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Tian Guan

Publications and source records attributed to Tian Guan.

At least 19 recordsLinked to original sources

Knowledge-structured and evidence-aware semantic self-distillation for glomerular pathology foundation model

Visual foundation models learn rich pathological morphology but lack explicit concept-level supervision. Vision--language pretraining can provide this supervision but requires costly image--text pairs. Here, we introduce GloSAGE, a semantic self-distillation framework that uses lesion profiles predicted by a pretrained visual teacher to construct structured pathology descriptions. Reliability-guided selection identifies image--text anchors, while Knowledge-Structured Pathology Text Synthesis and Evidence-Guided Negative-pair Construction account for partially observed lesions. Image--text alignment trains projection layers while retaining the frozen visual encoder; an intermediate Semantic Transfer Layer supplies features for downstream tasks. Developed on GloMillion and evaluated across seven glomerulus- and case-level cohorts, GloSAGE supported zero-shot lesion recognition, image--text retrieval, hard-negative discrimination and concept-intervention analyses. It outperformed its source visual model in most lesion-recognition tasks and improved lesion grading, while supporting competitive case-level disease classification, injury grading and baseline renal function estimation. Ablations supported the combined contributions of knowledge-structured text and evidence-guided negatives, and the intermediate transfer layer improved mean lesion-recognition ROC-AUC relative to the complete projection output. A frozen language model conditioned on GloSAGE features generated glomerular descriptions. These findings suggest that teacher-derived lesion profiles can provide annotation-efficient semantic supervision for extending a glomerular visual foundation model.

cs.CV↗

SpaFactor: Lightweight Spatial Context-Aware Gene Program Modeling for Histology-to-Transcriptomics Inference

Spatial transcriptomics (ST) profiles gene expression within tissue architecture, but its cost and experimental complexity limit routine use. Predicting spatial expression from routinely available hematoxylin and eosin (HE) images therefore offers a scalable alternative. However, conventional methods often fit high-dimensional gene outputs as independent targets, overlooking the biological coordination among genes while remaining vulnerable to high-dimensional noise and overfitting. Existing attempts to address this limitation often rely on computationally heavy graph networks or complex auxiliary supervision. We therefore introduce SpaFactor, a lightweight and efficient low-rank morphology-program-gene factorization framework. At the input, SpaFactor efficiently fuses the visual representation of the central spot with multiscale local and regional neighborhood context, yielding a histologic representation that captures cellular morphology and microenvironmental heterogeneity. For modeling, a residual MLP stably learns a nonlinear mapping from the tissue microenvironment to low-dimensional latent gene programs. These activities are decoded through shared gene loadings into coordinated multi-gene expression predictions. Across five public cohorts, SpaFactor achieves the best aggregate performance, with particularly clear improvements for spatially variable genes, and more faithfully recovers biologically organized spatial patterns. These results demonstrate that lightweight joint modeling of tissue context and gene programs can improve both predictive accuracy and biological fidelity.

cs.LG↗

Lantern: Finding Committable Transactions via Back-Propagation on DAGs

Existing concurrency control protocols either introduce nondeterminism, resulting in a serial execution-replay dependency between primary and replica nodes, or rely on impractical prior knowledge of transaction read-write sets. In this paper, we present Lantern, a deterministic concurrency control protocol tailored for high-performance transaction processing systems operating without prior knowledge. The key insight of Lantern is that all zero-out-degree transaction vertices in the local dependency graph can be safely committed in ascending order using an overwrite-permissive strategy. We further introduce a novel Back-Propagation mechanism that iteratively propagates dependency states from sink to source vertices to identify additional committable transactions. We also propose Conflict-Free Batch Selection (CFBS) for read-modify-write intensive scenarios. We integrate Lantern into the open-source blockchain platform ChainMaker. Extensive evaluations on YCSB and SmallBank benchmarks demonstrate that Lantern achieves up to a 4.2x throughput speedup over Aria and improves the throughput of ChainMaker's execution layer by at least 2.2x.

cs.DC↗

Learning latent progression states from spatial heterogeneity in uterine histopathology

Tumor progression is accompanied by changes in architecture, morphology and microenvironmental organization, yet progression-associated heterogeneity is usually compressed into static diagnostic categories in histopathology. Here we present SpaTIE, a uterus-specific computational pathology framework that learns morphology-aware representations and organizes spatial histopathological heterogeneity into progression-associated tumor states. SpaTIE was developed using 10,426 uterine hematoxylin and eosin whole-slide images and evaluated in TCGA-UCEC and TCGA-UCS cohorts. The learned representations formed morphology manifolds, supported diagnostic, molecular and survival-related prediction tasks, and localized attention to informative tumor regions. Beyond supervised prediction, SpaTIE inferred tumor-state axes from cross-sectional morphology without temporal or molecular supervision. These morphology-derived states were spatially coherent and showed associations with clinicopathological variables and survival outcomes, while not simply recapitulating staging or diagnostic labels. Integrative multi-omics analyses linked the inferred states to DNA methylation, somatic copy-number variation, mutation, RNA-seq and RPPA profiles, highlighting molecular programs related to chromatin regulation, copy-number-associated structural variation, receptor tyrosine kinase signaling, cell adhesion, extracellular-matrix remodeling and metabolic adaptation. Progression-guided virtual perturbation further prioritized molecular features coupled to the morphology-derived state organization. Together, these findings suggest that uterine histopathology contains recoverable progression-associated tumor-state information and establish SpaTIE as a framework for connecting spatial morphology with multi-omics-informed tumor-state discovery.

cs.CV↗

DeCo-MIL: Debiased Counterfactual Reasoning for Long-Tailed Whole Slide Image Analysis

Multiple instance learning (MIL) is widely used for weakly supervised whole slide image (WSI) analysis. However, under long-tailed distributions, MIL-based WSI analysis faces a nested dual long-tail: an inter-slide class long tail and an intra-slide long tail of instance-level discriminative evidence. The two long tails are coupled: tail classes have few training slides, while their limited diagnostic evidence is concentrated in a few patches and obscured by abundant within-bag redundancy. This coupling biases models toward head classes and degrades rare-class recognition. To address this, we propose DeCo-MIL for long-tailed WSI analysis, which jointly alleviates the nested dual long-tail through frequency-debiased counterfactual reasoning. For the inner long tail, DeCo-MIL clusters patches into tissue-morphology anchors, replaces each anchor with its matched normal prototype to perform a counterfactual intervention, and estimates its counterfactual contribution to the ground-truth class using class-frequency-corrected predictions. These contributions guide redundancy masking to preserve scarce discriminative instances. For the outer long tail, DeCo-MIL constructs anchor-stratified pseudo-bags from redundancy-reduced bags and combines tail-aware oversampling with consistency regularization, increasing effective supervision for tail classes while preserving tissue-morphology composition. Extensive experiments on three long-tailed WSI benchmarks demonstrate that DeCo-MIL achieves state-of-the-art performance in both tail-class recognition and overall classification.

cs.CV↗

ConRub-Med: Reinforcement Learning with Consensus Rubrics for Open-Ended Medical Question Answering

Reinforcement learning with verifiable rewards has been especially effective in mathematics and coding, where answers can be checked automatically. Many open-ended medical questions lack comparably cheap outcome verifiers: responses may be partly correct, incomplete, or contain clinically consequential errors. Rubrics written or validated by physicians offer strong clinical grounding, but involving experts in every instance is costly. Model-generated rubrics make this supervision scalable. We introduce ConRub-Med to preserve useful distinctions as rubric feedback moves from construction to policy optimization. For each prompt, three heterogeneous language models propose atomic criteria independently; a separate model reviews them, retaining only criteria with semantic support from all three generators. Three-State scoring distinguishes correct coverage, missing information, and incorrect claims. Errors receive negative rather than zero credit. When every response in a complete Group Relative Policy Optimization (GRPO) group receives the same final reward, a pairwise judge provides sequence advantages only if both candidate orders agree, without changing the scalar rewards. Groups without ties use vanilla GRPO. In a blinded study matched by question, two medical experts rate panels from the full pipeline as more clinically relevant than panels produced by one generator. Across the evaluated open models, ConRub-Med ranks first on six of nine benchmarks and achieves the highest medical and generalization averages. Using the resulting rubric dataset of 5,166 prompts, it scores $38.98 \pm 1.04$ (mean $\pm$ SD) on HealthBench-Hard, compared with InfiMed-ORBIT's 33.60 with 8,000 samples and 37.30 with 28,000.

cs.CL↗

Pretraining Multiple Instance Learning Networks with Multi-Teacher Distillation from Pathology Slide Foundation Models

Multiple instance learning (MIL) has become the main paradigm for whole-slide image (WSI) analysis in computational pathology. However, existing MIL aggregators are still typically trained from scratch for each downstream task, relying on limited slide-level labels to learn both aggregation mechanisms and downstream discriminative representations simultaneously. As a result, they often suffer from unstable optimization, overfitting, and limited transferability. Similar to pretrained ResNet and Vision Transformer models in natural image learning, MIL also requires reusable pretrained initialization. However, high-quality slide-level pretraining data remain scarce, and MIL models are usually lightweight and weakly supervised, making large-scale pretraining difficult in practice. To address this challenge, we propose a distillation-based pretraining framework for MIL, which leverages two slide-level foundation models, TITAN and CARE, as teachers to transfer their representational knowledge into a diverse set of MIL architectures. To effectively balance supervision from different teachers, we further introduce an angular dispersion normalized distillation loss. The distilled weights are then used as initialization for downstream adaptation. We conduct systematic evaluations on 15 benchmark datasets under both linear probing and full-parameter fine-tuning, and further validate its advantages in few-shot scenarios. Experimental results show that pretraining generally improves MIL aggregators over from scratch training, especially in linear-probing and few-shot settings, while maintaining the computational efficiency of lightweight MIL models. Code is available at https://github.com/fu0201/MIL_Pretrained.

cs.CV↗

ALICE: Learning a General-Purpose Pathology Foundation Model from Vision, Vision-Language, and Slide-Level Experts

Foundation models are reshaping computational pathology, yet their capabilities remain shaped by pretraining objectives, data sources, and spatial scales, fragmenting complementary expertise across separate backbones. Here we present ALICE, a unified foundation model trained through multi-stage agglomerative distillation that sequentially distills eight vision-only, vision-language, and slide-level teacher models into dedicated modules of a single backbone. ALICE is pretrained on 24,985,184 tile-level pathology images and 155,604 high-resolution images, and evaluated across 21 task scenarios, 96 downstream tasks, and 48 data sources, spanning region-of-interest tissue analysis, vision-language multimodal evaluation, and whole-slide clinical assessment. In all three evaluation settings, ALICE achieved the best average rank among task-matched pathology foundation models. These results demonstrate that agglomerative distillation can consolidate complementary capabilities from specialized models into a unified backbone for broad computational pathology applications. The model is available at https://github.com/WonderLandxD/ALICE.

cs.CV↗

SlideCheck: Guiding Self-Supervised Pretraining of Pathology Foundation Models via Dataset Distributions

Pathology foundation models are pretrained on large streams of WSI-derived patches, while supervision during data construction is often slide-level, sparse, or heterogeneous. This mismatch makes it difficult to understand and control which biological patterns enter the pretraining data. We propose SlideCheck, a lightweight pretraining data guidance tool built on frozen pathology foundation model patch features. Rather than serving as a standalone patch diagnostic model, SlideCheck provides explicit abnormality and malignancy scores for organizing, filtering, and auditing pathology pretraining data. SlideCheck uses a dual-head MLP to separately model broad abnormal morphology and malignant evidence. A regularized feature-space scorer provides a supervised anchor for patch-level evidence estimation, while score-attention agreement combines patch scores with WSI-level MIL attention to mine high-confidence pseudo labels. The same scores are then used to construct broad-positive ViT pretraining subsets, where a patch is selected if either abnormality or malignancy evidence exceeds a threshold. Experiments show that SlideCheck-defined data distributions influence the downstream behavior of self-supervised ViT pretraining, indicating that biological composition is an important controllable factor in pathology foundation model development. Curated subsets can approach full-data performance, suggesting that explicitly scored patch pools may support more efficient and auditable pretraining data construction. These findings position SlideCheck as a data guidance and auditing layer for transforming large, undifferentiated patch pools into controllable and reusable pretraining datasets.

cs.CV↗

Beyond ViT Tokens: Masked-Diffusion Pretrained Convolutional Pathology Foundation Model for Cell-Level Dense Prediction

Cell-level dense prediction is central to computational pathology, but remains challenging due to fine-grained histological structures, strong domain shifts, and costly dense annotations. Existing ViT-based pathology foundation models rely on patch tokenization, which can disrupt spatial continuity and weaken local morphological details needed for cell-level prediction. To address this, we propose Masked-Diffusion Convolutional Foundation Models, termed ConvNeXt Masked-Diffusion (CMD), a self-supervised convolutional generative pretraining framework for dense pathology representation learning. CMD uses a fully convolutional ConvNeXt-UNet backbone, performs masked-diffusion pretraining in pixel space, and incorporates frozen pathology foundation model features through adaptive normalization. Experimental results demonstrate that CMD consistently outperforms existing ViT-based pathology foundation models and even surpasses state-of-the-art end-to-end segmentation methods while fine-tuning only a small number of task-specific parameters across multiple pathology dense prediction tasks. The advantage is particularly pronounced under limited annotation settings, where CMD exhibits stronger robustness and generalization ability. Our findings suggest that purely convolutional architectures can also serve as competitive pathology foundation models for cell-level dense prediction, achieving leading performance within the current ViT-dominated paradigm and providing a scalable, high-performance solution that better preserves histological structural priors for fine-grained pathology understanding.

cs.CV↗

A Digital Pathology Resource for Liver Cancer Quantification with Datasets, Benchmarks, and Tools

Liver cancer, especially hepatocellular carcinoma (HCC), imposes a substantial global disease burden. Accurate diagnosis and prognostic assessment directly influence treatment selection and patient survival, and pathological examination remains the gold standard for liver cancer diagnosis. Identifying diverse tissue components and pathological subtypes on histopathology slides is crucial for estimating postoperative recurrence risk and overall prognosis. However, most publicly available resources are still provided at the whole-slide image (WSI) level, and well-annotated datasets for fine-grained tissue component identification in liver cancer are scarce, which hinders reproducible model development and the deployment of quantitative analysis tools. To address this gap, we release HepatoBench, a patch-level image database for liver cancer with annotations for seven key tissue categories. Based on HepatoBench, we train and open-source a deep learning classification model as a tissue recognition tool. Furthermore, we train a WSI-level tumor/non-tumor segmentation model to automatically localize lesion regions across entire slides. By integrating the patch-level tissue classifier with the WSI-level segmentation model, we build HepatoQuant, an end-to-end, disease-specific regional quantification tool for liver cancer, enabling a unified workflow from WSIs to tissue composition parsing and quantitative statistics. We also open-source HepatoBench, the benchmarking protocol, and supporting tools, providing a solid foundation for automated regional quantification and fair method comparison in liver cancer pathology.

cs.CV↗

GloPath: An Entity-Centric Foundation Model for Glomerular Lesion Assessment and Clinicopathological Insights

Glomerular pathology is central to the diagnosis and prognosis of renal diseases, yet the heterogeneity of glomerular morphology and fine-grained lesion patterns remain challenging for current AI approaches. We present GloPath, an entity-centric foundation model trained on over one million glomeruli extracted from 14,049 renal biopsy specimens using multi-scale and multi-view self-supervised learning. GloPath addresses two major challenges in nephropathology: glomerular lesion assessment and clinicopathological insights discovery. For lesion assessment, GloPath was benchmarked across three independent cohorts on 52 tasks, including lesion recognition, grading, few-shot classification, and cross-modality diagnosis-outperforming state-of-the-art methods in 42 tasks (80.8%). In the large-scale real-world study, it achieved an ROC-AUC of 91.51% for lesion recognition, demonstrating strong robustness in routine clinical settings. For clinicopathological insights, GloPath systematically revealed statistically significant associations between glomerular morphological parameters and clinical indicators across 224 morphology-clinical variable pairs, demonstrating its capacity to connect tissue-level pathology with patient-level outcomes. Together, these results position GloPath as a scalable and interpretable platform for glomerular lesion assessment and clinicopathological discovery, representing a step toward clinically translatable AI in renal pathology.

cs.CV↗

StainNet: Scaling Self-Supervised Foundation Models on Immunohistochemistry and Special Stains for Computational Pathology

Foundation models trained with self-supervised learning (SSL) on large-scale histological images have significantly accelerated the development of computational pathology. These models can serve as backbones for region-of-interest (ROI) image analysis or patch-level feature extractors in whole-slide images (WSIs) based on multiple instance learning (MIL). Existing pathology foundation models (PFMs) are typically pre-trained on Hematoxylin-Eosin (H\&E) stained pathology images. However, images such as immunohistochemistry (IHC) and special stains are also frequently used in clinical practice. PFMs pre-trained mainly on H\&E-stained images may be limited in clinical applications involving these non-H\&E images. To address this issue, we propose StainNet, a collection of self-supervised foundation models specifically trained for IHC and special stains in pathology images based on the vision transformer (ViT) architecture. StainNet contains a ViT-Small and a ViT-Base model, both of which are trained using a self-distillation SSL approach on over 1.4 million patch images extracted from 20,231 publicly available IHC and special staining WSIs in the HISTAI database. To evaluate StainNet models, we conduct experiments on three in-house slide-level IHC classification tasks, three in-house ROI-level special stain and two public ROI-level IHC classification tasks to demonstrate their strong ability. We also perform ablation studies such as few-ratio learning and retrieval evaluations, and compare StainNet models with recent larger PFMs to further highlight their strengths. The StainNet model weights are available at https://github.com/WonderLandxD/StainNet.

cs.CV↗

To What Extent Do Token-Level Representations from Pathology Foundation Models Improve Dense Prediction?

Pathology foundation models (PFMs) have rapidly advanced and are becoming a common backbone for downstream clinical tasks, offering strong transferability across tissues and institutions. However, for dense prediction (e.g., segmentation), practical deployment still lacks a clear, reproducible understanding of how different PFMs behave across datasets and how adaptation choices affect performance and stability. We present PFM-DenseBench, a large-scale benchmark for dense pathology prediction, evaluating 17 PFMs across 18 public segmentation datasets. Under a unified protocol, we systematically assess PFMs with multiple adaptation and fine-tuning strategies, and derive insightful, practice-oriented findings on when and why different PFMs and tuning choices succeed or fail across heterogeneous datasets. We release containers, configs, and dataset cards to enable reproducible evaluation and informed PFM selection for real-world dense pathology tasks. Project Website: https://m4a1tastegood.github.io/PFM-DenseBench

eess.IV↗

HookMIL: Revisiting Context Modeling in Multiple Instance Learning for Computational Pathology

Multiple Instance Learning (MIL) has enabled weakly supervised analysis of whole-slide images (WSIs) in computational pathology. However, traditional MIL approaches often lose crucial contextual information, while transformer-based variants, though more expressive, suffer from quadratic complexity and redundant computations. To address these limitations, we propose HookMIL, a context-aware and computationally efficient MIL framework that leverages compact, learnable hook tokens for structured contextual aggregation. These tokens can be initialized from (i) key-patch visual features, (ii) text embeddings from vision-language pathology models, and (iii) spatially grounded features from spatial transcriptomics-vision models. This multimodal initialization enables Hook Tokens to incorporate rich textual and spatial priors, accelerating convergence and enhancing representation quality. During training, Hook tokens interact with instances through bidirectional attention with linear complexity. To further promote specialization, we introduce a Hook Diversity Loss that encourages each token to focus on distinct histopathological patterns. Additionally, a hook-to-hook communication mechanism refines contextual interactions while minimizing redundancy. Extensive experiments on four public pathology datasets demonstrate that HookMIL achieves state-of-the-art performance, with improved computational efficiency and interpretability. Codes are available at https://github.com/lingxitong/HookMIL.

cs.CV↗

GAPS: A Clinically Grounded, Automated Benchmark for Evaluating AI Clinicians

Current benchmarks for AI clinician systems, often based on multiple-choice exams or manual rubrics, fail to capture the depth, robustness, and safety required for real-world clinical practice. To address this, we introduce the GAPS framework, a multidimensional paradigm for evaluating Grounding (cognitive depth), Adequacy (answer completeness), Perturbation (robustness), and Safety. Critically, we developed a fully automated, guideline-anchored pipeline to construct a GAPS-aligned benchmark end-to-end, overcoming the scalability and subjectivity limitations of prior work. Our pipeline assembles an evidence neighborhood, creates dual graph and tree representations, and automatically generates questions across G-levels. Rubrics are synthesized by a DeepResearch agent that mimics GRADE-consistent, PICO-driven evidence review in a ReAct loop. Scoring is performed by an ensemble of large language model (LLM) judges. Validation confirmed our automated questions are high-quality and align with clinician judgment (90% agreement, Cohen's Kappa 0.77). Evaluating state-of-the-art models on the benchmark revealed key failure modes: performance degrades sharply with increased reasoning depth (G-axis), models struggle with answer completeness (A-axis), and they are highly vulnerable to adversarial perturbations (P-axis) as well as certain safety issues (S-axis). This automated, clinically-grounded approach provides a reproducible and scalable method for rigorously evaluating AI clinician systems and guiding their development toward safer, more reliable clinical practice. The benchmark dataset GAPS-NSCLC-preview and evaluation code are publicly available at https://huggingface.co/datasets/AQ-MedAI/GAPS-NSCLC-preview and https://github.com/AQ-MedAI/MedicalAiBenchEval.

cs.CL↗

A Simple Linear Patch Revives Layer-Pruned Large Language Models

Layer pruning has emerged as a widely used technique for compressing large language models (LLMs). However, existing layer pruning approaches often incur substantial performance degradation. We identify the majority of this degradation to a single yet previously overlooked issue: \textit{the mismatch of activation magnitudes at the pruning interface}. The pre-interface activations exhibit significantly different scales from the post-interface ones, causing the distributional shift as it propagates through the remaining layers. To address this issue, we introduce \textsc{LinearPatch}, a lightweight and plug-and-play technique that fuses two operations into one matrix multiply at the pruning interface: (i) a Hadamard transformation that suppresses massive outliers at particular tokens and (ii) a channel-wise scaling that aligns activation statistics. On LLaMA-3-8B, \textsc{LinearPatch} preserves up to \textbf{94.15\%} of the original model's performance when pruning 5 out of 32 layers, outperforming the previous state of the art by \textbf{4\%}. The patch can be further refined with 5K unlabeled samples via memory-efficient offline distillation, pushing the retention to 95.16\% within only 30 minutes on a single GPU. Code is available at https://github.com/chenxinrui-tsinghua/LinearPatch.

cs.CL↗

From Generic to Specialized: A Subspecialty Diagnostic System Powered by Self-Supervised Learning for Cervical Histopathology

Cervical cancer remains a major malignancy, necessitating extensive and complex histopathological assessments and comprehensive support tools. Although deep learning shows promise, these models still lack accuracy and generalizability. General foundation models offer a broader reach but remain limited in capturing subspecialty-specific features and task adaptability. We introduce the Cervical Subspecialty Pathology (CerS-Path) diagnostic system, developed through two synergistic pretraining stages: self-supervised learning on approximately 190 million tissue patches from 140,000 slides to build a cervical-specific feature extractor, and multimodal enhancement with 2.5 million image-text pairs, followed by integration with multiple downstream diagnostic functions. Supporting eight diagnostic functions, including rare cancer classification and multimodal Q&A, CerS-Path surpasses prior foundation models in scope and clinical applicability. Comprehensive evaluations demonstrate a significant advance in cervical pathology, with prospective testing on 3,173 cases across five centers maintaining 99.38% screening sensitivity and excellent generalizability, highlighting its potential for subspecialty diagnostic translation and cervical cancer screening.

cs.CV↗