated to obtain an aggregated diagnostic conclusion, which is subsequently used to refine the generated report. Experiments on MIMIC-CXR demonstrate that our proposed PDD-RRG can effectively enhance the clinical efficacy of existing RRG models without any retraining.
Large EEG Models (LEMs) are drawing increasing attention in EEG, as large-scale pretraining yields transferable representations that improve generalization. As EEG research moves to real-world deployment, objectives and paradigms diversify, yielding increasingly heterogeneous and unevenly scaled datasets across institutions. This evolution induces distribution drift and scale imbalance, making static pretrained LEMs brittle and requiring adaptation to newly collected data. Under the constraints of the high cost of retraining and the privacy sensitivity of newly collected data, federated learning offers a practical route to update LEMs via decentralized parameter updates. Yet standard federated fine-tuning is unstable for pretrained LEMs, suffering backbone drift, misaligned updates under non-IID heterogeneity, and scale imbalance. We propose FedGLoRA: we freeze the backbone and communicate only LoRA adapters via a dual-branch design, with a shared global branch and a private on-device branch. FedGLoRA aggregates global updates on a Grassmann subspace with a Grassmann-proximal constraint, and uses bidirectional distillation to mitigate imbalance. Experiments on motor imagery and emotion recognition show consistent gains and improved stability over strong baselines.
Single-cell perturbation screens enable systematic discovery of gene regulatory mechanisms, yet the exponential expansion of perturbation space makes comprehensive experimentation impractical. Although in silico predictors have been increasingly proposed to address this challenge, most existing methods either assume static regulatory priors or learn unconstrained data-driven representations. As a result, they often suffer from poor adaptation to state-dependent shifts and weak out-of-distribution generalization. In response, we propose URFPert, an unrolled regulatory flow network tailored for single-cell perturbation prediction. Specifically, URFPert is composed of three fundamental modules: (i) Regulatory Structure Unrolling module, which employs an iterative unrolling optimization algorithm to infer state-dependent gene regulatory networks (GRNs); (ii) Heterogeneous Graph Flow Network, which incorporates the inferred GRNs into a conditional velocity field to yield state-consistent and perturbation-specific trajectories; (iii)Discriminative Optimization Strategy, which combines Mean Squared Error~(MSE) with Maximal Coding Rate Reduction~(MCR²) to promote discriminative perturbation responses and mitigate training confounders. Comprehensive evaluations on five single-cell perturbation datasets demonstrate that URFPert outperforms state-of-the-art methods in unseen perturbation regimes, providing a powerful tool for interpreting regulatory mechanisms. The project code is public via https://github.com/Jiniretttt/URFPert.
Medication recommendation plays a critical role in clinical decision-making by supporting personalized and safe treatment planning. Existing methods rely heavily on historical co-occurrence patterns and primarily optimize discrete prescription prediction objectives, limiting generalization in rare or emerging disease settings. We propose MGRec, a framework that shifts learning from discrete prescription prediction to condition-aware modeling in a continuous molecular representation space. MGRec treats molecular structure as the primary modeling target and employs a Therapeutic--Safety Factorized Conditional Variational Autoencoder to disentangle therapeutic and safety-related factors in a condition-aware molecular latent space. The model infers treatment-relevant molecular representations conditioned on current patient-specific clinical context, which are mapped to clinically approved medications for final recommendation. To improve clinical safety, we further introduce a DDI (drug-drug interaction)-guided latent regularization to integrate drug interaction knowledge at the representation level. Experiments on two real-world benchmarks demonstrate that MGRec achieves state-of-the-art accuracy and reduced interaction risk, particularly in data-sparse scenarios.
Generating protein sequences that reliably fold into target structures is a central challenge in computational biology and protein design. Progress in protein inverse folding (PIF), however, is fundamentally constrained by the scarcity of high-quality structural data, which limits the effectiveness of existing models. In this work, we propose TTS-Design, a test-time compute scaling framework that enhances protein sequence design without retraining models or relying on larger training data. For TTS-Design, its core design is a dedicated inverse folding reward model named IF-RM, which quantitatively evaluates structure–sequence compatibility and enables effective selection among multiple candidate sequences at inference time. By integrating IF-RM into existing PIF models, TTS-Design leverages additional computation during inference stage to explore and refine candidate solutions. Extensive experiments on the CATH 4.2 and CATH 4.3 demonstrate that TTS-Design consistently improves sequence recovery and structural reliability across different backbone models, without retraining or increasing model size. Case studies on real-world proteins further confirm its practical effectiveness. Overall, our results highlight test-time compute scaling as a promising and effective paradigm for advancing protein inverse folding and other scientific problems under data-limited scenarios.
Intracranial aneurysms are life-threatening and require accurate, timely detection. Traditional manual diagnosis by radiologists can be subjective, leading to misdiagnoses, while existing deep learning approaches struggle with small aneurysms or cases complicated by surrounding tissues. In this paper, we present the Multi-View Refinement Network (MVRNet), a framework that delivers clinically meaningful performance gains on the most challenging intracranial aneurysm cases. It directly addresses real-world diagnostic difficulties, particularly for small, obscured, or ambiguously bounded lesions that conventional methods often miss. In particular, we propose a feature enhancement technique to obtain boundary-clear CTA, an informative supplement to the bone-free CTA, to further reduce the impact of noise and enhance the robustness of IA recognition. Moreover, we develop a multi-view encoder with 2D slicing in different directions to mitigate tissue occlusion effects, coupled with a progressively refined decoder that iteratively corrects uncertain predictions, ensuring precise localization and segmentation. Experimental results indicate that MVRNet improves the F1-score by 24% and the IoU by 16% in comparison with the state-of-the-art methods. Remarkably, previous methods struggled with challenging cases, while our method still achieves satisfactory results, demonstrating a >2× improvement over prior arts on challenging test sets. Our code has been released in https://github.com/TheResearchWorks/MVRNet.
Immune Checkpoint Inhibitors (ICIs) have become a major therapeutic strategy in cancer treatment. However, widespread ICIs use can cause mild-to-severe immune-related Adverse Events (irAEs). Identifying factors associated with irAEs is beneficial for assessing the risk of irAEs occurrence during ICIs treatment. Nevertheless, the lack of sufficient irAEs-related clinical tabular data has slowed progress in this field. Thus, we proposed Tabular data-driven semi-Supervised Learning (Tab-semiSL), a novel Semi-Supervised Learning (SSL) method specifically designed for tabular data. Tab-semiSL can be divided into the pre-training phase and SSL phase. Specifically, in the pre-training, we used the collected dataset of 4,817 cancer patients without the irAEs label to train an auto-encoder. In the SSL phase, the predictor was fine-tuned using the collected dataset of 237 irAEs labeled cancer patients who treated with ICIs. We assigned class-specific thresholds and used samples as pseudo-labels only when their maximum confidence exceeded the threshold, with the thresholds dynamically adjusted during training to improve reliability. We tested Tab-semiSL against three traditional machine learning approaches and five semi-supervised or self-supervised methods using two public datasets plus the collected clinical data, achieving outperformed results across most metrics. SHapley Additive exPlanations (SHAP) analysis revealed ten key factors linked to irAEs. Code and Supplementary Material are available at https://github.com/RuhaoLiu/Tab-semiSL
3D molecular linker design is a critical task in structure-based drug discovery, which requires the precise synthesis of chemical bridges to connect fragments within the constrained environment of a protein binding pocket. Existing methods often suffer from environmental blindness, treating the inter-fragment space as a vacuum and yielding candidates with poor binding affinity or severe steric clashes. To address this, we propose LinkerBridge, an equivariant framework that unifies biochemical semantics with physical constraints through two innovations: a Contextual Interaction-Aware Representation module that internalizes pre-existing biochemical semantics, and a Differentiable Physical Guidance mechanism derived from Van der Waals potentials to steer generation away from collision zones. Extensive evaluations on ZINC, GEOM, and BindingMOAD benchmarks, as well as Hsp90 and JNK3 case studies, demonstrate that LinkerBridge significantly outperforms state-of-the-art methods in real-world drug discovery.
Spatial transcriptomics has significantly advanced tissue biology and makes it possible to study the spatial interactions of cells in the microenvironment of complex tissues. However, accurately inferring intercellular communication from these data remains challenging due to the need to effectively integrate spatial topology with high-dimensional gene expression information. To address this challenge, we propose DAHGT-CCI, a novel method for inferring intercellular communication from spatial transcriptomics data. By fusing multimodal heterogeneous features to construct a unified node representation and introducing a meta-relation-aware dynamic attention mechanism, DAHGT-CCI can adaptively learn the weights of edges in the graph, thereby achieving superior precision and fine-grained inference of intercellular interactions. We evaluated the performance of DAHGT-CCI on six different spatial transcriptomics datasets. In these benchmarks, DAHGT-CCI outperformed existing graph-based learning methods and cell-cell communication inference models in terms of accuracy, AUROC, recall, and F1 score. These results demonstrate that DAHGT-CCI can more accurately reconstruct cell communication networks in complex tissue microenvironments, offering an indispensable computational tool for studying developmental processes, disease mechanisms, and potential therapeutic targets from a spatially resolved perspective.
With the rising demand for trustworthy AI in clinical practice, strong interpretability is now a critical requirement as well as accuracy. However, the modality gap for medical visual question answering is quite severe when continuous visual signals are forcibly projected into discrete text space for reasoning, and the loss of necessary diagnostic information leads to low precision and black-box opacity. To address this problem, we propose MedVCoT, which incorporates latent visual reasoning into the medical visual question answering(VQA) domain. Rather than merely integrating modules, MedVCoT utilizes the specialized expertise of MedSAM to train a large vision-language model so that it can autonomously generate consistent and continuous latent visual tokens within Visual Chain-of-Thought. This mechanism forces the model to explicitly "see" the lesion in the latent space before formulating a textual diagnosis, ensuring answers are causally rooted in verifiable visual evidence rather than statistical hallucination. We achieve this through a progressive 3-stage training procedure: medical feature alignment, visual reasoning learning by utilizing latent tokens generated, and instruction tuning for complex clinical scenarios. Extensive experiments show that MedVCoT can achieve state-of-the-art performance on multiple benchmarks, outperforming other methods by large margins. Meanwhile, it provides pixel-level segmentation masks to validate its diagnostic reasoning. Our demo is available at https://zhuqh19.github.io/MedVCoT.
Deep learning has achieved remarkable success in automated electrocardiogram (ECG) diagnosis. However, the long-tailed distribution of real-world ECG data remains a critical challenge. Existing methods mainly operate at the signal feature level and fail to exploit semantic relationships among diagnostic labels, which limits their ability to effectively recognize rare categories. To address this issue, we propose a Semantics-Guided Representation Learning (SGRL) framework, designed to leverage semantic priors to guide feature learning and thereby correct feature bias under long-tailed distributions. Specifically, we propose a Label Semantic Prompt Adaptation (LSPA) strategy, which introduces ECG-calibrated learnable parameters into label prompts to generate adaptive label semantic embeddings under a semantic-consistency constraint, thereby overcoming the limitations of coarse-grained label prompts in characterizing fine-grained intra-class morphological variations. Subsequently, we propose Semantic-Guided Representation Decorrelation (SGRD) that fuses ECG embeddings with adaptive label semantics and suppresses inter-class semantic correlations to obtain discriminative class semantic anchors, thereby improving tail-class separability. Extensive experiments on multiple public datasets demonstrate the significant superiority of SGRL in long-tailed ECG classification tasks. Our code is available on https://github.com/gfywudi/SGRL.
Immune Checkpoint Inhibitors (ICIs) represent a cornerstone of modern cancer immunotherapy. However, their clinical application is frequently accompanied by immune-related Adverse Events (irAEs) of diverse severity. Predicting Gene-Disease Associations (GDAs) is crucial for identifying the related genes that cause irAEs but remains experimentally expensive in the context of cancer immunotherapy. While existing graph neural network-based methods provide solutions to this problem, they often overlook disease-disease and disease-gene associations that may exist but have not yet been identified, leading to contaminated representations. To address these limitations, we propose Gene-Disease Associations based on Optimal Transport (GDAs-OT), a novel framework for GDA prediction. GDAs-OT constructs gene-gene, disease-disease and gene-disease relationships as graphs. Optimal transport was utilized to identify potential disease-disease associations to expand the disease-disease graph structure, and select high-confidence negative pairs in the gene-disease graph. By mapping nodes into a refined embedding space, the processed gene-disease graph guides node representation learning, providing robust node representations. Comprehensive experiments demonstrate that GDAs-OT outperforms state-of-the-art methods across most evaluation metrics. In addition, GDAs-OT successfully identifies potential risk genes for irAEs, providing a computational foundation for understanding the mechanisms of immunotherapy toxicity. Code is available at https://github.com/RuhaoLiu/GDAs-OT.
Decide less, communicate more: On the construct validity of end-to-end fact-checking in medicine
PDF ↗Technological progress has led to concrete advancements in tasks that were regarded as challenging, such as automatic fact-checking. Interest in adopting these systems for public health and medicine has grown due to the high-stakes nature of medical decisions and challenges in critically appraising a vast and diverse medical literature. Evidence-based medicine connects to every individual, and yet the nature of it is highly technical, rendering the medical literacy of majority users inadequate to sufficiently navigate the domain. Such problems with medical communication ripen the ground for end-to-end fact-checking agents: check a claim against current medical literature and return with an evidence-backed verdict. And yet, such systems remain largely unused.In this position paper, developed with expert input, we present the first study examining how clinical experts verify real claims from social media by synthesizing medical evidence. In searching for this upper-bound, we reveal fundamental challenges in end-to-end fact-checking when applied to medicine: Difficulties connecting claims in the wild to scientific evidence in the form of clinical trials; ambiguities in underspecified claims mixed with mismatched intentions; and inherently subjective veracity labels. We argue that fact-checking should be approached as an interactive communication problem, rather than an end-to-end process.
LENS: LLM-Enabled Narrative Synthesis for Mental Health by Aligning Multimodal Sensing with Language Models
PDF ↗Multimodal health sensing offers rich behavioral signals for assessing mental health, yet translating these numerical time-series measurements into natural language remains challenging. Current LLMs cannot natively ingest long-duration sensor streams, and paired sensor–text datasets are scarce. To address these challenges, we introduce LENS, a framework that aligns multimodal sensing data with language models to generate clinically grounded mental-health narratives. LENS first constructs a large-scale dataset by transforming Ecological Momentary Assessment (EMA) responses related to depression and anxiety symptoms into natural-language descriptions, yielding over 100,000 sensor–text QA pairs from 258 participants. To enable native time-series integration, we train a patch-level encoder that projects raw sensor signals directly into an LLM’s representation space. Our results show that LENS outperforms strong baselines on standard NLP metrics and task-specific measures of symptom-severity accuracy. A user study with 13 mental-health professionals further indicates that LENS-produced narratives are comprehensive and clinically meaningful. Ultimately, our approach advances LLMs as interfaces for health sensing, providing a scalable path toward models that can reason over raw behavioral signals and support downstream clinical decision-making.
MediEval: A Unified Medical Benchmark for Patient-Contextual and Knowledge-Grounded Reasoning in LLMs
PDF ↗Large Language Models (LLMs) are increasingly applied to medicine, yet their adoption is limited by concerns over reliability and safety. Existing evaluations either test factual medical knowledge in isolation or assess patient-level reasoning without verifying correctness, leaving a critical gap. We introduce MediEval, a benchmark that links MIMIC-IV electronic health records (EHRs) to a unified knowledge base built from UMLS and other biomedical vocabularies. MediEval generates diverse factual and counterfactual medical statements within real patient contexts, enabling systematic evaluation across a 4-quadrant framework that jointly considers knowledge grounding and contextual consistency. Using this framework, we identify critical failure modes, including hallucinated support and truth inversion, that current proprietary, open-source, and domain-specific LLMs frequently exhibit. To address these risks, we propose Counterfactual Risk-Aware Fine-tuning (CoRFu), a DPO-based method with an asymmetric penalty targeting unsafe confusions. CoRFu improves by +16.4 macro-F1 points over the base model and eliminates truth inversion errors, demonstrating both higher accuracy and substantially greater safety.
Applications · Health / Medicine
Measuring single-cell protein abundance is essential for resolving biological mechanisms and disease progression with high resolution. However, due to the high costs and antibody throughput limitations of current proteomics, inferring protein levels from readily available RNA data has become a critical computational necessity. Existing regression and generative methods face a fundamental geometric bottleneck: enforcing deterministic constraints on noisy, heteroscedastic data collapses intrinsic uncertainty into a rough latent manifold, which destabilizes the learning process. To overcome this, we present scChord, a noise-decoupled conditional flow matching framework built on Probabilistic Manifold Rectification. Our approach utilizes a probabilistic decoder to disentangle technical noise and over-dispersion from the raw counts, absorbing them into distributional parameters. This allows the rectified latent manifold to focus more on biological signals, serving as a robust geometric regularizer for learning efficient transport trajectories. Extensive experiments on multiple multi-omics benchmarks demonstrate that scChord not only achieves state-of-the-art inference accuracy but also faithfully reconstructs high-fidelity biological heterogeneity and complex protein distributions.