Tao, Cui

Abstract Objectives To comprehensively evaluate the validity of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for both prevalent diagnoses and less common diseases, and to assess the performance of a large language model (LLM)-based system in validating these codes. Materials and Methods This retrospective study analyzed hospital admissions from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. We developed a validated LLM-based system using GPT-4o, refined through iterative prompt engineering, to assess ICD-10-CM code validity. We measured the positive predictive value (PPV) of ICD-10-CM codes, PPV of principal and secondary diagnoses, and the performance of an LLM-based system in code validation. Results Among 865 079 assigned codes, the PPV was 84.6% (95% CI, 84.5%-84.6%). Principal diagnoses had a PPV of 93.9% (95% CI, 93.7%-94.1%), while secondary diagnoses had a PPV of 83.8% (95% CI, 83.7%-83.9%). The LLM system demonstrated high performance in validating ICD codes, achieving 93.6% accuracy, 95.4% sensitivity, and 85.2% specificity. Among correctly assigned secondary diagnoses, the majority (67.9%) represented historical or baseline conditions, while 32.1% reflected active conditions that deviated from baseline status; 22.3% of these emerged after hospital admission. PPV decreases with later diagnosis positions, with the largest decline occurring between principal and secondary diagnoses. Discussion and Conclusion In this large-scale evaluation, ICD-10-CM codes exhibited generally high accuracy, though variability existed by position and condition type. A validated LLM system performed comparably to physician review and offers a scalable means to improve coding accuracy. These findings support the potential for integrating LLM-based auditing into routine workflows to strengthen the quality of administrative and research data.

Background: Generative AI and synthetic media have enabled realistic human Embodied Conversational Agents (ECAs) or avatars. A subset of this technology replicates faces and voices to create realistic likenesses. When combined with avatars, these methods enable the creation of “digital twins” of physicians, offering patients scalable, 24/7 clinical communication outside the immediate clinical environment. This study evaluated surgical patient perceptions of an AI-generated surgeon avatar for postoperative education. Methods: We conducted a pilot feasibility study with 30 plastic surgery patients at Mayo Clinic, USA (July–August 2025). A bespoke interactive surgeon avatar was developed in Python using the HeyGen IV model to reproduce the surgeon’s likeness. Patients interacted with the avatar through natural voice queries, which were mapped to predetermined, pre-recorded video responses covering ten common postoperative topics. Patient perceptions were assessed using validated scales of usability, engagement, trust, eeriness, and realism, supplemented by qualitative feedback. Results: The avatar system reliably answered 297 of 300 patient queries (99%). Usability was excellent (mean System Usability Scale score = 87.7 ± 11.5) and engagement high (mean 4.27 ± 0.23). Trust was the highest-rated domain, with all participants (100%) finding the avatar trustworthy and its information believable. Eeriness was minimal (mean = 1.57 ± 0.48), and 96.7% found the avatar visually pleasing. Most participants (86.6%) recognized the avatar as their surgeon, although many still identified it as artificial; voice resemblance was less convincing (70%). Interestingly, participants with prior exposure to deepfakes demonstrated consistently higher acceptance, rating usability, trust, and engagement 5–10% higher than those without prior exposure. Qualitative feedback highlighted clarity, efficiency, and convenience, while noting limitations in realism and conversational scope. Conclusions: The AI-generated physician avatar achieved high patient acceptance without triggering uncanny valley effects. Transparency about the synthetic nature of the technology enhanced, rather than diminished, trust. Familiarity with the physician and institutional credibility likely played a key role in the high trust scores observed. When implemented transparently and with appropriate safeguards, synthetic physician avatars may offer a scalable solution for postoperative education while preserving trust in clinical relationships.

Background: During postoperative recovery, patients and their caregivers often lack crucial information, leading to numerous repetitive inquiries that burden healthcare providers. Traditional discharge materials, including paper handouts and patient portals, are often static, overwhelming, or underutilized, leading to patient overwhelm and contributing to unnecessary ER visits and overall healthcare overutilization. Conversational chatbots offer a solution, but Natural Language Processing (NLP) systems are often inflexible and limited in understanding, while powerful Large Language Models (LLMs) are prone to generating “hallucinations”. Objective: To combine the deterministic framework of traditional NLP with the probabilistic capabilities of LLMs, we developed the AI Virtual Assistant (AIVA) Platform. This system utilizes a retrieval-augmented generation (RAG) architecture, integrating Gemini 2.0 Flash with a medically verified knowledge base via Google Vertex AI, to safely deliver dynamic, patient-facing postoperative guidance grounded in validated clinical content. Methods: The AIVA Platform was evaluated through 750 simulated patient interactions derived from 250 unique postoperative queries across 20 high-frequency recovery domains. Three blinded physician reviewers assessed formal system performance, evaluating classification metrics (accuracy, precision, recall, F1-score), relevance (SSI Index), completeness, and consistency (5-point Likert scale). Safety guardrails were tested with 120 out-of-scope queries and 30 emergency escalation scenarios. Additionally, groundedness, fluency, and readability were assessed using automated LLM metrics. Results: The system achieved 98.4% classification accuracy (precision 1.0, recall 0.98, F1-score 0.9899). Physician reviews showed high completeness (4.83/5), consistency (4.49/5), and relevance (SSI Index 2.68/3). Safety guardrails successfully identified 100% of out-of-scope and escalation scenarios. Groundedness evaluations demonstrated strong context precision (0.951), recall (0.910), and faithfulness (0.956), with 95.6% verification agreement. While fluency and semantic alignment were high (BERTScore F1 0.9013, ROUGE-1 0.8377), readability was 11th-grade level (Flesch–Kincaid 46.34). Conclusion: The simulated testing demonstrated strong technical accuracy, safety, and clinical relevance in simulated postoperative care. Its architecture effectively balances flexibility and safety, addressing key limitations of standalone NLP and LLMs. While readability remains a challenge, these findings establish a solid foundation, demonstrating readiness for clinical trials and real-world testing within surgical care pathways.

Abstract Alzheimer’s Disease (AD) 1 is a progressive neurodegenerative disorder with limited therapeutic options, driving interest in drug repurposing to accelerate treatment discovery. Drug repurposing has emerged as a promising strategy to accelerate therapeutic discovery by repositioning existing drugs for new clinical indications. Recent computational repurposing approaches, including knowledge graph reasoning, transcriptomic signature analysis, and integrative literature mining, have demonstrated strong predictive capabilities 2 . However, these methods often yield divergent drug rankings, which makes it difficult to decide which candidates to advance for experimental follow-up and results in substantial gaps between computational predictions and feasible in vivo validation 2 .To bridge this computational-experimental gap, we proposed an advanced prioritization framework leveraging large language models (LLMs). Our method systematically evaluated three state-of-the-art (SOTA) and representative computational methods (TxGNN 3 , Composition-based Graph Convolutional Network (CompGCN) 4 , and a regularized logistic regression (RLR) 5 , to analyze both their predictive performance and pharmaceutical class distributions. By integrating the strengths and divergences of these models, we generated a unified, streamlined list of 90 candidate drugs for further prioritization. We then utilized an LLM-based agent to perform evidence synthesis from biomedical literature abstracts for each candidate. This process mimics expert manual curation but significantly reduces human effort and time by efficiently distilling vast textual data into actionable insights. Applying consistent and transparent selection criteria, we obtained a refined and prioritized list of drug candidates suitable for subsequent in vivo experimental validation. The robustness and clinical relevance of our framework were validated using real-world data from Alzheimer’s patient cohorts, clinical trial registries, and expert pharmacological reviews. This comprehensive validation confirmed that our LLM-driven approach enhances efficiency, consistency, scalability, and generalizability. By integrating computational predictions with scalable evidence synthesis and multifaceted validation, our framework facilitated rapid and informed prioritization of repurposed drugs. Our framework can potentially accelerate the translational pathway toward viable AD therapeutics. Moreover, the versatility of our framework can also be applied to drug repurposing efforts for other diseases beyond AD.

Background: Artificial Intelligence (AI)-driven Decision Support Systems (DSSs) promise improvements in diagnostic accuracy and clinical workflow efficiency, but their adoption is hindered by inadequate confidence calibration, limited transparency, and poor alignment with real-world decision processes, which limit clinician trust and lead to high override rates. Methods: We developed and validated a dynamic scoring framework to enhance trust in AI-generated diagnoses by integrating AI confidence scores, semantic similarity measures, and transparency weighting into the override decision process using 6689 cardiovascular cases from the MIMIC-III dataset. Override thresholds were calibrated and validated across varying transparency and confidence levels, with override rate as the primary acceptance measure. Results: The implementation of this framework reduced the override rate to 33.29%, with high-confidence predictions (90–99%) overridden at a rate of only 1.7%, and low-confidence predictions (70–79%) at a rate of 99.3%. Minimal transparency diagnoses had a 73.9% override rate compared to 49.3% for moderate transparency. Statistical analyses confirmed significant associations between confidence, transparency, and override rates (p < 0.001). Conclusions: These findings suggest that enhanced transparency and confidence calibration can substantially reduce override rates and promote clinician acceptance of AI diagnostics. Future work should focus on clinical validation to optimize patient safety, diagnostic accuracy, and efficiency.

Abstract With the increasing volume of biomedical experimental data, standardizing, sharing, and integrating heterogeneous experimental data across domains has become a major challenge. To address this challenge, we have developed an ontology-supported Study-Experiment-Assay (SEA) common data model (CDM), which includes 10 core and 3 auxiliary classes based on object-oriented modeling. SEA CDM uses interoperable ontologies for data standardization and knowledge inference. Building on the SEA CDM, we developed the Ontology-based SEA Network (OSEAN) relational database and knowledge graph, along with a set of ETL (Extract, Transform, Load) and query tools, and further applied them to represent 1,278 immune studies with over two million samples from three resources: VIGET, ImmPort, and CELLxGENE. Using simple, robust queries and analyses, our research identified multiple scientific insights into sex-specific immune responses, such as neutrophil degranulation and TNF binding to physiological receptors, following live attenuated and trivalent inactivated influenza vaccination. The novel SEA CDM system lays a foundation for establishing an integrative biodata ecosystem across biological and biomedical domains.

Retrieval-Augmented Generation (RAG) offers a promising strategy to harness large language models (LLMs) for delivering up-to-date, accurate clinical guidance while reducing physicians’ cognitive burden, yet its effectiveness hinges on query clarity and structure. We propose an adaptive Self-Query Retrieval (SQR) framework that integrates three refinement modules—PICOT (Population, Intervention, Comparison, Outcome, Time), SPICE (Setting, Population, Intervention, Comparison, Evaluation), and Iterative Query Refinement (IQR)—to automatically restructure and iteratively enhance clinical questions until they meet predefined retrieval-quality thresholds. Implemented on Gemini-1.0 Pro, we benchmarked SQR using thirty postoperative rhinoplasty queries, evaluating responses for accuracy and relevance on a three-point Likert scale and for retrieval quality via precision, recall, and F1 score; statistical significance was assessed by one-way ANOVA with Tukey post-hoc testing. The full SQR pipeline achieved 87% accuracy (Likert 2.4 ± 0.7) and 100% relevance (Likert 3.0 ± 0.0), significantly outperforming a non-refined RAG baseline (50% accuracy, 80% relevance; p < 0.01 and p = 0.03). Precision, recall, and F1 rose from 0.17, 0.39 and 0.24 to 0.53, 1.00, and 0.70, respectively, while PICOT-only and SPICE-only variants yielded intermediate improvements. These findings demonstrate that automated structuring and iterative enhancement of queries via SQR substantially elevate LLM-based clinical decision support, and its model-agnostic architecture enables rapid adaptation across specialties, data sources, and LLM platforms.

Abstract Background/ Objectives: Agentic AI represents a promising evolution of AI technology applied to healthcare, with systems increasingly capable of operating autonomously to achieve defined clinical goals. However, the literature lacks conceptual clarity between “AI agents” and “agentic AI”, and few studies have rigorously explored their clinical applications. Therefore, this study aims to conduct a novel systematic review addressing this gap by examining agentic AI systems in healthcare settings, characterizing their applications, features, outcomes, and limitations, and clarifying the conceptual distinctions between AI agents and agentic AI systems using predefined and objective criteria. Methods A comprehensive search was conducted across PubMed, Embase, Cochrane, Scopus, and Google Scholar on April 6th, 2025. Studies were included if they involved AI systems in healthcare settings that demonstrated the following agentic features: autonomous operation, goal-directed behavior, and initiating action. Data on the clinical tasks achieved by the agents, key findings, features, and limitations were collected from the included studies. Screening and extraction followed PRISMA guidelines, with Risk of Bias assessed using ROBINS-I and Cochrane's Risk of Bias tools. Results Of 984 retrieved records, seven studies met the inclusion criteria, spanning domains such as emergency medicine, oncology, radiology, and rehabilitation. Multi-agent architecture was frequently used to decompose and coordinate complex workflows. Among the included studies, the AIs showed high accuracy in diagnosing cancer patients, conducting treatment plans, sending alerts, coaching messages, analysing image data, and adapting to challenging experimental scenarios. While demonstrating potential for improved efficiency, task accuracy, and patient engagement, significant limitations were noted: narrow task scope, lack of physical agency, limited clinical validation, and barriers to integration into real-world healthcare systems. Only one system had been deployed in a patient-facing trial setting. Conclusion The current literature suggests an emerging role and application of Agentic AI, holding promise with the potential to revolutionize diagnostics, triage, treatment planning, and patient management. However, real-world implementation and evaluations in the literature are limited. Future research must address critical validation, regulation, ethics, and clinical integration challenges to realize their full potential. Clear operational definitions and frameworks for evaluating agency are essential to support safe and effective deployment of these systems.