MIMIC-\RNum{4}-Ext-22MCTS: A 22 Millions-Event Temporal Clinical Time-Series Dataset with Relative Timestamp for Risk Prediction

Clinical risk prediction based on machine learning algorithms plays a vital role in modern healthcare. A crucial component in developing a reliable prediction model is collecting high-quality time series clinical events. In this work, we release such a dataset that consists of 22,588,586 Clinical Time Series events, which we term MIMIC-\RNum{4}-Ext-22MCTS. Our source data are discharge summaries selected from the well-known yet unstructured MIMIC-IV-Note \cite{Johnson2023-pg}. We then extract clinical events as short text span from the discharge summaries, along with the timestamps of these events as temporal information. The general-purpose MIMIC-IV-Note pose specific challenges for our work: it turns out that the discharge summaries are too lengthy for typical natural language models to process, and the clinical events of interest often are not accompanied with explicit timestamps. Therefore, we propose a new framework that works as follows: 1) we break each discharge summary into manageably small text chunks; 2) we apply contextual BM25 and contextual semantic search to retrieve chunks that have a high potential of containing clinical events; and 3) we carefully design prompts to teach the recently released Llama-3.1-8B \cite{touvron2023llama} model to identify or infer temporal information of the chunks. We show that the obtained dataset is so informative and transparent that standard models fine-tuned on our dataset are achieving significant improvements in healthcare applications. In particular, the BERT model fine-tuned based on our dataset achieves 10\% improvement in accuracy on medical question answering task, and 3\% improvement in clinical trial matching task compared with the classic BERT. The GPT-2 model, fine-tuned on our dataset, produces more clinically reliable results for clinical questions.

OpenTCM: A GraphRAG-Empowered LLM-based System for Traditional Chinese Medicine Knowledge Retrieval and Diagnosis

Traditional Chinese Medicine (TCM) represents a rich repository of ancient medical knowledge that continues to play an important role in modern healthcare. Due to the complexity and breadth of the TCM literature, the integration of AI technologies is critical for its modernization and broader accessibility. However, this integration poses considerable challenges, including the interpretation of obscure classical Chinese texts and the modeling of intricate semantic relationships among TCM concepts. In this paper, we develop OpenTCM, an LLM-based system that combines a domain-specific TCM knowledge graph and Graph-based Retrieval-Augmented Generation (GraphRAG). First, we extract more than 3.73 million classical Chinese characters from 68 gynecological books in the Chinese Medical Classics Database, with the help of TCM and gynecology experts. Second, we construct a comprehensive multi-relational knowledge graph comprising more than 48,000 entities and 152,000 interrelationships, using customized prompts and Chinese-oriented LLMs such as DeepSeek and Kimi to ensure high-fidelity semantic understanding. Last, we integrate OpenTCM with this knowledge graph, enabling high-fidelity ingredient knowledge retrieval and diagnostic question-answering without model fine-tuning. Experimental evaluations demonstrate that our prompt design and model selection significantly improve knowledge graph quality, achieving a precision of 98. 55% and an F1 score of 99. 55%. In addition, OpenTCM achieves mean expert scores of 4.5 in ingredient information retrieval and 3.8 in diagnostic question-answering tasks, outperforming state-of-the-art solutions in real-world TCM use cases.

MERA: Multimodal and Multiscale Self-Explanatory Model with Considerably Reduced Annotation for Lung Nodule Diagnosis

Lung cancer, a leading cause of cancer-related deaths globally, emphasises the importance of early detection for better patient outcomes. Pulmonary nodules, often early indicators of lung cancer, necessitate accurate, timely diagnosis. Despite Explainable Artificial Intelligence (XAI) advances, many existing systems struggle providing clear, comprehensive explanations, especially with limited labelled data. This study introduces MERA, a Multimodal and Multiscale self-Explanatory model designed for lung nodule diagnosis with considerably Reduced Annotation requirements. MERA integrates unsupervised and weakly supervised learning strategies (self-supervised learning techniques and Vision Transformer architecture for unsupervised feature extraction) and a hierarchical prediction mechanism leveraging sparse annotations via semi-supervised active learning in the learned latent space. MERA explains its decisions on multiple levels: model-level global explanations via semantic latent space clustering, instance-level case-based explanations showing similar instances, local visual explanations via attention maps, and concept explanations using critical nodule attributes. Evaluations on the public LIDC dataset show MERA's superior diagnostic accuracy and self-explainability. With only 1% annotated samples, MERA achieves diagnostic accuracy comparable to or exceeding state-of-the-art methods requiring full annotation. The model's inherent design delivers comprehensive, robust, multilevel explanations aligned closely with clinical practice, enhancing trustworthiness and transparency. Demonstrated viability of unsupervised and weakly supervised learning lowers the barrier to deploying diagnostic AI in broader medical domains. Our complete code is open-source available: https://github.com/diku-dk/credanno.

Research on Personalized Medical Intervention Strategy Generation System based on Group Relative Policy Optimization and Time-Series Data Fusion

With the timely formation of personalized intervention plans based on high-dimensional heterogeneous time series information becoming an important challenge in the medical field today, electronic medical records, wearables, and other multi-source medical data are increasingly generated and diversified. In this work, we develop a system to generate personalized medical intervention strategies based on Group Relative Policy Optimization (GRPO) and Time-Series Data Fusion. First, by incorporating relative policy constraints among the groups during policy gradient updates, we adaptively balance individual and group gains. To improve the robustness and interpretability of decision-making, a multi-layer neural network structure is employed to group-code patient characteristics. Second, for the rapid multi-modal fusion of multi-source heterogeneous time series, a multi-channel neural network combined with a self-attention mechanism is used for dynamic feature extraction. Key feature screening and aggregation are achieved through a differentiable gating network. Finally, a collaborative search process combining a genetic algorithm and Monte Carlo tree search is proposed to find the ideal intervention strategy, achieving global optimization. Experimental results show significant improvements in accuracy, coverage, and decision-making benefits compared with existing methods.

Towards prediction of morphological heart age from computed tomography angiography

Age prediction from medical images or other health-related non-imaging data is an important approach to data-driven aging research, providing knowledge of how much information a specific tissue or organ carries about the chronological age of the individual. In this work, we studied the prediction of age from computed tomography angiography (CTA) images, which provide detailed representations of the heart morphology, with the goals of (i) studying the relationship between morphology and aging, and (ii) developing a novel \emph{morphological heart age} biomarker. We applied an image registration-based method that standardizes the images from the whole cohort into a single space. We then extracted supervoxels (using unsupervised segmentation), and corresponding robust features of density and local volume, which provide a detailed representation of the heart morphology while being robust to registration errors. Machine learning models are then trained to fit regression models from these features to the chronological age. We applied the method to a subset of the images from the Swedish CArdioPulomonary bioImage Study (SCAPIS) dataset, consisting of 721 females and 666 males. We observe a mean absolute error of $2.74$ years for females and $2.77$ years for males. The predictions from different sub-regions of interest were observed to be more highly correlated with the predictions from the whole heart, compared to the chronological age, revealing a high consistency in the predictions from morphology. Saliency analysis was also performed on the prediction models to study what regions are associated positively and negatively with the predicted age. This resulted in detailed association maps where the density and volume of known, as well as some novel sub-regions of interest, are determined to be important. The saliency analysis aids in the interpretability of the models and their predictions.

MSAD-Net: Multiscale and Spatial Attention-based Dense Network for Lung Cancer Classification

Lung cancer, a severe form of malignant tumor that originates in the tissues of the lungs, can be fatal if not detected in its early stages. It ranks among the top causes of cancer-related mortality worldwide. Detecting lung cancer manually using chest X-Ray image or Computational Tomography (CT) scans image poses significant challenges for radiologists. Hence, there is a need for automatic diagnosis system of lung cancers from radiology images. With the recent emergence of deep learning, particularly through Convolutional Neural Networks (CNNs), the automated detection of lung cancer has become a much simpler task. Nevertheless, numerous researchers have addressed that the performance of conventional CNNs may be hindered due to class imbalance issue, which is prevalent in medical images. In this research work, we have proposed a novel CNN architecture ``Multi-Scale Dense Network (MSD-Net)'' (trained-from-scratch). The novelties we bring in the proposed model are (I) We introduce novel dense modules in the 4th block and 5th block of the CNN model. We have leveraged 3 depthwise separable convolutional (DWSC) layers, and one 1x1 convolutional layer in each dense module, in order to reduce complexity of the model considerably. (II) Additionally, we have incorporated one skip connection from 3rd block to 5th block and one parallel branch connection from 4th block to Global Average Pooling (GAP) layer. We have utilized dilated convolutional layer (with dilation rate=2) in the last parallel branch in order to extract multi-scale features. Extensive experiments reveal that our proposed model has outperformed latest CNN model ConvNext-Tiny, recent trend Vision Transformer (ViT), Pooling-based ViT (PiT), and other existing models by significant margins.

AI analysis of medical images at scale as a health disparities probe: a feasibility demonstration using chest radiographs

Health disparities (differences in non-genetic conditions that influence health) can be associated with differences in burden of disease by groups within a population. Social determinants of health (SDOH) are domains such as health care access, dietary access, and economics frequently studied for potential association with health disparities. Evaluating SDOH-related phenotypes using routine medical images as data sources may enhance health disparities research. We developed a pipeline for using quantitative measures automatically extracted from medical images as inputs into health disparities index calculations. Our study focused on the use case of two SDOH demographic correlates (sex and race) and data extracted from chest radiographs of 1,571 unique patients. The likelihood of severe disease within the lung parenchyma from each image type, measured using an established deep learning model, was merged into a single numerical image-based phenotype for each patient. Patients were then separated into phenogroups by unsupervised clustering of the image-based phenotypes. The health rate for each phenogroup was defined as the median image-based phenotype for each SDOH used as inputs to four imaging-derived health disparities indices (iHDIs): one absolute measure (between-group variance) and three relative measures (index of disparity, Theil index, and mean log deviation). The iHDI measures demonstrated feasible values for each SDOH demographic correlate, showing potential for medical images to serve as a novel probe for health disparities. Large-scale AI analysis of medical images can serve as a probe for a novel data source for health disparities research.

Hybrid CNN with Chebyshev Polynomial Expansion for Medical Image Analysis

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with early and accurate diagnosis playing a pivotal role in improving patient outcomes. Automated detection of pulmonary nodules in computed tomography (CT) scans is a challenging task due to variability in nodule size, shape, texture, and location. Traditional Convolutional Neural Networks (CNNs) have shown considerable promise in medical image analysis; however, their limited ability to capture fine-grained spatial-spectral variations restricts their performance in complex diagnostic scenarios. In this study, we propose a novel hybrid deep learning architecture that incorporates Chebyshev polynomial expansions into CNN layers to enhance expressive power and improve the representation of underlying anatomical structures. The proposed Chebyshev-CNN leverages the orthogonality and recursive properties of Chebyshev polynomials to extract high-frequency features and approximate complex nonlinear functions with greater fidelity. The model is trained and evaluated on benchmark lung cancer imaging datasets, including LUNA16 and LIDC-IDRI, achieving superior performance in classifying pulmonary nodules as benign or malignant. Quantitative results demonstrate significant improvements in accuracy, sensitivity, and specificity compared to traditional CNN-based approaches. This integration of polynomial-based spectral approximation within deep learning provides a robust framework for enhancing automated medical diagnostics and holds potential for broader applications in clinical decision support systems.

Extracting Patient History from Clinical Text: A Comparative Study of Clinical Large Language Models

Extracting medical history entities (MHEs) related to a patient's chief complaint (CC), history of present illness (HPI), and past, family, and social history (PFSH) helps structure free-text clinical notes into standardized EHRs, streamlining downstream tasks like continuity of care, medical coding, and quality metrics. Fine-tuned clinical large language models (cLLMs) can assist in this process while ensuring the protection of sensitive data via on-premises deployment. This study evaluates the performance of cLLMs in recognizing CC/HPI/PFSH-related MHEs and examines how note characteristics impact model accuracy. We annotated 1,449 MHEs across 61 outpatient-related clinical notes from the MTSamples repository. To recognize these entities, we fine-tuned seven state-of-the-art cLLMs. Additionally, we assessed the models' performance when enhanced by integrating, problems, tests, treatments, and other basic medical entities (BMEs). We compared the performance of these models against GPT-4o in a zero-shot setting. To further understand the textual characteristics affecting model accuracy, we conducted an error analysis focused on note length, entity length, and segmentation. The cLLMs showed potential in reducing the time required for extracting MHEs by over 20%. However, detecting many types of MHEs remained challenging due to their polysemous nature and the frequent involvement of non-medical vocabulary. Fine-tuned GatorTron and GatorTronS, two of the most extensively trained cLLMs, demonstrated the highest performance. Integrating pre-identified BME information improved model performance for certain entities. Regarding the impact of textual characteristics on model performance, we found that longer entities were harder to identify, note length did not correlate with a higher error rate, and well-organized segments with headings are beneficial for the extraction.

A Benchmark for End-to-End Zero-Shot Biomedical Relation Extraction with LLMs: Experiments with OpenAI Models

Objective: Zero-shot methodology promises to cut down on costs of dataset annotation and domain expertise needed to make use of NLP. Generative large language models trained to align with human goals have achieved high zero-shot performance across a wide variety of tasks. As of yet, it is unclear how well these models perform on biomedical relation extraction (RE). To address this knowledge gap, we explore patterns in the performance of OpenAI LLMs across a diverse sampling of RE tasks. Methods: We use OpenAI GPT-4-turbo and their reasoning model o1 to conduct end-to-end RE experiments on seven datasets. We use the JSON generation capabilities of GPT models to generate structured output in two ways: (1) by defining an explicit schema describing the structure of relations, and (2) using a setting that infers the structure from the prompt language. Results: Our work is the first to study and compare the performance of the GPT-4 and o1 for the end-to-end zero-shot biomedical RE task across a broad array of datasets. We found the zero-shot performances to be proximal to that of fine-tuned methods. The limitations of this approach are that it performs poorly on instances containing many relations and errs on the boundaries of textual mentions. Conclusion: Recent large language models exhibit promising zero-shot capabilities in complex biomedical RE tasks, offering competitive performance with reduced dataset curation and NLP modeling needs at the cost of increased computing, potentially increasing medical community accessibility. Addressing the limitations we identify could further boost reliability. The code, data, and prompts for all our experiments are publicly available: https://github.com/bionlproc/ZeroShotRE