Resolving the bias-precision paradox with stochastic causal representation learning for personalized medicine

Estimating individualized treatment effects from longitudinal observational data is central to data-driven medicine, yet existing methods face a fundamental limitation: reducing confounding bias often suppresses clinically informative heterogeneity, degrading patient-specific predictions. Here, we identify this tension as a bias-precision paradox in causal representation learning and introduce sampling-based maximum mean discrepancy (sMMD), a stochastic alignment strategy that replaces global adversarial balancing with subset-level matching. We instantiate this approach in a framework for counterfactual outcome prediction with attribution-grounded interpretability. Across two large-scale ICU cohorts (n = 27,783), our framework improves accuracy under distribution shift, reducing error by up to 11.5% and substantially increasing recall in high-risk tasks. Mechanistic analyses show that sMMD selectively preserves clinically decisive variables. In human-AI evaluation, our method outperforms clinicians-in-training and large language models, and improves clinician accuracy by 14.7% while reducing decision time, enabling interpretable, real-time clinical decision support.

Foundation Models to Unlock Real-World Evidence from Nationwide Medical Claims

Evidence derived from large-scale real-world data (RWD) is increasingly informing regulatory evaluation and healthcare decision-making. Administrative claims provide population-scale, longitudinal records of healthcare utilization, expenditure, and detailed coding of diagnoses, procedures, and medications, yet their potential as a substrate for healthcare foundation models remains largely unexplored. Here we present ReClaim, a generative transformer trained from scratch on 43.8 billion medical events from more than 200 million enrollees in the MarketScan claims data spanning 2008-2022. ReClaim models longitudinal trajectories across diagnoses, procedures, medications, and expenditure, and was scaled to 140 million, 700 million, and 1.7 billion parameters. Across over 1,000 disease-onset prediction tasks, ReClaim achieved a mean AUC of 75.6%, substantially outperforming disease-specific LightGBM (66.3%) and the transformer-based Delphi model (69.4%), with the largest gains for rare diseases. These advantages held across retrospective and prospective evaluations and in external validation on two independent datasets. Performance improved monotonically with scale, and post-training added 13.8 percentage points over pre-training alone. Beyond disease prediction, ReClaim captured financial outcomes and improved real-world evidence (RWE) analyses: for healthcare expenditure forecasting it increased explained variance from 0.28 to 0.37 relative to LightGBM, and in a target trial emulation it reduced systematic bias by 72% on average relative to Delphi. Together, these results establish administrative claims as a scalable substrate for healthcare foundation models and show that learned representations generalize across time periods and data sources, supporting disease surveillance, expenditure forecasting, and RWE generation.

OphMAE: Bridging Volumetric and Planar Imaging with a Foundation Model for Adaptive Ophthalmological Diagnosis

The advent of foundation models has heralded a new era in medical artificial intelligence (AI), enabling the extraction of generalizable representations from large-scale unlabeled datasets. However, current ophthalmic AI paradigms are predominantly constrained to single-modality inference, thereby creating a dissonance with clinical practice where diagnosis relies on the synthesis of complementary imaging modalities. Furthermore, the deployment of high-performance AI in resource-limited settings is frequently impeded by the unavailability of advanced three-dimensional imaging hardware. Here, we present the Ophthalmic multimodal Masked Autoencoder (OphMAE), a multi-imaging foundation model engineered to synergize the volumetric depth of 3D Optical Coherence Tomography (OCT) with the planar context of 2D en face OCT. By implementing a novel cross-modal fusion architecture and a unique adaptive inference mechanism, OphMAE was pre-trained on a massive dataset with of 183,875 paired OCT images derived from 32,765 patients. In a rigorous benchmark encompassing 17 diverse diagnostic tasks with 48,340 paired OCT images from 8,191 patients, the model demonstrated state-of-the-art performance, achieving an Area Under the Curve (AUC) of 96.9% for Age-related Macular Degeneration (AMD) and 97.2% for Diabetic Macular Edema (DME), consistently surpassing existing single-modal and multimodal foundation models. Crucially, OphMAE exhibits robust engineering adaptability: it maintains high diagnostic accuracy, such as 93.7\% AUC for AMD, even when restricted to single-modality 2D inputs, and demonstrates exceptional data efficiency by retaining 95.7% AUC with as few as 500 labeled samples. This work establishes a scalable and adaptable framework for ophthalmic AI, ensuring robust performance across different tasks.

VOLMO: Versatile and Open Large Models for Ophthalmology

Vision impairment affects millions globally, and early detection is critical to preventing irreversible vision loss. Ophthalmology workflows require clinicians to integrate medical images, structured clinical data, and free-text notes to determine disease severity and management, which is time-consuming and burdensome. Recent multimodal large language models (MLLMs) show promise, but existing general and medical MLLMs perform poorly in ophthalmology, and few ophthalmology-specific MLLMs are openly available. We present VOLMO (Versatile and Open Large Models for Ophthalmology), a model-agnostic, data-open framework for developing ophthalmology-specific MLLMs. VOLMO includes three stages: ophthalmology knowledge pretraining on 86,965 image-text pairs from 26,569 articles across 82 journals; domain task fine-tuning on 26,929 annotated instances spanning 12 eye conditions for disease screening and severity classification; and multi-step clinical reasoning on 913 patient case reports for assessment, planning, and follow-up care. Using this framework, we trained a compact 2B-parameter MLLM and compared it with strong baselines, including InternVL-2B, LLaVA-Med-7B, MedGemma-4B, MedGemma-27B, and RETFound. We evaluated these models on image description generation, disease screening and staging classification, and assessment-and-management generation, with additional manual review by two healthcare professionals and external validation on three independent cohorts for age-related macular degeneration and diabetic retinopathy. Across settings, VOLMO-2B consistently outperformed baselines, achieving stronger image description performance, an average F1 of 87.4% across 12 eye conditions, and higher scores in external validation.

FSVideo: Fast Speed Video Diffusion Model in a Highly-Compressed Latent Space

We introduce FSVideo, a fast speed transformer-based image-to-video (I2V) diffusion framework. We build our framework on the following key components: 1.) a new video autoencoder with highly-compressed latent space ($64\times64\times4$ spatial-temporal downsampling ratio), achieving competitive reconstruction quality; 2.) a diffusion transformer (DIT) architecture with a new layer memory design to enhance inter-layer information flow and context reuse within DIT, and 3.) a multi-resolution generation strategy via a few-step DIT upsampler to increase video fidelity. Our final model, which contains a 14B DIT base model and a 14B DIT upsampler, achieves competitive performance against other popular open-source models, while being an order of magnitude faster. We discuss our model design as well as training strategies in this report.

A Federated and Parameter-Efficient Framework for Large Language Model Training in Medicine

Large language models (LLMs) have demonstrated strong performance on medical benchmarks, including question answering and diagnosis. To enable their use in clinical settings, LLMs are typically further adapted through continued pretraining or post-training using clinical data. However, most medical LLMs are trained on data from a single institution, which faces limitations in generalizability and safety in heterogeneous systems. Federated learning (FL) is a promising solution for enabling collaborative model development across healthcare institutions. Yet applying FL to LLMs in medicine remains fundamentally limited. First, conventional FL requires transmitting the full model during each communication round, which becomes impractical for multi-billion-parameter LLMs given the limited computational resources. Second, many FL algorithms implicitly assume data homogeneity, whereas real-world clinical data are highly heterogeneous across patients, diseases, and institutional practices. We introduce the model-agnostic and parameter-efficient federated learning framework for adapting LLMs to medical applications. Fed-MedLoRA transmits only low-rank adapter parameters, reducing communication and computation overhead, while Fed-MedLoRA+ further incorporates adaptive, data-aware aggregation to improve convergence under cross-site heterogeneity. We apply the framework to clinical information extraction (IE), which transforms patient narratives into structured medical entities and relations. Accuracy was assessed across five patient cohorts through comparisons with BERT models, and LLaMA-3 and DeepSeek-R1, GPT-4o models. Evaluation settings included (1) in-domain training and testing, (2) external validation on independent cohorts, and (3) a low-resource new-site adaptation scenario using real-world clinical notes from the Yale New Haven Health System.

EHR-RAG: Bridging Long-Horizon Structured Electronic Health Records and Large Language Models via Enhanced Retrieval-Augmented Generation

Electronic Health Records (EHRs) provide rich longitudinal clinical evidence that is central to medical decision-making, motivating the use of retrieval-augmented generation (RAG) to ground large language model (LLM) predictions. However, long-horizon EHRs often exceed LLM context limits, and existing approaches commonly rely on truncation or vanilla retrieval strategies that discard clinically relevant events and temporal dependencies. To address these challenges, we propose EHR-RAG, a retrieval-augmented framework designed for accurate interpretation of long-horizon structured EHR data. EHR-RAG introduces three components tailored to longitudinal clinical prediction tasks: Event- and Time-Aware Hybrid EHR Retrieval to preserve clinical structure and temporal dynamics, Adaptive Iterative Retrieval to progressively refine queries in order to expand broad evidence coverage, and Dual-Path Evidence Retrieval and Reasoning to jointly retrieves and reasons over both factual and counterfactual evidence. Experiments across four long-horizon EHR prediction tasks show that EHR-RAG consistently outperforms the strongest LLM-based baselines, achieving an average Macro-F1 improvement of 10.76%. Overall, our work highlights the potential of retrieval-augmented LLMs to advance clinical prediction on structured EHR data in practice.

Benchmarking Direct Preference Optimization for Medical Large Vision-Language Models

Large Vision-Language Models (LVLMs) hold significant promise for medical applications, yet their deployment is often constrained by insufficient alignment and reliability. While Direct Preference Optimization (DPO) has emerged as a potent framework for refining model responses, its efficacy in high-stakes medical contexts remains underexplored, lacking the rigorous empirical groundwork necessary to guide future methodological advances. To bridge this gap, we present the first comprehensive examination of diverse DPO variants within the medical domain, evaluating nine distinct formulations across two medical LVLMs: LLaVA-Med and HuatuoGPT-Vision. Our results reveal several critical limitations: current DPO approaches often yield inconsistent gains over supervised fine-tuning, with their efficacy varying significantly across different tasks and backbones. Furthermore, they frequently fail to resolve fundamental visual misinterpretation errors. Building on these insights, we present a targeted preference construction strategy as a proof-of-concept that explicitly addresses visual misinterpretation errors frequently observed in existing DPO models. This design yields a 3.6% improvement over the strongest existing DPO baseline on visual question-answering tasks. To support future research, we release our complete framework, including all training data, model checkpoints, and our codebase at https://github.com/dmis-lab/med-vlm-dpo.

AI-generated data contamination erodes pathological variability and diagnostic reliability

Generative artificial intelligence (AI) is rapidly populating medical records with synthetic content, creating a feedback loop where future models are increasingly at risk of training on uncurated AI-generated data. However, the clinical consequences of this AI-generated data contamination remain unexplored. Here, we show that in the absence of mandatory human verification, this self-referential cycle drives a rapid erosion of pathological variability and diagnostic reliability. By analysing more than 800,000 synthetic data points across clinical text generation, vision-language reporting, and medical image synthesis, we find that models progressively converge toward generic phenotypes regardless of the model architecture. Specifically, rare but critical findings, including pneumothorax and effusions, vanish from the synthetic content generated by AI models, while demographic representations skew heavily toward middle-aged male phenotypes. Crucially, this degradation is masked by false diagnostic confidence; models continue to issue reassuring reports while failing to detect life-threatening pathology, with false reassurance rates tripling to 40%. Blinded physician evaluation confirms that this decoupling of confidence and accuracy renders AI-generated documentation clinically useless after just two generations. We systematically evaluate three mitigation strategies, finding that while synthetic volume scaling fails to prevent collapse, mixing real data with quality-aware filtering effectively preserves diversity. Ultimately, our results suggest that without policy-mandated human oversight, the deployment of generative AI threatens to degrade the very healthcare data ecosystems it relies upon.

EHRNavigator: A Multi-Agent System for Patient-Level Clinical Question Answering over Heterogeneous Electronic Health Records

Clinical decision-making increasingly relies on timely and context-aware access to patient information within Electronic Health Records (EHRs), yet most existing natural language question-answering (QA) systems are evaluated solely on benchmark datasets, limiting their practical relevance. To overcome this limitation, we introduce EHRNavigator, a multi-agent framework that harnesses AI agents to perform patient-level question answering across heterogeneous and multimodal EHR data. We assessed its performance using both public benchmark and institutional datasets under realistic hospital conditions characterized by diverse schemas, temporal reasoning demands, and multimodal evidence integration. Through quantitative evaluation and clinician-validated chart review, EHRNavigator demonstrated strong generalization, achieving 86% accuracy on real-world cases while maintaining clinically acceptable response times. Overall, these findings confirm that EHRNavigator effectively bridges the gap between benchmark evaluation and clinical deployment, offering a robust, adaptive, and efficient solution for real-world EHR question answering.