Yanshan Wang

David Oniani, Jordan Hilsman, Hang Dong et al. · oxford

The emergence of generative Large Language Models (LLMs) emphasizes the need for accurate and efficient prompting approaches. LLMs are often applied in Few-Shot Learning (FSL) contexts, where tasks are executed with minimal training data. FSL has become popular in many Artificial Intelligence (AI) subdomains, including AI for health. Rare diseases affect a small fraction of the population. Rare disease identification from clinical notes inherently requires FSL techniques due to limited data availability. Manual data collection and annotation is both expensive and time-consuming. In this paper, we propose Models-Vote Prompting (MVP), a flexible prompting approach for improving the performance of LLM queries in FSL settings. MVP works by prompting numerous LLMs to perform the same tasks and then conducting a majority vote on the resulting outputs. This method achieves improved results to any one model in the ensemble on one-shot rare disease identification and classification tasks. We also release a novel rare disease dataset for FSL, available to those who signed the MIMIC-IV Data Use Agreement (DUA). Furthermore, in using MVP, each model is prompted multiple times, substantially increasing the time needed for manual annotation, and to address this, we assess the feasibility of using JSON for automating generative LLM evaluation.

Gongbo Zhang, Qiao Jin, Denis Jered McInerney et al. · amazon-science, salesforce

Evidence-based medicine promises to improve the quality of healthcare by empowering medical decisions and practices with the best available evidence. The rapid growth of medical evidence, which can be obtained from various sources, poses a challenge in collecting, appraising, and synthesizing the evidential information. Recent advancements in generative AI, exemplified by large language models, hold promise in facilitating the arduous task. However, developing accountable, fair, and inclusive models remains a complicated undertaking. In this perspective, we discuss the trustworthiness of generative AI in the context of automated summarization of medical evidence.

Sonish Sivarajkumar, Mark Kelley, Alyssa Samolyk-Mazzanti et al.

Large language models (LLMs) have shown remarkable capabilities in Natural Language Processing (NLP), especially in domains where labeled data is scarce or expensive, such as clinical domain. However, to unlock the clinical knowledge hidden in these LLMs, we need to design effective prompts that can guide them to perform specific clinical NLP tasks without any task-specific training data. This is known as in-context learning, which is an art and science that requires understanding the strengths and weaknesses of different LLMs and prompt engineering approaches. In this paper, we present a comprehensive and systematic experimental study on prompt engineering for five clinical NLP tasks: Clinical Sense Disambiguation, Biomedical Evidence Extraction, Coreference Resolution, Medication Status Extraction, and Medication Attribute Extraction. We assessed the prompts proposed in recent literature, including simple prefix, simple cloze, chain of thought, and anticipatory prompts, and introduced two new types of prompts, namely heuristic prompting and ensemble prompting. We evaluated the performance of these prompts on three state-of-the-art LLMs: GPT-3.5, BARD, and LLAMA2. We also contrasted zero-shot prompting with few-shot prompting, and provide novel insights and guidelines for prompt engineering for LLMs in clinical NLP. To the best of our knowledge, this is one of the first works on the empirical evaluation of different prompt engineering approaches for clinical NLP in this era of generative AI, and we hope that it will inspire and inform future research in this area.

Sonish Sivarajkumar, Yanshan Wang

Deep learning algorithms are dependent on the availability of large-scale annotated clinical text datasets. The lack of such publicly available datasets is the biggest bottleneck for the development of clinical Natural Language Processing(NLP) systems. Zero-Shot Learning(ZSL) refers to the use of deep learning models to classify instances from new classes of which no training data have been seen before. Prompt-based learning is an emerging ZSL technique where we define task-based templates for NLP tasks. We developed a novel prompt-based clinical NLP framework called HealthPrompt and applied the paradigm of prompt-based learning on clinical texts. In this technique, rather than fine-tuning a Pre-trained Language Model(PLM), the task definitions are tuned by defining a prompt template. We performed an in-depth analysis of HealthPrompt on six different PLMs in a no-data setting. Our experiments prove that prompts effectively capture the context of clinical texts and perform remarkably well without any training data.

Sonish Sivarajkumar, Fengyi Gao, Parker E. Denny et al.

Post-stroke patient rehabilitation requires precise, personalized treatment plans. Natural Language Processing (NLP) offers potential to extract valuable exercise information from clinical notes, aiding in the development of more effective rehabilitation strategies. Objective: This study aims to develop and evaluate a variety of NLP algorithms to extract and categorize physical rehabilitation exercise information from the clinical notes of post-stroke patients treated at the University of Pittsburgh Medical Center. A cohort of 13,605 patients diagnosed with stroke was identified, and their clinical notes containing rehabilitation therapy notes were retrieved. A comprehensive clinical ontology was created to represent various aspects of physical rehabilitation exercises. State-of-the-art NLP algorithms were then developed and compared, including rule-based, machine learning-based algorithms, and large language model (LLM)-based algorithms (ChatGPT). Analysis was conducted on a dataset comprising 23,724 notes with detailed demographic and clinical characteristics. The rule-based NLP algorithm demonstrated superior performance in most areas, particularly in detecting the 'Right Side' location with an F1 score of 0.975, outperforming Gradient Boosting by 0.063. Gradient Boosting excelled in 'Lower Extremity' location detection (F1 score: 0.978), surpassing rule-based NLP by 0.023. It also showed notable performance in 'Passive Range of Motion' with an F1 score of 0.970, a 0.032 improvement over rule-based NLP. The rule-based algorithm efficiently handled 'Duration', 'Sets', and 'Reps' with F1 scores up to 0.65. LLM-based NLP, particularly ChatGPT with few-shot prompts, achieved high recall but generally lower precision and F1 scores. However, it notably excelled in 'Backward Plane' motion detection, achieving an F1 score of 0.846, surpassing the rule-based algorithm's 0.720.

David Oniani, Bambang Parmanto, Andi Saptono et al.

Rehabilitation research focuses on determining the components of a treatment intervention, the mechanism of how these components lead to recovery and rehabilitation, and ultimately the optimal intervention strategies to maximize patients' physical, psychologic, and social functioning. Traditional randomized clinical trials that study and establish new interventions face several challenges, such as high cost and time commitment. Observational studies that use existing clinical data to observe the effect of an intervention have shown several advantages over RCTs. Electronic Health Records (EHRs) have become an increasingly important resource for conducting observational studies. To support these studies, we developed a clinical research datamart, called ReDWINE (Rehabilitation Datamart With Informatics iNfrastructure for rEsearch), that transforms the rehabilitation-related EHR data collected from the UPMC health care system to the Observational Health Data Sciences and Informatics (OHDSI) Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to facilitate rehabilitation research. The standardized EHR data stored in ReDWINE will further reduce the time and effort required by investigators to pool, harmonize, clean, and analyze data from multiple sources, leading to more robust and comprehensive research findings. ReDWINE also includes deployment of data visualization and data analytics tools to facilitate cohort definition and clinical data analysis. These include among others the Open Health Natural Language Processing (OHNLP) toolkit, a high-throughput NLP pipeline, to provide text analytical capabilities at scale in ReDWINE. Using this comprehensive representation of patient data in ReDWINE for rehabilitation research will facilitate real-world evidence for health interventions and outcomes.

David Oniani, Jordan Hilsman, Yifan Peng et al.

In 2020, the U.S. Department of Defense officially disclosed a set of ethical principles to guide the use of Artificial Intelligence (AI) technologies on future battlefields. Despite stark differences, there are core similarities between the military and medical service. Warriors on battlefields often face life-altering circumstances that require quick decision-making. Medical providers experience similar challenges in a rapidly changing healthcare environment, such as in the emergency department or during surgery treating a life-threatening condition. Generative AI, an emerging technology designed to efficiently generate valuable information, holds great promise. As computing power becomes more accessible and the abundance of health data, such as electronic health records, electrocardiograms, and medical images, increases, it is inevitable that healthcare will be revolutionized by this technology. Recently, generative AI has captivated the research community, leading to debates about its application in healthcare, mainly due to concerns about transparency and related issues. Meanwhile, concerns about the potential exacerbation of health disparities due to modeling biases have raised notable ethical concerns regarding the use of this technology in healthcare. However, the ethical principles for generative AI in healthcare have been understudied, and decision-makers often fail to consider the significance of generative AI. In this paper, we propose GREAT PLEA ethical principles, encompassing governance, reliability, equity, accountability, traceability, privacy, lawfulness, empathy, and autonomy, for generative AI in healthcare. We aim to proactively address the ethical dilemmas and challenges posed by the integration of generative AI in healthcare.

Mahyar Abbasian, Elahe Khatibi, Iman Azimi et al.

Generative Artificial Intelligence is set to revolutionize healthcare delivery by transforming traditional patient care into a more personalized, efficient, and proactive process. Chatbots, serving as interactive conversational models, will probably drive this patient-centered transformation in healthcare. Through the provision of various services, including diagnosis, personalized lifestyle recommendations, and mental health support, the objective is to substantially augment patient health outcomes, all the while mitigating the workload burden on healthcare providers. The life-critical nature of healthcare applications necessitates establishing a unified and comprehensive set of evaluation metrics for conversational models. Existing evaluation metrics proposed for various generic large language models (LLMs) demonstrate a lack of comprehension regarding medical and health concepts and their significance in promoting patients' well-being. Moreover, these metrics neglect pivotal user-centered aspects, including trust-building, ethics, personalization, empathy, user comprehension, and emotional support. The purpose of this paper is to explore state-of-the-art LLM-based evaluation metrics that are specifically applicable to the assessment of interactive conversational models in healthcare. Subsequently, we present an comprehensive set of evaluation metrics designed to thoroughly assess the performance of healthcare chatbots from an end-user perspective. These metrics encompass an evaluation of language processing abilities, impact on real-world clinical tasks, and effectiveness in user-interactive conversations. Finally, we engage in a discussion concerning the challenges associated with defining and implementing these metrics, with particular emphasis on confounding factors such as the target audience, evaluation methods, and prompt techniques involved in the evaluation process.

David Oniani, Sreekanth Sreekumar, Renuk DeAlmeida et al.

Health literacy is the central focus of Healthy People 2030, the fifth iteration of the U.S. national goals and objectives. People with low health literacy usually have trouble understanding health information, following post-visit instructions, and using prescriptions, which results in worse health outcomes and serious health disparities. In this study, we propose to leverage natural language processing techniques to improve health literacy in patient education materials by automatically translating illiterate languages in a given sentence. We scraped patient education materials from four online health information websites: MedlinePlus.gov, Drugs.com, Mayoclinic.org and Reddit.com. We trained and tested the state-of-the-art neural machine translation (NMT) models on a silver standard training dataset and a gold standard testing dataset, respectively. The experimental results showed that the Bidirectional Long Short-Term Memory (BiLSTM) NMT model outperformed Bidirectional Encoder Representations from Transformers (BERT)-based NMT models. We also verified the effectiveness of NMT models in translating health illiterate languages by comparing the ratio of health illiterate language in the sentence. The proposed NMT models were able to identify the correct complicated words and simplify into layman language while at the same time the models suffer from sentence completeness, fluency, readability, and have difficulty in translating certain medical terms.

Sonish Sivarajkumar, Yufei Huang, Yanshan Wang

Objective: To pre-train fair and unbiased patient representations from Electronic Health Records (EHRs) using a novel weighted loss function that reduces bias and improves fairness in deep representation learning models. Methods: We defined a new loss function, called weighted loss function, in the deep representation learning model to balance the importance of different groups of patients and features. We applied the proposed model, called Fair Patient Model (FPM), to a sample of 34,739 patients from the MIMIC-III dataset and learned patient representations for four clinical outcome prediction tasks. Results: FPM outperformed the baseline models in terms of three fairness metrics: demographic parity, equality of opportunity difference, and equalized odds ratio. FPM also achieved comparable predictive performance with the baselines, with an average accuracy of 0.7912. Feature analysis revealed that FPM captured more information from clinical features than the baselines. Conclusion: FPM is a novel method to pre-train fair and unbiased patient representations from EHR data using a weighted loss function. The learned representations can be used for various downstream tasks in healthcare and can be extended to other domains where bias and fairness are important.

David Oniani, Sonish Sivarajkumar, Yanshan Wang

Clinical Natural Language Processing (NLP) has become an emerging technology in healthcare that leverages a large amount of free-text data in electronic health records (EHRs) to improve patient care, support clinical decisions, and facilitate clinical and translational science research. Recently, deep learning has achieved state-of-the-art performance in many clinical NLP tasks. However, training deep learning models usually requires large annotated datasets, which are normally not publicly available and can be time-consuming to build in clinical domains. Working with smaller annotated datasets is typical in clinical NLP and therefore, ensuring that deep learning models perform well is crucial for the models to be used in real-world applications. A widely adopted approach is fine-tuning existing Pre-trained Language Models (PLMs), but these attempts fall short when the training dataset contains only a few annotated samples. Few-Shot Learning (FSL) has recently been investigated to tackle this problem. Siamese Neural Network (SNN) has been widely utilized as an FSL approach in computer vision, but has not been studied well in NLP. Furthermore, the literature on its applications in clinical domains is scarce. In this paper, we propose two SNN-based FSL approaches for clinical NLP, including Pre-Trained SNN (PT-SNN) and SNN with Second-Order Embeddings (SOE-SNN). We evaluated the proposed approaches on two clinical tasks, namely clinical text classification and clinical named entity recognition. We tested three few-shot settings including 4-shot, 8-shot, and 16-shot learning. Both clinical NLP tasks were benchmarked using three PLMs, including BERT,BioBERT, and BioClinicalBERT. The experimental results verified the effectiveness of the proposed SNN-based FSL approaches in both NLP tasks.

Hunter Osterhoudt, Courtney E. Schneider, Haneef A Mohammad et al.

Strategy training is a multidisciplinary rehabilitation approach that teaches skills to reduce disability among those with cognitive impairments following a stroke. Strategy training has been shown in randomized, controlled clinical trials to be a more feasible and efficacious intervention for promoting independence than traditional rehabilitation approaches. A standardized fidelity assessment is used to measure adherence to treatment principles by examining guided and directed verbal cues in video recordings of rehabilitation sessions. Although the fidelity assessment for detecting guided and directed verbal cues is valid and feasible for single-site studies, it can become labor intensive, time consuming, and expensive in large, multi-site pragmatic trials. To address this challenge to widespread strategy training implementation, we leveraged natural language processing (NLP) techniques to automate the strategy training fidelity assessment, i.e., to automatically identify guided and directed verbal cues from video recordings of rehabilitation sessions. We developed a rule-based NLP algorithm, a long-short term memory (LSTM) model, and a bidirectional encoder representation from transformers (BERT) model for this task. The best performance was achieved by the BERT model with a 0.8075 F1-score. This BERT model was verified on an external validation dataset collected from a separate major regional health system and achieved an F1 score of 0.8259, which shows that the BERT model generalizes well. The findings from this study hold widespread promise in psychology and rehabilitation intervention research and practice.

Xizhi Wu, Nelly Estefanie Garduno-Rapp, Justin F Rousseau et al.

Unlike most primary headaches, secondary headaches need specialized care and can have devastating consequences if not treated promptly. Clinical guidelines highlight several 'red flag' features, such as thunderclap onset, meningismus, papilledema, focal neurologic deficits, signs of temporal arteritis, systemic illness, and the 'worst headache of their life' presentation. Despite these guidelines, determining which patients require urgent evaluation remains challenging in primary care settings. Clinicians often work with limited time, incomplete information, and diverse symptom presentations, which can lead to under-recognition and inappropriate care. We present a large language model (LLM)-based multi-agent clinical decision support system built on an orchestrator-specialist architecture, designed to perform explicit and interpretable secondary headache diagnosis from free-text clinical vignettes. The multi-agent system decomposes diagnosis into seven domain-specialized agents, each producing a structured and evidence-grounded rationale, while a central orchestrator performs task decomposition and coordinates agent routing. We evaluated the multi-agent system using 90 expert-validated secondary headache cases and compared its performance with a single-LLM baseline across two prompting strategies: question-based prompting (QPrompt) and clinical practice guideline-based prompting (GPrompt). We tested five open-source LLMs (Qwen-30B, GPT-OSS-20B, Qwen-14B, Qwen-8B, and Llama-3.1-8B), and found that the orchestrated multi-agent system with GPrompt consistently achieved the highest F1 scores, with larger gains in smaller models. These findings demonstrate that structured multi-agent reasoning improves accuracy beyond prompt engineering alone and offers a transparent, clinically aligned approach for explainable decision support in secondary headache diagnosis.

Mauro Nievas, Aditya Basu, Yanshan Wang et al.

The recent success of large language models (LLMs) has paved the way for their adoption in the high-stakes domain of healthcare. Specifically, the application of LLMs in patient-trial matching, which involves assessing patient eligibility against clinical trial's nuanced inclusion and exclusion criteria, has shown promise. Recent research has shown that GPT-3.5, a widely recognized LLM developed by OpenAI, can outperform existing methods with minimal 'variable engineering' by simply comparing clinical trial information against patient summaries. However, there are significant challenges associated with using closed-source proprietary LLMs like GPT-3.5 in practical healthcare applications, such as cost, privacy and reproducibility concerns. To address these issues, this study presents the first systematic examination of the efficacy of both proprietary (GPT-3.5, and GPT-4) and open-source LLMs (LLAMA 7B,13B, and 70B) for the task of patient-trial matching. Employing a multifaceted evaluation framework, we conducted extensive automated and human-centric assessments coupled with a detailed error analysis for each model. To enhance the adaptability of open-source LLMs, we have created a specialized synthetic dataset utilizing GPT-4, enabling effective fine-tuning under constrained data conditions. Our findings reveal that open-source LLMs, when fine-tuned on this limited and synthetic dataset, demonstrate performance parity with their proprietary counterparts. This presents a massive opportunity for their deployment in real-world healthcare applications. To foster further research and applications in this field, we release both the annotated evaluation dataset along with the fine-tuned LLM -- Trial-LLAMA -- for public use.

Can Zheng, Yanshan Wang, Xiaowei Jia

Semantic textual similarity (STS) in the clinical domain helps improve diagnostic efficiency and produce concise texts for downstream data mining tasks. However, given the high degree of domain knowledge involved in clinic text, it remains challenging for general language models to infer implicit medical relationships behind clinical sentences and output similarities correctly. In this paper, we present a graph-augmented cyclic learning framework for similarity estimation in the clinical domain. The framework can be conveniently implemented on a state-of-art backbone language model, and improve its performance by leveraging domain knowledge through co-training with an auxiliary graph convolution network (GCN) based network. We report the success of introducing domain knowledge in GCN and the co-training framework by improving the Bio-clinical BERT baseline by 16.3% and 27.9%, respectively.

Jiaqi Xue, Yancheng Zhang, Yanshan Wang et al.

Secure training, while protecting the confidentiality of both data and model weights, typically incurs significant training overhead. Traditional Fully Homomorphic Encryption (FHE)-based non-inter-active training models are heavily burdened by computationally demanding bootstrapping. To develop an efficient secure training system, we established a foundational framework, CryptoTrain-B, utilizing a hybrid cryptographic protocol that merges FHE with Oblivious Transfer (OT) for handling linear and non-linear operations, respectively. This integration eliminates the need for costly bootstrapping. Although CryptoTrain-B sets a new baseline in performance, reducing its training overhead remains essential. We found that ciphertext-ciphertext multiplication (CCMul) is a critical bottleneck in operations involving encrypted inputs and models. Our solution, the CCMul-Precompute technique, involves precomputing CCMul offline and resorting to the less resource-intensive ciphertext-plaintext multiplication (CPMul) during private training. Furthermore, conventional polynomial convolution in FHE systems tends to encode irrelevant and redundant values into polynomial slots, necessitating additional polynomials and ciphertexts for input representation and leading to extra multiplications. Addressing this, we introduce correlated polynomial convolution, which encodes only related input values into polynomials, thus drastically reducing the number of computations and overheads. By integrating CCMul-Precompute and correlated polynomial convolution into CryptoTrain-B, we facilitate a rapid and efficient secure training framework, CryptoTrain. Extensive experiments demonstrate that CryptoTrain achieves a ~5.3X training time reduction compared to prior methods.

Bernardo Consoli, Xizhi Wu, Song Wang et al.

Extracting social determinants of health (SDoH) from unstructured medical notes depends heavily on labor-intensive annotations, which are typically task-specific, hampering reusability and limiting sharing. In this study we introduced SDoH-GPT, a simple and effective few-shot Large Language Model (LLM) method leveraging contrastive examples and concise instructions to extract SDoH without relying on extensive medical annotations or costly human intervention. It achieved tenfold and twentyfold reductions in time and cost respectively, and superior consistency with human annotators measured by Cohen's kappa of up to 0.92. The innovative combination of SDoH-GPT and XGBoost leverages the strengths of both, ensuring high accuracy and computational efficiency while consistently maintaining 0.90+ AUROC scores. Testing across three distinct datasets has confirmed its robustness and accuracy. This study highlights the potential of leveraging LLMs to revolutionize medical note classification, demonstrating their capability to achieve highly accurate classifications with significantly reduced time and cost.

Shuofei Qiao, Yunxiang Wei, Xuehai Wang et al.

The rapid evolution of Large Language Models has catalyzed a surge in scientific idea production, yet this leap has not been accompanied by a matching advance in idea evaluation. The fundamental nature of scientific evaluation needs knowledgeable grounding, collective deliberation, and multi-criteria decision-making. However, existing idea evaluation methods often suffer from narrow knowledge horizons, flattened evaluation dimensions, and the inherent bias in LLM-as-a-Judge. To address these, we regard idea evaluation as a knowledge-grounded, multi-perspective reasoning problem and introduce InnoEval, a deep innovation evaluation framework designed to emulate human-level idea assessment. We apply a heterogeneous deep knowledge search engine that retrieves and grounds dynamic evidence from diverse online sources. We further achieve review consensus with an innovation review board containing reviewers with distinct academic backgrounds, enabling a multi-dimensional decoupled evaluation across multiple metrics. We construct comprehensive datasets derived from authoritative peer-reviewed submissions to benchmark InnoEval. Experiments demonstrate that InnoEval can consistently outperform baselines in point-wise, pair-wise, and group-wise evaluation tasks, exhibiting judgment patterns and consensus highly aligned with human experts.

David Oniani, Yanshan Wang

Large Language Models (LLMs) have proven effective at In-Context Learning (ICL), an ability that allows them to create predictors from labeled examples. Few studies have explored the interplay between ICL and specific properties of functions it attempts to approximate. In our study, we use a formal framework to explore ICL and propose a new task of approximating functions with varying number of minima. We implement a method that allows for producing functions with given inputs as minima. We find that increasing the number of minima degrades ICL performance. At the same time, our evaluation shows that ICL outperforms 2-layer Neural Network (2NN) model. Furthermore, ICL learns faster than 2NN in all settings. We validate the findings through a set of few-shot experiments across various hyperparameter configurations.

Sonish Sivarajkumar, Thomas Yu CHow Tam, Haneef Ahamed Mohammad et al.

Alzheimer's Disease (AD) is the most common form of dementia in the United States. Sleep is one of the lifestyle-related factors that has been shown critical for optimal cognitive function in old age. However, there is a lack of research studying the association between sleep and AD incidence. A major bottleneck for conducting such research is that the traditional way to acquire sleep information is time-consuming, inefficient, non-scalable, and limited to patients' subjective experience. A gold standard dataset is created from manual annotation of 570 randomly sampled clinical note documents from the adSLEEP, a corpus of 192,000 de-identified clinical notes of 7,266 AD patients retrieved from the University of Pittsburgh Medical Center (UPMC). We developed a rule-based Natural Language Processing (NLP) algorithm, machine learning models, and Large Language Model(LLM)-based NLP algorithms to automate the extraction of sleep-related concepts, including snoring, napping, sleep problem, bad sleep quality, daytime sleepiness, night wakings, and sleep duration, from the gold standard dataset. Rule-based NLP algorithm achieved the best performance of F1 across all sleep-related concepts. In terms of Positive Predictive Value (PPV), rule-based NLP algorithm achieved 1.00 for daytime sleepiness and sleep duration, machine learning models: 0.95 and for napping, 0.86 for bad sleep quality and 0.90 for snoring; and LLAMA2 with finetuning achieved PPV of 0.93 for Night Wakings, 0.89 for sleep problem, and 1.00 for sleep duration. The results show that the rule-based NLP algorithm consistently achieved the best performance for all sleep concepts. This study focused on the clinical notes of patients with AD, but could be extended to general sleep information extraction for other diseases.

Hang Zhang, Qian Lou, Yanshan Wang

Large language models (LLMs) are increasingly utilized in healthcare applications. However, their deployment in clinical practice raises significant safety concerns, including the potential spread of harmful information. This study systematically assesses the vulnerabilities of seven LLMs to three advanced black-box jailbreaking techniques within medical contexts. To quantify the effectiveness of these techniques, we propose an automated and domain-adapted agentic evaluation pipeline. Experiment results indicate that leading commercial and open-source LLMs are highly vulnerable to medical jailbreaking attacks. To bolster model safety and reliability, we further investigate the effectiveness of Continual Fine-Tuning (CFT) in defending against medical adversarial attacks. Our findings underscore the necessity for evolving attack methods evaluation, domain-specific safety alignment, and LLM safety-utility balancing. This research offers actionable insights for advancing the safety and reliability of AI clinicians, contributing to ethical and effective AI deployment in healthcare.

Ruiqi Deng, Geoffrey Martin, Tony Wang et al.

Clinical practice guidelines (CPGs) provide evidence-based recommendations for patient care; however, integrating them into Artificial Intelligence (AI) remains challenging. Previous approaches, such as rule-based systems, face significant limitations, including poor interpretability, inconsistent adherence to guidelines, and narrow domain applicability. To address this, we develop and validate CPGPrompt, an auto-prompting system that converts narrative clinical guidelines into large language models (LLMs). Our framework translates CPGs into structured decision trees and utilizes an LLM to dynamically navigate them for patient case evaluation. Synthetic vignettes were generated across three domains (headache, lower back pain, and prostate cancer) and distributed into four categories to test different decision scenarios. System performance was assessed on both binary specialty-referral decisions and fine-grained pathway-classification tasks. The binary specialty referral classification achieved consistently strong performance across all domains (F1: 0.85-1.00), with high recall (1.00 $\pm$ 0.00). In contrast, multi-class pathway assignment showed reduced performance, with domain-specific variations: headache (F1: 0.47), lower back pain (F1: 0.72), and prostate cancer (F1: 0.77). Domain-specific performance differences reflected the structure of each guideline. The headache guideline highlighted challenges with negation handling. The lower back pain guideline required temporal reasoning. In contrast, prostate cancer pathways benefited from quantifiable laboratory tests, resulting in more reliable decision-making.

Thomas Yu Chow Tam, Sonish Sivarajkumar, Sumit Kapoor et al.

With generative artificial intelligence (AI), particularly large language models (LLMs), continuing to make inroads in healthcare, it is critical to supplement traditional automated evaluations with human evaluations. Understanding and evaluating the output of LLMs is essential to assuring safety, reliability, and effectiveness. However, human evaluation's cumbersome, time-consuming, and non-standardized nature presents significant obstacles to comprehensive evaluation and widespread adoption of LLMs in practice. This study reviews existing literature on human evaluation methodologies for LLMs in healthcare. We highlight a notable need for a standardized and consistent human evaluation approach. Our extensive literature search, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, includes publications from January 2018 to February 2024. The review examines the human evaluation of LLMs across various medical specialties, addressing factors such as evaluation dimensions, sample types and sizes, selection, and recruitment of evaluators, frameworks and metrics, evaluation process, and statistical analysis type. Drawing on the diverse evaluation strategies employed in these studies, we propose a comprehensive and practical framework for human evaluation of LLMs: QUEST: Quality of Information, Understanding and Reasoning, Expression Style and Persona, Safety and Harm, and Trust and Confidence. This framework aims to improve the reliability, generalizability, and applicability of human evaluation of LLMs in different healthcare applications by defining clear evaluation dimensions and offering detailed guidelines.

Yi-Fei Zhao, Allyn Bove, David Thompson et al.

Low back pain (LBP) is a leading cause of disability globally. Following the onset of LBP and subsequent treatment, adequate patient education is crucial for improving functionality and long-term outcomes. Despite advancements in patient education strategies, significant gaps persist in delivering personalized, evidence-based information to patients with LBP. Recent advancements in large language models (LLMs) and generative artificial intelligence (GenAI) have demonstrated the potential to enhance patient education. However, their application and efficacy in delivering educational content to patients with LBP remain underexplored and warrant further investigation. In this study, we introduce a novel approach utilizing LLMs with Retrieval-Augmented Generation (RAG) and few-shot learning to generate tailored educational materials for patients with LBP. Physical therapists manually evaluated our model responses for redundancy, accuracy, and completeness using a Likert scale. In addition, the readability of the generated education materials is assessed using the Flesch Reading Ease score. The findings demonstrate that RAG-based LLMs outperform traditional LLMs, providing more accurate, complete, and readable patient education materials with less redundancy. Having said that, our analysis reveals that the generated materials are not yet ready for use in clinical practice. This study underscores the potential of AI-driven models utilizing RAG to improve patient education for LBP; however, significant challenges remain in ensuring the clinical relevance and granularity of content generated by these models.

Maneesh Bilalpur, Megan Hamm, Young Ji Lee et al.

Storytelling is a powerful form of communication and may provide insights into factors contributing to gaps in healthcare outcomes. To determine whether Large Language Models (LLMs) can identify potential underlying factors and avenues for intervention, we performed topic-aware hierarchical summarization of narratives from African American (AA) storytellers. Fifty transcribed stories of AA experiences were used to identify topics in their experience using the Latent Dirichlet Allocation (LDA) technique. Stories about a given topic were summarized using an open-source LLM-based hierarchical summarization approach. Topic summaries were generated by summarizing across story summaries for each story that addressed a given topic. Generated topic summaries were rated for fabrication, accuracy, comprehensiveness, and usefulness by the GPT4 model, and the model's reliability was validated against the original story summaries by two domain experts. 26 topics were identified in the fifty AA stories. The GPT4 ratings suggest that topic summaries were free from fabrication, highly accurate, comprehensive, and useful. The reliability of GPT ratings compared to expert assessments showed moderate to high agreement. Our approach identified AA experience-relevant topics such as health behaviors, interactions with medical team members, caregiving and symptom management, among others. Such insights could help researchers identify potential factors and interventions by learning from unstructured narratives in an efficient manner-leveraging the communicative power of storytelling. The use of LDA and LLMs to identify and summarize the experience of AA individuals suggests a variety of possible avenues for health research and possible clinical improvements to support patients and caregivers, thereby ultimately improving health outcomes.

Yanshan Wang, Hongfang Liu

Probabilistic language models are widely used in Information Retrieval (IR) to rank documents by the probability that they generate the query. However, the implementation of the probabilistic representations with programming languages that favor matrix calculations is challenging. In this paper, we utilize matrix representations to reformulate the probabilistic language models. The matrix representation is a superstructure for the probabilistic language models to organize the calculated probabilities and a potential formalism for standardization of language models and for further mathematical analysis. It facilitates implementations by matrix friendly programming languages. In this paper, we consider the matrix formulation of conventional language model with Dirichlet smoothing, and two language models based on Latent Dirichlet Allocation (LDA), i.e., LBDM and LDI. We release a Java software package--MatLM--implementing the proposed models. Code is available at: https://github.com/yanshanwang/JGibbLDA-v.1.0-MatLM.

Hang Zhang, Ruheng Wang, Yuelyu Ji et al.

Large language models have achieved strong performance on medical reasoning benchmarks, yet their deployment in clinical settings demands rigorous verification to ensure factual accuracy. While reward models offer a scalable approach for reasoning trace verification, existing methods face two limitations: they produce only scalar reward values without explicit justification, and they rely on single-pass retrieval that precludes adaptive knowledge access as verification unfolds. We introduce $\method$, an agentic framework that addresses these limitations by training medical reasoning verifiers to iteratively query external medical corpora during evaluation. Our approach combines tool-augmented verification with an iterative reinforcement learning paradigm that requires only trace-level supervision, alongside an adaptive curriculum mechanism that dynamically adjusts training data distribution. Across four medical reasoning benchmarks, $\method$ achieves substantial gains over existing methods, improving MedQA accuracy by 23.5% and MedXpertQA by 32.0% relative to the base generator in particular. Crucially, $\method$ demonstrates an $\mathbf{8\times}$ reduction in sampling budget requirement compared to prior reward model baselines. These findings establish that grounding verification in dynamically retrieved evidence offers a principled path toward more reliable medical reasoning systems.

Shashi Kant Gupta, Arijeet Pramanik, Jerrin John Thomas et al.

Unstructured notes within the electronic health record (EHR) contain rich clinical information vital for cancer treatment decision making and research, yet reliably extracting structured oncology data remains challenging due to extensive variability, specialized terminology, and inconsistent document formats. Manual abstraction, although accurate, is prohibitively costly and unscalable. Existing automated approaches typically address narrow scenarios - either using synthetic datasets, restricting focus to document-level extraction, or isolating specific clinical variables (e.g., staging, biomarkers, histology) - and do not adequately handle patient-level synthesis across the large number of clinical documents containing contradictory information. In this study, we propose an agentic framework that systematically decomposes complex oncology data extraction into modular, adaptive tasks. Specifically, we use large language models (LLMs) as reasoning agents, equipped with context-sensitive retrieval and iterative synthesis capabilities, to exhaustively and comprehensively extract structured clinical variables from real-world oncology notes. Evaluated on a large-scale dataset of over 400,000 unstructured clinical notes and scanned PDF reports spanning 2,250 cancer patients, our method achieves an average F1-score of 0.93, with 100 out of 103 oncology-specific clinical variables exceeding 0.85, and critical variables (e.g., biomarkers and medications) surpassing 0.95. Moreover, integration of the agentic system into a data curation workflow resulted in 0.94 direct manual approval rate, significantly reducing annotation costs. To our knowledge, this constitutes the first exhaustive, end-to-end application of LLM-based agents for structured oncology data extraction at scale

Yuelyu Ji, Zhuochun Li, Rui Meng et al.

This paper introduces the RAG-RLRC-LaySum framework, designed to make complex biomedical research understandable to laymen through advanced Natural Language Processing (NLP) techniques. Our Retrieval Augmented Generation (RAG) solution, enhanced by a reranking method, utilizes multiple knowledge sources to ensure the precision and pertinence of lay summaries. Additionally, our Reinforcement Learning for Readability Control (RLRC) strategy improves readability, making scientific content comprehensible to non-specialists. Evaluations using the publicly accessible PLOS and eLife datasets show that our methods surpass Plain Gemini model, demonstrating a 20% increase in readability scores, a 15% improvement in ROUGE-2 relevance scores, and a 10% enhancement in factual accuracy. The RAG-RLRC-LaySum framework effectively democratizes scientific knowledge, enhancing public engagement with biomedical discoveries.

David Oniani, Jordan Hilsman, Chengxi Zang et al.

A drug molecule is a substance that changes the organism's mental or physical state. Every approved drug has an indication, which refers to the therapeutic use of that drug for treating a particular medical condition. While the Large Language Model (LLM), a generative Artificial Intelligence (AI) technique, has recently demonstrated effectiveness in translating between molecules and their textual descriptions, there remains a gap in research regarding their application in facilitating the translation between drug molecules and indications, or vice versa, which could greatly benefit the drug discovery process. The capability of generating a drug from a given indication would allow for the discovery of drugs targeting specific diseases or targets and ultimately provide patients with better treatments. In this paper, we first propose a new task, which is the translation between drug molecules and corresponding indications, and then test existing LLMs on this new task. Specifically, we consider nine variations of the T5 LLM and evaluate them on two public datasets obtained from ChEMBL and DrugBank. Our experiments show the early results of using LLMs for this task and provide a perspective on the state-of-the-art. We also emphasize the current limitations and discuss future work that has the potential to improve the performance on this task. The creation of molecules from indications, or vice versa, will allow for more efficient targeting of diseases and significantly reduce the cost of drug discovery, with the potential to revolutionize the field of drug discovery in the era of generative AI.

Mengxin Zheng, Jiaqi Xue, Xun Chen et al.

Prompt tuning is one of the most effective solutions to adapting a fixed pre-trained language model (PLM) for various downstream tasks, especially with only a few input samples. However, the security issues, e.g., Trojan attacks, of prompt tuning on a few data samples are not well-studied. Transferring established data poisoning attacks directly to few-shot prompt tuning presents multiple challenges. One significant issue is the \textit{poisoned imbalance issue}, where non-target class samples are added to the target class, resulting in a greater number of target-class samples compared to non-target class. While this issue is not critical in regular tuning, it significantly hampers the few-shot prompt tuning, making it difficult to simultaneously achieve a high attack success rate (ASR) and maintain clean data accuracy (CDA). Additionally, few-shot prompting is prone to overfitting in terms of both ASR and CDA. In this paper, we introduce \textit{TrojFSP}, a method designed to address the challenges. To solve the poisoned imbalance issue, we develop a \textit{Target-Class Shrink (TC-Shrink)} technique, which aims to equalize the number of poisoning samples. To combat overfitting, we employ a \textit{Selective Token Poisoning} technique to boost attack performance. Furthermore, we introduce a \textit{Trojan-Trigger Attention} objective function to amplify the attention of the poisoned trojan prompt on triggers. Experiments show that our TrojFSP achieves an ASR of over 99\% while maintaining negligible decreases in CDA across various PLMs and datasets.

Shashi Kant Gupta, Aditya Basu, Mauro Nievas et al.

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

Maneesh Bilalpur, Saurabh Hinduja, Sonish Sivarajkumar et al.

The classical approach to detecting depression from vision emphasizes interpretable features, such as facial expression, and classifiers such as the Support Vector Machine (SVM). With the advent of deep learning, there has been a shift in feature representations and classification approaches. Contemporary approaches use learnt features from general-purpose vision models such as VGGNet to train machine learning models. Little is known about how classical and deep approaches compare in depression detection with respect to accuracy, fairness, and generalizability, especially across contexts. To address these questions, we compared classical and deep approaches to the detection of depression in the visual modality in two different contexts: Mother-child interactions in the TPOT database and patient-clinician interviews in the Pitt database. In the former, depression was operationalized as a history of depression per the DSM and current or recent clinically significant symptoms. In the latter, all participants met initial criteria for depression per DSM, and depression was reassessed over the course of treatment. The classical approach included handcrafted features with SVM classifiers. Learnt features were turn-level embeddings from the FMAE-IAT that were combined with Multi-Layer Perceptron classifiers. The classical approach achieved higher accuracy in both contexts. It was also significantly fairer than the deep approach in the patient-clinician context. Cross-context generalizability was modest at best for both approaches, which suggests that depression may be context-specific.

Chenyu Li, Zohaib Akhtar, Mingu Kwak et al.

As large language models (LLMs) increasingly generate and process clinical text, scalable evaluation has become critical. LLM-as-a-Judge (LaaJ), which uses LLMs to evaluate model outputs, offers a scalable alternative to costly expert review, but its healthcare adoption raises safety and bias concerns. We conducted a PRISMA-ScR scoping review of six databases (January 2020-January 2026), screening 11,727 studies and including 49. The landscape was dominated by evaluation and benchmarking applications (n=37, 75.5%), pointwise scoring (n=42, 85.7%), and GPT-family judges (n=36, 73.5%). Despite growing adoption, validation rigor was limited: among 36 studies with human involvement, the median number of expert validators was 3, while 13 (26.5%) used none. Risk of bias testing was absent in 36 studies (73.5%), only 1 (2.0%) examined demographic fairness, and none assessed temporal stability or patient context. Deployment remained limited, with 1 study (2.0%) reaching production and four (8.2%) prototype stage. Importantly, these gaps may interact: when judges and evaluated systems share training data or architectures, they may inherit similar blind spots, and agreement metrics may fail to distinguish true validity from shared errors. Minimal human oversight, limited bias assessment, and model monoculture together represent a governance gap where current validation may miss clinically significant errors. To address this, we propose MedJUDGE (Medical Judge Utility, De-biasing, Governance and Evaluation), a risk-stratified three-pillar framework organized around validity, safety, and accountability across clinical risk tiers, providing deployment-oriented evaluation guidance for healthcare LaaJ systems.

Yuelyu Ji, Hang Zhang, Shiven Verma et al.

We propose DeepRAG, a novel framework that integrates DeepSeek hierarchical question decomposition capabilities with RAG Gym unified retrieval-augmented generation optimization using process level supervision. Targeting the challenging MedHopQA biomedical question answering task, DeepRAG systematically decomposes complex queries into precise sub-queries and employs concept level reward signals informed by the UMLS ontology to enhance biomedical accuracy. Preliminary evaluations on the MedHopQA dataset indicate that DeepRAG significantly outperforms baseline models, including standalone DeepSeek and RAG Gym, achieving notable improvements in both Exact Match and concept level accuracy.

Yuhan Zhang, Yishu Wei, Yanshan Wang et al.

Suicide remains one of the main preventable causes of death among active service members and veterans. Early detection and prediction are crucial in suicide prevention. Machine learning techniques have yielded promising results in this area recently. This study aims to assess and summarize current research and provides a comprehensive review regarding the application of machine learning techniques in assessing and predicting suicidal ideation, attempts, and mortality among members of military and veteran populations. A keyword search using PubMed, IEEE, ACM, and Google Scholar was conducted, and the PRISMA protocol was adopted for relevant study selection. Thirty-two articles met the inclusion criteria. These studies consistently identified risk factors relevant to mental health issues such as depression, post-traumatic stress disorder (PTSD), suicidal ideation, prior attempts, physical health problems, and demographic characteristics. Machine learning models applied in this area have demonstrated reasonable predictive accuracy. However, additional research gaps still exist. First, many studies have overlooked metrics that distinguish between false positives and negatives, such as positive predictive value and negative predictive value, which are crucial in the context of suicide prevention policies. Second, more dedicated approaches to handling survival and longitudinal data should be explored. Lastly, most studies focused on machine learning methods, with limited discussion of their connection to clinical rationales. In summary, machine learning analyses have identified a wide range of risk factors associated with suicide in military populations. The diversity and complexity of these factors also demonstrates that effective prevention strategies must be comprehensive and flexible.

Sonish Sivarajkumar, Kimia Ameri, Chuqin Li et al.

Cardiovascular events, such as heart attacks and strokes, remain a leading cause of mortality globally, necessitating meticulous monitoring and adjudication in clinical trials. This process, traditionally performed manually by clinical experts, is time-consuming, resource-intensive, and prone to inter-reviewer variability, potentially introducing bias and hindering trial progress. This study addresses these critical limitations by presenting a novel framework for automating the adjudication of cardiovascular events in clinical trials using Large Language Models (LLMs). We developed a two-stage approach: first, employing an LLM-based pipeline for event information extraction from unstructured clinical data and second, using an LLM-based adjudication process guided by a Tree of Thoughts approach and clinical endpoint committee (CEC) guidelines. Using cardiovascular event-specific clinical trial data, the framework achieved an F1-score of 0.82 for event extraction and an accuracy of 0.68 for adjudication. Furthermore, we introduce the CLEART score, a novel, automated metric specifically designed for evaluating the quality of AI-generated clinical reasoning in adjudicating cardiovascular events. This approach demonstrates significant potential for substantially reducing adjudication time and costs while maintaining high-quality, consistent, and auditable outcomes in clinical trials. The reduced variability and enhanced standardization also allow for faster identification and mitigation of risks associated with cardiovascular therapies.

Yuelyu Ji, Hang Zhang, Yanshan Wang

Medical Question Answering systems based on Retrieval Augmented Generation is promising for clinical decision support because they can integrate external knowledge, thus reducing inaccuracies inherent in standalone large language models (LLMs). However, these systems may unintentionally propagate or amplify biases associated with sensitive demographic attributes like race, gender, and socioeconomic factors. This study systematically evaluates demographic biases within medical RAG pipelines across multiple QA benchmarks, including MedQA, MedMCQA, MMLU, and EquityMedQA. We quantify disparities in retrieval consistency and answer correctness by generating and analyzing queries sensitive to demographic variations. We further implement and compare several bias mitigation strategies to address identified biases, including Chain of Thought reasoning, Counterfactual filtering, Adversarial prompt refinement, and Majority Vote aggregation. Experimental results reveal significant demographic disparities, highlighting that Majority Vote aggregation notably improves accuracy and fairness metrics. Our findings underscore the critical need for explicitly fairness-aware retrieval methods and prompt engineering strategies to develop truly equitable medical QA systems.

Yuelyu Ji, Zeshui Yu, Yanshan Wang

In this study, we aim to address the task of assertion detection when extracting medical concepts from clinical notes, a key process in clinical natural language processing (NLP). Assertion detection in clinical NLP usually involves identifying assertion types for medical concepts in the clinical text, namely certainty (whether the medical concept is positive, negated, possible, or hypothetical), temporality (whether the medical concept is for present or the past history), and experiencer (whether the medical concept is described for the patient or a family member). These assertion types are essential for healthcare professionals to quickly and clearly understand the context of medical conditions from unstructured clinical texts, directly influencing the quality and outcomes of patient care. Although widely used, traditional methods, particularly rule-based NLP systems and machine learning or deep learning models, demand intensive manual efforts to create patterns and tend to overlook less common assertion types, leading to an incomplete understanding of the context. To address this challenge, our research introduces a novel methodology that utilizes Large Language Models (LLMs) pre-trained on a vast array of medical data for assertion detection. We enhanced the current method with advanced reasoning techniques, including Tree of Thought (ToT), Chain of Thought (CoT), and Self-Consistency (SC), and refine it further with Low-Rank Adaptation (LoRA) fine-tuning. We first evaluated the model on the i2b2 2010 assertion dataset. Our method achieved a micro-averaged F-1 of 0.89, with 0.11 improvements over the previous works. To further assess the generalizability of our approach, we extended our evaluation to a local dataset that focused on sleep concept extraction. Our approach achieved an F-1 of 0.74, which is 0.31 higher than the previous method.

Xizhi Wu, Madeline S. Kreider, Philip E. Empey et al.

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.

Sonish Sivarajkumar, Hang Zhang, Yuelyu Ji et al.

Electronic health records (EHRs) are rich clinical data sources but complex repositories of patient data, spanning structured elements (demographics, vitals, lab results, codes), unstructured clinical notes and other modalities of data. Harnessing this heterogeneity is critical for improving patient outcomes. Recent advances in large language models (LLMs) have enabled foundation models that can learn from multiple data modalities and support clinical tasks. However, most current approaches simply serialize numeric EHR data into text, which risks losing temporal and quantitative detail. We introduce Generative Deep Patient (GDP), a multimodal foundation model that natively encodes structured EHR time-series via a CNN-Transformer encoder and fuses it with unstructured EHRs through cross-modal attention into a LLaMA-based decoder. GDP is trained in two stages: (1) generative pretraining, where it learns to produce clinical narratives from raw patient timelines while also performing masked feature prediction (MFP) and next time-step prediction (NTP) to capture temporal dynamics; and (2) multi-task fine-tuning for clinically meaningful predictions (e.g., heart failure, type 2 diabetes, 30-day readmission). In clinical prediction, GDP demonstrated superior performance on MIMIC-IV: heart failure AUROC = 0.923, type 2 diabetes AUROC = 0.817, and 30-day readmission AUROC = 0.627. For narrative generation, GDP achieved ROUGE-L = 0.135 and BERTScore-F1 = 0.545. In a blinded human evaluation, GDP-Instruct scored highest on faithfulness, fluency, and overall clinical utility, suggesting reduced hospital documentation workload without sacrificing accuracy. Our results demonstrate that a single multimodal foundation model can both predict clinically actionable events and generate high-quality clinical narratives. Furthermore, GDP's flexible architecture can be extended to additional modalities.

Fengyi Gao, Xingyu Zhang, Sonish Sivarajkumar et al.

In this study, we utilized statistical analysis and machine learning methods to examine whether rehabilitation exercises can improve patients post-stroke functional abilities, as well as forecast the improvement in functional abilities. Our dataset is patients' rehabilitation exercises and demographic information recorded in the unstructured electronic health records (EHRs) data and free-text rehabilitation procedure notes. We collected data for 265 stroke patients from the University of Pittsburgh Medical Center. We employed a pre-existing natural language processing (NLP) algorithm to extract data on rehabilitation exercises and developed a rule-based NLP algorithm to extract Activity Measure for Post-Acute Care (AM-PAC) scores, covering basic mobility (BM) and applied cognitive (AC) domains, from procedure notes. Changes in AM-PAC scores were classified based on the minimal clinically important difference (MCID), and significance was assessed using Friedman and Wilcoxon tests. To identify impactful exercises, we used Chi-square tests, Fisher's exact tests, and logistic regression for odds ratios. Additionally, we developed five machine learning models-logistic regression (LR), Adaboost (ADB), support vector machine (SVM), gradient boosting (GB), and random forest (RF)-to predict outcomes in functional ability. Statistical analyses revealed significant associations between functional improvements and specific exercises. The RF model achieved the best performance in predicting functional outcomes. In this study, we identified three rehabilitation exercises that significantly contributed to patient post-stroke functional ability improvement in the first two months. Additionally, the successful application of a machine learning model to predict patient-specific functional outcomes underscores the potential for precision rehabilitation.

David Oniani, Xizhi Wu, Shyam Visweswaran et al.

Background Large Language Models (LLMs), enhanced with Clinical Practice Guidelines (CPGs), can significantly improve Clinical Decision Support (CDS). However, methods for incorporating CPGs into LLMs are not well studied. Methods We develop three distinct methods for incorporating CPGs into LLMs: Binary Decision Tree (BDT), Program-Aided Graph Construction (PAGC), and Chain-of-Thought-Few-Shot Prompting (CoT-FSP). To evaluate the effectiveness of the proposed methods, we create a set of synthetic patient descriptions and conduct both automatic and human evaluation of the responses generated by four LLMs: GPT-4, GPT-3.5 Turbo, LLaMA, and PaLM 2. Zero-Shot Prompting (ZSP) was used as the baseline method. We focus on CDS for COVID-19 outpatient treatment as the case study. Results All four LLMs exhibit improved performance when enhanced with CPGs compared to the baseline ZSP. BDT outperformed both CoT-FSP and PAGC in automatic evaluation. All of the proposed methods demonstrated high performance in human evaluation. Conclusion LLMs enhanced with CPGs demonstrate superior performance, as compared to plain LLMs with ZSP, in providing accurate recommendations for COVID-19 outpatient treatment, which also highlights the potential for broader applications beyond the case study.

Liyan Tang, Yifan Peng, Yanshan Wang et al.

A human decision-maker benefits the most from an AI assistant that corrects for their biases. For problems such as generating interpretation of a radiology report given findings, a system predicting only highly likely outcomes may be less useful, where such outcomes are already obvious to the user. To alleviate biases in human decision-making, it is worth considering a broad differential diagnosis, going beyond the most likely options. We introduce a new task, "less likely brainstorming," that asks a model to generate outputs that humans think are relevant but less likely to happen. We explore the task in two settings: a brain MRI interpretation generation setting and an everyday commonsense reasoning setting. We found that a baseline approach of training with less likely hypotheses as targets generates outputs that humans evaluate as either likely or irrelevant nearly half of the time; standard MLE training is not effective. To tackle this problem, we propose a controlled text generation method that uses a novel contrastive learning strategy to encourage models to differentiate between generating likely and less likely outputs according to humans. We compare our method with several state-of-the-art controlled text generation models via automatic and human evaluations and show that our models' capability of generating less likely outputs is improved.

Bhavani Singh Agnikula Kshatriya, Nicolas A Nunez, Manuel Gardea- Resendez et al.

Major depressive disorder (MDD) is a prevalent psychiatric disorder that is associated with significant healthcare burden worldwide. Phenotyping of MDD can help early diagnosis and consequently may have significant advantages in patient management. In prior research MDD phenotypes have been extracted from structured Electronic Health Records (EHR) or using Electroencephalographic (EEG) data with traditional machine learning models to predict MDD phenotypes. However, MDD phenotypic information is also documented in free-text EHR data, such as clinical notes. While clinical notes may provide more accurate phenotyping information, natural language processing (NLP) algorithms must be developed to abstract such information. Recent advancements in NLP resulted in state-of-the-art neural language models, such as Bidirectional Encoder Representations for Transformers (BERT) model, which is a transformer-based model that can be pre-trained from a corpus of unsupervised text data and then fine-tuned on specific tasks. However, such neural language models have been underutilized in clinical NLP tasks due to the lack of large training datasets. In the literature, researchers have utilized the distant supervision paradigm to train machine learning models on clinical text classification tasks to mitigate the issue of lacking annotated training data. It is still unknown whether the paradigm is effective for neural language models. In this paper, we propose to leverage the neural language models in a distant supervision paradigm to identify MDD phenotypes from clinical notes. The experimental results indicate that our proposed approach is effective in identifying MDD phenotypes and that the Bio- Clinical BERT, a specific BERT model for clinical data, achieved the best performance in comparison with conventional machine learning models.

Zitao Shen, Yoonkwon Yi, Anusha Bompelli et al.

Since no effective therapies exist for Alzheimer's disease (AD), prevention has become more critical through lifestyle factor changes and interventions. Analyzing electronic health records (EHR) of patients with AD can help us better understand lifestyle's effect on AD. However, lifestyle information is typically stored in clinical narratives. Thus, the objective of the study was to demonstrate the feasibility of natural language processing (NLP) models to classify lifestyle factors (e.g., physical activity and excessive diet) from clinical texts. We automatically generated labels for the training data by using a rule-based NLP algorithm. We conducted weak supervision for pre-trained Bidirectional Encoder Representations from Transformers (BERT) models on the weakly labeled training corpus. These models include the BERT base model, PubMedBERT(abstracts + full text), PubMedBERT(only abstracts), Unified Medical Language System (UMLS) BERT, Bio BERT, and Bio-clinical BERT. We performed two case studies: physical activity and excessive diet, in order to validate the effectiveness of BERT models in classifying lifestyle factors for AD. These models were compared on the developed Gold Standard Corpus (GSC) on the two case studies. The PubmedBERT(Abs) model achieved the best performance for physical activity, with its precision, recall, and F-1 scores of 0.96, 0.96, and 0.96, respectively. Regarding classifying excessive diet, the Bio BERT model showed the highest performance with perfect precision, recall, and F-1 scores. The proposed approach leveraging weak supervision could significantly increase the sample size, which is required for training the deep learning models. The study also demonstrates the effectiveness of BERT models for extracting lifestyle factors for Alzheimer's disease from clinical notes.

Anusha Bompelli, Yanshan Wang, Ruyuan Wan et al.

Background: There is growing evidence that social and behavioral determinants of health (SBDH) play a substantial effect in a wide range of health outcomes. Electronic health records (EHRs) have been widely employed to conduct observational studies in the age of artificial intelligence (AI). However, there has been little research into how to make the most of SBDH information from EHRs. Methods: A systematic search was conducted in six databases to find relevant peer-reviewed publications that had recently been published. Relevance was determined by screening and evaluating the articles. Based on selected relevant studies, a methodological analysis of AI algorithms leveraging SBDH information in EHR data was provided. Results: Our synthesis was driven by an analysis of SBDH categories, the relationship between SBDH and healthcare-related statuses, and several NLP approaches for extracting SDOH from clinical literature. Discussion: The associations between SBDH and health outcomes are complicated and diverse; several pathways may be involved. Using Natural Language Processing (NLP) technology to support the extraction of SBDH and other clinical ideas simplifies the identification and extraction of essential concepts from clinical data, efficiently unlocks unstructured data, and aids in the resolution of unstructured data-related issues. Conclusion: Despite known associations between SBDH and disease, SBDH factors are rarely investigated as interventions to improve patient outcomes. Gaining knowledge about SBDH and how SBDH data can be collected from EHRs using NLP approaches and predictive models improves the chances of influencing health policy change for patient wellness, and ultimately promoting health and health equity. Keywords: Social and Behavioral Determinants of Health, Artificial Intelligence, Electronic Health Records, Natural Language Processing, Predictive Model

David Oniani, Yanshan Wang

COVID-19 has resulted in an ongoing pandemic and as of 12 June 2020, has caused more than 7.4 million cases and over 418,000 deaths. The highly dynamic and rapidly evolving situation with COVID-19 has made it difficult to access accurate, on-demand information regarding the disease. Online communities, forums, and social media provide potential venues to search for relevant questions and answers, or post questions and seek answers from other members. However, due to the nature of such sites, there are always a limited number of relevant questions and responses to search from, and posted questions are rarely answered immediately. With the advancements in the field of natural language processing, particularly in the domain of language models, it has become possible to design chatbots that can automatically answer consumer questions. However, such models are rarely applied and evaluated in the healthcare domain, to meet the information needs with accurate and up-to-date healthcare data. In this paper, we propose to apply a language model for automatically answering questions related to COVID-19 and qualitatively evaluate the generated responses. We utilized the GPT-2 language model and applied transfer learning to retrain it on the COVID-19 Open Research Dataset (CORD-19) corpus. In order to improve the quality of the generated responses, we applied 4 different approaches, namely tf-idf, BERT, BioBERT, and USE to filter and retain relevant sentences in the responses. In the performance evaluation step, we asked two medical experts to rate the responses. We found that BERT and BioBERT, on average, outperform both tf-idf and USE in relevance-based sentence filtering tasks. Additionally, based on the chatbot, we created a user-friendly interactive web application to be hosted online.

Sunyang Fu, David Chen, Huan He et al.

Background Concept extraction, a subdomain of natural language processing (NLP) with a focus on extracting concepts of interest, has been adopted to computationally extract clinical information from text for a wide range of applications ranging from clinical decision support to care quality improvement. Objectives In this literature review, we provide a methodology review of clinical concept extraction, aiming to catalog development processes, available methods and tools, and specific considerations when developing clinical concept extraction applications. Methods Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search was conducted for retrieving EHR-based information extraction articles written in English and published from January 2009 through June 2019 from Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, Web of Science, and the ACM Digital Library. Results A total of 6,686 publications were retrieved. After title and abstract screening, 228 publications were selected. The methods used for developing clinical concept extraction applications were discussed in this review.

Krishna B. Soundararajan, Sunyang Fu, Luke A. Carlson et al.

Alzheimer's Disease (AD) is the most common type of dementia, comprising 60-80% of cases. There were an estimated 5.8 million Americans living with Alzheimer's dementia in 2019, and this number will almost double every 20 years. The total lifetime cost of care for someone with dementia is estimated to be $350,174 in 2018, 70% of which is associated with family-provided care. Most family caregivers face emotional, financial and physical difficulties. As a medium to relieve this burden, online communities in social media websites such as Twitter, Reddit, and Yahoo! Answers provide potential venues for caregivers to search relevant questions and answers, or post questions and seek answers from other members. However, there are often a limited number of relevant questions and responses to search from, and posted questions are rarely answered immediately. Due to recent advancement in Artificial Intelligence (AI), particularly Natural Language Processing (NLP), we propose to utilize AI to automatically generate answers to AD-related consumer questions posted by caregivers and evaluate how good AI is at answering those questions. To the best of our knowledge, this is the first study in the literature applying and evaluating AI models designed to automatically answer consumer questions related to AD.