A Pathology Foundation Model for Gastric Cancer with Real-World Validation

Gastric cancer remains a major cause of cancer mortality, yet its histological and molecular heterogeneity complicates diagnosis and risk stratification. General-purpose pathology foundation models (PFMs) often plateau on fine-grained endpoints central to gastric cancer care, and few have undergone rigorous prospective validation or clinical reader studies. We present GRACE, a Gastric-specific foundation model for Real-world Assessment and Clinical dEcision support. GRACE was developed from multicenter gastric pathology datasets totaling 48,364 primarily HE-stained whole-slide images from 37,493 patients. When evaluated on 28 clinically relevant tasks, GRACE consistently outperformed representative pancancer PFMs, achieving a macro-AUC of 0.9188, with strong performance for precancerous lesion diagnosis (macro-AUC 0.9322), tumor histopathological assessment (macro-AUC 0.9119), molecular profiling (macro-AUC 0.8682), and prognostic prediction. Beyond benchmarking, GRACE's translational value was substantiated through a rigorous evidence chain. Under safety-gated criteria requiring 100% NPV for rule-out and 100% PPV for rule-in, GRACE streamlined review for up to 69.6% of malignancy-diagnosis cases and triaged 46.8% of MMR-IHC follow-up requests. This translational feasibility was further strengthened by a randomized crossover reader study of pathologist-AI collaboration. With GRACE assistance, diagnostic accuracy improved from 82.0% to 89.9%, yielding nearly twofold higher adjusted odds of a correct diagnosis (OR 1.987) alongside concurrent gains in sensitivity and specificity. AI assistance also reduced diagnostic time by 14.9%, elevated diagnostic confidence by 9.0%, and markedly improved inter-rater agreement. When calibrated to maintain non-inferior performance to senior pathologists, the AI-assisted workflow could triage 60.7% of atrophy and 82.7% of intestinal metaplasia cases.

Spatial Transcriptomics-Guided Alignment Enhances Molecular Profiling in Pathology Foundation Model

Comprehensive molecular profiling is essential for modern precision oncology but remains hindered by prohibitive costs, specimen exhaustion, and protracted turnaround times. While pathology foundation models (PFMs) have demonstrated potential for inferring molecular phenotypes from routine hematoxylin and eosin (H&E) whole-slide images (WSIs), current architectures primarily rely on vision-centric self-supervised learning or vision-language alignment, lacking the spatially resolved molecular supervision required to connect subtle morphological features with underlying genomic alterations. Spatial transcriptomics (ST) emerges as a transformative technology that enables transcriptomic quantification within intact tissue sections, thereby preserving the precise spatial link between histology and molecular profiles. In this study, we present a Spatial Transcriptomics-guided Alignment framework for Molecular Profiling (STAMP), which endows PFMs with intrinsic molecular awareness. To support this paradigm, we curated HumanST-1k, a human ST dataset spanning diverse anatomical organs and sequencing platforms. This atlas yields 1.8 million pairs of H&E patches and corresponding transcriptomic profiles, providing a corpus that links histological structures with their molecular states. To mitigate the technical noise inherent to raw transcriptomics, STAMP applies a pathway-informed alignment strategy that aggregates transcriptomic data into biologically functional pathways, which are subsequently integrated into PFMs via parameter-efficient fine-tuning. This alignment enriches the representation space of PFMs and unlocks their capacity to resolve sub-visual molecular signatures. The clinical utility of these augmented representations was validated through a multi-tier evaluation framework.

A Clinically Validated Foundation Model for Comprehensive Lung Pathology Interpretation

Pathological assessment guides lung cancer diagnosis, treatment selection, and prognostic evaluation, yet current CPath approaches rely on task-specific models for isolated objectives. Although pan-cancer foundation models offer versatility, they lack subspecialty-level depth and have not been evaluated across clinical workflows or prospectively validated in real-world settings. We introduce PulmoFoundation, a multi-center, prospectively validated, randomized controlled trial (RCT)-evaluated foundation model for comprehensive lung pathology assessment across pre-operative, intra-operative, and post-operative care. Built upon Virchow2 via subspecialty-specific pretraining using ~40,000 diagnostic H&E-stained whole-slide images (WSIs), PulmoFoundation was systematically evaluated on ~26,000 WSIs across 32 clinically relevant tasks. In addition to accurately predicting molecular markers and patient survival, our model achieves clinical-grade performance in core diagnostic tasks across biopsy, frozen section, and surgical resection slides. In a registered prospective study of 1,357 patients across 11 diagnostic tasks, our model achieved an average AUC of 92.3%. Using pre-specified triage thresholds, PulmoFoundation could reduce additional second-review burden for 68.8% of biopsies and 83.0% of frozen sections, and defer 44.5% of IHC stain orders, with PPVs of 1.0, 0.991, and 0.966. Beyond prospective validation, we conducted a crossover RCT with eight pathologists, in which AI assistance improved diagnostic accuracy across 4,928 case-reader pairs (91.7% w/ AI vs. 83.8% w/o AI). AI assistance also reduced median diagnostic time by 19.6%, increased diagnostic confidence by 8.7%, and improved inter-rater agreement from moderate (kappa = 0.56) to substantial (kappa = 0.76). Together, these evaluations support PulmoFoundation as a clinically validated decision-support system for lung pathology.

Holistic Scaling Laws for Optimal Mixture-of-Experts Architecture Optimization

Scaling laws for Large Language Models govern macroscopic resource allocation, yet translating them into precise Mixture-of-Experts (MoE) architectural configurations remains an open problem due to the combinatorially vast design space. Existing MoE scaling studies are constrained by experimental budgets to either augment scaling formulas with extra MoE variables, risking unreliable fits, or fix all non-MoE factors, ignoring global interactions. We propose a reusable framework for holistic MoE architectural optimization that bridges this gap. We first show that FLOPs per token alone is an inadequate fairness metric for MoE models because differing computational densities across layer types can inflate parameters without proportional compute cost, and establish a joint constraint triad of FLOPs per token, active parameters, and total parameters. We then reduce the 16-dimensional architectural search space to two sequential low-dimensional phases through algebraic constraints and a rank-preserving property of the hidden dimension. Validated across hundreds of MoE models spanning six orders of magnitude in compute, our framework yields robust scaling laws that map any compute budget to a complete, optimal MoE architecture. A key finding is that the near-optimal configuration band widens with scale, giving practitioners quantitative flexibility to balance scaling law recommendations against infrastructure constraints.

AutoQRA: Joint Optimization of Mixed-Precision Quantization and Low-rank Adapters for Efficient LLM Fine-Tuning

Quantization followed by parameter-efficient fine-tuning has emerged as a promising paradigm for downstream adaptation under tight GPU memory constraints. However, this sequential pipeline fails to leverage the intricate interaction between quantization bit-width and LoRA rank. Specifically, a carefully optimized quantization allocation with low quantization error does not always translate to strong fine-tuning performance, and different bit-width and rank configurations can lead to significantly varying outcomes under the same memory budget. To address this limitation, we propose AutoQRA, a joint optimization framework that simultaneously optimizes the bit-width and LoRA rank configuration for each layer during the mixed quantized fine-tuning process. To tackle the challenges posed by the large discrete search space and the high evaluation cost associated with frequent fine-tuning iterations, AutoQRA decomposes the optimization process into two stages. First, it first conducts a global multi-fidelity evolutionary search, where the initial population is warm-started by injecting layer-wise importance priors. This stage employs specific operators and a performance model to efficiently screen candidate configurations. Second, trust-region Bayesian optimization is applied to locally refine promising regions of the search space and identify optimal configurations under the given memory budget. This approach enables active compensation for quantization noise in specific layers during training. Experiments show that AutoQRA achieves performance close to full-precision fine-tuning with a memory footprint comparable to uniform 4-bit methods.

A Deployment-Friendly Foundational Framework for Efficient Computational Pathology

Pathology foundation models (PFMs) have enabled robust generalization in computational pathology through large-scale datasets and expansive architectures, but their substantial computational cost, particularly for gigapixel whole slide images, limits clinical accessibility and scalability. Here, we present LitePath, a deployment-friendly foundational framework designed to mitigate model over-parameterization and patch level redundancy. LitePath integrates LiteFM, a compact model distilled from three large PFMs (Virchow2, H-Optimus-1 and UNI2) using 190 million patches, and the Adaptive Patch Selector (APS), a lightweight component for task-specific patch selection. The framework reduces model parameters by 28x and lowers FLOPs by 403.5x relative to Virchow2, enabling deployment on low-power edge hardware such as the NVIDIA Jetson Orin Nano Super. On this device, LitePath processes 208 slides per hour, 104.5x faster than Virchow2, and consumes 0.36 kWh per 3,000 slides, 171x lower than Virchow2 on an RTX3090 GPU. We validated accuracy using 37 cohorts across four organs and 26 tasks (26 internal, 9 external, and 2 prospective), comprising 15,672 slides from 9,808 patients disjoint from the pretraining data. LitePath ranks second among 19 evaluated models and outperforms larger models including H-Optimus-1, mSTAR, UNI2 and GPFM, while retaining 99.71% of the AUC of Virchow2 on average. To quantify the balance between accuracy and efficiency, we propose the Deployability Score (D-Score), defined as the weighted geometric mean of normalized AUC and normalized FLOP, where LitePath achieves the highest value, surpassing Virchow2 by 10.64%. These results demonstrate that LitePath enables rapid, cost-effective and energy-efficient pathology image analysis on accessible hardware while maintaining accuracy comparable to state-of-the-art PFMs and reducing the carbon footprint of AI deployment.

DeepGen 1.0: A Lightweight Unified Multimodal Model for Advancing Image Generation and Editing

Current unified multimodal models for image generation and editing typically rely on massive parameter scales (e.g., >10B), entailing prohibitive training costs and deployment footprints. In this work, we present DeepGen 1.0, a lightweight 5B unified model that achieves comprehensive capabilities competitive with or surpassing much larger counterparts. To overcome the limitations of compact models in semantic understanding and fine-grained control, we introduce Stacked Channel Bridging (SCB), a deep alignment framework that extracts hierarchical features from multiple VLM layers and fuses them with learnable 'think tokens' to provide the generative backbone with structured, reasoning-rich guidance. We further design a data-centric training strategy spanning three progressive stages: (1) Alignment Pre-training on large-scale image-text pairs and editing triplets to synchronize VLM and DiT representations, (2) Joint Supervised Fine-tuning on a high-quality mixture of generation, editing, and reasoning tasks to foster omni-capabilities, and (3) Reinforcement Learning with MR-GRPO, which leverages a mixture of reward functions and supervision signals, resulting in substantial gains in generation quality and alignment with human preferences, while maintaining stable training progress and avoiding visual artifacts. Despite being trained on only ~50M samples, DeepGen 1.0 achieves leading performance across diverse benchmarks, surpassing the 80B HunyuanImage by 28% on WISE and the 27B Qwen-Image-Edit by 37% on UniREditBench. By open-sourcing our training code, weights, and datasets, we provide an efficient, high-performance alternative to democratize unified multimodal research.

Unified Personalized Reward Model for Vision Generation

Recent advancements in multimodal reward models (RMs) have significantly propelled the development of visual generation. Existing frameworks typically adopt Bradley-Terry-style preference modeling or leverage generative VLMs as judges, and subsequently optimize visual generation models via reinforcement learning. However, current RMs suffer from inherent limitations: they often follow a one-size-fits-all paradigm that assumes a monolithic preference distribution or relies on fixed evaluation rubrics. As a result, they are insensitive to content-specific visual cues, leading to systematic misalignment with subjective and context-dependent human preferences. To this end, inspired by human assessment, we propose UnifiedReward-Flex, a unified personalized reward model for vision generation that couples reward modeling with flexible and context-adaptive reasoning. Specifically, given a prompt and the generated visual content, it first interprets the semantic intent and grounds on visual evidence, then dynamically constructs a hierarchical assessment by instantiating fine-grained criteria under both predefined and self-generated high-level dimensions. Our training pipeline follows a two-stage process: (1) we first distill structured, high-quality reasoning traces from advanced closed-source VLMs to bootstrap SFT, equipping the model with flexible and context-adaptive reasoning behaviors; (2) we then perform direct preference optimization (DPO) on carefully curated preference pairs to further strengthen reasoning fidelity and discriminative alignment. To validate the effectiveness, we integrate UnifiedReward-Flex into the GRPO framework for image and video synthesis, and extensive results demonstrate its superiority.

Investigating Data Pruning for Pretraining Biological Foundation Models at Scale

Biological foundation models (BioFMs), pretrained on large-scale biological sequences, have recently shown strong potential in providing meaningful representations for diverse downstream bioinformatics tasks. However, such models often rely on millions to billions of training sequences and billions of parameters, resulting in prohibitive computational costs and significant barriers to reproducibility and accessibility, particularly for academic labs. To address these challenges, we investigate the feasibility of data pruning for BioFM pretraining and propose a post-hoc influence-guided data pruning framework tailored to biological domains. Our approach introduces a subset-based self-influence formulation that enables efficient estimation of sample importance at low computational cost, and builds upon it two simple yet effective selection strategies, namely Top-k Influence (Top I) and Coverage-Centric Influence (CCI). We empirically validate our method on two representative BioFMs, RNA-FM and ESM-C. For RNA, our framework consistently outperforms random selection baselines under an extreme pruning rate of over 99 percent, demonstrating its effectiveness. Furthermore, we show the generalizability of our framework on protein-related tasks using ESM-C. In particular, our coreset even outperforms random subsets that are ten times larger in both RNA and protein settings, revealing substantial redundancy in biological sequence datasets. These findings underscore the potential of influence-guided data pruning to substantially reduce the computational cost of BioFM pretraining, paving the way for more efficient, accessible, and sustainable biological AI research.

Explore and Establish Synergistic Effects Between Weight Pruning and Coreset Selection in Neural Network Training

Modern deep neural networks rely heavily on massive model weights and training samples, incurring substantial computational costs. Weight pruning and coreset selection are two emerging paradigms proposed to improve computational efficiency. In this paper, we first explore the interplay between redundant weights and training samples through a transparent analysis: redundant samples, particularly noisy ones, cause model weights to become unnecessarily overtuned to fit them, complicating the identification of irrelevant weights during pruning; conversely, irrelevant weights tend to overfit noisy data, undermining coreset selection effectiveness. To further investigate and harness this interplay in deep learning, we develop a Simultaneous Weight and Sample Tailoring mechanism (SWaST) that alternately performs weight pruning and coreset selection to establish a synergistic effect in training. During this investigation, we observe that when simultaneously removing a large number of weights and samples, a phenomenon we term critical double-loss can occur, where important weights and their supportive samples are mistakenly eliminated at the same time, leading to model instability and nearly irreversible degradation that cannot be recovered in subsequent training. Unlike classic machine learning models, this issue can arise in deep learning due to the lack of theoretical guarantees on the correctness of weight pruning and coreset selection, which explains why these paradigms are often developed independently. We mitigate this by integrating a state preservation mechanism into SWaST, enabling stable joint optimization. Extensive experiments reveal a strong synergy between pruning and coreset selection across varying prune rates and coreset sizes, delivering accuracy boosts of up to 17.83% alongside 10% to 90% FLOPs reductions.