The advent of multimodal large language models (MLLMs) has sparked interest in their application to electrocardiogram (ECG) analysis. However, existing ECG-focused MLLMs primarily focus on report generation tasks, often limited to single 12-lead, short-duration (10s) ECG inputs, thereby underutilizing the potential of MLLMs. To this end, we aim to develop a MLLM for ECG analysis that supports a broader range of tasks and more flexible ECG inputs. However, existing ECG-QA datasets are often monotonous. To address this gap, we first constructed the anyECG dataset, which encompasses a wide variety of tasks, including report generation, abnormal waveform localization, and open-ended question answering. In addition to standard hospital ECGs, we introduced long-duration reduced-lead ECGs for home environments and multiple ECG comparison scenarios commonly encountered in clinical practice. Furthermore, we propose the anyECG-chat model, which supports dynamic-length ECG inputs and multiple ECG inputs. We trained the model using a three-stage curriculum training recipe with the anyECG dataset. A comprehensive evaluation was conducted, demonstrating that anyECG-chat is capable of supporting various practical application scenarios, including not only common report generation tasks but also abnormal waveform localization for long-duration reduced-lead ECGs in home environments and comprehensive comparative analysis of multiple ECGs.

Vision Transformer, with the distinctive architecture and self-attention mechanisms, had profoundly influenced the field of computer vision, establishing Transformer-based models as benchmarks for semantic segmentation. In this study, we propose a pioneering hybrid model that fuses Kolmogorov-Arnold convolutions with ViT architecture to tackle the intrinsic challenges of semantic segmentation. By leveraging the unique attributes of Kolmogorov-Arnold convolutions, our approach introduces a convolutional attention mechanism within the Vision Transformer framework, effectively alleviating the quadratic complexity associated with self-attention. Furthermore, we integrate large-kernel convolutions and an upsampling module into the decoder, which is designed to enhance feature resolution, capture fine details, and maintain robust performance in complex scenarios for dense prediction tasks. Comprehensive experiments conducted on the ADE20K, Cityscapes, and COCO-Stuff datasets reveal that our method achieves mean Intersection over Union (mIoU) scores of 55.52%, 83.6%, and 51.8%, respectively.

Non-communicable disease is the leading cause of death, emphasizing the need for accurate prediction of disease progression and informed clinical decision-making. Machine learning (ML) models have shown promise in this domain by capturing non-linear patterns within patient features. However, existing ML-based models cannot provide causal interpretable predictions and estimate treatment effects, limiting their decision-making perspective. In this study, we propose a novel model called causal trajectory prediction (CTP) to tackle the limitation. The CTP model combines trajectory prediction and causal discovery to enable accurate prediction of disease progression trajectories and uncover causal relationships between features. By incorporating a causal graph into the prediction process, CTP ensures that ancestor features are not influenced by the treatment of descendant features, thereby enhancing the interpretability of the prediction. By estimating the bounds of treatment effects, the CTP provides valuable insights for clinical decision-making. We evaluate the performance of the CTP using simulated and real medical datasets. Experimental results demonstrate that our model has the potential to assist clinical decisions.

Unraveling the intricate network of associations among microRNAs (miRNAs), genes, and diseases is pivotal for deciphering molecular mechanisms, refining disease diagnosis, and crafting targeted therapies. Computational strategies, leveraging link prediction within biological graphs, present a cost-efficient alternative to high-cost empirical assays. However, while plenty of methods excel at predicting specific associations, such as miRNA-disease associations (MDAs), miRNA-target interactions (MTIs), and disease-gene associations (DGAs), a holistic approach harnessing diverse data sources for multifaceted association prediction remains largely unexplored. The limited availability of high-quality data, as vitro experiments to comprehensively confirm associations are often expensive and time-consuming, results in a sparse and noisy heterogeneous graph, hindering an accurate prediction of these complex associations. To address this challenge, we propose a novel framework called Global-local aware Heterogeneous Graph Contrastive Learning (GlaHGCL). GlaHGCL combines global and local contrastive learning to improve node embeddings in the heterogeneous graph. In particular, global contrastive learning enhances the robustness of node embeddings against noise by aligning global representations of the original graph and its augmented counterpart. Local contrastive learning enforces representation consistency between functionally similar or connected nodes across diverse data sources, effectively leveraging data heterogeneity and mitigating the issue of data scarcity. The refined node representations are applied to downstream tasks, such as MDA, MTI, and DGA prediction. Experiments show GlaHGCL outperforming state-of-the-art methods, and case studies further demonstrate its ability to accurately uncover new associations among miRNAs, genes, and diseases. We have made the datasets and source code publicly available at https://github.com/Sue-syx/GlaHGCL.

Objective: To combine medical knowledge and medical data to interpretably predict the risk of disease. Methods: We formulated the disease progression prediction task as a random walk along a knowledge graph (KG). Specifically, we build a KG to record relationships between diseases and risk factors according to validated medical knowledge. Then, an object walks along the KG. It starts walking at a patient entity, which connects the KG based on the patient’s current diseases or risk factors and stops at a disease entity representing the predicted disease. The trajectory generated by the object represents an interpretable disease progression path of the given patient. The dynamics of the object are controlled by a policy-based reinforcement learning module, which is trained by electronic health records (EHRs). Experiments: We utilized three real-world EHR datasets to evaluate the performance of our model. In the disease progression prediction task, our model achieves 0.743, 0.639, and 0.643 in terms of macro area under the curve (AUC) in predicting 53 circulation system diseases in the three datasets, respectively. This performance is comparable to medical research’s commonly used machine learning models. In qualitative analysis, our clinical collaborator reviewed the disease progression paths generated by our model and advocated their interpretability and reliability. Conclusion: Experimental results validate the proposed model in interpretably evaluating and optimizing disease progression prediction. Significance: Our work contributes to leveraging the potential of medical knowledge and medical data jointly for interpretable prediction tasks.

Retrosynthesis aided by artificial intelligence has been a very active and bourgeoning area of research, for its critical role in drug discovery as well as material science. Three categories of solutions, i.e., template-based, template-free, and semi-template methods, constitute mainstream solutions to this problem. In this paper, we focus on template-free methods which are known to be less bothered by the template generalization issue and the atom mapping challenge. Among several remaining problems regarding template-free methods, failing to conform to chemical rules is pronounced. To address the issue, we seek for a pre-training solution to empower the pre-trained model with chemical rules encoded. Concretely, we enforce the atom conservation rule via a molecule reconstruction pre-training task, and the reaction rule that dictates reaction centers via a reaction type guided contrastive pre-training task. In our empirical evaluation, the proposed pre-training solution substantially improves the single-step retrosynthesis accuracies in three downstream datasets.

Infectious keratitis is a major cause of visual impairment and a common blinding eye disease. Deep learning based prior researches mainly regard infectious keratitis diagnosis as a classification task on the slit-lamp images of single-visit. However, in real clinical applications, it is critical to analyze the lesion evolution characteristics represented by time-varying features over multiple-visits. To bridge this gap, in this paper, we focus on the problem with sequential clinical images of patients, and propose a novel disentangled sequential auto-encoder (DSLC-VAE) algorithm to separate the time-varying pathological features from the time-invariant ones for infectious keratitis diagnosis. Specifically, a inference model is exploited to generate time series of the shape and appearance of corneal lesions to represent keratitis progression, which are combined with location-related features to identify keratitis pathogen. Moreover, we construct a local consistent regularizer with a self-supervised task to enhance the consistency of the time-varying features across different infectious keratitis. Extensive experiments on real world dataset demonstrate superiority of our DSLC-VAE on both representation disentanglement and diagnosis accuracy.

Dialogue state tracking (DST) is a component of the task oriented dialogue system. It is responsible for extracting and managing slots, where each slot represents a part of the information to accomplish a task, and slot value is updated recurrently in each dialogue turn. However, many DST models cannot update slot values appropriately. These models may repeatedly inherit wrong slot values extracted in previous turns, resulting in the fail of the entire DST task. They cannot update indirectly mentioned slots well, either. This study designed a model with a mentioned slot pool (MSP) to tackle the update problem. The MSP is a slot specific memory that records all mentioned slot values that may be inherited, and our model updates slot values according to the MSP and the dialogue context. Our model rejects inheriting the previous slot value when it predicates the value is wrong. Then, it extracts the slot value from the current dialogue context. As the contextual information accumulates, the new value is more likely to be correct. It also can track the indirectly mentioned slot by picking a value from the MSP. Experimental results showed our model reached state of the art DST performance on MultiWOZ datasets.

Retrosynthetic planning occupies a crucial position in synthetic chemistry and, accordingly, drug discovery, which aims to find synthetic pathways of a target molecule through a sequential decision-making process on a set of feasible reactions. While the majority of recent works focus on the prediction of feasible reactions at each step, there have been limited attempts toward improving the sequential decision-making policy. Existing strategies rely on either the expensive and high-variance value estimation by online rollout, or a settled value estimation neural network pre-trained with simulated pathways of limited diversity and no negative feedback. Besides, how to return multiple candidate pathways that are not only diverse but also desirable for chemists (e.g., affordable building block materials) remains an open challenge. To this end, we propose a Goal-dRiven Actor-critic retroSynthetic Planning (GRASP) framework, where we identify the policy that performs goal-driven retrosynthesis navigation toward a user-demand objective. Our experiments on the benchmark Pistachio dataset and a chemists-designed dataset demonstrate that the framework outperforms state-of-the-art approaches by up to 32.2% on search efficiency and 5.6% on quality. Remarkably, our user studies show that GRASP successfully plans pathways that accomplish the goal prescribed with a designated goal (building block materials).

Survival analysis (SA) is widely used to analyze data in which the time until the event is of interest. Conventional SA techniques assume a specific form for viewing the distribution of survival time as the hitting time of a stochastic process, and explicitly model the relationship between covariates and the distribution of the events hitting time. Although valuable, existing SA models seldom consider to model the dynamic correlations between covariates and more than one event of interest (i.e., competing risks) in the disease progression of subjects. To alleviate this critical problem, we propose a novel deep contrastive learning model to obtain a deep understanding of disease progression of subjects with competing risks from their longitudinal observational data. Specifically, we design a self-supervised objective for learning dynamic representations of subjects suffering from multiple competing risks, such that the relationship between covariates and each specific competing risk changes over time can be well captured. Experiments on two open-source clinical datasets, i.e., MIMIC-III and EICU, demonstrate the effectiveness of our proposed model, with remarkable improvements over the state-of-the-art SA models.

Cohort selection is an essential prerequisite for clinical research, determining whether an individual satisfies given selection criteria. Previous works for cohort selection usually treated each selection criterion independently and ignored not only the meaning of each selection criterion but the relations among cohort selection criteria. To solve the problems above, we propose a novel unified machine reading comprehension (MRC) framework. In this MRC framework, we design simple rules to generate questions for each criterion from cohort selection guidelines and treat clues extracted by trigger words from patients' medical records as passages. A series of state-of-the-art MRC models based on BiDAF, BIMPM, BERT, BioBERT, NCBI-BERT, and RoBERTa are deployed to determine which question and passage pairs match. We also introduce a cross-criterion attention mechanism on representations of question and passage pairs to model relations among cohort selection criteria. Results on two datasets, that is, the dataset of the 2018 National NLP Clinical Challenge (N2C2) for cohort selection and a dataset from the MIMIC-III dataset, show that our NCBI-BERT MRC model with cross-criterion attention mechanism achieves the highest micro-averaged F1-score of 0.9070 on the N2C2 dataset and 0.8353 on the MIMIC-III dataset. It is competitive to the best system that relies on a large number of rules defined by medical experts on the N2C2 dataset. Comparing these two models, we find that the NCBI-BERT MRC model mainly performs worse on mathematical logic criteria. When using rules instead of the NCBI-BERT MRC model on some criteria regarding mathematical logic on the N2C2 dataset, we obtain a new benchmark with an F1-score of 0.9163, indicating that it is easy to integrate rules into MRC models for improvement.

Survival analysis exhibits profound effects on health service management. Traditional approaches for survival analysis have a pre-assumption on the time-to-event probability distribution and seldom consider sequential visits of patients on medical facilities. Although recent studies leverage the merits of deep learning techniques to capture non-linear features and long-term dependencies within multiple visits for survival analysis, the lack of interpretability prevents deep learning models from being applied to clinical practice. To address this challenge, this article proposes a novel attention-based deep recurrent model, named AttenSurv , for clinical survival analysis. Specifically, a global attention mechanism is proposed to extract essential/critical risk factors for interpretability improvement. Thereafter, Bi-directional Long Short-Term Memory is employed to capture the long-term dependency on data from a series of visits of patients. To further improve both the prediction performance and the interpretability of the proposed model, we propose another model, named GNNAttenSurv , by incorporating a graph neural network into AttenSurv, to extract the latent correlations between risk factors. We validated our solution on three public follow-up datasets and two electronic health record datasets. The results demonstrated that our proposed models yielded consistent improvement compared to the state-of-the-art baselines on survival analysis.

Massively available longitudinal data about long-term disease trajectories of patients provides a golden mine for the understanding of disease progression and efficient health service delivery. It calls for quantitative modeling of disease progression, which is a tricky problem due to the complexity of the disease progression process as well as the irregularity of time documented in trajectories. In this study, we tackle the problem with the goal of predictively analyzing disease progression. Specifically, we propose a novel Variational Hawkes Process (VHP) model to generalize disease progression and predict future patient states based on the clinical observational data of past disease trajectories. First, Hawkes Process captures the intensity of irregular visits in a trajectory documented to medical facilities and controls the aforementioned information flowing into future visits. Thereafter, the captured intensity is incorporated into a Variational Auto-Encoder to generate the representation of the future partial disease trajectory for a target patient in a predictive manner. To further improve the prediction performance, we equip the proposed model with a disease trajectory discriminator to distinguish the generated trajectories from real ones. We evaluate the proposed model on two public datasets from the MIMIC-III database pertaining to heart failure and sepsis patients, respectively, and one real-world dataset from a Chinese hospital pertaining to heart failure patients with multiple admissions. Experimental results demonstrate that the proposed model significantly outperforms state-of-the-art baselines, and may derive a set of practical implications that can benefit a wide spectrum of management and applications on disease progression.

Healthcare process leaves patient treatment trajectory (PTT), described as a sequence of interdependent clinical events affiliated with a large volume of longitudinal therapy and treatment information. Predicting the future clinical event in PTT, as a vital and essential task for providing insights into the entire treatment trajectory, can serve as an efficient and proactive altering service for health service delivery. However, it is challenging because there are long-term dependencies between clinical events, which are irregularly distributed along the temporal axis with varying time intervals. This characteristic inevitably impedes the performance of clinical event prediction (CEP) using the existing approaches. To address this challenge, we propose a novel approach to learn representative and discriminative PTT features for CEP. In detail, multivariate Hawkes process (HP) is adopted to uncover the mutual excitation intensities between clinical event pairs in an interpretable manner. Thereafter, the captured spontaneous and interactional intensities of events are incorporated into recurrent neural networks (RNN) to encode PTT in latent representations, while jointly performing the CEP task based on the extracted trajectory representations. We evaluate the performance of the proposed approach on a real clinical dataset consisting of 13,545 visits of 2,102 heart failure patients. Compared to state-of-the-art methods, our best model achieves 6.4% and 4.1% AUC performance gains on three-months and one-year CEP tasks, respectively. The experimental results demonstrate that the proposed approach outperforms state-of-the-art models in CEP, and can be profitably exploited as a basis for PTT analysis and optimization.

Acute coronary syndrome (ACS), as an emergent and severe syndrome due to decreased blood flow in the coronary arteries, is a leading cause of death and serious long-term disability globally. ACS is usually caused by one of three problems: ST elevation myocardial infarction, non-ST elevation myocardial infarction, or unstable angina. Major adverse cardiac event (MACE) prediction, as a critical tool to estimate the likelihood an individual is at risk of ACS, has been widely adopted in the early prevention and intervention of ACS. Although valuable, existing MACE prediction models are designed to predict the overall probability of MACE occurrence for ACS patients, and lack the ability to look for insight into the disease to distinguish the different subtypes of ACS in a fine-grained manner. It is interesting to exploit the different subtypes of ACS and mine their private and shared underlying knowledge to improve the performance of MACE prediction. In this study, we propose utilizing a large volume of heterogeneous electronic health records for the application of MACE prediction. In detail, we address the multi-subtype-oriented MACE prediction for ACS as a multi-task learning (MTL) problem, present a MTL-based model to predict MACE of ACS patients with the different subtypes, and incorporate adversarial learning into the model to alleviate both the shared and private latent feature spaces of each subtype of ACS from interfering with each other. A real clinical dataset containing 2,863 ACS patient samples is collected from a Chinese hospital to validate the proposed model. Experimental results demonstrate that the prediction performance of our proposed model obtains a significant improvement, compared to single-subtype-oriented MACE prediction models.

Clinical pathways leave traces, described as event sequences with regard to a mixture of various latent treatment behaviors. Measuring similarities between patient traces can profitably be exploited further as a basis for providing insights into the pathways, and complementing existing techniques of clinical pathway analysis (CPA), which mainly focus on looking at aggregated data seen from an external perspective. Most existing methods measure similarities between patient traces via computing the relative distance between their event sequences. However, clinical pathways, as typical human-centered processes, always take place in an unstructured fashion, i.e., clinical events occur arbitrarily without a particular order. Bringing order in the chaos of clinical pathways may decline the accuracy of similarity measure between patient traces, and may distort the efficiency of further analysis tasks. In this paper, we present a behavioral topic analysis approach to measure similarities between patient traces. More specifically, a probabilistic graphical model, i.e., latent Dirichlet allocation (LDA), is employed to discover latent treatment behaviors of patient traces for clinical pathways such that similarities of pairwise patient traces can be measured based on their underlying behavioral topical features. The presented method provides a basis for further applications in CPA. In particular, three possible applications are introduced in this paper, i.e., patient trace retrieval, clustering, and anomaly detection. The proposed approach and the presented applications are evaluated via a real-world dataset of several specific clinical pathways collected from a Chinese hospital.

Least mean square (LMS)-type adaptive sparse algorithms have been attracting much attention on sparse multipath channel estimation (SMPC) due to their two advantages: low computational complexity and reliability. By introducing ℓ1-norm sparse constraint function into LMS algorithm, both zero-attracting least mean square (ZA-LMS) and reweighted zero-attracting least mean square (RZA-LMS) have been proposed for SMPC. It is well known that the performance of the SMPC is decided by regularization parameter which balances channel estimation error and sparse penalty strength. However, optimal regularization parameter selection has not yet considered in the two proposed algorithms. Based on the compressive sensing theory, in this paper, we explain the mathematical relationship between Lasso and LMS-type adaptive sparse algorithms. Later, an approximate optimal regulation parameter selection method is proposed for ZA-LMS and RZA-LMS, respectively. Monte Carlo based computer simulations are presented to show the effectiveness of our propose method.

Resource allocation, as an integral part of business process management (BPM), is more widely acknowledged by its importance for process-aware information systems. Despite the industrial need for efficient and effective resource allocation in BPM, few scientifically-grounded approaches exist to support these initiatives. In this paper, a new approach of resource allocation optimization is proposed, built on the concepts that is part of an operation-oriented view on process optimization. Essentially, the proposed approach automatically generates a specific task operation model (TOM) for a particular business process. In addition, in order to support end users in making sensible resource allocations, an ant colony optimization-based algorithm is presented, which makes it possible to search an optimal task operation path on the generated TOM. This allows one to suggest how a business user should efficiently allocate resources to perform the tasks of a particular process case. The feasibility of the presented approach is demonstrated by a simulation experiment. The experimental results show that the proposed approach outperforms reasonable heuristic approaches to satisfy process performance goals, and it is possible to improve the current state of BPM.