PAST: A multimodal single-cell foundation model for histopathology and spatial transcriptomics in cancer

While pathology foundation models have transformed cancer image analysis, they often lack integration with molecular data at single-cell resolution, limiting their utility for precision oncology. Here, we present PAST, a pan-cancer single-cell foundation model trained on 20 million paired histopathology images and single-cell transcriptomes spanning multiple tumor types and tissue contexts. By jointly encoding cellular morphology and gene expression, PAST learns unified cross-modal representations that capture both spatial and molecular heterogeneity at the cellular level. This approach enables accurate prediction of single-cell gene expression, virtual molecular staining, and multimodal survival analysis directly from routine pathology slides. Across diverse cancers and downstream tasks, PAST consistently exceeds the performance of existing approaches, demonstrating robust generalizability and scalability. Our work establishes a new paradigm for pathology foundation models, providing a versatile tool for high-resolution spatial omics, mechanistic discovery, and precision cancer research.

Structure-aware Semantic Discrepancy and Consistency for 3D Medical Image Self-supervised Learning

3D medical image self-supervised learning (mSSL) holds great promise for medical analysis. Effectively supporting broader applications requires considering anatomical structure variations in location, scale, and morphology, which are crucial for capturing meaningful distinctions. However, previous mSSL methods partition images with fixed-size patches, often ignoring the structure variations. In this work, we introduce a novel perspective on 3D medical images with the goal of learning structure-aware representations. We assume that patches within the same structure share the same semantics (semantic consistency) while those from different structures exhibit distinct semantics (semantic discrepancy). Based on this assumption, we propose an mSSL framework named $S^2DC$, achieving Structure-aware Semantic Discrepancy and Consistency in two steps. First, $S^2DC$ enforces distinct representations for different patches to increase semantic discrepancy by leveraging an optimal transport strategy. Second, $S^2DC$ advances semantic consistency at the structural level based on neighborhood similarity distribution. By bridging patch-level and structure-level representations, $S^2DC$ achieves structure-aware representations. Thoroughly evaluated across 10 datasets, 4 tasks, and 3 modalities, our proposed method consistently outperforms the state-of-the-art methods in mSSL.

Efficient Network Automatic Relevance Determination

We propose Network Automatic Relevance Determination (NARD), an extension of ARD for linearly probabilistic models, to simultaneously model sparse relationships between inputs $X \in \mathbb R^{d \times N}$ and outputs $Y \in \mathbb R^{m \times N}$, while capturing the correlation structure among the $Y$. NARD employs a matrix normal prior which contains a sparsity-inducing parameter to identify and discard irrelevant features, thereby promoting sparsity in the model. Algorithmically, it iteratively updates both the precision matrix and the relationship between $Y$ and the refined inputs. To mitigate the computational inefficiencies of the $\mathcal O(m^3 + d^3)$ cost per iteration, we introduce Sequential NARD, which evaluates features sequentially, and a Surrogate Function Method, leveraging an efficient approximation of the marginal likelihood and simplifying the calculation of determinant and inverse of an intermediate matrix. Combining the Sequential update with the Surrogate Function method further reduces computational costs. The computational complexity per iteration for these three methods is reduced to $\mathcal O(m^3+p^3)$, $\mathcal O(m^3 + d^2)$, $\mathcal O(m^3+p^2)$, respectively, where $p \ll d$ is the final number of features in the model. Our methods demonstrate significant improvements in computational efficiency with comparable performance on both synthetic and real-world datasets.

Harnessing Negative Signals: Reinforcement Distillation from Teacher Data for LLM Reasoning

Recent advances in model distillation demonstrate that data from advanced reasoning models (e.g., DeepSeek-R1, OpenAI's o1) can effectively transfer complex reasoning abilities to smaller, efficient student models. However, standard practices employ rejection sampling, discarding incorrect reasoning examples -- valuable, yet often underutilized data. This paper addresses the critical question: How can both positive and negative distilled reasoning traces be effectively leveraged to maximize LLM reasoning performance in an offline setting? To this end, We propose Reinforcement Distillation (REDI), a two-stage framework. Stage 1 learns from positive traces via Supervised Fine-Tuning (SFT). Stage 2 further refines the model using both positive and negative traces through our proposed REDI objective. This novel objective is a simple, reference-free loss function that outperforms established methods like DPO and SimPO in this distillation context. Our empirical evaluations demonstrate REDI's superiority over baseline Rejection Sampling SFT or SFT combined with DPO/SimPO on mathematical reasoning tasks. Notably, the Qwen-REDI-1.5B model, post-trained on just 131k positive and negative examples from the open Open-R1 dataset, achieves an 83.1% score on MATH-500 (pass@1). Its performance matches or surpasses that of DeepSeek-R1-Distill-Qwen-1.5B (a model post-trained on 800k proprietary data) across various mathematical reasoning benchmarks, establishing a new state-of-the-art for 1.5B models post-trained offline with openly available data.

Equivariant Spherical Transformer for Efficient Molecular Modeling

SE(3)-equivariant Graph Neural Networks (GNNs) have significantly advanced molecular system modeling by employing group representations. However, their message passing processes, which rely on tensor product-based convolutions, are limited by insufficient non-linearity and incomplete group representations, thereby restricting expressiveness. To overcome these limitations, we introduce the Equivariant Spherical Transformer (EST), a novel framework that leverages a Transformer structure within the spatial domain of group representations after Fourier transform. We theoretically and empirically demonstrate that EST can encompass the function space of tensor products while achieving superior expressiveness. Furthermore, EST's equivariant inductive bias is guaranteed through a uniform sampling strategy for the Fourier transform. Our experiments demonstrate state-of-the-art performance by EST on various molecular benchmarks, including OC20 and QM9.

ChemHAS: Hierarchical Agent Stacking for Enhancing Chemistry Tools

Large Language Model (LLM)-based agents have demonstrated the ability to improve performance in chemistry-related tasks by selecting appropriate tools. However, their effectiveness remains limited by the inherent prediction errors of chemistry tools. In this paper, we take a step further by exploring how LLMbased agents can, in turn, be leveraged to reduce prediction errors of the tools. To this end, we propose ChemHAS (Chemical Hierarchical Agent Stacking), a simple yet effective method that enhances chemistry tools through optimizing agent-stacking structures from limited data. ChemHAS achieves state-of-the-art performance across four fundamental chemistry tasks, demonstrating that our method can effectively compensate for prediction errors of the tools. Furthermore, we identify and characterize four distinct agent-stacking behaviors, potentially improving interpretability and revealing new possibilities for AI agent applications in scientific research. Our code and dataset are publicly available at https: //anonymous.4open.science/r/ChemHAS-01E4/README.md.

ChromFound: Towards A Universal Foundation Model for Single-Cell Chromatin Accessibility Data

The advent of single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) offers an innovative perspective for deciphering regulatory mechanisms by assembling a vast repository of single-cell chromatin accessibility data. While foundation models have achieved significant success in single-cell transcriptomics, there is currently no foundation model for scATAC-seq that supports zero-shot high-quality cell identification and comprehensive multi-omics analysis simultaneously. Key challenges lie in the high dimensionality and sparsity of scATAC-seq data, as well as the lack of a standardized schema for representing open chromatin regions (OCRs). Here, we present \textbf{ChromFound}, a foundation model tailored for scATAC-seq. ChromFound utilizes a hybrid architecture and genome-aware tokenization to effectively capture genome-wide long contexts and regulatory signals from dynamic chromatin landscapes. Pretrained on 1.97 million cells from 30 tissues and 6 disease conditions, ChromFound demonstrates broad applicability across 6 diverse tasks. Notably, it achieves robust zero-shot performance in generating universal cell representations and exhibits excellent transferability in cell type annotation and cross-omics prediction. By uncovering enhancer-gene links undetected by existing computational methods, ChromFound offers a promising framework for understanding disease risk variants in the noncoding genome.

SemiSAM+: Rethinking Semi-Supervised Medical Image Segmentation in the Era of Foundation Models

Deep learning-based medical image segmentation typically requires large amount of labeled data for training, making it less applicable in clinical settings due to high annotation cost. Semi-supervised learning (SSL) has emerged as an appealing strategy due to its less dependence on acquiring abundant annotations from experts compared to fully supervised methods. Beyond existing model-centric advancements of SSL by designing novel regularization strategies, we anticipate a paradigmatic shift due to the emergence of promptable segmentation foundation models with universal segmentation capabilities using positional prompts represented by Segment Anything Model (SAM). In this paper, we present SemiSAM+, a foundation model-driven SSL framework to efficiently learn from limited labeled data for medical image segmentation. SemiSAM+ consists of one or multiple promptable foundation models as generalist models, and a trainable task-specific segmentation model as specialist model. For a given new segmentation task, the training is based on the specialist-generalist collaborative learning procedure, where the trainable specialist model delivers positional prompts to interact with the frozen generalist models to acquire pseudo-labels, and then the generalist model output provides the specialist model with informative and efficient supervision which benefits the automatic segmentation and prompt generation in turn. Extensive experiments on two public datasets and one in-house clinical dataset demonstrate that SemiSAM+ achieves significant performance improvement, especially under extremely limited annotation scenarios, and shows strong efficiency as a plug-and-play strategy that can be easily adapted to different specialist and generalist models.

SegAnyPET: Universal Promptable Segmentation from Positron Emission Tomography Images

Positron Emission Tomography (PET) imaging plays a crucial role in modern medical diagnostics by revealing the metabolic processes within a patient's body, which is essential for quantification of therapy response and monitoring treatment progress. However, the segmentation of PET images presents unique challenges due to their lower contrast and less distinct boundaries compared to other structural medical modalities. Recent developments in segmentation foundation models have shown superior versatility across diverse natural image segmentation tasks. Despite the efforts of medical adaptations, these works primarily focus on structural medical images with detailed physiological structural information and exhibit poor generalization ability when adapted to molecular PET imaging. In this paper, we collect and construct PETS-5k, the largest PET segmentation dataset to date, comprising 5,731 three-dimensional whole-body PET images and encompassing over 1.3M 2D images. Based on the established dataset, we develop SegAnyPET, a modality-specific 3D foundation model for universal promptable segmentation from PET images. To issue the challenge of discrepant annotation quality of PET images, we adopt a cross prompting confident learning (CPCL) strategy with an uncertainty-guided self-rectification process to robustly learn segmentation from high-quality labeled data and low-quality noisy labeled data. Experimental results demonstrate that SegAnyPET can correctly segment seen and unseen targets using only one or a few prompt points, outperforming state-of-the-art foundation models and task-specific fully supervised models with higher accuracy and strong generalization ability for universal segmentation. As the first foundation model for PET images, we believe that SegAnyPET will advance the applications to various downstream tasks for molecular imaging.

AURORA:Automated Training Framework of Universal Process Reward Models via Ensemble Prompting and Reverse Verification

The reasoning capabilities of advanced large language models (LLMs) like o1 have revolutionized artificial intelligence applications. Nevertheless, evaluating and optimizing complex reasoning processes remain significant challenges due to diverse policy distributions and the inherent limitations of human effort and accuracy. In this paper, we present AURORA, a novel automated framework for training universal process reward models (PRMs) using ensemble prompting and reverse verification. The framework employs a two-phase approach: First, it uses diverse prompting strategies and ensemble methods to perform automated annotation and evaluation of processes, ensuring robust assessments for reward learning. Second, it leverages practical reference answers for reverse verification, enhancing the model's ability to validate outputs and improving training accuracy. To assess the framework's performance, we extend beyond the existing ProcessBench benchmark by introducing UniversalBench, which evaluates reward predictions across full trajectories under diverse policy distribtion with long Chain-of-Thought (CoT) outputs. Experimental results demonstrate that AURORA enhances process evaluation accuracy, improves PRMs' accuracy for diverse policy distributions and long-CoT responses. The project will be open-sourced at https://auroraprm.github.io/. The Universal-PRM-7B is available at https://huggingface.co/infly/Universal-PRM-7B.