This research aims to develop a dynamic and scalable framework to facilitate harmonization of Common Data Elements (CDEs) across heterogeneous biomedical datasets by addressing challenges such as semantic heterogeneity, structural variability, and context dependence to streamline integration, enhance interoperability, and accelerate scientific discovery. Our methodology leverages Large Language Models (LLMs) for context-aware text embeddings that convert CDEs into dense vectors capturing semantic relationships and patterns. These embeddings are clustered using Hierarchical Density-Based Spatial Clustering of Applications with Noise (HDBSCAN) to group semantically similar CDEs. The framework incorporates four key steps: (1) LLM-based text embedding to mathematically represent semantic context, (2) unsupervised clustering of embeddings via HDBSCAN, (3) automated labeling using LLM summarization, and (4) supervised learning to train a classifier assigning new or unclustered CDEs to labeled clusters. Evaluated on the NIH NLM CDE Repository with over 24,000 CDEs, the system identified 118 meaningful clusters at an optimized minimum cluster size of 20. The classifier achieved 90.46 percent overall accuracy, performing best in larger categories. External validation against Gravity Projects Social Determinants of Health domains showed strong agreement (Adjusted Rand Index 0.52, Normalized Mutual Information 0.78), indicating that embeddings effectively capture cluster characteristics. This adaptable and scalable approach offers a practical solution to CDE harmonization, improving selection efficiency and supporting ongoing data interoperability.

Social determinants of health (SDOH) $-$ the myriad of circumstances in which people live, grow, and age $-$ play an important role in health outcomes. However, existing outcome prediction models often only use proxies of SDOH as features. Recent open data initiatives present an opportunity to construct a more comprehensive view of SDOH, but manually integrating the most relevant data for individual patients becomes increasingly challenging as the volume and diversity of public SDOH data grows. Large language models (LLMs) have shown promise at automatically annotating structured data. Here, we conduct an end-to-end case study evaluating the feasibility of using LLMs to integrate SDOH data, and the utility of these SDOH features for clinical prediction. We first manually label 700+ variables from two publicly-accessible SDOH data sources to one of five semantic SDOH categories. Then, we benchmark performance of 9 open-source LLMs on this classification task. Finally, we train ML models to predict 30-day hospital readmission among 39k heart failure (HF) patients, and we compare the prediction performance of the categorized SDOH variables with standard clinical variables. Additionally, we investigate the impact of few-shot LLM prompting on LLM annotation performance, and perform a metadata ablation study on prompts to evaluate which information helps LLMs accurately annotate these variables. We find that some open-source LLMs can effectively, accurately annotate SDOH variables with zero-shot prompting without the need for fine-tuning. Crucially, when combined with standard clinical features, the LLM-annotated Neighborhood and Built Environment subset of the SDOH variables shows the best performance predicting 30-day readmission of HF patients.