MSRepaint: Multiple Sclerosis Repaint with Conditional Denoising Diffusion Implicit Model for Bidirectional Lesion Filling and Synthesis

In multiple sclerosis, lesions interfere with automated magnetic resonance imaging analyses such as brain parcellation and deformable registration, while lesion segmentation models are hindered by the limited availability of annotated training data. To address both issues, we propose MSRepaint, a unified diffusion-based generative model for bidirectional lesion filling and synthesis that restores anatomical continuity for downstream analyses and augments segmentation through realistic data generation. MSRepaint conditions on spatial lesion masks for voxel-level control, incorporates contrast dropout to handle missing inputs, integrates a repainting mechanism to preserve surrounding anatomy during lesion filling and synthesis, and employs a multi-view DDIM inversion and fusion pipeline for 3D consistency with fast inference. Extensive evaluations demonstrate the effectiveness of MSRepaint across multiple tasks. For lesion filling, we evaluate both the accuracy within the filled regions and the impact on downstream tasks including brain parcellation and deformable registration. MSRepaint outperforms the traditional lesion filling methods FSL and NiftySeg, and achieves accuracy on par with FastSurfer-LIT, a recent diffusion model-based inpainting method, while offering over 20 times faster inference. For lesion synthesis, state-of-the-art MS lesion segmentation models trained on MSRepaint-synthesized data outperform those trained on CarveMix-synthesized data or real ISBI challenge training data across multiple benchmarks, including the MICCAI 2016 and UMCL datasets. Additionally, we demonstrate that MSRepaint's unified bidirectional filling and synthesis capability, with full spatial control over lesion appearance, enables high-fidelity simulation of lesion evolution in longitudinal MS progression.

UniMapGen: A Generative Framework for Large-Scale Map Construction from Multi-modal Data

Large-scale map construction is foundational for critical applications such as autonomous driving and navigation systems. Traditional large-scale map construction approaches mainly rely on costly and inefficient special data collection vehicles and labor-intensive annotation processes. While existing satellite-based methods have demonstrated promising potential in enhancing the efficiency and coverage of map construction, they exhibit two major limitations: (1) inherent drawbacks of satellite data (e.g., occlusions, outdatedness) and (2) inefficient vectorization from perception-based methods, resulting in discontinuous and rough roads that require extensive post-processing. This paper presents a novel generative framework, UniMapGen, for large-scale map construction, offering three key innovations: (1) representing lane lines as \textbf{discrete sequence} and establishing an iterative strategy to generate more complete and smooth map vectors than traditional perception-based methods. (2) proposing a flexible architecture that supports \textbf{multi-modal} inputs, enabling dynamic selection among BEV, PV, and text prompt, to overcome the drawbacks of satellite data. (3) developing a \textbf{state update} strategy for global continuity and consistency of the constructed large-scale map. UniMapGen achieves state-of-the-art performance on the OpenSatMap dataset. Furthermore, UniMapGen can infer occluded roads and predict roads missing from dataset annotations. Our code will be released.

Ideal Registration? Segmentation is All You Need

Deep learning has revolutionized image registration by its ability to handle diverse tasks while achieving significant speed advantages over conventional approaches. Current approaches, however, often employ globally uniform smoothness constraints that fail to accommodate the complex, regionally varying deformations characteristic of anatomical motion. To address this limitation, we propose SegReg, a Segmentation-driven Registration framework that implements anatomically adaptive regularization by exploiting region-specific deformation patterns. Our SegReg first decomposes input moving and fixed images into anatomically coherent subregions through segmentation. These localized domains are then processed by the same registration backbone to compute optimized partial deformation fields, which are subsequently integrated into a global deformation field. SegReg achieves near-perfect structural alignment (98.23% Dice on critical anatomies) using ground-truth segmentation, and outperforms existing methods by 2-12% across three clinical registration scenarios (cardiac, abdominal, and lung images) even with automatic segmentation. Our SegReg demonstrates a near-linear dependence of registration accuracy on segmentation quality, transforming the registration challenge into a segmentation problem. The source code will be released upon manuscript acceptance.

Gaussian Primitive Optimized Deformable Retinal Image Registration

Deformable retinal image registration is notoriously difficult due to large homogeneous regions and sparse but critical vascular features, which cause limited gradient signals in standard learning-based frameworks. In this paper, we introduce Gaussian Primitive Optimization (GPO), a novel iterative framework that performs structured message passing to overcome these challenges. After an initial coarse alignment, we extract keypoints at salient anatomical structures (e.g., major vessels) to serve as a minimal set of descriptor-based control nodes (DCN). Each node is modelled as a Gaussian primitive with trainable position, displacement, and radius, thus adapting its spatial influence to local deformation scales. A K-Nearest Neighbors (KNN) Gaussian interpolation then blends and propagates displacement signals from these information-rich nodes to construct a globally coherent displacement field; focusing interpolation on the top (K) neighbors reduces computational overhead while preserving local detail. By strategically anchoring nodes in high-gradient regions, GPO ensures robust gradient flow, mitigating vanishing gradient signal in textureless areas. The framework is optimized end-to-end via a multi-term loss that enforces both keypoint consistency and intensity alignment. Experiments on the FIRE dataset show that GPO reduces the target registration error from 6.2\,px to ~2.4\,px and increases the AUC at 25\,px from 0.770 to 0.938, substantially outperforming existing methods. The source code can be accessed via https://github.com/xintian-99/GPOreg.

PepThink-R1: LLM for Interpretable Cyclic Peptide Optimization with CoT SFT and Reinforcement Learning

Designing therapeutic peptides with tailored properties is hindered by the vastness of sequence space, limited experimental data, and poor interpretability of current generative models. To address these challenges, we introduce PepThink-R1, a generative framework that integrates large language models (LLMs) with chain-of-thought (CoT) supervised fine-tuning and reinforcement learning (RL). Unlike prior approaches, PepThink-R1 explicitly reasons about monomer-level modifications during sequence generation, enabling interpretable design choices while optimizing for multiple pharmacological properties. Guided by a tailored reward function balancing chemical validity and property improvements, the model autonomously explores diverse sequence variants. We demonstrate that PepThink-R1 generates cyclic peptides with significantly enhanced lipophilicity, stability, and exposure, outperforming existing general LLMs (e.g., GPT-5) and domain-specific baseline in both optimization success and interpretability. To our knowledge, this is the first LLM-based peptide design framework that combines explicit reasoning with RL-driven property control, marking a step toward reliable and transparent peptide optimization for therapeutic discovery.

Beyond the LUMIR challenge: The pathway to foundational registration models

Medical image challenges have played a transformative role in advancing the field, catalyzing algorithmic innovation and establishing new performance standards across diverse clinical applications. Image registration, a foundational task in neuroimaging pipelines, has similarly benefited from the Learn2Reg initiative. Building on this foundation, we introduce the Large-scale Unsupervised Brain MRI Image Registration (LUMIR) challenge, a next-generation benchmark designed to assess and advance unsupervised brain MRI registration. Distinct from prior challenges that leveraged anatomical label maps for supervision, LUMIR removes this dependency by providing over 4,000 preprocessed T1-weighted brain MRIs for training without any label maps, encouraging biologically plausible deformation modeling through self-supervision. In addition to evaluating performance on 590 held-out test subjects, LUMIR introduces a rigorous suite of zero-shot generalization tasks, spanning out-of-domain imaging modalities (e.g., FLAIR, T2-weighted, T2*-weighted), disease populations (e.g., Alzheimer's disease), acquisition protocols (e.g., 9.4T MRI), and species (e.g., macaque brains). A total of 1,158 subjects and over 4,000 image pairs were included for evaluation. Performance was assessed using both segmentation-based metrics (Dice coefficient, 95th percentile Hausdorff distance) and landmark-based registration accuracy (target registration error). Across both in-domain and zero-shot tasks, deep learning-based methods consistently achieved state-of-the-art accuracy while producing anatomically plausible deformation fields. The top-performing deep learning-based models demonstrated diffeomorphic properties and inverse consistency, outperforming several leading optimization-based methods, and showing strong robustness to most domain shifts, the exception being a drop in performance on out-of-domain contrasts.

ViewSpatial-Bench: Evaluating Multi-perspective Spatial Localization in Vision-Language Models

Vision-language models (VLMs) have demonstrated remarkable capabilities in understanding and reasoning about visual content, but significant challenges persist in tasks requiring cross-viewpoint understanding and spatial reasoning. We identify a critical limitation: current VLMs excel primarily at egocentric spatial reasoning (from the camera's perspective) but fail to generalize to allocentric viewpoints when required to adopt another entity's spatial frame of reference. We introduce ViewSpatial-Bench, the first comprehensive benchmark designed specifically for multi-viewpoint spatial localization recognition evaluation across five distinct task types, supported by an automated 3D annotation pipeline that generates precise directional labels. Comprehensive evaluation of diverse VLMs on ViewSpatial-Bench reveals a significant performance disparity: models demonstrate reasonable performance on camera-perspective tasks but exhibit reduced accuracy when reasoning from a human viewpoint. By fine-tuning VLMs on our multi-perspective spatial dataset, we achieve an overall performance improvement of 46.24% across tasks, highlighting the efficacy of our approach. Our work establishes a crucial benchmark for spatial intelligence in embodied AI systems and provides empirical evidence that modeling 3D spatial relationships enhances VLMs' corresponding spatial comprehension capabilities.

The Hitchhiker's Guide to Program Analysis, Part II: Deep Thoughts by LLMs

Static analysis is a cornerstone for software vulnerability detection, yet it often struggles with the classic precision-scalability trade-off. In practice, such tools often produce high false positive rates, particularly in large codebases like the Linux kernel. This imprecision can arise from simplified vulnerability modeling and over-approximation of path and data constraints. While large language models (LLMs) show promise in code understanding, their naive application to program analysis yields unreliable results due to inherent reasoning limitations. We introduce BugLens, a post-refinement framework that significantly improves static analysis precision. BugLens guides an LLM to follow traditional analysis steps by assessing buggy code patterns for security impact and validating the constraints associated with static warnings. Evaluated on real-world Linux kernel bugs, BugLens raises precision from 0.10 (raw) and 0.50 (semi-automated refinement) to 0.72, substantially reducing false positives and revealing four previously unreported vulnerabilities. Our results suggest that a structured LLM-based workflow can meaningfully enhance the effectiveness of static analysis tools.

Embodied-Reasoner: Synergizing Visual Search, Reasoning, and Action for Embodied Interactive Tasks

Recent advances in deep thinking models have demonstrated remarkable reasoning capabilities on mathematical and coding tasks. However, their effectiveness in embodied domains which require continuous interaction with environments through image action interleaved trajectories remains largely -unexplored. We present Embodied Reasoner, a model that extends o1 style reasoning to interactive embodied search tasks. Unlike mathematical reasoning that relies primarily on logical deduction, embodied scenarios demand spatial understanding, temporal reasoning, and ongoing self-reflection based on interaction history. To address these challenges, we synthesize 9.3k coherent Observation-Thought-Action trajectories containing 64k interactive images and 90k diverse thinking processes (analysis, spatial reasoning, reflection, planning, and verification). We develop a three-stage training pipeline that progressively enhances the model's capabilities through imitation learning, self-exploration via rejection sampling, and self-correction through reflection tuning. The evaluation shows that our model significantly outperforms those advanced visual reasoning models, e.g., it exceeds OpenAI o1, o3-mini, and Claude-3.7 by +9\%, 24\%, and +13\%. Analysis reveals our model exhibits fewer repeated searches and logical inconsistencies, with particular advantages in complex long-horizon tasks. Real-world environments also show our superiority while exhibiting fewer repeated searches and logical inconsistency cases.

Evaluating Bias in Retrieval-Augmented Medical Question-Answering Systems

Medical QA systems powered by Retrieval-Augmented Generation (RAG) models support clinical decision-making but may introduce biases related to race, gender, and social determinants of health. We systematically evaluate biases in RAG-based LLM by examining demographic-sensitive queries and measuring retrieval discrepancies. Using datasets like MMLU and MedMCQA, we analyze retrieval overlap and correctness disparities. Our findings reveal substantial demographic disparities within RAG pipelines, emphasizing the critical need for retrieval methods that explicitly account for fairness to ensure equitable clinical decision-making.