Chuan Hong

Siqi Li, Pinyan Liu, Gustavo G. Nascimento et al.

Federated learning (FL) has gained popularity in clinical research in recent years to facilitate privacy-preserving collaboration. Structured data, one of the most prevalent forms of clinical data, has experienced significant growth in volume concurrently, notably with the widespread adoption of electronic health records in clinical practice. This review examines FL applications on structured medical data, identifies contemporary limitations and discusses potential innovations. We searched five databases, SCOPUS, MEDLINE, Web of Science, Embase, and CINAHL, to identify articles that applied FL to structured medical data and reported results following the PRISMA guidelines. Each selected publication was evaluated from three primary perspectives, including data quality, modeling strategies, and FL frameworks. Out of the 1160 papers screened, 34 met the inclusion criteria, with each article consisting of one or more studies that used FL to handle structured clinical/medical data. Of these, 24 utilized data acquired from electronic health records, with clinical predictions and association studies being the most common clinical research tasks that FL was applied to. Only one article exclusively explored the vertical FL setting, while the remaining 33 explored the horizontal FL setting, with only 14 discussing comparisons between single-site (local) and FL (global) analysis. The existing FL applications on structured medical data lack sufficient evaluations of clinically meaningful benefits, particularly when compared to single-site analyses. Therefore, it is crucial for future FL applications to prioritize clinical motivations and develop designs and methodologies that can effectively support and aid clinical practice and research.

Siqi Li, Yilin Ning, Marcus Eng Hock Ong et al.

We propose FedScore, a privacy-preserving federated learning framework for scoring system generation across multiple sites to facilitate cross-institutional collaborations. The FedScore framework includes five modules: federated variable ranking, federated variable transformation, federated score derivation, federated model selection and federated model evaluation. To illustrate usage and assess FedScore's performance, we built a hypothetical global scoring system for mortality prediction within 30 days after a visit to an emergency department using 10 simulated sites divided from a tertiary hospital in Singapore. We employed a pre-existing score generator to construct 10 local scoring systems independently at each site and we also developed a scoring system using centralized data for comparison. We compared the acquired FedScore model's performance with that of other scoring models using the receiver operating characteristic (ROC) analysis. The FedScore model achieved an average area under the curve (AUC) value of 0.763 across all sites, with a standard deviation (SD) of 0.020. We also calculated the average AUC values and SDs for each local model, and the FedScore model showed promising accuracy and stability with a high average AUC value which was closest to the one of the pooled model and SD which was lower than that of most local models. This study demonstrates that FedScore is a privacy-preserving scoring system generator with potentially good generalizability.

Siqi Li, Di Miao, Qiming Wu et al.

Federated learning (FL) has shown promising potential in safeguarding data privacy in healthcare collaborations. While the term "FL" was originally coined by the engineering community, the statistical field has also explored similar privacy-preserving algorithms. Statistical FL algorithms, however, remain considerably less recognized than their engineering counterparts. Our goal was to bridge the gap by presenting the first comprehensive comparison of FL frameworks from both engineering and statistical domains. We evaluated five FL frameworks using both simulated and real-world data. The results indicate that statistical FL algorithms yield less biased point estimates for model coefficients and offer convenient confidence interval estimations. In contrast, engineering-based methods tend to generate more accurate predictions, sometimes surpassing central pooled and statistical FL models. This study underscores the relative strengths and weaknesses of both types of methods, emphasizing the need for increased awareness and their integration in future FL applications.

Bohao Yang, Rui Yang, Joshua M. Biro et al.

Clinical communication is central to patient outcomes, yet large-scale human annotation of patient-provider conversation remains labor-intensive, inconsistent, and difficult to scale. Existing approaches based on large language models typically rely on single-task models that lack adaptability, interpretability, and reliability, especially when applied across various communication frameworks and clinical domains. In this study, we developed a Multi-framework Structured Agentic AI system for Clinical Communication (MOSAIC), built on a LangGraph-based architecture that orchestrates four core agents, including a Plan Agent for codebook selection and workflow planning, an Update Agent for maintaining up-to-date retrieval databases, a set of Annotation Agents that applies codebook-guided retrieval-augmented generation (RAG) with dynamic few-shot prompting, and a Verification Agent that provides consistency checks and feedback. To evaluate performance, we compared MOSAIC outputs against gold-standard annotations created by trained human coders. We developed and evaluated MOSAIC using 26 gold standard annotated transcripts for training and 50 transcripts for testing, spanning rheumatology and OB/GYN domains. On the test set, MOSAIC achieved an overall F1 score of 0.928. Performance was highest in the Rheumatology subset (F1 = 0.962) and strongest for Patient Behavior (e.g., patients asking questions, expressing preferences, or showing assertiveness). Ablations revealed that MOSAIC outperforms baseline benchmarking.

Siqi Li, Xin Li, Kunyu Yu et al.

Clinical and biomedical research in low-resource settings often faces significant challenges due to the need for high-quality data with sufficient sample sizes to construct effective models. These constraints hinder robust model training and prompt researchers to seek methods for leveraging existing knowledge from related studies to support new research efforts. Transfer learning (TL), a machine learning technique, emerges as a powerful solution by utilizing knowledge from pre-trained models to enhance the performance of new models, offering promise across various healthcare domains. Despite its conceptual origins in the 1990s, the application of TL in medical research has remained limited, especially beyond image analysis. In our review of TL applications in structured clinical and biomedical data, we screened 3,515 papers, with 55 meeting the inclusion criteria. Among these, only 2% (one out of 55) utilized external studies, and 7% (four out of 55) addressed scenarios involving multi-site collaborations with privacy constraints. To achieve actionable TL with structured medical data while addressing regional disparities, inequality, and privacy constraints in healthcare research, we advocate for the careful identification of appropriate source data and models, the selection of suitable TL frameworks, and the validation of TL models with proper baselines.

Rui Yang, Huitao Li, Weihao Xuan et al.

Despite continuous advances in medical technology, the global distribution of health care resources remains uneven. The development of large language models (LLMs) has transformed the landscape of medicine and holds promise for improving health care quality and expanding access to medical information globally. However, existing LLMs are primarily trained on high-resource languages, limiting their applicability in global medical scenarios. To address this gap, we constructed GlobMed, a large multilingual medical dataset, containing over 500,000 entries spanning 12 languages, including four low-resource languages. Building on this, we established GlobMed-Bench, which systematically assesses 56 state-of-the-art proprietary and open-weight LLMs across multiple multilingual medical tasks, revealing significant performance disparities across languages, particularly for low-resource languages. Additionally, we introduced GlobMed-LLMs, a suite of multilingual medical LLMs trained on GlobMed, with parameters ranging from 1.7B to 8B. GlobMed-LLMs achieved an average performance improvement of over 40% relative to baseline models, with a more than threefold increase in performance on low-resource languages. Together, these resources provide an important foundation for advancing the equitable development and application of LLMs globally, enabling broader language communities to benefit from technological advances.

Siqi Li, Chuan Hong, Ziye Tian et al.

Deploying clinical prediction models across healthcare systems often fails when key training covariates are unavailable at deployment and labeled outcomes are limited in the target domain. For example, high-performing models for out-of-hospital cardiac arrest (OHCA) rely on detailed prehospital measurements routinely collected in high-resource settings but unavailable in many international registries. Existing methods either discard missing covariates, sacrificing predictive information, or rely on untestable assumptions about their target distribution. We propose DRUM (\underline{D}istributionally \underline{R}obust \underline{U}nsupervised transfer learning with structurally \underline{M}issing covariates), a framework that transfers prediction models to target populations where certain covariates are structurally absent and outcome labels are unavailable. DRUM partitions covariates into shared components ($X$), observed across all settings, and missing components ($A$), observed only in the source. Rather than imputing missing covariates, DRUM optimizes worst-case predictive performance over the unknown target distribution of $A \mid X$ using a neural network generator, with a robustness parameter controlling allowable deviation from the source conditional. We further develop a bias correction procedure that reduces sensitivity to nuisance estimation error. Simulations show substantial improvements in both mean and worst-case prediction error under distribution shift. Applied to cross-national OHCA prediction, transferring models from a US registry to multiple Asian registries where prehospital variables are unrecorded, DRUM yields better-calibrated predictions and improved clinical classification performance across sites.

Rui Yang, Matthew Yu Heng Wong, Huitao Li et al.

The rapid growth of medical knowledge and increasing complexity of clinical practice pose challenges. In this context, large language models (LLMs) have demonstrated value; however, inherent limitations remain. Retrieval-augmented generation (RAG) technologies show potential to enhance their clinical applicability. This study reviewed RAG applications in medicine. We found that research primarily relied on publicly available data, with limited application in private data. For retrieval, approaches commonly relied on English-centric embedding models, while LLMs were mostly generic, with limited use of medical-specific LLMs. For evaluation, automated metrics evaluated generation quality and task performance, whereas human evaluation focused on accuracy, completeness, relevance, and fluency, with insufficient attention to bias and safety. RAG applications were concentrated on question answering, report generation, text summarization, and information extraction. Overall, medical RAG remains at an early stage, requiring advances in clinical validation, cross-linguistic adaptation, and support for low-resource settings to enable trustworthy and responsible global use.

Yun-Chung Liu, Rui Yang, Jonathan Chong Kai Liew et al.

Systematic reviews are a key component of evidence-based medicine, playing a critical role in synthesizing existing research evidence and guiding clinical decisions. However, with the rapid growth of research publications, conducting systematic reviews has become increasingly burdensome, with title and abstract screening being one of the most time-consuming and resource-intensive steps. To mitigate this issue, we designed a two-stage dynamic few-shot learning (DFSL) approach aimed at improving the efficiency and performance of large language models (LLMs) in the title and abstract screening task. Specifically, this approach first uses a low-cost LLM for initial screening, then re-evaluates low-confidence instances using a high-performance LLM, thereby enhancing screening performance while controlling computational costs. We evaluated this approach across 10 systematic reviews, and the results demonstrate its strong generalizability and cost-effectiveness, with potential to reduce manual screening burden and accelerate the systematic review process in practical applications.

Yang Yang, Kathryn Pollak, Bibhas Chakraborty et al.

Objective: Electronic health record (EHR) phenotyping often relies on noisy proxy labels, which undermine the reliability of downstream risk prediction. Active learning can reduce annotation costs, but most rely on fixed heuristics and do not ensure that phenotype refinement improves prediction performance. Our goal was to develop a framework that directly uses downstream prediction performance as feedback to guide phenotype correction and sample selection under constrained labeling budgets. Materials and Methods: We propose Reinforcement-Enhanced Label-Efficient Active Phenotyping (RELEAP), a reinforcement learning-based active learning framework. RELEAP adaptively integrates multiple querying strategies and, unlike prior methods, updates its policy based on feedback from downstream models. We evaluated RELEAP on a de-identified Duke University Health System (DUHS) cohort (2014-2024) for incident lung cancer risk prediction, using logistic regression and penalized Cox survival models. Performance was benchmarked against noisy-label baselines and single-strategy active learning. Results: RELEAP consistently outperformed all baselines. Logistic AUC increased from 0.774 to 0.805 and survival C-index from 0.718 to 0.752. Using downstream performance as feedback, RELEAP produced smoother and more stable gains than heuristic methods under the same labeling budget. Discussion: By linking phenotype refinement to prediction outcomes, RELEAP learns which samples most improve downstream discrimination and calibration, offering a more principled alternative to fixed active learning rules. Conclusion: RELEAP optimizes phenotype correction through downstream feedback, offering a scalable, label-efficient paradigm that reduces manual chart review and enhances the reliability of EHR-based risk prediction.

Han Yuan, Chuan Hong, Nguyen Tuan Anh Tran et al.

Pneumothorax is a medical emergency caused by abnormal accumulation of air in the pleural space - the potential space between the lungs and chest wall. On 2D chest radiographs, pneumothorax occurs within the thoracic cavity and outside of the mediastinum and we refer to this area as "lung+ space". While deep learning (DL) has increasingly been utilized to segment pneumothorax lesions in chest radiographs, many existing DL models employ an end-to-end approach. These models directly map chest radiographs to clinician-annotated lesion areas, often neglecting the vital domain knowledge that pneumothorax is inherently location-sensitive. We propose a novel approach that incorporates the lung+ space as a constraint during DL model training for pneumothorax segmentation on 2D chest radiographs. To circumvent the need for additional annotations and to prevent potential label leakage on the target task, our method utilizes external datasets and an auxiliary task of lung segmentation. This approach generates a specific constraint of lung+ space for each chest radiograph. Furthermore, we have incorporated a discriminator to eliminate unreliable constraints caused by the domain shift between the auxiliary and target datasets. Our results demonstrated significant improvements, with average performance gains of 4.6%, 3.6%, and 3.3% regarding Intersection over Union (IoU), Dice Similarity Coefficient (DSC), and Hausdorff Distance (HD). Our research underscores the significance of incorporating medical domain knowledge about the location-specific nature of pneumothorax to enhance DL-based lesion segmentation.

Wangxuan Fan, Siqi Li, Doudou Zhou et al.

Explainable artificial intelligence (XAI) is essential for trustworthy machine learning (ML), particularly in high-stakes domains such as healthcare and finance. Shapley value (SV) methods provide a principled framework for feature attribution in complex models but incur high computational costs, limiting their scalability in high-dimensional settings. We propose Stochastic Iterative Momentum for Shapley Value Approximation (SIM-Shapley), a stable and efficient SV approximation method inspired by stochastic optimization. We analyze variance theoretically, prove linear $Q$-convergence, and demonstrate improved empirical stability and low bias in practice on real-world datasets. In our numerical experiments, SIM-Shapley reduces computation time by up to 85% relative to state-of-the-art baselines while maintaining comparable feature attribution quality. Beyond feature attribution, our stochastic mini-batch iterative framework extends naturally to a broader class of sample average approximation problems, offering a new avenue for improving computational efficiency with stability guarantees. Code is publicly available at https://github.com/nliulab/SIM-Shapley.

Mingxuan Liu, Yuhe Ke, Wentao Zhu et al.

The integration of large language models (LLMs) into healthcare holds promise to enhance clinical decision-making, yet their susceptibility to biases remains a critical concern. Gender has long influenced physician behaviors and patient outcomes, raising concerns that LLMs assuming human-like roles, such as clinicians or medical educators, may replicate or amplify gender-related biases. Using case studies from the New England Journal of Medicine Challenge (NEJM), we assigned genders (female, male, or unspecified) to multiple open-source and proprietary LLMs. We evaluated their response consistency across LLM-gender assignments regarding both LLM-based diagnosis and models' judgments on the clinical relevance or necessity of patient gender. In our findings, diagnoses were relatively consistent across LLM genders for most models. However, for patient gender's relevance and necessity in LLM-based diagnosis, all models demonstrated substantial inconsistency across LLM genders, particularly for relevance judgements. Some models even displayed a systematic female-male disparity in their interpretation of patient gender. These findings present an underexplored bias that could undermine the reliability of LLMs in clinical practice, underscoring the need for routine checks of identity-assignment consistency when interacting with LLMs to ensure reliable and equitable AI-supported clinical care.

Jessica Gronsbell, Vidul Ayakulangara Panickan, Chris Lin et al.

Integrative analysis of multi-institutional Electronic Health Record (EHR) data enhances the reliability and generalizability of translational research by leveraging larger, more diverse patient cohorts and incorporating multiple data modalities. However, harmonizing EHR data across institutions poses major challenges due to data heterogeneity, semantic differences, and privacy concerns. To address these challenges, we introduce $\textit{PEHRT}$, a standardized pipeline for efficient EHR data harmonization consisting of two core modules: (1) data pre-processing and (2) representation learning. PEHRT maps EHR data to standard coding systems and uses advanced machine learning to generate research-ready datasets without requiring individual-level data sharing. Our pipeline is also data model agnostic and designed for streamlined execution across institutions based on our extensive real-world experience. We provide a complete suite of open source software, accompanied by a user-friendly tutorial, and demonstrate the utility of PEHRT in a variety of tasks using data from diverse healthcare systems.

Han Yuan, Chuan Hong, Pengtao Jiang et al.

Background: Pneumothorax is an acute thoracic disease caused by abnormal air collection between the lungs and chest wall. To address the opaqueness often associated with deep learning (DL) models, explainable artificial intelligence (XAI) methods have been introduced to outline regions related to pneumothorax diagnoses made by DL models. However, these explanations sometimes diverge from actual lesion areas, highlighting the need for further improvement. Method: We propose a template-guided approach to incorporate the clinical knowledge of pneumothorax into model explanations generated by XAI methods, thereby enhancing the quality of these explanations. Utilizing one lesion delineation created by radiologists, our approach first generates a template that represents potential areas of pneumothorax occurrence. This template is then superimposed on model explanations to filter out extraneous explanations that fall outside the template's boundaries. To validate its efficacy, we carried out a comparative analysis of three XAI methods with and without our template guidance when explaining two DL models in two real-world datasets. Results: The proposed approach consistently improved baseline XAI methods across twelve benchmark scenarios built on three XAI methods, two DL models, and two datasets. The average incremental percentages, calculated by the performance improvements over the baseline performance, were 97.8% in Intersection over Union (IoU) and 94.1% in Dice Similarity Coefficient (DSC) when comparing model explanations and ground-truth lesion areas. Conclusions: In the context of pneumothorax diagnoses, we proposed a template-guided approach for improving AI explanations. We anticipate that our template guidance will forge a fresh approach to elucidating AI models by integrating clinical domain expertise.

Doudou Zhou, Han Tong, Linshanshan Wang et al.

The adoption of EHRs has expanded opportunities to leverage data-driven algorithms in clinical care and research. A major bottleneck in effectively conducting multi-institutional EHR studies is the data heterogeneity across systems with numerous codes that either do not exist or represent different clinical concepts across institutions. The need for data privacy further limits the feasibility of including multi-institutional patient-level data required to study similarities and differences across patient subgroups. To address these challenges, we developed the GAME algorithm. Tested and validated across 7 institutions and 2 languages, GAME integrates data in several levels: (1) at the institutional level with knowledge graphs to establish relationships between codes and existing knowledge sources, providing the medical context for standard codes and their relationship to each other; (2) between institutions, leveraging language models to determine the relationships between institution-specific codes with established standard codes; and (3) quantifying the strength of the relationships between codes using a graph attention network. Jointly trained embeddings are created using transfer and federated learning to preserve data privacy. In this study, we demonstrate the applicability of GAME in selecting relevant features as inputs for AI-driven algorithms in a range of conditions, e.g., heart failure, rheumatoid arthritis. We then highlight the application of GAME harmonized multi-institutional EHR data in a study of Alzheimer's disease outcomes and suicide risk among patients with mental health disorders, without sharing patient-level data outside individual institutions.

Rui Yang, Jiayi Tong, Haoyuan Wang et al.

Background. Systematic reviews in comparative effectiveness research require timely evidence synthesis. Preprints accelerate knowledge dissemination but vary in quality, posing challenges for systematic reviews. Methods. We propose AutoConfidence (automated confidence assessment), an advanced framework for predicting preprint publication, which reduces reliance on manual curation and expands the range of predictors, including three key advancements: (1) automated data extraction using natural language processing techniques, (2) semantic embeddings of titles and abstracts, and (3) large language model (LLM)-driven evaluation scores. Additionally, we employed two prediction models: a random forest classifier for binary outcome and a survival cure model that predicts both binary outcome and publication risk over time. Results. The random forest classifier achieved AUROC 0.692 with LLM-driven scores, improving to 0.733 with semantic embeddings and 0.747 with article usage metrics. The survival cure model reached AUROC 0.716 with LLM-driven scores, improving to 0.731 with semantic embeddings. For publication risk prediction, it achieved a concordance index of 0.658, increasing to 0.667 with semantic embeddings. Conclusion. Our study advances the framework for preprint publication prediction through automated data extraction and multiple feature integration. By combining semantic embeddings with LLM-driven evaluations, AutoConfidence enhances predictive performance while reducing manual annotation burden. The framework has the potential to facilitate incorporation of preprint articles during the appraisal phase of systematic reviews, supporting researchers in more effective utilization of preprint resources.

Siqi Li, Yuqing Shang, Ziwen Wang et al.

Survival analysis serves as a fundamental component in numerous healthcare applications, where the determination of the time to specific events (such as the onset of a certain disease or death) for patients is crucial for clinical decision-making. Scoring systems are widely used for swift and efficient risk prediction. However, existing methods for constructing survival scores presume that data originates from a single source, posing privacy challenges in collaborations with multiple data owners. We propose a novel framework for building federated scoring systems for multi-site survival outcomes, ensuring both privacy and communication efficiency. We applied our approach to sites with heterogeneous survival data originating from emergency departments in Singapore and the United States. Additionally, we independently developed local scores at each site. In testing datasets from each participant site, our proposed federated scoring system consistently outperformed all local models, evidenced by higher integrated area under the receiver operating characteristic curve (iAUC) values, with a maximum improvement of 11.6%. Additionally, the federated score's time-dependent AUC(t) values showed advantages over local scores, exhibiting narrower confidence intervals (CIs) across most time points. The model developed through our proposed method exhibits effective performance on each local site, signifying noteworthy implications for healthcare research. Sites participating in our proposed federated scoring model training gained benefits by acquiring survival models with enhanced prediction accuracy and efficiency. This study demonstrates the effectiveness of our privacy-preserving federated survival score generation framework and its applicability to real-world heterogeneous survival data.

Mengying Yan, Ziye Tian, Siqi Li et al.

Clinical decision support tools built on electronic health records often experience performance drift due to temporal population shifts, particularly when changes in the clinical environment initially affect only a subset of patients, resulting in a transition to mixed populations. Such case-mix changes commonly arise following system-level operational updates or the emergence of new diseases, such as COVID-19. We propose TRACER (Transfer Learning-based Real-time Adaptation for Clinical Evolving Risk), a framework that identifies encounter-level transition membership and adapts predictive models using transfer learning without full retraining. In simulation studies, TRACER outperformed static models trained on historical or contemporary data. In a real-world application predicting hospital admission following emergency department visits across the COVID-19 transition, TRACER improved both discrimination and calibration. TRACER provides a scalable approach for maintaining robust predictive performance under evolving and heterogeneous clinical conditions.

Mingxuan Liu, Yilin Ning, Haoyuan Wang et al.

As machine learning models become increasingly integrated into healthcare, structural inequities and social biases embedded in clinical data can be perpetuated or even amplified by data-driven models. In survival analysis, censoring and time dynamics can further add complexity to fair model development. Additionally, algorithmic fairness approaches often overlook disparities in cross-group rankings, e.g., high-risk Black patients may be ranked below lower-risk White patients who do not experience the event of mortality. Such misranking can reinforce biological essentialism and undermine equitable care. We propose a Fairness-Aware Survival Modeling (FASM), designed to mitigate algorithmic bias regarding both intra-group and cross-group risk rankings over time. Using breast cancer prognosis as a representative case and applying FASM to SEER breast cancer data, we show that FASM substantially improves fairness while preserving discrimination performance comparable to fairness-unaware survival models. Time-stratified evaluations show that FASM maintains stable fairness over a 10-year horizon, with the greatest improvements observed during the mid-term of follow-up. Our approach enables the development of survival models that prioritize both accuracy and equity in clinical decision-making, advancing fairness as a core principle in clinical care.

Siqi Li, Molei Liu, Ziye Tian et al.

Standard machine learning models optimized for average performance often fail on minority subgroups and lack robustness to distribution shifts. This challenge worsens when subgroups are latent and affected by complex interactions among continuous and discrete features. We introduce ROME (RObust Mixture Ensemble), a framework that learns latent group structure from data while optimizing for worst-group performance. ROME employs two approaches: an Expectation-Maximization algorithm for linear models and a neural Mixture-of-Experts for nonlinear settings. Through simulations and experiments on real-world datasets, we demonstrate that ROME significantly improves algorithmic fairness compared to standard methods while maintaining competitive average performance. Importantly, our method requires no predefined group labels, making it practical when sources of disparities are unknown or evolving.

Rui Yang, Huitao Li, Matthew Yu Heng Wong et al.

Natural language processing (NLP) has been traditionally applied to medicine, and generative large language models (LLMs) have become prominent recently. However, the differences between them across different medical tasks remain underexplored. We analyzed 19,123 studies, finding that generative LLMs demonstrate advantages in open-ended tasks, while traditional NLP dominates in information extraction and analysis tasks. As these technologies advance, ethical use of them is essential to ensure their potential in medical applications.

Rui Yang, Yilin Ning, Emilia Keppo et al.

Generative artificial intelligence (AI) has brought revolutionary innovations in various fields, including medicine. However, it also exhibits limitations. In response, retrieval-augmented generation (RAG) provides a potential solution, enabling models to generate more accurate contents by leveraging the retrieval of external knowledge. With the rapid advancement of generative AI, RAG can pave the way for connecting this transformative technology with medical applications and is expected to bring innovations in equity, reliability, and personalization to health care.

Jianhui Gao, Benson Chou, Zachary R. McCaw et al.

Ensuring that machine learning (ML) models are safe, effective, and equitable across all patients is critical for clinical decision-making and for preventing the amplification of existing health disparities. In this work, we examine how fairness is conceptualized in ML for health, including why ML models may lead to unfair decisions and how fairness has been measured in diverse real-world applications. We review commonly used fairness notions within group, individual, and causal-based frameworks. We also discuss the outlook for future research and highlight opportunities and challenges in operationalizing fairness in health-focused applications.

Han Yuan, Chuan Hong

Active learning selects the most informative samples from the unlabelled dataset to annotate in the context of a limited annotation budget. While numerous methods have been proposed for subsequent sample selection based on an initialized model, scant attention has been paid to the indispensable phase of active learning: selecting samples for model cold-start initialization. Most of the previous studies resort to random sampling or naive clustering. However, random sampling is prone to fluctuation, and naive clustering suffers from convergence speed, particularly when dealing with high-dimensional data such as imaging data. In this work, we propose to integrate foundation models with clustering methods to select samples for cold-start active learning initialization. Foundation models refer to those trained on massive datasets by the self-supervised paradigm and capable of generating informative and compacted embeddings for various downstream tasks. Leveraging these embeddings to replace raw features such as pixel values, clustering quickly converges and identifies better initial samples. For a comprehensive comparison, we included a classic ImageNet-supervised model to acquire embeddings. Experiments on two clinical tasks of image classification and segmentation demonstrated that foundation model-based clustering efficiently pinpointed informative initial samples, leading to models showcasing enhanced performance than the baseline methods. We envisage that this study provides an effective paradigm for future cold-start active learning.

Jun Wen, Jue Hou, Clara-Lea Bonzel et al.

Electronic health record (EHR) data are increasingly used to support real-world evidence (RWE) studies. Yet its ability to generate reliable RWE is limited by the lack of readily available precise information on the timing of clinical events such as the onset time of heart failure. We propose a LAbel-efficienT incidenT phEnotyping (LATTE) algorithm to accurately annotate the timing of clinical events from longitudinal EHR data. By leveraging the pre-trained semantic embedding vectors from large-scale EHR data as prior knowledge, LATTE selects predictive EHR features in a concept re-weighting module by mining their relationship to the target event and compresses their information into longitudinal visit embeddings through a visit attention learning network. LATTE employs a recurrent neural network to capture the sequential dependency between the target event and visit embeddings before/after it. To improve label efficiency, LATTE constructs highly informative longitudinal silver-standard labels from large-scale unlabeled patients to perform unsupervised pre-training and semi-supervised joint training. Finally, LATTE enhances cross-site portability via contrastive representation learning. LATTE is evaluated on three analyses: the onset of type-2 diabetes, heart failure, and the onset and relapses of multiple sclerosis. We use various evaluation metrics present in the literature including the $ABC_{gain}$, the proportion of reduction in the area between the observed event indicator and the predicted cumulative incidences in reference to the prediction per incident prevalence. LATTE consistently achieves substantial improvement over benchmark methods such as SAMGEP and RETAIN in all settings.

Yucong Lin, Keming Lu, Yulin Chen et al.

Objective: Medical relations are the core components of medical knowledge graphs that are needed for healthcare artificial intelligence. However, the requirement of expert annotation by conventional algorithm development processes creates a major bottleneck for mining new relations. In this paper, we present Hi-RES, a framework for high-throughput relation extraction algorithm development. We also show that combining knowledge articles with electronic health records (EHRs) significantly increases the classification accuracy. Methods: We use relation triplets obtained from structured databases and semistructured webpages to label sentences from target corpora as positive training samples. Two methods are also provided for creating improved negative samples by combining positive samples with naïve negative samples. We propose a common model that summarizes sentence information using large-scale pretrained language models and multi-instance attention, which then joins with the concept embeddings trained from the EHRs for relation prediction. Results: We apply the Hi-RES framework to develop classification algorithms for disorder-disorder relations and disorder-location relations. Millions of sentences are created as training data. Using pretrained language models and EHR-based embeddings individually provides considerable accuracy increases over those of previous models. Joining them together further tremendously increases the accuracy to 0.947 and 0.998 for the two sets of relations, respectively, which are 10-17 percentage points higher than those of previous models. Conclusion: Hi-RES is an efficient framework for achieving high-throughput and accurate relation extraction algorithm development.