Advancing Problem-Based Learning in Biomedical Engineering in the Era of Generative AI

Problem-Based Learning (PBL) has significantly impacted biomedical engineering (BME) education since its introduction in the early 2000s, effectively enhancing critical thinking and real-world knowledge application among students. With biomedical engineering rapidly converging with artificial intelligence (AI), integrating effective AI education into established curricula has become challenging yet increasingly necessary. Recent advancements, including AI's recognition by the 2024 Nobel Prize, have highlighted the importance of training students comprehensively in biomedical AI. However, effective biomedical AI education faces substantial obstacles, such as diverse student backgrounds, limited personalized mentoring, constrained computational resources, and difficulties in safely scaling hands-on practical experiments due to privacy and ethical concerns associated with biomedical data. To overcome these issues, we conducted a three-year (2021-2023) case study implementing an advanced PBL framework tailored specifically for biomedical AI education, involving 92 undergraduate and 156 graduate students from the joint Biomedical Engineering program of Georgia Institute of Technology and Emory University. Our approach emphasizes collaborative, interdisciplinary problem-solving through authentic biomedical AI challenges. The implementation led to measurable improvements in learning outcomes, evidenced by high research productivity (16 student-authored publications), consistently positive peer evaluations, and successful development of innovative computational methods addressing real biomedical challenges. Additionally, we examined the role of generative AI both as a teaching subject and an educational support tool within the PBL framework. Our study presents a practical and scalable roadmap for biomedical engineering departments aiming to integrate robust AI education into their curricula.

MedAgentsBench: Benchmarking Thinking Models and Agent Frameworks for Complex Medical Reasoning

Large Language Models (LLMs) have shown impressive performance on existing medical question-answering benchmarks. This high performance makes it increasingly difficult to meaningfully evaluate and differentiate advanced methods. We present MedAgentsBench, a benchmark that focuses on challenging medical questions requiring multi-step clinical reasoning, diagnosis formulation, and treatment planning-scenarios where current models still struggle despite their strong performance on standard tests. Drawing from seven established medical datasets, our benchmark addresses three key limitations in existing evaluations: (1) the prevalence of straightforward questions where even base models achieve high performance, (2) inconsistent sampling and evaluation protocols across studies, and (3) lack of systematic analysis of the interplay between performance, cost, and inference time. Through experiments with various base models and reasoning methods, we demonstrate that the latest thinking models, DeepSeek R1 and OpenAI o3, exhibit exceptional performance in complex medical reasoning tasks. Additionally, advanced search-based agent methods offer promising performance-to-cost ratios compared to traditional approaches. Our analysis reveals substantial performance gaps between model families on complex questions and identifies optimal model selections for different computational constraints. Our benchmark and evaluation framework are publicly available at https://github.com/gersteinlab/medagents-benchmark.

MedAdapter: Efficient Test-Time Adaptation of Large Language Models towards Medical Reasoning

Despite their improved capabilities in generation and reasoning, adapting large language models (LLMs) to the biomedical domain remains challenging due to their immense size and corporate privacy. In this work, we propose MedAdapter, a unified post-hoc adapter for test-time adaptation of LLMs towards biomedical applications. Instead of fine-tuning the entire LLM, MedAdapter effectively adapts the original model by fine-tuning only a small BERT-sized adapter to rank candidate solutions generated by LLMs. Experiments demonstrate that MedAdapter effectively adapts both white-box and black-box LLMs in biomedical reasoning, achieving average performance improvements of 25.48% and 11.31%, respectively, without requiring extensive computational resources or sharing data with third parties. MedAdapter also yields superior performance when combined with train-time adaptation, highlighting a flexible and complementary solution to existing adaptation methods. Faced with the challenges of balancing model performance, computational resources, and data privacy, MedAdapter provides an efficient, privacy-preserving, cost-effective, and transparent solution for adapting LLMs to the biomedical domain.

BMRetriever: Tuning Large Language Models as Better Biomedical Text Retrievers

Developing effective biomedical retrieval models is important for excelling at knowledge-intensive biomedical tasks but still challenging due to the deficiency of sufficient publicly annotated biomedical data and computational resources. We present BMRetriever, a series of dense retrievers for enhancing biomedical retrieval via unsupervised pre-training on large biomedical corpora, followed by instruction fine-tuning on a combination of labeled datasets and synthetic pairs. Experiments on 5 biomedical tasks across 11 datasets verify BMRetriever's efficacy on various biomedical applications. BMRetriever also exhibits strong parameter efficiency, with the 410M variant outperforming baselines up to 11.7 times larger, and the 2B variant matching the performance of models with over 5B parameters. The training data and model checkpoints are released at \url{https://huggingface.co/BMRetriever} to ensure transparency, reproducibility, and application to new domains.

RAM-EHR: Retrieval Augmentation Meets Clinical Predictions on Electronic Health Records

We present RAM-EHR, a Retrieval AugMentation pipeline to improve clinical predictions on Electronic Health Records (EHRs). RAM-EHR first collects multiple knowledge sources, converts them into text format, and uses dense retrieval to obtain information related to medical concepts. This strategy addresses the difficulties associated with complex names for the concepts. RAM-EHR then augments the local EHR predictive model co-trained with consistency regularization to capture complementary information from patient visits and summarized knowledge. Experiments on two EHR datasets show the efficacy of RAM-EHR over previous knowledge-enhanced baselines (3.4% gain in AUROC and 7.2% gain in AUPR), emphasizing the effectiveness of the summarized knowledge from RAM-EHR for clinical prediction tasks. The code will be published at \url{https://github.com/ritaranx/RAM-EHR}.

EHRAgent: Code Empowers Large Language Models for Complex Tabular Reasoning on Electronic Health Records

Large language models (LLMs) have demonstrated exceptional capabilities in planning and tool utilization as autonomous agents, but few have been developed for medical problem-solving. We propose EHRAgent1, an LLM agent empowered with a code interface, to autonomously generate and execute code for complex clinical tasks within electronic health records (EHRs). First, we formulate an EHR question-answering task into a tool-use planning process, efficiently decomposing a complicated task into a sequence of manageable actions. By integrating interactive coding and execution feedback, EHRAgent learns from error messages and improves the originally generated code through iterations. Furthermore, we enhance the LLM agent by incorporating long-term memory, which allows EHRAgent to effectively select and build upon the most relevant successful cases from past experiences. Experiments on two real-world EHR datasets show that EHRAgent outperforms the strongest LLM agent baseline by 36.48% and 12.41%, respectively. EHRAgent leverages the emerging few-shot learning capabilities of LLMs, enabling autonomous code generation and execution to tackle complex clinical tasks with minimal demonstrations.

Knowledge-Infused Prompting: Assessing and Advancing Clinical Text Data Generation with Large Language Models

Clinical natural language processing requires methods that can address domain-specific challenges, such as complex medical terminology and clinical contexts. Recently, large language models (LLMs) have shown promise in this domain. Yet, their direct deployment can lead to privacy issues and are constrained by resources. To address this challenge, we delve into synthetic clinical text generation using LLMs for clinical NLP tasks. We propose an innovative, resource-efficient approach, ClinGen, which infuses knowledge into the process. Our model involves clinical knowledge extraction and context-informed LLM prompting. Both clinical topics and writing styles are drawn from external domain-specific knowledge graphs and LLMs to guide data generation. Our extensive empirical study across 7 clinical NLP tasks and 16 datasets reveals that ClinGen consistently enhances performance across various tasks, effectively aligning the distribution of real datasets and significantly enriching the diversity of generated training instances. We will publish our code and all the generated data in \url{https://github.com/ritaranx/ClinGen}.

Autonomous Soft Tissue Retraction Using Demonstration-Guided Reinforcement Learning

In the context of surgery, robots can provide substantial assistance by performing small, repetitive tasks such as suturing, needle exchange, and tissue retraction, thereby enabling surgeons to concentrate on more complex aspects of the procedure. However, existing surgical task learning mainly pertains to rigid body interactions, whereas the advancement towards more sophisticated surgical robots necessitates the manipulation of soft bodies. Previous work focused on tissue phantoms for soft tissue task learning, which can be expensive and can be an entry barrier to research. Simulation environments present a safe and efficient way to learn surgical tasks before their application to actual tissue. In this study, we create a Robot Operating System (ROS)-compatible physics simulation environment with support for both rigid and soft body interactions within surgical tasks. Furthermore, we investigate the soft tissue interactions facilitated by the patient-side manipulator of the DaVinci surgical robot. Leveraging the pybullet physics engine, we simulate kinematics and establish anchor points to guide the robotic arm when manipulating soft tissue. Using demonstration-guided reinforcement learning (RL) algorithms, we investigate their performance in comparison to traditional reinforcement learning algorithms. Our in silico trials demonstrate a proof-of-concept for autonomous surgical soft tissue retraction. The results corroborate the feasibility of learning soft body manipulation through the application of reinforcement learning agents. This work lays the foundation for future research into the development and refinement of surgical robots capable of managing both rigid and soft tissue interactions. Code is available at https://github.com/amritpal-001/tissue_retract.

Nonlinear Causal Discovery via Kernel Anchor Regression

Learning causal relationships is a fundamental problem in science. Anchor regression has been developed to address this problem for a large class of causal graphical models, though the relationships between the variables are assumed to be linear. In this work, we tackle the nonlinear setting by proposing kernel anchor regression (KAR). Beyond the natural formulation using a classic two-stage least square estimator, we also study an improved variant that involves nonparametric regression in three separate stages. We provide convergence results for the proposed KAR estimators and the identifiability conditions for KAR to learn the nonlinear structural equation models (SEM). Experimental results demonstrate the superior performances of the proposed KAR estimators over existing baselines.

Explainable Artificial Intelligence Methods in Combating Pandemics: A Systematic Review

Despite the myriad peer-reviewed papers demonstrating novel Artificial Intelligence (AI)-based solutions to COVID-19 challenges during the pandemic, few have made significant clinical impact. The impact of artificial intelligence during the COVID-19 pandemic was greatly limited by lack of model transparency. This systematic review examines the use of Explainable Artificial Intelligence (XAI) during the pandemic and how its use could overcome barriers to real-world success. We find that successful use of XAI can improve model performance, instill trust in the end-user, and provide the value needed to affect user decision-making. We introduce the reader to common XAI techniques, their utility, and specific examples of their application. Evaluation of XAI results is also discussed as an important step to maximize the value of AI-based clinical decision support systems. We illustrate the classical, modern, and potential future trends of XAI to elucidate the evolution of novel XAI techniques. Finally, we provide a checklist of suggestions during the experimental design process supported by recent publications. Common challenges during the implementation of AI solutions are also addressed with specific examples of potential solutions. We hope this review may serve as a guide to improve the clinical impact of future AI-based solutions.