Accurate disease detection is of paramount importance for effective medical treatment and patient care. However, the process of disease detection is often associated with extensive medical testing and considerable costs, making it impractical to perform all possible medical tests on a patient to diagnose or predict hundreds or thousands of diseases. In this work, we propose Collaborative Learning for Disease Detection (CLDD), a novel graph-based deep learning model that formulates disease detection as a collaborative learning task by exploiting associations among diseases and similarities among patients adaptively. CLDD integrates patient-disease interactions and demographic features from electronic health records to detect hundreds or thousands of diseases for every patient, with little to no reliance on the corresponding medical tests. Extensive experiments on a processed version of the MIMIC-IV dataset comprising 61,191 patients and 2,000 diseases demonstrate that CLDD consistently outperforms representative baselines across multiple metrics, achieving a 6.33\% improvement in recall and 7.63\% improvement in precision. Furthermore, case studies on individual patients illustrate that CLDD can successfully recover masked diseases within its top-ranked predictions, demonstrating both interpretability and reliability in disease prediction. By reducing diagnostic costs and improving accessibility, CLDD holds promise for large-scale disease screening and social health security.

Heart failure (HF) is one of the leading causes of rehospitalization among older adults in the United States. Although clinical notes contain rich, detailed patient information and make up a large portion of electronic health records (EHRs), they remain underutilized for HF readmission risk analysis. Traditional computational models for HF readmission often rely on expert-crafted rules, medical thesauri, and ontologies to interpret clinical notes, which are typically written under time pressure and may contain misspellings, abbreviations, and domain-specific jargon. We present ClinNoteAgents, an LLM-based multi-agent framework that transforms free-text clinical notes into (1) structured representations of clinical and social risk factors for association analysis and (2) clinician-style abstractions for HF 30-day readmission prediction. We evaluate ClinNoteAgents on 3,544 notes from 2,065 patients (readmission rate=35.16%), demonstrating strong performance in extracting risk factors from free-text, identifying key contributing factors, and predicting readmission risk. By reducing reliance on structured fields and minimizing manual annotation and model training, ClinNoteAgents provides a scalable and interpretable approach to note-based HF readmission risk modeling in data-limited healthcare systems.

Objective: Machine learning (ML) predictive models are often developed without considering downstream value trade-offs and clinical interpretability. This paper introduces a cost-aware prediction (CAP) framework that combines cost-benefit analysis assisted by large language model (LLM) agents to communicate the trade-offs involved in applying ML predictions. Materials and Methods: We developed an ML model predicting 1-year mortality in patients with heart failure (N = 30,021, 22% mortality) to identify those eligible for home care. We then introduced clinical impact projection (CIP) curves to visualize important cost dimensions - quality of life and healthcare provider expenses, further divided into treatment and error costs, to assess the clinical consequences of predictions. Finally, we used four LLM agents to generate patient-specific descriptions. The system was evaluated by clinicians for its decision support value. Results: The eXtreme gradient boosting (XGB) model achieved the best performance, with an area under the receiver operating characteristic curve (AUROC) of 0.804 (95% confidence interval (CI) 0.792-0.816), area under the precision-recall curve (AUPRC) of 0.529 (95% CI 0.502-0.558) and a Brier score of 0.135 (95% CI 0.130-0.140). Discussion: The CIP cost curves provided a population-level overview of cost composition across decision thresholds, whereas LLM-generated cost-benefit analysis at individual patient-levels. The system was well received according to the evaluation by clinicians. However, feedback emphasizes the need to strengthen the technical accuracy for speculative tasks. Conclusion: CAP utilizes LLM agents to integrate ML classifier outcomes and cost-benefit analysis for more transparent and interpretable decision support.

Right heart failure (RHF) is a disease characterized by abnormalities in the structure or function of the right ventricle (RV), which is associated with high morbidity and mortality. Lung disease often causes increased right ventricular load, leading to RHF. Therefore, it is very important to screen out patients with cor pulmonale who develop RHF from people with underlying lung diseases. In this work, we propose a self-supervised representation learning method to early detecting RHF from patients with cor pulmonale, which uses spirogram time series to predict patients with RHF at an early stage. The proposed model is divided into two stages. The first stage is the self-supervised representation learning-based spirogram embedding (SLSE) network training process, where the encoder of the Variational autoencoder (VAE-encoder) learns a robust low-dimensional representation of the spirogram time series from the data-augmented unlabeled data. Second, this low-dimensional representation is fused with demographic information and fed into a CatBoost classifier for the downstream RHF prediction task. Trained and tested on a carefully selected subset of 26,617 individuals from the UK Biobank, our model achieved an AUROC of 0.7501 in detecting RHF, demonstrating strong population-level distinction ability. We further evaluated the model on high-risk clinical subgroups, achieving AUROC values of 0.8194 on a test set of 74 patients with chronic kidney disease (CKD) and 0.8413 on a set of 64 patients with valvular heart disease (VHD). These results highlight the model's potential utility in predicting RHF among clinically elevated-risk populations. In conclusion, this study presents a self-supervised representation learning approach combining spirogram time series and demographic data, demonstrating promising potential for early RHF detection in clinical practice.

R1: "I am not entirely convinced that an amortized explanation model is a reasonable thing. R2: "I would appreciate some clarification about what is gained by learning ˆ A and not just reporting Ω directly." We thank R1, R2 and R3 for their insightful feedback. R1: "(The objective) does not attribute importance to features that change how the model goes wrong (...)" R1: "Why is the rank-based method necessary? R2: "Additionally, can the authors clarify what is being averaged in the definition of the causal objective? R2: "If the goal is to determine what might happen to our predictions if we change a particular feature slightly Our goal is not to estimate what would happen if a particular feature's value changed, but to provide a causal explanation R2: "Some additional clarity on why the authors are using a KL discrepancy is merited. R3: "Masking one by one; this is essentially equivalent to assuming that feature contributions are additive." We do not define a feature's importance as its additive contribution to the model output, but as it's marginal reduction This subtle change in definition allows us to efficiently compute feature importance one by one. R3: "Replacing a masked value by a point-wise estimation can be very bad, especially when the classifiers output Why would the average value (or, even worse, zero) be meaningful?" We will clarify this point in the next revision. R3: "It would also be interesting to compare the proposed method with causal inference technique for SEMs." Recent work [29] has explored the use of SEMs for model attribution in deep learning. CXPlain can explain any machine-learning model, and (ii) attribution time was considerably slower than CXPlain. R3: "It seems to me that the chosen performance measure may correlate much more with the Granger-causal loss

Objective: Fluoropyrimidines are widely prescribed for colorectal and breast cancers, but are associated with toxicities such as hand-foot syndrome and cardiotoxicity. Since toxicity documentation is often embedded in clinical notes, we aimed to develop and evaluate natural language processing (NLP) methods to extract treatment and toxicity information. Materials and Methods: We constructed a gold-standard dataset of 236 clinical notes from 204,165 adult oncology patients. Domain experts annotated categories related to treatment regimens and toxicities. We developed rule-based, machine learning-based (Random Forest, Support Vector Machine [SVM], Logistic Regression [LR]), deep learning-based (BERT, ClinicalBERT), and large language models (LLM)-based NLP approaches (zero-shot and error-analysis prompting). Models used an 80:20 train-test split. Results: Sufficient data existed to train and evaluate 5 annotated categories. Error-analysis prompting achieved optimal precision, recall, and F1 scores (F1=1.000) for treatment and toxicities extraction, whereas zero-shot prompting reached F1=1.000 for treatment and F1=0.876 for toxicities extraction.LR and SVM ranked second for toxicities (F1=0.937). Deep learning underperformed, with BERT (F1=0.873 treatment; F1= 0.839 toxicities) and ClinicalBERT (F1=0.873 treatment; F1 = 0.886 toxicities). Rule-based methods served as our baseline with F1 scores of 0.857 in treatment and 0.858 in toxicities. Discussion: LMM-based approaches outperformed all others, followed by machine learning methods. Machine and deep learning approaches were limited by small training data and showed limited generalizability, particularly for rare categories. Conclusion: LLM-based NLP most effectively extracted fluoropyrimidine treatment and toxicity information from clinical notes, and has strong potential to support oncology research and pharmacovigilance.

Cardiovascular diseases are becoming increasingly prevalent in modern society, with a profound impact on global health and well-being. These Cardiovascular disorders are complex and multifactorial, influenced by genetic predispositions, lifestyle choices, and diverse socioeconomic and clinical factors. Information about these interrelated factors is dispersed across multiple types of textual data, including patient narratives, medical records, and scientific literature. Natural language processing (NLP) has emerged as a powerful approach for analysing such unstructured data, enabling healthcare professionals and researchers to gain deeper insights that may transform the diagnosis, treatment, and prevention of cardiac disorders. This review provides a comprehensive overview of NLP research in cardiology from 2014 to 2025. We systematically searched six literature databases for studies describing NLP applications across a range of cardiovascular diseases. After a rigorous screening process, we identified 265 relevant articles. Each study was analysed across multiple dimensions, including NLP paradigms, cardiology-related tasks, disease types, and data sources. Our findings reveal substantial diversity within these dimensions, reflecting the breadth and evolution of NLP research in cardiology. A temporal analysis further highlights methodological trends, showing a progression from rule-based systems to large language models. Finally, we discuss key challenges and future directions, such as developing interpretable LLMs and integrating multimodal data. To the best of our knowledge, this review represents the most comprehensive synthesis of NLP research in cardiology to date.

Counterfactual inference provides a mathematical framework for reasoning about hypothetical outcomes under alternative interventions, bridging causal reasoning and predictive modeling. We present a counterfactual inference framework for individualized risk estimation and intervention analysis, illustrated through a clinical application to post-acute sequelae of COVID-19 (PASC) among patients with pre-existing heart failure (HF). Using longitudinal diagnosis, laboratory, and medication data from a large health-system cohort, we integrate regularized predictive modeling with counterfactual search to identify actionable pathways to PASC-related HF hospital admissions. The framework combines exact enumeration with optimization-based methods, including the Nearest Instance Counterfactual Explanations (NICE) and Multi-Objective Counterfactuals (MOC) algorithms, to efficiently explore high-dimensional intervention spaces. Applied to more than 2700 individuals with confirmed SARS-CoV-2 infection and prior HF, the model achieved strong discriminative performance (AUROC: 0.88, 95% CI: 0.84-0.91) and generated interpretable, patient-specific counterfactuals that quantify how modifying comorbidity patterns or treatment factors could alter predicted outcomes. This work demonstrates how counterfactual reasoning can be formalized as an optimization problem over predictive functions, offering a rigorous, interpretable, and computationally efficient approach to personalized inference in complex biomedical systems.

Background: Heart failure (HF) research is constrained by limited access to large, shareable datasets due to privacy regulations and institutional barriers. Synthetic data generation offers a promising solution to overcome these challenges while preserving patient confidentiality. Methods: We generated synthetic HF datasets from institutional data comprising 12,552 unique patients using five deep learning models: tabular variational autoencoder (TVAE), normalizing flow, ADSGAN, SurvivalGAN, and tabular denoising diffusion probabilistic models (TabDDPM). We comprehensively evaluated synthetic data utility through statistical similarity metrics, survival prediction using machine learning and privacy assessments. Results: SurvivalGAN and TabDDPM demonstrated high fidelity to the original dataset, exhibiting similar variable distributions and survival curves after applying histogram equalization. SurvivalGAN (C-indices: 0.71-0.76) and TVAE (C-indices: 0.73-0.76) achieved the strongest performance in survival prediction evaluation, closely matched real data performance (C-indices: 0.73-0.76). Privacy evaluation confirmed protection against re-identification attacks. Conclusions: Deep learning-based synthetic data generation can produce high-fidelity, privacy-preserving HF datasets suitable for research applications. This publicly available synthetic dataset addresses critical data sharing barriers and provides a valuable resource for advancing HF research and predictive modeling.