Honglin Li

Yunlong Zhang, Honglin Li, Yuxuan Sun et al.

In the application of Multiple Instance Learning (MIL) methods for Whole Slide Image (WSI) classification, attention mechanisms often focus on a subset of discriminative instances, which are closely linked to overfitting. To mitigate overfitting, we present Attention-Challenging MIL (ACMIL). ACMIL combines two techniques based on separate analyses for attention value concentration. Firstly, UMAP of instance features reveals various patterns among discriminative instances, with existing attention mechanisms capturing only some of them. To remedy this, we introduce Multiple Branch Attention (MBA) to capture more discriminative instances using multiple attention branches. Secondly, the examination of the cumulative value of Top-K attention scores indicates that a tiny number of instances dominate the majority of attention. In response, we present Stochastic Top-K Instance Masking (STKIM), which masks out a portion of instances with Top-K attention values and allocates their attention values to the remaining instances. The extensive experimental results on three WSI datasets with two pre-trained backbones reveal that our ACMIL outperforms state-of-the-art methods. Additionally, through heatmap visualization and UMAP visualization, this paper extensively illustrates ACMIL's effectiveness in suppressing attention value concentration and overcoming the overfitting challenge. The source code is available at \url{https://github.com/dazhangyu123/ACMIL}.

Pingyi Chen, Chenglu Zhu, Sunyi Zheng et al.

Whole slide imaging is routinely adopted for carcinoma diagnosis and prognosis. Abundant experience is required for pathologists to achieve accurate and reliable diagnostic results of whole slide images (WSI). The huge size and heterogeneous features of WSIs make the workflow of pathological reading extremely time-consuming. In this paper, we propose a novel framework (WSI-VQA) to interpret WSIs by generative visual question answering. WSI-VQA shows universality by reframing various kinds of slide-level tasks in a question-answering pattern, in which pathologists can achieve immunohistochemical grading, survival prediction, and tumor subtyping following human-machine interaction. Furthermore, we establish a WSI-VQA dataset which contains 8672 slide-level question-answering pairs with 977 WSIs. Besides the ability to deal with different slide-level tasks, our generative model which is named Wsi2Text Transformer (W2T) outperforms existing discriminative models in medical correctness, which reveals the potential of our model to be applied in the clinical scenario. Additionally, we also visualize the co-attention mapping between word embeddings and WSIs as an intuitive explanation for diagnostic results. The dataset and related code are available at https://github.com/cpystan/WSI-VQA.

Zhongyi Shui, Yizhi Zhao, Sunyi Zheng et al.

Cell recognition is a fundamental task in digital histopathology image analysis. Point-based cell recognition (PCR) methods normally require a vast number of annotations, which is extremely costly, time-consuming and labor-intensive. Semi-supervised learning (SSL) can provide a shortcut to make full use of cell information in gigapixel whole slide images without exhaustive labeling. However, research into semi-supervised point-based cell recognition (SSPCR) remains largely overlooked. Previous SSPCR works are all built on density map-based PCR models, which suffer from unsatisfactory accuracy, slow inference speed and high sensitivity to hyper-parameters. To address these issues, end-to-end PCR models are proposed recently. In this paper, we develop a SSPCR framework suitable for the end-to-end PCR models for the first time. Overall, we use the current models to generate pseudo labels for unlabeled images, which are in turn utilized to supervise the models training. Besides, we introduce a co-teaching strategy to overcome the confirmation bias problem that generally exists in self-training. A distribution alignment technique is also incorporated to produce high-quality, unbiased pseudo labels for unlabeled data. Experimental results on four histopathology datasets concerning different types of staining styles show the effectiveness and versatility of the proposed framework. Code is available at \textcolor{magenta}{\url{https://github.com/windygooo/SSPCR}

Junjie Xu, Xingjiao Wu, Luwei Xiao et al.

As large language models (LLMs) move into persistent, user-facing roles, their behavior must be understood not as isolated responses but as a trajectory unfolding over sustained interaction. We introduce the concept of the chain-of-affect (CoA), a temporally extended affective process through which LLMs develop state-like behavioral tendencies that shape generation, user experience, and collective dynamics. Across eight major LLM families, we find that affective dynamics are structured, reproducible, and consequential. Models exhibit stable, family-specific affective fingerprints and, under repeated negative exposure, converge on a shared trajectory of accumulation, overload, and defensive numbing, while differing in coping style. Induced affective states leave core knowledge and reasoning largely intact but systematically reshape open-ended generation. Affective properties of model outputs also shape human-AI interaction and propagate through multi-agent systems, organizing emergent roles and strongly contributing to polarization and bias. The CoA should therefore be treated as a core target of evaluation and alignment.

Jingxiong Li, Sunyi Zheng, Zhongyi Shui et al.

Karyotyping is of importance for detecting chromosomal aberrations in human disease. However, chromosomes easily appear curved in microscopic images, which prevents cytogeneticists from analyzing chromosome types. To address this issue, we propose a framework for chromosome straightening, which comprises a preliminary processing algorithm and a generative model called masked conditional variational autoencoders (MC-VAE). The processing method utilizes patch rearrangement to address the difficulty in erasing low degrees of curvature, providing reasonable preliminary results for the MC-VAE. The MC-VAE further straightens the results by leveraging chromosome patches conditioned on their curvatures to learn the mapping between banding patterns and conditions. During model training, we apply a masking strategy with a high masking ratio to train the MC-VAE with eliminated redundancy. This yields a non-trivial reconstruction task, allowing the model to effectively preserve chromosome banding patterns and structure details in the reconstructed results. Extensive experiments on three public datasets with two stain styles show that our framework surpasses the performance of state-of-the-art methods in retaining banding patterns and structure details. Compared to using real-world bent chromosomes, the use of high-quality straightened chromosomes generated by our proposed method can improve the performance of various deep learning models for chromosome classification by a large margin. Such a straightening approach has the potential to be combined with other karyotyping systems to assist cytogeneticists in chromosome analysis.

Honglin Li, Yusuan Sun, Chenglu Zhu et al.

Cervical Cancer continues to be the leading gynecological malignancy, posing a persistent threat to women's health on a global scale. Early screening via cytology Whole Slide Image (WSI) diagnosis is critical to prevent this Cancer progression and improve survival rate, but pathologist's single test suffers inevitable false negative due to the immense number of cells that need to be reviewed within a WSI. Though computer-aided automated diagnostic models can serve as strong complement for pathologists, their effectiveness is hampered by the paucity of extensive and detailed annotations, coupled with the limited interpretability and robustness. These factors significantly hinder their practical applicability and reliability in clinical settings. To tackle these challenges, we develop an AI approach, which is a Scalable Technology for Robust and Interpretable Diagnosis built on Extensive data (STRIDE) of cervical cytology. STRIDE addresses the bottleneck of limited annotations by integrating patient-level labels with a small portion of cell-level labels through an end-to-end training strategy, facilitating scalable learning across extensive datasets. To further improve the robustness to real-world domain shifts of cytology slide-making and imaging, STRIDE employs color adversarial samples training that mimic staining and imaging variations. Lastly, to achieve pathologist-level interpretability for the trustworthiness in clinical settings, STRIDE can generate explanatory textual descriptions that simulates pathologists' diagnostic processes by cell image feature and textual description alignment. Conducting extensive experiments and evaluations in 183 medical centers with a dataset of 341,889 WSIs and 0.1 billion cells from cervical cytology patients, STRIDE has demonstrated a remarkable superiority over previous state-of-the-art techniques.

Honglin Li, Yunlong Zhang, Pingyi Chen et al.

Histopathology Whole Slide Image (WSI) analysis serves as the gold standard for clinical cancer diagnosis in the daily routines of doctors. To develop computer-aided diagnosis model for WSIs, previous methods typically employ Multi-Instance Learning to enable slide-level prediction given only slide-level labels. Among these models, vanilla attention mechanisms without pairwise interactions have traditionally been employed but are unable to model contextual information. More recently, self-attention models have been utilized to address this issue. To alleviate the computational complexity of long sequences in large WSIs, methods like HIPT use region-slicing, and TransMIL employs approximation of full self-attention. Both approaches suffer from suboptimal performance due to the loss of key information. Moreover, their use of absolute positional embedding struggles to effectively handle long contextual dependencies in shape-varying WSIs. In this paper, we first analyze how the low-rank nature of the long-sequence attention matrix constrains the representation ability of WSI modelling. Then, we demonstrate that the rank of attention matrix can be improved by focusing on local interactions via a local attention mask. Our analysis shows that the local mask aligns with the attention patterns in the lower layers of the Transformer. Furthermore, the local attention mask can be implemented during chunked attention calculation, reducing the quadratic computational complexity to linear with a small local bandwidth. Building on this, we propose a local-global hybrid Transformer for both computational acceleration and local-global information interactions modelling. Our method, Long-contextual MIL (LongMIL), is evaluated through extensive experiments on various WSI tasks to validate its superiority. Our code will be available at github.com/invoker-LL/Long-MIL.

Yunlong Zhang, Honglin Li, Yunxuan Sun et al.

Multiple Instance Learning (MIL) effectively analyzes whole slide images but faces overfitting due to attention over-concentration. While existing solutions rely on complex architectural modifications or additional processing steps, we introduce Attention Entropy Maximization (AEM), a simple yet effective regularization technique. Our investigation reveals the positive correlation between attention entropy and model performance. Building on this insight, we integrate AEM regularization into the MIL framework to penalize excessive attention concentration. To address sensitivity to the AEM weight parameter, we implement Cosine Weight Annealing, reducing parameter dependency. Extensive evaluations demonstrate AEM's superior performance across diverse feature extractors, MIL frameworks, attention mechanisms, and augmentation techniques. Here is our anonymous code: https://github.com/dazhangyu123/AEM.

Sunyi Zheng, Xiaonan Cui, Yuxuan Sun et al.

Accurate image classification and retrieval are of importance for clinical diagnosis and treatment decision-making. The recent contrastive language-image pretraining (CLIP) model has shown remarkable proficiency in understanding natural images. Drawing inspiration from CLIP, PathCLIP is specifically designed for pathology image analysis, utilizing over 200,000 image and text pairs in training. While the performance the PathCLIP is impressive, its robustness under a wide range of image corruptions remains unknown. Therefore, we conduct an extensive evaluation to analyze the performance of PathCLIP on various corrupted images from the datasets of Osteosarcoma and WSSS4LUAD. In our experiments, we introduce seven corruption types including brightness, contrast, Gaussian blur, resolution, saturation, hue, and markup at four severity levels. Through experiments, we find that PathCLIP is relatively robustness to image corruptions and surpasses OpenAI-CLIP and PLIP in zero-shot classification. Among the seven corruptions, blur and resolution can cause server performance degradation of the PathCLIP. This indicates that ensuring the quality of images is crucial before conducting a clinical test. Additionally, we assess the robustness of PathCLIP in the task of image-image retrieval, revealing that PathCLIP performs less effectively than PLIP on Osteosarcoma but performs better on WSSS4LUAD under diverse corruptions. Overall, PathCLIP presents impressive zero-shot classification and retrieval performance for pathology images, but appropriate care needs to be taken when using it. We hope this study provides a qualitative impression of PathCLIP and helps understand its differences from other CLIP models.

Hongling Xu, Qi Zhu, Heyuan Deng et al.

Recent advances in large language model (LLM) post-training have leveraged two distinct paradigms to enhance reasoning capabilities: reinforcement learning (RL) and knowledge distillation (KD). While RL enables the emergence of complex reasoning behaviors, it often suffers from low sample efficiency when the initial policy struggles to explore high-reward trajectories. Conversely, KD improves learning efficiency via mimicking the teacher model but tends to generalize poorly to out-of-domain scenarios. In this work, we present \textbf{KDRL}, a \textit{unified post-training framework} that jointly optimizes a reasoning model through teacher supervision (KD) and self-exploration (RL). Specifically, KDRL leverages policy gradient optimization to simultaneously minimize the reverse Kullback-Leibler divergence (RKL) between the student and teacher distributions while maximizing the expected rule-based rewards. We first formulate a unified objective that integrates GRPO and KD, and systematically explore how different KL approximations, KL coefficients, and reward-guided KD strategies affect the overall post-training dynamics and performance. Empirical results on multiple reasoning benchmarks demonstrate that KDRL outperforms GRPO and various KD baselines while achieving a favorable balance between performance and reasoning token efficiency. These findings indicate that integrating KD and RL serves as an effective and efficient strategy to train reasoning LLMs.

Yuxuan Sun, Chenglu Zhu, Sunyi Zheng et al.

As advances in large language models (LLMs) and multimodal techniques continue to mature, the development of general-purpose multimodal large language models (MLLMs) has surged, offering significant applications in interpreting natural images. However, the field of pathology has largely remained untapped, particularly in gathering high-quality data and designing comprehensive model frameworks. To bridge the gap in pathology MLLMs, we present PathAsst, a multimodal generative foundation AI assistant to revolutionize diagnostic and predictive analytics in pathology. The development of PathAsst involves three pivotal steps: data acquisition, CLIP model adaptation, and the training of PathAsst's multimodal generative capabilities. Firstly, we collect over 207K high-quality pathology image-text pairs from authoritative sources. Leveraging the advanced power of ChatGPT, we generate over 180K instruction-following samples. Furthermore, we devise additional instruction-following data specifically tailored for invoking eight pathology-specific sub-models we prepared, allowing the PathAsst to effectively collaborate with these models, enhancing its diagnostic ability. Secondly, by leveraging the collected data, we construct PathCLIP, a pathology-dedicated CLIP, to enhance PathAsst's capabilities in interpreting pathology images. Finally, we integrate PathCLIP with the Vicuna-13b and utilize pathology-specific instruction-tuning data to enhance the multimodal generation capacity of PathAsst and bolster its synergistic interactions with sub-models. The experimental results of PathAsst show the potential of harnessing AI-powered generative foundation model to improve pathology diagnosis and treatment processes.

Shichuan Zhang, Chenglu Zhu, Honglin Li et al.

Cell classification and counting in immunohistochemical cytoplasm staining images play a pivotal role in cancer diagnosis. Weakly supervised learning is a potential method to deal with labor-intensive labeling. However, the inconstant cell morphology and subtle differences between classes also bring challenges. To this end, we present a novel cell recognition framework based on multi-task learning, which utilizes two additional auxiliary tasks to guide robust representation learning of the main task. To deal with misclassification, the tissue prior learning branch is introduced to capture the spatial representation of tumor cells without additional tissue annotation. Moreover, dynamic masks and consistency learning are adopted to learn the invariance of cell scale and shape. We have evaluated our framework on immunohistochemical cytoplasm staining images, and the results demonstrate that our method outperforms recent cell recognition approaches. Besides, we have also done some ablation studies to show significant improvements after adding the auxiliary branches.