FAR-DPO: Feasibility-Aware and Robust Direct Preference Optimization for Cyclic Peptide Design

Cyclic peptides are emerging as promising molecular scaffolds in drug discovery due to their high binding affinity and structural stability. However, extending generative models from linear to cyclic peptide design remains challenging, as cyclization sharply restricts the feasible design space through coupled geometric and biophysical constraints. Moreover, limited training data has led existing approaches to rely largely on zero-shot generation or post hoc filtering, resulting in low yields of feasible designs and limited control over multi-objective trade-offs. To address these limitations, we propose FAR-DPO (Feasibility-Aware and Robust Direct Preference Optimization), an architecture-agnostic framework that steers generative models toward structurally and biophysically feasible cyclic peptide designs, particularly for challenging targets. FAR-DPO integrates feasibility-aware preference construction with difficulty-aware group-robust optimization. Specifically, it constructs within-target preference pairs through feasibility-gated multi-objective dominance and adaptively reweights predefined difficulty groups according to their current preference losses. On the CPSea LNR benchmark, under a fixed generation budget, FAR-DPO increases overall success rate from 46.89% to 57.79% on PepGLAD and from 47.96% to 49.57% on PepFlow. These gains also extend to the hardest target quartile and are accompanied by more favorable best-per-target binding scores. Together, these results demonstrate FAR-DPO's effectiveness in improving feasibility and target-wise robustness.

Towards World Models in Biomedical Research

A central goal of biomedicine is to understand, predict and ultimately control the dynamic mechanisms by which biological systems respond to perturbations, disease progression and therapeutic intervention. Although foundation models and large language models have accelerated biomedical data interpretation, most current systems remain focused on static pattern recognition rather than prospective simulation of biological futures. Here we propose biomedical world models as a paradigm for AI-driven discovery. These models learn latent representations of molecular, cellular, tissue and clinical states, together with intervention-conditioned dynamics that allow future trajectories to be simulated before actions are taken. We discuss how biomedical world models could function as data engines, environment simulators and scientific planning substrates across applications including virtual cells, organoids, virtual patients and surgical simulation. We outline the data infrastructure, evaluation benchmarks, safety constraints and governance frameworks required. Biomedical world models may provide a foundation for simulation-guided, closed-loop and experimentally actionable biomedical discovery.

MULTIBENCH++: A Unified and Comprehensive Multimodal Fusion Benchmarking Across Specialized Domains

Although multimodal fusion has made significant progress, its advancement is severely hindered by the lack of adequate evaluation benchmarks. Current fusion methods are typically evaluated on a small selection of public datasets, a limited scope that inadequately represents the complexity and diversity of real-world scenarios, potentially leading to biased evaluations. This issue presents a twofold challenge. On one hand, models may overfit to the biases of specific datasets, hindering their generalization to broader practical applications. On the other hand, the absence of a unified evaluation standard makes fair and objective comparisons between different fusion methods difficult. Consequently, a truly universal and high-performance fusion model has yet to emerge. To address these challenges, we have developed a large-scale, domain-adaptive benchmark for multimodal evaluation. This benchmark integrates over 30 datasets, encompassing 15 modalities and 20 predictive tasks across key application domains. To complement this, we have also developed an open-source, unified, and automated evaluation pipeline that includes standardized implementations of state-of-the-art models and diverse fusion paradigms. Leveraging this platform, we have conducted large-scale experiments, successfully establishing new performance baselines across multiple tasks. This work provides the academic community with a crucial platform for rigorous and reproducible assessment of multimodal models, aiming to propel the field of multimodal artificial intelligence to new heights.

MedSG-Bench: A Benchmark for Medical Image Sequences Grounding

Visual grounding is essential for precise perception and reasoning in multimodal large language models (MLLMs), especially in medical imaging domains. While existing medical visual grounding benchmarks primarily focus on single-image scenarios, real-world clinical applications often involve sequential images, where accurate lesion localization across different modalities and temporal tracking of disease progression (e.g., pre- vs. post-treatment comparison) require fine-grained cross-image semantic alignment and context-aware reasoning. To remedy the underrepresentation of image sequences in existing medical visual grounding benchmarks, we propose MedSG-Bench, the first benchmark tailored for Medical Image Sequences Grounding. It comprises eight VQA-style tasks, formulated into two paradigms of the grounding tasks, including 1) Image Difference Grounding, which focuses on detecting change regions across images, and 2) Image Consistency Grounding, which emphasizes detection of consistent or shared semantics across sequential images. MedSG-Bench covers 76 public datasets, 10 medical imaging modalities, and a wide spectrum of anatomical structures and diseases, totaling 9,630 question-answer pairs. We benchmark both general-purpose MLLMs (e.g., Qwen2.5-VL) and medical-domain specialized MLLMs (e.g., HuatuoGPT-vision), observing that even the advanced models exhibit substantial limitations in medical sequential grounding tasks. To advance this field, we construct MedSG-188K, a large-scale instruction-tuning dataset tailored for sequential visual grounding, and further develop MedSeq-Grounder, an MLLM designed to facilitate future research on fine-grained understanding across medical sequential images. The benchmark, dataset, and model are available at https://huggingface.co/MedSG-Bench

Turing Machine Evaluation for Large Language Model

With the rapid development and widespread application of Large Language Models (LLMs), rigorous evaluation has become particularly crucial. This research adopts a novel perspective, focusing on evaluating the core computational reasoning ability of LLMs, defined as the capacity of model to accurately understand rules, and execute logically computing operations. This capability assesses the reliability of LLMs as precise executors, and is critical to advanced tasks such as complex code generation and multi-step problem-solving. We propose an evaluation framework based on Universal Turing Machine (UTM) simulation. This framework requires LLMs to strictly follow instructions and track dynamic states, such as tape content and read/write head position, during multi-step computations. To enable standardized evaluation, we developed TMBench, a benchmark for systematically studying the computational reasoning capabilities of LLMs. TMBench provides several key advantages, including knowledge-agnostic evaluation, adjustable difficulty, foundational coverage through Turing machine encoding, and unlimited capacity for instance generation, ensuring scalability as models continue to evolve. We find that model performance on TMBench correlates strongly with performance on other recognized reasoning benchmarks (Pearson correlation coefficient is 0.73), clearly demonstrating that computational reasoning is a significant dimension for measuring the deep capabilities of LLMs. Code and data are available at https://github.com/HaitaoWuTJU/Turing-Machine-Bench.

DOTA: Distributional Test-Time Adaptation of Vision-Language Models

Vision-language foundation models (e.g., CLIP) have shown remarkable performance across a wide range of tasks. However, deploying these models may be unreliable when significant distribution gaps exist between the training and test data. The training-free test-time dynamic adapter (TDA) is a promising approach to address this issue by storing representative test samples to guide the classification of subsequent ones. However, TDA only naively maintains a limited number of reference samples in the cache, leading to severe test-time catastrophic forgetting when the cache is updated by dropping samples. In this paper, we propose a simple yet effective method for DistributiOnal Test-time Adaptation (Dota). Instead of naively memorizing representative test samples, Dota continually estimates the distributions of test samples, allowing the model to continually adapt to the deployment environment. The test-time posterior probabilities are then computed using the estimated distributions based on Bayes' theorem for adaptation purposes. To further enhance the adaptability on the uncertain samples, we introduce a new human-in-the-loop paradigm which identifies uncertain samples, collects human-feedback, and incorporates it into the Dota framework. Extensive experiments validate that Dota enables CLIP to continually learn, resulting in a significant improvement compared to current state-of-the-art methods.

Confidence-aware multi-modality learning for eye disease screening

Multi-modal ophthalmic image classification plays a key role in diagnosing eye diseases, as it integrates information from different sources to complement their respective performances. However, recent improvements have mainly focused on accuracy, often neglecting the importance of confidence and robustness in predictions for diverse modalities. In this study, we propose a novel multi-modality evidential fusion pipeline for eye disease screening. It provides a measure of confidence for each modality and elegantly integrates the multi-modality information using a multi-distribution fusion perspective. Specifically, our method first utilizes normal inverse gamma prior distributions over pre-trained models to learn both aleatoric and epistemic uncertainty for uni-modality. Then, the normal inverse gamma distribution is analyzed as the Student's t distribution. Furthermore, within a confidence-aware fusion framework, we propose a mixture of Student's t distributions to effectively integrate different modalities, imparting the model with heavy-tailed properties and enhancing its robustness and reliability. More importantly, the confidence-aware multi-modality ranking regularization term induces the model to more reasonably rank the noisy single-modal and fused-modal confidence, leading to improved reliability and accuracy. Experimental results on both public and internal datasets demonstrate that our model excels in robustness, particularly in challenging scenarios involving Gaussian noise and modality missing conditions. Moreover, our model exhibits strong generalization capabilities to out-of-distribution data, underscoring its potential as a promising solution for multimodal eye disease screening.

Hallucination of Multimodal Large Language Models: A Survey

This survey presents a comprehensive analysis of the phenomenon of hallucination in multimodal large language models (MLLMs), also known as Large Vision-Language Models (LVLMs), which have demonstrated significant advancements and remarkable abilities in multimodal tasks. Despite these promising developments, MLLMs often generate outputs that are inconsistent with the visual content, a challenge known as hallucination, which poses substantial obstacles to their practical deployment and raises concerns regarding their reliability in real-world applications. This problem has attracted increasing attention, prompting efforts to detect and mitigate such inaccuracies. We review recent advances in identifying, evaluating, and mitigating these hallucinations, offering a detailed overview of the underlying causes, evaluation benchmarks, metrics, and strategies developed to address this issue. Additionally, we analyze the current challenges and limitations, formulating open questions that delineate potential pathways for future research. By drawing the granular classification and landscapes of hallucination causes, evaluation benchmarks, and mitigation methods, this survey aims to deepen the understanding of hallucinations in MLLMs and inspire further advancements in the field. Through our thorough and in-depth review, we contribute to the ongoing dialogue on enhancing the robustness and reliability of MLLMs, providing valuable insights and resources for researchers and practitioners alike. Resources are available at: https://github.com/showlab/Awesome-MLLM-Hallucination.

Multimodal Fusion on Low-quality Data: A Comprehensive Survey

Multimodal fusion focuses on integrating information from multiple modalities with the goal of more accurate prediction, which has achieved remarkable progress in a wide range of scenarios, including autonomous driving and medical diagnosis. However, the reliability of multimodal fusion remains largely unexplored especially under low-quality data settings. This paper surveys the common challenges and recent advances of multimodal fusion in the wild and presents them in a comprehensive taxonomy. From a data-centric view, we identify four main challenges that are faced by multimodal fusion on low-quality data, namely (1) noisy multimodal data that are contaminated with heterogeneous noises, (2) incomplete multimodal data that some modalities are missing, (3) imbalanced multimodal data that the qualities or properties of different modalities are significantly different and (4) quality-varying multimodal data that the quality of each modality dynamically changes with respect to different samples. This new taxonomy will enable researchers to understand the state of the field and identify several potential directions. We also provide discussion for the open problems in this field together with interesting future research directions.

Selective Learning: Towards Robust Calibration with Dynamic Regularization

Miscalibration in deep learning refers to there is a discrepancy between the predicted confidence and performance. This problem usually arises due to the overfitting problem, which is characterized by learning everything presented in the training set, resulting in overconfident predictions during testing. Existing methods typically address overfitting and mitigate the miscalibration by adding a maximum-entropy regularizer to the objective function. The objective can be understood as seeking a model that fits the ground-truth labels by increasing the confidence while also maximizing the entropy of predicted probabilities by decreasing the confidence. However, previous methods lack clear guidance on confidence adjustment, leading to conflicting objectives (increasing but also decreasing confidence). Therefore, we introduce a method called Dynamic Regularization (DReg), which aims to learn what should be learned during training thereby circumventing the confidence adjusting trade-off. At a high level, DReg aims to obtain a more reliable model capable of acknowledging what it knows and does not know. Specifically, DReg effectively fits the labels for in-distribution samples (samples that should be learned) while applying regularization dynamically to samples beyond model capabilities (e.g., outliers), thereby obtaining a robust calibrated model especially on the samples beyond model capabilities. Both theoretical and empirical analyses sufficiently demonstrate the superiority of DReg compared with previous methods.