Spatial Transcriptomics (ST) reveals the spatial distribution of gene expression in tissues, offering critical insights into biological processes and disease mechanisms. However, the high cost, limited coverage, and technical complexity of current ST technologies restrict their widespread use in clinical and research settings, making obtaining high-resolution transcriptomic profiles across large tissue areas challenging. Predicting ST from H&E-stained histology images has emerged as a promising alternative to address these limitations but remains challenging due to the heterogeneous relationship between histomorphology and gene expression, which is affected by substantial variability across patients and tissue sections. In response, we propose PH2ST, a prompt-guided hypergraph learning framework, which leverages limited ST signals to guide multi-scale histological representation learning for accurate and robust spatial gene expression prediction. Extensive evaluations on two public ST datasets and multiple prompt sampling strategies simulating real-world scenarios demonstrate that PH2ST not only outperforms existing state-of-the-art methods, but also shows strong potential for practical applications such as imputing missing spots, ST super-resolution, and local-to-global prediction, highlighting its value for scalable and cost-effective spatial gene expression mapping in biomedical contexts.

Retrieval-Augmented Generation (RAG) offers a promising solution to the limitations of static knowledge and hallucinations in Large Language Models (LLMs). While prior research has introduced numerous enhancements to RAG systems, a significant challenge remains under-explored: the potential conflict between external retrievals and LLMs' internal priors, which can undermine the quality of generated outputs. To tackle this issue, we present theEpitome-AugmentedGeneration (EAG) framework, which strategically aligns queries, external retrievals, and internal priors to produce high-quality LLM generations by selecting fuzzy inputs. EAG employs two novel lightweight modules, Criticism and Distillation, allowing traditional RAGs to be upgraded to EAGs without the need for specialized training data. Extensive experiments on five datasets across general and medical domains, including both open-ended and closed-ended tasks, validate the effectiveness of EAG. Our framework achieves substantial F1 score improvements: 7.03%, 23.35%, and 21.58% over baseline RAGs in medical QA tasks, 11.80% in law domain, 7.95% in finance domain, and 4.13% and 5.16% in general domain. Beyond performance gains, our study delves into the interplay between LLMs' internal priors and external retrievals, uncovering key principles that govern generation quality and providing valuable insights for future retrieval-augmented frameworks.

Interactive segmentation offers greater clinical potential in computational pathology compared to traditional automatic segmentation. By incorporating interactive input, it addresses the limitations of fully automatic segmentation models, which often fail to meet pathologists' requirements and rely heavily on large-scale, pixel-level annotated datasets. However, current interactive segmentation methods struggle to balance interaction cost and segmentation performance, and they fail to adapt effectively to slide-level segmentation, a task that is even more crucial in routine pathology analysis. In this study, we propose a Prototype-Guided Interactive Segmentation (ProGIS) framework for pathological image segmentation, designed to deliver precise segmentation results efficiently with minimal interaction signals. ProGIS identifies all same-type tissue connected components in a single interaction and supports multi-class segmentation without predefined categories during inference. Moreover, ProGIS can be easily adapted for slide-level interactive segmentation. Specifically, ProGIS consists of three modules: Prototype Initialization, Prototype Navigation, and Local Refinement. First, the Prototype Initialization module identifies categorical prototypes, which are then utilized in the Prototype Navigation module to identify all tissue connected components belonging to the same type. The local refinement module further refines the segmentation results using detailed correction signals to ensure the accuracy of challenging-to-distinguish regions. We evaluate our framework on two regions of interest level and two slide-level pathological segmentation datasets, achieving new state-of-the-art performance with fewer interactions than existing methods. Our code is available at https://github.com/JSGe-AI/ProGIS.

Medical AI has achieved strong predictive performance, yet most systems remain limited by shallow reasoning, poor transparency, and weak generalisation in safety-critical settings. Neurosymbolic AI offers a path beyond these constraints by combining neural models' ability to learn from complex clinical data with the explicit structure, logic, and domain knowledge of symbolic methods. This article examines how neurosymbolic approaches can address core challenges in healthcare AI through five key areas: hybrid reasoning that unifies learning and logic; symbol grounding that links internal representations to clinically meaningful concepts; clinical interpretability that exposes reasoning steps; human-integrated decision-making that keeps clinicians in control; and knowledge-driven diagnosis that incorporates guidelines, ontologies, and causal understanding. Together, these elements outline how neurosymbolic AI can support systems that are not only accurate but also transparent, clinically aligned, and robust in complex or data-sparse scenarios. Advancing this paradigm will require collaboration across AI research, clinical practice, and knowledge engineering, as well as governance mechanisms that ensure fairness and accountability. Neurosymbolic AI thus represents a promising direction for building trustworthy, knowledge-rich intelligence in healthcare.

MOTIVATION: Artificially making clinical decisions for patients with multi-morbidity has long been considered a thorny problem due to the complexity of the disease. Drug recommendations can assist doctors in automatically providing effective and safe drug combinations conducive to treatment and reducing adverse reactions. However, the existing drug recommendation works ignored two critical information. (i) Different types of medical information and their interrelationships in the patient's visit history can be used to construct a comprehensive patient representation. (ii) Patients with similar disease characteristics and their corresponding medication information can be used as a reference for predicting drug combinations. RESULTS: To address these limitations, we propose DAPSNet, which encodes multi-type medical codes into patient representations through code- and visit-level attention mechanisms, while integrating drug information corresponding to similar patient states to improve the performance of drug recommendation. Specifically, our DAPSNet is enlightened by the decision-making process of human doctors. Given a patient, DAPSNet first learns the importance of patient history records between diagnosis, procedure and drug in different visits, then retrieves the drug information corresponding to similar patient disease states for assisting drug combination prediction. Moreover, in the training stage, we introduce a novel information constraint loss function based on the information bottleneck principle to constrain the learned representation and enhance the robustness of DAPSNet. We evaluate the proposed DAPSNet on the public MIMIC-III dataset, our model achieves relative improvements of 1.33%, 1.20% and 2.03% in Jaccard, F1 and PR-AUC scores, respectively, compared to state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: The source code is available at the github repository: https://github.com/andylun96/DAPSNet.

The capability of generating speech with a specific type of emotion is desired for many human-computer interaction applications. Cross-speaker emotion transfer is a common approach to generating emotional speech when speech data with emotion labels from target speakers is not available for model training. This paper presents a novel cross-speaker emotion transfer system named iEmoTTS. The system is composed of an emotion encoder, a prosody predictor, and a timbre encoder. The emotion encoder extracts the identity of emotion type and the respective emotion intensity from the mel-spectrogram of input speech. The emotion intensity is measured by the posterior probability that the input utterance carries that emotion. The prosody predictor is used to provide prosodic features for emotion transfer. The timbre encoder provides timbre-related information for the system. Unlike many other studies which focus on disentangling speaker and style factors of speech, the iEmoTTS is designed to achieve cross-speaker emotion transfer via disentanglement between prosody and timbre. Prosody is considered the primary carrier of emotion-related speech characteristics, and timbre accounts for the essential characteristics for speaker identification. Zero-shot emotion transfer, meaning that the speech of target speakers is not seen in model training, is also realized with iEmoTTS. Extensive experiments of subjective evaluation have been carried out. The results demonstrate the effectiveness of iEmoTTS compared with other recently proposed systems of cross-speaker emotion transfer. It is shown that iEmoTTS can produce speech with designated emotion types and controllable emotion intensity. With appropriate information bottleneck capacity, iEmoTTS is able to transfer emotional information to a new speaker effectively. Audio samples are publicly available.

Leukemia classification relies on a detailed cytomorphological examination of Bone Marrow (BM) smear. However, applying existing deep-learning methods to it is facing two significant limitations. Firstly, these methods require large-scale datasets with expert annotations at the cell level for good results and typically suffer from poor generalization. Secondly, they simply treat the BM cytomorphological examination as a multi-class cell classification task, thus failing to exploit the correlation among leukemia subtypes over different hierarchies. Therefore, BM cytomorphological estimation as a time-consuming and repetitive process still needs to be done manually by experienced cytologists. Recently, Multi-Instance Learning (MIL) has achieved much progress in data-efficient medical image processing, which only requires patient-level labels (which can be extracted from the clinical reports). In this paper, we propose a hierarchical MIL framework and equip it with Information Bottleneck (IB) to tackle the above limitations. First, to handle the patient-level label, our hierarchical MIL framework uses attention-based learning to identify cells with high diagnostic values for leukemia classification in different hierarchies. Then, following the information bottleneck principle, we propose a hierarchical IB to constrain and refine the representations of different hierarchies for better accuracy and generalization. By applying our framework to a large-scale childhood acute leukemia dataset with corresponding BM smear images and clinical reports, we show that it can identify diagnostic-related cells without the need for cell-level annotations and outperforms other comparison methods. Furthermore, the evaluation conducted on an independent test cohort demonstrates the high generalizability of our framework.

Computational Pathology (CPATH) offers the possibility for highly accurate and low-cost automated pathological diagnosis. However, the high time cost of model inference is one of the main issues limiting the application of CPATH methods. Due to the large size of Whole-Slide Image (WSI), commonly used CPATH methods divided a WSI into a large number of image patches at relatively high magnification, then predicted each image patch individually, which is time-consuming. In this paper, we propose a novel Uncertainty-based Model Acceleration (UMA) method for reducing the time cost of model inference, thereby relieving the deployment burden of CPATH applications. Enlightened by the slide-viewing process of pathologists, only a few high-uncertain regions are regarded as “suspicious” regions that need to be predicted at high magnification, and most of the regions in WSI are predicted at low magnification, thereby reducing the times of image patch extraction and prediction. Meanwhile, uncertainty estimation ensures prediction accuracy at low magnification. We take two fundamental CPATH classification tasks (i.e., cancer region detection and subtyping) as examples. Extensive experiments on two large-scale renal cell carcinoma classification datasets demonstrate that our UMA can significantly reduce the time cost of model inference while maintaining competitive classification performance.

Coreference resolution aims at linking all mentions that refer to the same entity, which are widely adopted in many biomedical and bioinformatics tasks, such as biomedical knowledge graph construction and metabolic pathway integration. Many recent studies focus on improving neural model structures. However, we argue that a practical method that integrates commonsense knowledge can further improve coreference resolution performance, because commonsense delivers extra prior knowledge for reasoning and can enhance related representations, rather than naive mention-context occurrence modeling. In this work, we propose an effective method to integrate external commonsense knowledge into a neural coreference resolution model. Specially, a gated attention mechanism is employed in our method to leverage commonsense according to different contexts. By using ConceptNet as the knowledge base in three span-ranking backbone models, the models can yield significant performance gains on used datasets. We also achieve improvements in tasks of long-term mention detection and cross-sentence coreferences after incorporating knowledge.

Biomedical relation extraction seeks to automatically extract biomedical relations from biomedical text, which plays an important role in biomedical studies. However, constructing high-quality biomedical annotation data is not only time-consuming but also requires a high level of knowledge in the biomedical field. To alleviate this problem, Semi-supervised Biomedical Relation Extraction aims to extract relation facts from the limited labeled data and the more readily available unlabeled samples. Existing works can be roughly categorized as self-training methods and self-ensembling methods. The former aims to generate pseudo labels, which may lead to the gradual drift problem. The latter aims to encourage the output of one model to be consistent with the other model, where the acquisition of the model is tedious. To alleviate these issues, we propose a novel Uncertainty-Guided Mutual Consistency Training framework(UG-MCT) for semi-supervised Biomedical relation extraction. Specifically, our framework consists of two models with the same structure, which differ only when updating their weights, and then an intersecting pseudo-label mechanism is designed to convert the prediction discrepancies of the two models into mutual consistency training loss, thus promoting the consistency of model predictions. In addition, we utilize uncertainty as guided information to assist the model in focusing on the confident pseudo labels and mitigate the noise of inaccurate pseudo labeling during training. Thus, our model is very simple and efficient while mitigating the noise introduced by pseudo-labels. UG-MCT is evaluated on multiple datasets in different settings and the experimental results demonstrate that our method is highly effective in semi-supervised biomedical relation extraction compared to the state-of-the-art.

Predicting drug combinations according to patients' electronic health records is an essential task in intelligent healthcare systems, which can assist clinicians in ordering safe and effective prescriptions. However, existing work either missed/underutilized the important information lying in the drug molecule structure in drug encoding or has insufficient control over Drug-Drug Interactions (DDIs) rates within the predictions. To address these limitations, we propose CSEDrug, which enhances the drug encoding and DDIs controlling by leveraging multi-faceted drug knowledge, including molecule structures of drugs, Synergistic DDIs (SDDIs), and Antagonistic DDIs (ADDIs). We integrate these types of knowledge into CSEDrug by a graph-based drug encoder and multiple loss functions, including a novel triplet learning loss and a comprehensive DDI controllable loss. We evaluate the performance of CSEDrug in terms of accuracy, effectiveness, and safety on the public MIMIC-III dataset. The experimental results demonstrate that CSEDrug outperforms several state-of-the-art methods and achieves a 2.93% and a 2.77% increase in the Jaccard similarity scores and F1 scores, meanwhile, a 0.68% reduction of the ADDI rate (safer drug combinations), and 0.69% improvement of the SDDI rate (more effective drug combinations).

Tissue segmentation is an essential task in computational pathology. However, relevant datasets for such a pixel-level classification task are hard to obtain due to the difficulty of annotation, bringing obstacles for training a deep learning-based segmentation model. Recently, contrastive learning has provided a feasible solution for mitigating the heavy reliance of deep learning models on annotation. Nevertheless, applying contrastive loss to the most abstract image representations, existing contrastive learning frameworks focus on global features, therefore, are less capable of encoding finer-grained features (e.g., pixel-level discrimination) for the tissue segmentation task. Enlightened by domain knowledge, we design three contrastive learning tasks with multi-granularity views (from global to local) for encoding necessary features into representations without accessing annotations. Specifically, we construct: (1) an image-level task to capture the difference between tissue components, i.e., encoding the component discrimination; (2) a superpixel-level task to learn discriminative representations of local regions with different tissue components, i.e., encoding the prototype discrimination; (3) a pixel-level task to encourage similar representations of different tissue components within a local region, i.e., encoding the spatial smoothness. Through our global-to-local pre-training strategy, the learned representations can reasonably capture the domain-specific and fine-grained patterns, making them easily transferable to various tissue segmentation tasks in histopathological images. We conduct extensive experiments on two tissue segmentation datasets, while considering two real-world scenarios with limited or sparse annotations. The experimental results demonstrate that our framework is superior to existing contrastive learning methods and can be easily combined with weakly supervised and semi-supervised segmentation methods.

Healthcare Representation learning has been a key element to achieving state-of-the-art performance on healthcare prediction. Recent advances based Electronic Healthcare Records(EHRs) are mostly devoted to extracting temporal progression patterns with temporal model and their variants. Although these works have shown excellent performances in healthcare prediction, the unified temporal pattern may not be suitable for individuals in all healthcare conditions. Moreover, some studies ususally introduce complex Deep Neural Networks models and medical prior knowledge to get compact representation, causing great computational burden. In this paper, we propose a general health care representation model, named AEFNet. We only leverage three simple convolution operations and a set of up and down sampling to ensure performance and model complexity equally, which achieves adaptively extract distinct individual key feature in a light manner. AEFNet can shrink and refine highly suitable scale information adaptively and comletely. Breaking traditional fixed convolution scale or multi-scale, AEFNet achieves scale adaptively to extract the most significant information and context relationship. Finally, We validate our method on the public dataset MIMIC-III, and the evaluation results indicate that our method can significantly outperform other remarkable baseline models.

Pathological diagnosis is the gold standard for cancer diagnosis, but it is labor-intensive, in which tasks such as cell detection, classification, a nd c ounting a re particularly prominent. A common solution for automating these tasks is using nucleus segmentation technology. However, it is hard to train a robust nucleus segmentation model, due to several challenging problems,i.e., the nucleus adhesion, stacking, and excessive fusion with the background. Recently, some researchers proposed a series of automatic nucleus segmentation methods based on point annotation, which can significant i mprove t he m odel performance. Nevertheless, the point annotation needs to be marked by experienced pathologists. In order to take advantage of segmentation methods based on point annotation, further alleviate the manual workload, and make cancer diagnosis more efficient and accurate, it is necessary to develop an automatic nucleus detection algorithm, which can automatically and efficiently l ocate the position of the nucleus in the pathological image and extract valuable information for pathologists. In this paper, we propose a W-shaped network for automatic nucleus detection. Different from the traditional U-Net based method, mapping the original pathology image to the target mask directly, our proposed method split the detection task into two sub-tasks. The first sub-task maps the original pathology image to the binary mask, then the binary mask is mapped to the density mask in the second subtask. After the task is split, the task's difficulty i s significantly reduced, and the network's overall performance is improved. Our proposed network can automatic identify the center of each nucleus. Combined with the NuClick, a semi-supervised recognition model based on point annotation, we implement a fully automatic nucleus annotation framework.

Digital pathology plays a crucial role in the development of artificial intelligence in the medical field. The digital pathology platform can make the pathological resources digital and networked, and realize the permanent storage of visual data and the synchronous browsing processing without the limitation of time and space. It has been widely used in various fields of pathology. However, there is still a lack of an open and universal digital pathology platform to assist doctors in the management and analysis of digital pathological sections, as well as the management and structured description of relevant patient information. Most platforms cannot integrate image viewing, annotation and analysis, and text information management. To solve the above problems, we propose a comprehensive and extensible platform, PIMIP (Pathology Information Management & Integration Platform). PIMIP has developed the image annotation functions based on the visualization of digital pathological sections. Our annotation functions support multi-user collaborative annotation and multi-device annotation, and realize the automation of some annotation tasks. In the annotation task, we invited a professional pathologist for guidance. We introduce a machine learning module for image analysis. The data we collected included public data from local hospitals and clinical examples. Our platform is more clinical and suitable for clinical use. In addition to image data, we also structured the management and display of text information. So our platform is comprehensive. The platform framework is built in a modular way to support users to add machine learning modules independently, which makes our platform extensible.

Diagnostic pathology, which is the basis and gold standard of cancer diagnosis, provides essential information on the prognosis of the disease and vital evidence for clinical treatment. However, pathological diagnosis is subjective, and differences in observation and diagnosis between pathologists are common. This phenomenon is more evident in hospitals with insufficient medical resources. Deep learning (DL) can be used to identify and classify structures in digital pathology. In order to solve the above difficulties, in this work, we propose a DL framework for generating pathological diagnosis by analyzing histopathological images of renal cell carcinoma. A deep neural network is trained on a large high-quality annotated dataset for accurate tumor area detection, subtyping, and grading. The results show that our framework has achieved pathologist-level accuracy in diagnosis, can generate pathology reports with tumor indicators, and provide pathologists with interpretable auxiliary diagnoses

Constructing large-scaled medical knowledge graphs (MKGs) can significantly boost healthcare applications for medical surveillance, bring much attention from recent research. An essential step in constructing large-scale MKG is extracting information from medical reports. Recently, information extraction techniques have been proposed and show promising performance in biomedical information extraction. However, these methods only consider limited types of entity and relation due to the noisy biomedical text data with complex entity correlations. Thus, they fail to provide enough information for constructing MKGs and restrict the downstream applications. To address this issue, we propose Biomedical Information Extraction (BioIE), a hybrid neural network to extract relations from biomedical text and unstructured medical reports. Our model utilizes a multi-head attention enhanced graph convolutional network (GCN) to capture the complex relations and context information while resisting the noise from the data. We evaluate our model on two major biomedical relationship extraction tasks, chemical-disease relation (CDR) and chemical-protein interaction (CPI), and a cross-hospital pan-cancer pathology report corpus. The results show that our method achieves superior performance than baselines. Furthermore, we evaluate the applicability of our method under a transfer learning setting and show that BioIE achieves promising performance in processing medical text from different formats and writing styles.

Personalized diagnoses have not been possible due to a sear amount of data pathologists have to bear during the day-to-day routine, leading to the current generalized standards being continuously updated as new findings are reported. It is noticeable that these practical standards are developed based on multi-source heterogeneous data, including whole-slide images and pathology and clinical reports. In this study, we propose a framework that combines pathological images and medical reports to generate a personalized diagnosis result for an individual patient. We use nuclei-level image feature similarity and content-based deep learning method to search for a personalized group of populations with similar pathological characteristics, extract structured prognostic information from descriptive pathology reports of the similar patient population, and assign importance of different prognostic factors to generate a personalized pathological diagnosis result. We use multi-source heterogeneous data from TCGA (The Cancer Genome Atlas) database. The result demonstrates that our framework matches the performance of pathologists in the diagnosis of renal cell carcinoma. This framework is designed to be generic, and this could be applied to other types of cancer. The weights could provide insights into the known prognostic factors and further guide more precise clinical treatment protocols.

Electronic medical data contains biochemical, imaging, pathological information during diagnosis and treatment. The pathology report is a kind of highly liberalized unstructured textual data, which is the basis and gold standard of cancer diagnosis and is very important for the prognosis and treatment of patients. The application of information extraction technology to pathological reports can obtain structured data that can be understood and analyzed by computers, helping pathologists make appropriate decisions. In this work, we proposed an attention-based graph convolutional network (GCN) for converting unstructured pathological reports into a structured form suitable for computer analysis to improve the current pathologist's workflow, collected medical data from different platforms, and provided more accurate assistance for diagnosis and treatment. We used pathology reports data from TCGA (The Cancer Genome Atlas) database with fine-grained annotations on 3632 pathology reports including four types of cancers. Our method performs better in our pathology report dataset with higher F1 score than traditional methods and deep learning methods. The results indicate that our method is robust, thus may work with other types of cancer pathology report.