Daily Papers

Access to real-world medication prescriptions is essential for medical research and healthcare quality improvement. However, access to real medication prescriptions is often limited due to the sensitive nature of the information expressed. Additionally, manually labelling these instructions for training and fine-tuning Natural Language Processing (NLP) models can be tedious and expensive. We introduce a novel task-specific model architecture, Label-To-Text-Transformer (LT3), tailored to generate synthetic medication prescriptions based on provided labels, such as a vocabulary list of medications and their attributes. LT3 is trained on a set of around 2K lines of medication prescriptions extracted from the MIMIC-III database, allowing the model to produce valuable synthetic medication prescriptions. We evaluate LT3's performance by contrasting it with a state-of-the-art Pre-trained Language Model (PLM), T5, analysing the quality and diversity of generated texts. We deploy the generated synthetic data to train the SpacyNER model for the Named Entity Recognition (NER) task over the n2c2-2018 dataset. The experiments show that the model trained on synthetic data can achieve a 96-98\% F1 score at Label Recognition on Drug, Frequency, Route, Strength, and Form. LT3 codes and data will be shared at https://github.com/HECTA-UoM/Label-To-Text-Transformer

Hospital information systems (HIS) have become an essential part of healthcare institutions and now incorporate prescribing support software. Prescription support software allows for structured information capture, which improves the safety, appropriateness and efficiency of prescriptions and reduces the number of adverse drug events (ADEs). However, such a system increases the amount of time physicians spend at a computer entering information instead of providing medical care. In addition, any new visiting clinician must learn to manage complex interfaces since each HIS has its own interfaces. In this paper, we present a natural language interface for e-prescribing software in the form of a spoken dialogue system accessible on a smartphone. This system allows prescribers to record their prescriptions verbally, a form of interaction closer to their usual practice. The system extracts the formal representation of the prescription ready to be checked by the prescribing software and uses the dialogue to request mandatory information, correct errors or warn of particular situations. Since, to the best of our knowledge, there is no existing voice-based prescription dialogue system, we present the system developed in a low-resource environment, focusing on dialogue modeling, semantic extraction and data augmentation. The system was evaluated in the wild with 55 participants. This evaluation showed that our system has an average prescription time of 66.15 seconds for physicians and 35.64 seconds for other experts, and a task success rate of 76\% for physicians and 72\% for other experts. All evaluation data were recorded and annotated to form PxCorpus, the first spoken drug prescription corpus that has been made fully available to the community (https://doi.org/10.5281/zenodo.6524162).

Spoken medical dialogue systems are increasingly attracting interest to enhance access to healthcare services and improve quality and traceability of patient care. In this paper, we focus on medical drug prescriptions acquired on smartphones through spoken dialogue. Such systems would facilitate the traceability of care and would free clinicians' time. However, there is a lack of speech corpora to develop such systems since most of the related corpora are in text form and in English. To facilitate the research and development of spoken medical dialogue systems, we present, to the best of our knowledge, the first spoken medical drug prescriptions corpus, named PxSLU. It contains 4 hours of transcribed and annotated dialogues of drug prescriptions in French acquired through an experiment with 55 participants experts and non-experts in prescriptions. We also present some experiments that demonstrate the interest of this corpus for the evaluation and development of medical dialogue systems.

Generating synthetic text addresses the challenge of data availability in privacy-sensitive domains such as healthcare. This study explores the applicability of synthetic data in real-world medical settings. We introduce MedSyn, a novel medical text generation framework that integrates large language models with a Medical Knowledge Graph (MKG). We use MKG to sample prior medical information for the prompt and generate synthetic clinical notes with GPT-4 and fine-tuned LLaMA models. We assess the benefit of synthetic data through application in the ICD code prediction task. Our research indicates that synthetic data can increase the classification accuracy of vital and challenging codes by up to 17.8% compared to settings without synthetic data. Furthermore, to provide new data for further research in the healthcare domain, we present the largest open-source synthetic dataset of clinical notes for the Russian language, comprising over 41k samples covering 219 ICD-10 codes.

The recommendation of medication is a vital aspect of intelligent healthcare systems, as it involves prescribing the most suitable drugs based on a patient's specific health needs. Unfortunately, many sophisticated models currently in use tend to overlook the nuanced semantics of medical data, while only relying heavily on identities. Furthermore, these models face significant challenges in handling cases involving patients who are visiting the hospital for the first time, as they lack prior prescription histories to draw upon. To tackle these issues, we harness the powerful semantic comprehension and input-agnostic characteristics of Large Language Models (LLMs). Our research aims to transform existing medication recommendation methodologies using LLMs. In this paper, we introduce a novel approach called Large Language Model Distilling Medication Recommendation (LEADER). We begin by creating appropriate prompt templates that enable LLMs to suggest medications effectively. However, the straightforward integration of LLMs into recommender systems leads to an out-of-corpus issue specific to drugs. We handle it by adapting the LLMs with a novel output layer and a refined tuning loss function. Although LLM-based models exhibit remarkable capabilities, they are plagued by high computational costs during inference, which is impractical for the healthcare sector. To mitigate this, we have developed a feature-level knowledge distillation technique, which transfers the LLM's proficiency to a more compact model. Extensive experiments conducted on two real-world datasets, MIMIC-III and MIMIC-IV, demonstrate that our proposed model not only delivers effective results but also is efficient. To ease the reproducibility of our experiments, we release the implementation code online.

Numerous medical systems powered by Large Language Models (LLMs) have achieved remarkable progress in diverse healthcare tasks. However, research on their medication safety remains limited due to the lack of real world datasets, constrained by privacy and accessibility issues. Moreover, evaluation of LLMs in realistic clinical consultation settings, particularly regarding medication safety, is still underexplored. To address these gaps, we propose a framework that simulates and evaluates clinical consultations to systematically assess the medication safety capabilities of LLMs. Within this framework, we generate inquiry diagnosis dialogues with embedded medication risks and construct a dedicated medication safety database, RxRisk DB, containing 6,725 contraindications, 28,781 drug interactions, and 14,906 indication-drug pairs. A two-stage filtering strategy ensures clinical realism and professional quality, resulting in the benchmark RxSafeBench with 2,443 high-quality consultation scenarios. We evaluate leading open-source and proprietary LLMs using structured multiple choice questions that test their ability to recommend safe medications under simulated patient contexts. Results show that current LLMs struggle to integrate contraindication and interaction knowledge, especially when risks are implied rather than explicit. Our findings highlight key challenges in ensuring medication safety in LLM-based systems and provide insights into improving reliability through better prompting and task-specific tuning. RxSafeBench offers the first comprehensive benchmark for evaluating medication safety in LLMs, advancing safer and more trustworthy AI-driven clinical decision support.

Hospitals in India still rely on handwritten medical records despite the availability of Electronic Medical Records (EMR), complicating statistical analysis and record retrieval. Handwritten records pose a unique challenge, requiring specialized data for training models to recognize medications and their recommendation patterns. While traditional handwriting recognition approaches employ 2-D LSTMs, recent studies have explored using Multimodal Large Language Models (MLLMs) for OCR tasks. Building on this approach, we focus on extracting medication names and dosages from simulated medical records. Our methodology MIRAGE (Multimodal Identification and Recognition of Annotations in indian GEneral prescriptions) involves fine-tuning the QWEN VL, LLaVA 1.6 and Idefics2 models on 743,118 high resolution simulated medical record images-fully annotated from 1,133 doctors across India. Our approach achieves 82% accuracy in extracting medication names and dosages.

Access to real-world medical data is often restricted due to privacy regulations, posing a significant barrier to the advancement of healthcare research. Synthetic data offers a promising alternative; however, generating realistic, clinically valid, and privacy-conscious records remains a major challenge. Recent advancements in Large Language Models (LLMs) offer new opportunities for structured data generation; however, existing approaches frequently lack systematic prompting strategies and comprehensive, multi-dimensional evaluation frameworks. In this paper, we present SynLLM, a modular framework for generating high-quality synthetic medical tabular data using 20 state-of-the-art open-source LLMs, including LLaMA, Mistral, and GPT variants, guided by structured prompts. We propose four distinct prompt types, ranging from example-driven to rule-based constraints, that encode schema, metadata, and domain knowledge to control generation without model fine-tuning. Our framework features a comprehensive evaluation pipeline that rigorously assesses generated data across statistical fidelity, clinical consistency, and privacy preservation. We evaluate SynLLM across three public medical datasets, including Diabetes, Cirrhosis, and Stroke, using 20 open-source LLMs. Our results show that prompt engineering significantly impacts data quality and privacy risk, with rule-based prompts achieving the best privacy-quality balance. SynLLM establishes that, when guided by well-designed prompts and evaluated with robust, multi-metric criteria, LLMs can generate synthetic medical data that is both clinically plausible and privacy-aware, paving the way for safer and more effective data sharing in healthcare research.

Large language models (LLMs) are increasingly envisioned as decision-support tools in clinical practice, yet safe clinical reasoning demands integrating heterogeneous knowledge bases -- trials, primary studies, regulatory documents, and cost data -- under strict accuracy constraints. Existing evaluations often rely on synthetic prompts, reduce the task to single-hop factoid queries, or conflate reasoning with open-ended generation, leaving their real-world utility unclear. To close this gap, we present MedBrowseComp, the first benchmark that systematically tests an agent's ability to reliably retrieve and synthesize multi-hop medical facts from live, domain-specific knowledge bases. MedBrowseComp contains more than 1,000 human-curated questions that mirror clinical scenarios where practitioners must reconcile fragmented or conflicting information to reach an up-to-date conclusion. Applying MedBrowseComp to frontier agentic systems reveals performance shortfalls as low as ten percent, exposing a critical gap between current LLM capabilities and the rigor demanded in clinical settings. MedBrowseComp therefore offers a clear testbed for reliable medical information seeking and sets concrete goals for future model and toolchain upgrades. You can visit our project page at: https://moreirap12.github.io/mbc-browse-app/

Doctors typically write in incomprehensible handwriting, making it difficult for both the general public and some pharmacists to understand the medications they have prescribed. It is not ideal for them to write the prescription quietly and methodically because they will be dealing with dozens of patients every day and will be swamped with work.As a result, their handwriting is illegible. This may result in reports or prescriptions consisting of short forms and cursive writing that a typical person or pharmacist won't be able to read properly, which will cause prescribed medications to be misspelled. However, some individuals are accustomed to writing prescriptions in regional languages because we all live in an area with a diversity of regional languages. It makes analyzing the content much more challenging. So, in this project, we'll use a recognition system to build a tool that can translate the handwriting of physicians in any language. This system will be made into an application which is fully autonomous in functioning. As the user uploads the prescription image the program will pre-process the image by performing image pre-processing, and word segmentations initially before processing the image for training. And it will be done for every language we require the model to detect. And as of the deduction model will be made using deep learning techniques including CNN, RNN, and LSTM, which are utilized to train the model. To match words from various languages that will be written in the system, Unicode will be used. Furthermore, fuzzy search and market basket analysis are employed to offer an end result that will be optimized from the pharmaceutical database and displayed to the user as a structured output.

The development of large language models tailored for handling patients' clinical notes is often hindered by the limited accessibility and usability of these notes due to strict privacy regulations. To address these challenges, we first create synthetic large-scale clinical notes using publicly available case reports extracted from biomedical literature. We then use these synthetic notes to train our specialized clinical large language model, Asclepius. While Asclepius is trained on synthetic data, we assess its potential performance in real-world applications by evaluating it using real clinical notes. We benchmark Asclepius against several other large language models, including GPT-3.5-turbo and other open-source alternatives. To further validate our approach using synthetic notes, we also compare Asclepius with its variants trained on real clinical notes. Our findings convincingly demonstrate that synthetic clinical notes can serve as viable substitutes for real ones when constructing high-performing clinical language models. This conclusion is supported by detailed evaluations conducted by both GPT-4 and medical professionals. All resources including weights, codes, and data used in the development of Asclepius are made publicly accessible for future research.

We survey clinical document corpora, with focus on German textual data. Due to rigid data privacy legislation in Germany these resources, with only few exceptions, are stored in safe clinical data spaces and locked against clinic-external researchers. This situation stands in stark contrast with established workflows in the field of natural language processing where easy accessibility and reuse of data collections are common practice. Hence, alternative corpus designs have been examined to escape from this data poverty. Besides machine translation of English clinical datasets and the generation of synthetic corpora with fictitious clinical contents, several other types of domain proxies have come up as substitutes for authentic clinical documents. Common instances of close proxies are medical journal publications, clinical therapy guidelines, drug labels, etc., more distant proxies include online encyclopedic medical articles or medical contents from social media channels. After PRISM-conformant screening of 359 hits from four bibliographic systems, 75 relevant documents were finally selected for this review and 59 distinct corpora were determined. We identified 24 real clinical corpora (from 40 publications) out of which only 5 are publicly distributable. 2 translations of real corpora and 3 synthetic ones complement the set of clinical corpora. 14 corpora were categorized as close domain proxies, 16 as distant ones. There is a clear divide between the large number of non-accessible authentic clinical German-language corpora and their publicly accessible substitutes: translated or synthetic, close or more distant proxies. So on first sight, the data bottleneck seems broken. Intuitively yet, differences in genre-specific writing style, wording and medical domain expertise in this typological space are also obvious. This raises the question how valid alternative corpus designs really are.

Synthetic Data Generation (SDG) based on Artificial Intelligence (AI) can transform the way clinical medicine is delivered by overcoming privacy barriers that currently render clinical data sharing difficult. This is the key to accelerating the development of digital tools contributing to enhanced patient safety. Such tools include robust data-driven clinical decision support systems, and example-based digital training tools that will enable healthcare professionals to improve their diagnostic performance for enhanced patient safety. This study focuses on the clinical evaluation of medical SDG, with a proof-of-concept investigation on diagnosing Inflammatory Bowel Disease (IBD) using Wireless Capsule Endoscopy (WCE) images. Its scientific contributions include a) a novel protocol for the systematic Clinical Evaluation of Medical Image Synthesis (CEMIS); b) a novel variational autoencoder-based model for the generation of high-resolution synthetic WCE images; and c) a comprehensive evaluation of the synthetic images using the CEMIS protocol by 10 international WCE specialists, in terms of image quality, diversity, and realism, as well as their utility for clinical decision-making. The results show that TIDE-II generates clinically plausible, very realistic WCE images, of improved quality compared to relevant state-of-the-art generative models. Concludingly, CEMIS can serve as a reference for future research on medical image-generation techniques, while the adaptation/extension of the architecture of TIDE-II to other imaging domains can be promising.

Problem: Effective patient-centered communication is a core competency for physicians. However, both seasoned providers and medical trainees report decreased confidence in leading conversations on sensitive topics such as goals of care or end-of-life discussions. The significant administrative burden and the resources required to provide dedicated training in leading difficult conversations has been a long-standing problem in medical education. Approach: In this work, we present a novel educational tool designed to facilitate interactive, real-time simulations of difficult conversations in a video-based format through the use of multimodal generative artificial intelligence (AI). Leveraging recent advances in language modeling, computer vision, and generative audio, this tool creates realistic, interactive scenarios with avatars, or "synthetic patients." These synthetic patients interact with users throughout various stages of medical care using a custom-built video chat application, offering learners the chance to practice conversations with patients from diverse belief systems, personalities, and ethnic backgrounds. Outcomes: While the development of this platform demanded substantial upfront investment in labor, it offers a highly-realistic simulation experience with minimal financial investment. For medical trainees, this educational tool can be implemented within programs to simulate patient-provider conversations and can be incorporated into existing palliative care curriculum to provide a scalable, high-fidelity simulation environment for mastering difficult conversations. Next Steps: Future developments will explore enhancing the authenticity of these encounters by working with patients to incorporate their histories and personalities, as well as employing the use of AI-generated evaluations to offer immediate, constructive feedback to learners post-simulation.

Manual assignment of Anatomical Therapeutic Chemical (ATC) codes to prescription records is a significant bottleneck in healthcare research and operations at Ontario Health and InterRAI Canada, requiring extensive expert time and effort. To automate this process while maintaining data privacy, we develop a practical approach using locally deployable large language models (LLMs). Inspired by recent advances in automatic International Classification of Diseases (ICD) coding, our method frames ATC coding as a hierarchical information extraction task, guiding LLMs through the ATC ontology level by level. We evaluate our approach using GPT-4o as an accuracy ceiling and focus development on open-source Llama models suitable for privacy-sensitive deployment. Testing across Health Canada drug product data, the RABBITS benchmark, and real clinical notes from Ontario Health, our method achieves 78% exact match accuracy with GPT-4o and 60% with Llama 3.1 70B. We investigate knowledge grounding through drug definitions, finding modest improvements in accuracy. Further, we show that fine-tuned Llama 3.1 8B matches zero-shot Llama 3.1 70B accuracy, suggesting that effective ATC coding is feasible with smaller models. Our results demonstrate the feasibility of automatic ATC coding in privacy-sensitive healthcare environments, providing a foundation for future deployments.

Synthetic data generation offers a promising solution to enhance the usefulness of Electronic Healthcare Records (EHR) by generating realistic de-identified data. However, the existing literature primarily focuses on the quality of synthetic health data, neglecting the crucial aspect of fairness in downstream predictions. Consequently, models trained on synthetic EHR have faced criticism for producing biased outcomes in target tasks. These biases can arise from either spurious correlations between features or the failure of models to accurately represent sub-groups. To address these concerns, we present Bias-transforming Generative Adversarial Networks (Bt-GAN), a GAN-based synthetic data generator specifically designed for the healthcare domain. In order to tackle spurious correlations (i), we propose an information-constrained Data Generation Process that enables the generator to learn a fair deterministic transformation based on a well-defined notion of algorithmic fairness. To overcome the challenge of capturing exact sub-group representations (ii), we incentivize the generator to preserve sub-group densities through score-based weighted sampling. This approach compels the generator to learn from underrepresented regions of the data manifold. We conduct extensive experiments using the MIMIC-III database. Our results demonstrate that Bt-GAN achieves SOTA accuracy while significantly improving fairness and minimizing bias amplification. We also perform an in-depth explainability analysis to provide additional evidence supporting the validity of our study. In conclusion, our research introduces a novel and professional approach to addressing the limitations of synthetic data generation in the healthcare domain. By incorporating fairness considerations and leveraging advanced techniques such as GANs, we pave the way for more reliable and unbiased predictions in healthcare applications.

The digitization of medical records ushered in a new era of big data to clinical science, and with it the possibility that data could be shared, to multiply insights beyond what investigators could abstract from paper records. The need to share individual-level medical data to accelerate innovation in precision medicine continues to grow, and has never been more urgent, as scientists grapple with the COVID-19 pandemic. However, enthusiasm for the use of big data has been tempered by a fully appropriate concern for patient autonomy and privacy. That is, the ability to extract private or confidential information about an individual, in practice, renders it difficult to share data, since significant infrastructure and data governance must be established before data can be shared. Although HIPAA provided de-identification as an approved mechanism for data sharing, linkage attacks were identified as a major vulnerability. A variety of mechanisms have been established to avoid leaking private information, such as field suppression or abstraction, strictly limiting the amount of information that can be shared, or employing mathematical techniques such as differential privacy. Another approach, which we focus on here, is creating synthetic data that mimics the underlying data. For synthetic data to be a useful mechanism in support of medical innovation and a proxy for real-world evidence, one must demonstrate two properties of the synthetic dataset: (1) any analysis on the real data must be matched by analysis of the synthetic data (statistical fidelity) and (2) the synthetic data must preserve privacy, with minimal risk of re-identification (privacy guarantee). In this paper we propose a framework for quantifying the statistical fidelity and privacy preservation properties of synthetic datasets and demonstrate these metrics for synthetic data generated by Syntegra technology.

The widespread adoption of electronic health records and digital healthcare data has created a demand for data-driven insights to enhance patient outcomes, diagnostics, and treatments. However, using real patient data presents privacy and regulatory challenges, including compliance with HIPAA and GDPR. Synthetic data generation, using generative AI models like GANs and VAEs offers a promising solution to balance valuable data access and patient privacy protection. In this paper, we examine generative AI models for creating realistic, anonymized patient data for research and training, explore synthetic data applications in healthcare, and discuss its benefits, challenges, and future research directions. Synthetic data has the potential to revolutionize healthcare by providing anonymized patient data while preserving privacy and enabling versatile applications.

Background: Electronic Health Records hold detailed longitudinal information about each patient's health status and general clinical history, a large portion of which is stored within the unstructured text. Existing approaches focus mostly on structured data and a subset of single-domain outcomes. We explore how temporal modelling of patients from free text and structured data, using deep generative transformers can be used to forecast a wide range of future disorders, substances, procedures or findings. Methods: We present Foresight, a novel transformer-based pipeline that uses named entity recognition and linking tools to convert document text into structured, coded concepts, followed by providing probabilistic forecasts for future medical events such as disorders, substances, procedures and findings. We processed the entire free-text portion from three different hospital datasets totalling 811336 patients covering both physical and mental health. Findings: On tests in two UK hospitals (King's College Hospital, South London and Maudsley) and the US MIMIC-III dataset precision@10 0.68, 0.76 and 0.88 was achieved for forecasting the next disorder in a patient timeline, while precision@10 of 0.80, 0.81 and 0.91 was achieved for forecasting the next biomedical concept. Foresight was also validated on 34 synthetic patient timelines by five clinicians and achieved relevancy of 97% for the top forecasted candidate disorder. As a generative model, it can forecast follow-on biomedical concepts for as many steps as required. Interpretation: Foresight is a general-purpose model for biomedical concept modelling that can be used for real-world risk forecasting, virtual trials and clinical research to study the progression of disorders, simulate interventions and counterfactuals, and educational purposes.

In recent years, the machine learning research community has benefited tremendously from the availability of openly accessible benchmark datasets. Clinical data are usually not openly available due to their highly confidential nature. This has hampered the development of reproducible and generalisable machine learning applications in health care. Here we introduce the Health Gym - a growing collection of highly realistic synthetic medical datasets that can be freely accessed to prototype, evaluate, and compare machine learning algorithms, with a specific focus on reinforcement learning. The three synthetic datasets described in this paper present patient cohorts with acute hypotension and sepsis in the intensive care unit, and people with human immunodeficiency virus (HIV) receiving antiretroviral therapy in ambulatory care. The datasets were created using a novel generative adversarial network (GAN). The distributions of variables, and correlations between variables and trends over time in the synthetic datasets mirror those in the real datasets. Furthermore, the risk of sensitive information disclosure associated with the public distribution of the synthetic datasets is estimated to be very low.

Medical conversational AI (AI) plays a pivotal role in the development of safer and more effective medical dialogue systems. However, existing benchmarks and evaluation frameworks for assessing the information-gathering and diagnostic reasoning abilities of medical large language models (LLMs) have not been rigorously evaluated. To address these gaps, we present MedDialogRubrics, a novel benchmark comprising 5,200 synthetically constructed patient cases and over 60,000 fine-grained evaluation rubrics generated by LLMs and subsequently refined by clinical experts, specifically designed to assess the multi-turn diagnostic capabilities of LLM. Our framework employs a multi-agent system to synthesize realistic patient records and chief complaints from underlying disease knowledge without accessing real-world electronic health records, thereby mitigating privacy and data-governance concerns. We design a robust Patient Agent that is limited to a set of atomic medical facts and augmented with a dynamic guidance mechanism that continuously detects and corrects hallucinations throughout the dialogue, ensuring internal coherence and clinical plausibility of the simulated cases. Furthermore, we propose a structured LLM-based and expert-annotated rubric-generation pipeline that retrieves Evidence-Based Medicine (EBM) guidelines and utilizes the reject sampling to derive a prioritized set of rubric items ("must-ask" items) for each case. We perform a comprehensive evaluation of state-of-the-art models and demonstrate that, across multiple assessment dimensions, current models face substantial challenges. Our results indicate that improving medical dialogue will require advances in dialogue management architectures, not just incremental tuning of the base-model.

Medical imaging is essential in modern radiotherapy, supporting diagnosis, treatment planning, and monitoring. Synthetic imaging, particularly synthetic computed tomography (sCT), is gaining traction in radiotherapy. The SynthRAD2025 dataset and Grand Challenge promote advancements in sCT generation by providing a benchmarking platform for algorithms using cone-beam CT (CBCT) and magnetic resonance imaging (MRI). The dataset includes 2362 cases: 890 MRI-CT and 1472 CBCT-CT pairs from head-and-neck, thoracic, and abdominal cancer patients treated at five European university medical centers (UMC Groningen, UMC Utrecht, Radboud UMC, LMU University Hospital Munich, and University Hospital of Cologne). Data were acquired with diverse scanners and protocols. Pre-processing, including rigid and deformable image registration, ensures high-quality, modality-aligned images. Extensive quality assurance validates image consistency and usability. All imaging data is provided in MetaImage (.mha) format, ensuring compatibility with medical image processing tools. Metadata, including acquisition parameters and registration details, is available in structured CSV files. To maintain dataset integrity, SynthRAD2025 is divided into training (65%), validation (10%), and test (25%) sets. The dataset is accessible at https://doi.org/10.5281/zenodo.14918089 under the SynthRAD2025 collection. This dataset supports benchmarking and the development of synthetic imaging techniques for radiotherapy applications. Use cases include sCT generation for MRI-only and MR-guided photon/proton therapy, CBCT-based dose calculations, and adaptive radiotherapy workflows. By integrating diverse acquisition settings, SynthRAD2025 fosters robust, generalizable image synthesis algorithms, advancing personalized cancer care and adaptive radiotherapy.

Deep learning algorithms require extensive data to achieve robust performance. However, data availability is often restricted in the medical domain due to patient privacy concerns. Synthetic data presents a possible solution to these challenges. Recently, image generative models have found increasing use for medical applications but are often designed for singular medical specialties and imaging modalities, thus limiting their broader utility. To address this, we introduce MediSyn: a text-guided, latent diffusion model capable of generating synthetic images from 6 medical specialties and 10 image types. The synthetic images are validated by expert clinicians for alignment with their corresponding text prompts. Furthermore, a direct comparison of the synthetic images against the real images confirms that our model synthesizes novel images and, crucially, may preserve patient privacy. Finally, classifiers trained on a mixture of synthetic and real data achieve similar performance to those trained on twice the amount of real data. Our findings highlight the immense potential for generalist image generative models to accelerate algorithmic research and development in medicine.

Adverse Drug Reactions (ADRs) from psychiatric medications are the leading cause of hospitalizations among mental health patients. With healthcare systems and online communities facing limitations in resolving ADR-related issues, Large Language Models (LLMs) have the potential to fill this gap. Despite the increasing capabilities of LLMs, past research has not explored their capabilities in detecting ADRs related to psychiatric medications or in providing effective harm reduction strategies. To address this, we introduce the Psych-ADR benchmark and the Adverse Drug Reaction Response Assessment (ADRA) framework to systematically evaluate LLM performance in detecting ADR expressions and delivering expert-aligned mitigation strategies. Our analyses show that LLMs struggle with understanding the nuances of ADRs and differentiating between types of ADRs. While LLMs align with experts in terms of expressed emotions and tone of the text, their responses are more complex, harder to read, and only 70.86% aligned with expert strategies. Furthermore, they provide less actionable advice by a margin of 12.32% on average. Our work provides a comprehensive benchmark and evaluation framework for assessing LLMs in strategy-driven tasks within high-risk domains.

Clinical predictive models often rely on patients' electronic health records (EHR), but integrating medical knowledge to enhance predictions and decision-making is challenging. This is because personalized predictions require personalized knowledge graphs (KGs), which are difficult to generate from patient EHR data. To address this, we propose GraphCare, an open-world framework that uses external KGs to improve EHR-based predictions. Our method extracts knowledge from large language models (LLMs) and external biomedical KGs to build patient-specific KGs, which are then used to train our proposed Bi-attention AugmenTed (BAT) graph neural network (GNN) for healthcare predictions. On two public datasets, MIMIC-III and MIMIC-IV, GraphCare surpasses baselines in four vital healthcare prediction tasks: mortality, readmission, length of stay (LOS), and drug recommendation. On MIMIC-III, it boosts AUROC by 17.6\% and 6.6\% for mortality and readmission, and F1-score by 7.9\% and 10.8\% for LOS and drug recommendation, respectively. Notably, GraphCare demonstrates a substantial edge in scenarios with limited data availability. Our findings highlight the potential of using external KGs in healthcare prediction tasks and demonstrate the promise of GraphCare in generating personalized KGs for promoting personalized medicine.

With the advent of Large Language Models (LLMs), medical artificial intelligence (AI) has experienced substantial technological progress and paradigm shifts, highlighting the potential of LLMs to streamline healthcare delivery and improve patient outcomes. Considering this rapid technical progress, in this survey, we trace the recent advances of Medical Large Language Models (Med-LLMs), including the background, key findings, and mainstream techniques, especially for the evolution from general-purpose models to medical-specialized applications. Firstly, we delve into the foundational technology of Med-LLMs, indicating how general models can be progressively adapted and refined for the complicated medical tasks. Secondly, the wide-ranging applications of Med-LLMs are investigated across various healthcare domains, as well as an up-to-date review of existing Med-LLMs. The transformative impact of these models on daily medical practice is evident through their ability to assist clinicians, educators, and patients. Recognizing the importance of responsible innovation, we discuss the challenges associated with ensuring fairness, accountability, privacy, and robustness. Ethical considerations, rigorous evaluation methodologies, and the establishment of regulatory frameworks are crucial for building trustworthiness in the real-world system. We emphasize the need for ongoing scrutiny and development to maintain high standards of safety and reliability. Finally, we anticipate possible future trajectories for Med-LLMs, identifying key avenues for prudent expansion. By consolidating these insights, our review aims to provide professionals and researchers with a thorough understanding of the strengths and limitations of Med-LLMs, fostering a balanced and ethical approach to their integration into the healthcare ecosystem.

Synthetic data generation is an important application of machine learning in the field of medical imaging. While existing approaches have successfully applied fine-tuned diffusion models for synthesizing medical images, we explore potential improvements to this pipeline through feature-aligned diffusion. Our approach aligns intermediate features of the diffusion model to the output features of an expert, and our preliminary findings show an improvement of 9% in generation accuracy and ~0.12 in SSIM diversity. Our approach is also synergistic with existing methods, and easily integrated into diffusion training pipelines for improvements. We make our code available at https://github.com/lnairGT/Feature-Aligned-Diffusion.

State-of-the-art information extraction methods are limited by OCR errors. They work well for printed text in form-like documents, but unstructured, handwritten documents still remain a challenge. Adapting existing models to domain-specific training data is quite expensive, because of two factors, 1) limited availability of the domain-specific documents (such as handwritten prescriptions, lab notes, etc.), and 2) annotations become even more challenging as one needs domain-specific knowledge to decode inscrutable handwritten document images. In this work, we focus on the complex problem of extracting medicine names from handwritten prescriptions using only weakly labeled data. The data consists of images along with the list of medicine names in it, but not their location in the image. We solve the problem by first identifying the regions of interest, i.e., medicine lines from just weak labels and then injecting a domain-specific medicine language model learned using only synthetically generated data. Compared to off-the-shelf state-of-the-art methods, our approach performs >2.5x better in medicine names extraction from prescriptions.

Social determinants of health (SDoH) have an important impact on patient outcomes but are incompletely collected from the electronic health records (EHR). This study researched the ability of large language models to extract SDoH from free text in EHRs, where they are most commonly documented, and explored the role of synthetic clinical text for improving the extraction of these scarcely documented, yet extremely valuable, clinical data. 800 patient notes were annotated for SDoH categories, and several transformer-based models were evaluated. The study also experimented with synthetic data generation and assessed for algorithmic bias. Our best-performing models were fine-tuned Flan-T5 XL (macro-F1 0.71) for any SDoH, and Flan-T5 XXL (macro-F1 0.70). The benefit of augmenting fine-tuning with synthetic data varied across model architecture and size, with smaller Flan-T5 models (base and large) showing the greatest improvements in performance (delta F1 +0.12 to +0.23). Model performance was similar on the in-hospital system dataset but worse on the MIMIC-III dataset. Our best-performing fine-tuned models outperformed zero- and few-shot performance of ChatGPT-family models for both tasks. These fine-tuned models were less likely than ChatGPT to change their prediction when race/ethnicity and gender descriptors were added to the text, suggesting less algorithmic bias (p<0.05). At the patient-level, our models identified 93.8% of patients with adverse SDoH, while ICD-10 codes captured 2.0%. Our method can effectively extracted SDoH information from clinic notes, performing better compare to GPT zero- and few-shot settings. These models could enhance real-world evidence on SDoH and aid in identifying patients needing social support.

To generate evidence regarding the safety and efficacy of artificial intelligence (AI) enabled medical devices, AI models need to be evaluated on a diverse population of patient cases, some of which may not be readily available. We propose an evaluation approach for testing medical imaging AI models that relies on in silico imaging pipelines in which stochastic digital models of human anatomy (in object space) with and without pathology are imaged using a digital replica imaging acquisition system to generate realistic synthetic image datasets. Here, we release M-SYNTH, a dataset of cohorts with four breast fibroglandular density distributions imaged at different exposure levels using Monte Carlo x-ray simulations with the publicly available Virtual Imaging Clinical Trial for Regulatory Evaluation (VICTRE) toolkit. We utilize the synthetic dataset to analyze AI model performance and find that model performance decreases with increasing breast density and increases with higher mass density, as expected. As exposure levels decrease, AI model performance drops with the highest performance achieved at exposure levels lower than the nominal recommended dose for the breast type.

Synthetic medical data generation has opened up new possibilities in the healthcare domain, offering a powerful tool for simulating clinical scenarios, enhancing diagnostic and treatment quality, gaining granular medical knowledge, and accelerating the development of unbiased algorithms. In this context, we present a novel approach called ViewXGen, designed to overcome the limitations of existing methods that rely on general domain pipelines using only radiology reports to generate frontal-view chest X-rays. Our approach takes into consideration the diverse view positions found in the dataset, enabling the generation of chest X-rays with specific views, which marks a significant advancement in the field. To achieve this, we introduce a set of specially designed tokens for each view position, tailoring the generation process to the user's preferences. Furthermore, we leverage multi-view chest X-rays as input, incorporating valuable information from different views within the same study. This integration rectifies potential errors and contributes to faithfully capturing abnormal findings in chest X-ray generation. To validate the effectiveness of our approach, we conducted statistical analyses, evaluating its performance in a clinical efficacy metric on the MIMIC-CXR dataset. Also, human evaluation demonstrates the remarkable capabilities of ViewXGen, particularly in producing realistic view-specific X-rays that closely resemble the original images.

Identifying prescription medications is a frequent task for patients and medical professionals; however, this is an error-prone task as many pills have similar appearances (e.g. white round pills), which increases the risk of medication errors. In this paper, we introduce ePillID, the largest public benchmark on pill image recognition, composed of 13k images representing 9804 appearance classes (two sides for 4902 pill types). For most of the appearance classes, there exists only one reference image, making it a challenging low-shot recognition setting. We present our experimental setup and evaluation results of various baseline models on the benchmark. The best baseline using a multi-head metric-learning approach with bilinear features performed remarkably well; however, our error analysis suggests that they still fail to distinguish particularly confusing classes. The code and data are available at https://github.com/usuyama/ePillID-benchmark.

In the era of Large Language Models (LLMs), given their remarkable text understanding and generation abilities, there is an unprecedented opportunity to develop new, LLM-based methods for trustworthy medical knowledge synthesis, extraction and summarization. This paper focuses on the problem of Pharmacovigilance (PhV), where the significance and challenges lie in identifying Adverse Drug Events (ADEs) from diverse text sources, such as medical literature, clinical notes, and drug labels. Unfortunately, this task is hindered by factors including variations in the terminologies of drugs and outcomes, and ADE descriptions often being buried in large amounts of narrative text. We present MALADE, the first effective collaborative multi-agent system powered by LLM with Retrieval Augmented Generation for ADE extraction from drug label data. This technique involves augmenting a query to an LLM with relevant information extracted from text resources, and instructing the LLM to compose a response consistent with the augmented data. MALADE is a general LLM-agnostic architecture, and its unique capabilities are: (1) leveraging a variety of external sources, such as medical literature, drug labels, and FDA tools (e.g., OpenFDA drug information API), (2) extracting drug-outcome association in a structured format along with the strength of the association, and (3) providing explanations for established associations. Instantiated with GPT-4 Turbo or GPT-4o, and FDA drug label data, MALADE demonstrates its efficacy with an Area Under ROC Curve of 0.90 against the OMOP Ground Truth table of ADEs. Our implementation leverages the Langroid multi-agent LLM framework and can be found at https://github.com/jihyechoi77/malade.

Chest X-rays (CXR) are the most common medical imaging study and are used to diagnose multiple medical conditions. This study examines the impact of synthetic data supplementation, using diffusion models, on the performance of deep learning (DL) classifiers for CXR analysis. We employed three datasets: CheXpert, MIMIC-CXR, and Emory Chest X-ray, training conditional denoising diffusion probabilistic models (DDPMs) to generate synthetic frontal radiographs. Our approach ensured that synthetic images mirrored the demographic and pathological traits of the original data. Evaluating the classifiers' performance on internal and external datasets revealed that synthetic data supplementation enhances model accuracy, particularly in detecting less prevalent pathologies. Furthermore, models trained on synthetic data alone approached the performance of those trained on real data. This suggests that synthetic data can potentially compensate for real data shortages in training robust DL models. However, despite promising outcomes, the superiority of real data persists.

Simulating high-fidelity patients offers a powerful avenue for studying complex diseases while addressing the challenges of fragmented, biased, and privacy-restricted real-world data. In this study, we introduce SynthAgent, a novel Multi-Agent System (MAS) framework designed to model obesity patients with comorbid mental disorders, including depression, anxiety, social phobia, and binge eating disorder. SynthAgent integrates clinical and medical evidence from claims data, population surveys, and patient-centered literature to construct personalized virtual patients enriched with personality traits that influence adherence, emotion regulation, and lifestyle behaviors. Through autonomous agent interactions, the system simulates disease progression, treatment response, and life management across diverse psychosocial contexts. Evaluation of more than 100 generated patients demonstrated that GPT-5 and Claude 4.5 Sonnet achieved the highest fidelity as the core engine in the proposed MAS framework, outperforming Gemini 2.5 Pro and DeepSeek-R1. SynthAgent thus provides a scalable and privacy-preserving framework for exploring patient journeys, behavioral dynamics, and decision-making processes in both medical and psychological domains.

Despite their ability to understand chemical knowledge, large language models (LLMs) remain limited in their capacity to propose novel molecules with desired functions (e.g., drug-like properties). In addition, the molecules that LLMs propose can often be challenging to make, and are almost never compatible with automated synthesis approaches. To better enable the discovery of functional small molecules, LLMs need to learn a new molecular language that is more effective in predicting properties and inherently synced with automated synthesis technology. Current molecule LLMs are limited by representing molecules based on atoms. In this paper, we argue that just like tokenizing texts into meaning-bearing (sub-)word tokens instead of characters, molecules should be tokenized at the level of functional building blocks, i.e., parts of molecules that bring unique functions and serve as effective building blocks for real-world automated laboratory synthesis. This motivates us to propose mCLM, a modular Chemical-Language Model that comprises a bilingual language model that understands both natural language descriptions of functions and molecular blocks. mCLM front-loads synthesizability considerations while improving the predicted functions of molecules in a principled manner. mCLM, with only 3B parameters, achieves improvements in synthetic accessibility relative to 7 other leading generative AI methods including GPT-5. When tested on 122 out-of-distribution medicines using only building blocks/tokens that are compatible with automated modular synthesis, mCLM outperforms all baselines in property scores and synthetic accessibility. mCLM can also reason on multiple functions and iteratively self-improve to rescue drug candidates that failed late in clinical trials ("fallen angels").

Artificial Intelligence (AI) advancement is heavily dependent on access to large-scale, high-quality training data. However, in specialized domains such as healthcare, data acquisition faces significant constraints due to privacy regulations, ethical considerations, and limited availability. While synthetic data generation offers a promising solution, conventional approaches typically require substantial real data for training generative models. The emergence of large-scale prompt-based models presents new opportunities for synthetic data generation without direct access to protected data. However, crafting effective prompts for domain-specific data generation remains challenging, and manual prompt engineering proves insufficient for achieving output with sufficient precision and authenticity. We review recent developments in automatic prompt optimization, following PRISMA guidelines. We analyze six peer-reviewed studies published between 2020 and 2024 that focus on automatic data-free prompt optimization methods. Our analysis reveals three approaches: feedback-driven, error-based, and control-theoretic. Although all approaches demonstrate promising capabilities in prompt refinement and adaptation, our findings suggest the need for an integrated framework that combines complementary optimization techniques to enhance synthetic data generation while minimizing manual intervention. We propose future research directions toward developing robust, iterative prompt optimization frameworks capable of improving the quality of synthetic data. This advancement can be particularly crucial for sensitive fields and in specialized domains where data access is restricted, potentially transforming how we approach synthetic data generation for AI development.

User-generated data sources have gained significance in uncovering Adverse Drug Reactions (ADRs), with an increasing number of discussions occurring in the digital world. However, the existing clinical corpora predominantly revolve around scientific articles in English. This work presents a multilingual corpus of texts concerning ADRs gathered from diverse sources, including patient fora, social media, and clinical reports in German, French, and Japanese. Our corpus contains annotations covering 12 entity types, four attribute types, and 13 relation types. It contributes to the development of real-world multilingual language models for healthcare. We provide statistics to highlight certain challenges associated with the corpus and conduct preliminary experiments resulting in strong baselines for extracting entities and relations between these entities, both within and across languages.

Traditional Chinese Medicine (TCM) has seen increasing adoption in healthcare, with specialized Large Language Models (LLMs) emerging to support clinical applications. A fundamental requirement for these models is accurate identification of TCM drug ingredients. In this paper, we evaluate how general and TCM-specialized LLMs perform when identifying ingredients of Chinese drugs. Our systematic analysis reveals consistent failure patterns: models often interpret drug names literally, overuse common herbs regardless of relevance, and exhibit erratic behaviors when faced with unfamiliar formulations. LLMs also fail to understand the verification task. These findings demonstrate that current LLMs rely primarily on drug names rather than possessing systematic pharmacological knowledge. To address these limitations, we propose a Retrieval Augmented Generation (RAG) approach focused on ingredient names. Experiments across 220 TCM formulations show our method significantly improves accuracy from approximately 50% to 82% in ingredient verification tasks. Our work highlights critical weaknesses in current TCM-specific LLMs and offers a practical solution for enhancing their clinical reliability.

In this paper, we introduce a simulacrum of hospital called Agent Hospital that simulates the entire process of treating illness. All patients, nurses, and doctors are autonomous agents powered by large language models (LLMs). Our central goal is to enable a doctor agent to learn how to treat illness within the simulacrum. To do so, we propose a method called MedAgent-Zero. As the simulacrum can simulate disease onset and progression based on knowledge bases and LLMs, doctor agents can keep accumulating experience from both successful and unsuccessful cases. Simulation experiments show that the treatment performance of doctor agents consistently improves on various tasks. More interestingly, the knowledge the doctor agents have acquired in Agent Hospital is applicable to real-world medicare benchmarks. After treating around ten thousand patients (real-world doctors may take over two years), the evolved doctor agent achieves a state-of-the-art accuracy of 93.06% on a subset of the MedQA dataset that covers major respiratory diseases. This work paves the way for advancing the applications of LLM-powered agent techniques in medical scenarios.

Precision therapeutics require multimodal adaptive models that generate personalized treatment recommendations. We introduce TxAgent, an AI agent that leverages multi-step reasoning and real-time biomedical knowledge retrieval across a toolbox of 211 tools to analyze drug interactions, contraindications, and patient-specific treatment strategies. TxAgent evaluates how drugs interact at molecular, pharmacokinetic, and clinical levels, identifies contraindications based on patient comorbidities and concurrent medications, and tailors treatment strategies to individual patient characteristics. It retrieves and synthesizes evidence from multiple biomedical sources, assesses interactions between drugs and patient conditions, and refines treatment recommendations through iterative reasoning. It selects tools based on task objectives and executes structured function calls to solve therapeutic tasks that require clinical reasoning and cross-source validation. The ToolUniverse consolidates 211 tools from trusted sources, including all US FDA-approved drugs since 1939 and validated clinical insights from Open Targets. TxAgent outperforms leading LLMs, tool-use models, and reasoning agents across five new benchmarks: DrugPC, BrandPC, GenericPC, TreatmentPC, and DescriptionPC, covering 3,168 drug reasoning tasks and 456 personalized treatment scenarios. It achieves 92.1% accuracy in open-ended drug reasoning tasks, surpassing GPT-4o and outperforming DeepSeek-R1 (671B) in structured multi-step reasoning. TxAgent generalizes across drug name variants and descriptions. By integrating multi-step inference, real-time knowledge grounding, and tool-assisted decision-making, TxAgent ensures that treatment recommendations align with established clinical guidelines and real-world evidence, reducing the risk of adverse events and improving therapeutic decision-making.

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.

Foundation Models that are capable of processing and generating multi-modal data have transformed AI's role in medicine. However, a key limitation of their reliability is hallucination, where inaccurate or fabricated information can impact clinical decisions and patient safety. We define medical hallucination as any instance in which a model generates misleading medical content. This paper examines the unique characteristics, causes, and implications of medical hallucinations, with a particular focus on how these errors manifest themselves in real-world clinical scenarios. Our contributions include (1) a taxonomy for understanding and addressing medical hallucinations, (2) benchmarking models using medical hallucination dataset and physician-annotated LLM responses to real medical cases, providing direct insight into the clinical impact of hallucinations, and (3) a multi-national clinician survey on their experiences with medical hallucinations. Our results reveal that inference techniques such as Chain-of-Thought (CoT) and Search Augmented Generation can effectively reduce hallucination rates. However, despite these improvements, non-trivial levels of hallucination persist. These findings underscore the ethical and practical imperative for robust detection and mitigation strategies, establishing a foundation for regulatory policies that prioritize patient safety and maintain clinical integrity as AI becomes more integrated into healthcare. The feedback from clinicians highlights the urgent need for not only technical advances but also for clearer ethical and regulatory guidelines to ensure patient safety. A repository organizing the paper resources, summaries, and additional information is available at https://github.com/mitmedialab/medical hallucination.

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 https://github.com/ritaranx/ClinGen.

Doctor-patient consultations require multi-turn, context-aware communication tailored to diverse patient personas. Training or evaluating doctor LLMs in such settings requires realistic patient interaction systems. However, existing simulators often fail to reflect the full range of personas seen in clinical practice. To address this, we introduce PatientSim, a patient simulator that generates realistic and diverse patient personas for clinical scenarios, grounded in medical expertise. PatientSim operates using: 1) clinical profiles, including symptoms and medical history, derived from real-world data in the MIMIC-ED and MIMIC-IV datasets, and 2) personas defined by four axes: personality, language proficiency, medical history recall level, and cognitive confusion level, resulting in 37 unique combinations. We evaluated eight LLMs for factual accuracy and persona consistency. The top-performing open-source model, Llama 3.3, was validated by four clinicians to confirm the robustness of our framework. As an open-source, customizable platform, PatientSim provides a reproducible and scalable solution that can be customized for specific training needs. Offering a privacy-compliant environment, it serves as a robust testbed for evaluating medical dialogue systems across diverse patient presentations and shows promise as an educational tool for healthcare.

Large language models (LLMs) have revolutionized Natural Language Processing (NLP) by minimizing the need for complex feature engineering. However, the application of LLMs in specialized domains like biopharmaceuticals and chemistry remains largely unexplored. These fields are characterized by intricate terminologies, specialized knowledge, and a high demand for precision areas where general purpose LLMs often fall short. In this study, we introduce PharmaGPT, a suite of domain specilized LLMs with 13 billion and 70 billion parameters, specifically trained on a comprehensive corpus tailored to the Bio-Pharmaceutical and Chemical domains. Our evaluation shows that PharmaGPT surpasses existing general models on specific-domain benchmarks such as NAPLEX, demonstrating its exceptional capability in domain-specific tasks. Remarkably, this performance is achieved with a model that has only a fraction, sometimes just one-tenth-of the parameters of general-purpose large models. This advancement establishes a new benchmark for LLMs in the bio-pharmaceutical and chemical fields, addressing the existing gap in specialized language modeling. It also suggests a promising path for enhanced research and development, paving the way for more precise and effective NLP applications in these areas.

Drug-side effect research is vital for understanding adverse reactions arising in complex multi-drug therapies. However, the scarcity of higher-order datasets that capture the combinatorial effects of multiple drugs severely limits progress in this field. Existing resources such as TWOSIDES primarily focus on pairwise interactions. To fill this critical gap, we introduce HODDI, the first Higher-Order Drug-Drug Interaction Dataset, constructed from U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) records spanning the past decade, to advance computational pharmacovigilance. HODDI contains 109,744 records involving 2,506 unique drugs and 4,569 unique side effects, specifically curated to capture multi-drug interactions and their collective impact on adverse effects. Comprehensive statistical analyses demonstrate HODDI's extensive coverage and robust analytical metrics, making it a valuable resource for studying higher-order drug relationships. Evaluating HODDI with multiple models, we found that simple Multi-Layer Perceptron (MLP) can outperform graph models, while hypergraph models demonstrate superior performance in capturing complex multi-drug interactions, further validating HODDI's effectiveness. Our findings highlight the inherent value of higher-order information in drug-side effect prediction and position HODDI as a benchmark dataset for advancing research in pharmacovigilance, drug safety, and personalized medicine. The dataset and codes are available at https://github.com/TIML-Group/HODDI.

Medical coding is the task of assigning medical codes to clinical free-text documentation. Healthcare professionals manually assign such codes to track patient diagnoses and treatments. Automated medical coding can considerably alleviate this administrative burden. In this paper, we reproduce, compare, and analyze state-of-the-art automated medical coding machine learning models. We show that several models underperform due to weak configurations, poorly sampled train-test splits, and insufficient evaluation. In previous work, the macro F1 score has been calculated sub-optimally, and our correction doubles it. We contribute a revised model comparison using stratified sampling and identical experimental setups, including hyperparameters and decision boundary tuning. We analyze prediction errors to validate and falsify assumptions of previous works. The analysis confirms that all models struggle with rare codes, while long documents only have a negligible impact. Finally, we present the first comprehensive results on the newly released MIMIC-IV dataset using the reproduced models. We release our code, model parameters, and new MIMIC-III and MIMIC-IV training and evaluation pipelines to accommodate fair future comparisons.

Recent developments in Large Language Model (LLM)-based agents have shown impressive capabilities spanning multiple domains, exemplified by deep research systems that demonstrate superior performance on complex information-seeking and synthesis tasks. While general-purpose deep research agents have shown impressive capabilities, they struggle significantly with medical domain challenges, as evidenced by leading proprietary systems achieving limited accuracy on complex medical benchmarks. The key limitations are: (1) the model lacks sufficient dense medical knowledge for clinical reasoning, and (2) the framework is constrained by the absence of specialized retrieval tools tailored for medical contexts.We present a medical deep research agent that addresses these challenges through two core innovations. First, we develop a novel data synthesis framework using medical knowledge graphs, extracting the longest chains from subgraphs around rare medical entities to generate complex multi-hop question-answer pairs. Second, we integrate a custom-built private medical retrieval engine alongside general-purpose tools, enabling accurate medical information synthesis. Our approach generates 2100+ diverse trajectories across 12 medical specialties, each averaging 4.2 tool interactions.Through a two-stage training paradigm combining supervised fine-tuning and online reinforcement learning with composite rewards, our MedResearcher-R1-32B model demonstrates exceptional performance, establishing new state-of-the-art results on medical benchmarks while maintaining competitive performance on general deep research tasks. Our work demonstrates that strategic domain-specific innovations in architecture, tool design, and training data construction can enable smaller open-source models to outperform much larger proprietary systems in specialized domains.

While hundreds of artificial intelligence (AI) algorithms are now approved or cleared by the US Food and Drugs Administration (FDA), many studies have shown inconsistent generalization or latent bias, particularly for underrepresented populations. Some have proposed that generative AI could reduce the need for real data, but its utility in model development remains unclear. Skin disease serves as a useful case study in synthetic image generation due to the diversity of disease appearance, particularly across the protected attribute of skin tone. Here we show that latent diffusion models can scalably generate images of skin disease and that augmenting model training with these data improves performance in data-limited settings. These performance gains saturate at synthetic-to-real image ratios above 10:1 and are substantially smaller than the gains obtained from adding real images. As part of our analysis, we generate and analyze a new dataset of 458,920 synthetic images produced using several generation strategies. Our results suggest that synthetic data could serve as a force-multiplier for model development, but the collection of diverse real-world data remains the most important step to improve medical AI algorithms.

In this work, we introduce MedAgentSim, an open-source simulated clinical environment with doctor, patient, and measurement agents designed to evaluate and enhance LLM performance in dynamic diagnostic settings. Unlike prior approaches, our framework requires doctor agents to actively engage with patients through multi-turn conversations, requesting relevant medical examinations (e.g., temperature, blood pressure, ECG) and imaging results (e.g., MRI, X-ray) from a measurement agent to mimic the real-world diagnostic process. Additionally, we incorporate self improvement mechanisms that allow models to iteratively refine their diagnostic strategies. We enhance LLM performance in our simulated setting by integrating multi-agent discussions, chain-of-thought reasoning, and experience-based knowledge retrieval, facilitating progressive learning as doctor agents interact with more patients. We also introduce an evaluation benchmark for assessing the LLM's ability to engage in dynamic, context-aware diagnostic interactions. While MedAgentSim is fully automated, it also supports a user-controlled mode, enabling human interaction with either the doctor or patient agent. Comprehensive evaluations in various simulated diagnostic scenarios demonstrate the effectiveness of our approach. Our code, simulation tool, and benchmark are available at https://medagentsim.netlify.app/.

Access to Kurdish medicine brochures is limited, depriving Kurdish-speaking communities of critical health information. To address this problem, we developed a specialized Machine Translation (MT) model to translate English medicine brochures into Sorani Kurdish using a parallel corpus of 22,940 aligned sentence pairs from 319 brochures, sourced from two pharmaceutical companies in the Kurdistan Region of Iraq (KRI). We trained a Statistical Machine Translation (SMT) model using the Moses toolkit, conducting seven experiments that resulted in BLEU scores ranging from 22.65 to 48.93. We translated three new brochures to improve the evaluation process and encountered unknown words. We addressed unknown words through post-processing with a medical dictionary, resulting in BLEU scores of 56.87, 31.05, and 40.01. Human evaluation by native Kurdish-speaking pharmacists, physicians, and medicine users showed that 50% of professionals found the translations consistent, while 83.3% rated them accurate. Among users, 66.7% considered the translations clear and felt confident using the medications.

Deep neural networks have brought remarkable breakthroughs in medical image analysis. However, due to their data-hungry nature, the modest dataset sizes in medical imaging projects might be hindering their full potential. Generating synthetic data provides a promising alternative, allowing to complement training datasets and conducting medical image research at a larger scale. Diffusion models recently have caught the attention of the computer vision community by producing photorealistic synthetic images. In this study, we explore using Latent Diffusion Models to generate synthetic images from high-resolution 3D brain images. We used T1w MRI images from the UK Biobank dataset (N=31,740) to train our models to learn about the probabilistic distribution of brain images, conditioned on covariables, such as age, sex, and brain structure volumes. We found that our models created realistic data, and we could use the conditioning variables to control the data generation effectively. Besides that, we created a synthetic dataset with 100,000 brain images and made it openly available to the scientific community.

Recent advances in video generation have shown remarkable progress in open-domain settings, yet medical video generation remains largely underexplored. Medical videos are critical for applications such as clinical training, education, and simulation, requiring not only high visual fidelity but also strict medical accuracy. However, current models often produce unrealistic or erroneous content when applied to medical prompts, largely due to the lack of large-scale, high-quality datasets tailored to the medical domain. To address this gap, we introduce MedVideoCap-55K, the first large-scale, diverse, and caption-rich dataset for medical video generation. It comprises over 55,000 curated clips spanning real-world medical scenarios, providing a strong foundation for training generalist medical video generation models. Built upon this dataset, we develop MedGen, which achieves leading performance among open-source models and rivals commercial systems across multiple benchmarks in both visual quality and medical accuracy. We hope our dataset and model can serve as a valuable resource and help catalyze further research in medical video generation. Our code and data is available at https://github.com/FreedomIntelligence/MedGen

Traditional drug design faces significant challenges due to inherent chemical and biological complexities, often resulting in high failure rates in clinical trials. Deep learning advancements, particularly generative models, offer potential solutions to these challenges. One promising algorithm is DrugGPT, a transformer-based model, that generates small molecules for input protein sequences. Although promising, it generates both chemically valid and invalid structures and does not incorporate the features of approved drugs, resulting in time-consuming and inefficient drug discovery. To address these issues, we introduce DrugGen, an enhanced model based on the DrugGPT structure. DrugGen is fine-tuned on approved drug-target interactions and optimized with proximal policy optimization. By giving reward feedback from protein-ligand binding affinity prediction using pre-trained transformers (PLAPT) and a customized invalid structure assessor, DrugGen significantly improves performance. Evaluation across multiple targets demonstrated that DrugGen achieves 100% valid structure generation compared to 95.5% with DrugGPT and produced molecules with higher predicted binding affinities (7.22 [6.30-8.07]) compared to DrugGPT (5.81 [4.97-6.63]) while maintaining diversity and novelty. Docking simulations further validate its ability to generate molecules targeting binding sites effectively. For example, in the case of fatty acid-binding protein 5 (FABP5), DrugGen generated molecules with superior docking scores (FABP5/11, -9.537 and FABP5/5, -8.399) compared to the reference molecule (Palmitic acid, -6.177). Beyond lead compound generation, DrugGen also shows potential for drug repositioning and creating novel pharmacophores for existing targets. By producing high-quality small molecules, DrugGen provides a high-performance medium for advancing pharmaceutical research and drug discovery.

With the rapid development of artificial intelligence, large language models (LLMs) have shown promising capabilities in mimicking human-level language comprehension and reasoning. This has sparked significant interest in applying LLMs to enhance various aspects of healthcare, ranging from medical education to clinical decision support. However, medicine involves multifaceted data modalities and nuanced reasoning skills, presenting challenges for integrating LLMs. This paper provides a comprehensive review on the applications and implications of LLMs in medicine. It begins by examining the fundamental applications of general-purpose and specialized LLMs, demonstrating their utilities in knowledge retrieval, research support, clinical workflow automation, and diagnostic assistance. Recognizing the inherent multimodality of medicine, the review then focuses on multimodal LLMs, investigating their ability to process diverse data types like medical imaging and EHRs to augment diagnostic accuracy. To address LLMs' limitations regarding personalization and complex clinical reasoning, the paper explores the emerging development of LLM-powered autonomous agents for healthcare. Furthermore, it summarizes the evaluation methodologies for assessing LLMs' reliability and safety in medical contexts. Overall, this review offers an extensive analysis on the transformative potential of LLMs in modern medicine. It also highlights the pivotal need for continuous optimizations and ethical oversight before these models can be effectively integrated into clinical practice. Visit https://github.com/mingze-yuan/Awesome-LLM-Healthcare for an accompanying GitHub repository containing latest papers.

Electronic health records (EHRs) contain vast amounts of complex data, but harmonizing and processing this information remains a challenging and costly task requiring significant clinical expertise. While large language models (LLMs) have shown promise in various healthcare applications, their potential for abstracting medical concepts from EHRs remains largely unexplored. We introduce EHRmonize, a framework leveraging LLMs to abstract medical concepts from EHR data. Our study uses medication data from two real-world EHR databases to evaluate five LLMs on two free-text extraction and six binary classification tasks across various prompting strategies. GPT-4o's with 10-shot prompting achieved the highest performance in all tasks, accompanied by Claude-3.5-Sonnet in a subset of tasks. GPT-4o achieved an accuracy of 97% in identifying generic route names, 82% for generic drug names, and 100% in performing binary classification of antibiotics. While EHRmonize significantly enhances efficiency, reducing annotation time by an estimated 60%, we emphasize that clinician oversight remains essential. Our framework, available as a Python package, offers a promising tool to assist clinicians in EHR data abstraction, potentially accelerating healthcare research and improving data harmonization processes.

In the medical domain, the lack of large training data sets and benchmarks is often a limiting factor for training deep neural networks. In contrast to expensive manual labeling, computer simulations can generate large and fully labeled data sets with a minimum of manual effort. However, models that are trained on simulated data usually do not translate well to real scenarios. To bridge the domain gap between simulated and real laparoscopic images, we exploit recent advances in unpaired image-to-image translation. We extent an image-to-image translation method to generate a diverse multitude of realistically looking synthetic images based on images from a simple laparoscopy simulation. By incorporating means to ensure that the image content is preserved during the translation process, we ensure that the labels given for the simulated images remain valid for their realistically looking translations. This way, we are able to generate a large, fully labeled synthetic data set of laparoscopic images with realistic appearance. We show that this data set can be used to train models for the task of liver segmentation of laparoscopic images. We achieve average dice scores of up to 0.89 in some patients without manually labeling a single laparoscopic image and show that using our synthetic data to pre-train models can greatly improve their performance. The synthetic data set will be made publicly available, fully labeled with segmentation maps, depth maps, normal maps, and positions of tools and camera (http://opencas.dkfz.de/image2image).

With the advent of Vision-Language Models (VLMs), medical artificial intelligence (AI) has experienced significant technological progress and paradigm shifts. This survey provides an extensive review of recent advancements in Medical Vision-Language Models (Med-VLMs), which integrate visual and textual data to enhance healthcare outcomes. We discuss the foundational technology behind Med-VLMs, illustrating how general models are adapted for complex medical tasks, and examine their applications in healthcare. The transformative impact of Med-VLMs on clinical practice, education, and patient care is highlighted, alongside challenges such as data scarcity, narrow task generalization, interpretability issues, and ethical concerns like fairness, accountability, and privacy. These limitations are exacerbated by uneven dataset distribution, computational demands, and regulatory hurdles. Rigorous evaluation methods and robust regulatory frameworks are essential for safe integration into healthcare workflows. Future directions include leveraging large-scale, diverse datasets, improving cross-modal generalization, and enhancing interpretability. Innovations like federated learning, lightweight architectures, and Electronic Health Record (EHR) integration are explored as pathways to democratize access and improve clinical relevance. This review aims to provide a comprehensive understanding of Med-VLMs' strengths and limitations, fostering their ethical and balanced adoption in healthcare.

Online medical consultation (OMC) restricts doctors to gathering patient information solely through inquiries, making the already complex sequential decision-making process of diagnosis even more challenging. Recently, the rapid advancement of large language models has demonstrated a significant potential to transform OMC. However, most studies have primarily focused on improving diagnostic accuracy under conditions of relatively sufficient information, while paying limited attention to the "inquiry" phase of the consultation process. This lack of focus has left the relationship between "inquiry" and "diagnosis" insufficiently explored. In this paper, we first extract real patient interaction strategies from authentic doctor-patient conversations and use these strategies to guide the training of a patient simulator that closely mirrors real-world behavior. By inputting medical records into our patient simulator to simulate patient responses, we conduct extensive experiments to explore the relationship between "inquiry" and "diagnosis" in the consultation process. Experimental results demonstrate that inquiry and diagnosis adhere to the Liebig's law: poor inquiry quality limits the effectiveness of diagnosis, regardless of diagnostic capability, and vice versa. Furthermore, the experiments reveal significant differences in the inquiry performance of various models. To investigate this phenomenon, we categorize the inquiry process into four types: (1) chief complaint inquiry; (2) specification of known symptoms; (3) inquiry about accompanying symptoms; and (4) gathering family or medical history. We analyze the distribution of inquiries across the four types for different models to explore the reasons behind their significant performance differences. We plan to open-source the weights and related code of our patient simulator at https://github.com/LIO-H-ZEN/PatientSimulator.

Background: Large language models (LLMs) are trained to follow directions, but this introduces a vulnerability to blindly comply with user requests even if they generate wrong information. In medicine, this could accelerate the generation of misinformation that impacts human well-being. Objectives/Methods: We analyzed compliance to requests to generate misleading content about medications in settings where models know the request is illogical. We investigated whether in-context directions and instruction-tuning of LLMs to prioritize logical reasoning over compliance reduced misinformation risk. Results: While all frontier LLMs complied with misinformation requests, both prompt-based and parameter-based approaches can improve the detection of logic flaws in requests and prevent the dissemination of medical misinformation. Conclusion: Shifting LLMs to prioritize logic over compliance could reduce risks of exploitation for medical misinformation.

Recent large language models (LLMs) have demonstrated significant advancements, particularly in their ability to serve as agents thereby surpassing their traditional role as chatbots. These agents can leverage their planning and tool utilization capabilities to address tasks specified at a high level. However, a standardized dataset to benchmark the agent capabilities of LLMs in medical applications is currently lacking, making the evaluation of LLMs on complex tasks in interactive healthcare environments challenging. To address this gap, we introduce MedAgentBench, a broad evaluation suite designed to assess the agent capabilities of large language models within medical records contexts. MedAgentBench encompasses 300 patient-specific clinically-derived tasks from 10 categories written by human physicians, realistic profiles of 100 patients with over 700,000 data elements, a FHIR-compliant interactive environment, and an accompanying codebase. The environment uses the standard APIs and communication infrastructure used in modern EMR systems, so it can be easily migrated into live EMR systems. MedAgentBench presents an unsaturated agent-oriented benchmark that current state-of-the-art LLMs exhibit some ability to succeed at. The best model (Claude 3.5 Sonnet v2) achieves a success rate of 69.67%. However, there is still substantial space for improvement which gives the community a next direction to optimize. Furthermore, there is significant variation in performance across task categories. MedAgentBench establishes this and is publicly available at https://github.com/stanfordmlgroup/MedAgentBench , offering a valuable framework for model developers to track progress and drive continuous improvements in the agent capabilities of large language models within the medical domain.

Recent advances in medical large language models (LLMs), multimodal models, and agents demand evaluation frameworks that reflect real clinical workflows and safety constraints. We present MedBench v4, a nationwide, cloud-based benchmarking infrastructure comprising over 700,000 expert-curated tasks spanning 24 primary and 91 secondary specialties, with dedicated tracks for LLMs, multimodal models, and agents. Items undergo multi-stage refinement and multi-round review by clinicians from more than 500 institutions, and open-ended responses are scored by an LLM-as-a-judge calibrated to human ratings. We evaluate 15 frontier models. Base LLMs reach a mean overall score of 54.1/100 (best: Claude Sonnet 4.5, 62.5/100), but safety and ethics remain low (18.4/100). Multimodal models perform worse overall (mean 47.5/100; best: GPT-5, 54.9/100), with solid perception yet weaker cross-modal reasoning. Agents built on the same backbones substantially improve end-to-end performance (mean 79.8/100), with Claude Sonnet 4.5-based agents achieving up to 85.3/100 overall and 88.9/100 on safety tasks. MedBench v4 thus reveals persisting gaps in multimodal reasoning and safety for base models, while showing that governance-aware agentic orchestration can markedly enhance benchmarked clinical readiness without sacrificing capability. By aligning tasks with Chinese clinical guidelines and regulatory priorities, the platform offers a practical reference for hospitals, developers, and policymakers auditing medical AI.

Machine translation is indispensable in healthcare for enabling the global dissemination of medical knowledge across languages. However, complex medical terminology poses unique challenges to achieving adequate translation quality and accuracy. This study introduces a novel "LLMs-in-the-loop" approach to develop supervised neural machine translation models optimized specifically for medical texts. While large language models (LLMs) have demonstrated powerful capabilities, this research shows that small, specialized models trained on high-quality in-domain (mostly synthetic) data can outperform even vastly larger LLMs. Custom parallel corpora in six languages were compiled from scientific articles, synthetically generated clinical documents, and medical texts. Our LLMs-in-the-loop methodology employs synthetic data generation, rigorous evaluation, and agent orchestration to enhance performance. We developed small medical translation models using the MarianMT base model. We introduce a new medical translation test dataset to standardize evaluation in this domain. Assessed using BLEU, METEOR, ROUGE, and BERT scores on this test set, our MarianMT-based models outperform Google Translate, DeepL, and GPT-4-Turbo. Results demonstrate that our LLMs-in-the-loop approach, combined with fine-tuning high-quality, domain-specific data, enables specialized models to outperform general-purpose and some larger systems. This research, part of a broader series on expert small models, paves the way for future healthcare-related AI developments, including deidentification and bio-medical entity extraction models. Our study underscores the potential of tailored neural translation models and the LLMs-in-the-loop methodology to advance the field through improved data generation, evaluation, agent, and modeling techniques.

Clinical information extraction, which involves structuring clinical concepts from unstructured medical text, remains a challenging problem that could benefit from the inclusion of tabular background information available in electronic health records. Existing open-source datasets lack explicit links between structured features and clinical concepts in the text, motivating the need for a new research dataset. We introduce SimSUM, a benchmark dataset of 10,000 simulated patient records that link unstructured clinical notes with structured background variables. Each record simulates a patient encounter in the domain of respiratory diseases and includes tabular data (e.g., symptoms, diagnoses, underlying conditions) generated from a Bayesian network whose structure and parameters are defined by domain experts. A large language model (GPT-4o) is prompted to generate a clinical note describing the encounter, including symptoms and relevant context. These notes are annotated with span-level symptom mentions. We conduct an expert evaluation to assess note quality and run baseline predictive models on both the tabular and textual data. The SimSUM dataset is primarily designed to support research on clinical information extraction in the presence of tabular background variables, which can be linked through domain knowledge to concepts of interest to be extracted from the text -- namely, symptoms in the case of SimSUM. Secondary uses include research on the automation of clinical reasoning over both tabular data and text, causal effect estimation in the presence of tabular and/or textual confounders, and multi-modal synthetic data generation. SimSUM is not intended for training clinical decision support systems or production-grade models, but rather to facilitate reproducible research in a simplified and controlled setting.

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.