APCyc: Property-Informed Design of Cyclic Peptides via Automated Cyclization

Cyclic peptides represent a promising class of therapeutic compounds in modern drug discovery, often offering improved stability and binding affinity. However, the de novo design of cyclic peptides remains challenging because methods must identify pocket-adaptive cyclization patterns and linkage sites while simultaneously controlling drug-relevant properties. This challenge is particularly pronounced for recent generative models trained predominantly on linear peptide data, which may fail to capture cyclization-specific constraints. To address the limitation, we introduce APCyc, a target-aware de novo cyclic peptide generation framework that explicitly models cyclization and jointly optimizes multiple essential physicochemical properties. By using an expanded residue vocabulary and explicitly encoding cyclization-site and linkage-type information, APCyc learns cyclization-aware representations and leverages Bayesian posterior guidance to steer sampling toward cyclic peptides satisfying multiple property objectives. Experimental results demonstrate that our model learns target-dependent cyclization preferences, and enables effective and controllable multi-property optimization for cyclic peptide design. The source code of this paper is available at https://github.com/HKUSTGZ-ML4Health-Lab/APCyc.

Can Broad Biomedical Knowledge be Contextualized into Scenario-Grounded Propositions?

Biomedical discovery often requires connecting broad biomedical knowledge with specific experimental or clinical data. Background knowledge suggests relevant mechanisms but is usually too general to map directly onto dataset variables, while data-driven patterns can be dataset-specific and hard to interpret mechanistically. We study this missing link as knowledge contextualization: transforming broad biomedical knowledge into evidence-supported, scenario-grounded propositions that domain experts can inspect, replay, and validate. We propose SCENE, a bi-level multi-agent framework that treats knowledge contextualization as iterative search. The upper level converts broad knowledge into search directions and grounds them in the dataset schema. The lower level executes these directions through multi-objective optimization to identify concrete propositions that balance evidential strength and data support. Feedback between the two levels progressively refines the search. We evaluate SCENE in two settings: discovering patient subgroups with heterogeneous treatment benefits in clinical trial scenarios, and identifying context-specific biological responses in LINCS L1000 studies. In clinical trials, SCENE discovers specific, well-supported subgroups and outperforms existing baselines. In L1000 studies, SCENE identifies perturbational contexts with strong target-response matching and high positive rates. These results show that SCENE bridges broad knowledge and scenario-specific evidence, producing traceable, inspectable hypotheses for follow-up validation.

Don't Retrain, Just Reuse: Recovering Dual-Target Molecules from Single-Target Diffusion Models

Designing a single molecule that modulates two targets is a promising strategy for polypharmacology, but it remains substantially harder than standard single-target generation because one candidate must satisfy two binding requirements while preserving drug-likeness and synthesizability. Existing dual-target generative methods typically introduce dual-target capability by either retraining the generator or intervening in the diffusion process during sampling. The former can be costly and difficult to stabilize when dual-target supervision is sparse, while the latter may be sensitive to denoising-time target balancing and competing update directions. These limitations motivate a generator-preserving alternative that keeps the pretrained prior intact: can dual-target candidates instead be recovered from the input space of a frozen single-target diffusion model, without modifying its parameters or denoising dynamics? We formulate this task as a constrained multi-objective optimization problem and propose REUSE, a hierarchical evolutionary input-space search framework that combines pair-conditioned exploration with structured multi-stage selection to enforce dual-target affinity, chemical quality, and diversity. Experiments show that, compared with methods that modify the diffusion process, REUSE consistently improves dual-target affinity and balance, achieving a 20.9-percentage-point gain in Dual High Affinity over the strongest prior baseline while maintaining competitive molecular quality.

Learning What Matters: Dynamic Dimension Selection and Aggregation for Interpretable Vision-Language Reward Modeling

Vision-language reward modeling faces a dilemma: generative approaches are interpretable but slow, while discriminative ones are efficient but act as opaque "black boxes." To bridge this gap, we propose VL-MDR (Vision-Language Multi-Dimensional Reward), a framework that dynamically decomposes evaluation into granular, interpretable dimensions. Instead of outputting a monolithic scalar, VL-MDR employs a visual-aware gating mechanism to identify relevant dimensions and adaptively weight them (e.g., Hallucination, Reasoning) for each specific input. To support this, we curate a dataset of 321k vision-language preference pairs annotated across 21 fine-grained dimensions. Extensive experiments show that VL-MDR consistently outperforms existing open-source reward models on benchmarks like VL-RewardBench. Furthermore, we show that VL-MDR-constructed preference pairs effectively enable DPO alignment to mitigate visual hallucinations and improve reliability, providing a scalable solution for VLM alignment.

Med-Scout: Curing MLLMs' Geometric Blindness in Medical Perception via Geometry-Aware RL Post-Training

Despite recent Multimodal Large Language Models (MLLMs)' linguistic prowess in medical diagnosis, we find even state-of-the-art MLLMs suffer from a critical perceptual deficit: geometric blindness. This failure to ground outputs in objective geometric constraints leads to plausible yet factually incorrect hallucinations, rooted in training paradigms that prioritize linguistic fluency over geometric fidelity. This paper introduces Med-Scout, a novel framework that "cures" this blindness via Reinforcement Learning (RL) that leverages the intrinsic geometric logic latent within unlabeled medical images. Instead of relying on costly expert annotations, Med-Scout derives verifiable supervision signals through three strategic proxy tasks: Hierarchical Scale Localization, Topological Jigsaw Reconstruction, and Anomaly Consistency Detection. To rigorously quantify this deficit, we present Med-Scout-Bench, a new benchmark specifically designed to evaluate geometric perception. Extensive evaluations show that Med-Scout significantly mitigates geometric blindness, outperforming leading proprietary and open-source MLLMs by over 40% on our benchmark. Furthermore, this enhanced geometric perception generalizes to broader medical understanding, achieving superior results on radiological and comprehensive medical VQA tasks.

ClinicalReTrial: A Self-Evolving AI Agent for Clinical Trial Protocol Optimization

Clinical trial failure remains a central bottleneck in drug development, where minor protocol design flaws can irreversibly compromise outcomes despite promising therapeutics. Although cutting-edge AI methods achieve strong performance in predicting trial success, they are inherently reactive for merely diagnosing risk without offering actionable remedies once failure is anticipated. To fill this gap, this paper proposes ClinicalReTrial, a self-evolving AI agent framework that addresses this gap by casting clinical trial reasoning as an iterative protocol redesign problem. Our method integrates failure diagnosis, safety-aware modification, and candidate evaluation in a closed-loop, reward-driven optimization framework. Serving the outcome prediction model as a simulation environment, ClinicalReTrial enables low-cost evaluation of protocol modifications and provides dense reward signals for continuous self-improvement. To support efficient exploration, the framework maintains hierarchical memory that captures iteration-level feedback within trials and distills transferable redesign patterns across trials. Empirically, ClinicalReTrial improves 83.3% of trial protocols with a mean success probability gain of 5.7%, and retrospective case studies demonstrate strong alignment between the discovered redesign strategies and real-world clinical trial modifications.

Incentivizing Tool-augmented Thinking with Images for Medical Image Analysis

Recent reasoning based medical MLLMs have made progress in generating step by step textual reasoning chains. However, they still struggle with complex tasks that necessitate dynamic and iterative focusing on fine-grained visual regions to achieve precise grounding and diagnosis. We introduce Ophiuchus, a versatile, tool-augmented framework that equips an MLLM to (i) decide when additional visual evidence is needed, (ii) determine where to probe and ground within the medical image, and (iii) seamlessly weave the relevant sub-image content back into an interleaved, multimodal chain of thought. In contrast to prior approaches limited by the performance ceiling of specialized tools, Ophiuchus integrates the model's inherent grounding and perception capabilities with external tools, thereby fostering higher-level reasoning. The core of our method is a three-stage training strategy: cold-start training with tool-integrated reasoning data to achieve basic tool selection and adaptation for inspecting key regions; self-reflection fine-tuning to strengthen reflective reasoning and encourage revisiting tool outputs; and Agentic Tool Reinforcement Learning to directly optimize task-specific rewards and emulate expert-like diagnostic behavior. Extensive experiments show that Ophiuchus consistently outperforms both closed-source and open-source SOTA methods across diverse medical benchmarks, including VQA, detection, and reasoning-based segmentation. Our approach illuminates a path toward medical AI agents that can genuinely "think with images" through tool-integrated reasoning. Datasets, codes, and trained models will be released publicly.

SpectralAdapt: Semi-Supervised Domain Adaptation with Spectral Priors for Human-Centered Hyperspectral Image Reconstruction

Hyperspectral imaging (HSI) holds great potential for healthcare due to its rich spectral information. However, acquiring HSI data remains costly and technically demanding. Hyperspectral image reconstruction offers a practical solution by recovering HSI data from accessible modalities, such as RGB. While general domain datasets are abundant, the scarcity of human HSI data limits progress in medical applications. To tackle this, we propose SpectralAdapt, a semi-supervised domain adaptation (SSDA) framework that bridges the domain gap between general and human-centered HSI datasets. To fully exploit limited labels and abundant unlabeled data, we enhance spectral reasoning by introducing Spectral Density Masking (SDM), which adaptively masks RGB channels based on their spectral complexity, encouraging recovery of informative regions from complementary cues during consistency training. Furthermore, we introduce Spectral Endmember Representation Alignment (SERA), which derives physically interpretable endmembers from valuable labeled pixels and employs them as domain-invariant anchors to guide unlabeled predictions, with momentum updates ensuring adaptability and stability. These components are seamlessly integrated into SpectralAdapt, a spectral prior-guided framework that effectively mitigates domain shift, spectral degradation, and data scarcity in HSI reconstruction. Experiments on benchmark datasets demonstrate consistent improvements in spectral fidelity, cross-domain generalization, and training stability, highlighting the promise of SSDA as an efficient solution for hyperspectral imaging in healthcare.

Versatile and Risk-Sensitive Cardiac Diagnosis via Graph-Based ECG Signal Representation

Despite the rapid advancements of electrocardiogram (ECG) signal diagnosis and analysis methods through deep learning, two major hurdles still limit their clinical adoption: the lack of versatility in processing ECG signals with diverse configurations, and the inadequate detection of risk signals due to sample imbalances. Addressing these challenges, we introduce VersAtile and Risk-Sensitive cardiac diagnosis (VARS), an innovative approach that employs a graph-based representation to uniformly model heterogeneous ECG signals. VARS stands out by transforming ECG signals into versatile graph structures that capture critical diagnostic features, irrespective of signal diversity in the lead count, sampling frequency, and duration. This graph-centric formulation also enhances diagnostic sensitivity, enabling precise localization and identification of abnormal ECG patterns that often elude standard analysis methods. To facilitate representation transformation, our approach integrates denoising reconstruction with contrastive learning to preserve raw ECG information while highlighting pathognomonic patterns. We rigorously evaluate the efficacy of VARS on three distinct ECG datasets, encompassing a range of structural variations. The results demonstrate that VARS not only consistently surpasses existing state-of-the-art models across all these datasets but also exhibits substantial improvement in identifying risk signals. Additionally, VARS offers interpretability by pinpointing the exact waveforms that lead to specific model outputs, thereby assisting clinicians in making informed decisions. These findings suggest that our VARS will likely emerge as an invaluable tool for comprehensive cardiac health assessment.

Utilizing Training Data to Improve LLM Reasoning for Tabular Understanding

Automated tabular understanding and reasoning are essential tasks for data scientists. Recently, Large language models (LLMs) have become increasingly prevalent in tabular reasoning tasks. Previous work focuses on (1) finetuning LLMs using labeled data or (2) Training-free prompting LLM agents using chain-of-thought (CoT). Finetuning offers dataset-specific learning at the cost of generalizability. Training-free prompting is highly generalizable but does not take full advantage of training data. In this paper, we propose a novel prompting-based reasoning approach, Learn then Retrieve: LRTab, which integrates the benefits of both by retrieving relevant information learned from training data. We first use prompting to obtain CoT responses over the training data. For incorrect CoTs, we prompt the LLM to predict Prompt Conditions to avoid the error, learning insights from the data. We validate the effectiveness of Prompt Conditions using validation data. Finally, at inference time, we retrieve the most relevant Prompt Conditions for additional context for table understanding. We provide comprehensive experiments on WikiTQ and Tabfact, showing that LRTab is interpretable, cost-efficient, and can outperform previous baselines in tabular reasoning.