Daily Papers

Fairness in artificial intelligence models has gained significantly more attention in recent years, especially in the area of medicine, as fairness in medical models is critical to people's well-being and lives. High-quality medical fairness datasets are needed to promote fairness learning research. Existing medical fairness datasets are all for classification tasks, and no fairness datasets are available for medical segmentation, while medical segmentation is an equally important clinical task as classifications, which can provide detailed spatial information on organ abnormalities ready to be assessed by clinicians. In this paper, we propose the first fairness dataset for medical segmentation named Harvard-FairSeg with 10,000 subject samples. In addition, we propose a fair error-bound scaling approach to reweight the loss function with the upper error-bound in each identity group, using the segment anything model (SAM). We anticipate that the segmentation performance equity can be improved by explicitly tackling the hard cases with high training errors in each identity group. To facilitate fair comparisons, we utilize a novel equity-scaled segmentation performance metric to compare segmentation metrics in the context of fairness, such as the equity-scaled Dice coefficient. Through comprehensive experiments, we demonstrate that our fair error-bound scaling approach either has superior or comparable fairness performance to the state-of-the-art fairness learning models. The dataset and code are publicly accessible via https://ophai.hms.harvard.edu/datasets/harvard-fairseg10k.

Biomedical data is inherently multimodal, consisting of electronic health records, medical imaging, digital pathology, genome sequencing, wearable sensors, and more. The application of artificial intelligence tools to these multifaceted sensing technologies has the potential to revolutionize the prognosis, diagnosis, and management of human health and disease. However, current approaches to biomedical AI typically only train and evaluate with one or a small set of medical modalities and tasks. This limitation hampers the development of comprehensive tools that can leverage the rich interconnected information across many heterogeneous biomedical sensors. To address this challenge, we present MultiMed, a benchmark designed to evaluate and enable large-scale learning across a wide spectrum of medical modalities and tasks. MultiMed consists of 2.56 million samples across ten medical modalities such as medical reports, pathology, genomics, and protein data, and is structured into eleven challenging tasks, including disease prognosis, protein structure prediction, and medical question answering. Using MultiMed, we conduct comprehensive experiments benchmarking state-of-the-art unimodal, multimodal, and multitask models. Our analysis highlights the advantages of training large-scale medical models across many related modalities and tasks. Moreover, MultiMed enables studies of generalization across related medical concepts, robustness to real-world noisy data and distribution shifts, and novel modality combinations to improve prediction performance. MultiMed will be publicly available and regularly updated and welcomes inputs from the community.

Humans effortlessly interpret images by parsing them into part-whole hierarchies; deep learning excels in learning multi-level feature spaces, but they often lack explicit coding of part-whole relations, a prominent property of medical imaging. To overcome this limitation, we introduce Adam-v2, a new self-supervised learning framework extending Adam [79] by explicitly incorporating part-whole hierarchies into its learning objectives through three key branches: (1) Localizability, acquiring discriminative representations to distinguish different anatomical patterns; (2) Composability, learning each anatomical structure in a parts-to-whole manner; and (3) Decomposability, comprehending each anatomical structure in a whole-to-parts manner. Experimental results across 10 tasks, compared to 11 baselines in zero-shot, few-shot transfer, and full fine-tuning settings, showcase Adam-v2's superior performance over large-scale medical models and existing SSL methods across diverse downstream tasks. The higher generality and robustness of Adam-v2's representations originate from its explicit construction of hierarchies for distinct anatomical structures from unlabeled medical images. Adam-v2 preserves a semantic balance of anatomical diversity and harmony in its embedding, yielding representations that are both generic and semantically meaningful, yet overlooked in existing SSL methods. All code and pretrained models are available at https://github.com/JLiangLab/Eden.

Humans can develop internal world models that encode common sense knowledge, telling them how the world works and predicting the consequences of their actions. This concept has emerged as a promising direction for establishing general-purpose machine-learning models in recent preliminary works, e.g., for visual representation learning. In this paper, we present CheXWorld, the first effort towards a self-supervised world model for radiographic images. Specifically, our work develops a unified framework that simultaneously models three aspects of medical knowledge essential for qualified radiologists, including 1) local anatomical structures describing the fine-grained characteristics of local tissues (e.g., architectures, shapes, and textures); 2) global anatomical layouts describing the global organization of the human body (e.g., layouts of organs and skeletons); and 3) domain variations that encourage CheXWorld to model the transitions across different appearance domains of radiographs (e.g., varying clarity, contrast, and exposure caused by collecting radiographs from different hospitals, devices, or patients). Empirically, we design tailored qualitative and quantitative analyses, revealing that CheXWorld successfully captures these three dimensions of medical knowledge. Furthermore, transfer learning experiments across eight medical image classification and segmentation benchmarks showcase that CheXWorld significantly outperforms existing SSL methods and large-scale medical foundation models. Code & pre-trained models are available at https://github.com/LeapLabTHU/CheXWorld.

Large-scale models pre-trained on large-scale datasets have profoundly advanced the development of deep learning. However, the state-of-the-art models for medical image segmentation are still small-scale, with their parameters only in the tens of millions. Further scaling them up to higher orders of magnitude is rarely explored. An overarching goal of exploring large-scale models is to train them on large-scale medical segmentation datasets for better transfer capacities. In this work, we design a series of Scalable and Transferable U-Net (STU-Net) models, with parameter sizes ranging from 14 million to 1.4 billion. Notably, the 1.4B STU-Net is the largest medical image segmentation model to date. Our STU-Net is based on nnU-Net framework due to its popularity and impressive performance. We first refine the default convolutional blocks in nnU-Net to make them scalable. Then, we empirically evaluate different scaling combinations of network depth and width, discovering that it is optimal to scale model depth and width together. We train our scalable STU-Net models on a large-scale TotalSegmentator dataset and find that increasing model size brings a stronger performance gain. This observation reveals that a large model is promising in medical image segmentation. Furthermore, we evaluate the transferability of our model on 14 downstream datasets for direct inference and 3 datasets for further fine-tuning, covering various modalities and segmentation targets. We observe good performance of our pre-trained model in both direct inference and fine-tuning. The code and pre-trained models are available at https://github.com/Ziyan-Huang/STU-Net.

Obtaining large pre-trained models that can be fine-tuned to new tasks with limited annotated samples has remained an open challenge for medical imaging data. While pre-trained deep networks on ImageNet and vision-language foundation models trained on web-scale data are prevailing approaches, their effectiveness on medical tasks is limited due to the significant domain shift between natural and medical images. To bridge this gap, we introduce LVM-Med, the first family of deep networks trained on large-scale medical datasets. We have collected approximately 1.3 million medical images from 55 publicly available datasets, covering a large number of organs and modalities such as CT, MRI, X-ray, and Ultrasound. We benchmark several state-of-the-art self-supervised algorithms on this dataset and propose a novel self-supervised contrastive learning algorithm using a graph-matching formulation. The proposed approach makes three contributions: (i) it integrates prior pair-wise image similarity metrics based on local and global information; (ii) it captures the structural constraints of feature embeddings through a loss function constructed via a combinatorial graph-matching objective; and (iii) it can be trained efficiently end-to-end using modern gradient-estimation techniques for black-box solvers. We thoroughly evaluate the proposed LVM-Med on 15 downstream medical tasks ranging from segmentation and classification to object detection, and both for the in and out-of-distribution settings. LVM-Med empirically outperforms a number of state-of-the-art supervised, self-supervised, and foundation models. For challenging tasks such as Brain Tumor Classification or Diabetic Retinopathy Grading, LVM-Med improves previous vision-language models trained on 1 billion masks by 6-7% while using only a ResNet-50.

The rapid advancement of large-scale vision-language models has showcased remarkable capabilities across various tasks. However, the lack of extensive and high-quality image-text data in medicine has greatly hindered the development of large-scale medical vision-language models. In this work, we present a diagnosis-guided bootstrapping strategy that exploits both image and label information to construct vision-language datasets. Based on the constructed dataset, we developed MedDr, a generalist foundation model for healthcare capable of handling diverse medical data modalities, including radiology, pathology, dermatology, retinography, and endoscopy. Moreover, during inference, we propose a simple but effective retrieval-augmented medical diagnosis strategy, which enhances the model's generalization ability. Extensive experiments on visual question answering, medical report generation, and medical image diagnosis demonstrate the superiority of our method.

Foundation models (FMs) have shown transformative potential in radiology by performing diverse, complex tasks across imaging modalities. Here, we developed CT-FM, a large-scale 3D image-based pre-trained model designed explicitly for various radiological tasks. CT-FM was pre-trained using 148,000 computed tomography (CT) scans from the Imaging Data Commons through label-agnostic contrastive learning. We evaluated CT-FM across four categories of tasks, namely, whole-body and tumor segmentation, head CT triage, medical image retrieval, and semantic understanding, showing superior performance against state-of-the-art models. Beyond quantitative success, CT-FM demonstrated the ability to cluster regions anatomically and identify similar anatomical and structural concepts across scans. Furthermore, it remained robust across test-retest settings and indicated reasonable salient regions attached to its embeddings. This study demonstrates the value of large-scale medical imaging foundation models and by open-sourcing the model weights, code, and data, aims to support more adaptable, reliable, and interpretable AI solutions in radiology.

The emerging trend of advancing generalist artificial intelligence, such as GPTv4 and Gemini, has reshaped the landscape of research (academia and industry) in machine learning and many other research areas. However, domain-specific applications of such foundation models (e.g., in medicine) remain untouched or often at their very early stages. It will require an individual set of transfer learning and model adaptation techniques by further expanding and injecting these models with domain knowledge and data. The development of such technologies could be largely accelerated if the bundle of data, algorithms, and pre-trained foundation models were gathered together and open-sourced in an organized manner. In this work, we present OpenMEDLab, an open-source platform for multi-modality foundation models. It encapsulates not only solutions of pioneering attempts in prompting and fine-tuning large language and vision models for frontline clinical and bioinformatic applications but also building domain-specific foundation models with large-scale multi-modal medical data. Importantly, it opens access to a group of pre-trained foundation models for various medical image modalities, clinical text, protein engineering, etc. Inspiring and competitive results are also demonstrated for each collected approach and model in a variety of benchmarks for downstream tasks. We welcome researchers in the field of medical artificial intelligence to continuously contribute cutting-edge methods and models to OpenMEDLab, which can be accessed via https://github.com/openmedlab.

Automatic medical report generation (MRG), which possesses significant research value as it can aid radiologists in clinical diagnosis and report composition, has garnered increasing attention. Despite recent progress, generating accurate reports remains arduous due to the requirement for precise clinical comprehension and disease diagnosis inference. Furthermore, owing to the limited accessibility of medical data and the imbalanced distribution of diseases, the underrepresentation of rare diseases in training data makes large-scale medical visual language models (LVLMs) prone to hallucinations, such as omissions or fabrications, severely undermining diagnostic performance and further intensifying the challenges for MRG in practice. In this study, to effectively mitigate hallucinations in medical report generation, we propose a chain-of-medical-thought approach (CoMT), which intends to imitate the cognitive process of human doctors by decomposing diagnostic procedures. The radiological features with different importance are structured into fine-grained medical thought chains to enhance the inferential ability during diagnosis, thereby alleviating hallucination problems and enhancing the diagnostic accuracy of MRG. The code and dataset have been released at https://github.com/FRENKIE-CHIANG/CoMT.

Compound figures, which are multi-panel composites containing diverse subfigures, are ubiquitous in biomedical literature, yet large-scale subfigure extraction remains largely unaddressed. Prior work on subfigure extraction has been limited in both dataset size and generalizability, leaving a critical open question: How does high-fidelity image-text alignment via large-scale subfigure extraction impact representation learning in vision-language models? We address this gap by introducing a scalable subfigure extraction pipeline based on transformer-based object detection, trained on a synthetic corpus of 500,000 compound figures, and achieving state-of-the-art performance on both ImageCLEF 2016 and synthetic benchmarks. Using this pipeline, we release OPEN-PMC-18M, a large-scale high quality biomedical vision-language dataset comprising 18 million clinically relevant subfigure-caption pairs spanning radiology, microscopy, and visible light photography. We train and evaluate vision-language models on our curated datasets and show improved performance across retrieval, zero-shot classification, and robustness benchmarks, outperforming existing baselines. We release our dataset, models, and code to support reproducible benchmarks and further study into biomedical vision-language modeling and representation learning.

Large language models (LLMs) can potentially democratize access to medical knowledge. While many efforts have been made to harness and improve LLMs' medical knowledge and reasoning capacities, the resulting models are either closed-source (e.g., PaLM, GPT-4) or limited in scale (<= 13B parameters), which restricts their abilities. In this work, we improve access to large-scale medical LLMs by releasing MEDITRON: a suite of open-source LLMs with 7B and 70B parameters adapted to the medical domain. MEDITRON builds on Llama-2 (through our adaptation of Nvidia's Megatron-LM distributed trainer), and extends pretraining on a comprehensively curated medical corpus, including selected PubMed articles, abstracts, and internationally-recognized medical guidelines. Evaluations using four major medical benchmarks show significant performance gains over several state-of-the-art baselines before and after task-specific finetuning. Overall, MEDITRON achieves a 6% absolute performance gain over the best public baseline in its parameter class and 3% over the strongest baseline we finetuned from Llama-2. Compared to closed-source LLMs, MEDITRON-70B outperforms GPT-3.5 and Med-PaLM and is within 5% of GPT-4 and 10% of Med-PaLM-2. We release our code for curating the medical pretraining corpus and the MEDITRON model weights to drive open-source development of more capable medical LLMs.

Medical tasks such as diagnosis and treatment planning require precise and complex reasoning, particularly in life-critical domains. Unlike mathematical reasoning, medical reasoning demands meticulous, verifiable thought processes to ensure reliability and accuracy. However, there is a notable lack of datasets that provide transparent, step-by-step reasoning to validate and enhance the medical reasoning ability of AI models. To bridge this gap, we introduce MedReason, a large-scale high-quality medical reasoning dataset designed to enable faithful and explainable medical problem-solving in large language models (LLMs). We utilize a structured medical knowledge graph (KG) to convert clinical QA pairs into logical chains of reasoning, or ``thinking paths'', which trace connections from question elements to answers via relevant KG entities. Each path is validated for consistency with clinical logic and evidence-based medicine. Our pipeline generates detailed reasoning for various medical questions from 7 medical datasets, resulting in a dataset of 32,682 question-answer pairs, each with detailed, step-by-step explanations. Experiments demonstrate that fine-tuning with our dataset consistently boosts medical problem-solving capabilities, achieving significant gains of up to 7.7% for DeepSeek-Ditill-8B. Our top-performing model, MedReason-8B, outperforms the Huatuo-o1-8B, a state-of-the-art medical reasoning model, by up to 4.2% on the clinical benchmark MedBullets. We also engage medical professionals from diverse specialties to assess our dataset's quality, ensuring MedReason offers accurate and coherent medical reasoning. Our data, models, and code will be publicly available.

The scarcity of annotations poses a significant challenge in medical image analysis. Large-scale pre-training has emerged as a promising label-efficient solution, owing to the utilization of large-scale data, large models, and advanced pre-training techniques. However, its development in medical images remains underexplored. The primary challenge lies in harnessing large-scale unlabeled data and learning high-level semantics without annotations. We observe that 3D medical images exhibit consistent geometric context, i.e., consistent geometric relations between different organs, which leads to a promising way for learning consistent representations. Motivated by this, we introduce a simple-yet-effective Volume Contrast (VoCo) framework to leverage geometric context priors for self-supervision. Given an input volume, we extract base crops from different regions to construct positive and negative pairs for contrastive learning. Then we predict the contextual position of a random crop by contrasting its similarity to the base crops. In this way, VoCo encodes the inherent geometric context into model representations, facilitating high-level semantic learning without annotations. Specifically, we (1) introduce the largest medical pre-training dataset PreCT-160K; (2) investigate scaling laws and propose guidelines for tailoring different model sizes to various medical tasks; (3) build a benchmark encompassing 48 medical tasks. Extensive experiments highlight the superiority of VoCo. Codes at https://github.com/Luffy03/Large-Scale-Medical.

In this paper, we release a largest ever medical Question Answering (QA) dataset with 26 million QA pairs. We benchmark many existing approaches in our dataset in terms of both retrieval and generation. Experimental results show that the existing models perform far lower than expected and the released dataset is still challenging in the pre-trained language model era. Moreover, we also experimentally show the benefit of the proposed dataset in many aspects: (i) trained models for other QA datasets in a zero-shot fashion; and (ii) as external knowledge for retrieval-augmented generation (RAG); and (iii) improving existing pre-trained language models by using the QA pairs as a pre-training corpus in continued training manner. We believe that this dataset will not only contribute to medical research but also facilitate both the patients and clinical doctors. See https://github.com/FreedomIntelligence/Huatuo-26M.

This paper explores the advancements and applications of large-scale models in the medical field, with a particular focus on Medical Large Models (MedLMs). These models, encompassing Large Language Models (LLMs), Vision Models, 3D Large Models, and Multimodal Models, are revolutionizing healthcare by enhancing disease prediction, diagnostic assistance, personalized treatment planning, and drug discovery. The integration of graph neural networks in medical knowledge graphs and drug discovery highlights the potential of Large Graph Models (LGMs) in understanding complex biomedical relationships. The study also emphasizes the transformative role of Vision-Language Models (VLMs) and 3D Large Models in medical image analysis, anatomical modeling, and prosthetic design. Despite the challenges, these technologies are setting new benchmarks in medical innovation, improving diagnostic accuracy, and paving the way for personalized healthcare solutions. This paper aims to provide a comprehensive overview of the current state and future directions of large models in medicine, underscoring their significance in advancing global health.

Recently, both closed-source LLMs and open-source communities have made significant strides, outperforming humans in various general domains. However, their performance in specific professional fields such as medicine, especially within the open-source community, remains suboptimal due to the complexity of medical knowledge. We propose Aquila-Med, a bilingual medical LLM based on Aquila, addressing these challenges through continue pre-training, supervised fine-tuning (SFT), and reinforcement learning from human feedback (RLHF). We construct a large-scale Chinese and English medical dataset for continue pre-training and a high-quality SFT dataset, covering extensive medical specialties. Additionally, we develop a high-quality Direct Preference Optimization (DPO) dataset for further alignment. Aquila-Med achieves notable results across single-turn, multi-turn dialogues, and medical multiple-choice questions, demonstrating the effectiveness of our approach. We open-source the datasets and the entire training process, contributing valuable resources to the research community. Our models and datasets will released at https://huggingface.co/BAAI/AquilaMed-RL.

This paper introduces MedTrinity-25M, a comprehensive, large-scale multimodal dataset for medicine, covering over 25 million images across 10 modalities, with multigranular annotations for more than 65 diseases. These enriched annotations encompass both global textual information, such as disease/lesion type, modality, region-specific descriptions, and inter-regional relationships, as well as detailed local annotations for regions of interest (ROIs), including bounding boxes, segmentation masks. Unlike existing approach which is limited by the availability of image-text pairs, we have developed the first automated pipeline that scales up multimodal data by generating multigranular visual and texual annotations (in the form of image-ROI-description triplets) without the need for any paired text descriptions. Specifically, data from over 90 different sources have been collected, preprocessed, and grounded using domain-specific expert models to identify ROIs related to abnormal regions. We then build a comprehensive knowledge base and prompt multimodal large language models to perform retrieval-augmented generation with the identified ROIs as guidance, resulting in multigranular texual descriptions. Compared to existing datasets, MedTrinity-25M provides the most enriched annotations, supporting a comprehensive range of multimodal tasks such as captioning and report generation, as well as vision-centric tasks like classification and segmentation. Pretraining on MedTrinity-25M, our model achieves state-of-the-art performance on VQA-RAD and PathVQA, surpassing both multimodal large language models and other representative SoTA approaches. This dataset can also be utilized to support large-scale pre-training of multimodal medical AI models, contributing to the development of future foundation models in the medical domain.

Existing volumetric medical image segmentation models are typically task-specific, excelling at specific target but struggling to generalize across anatomical structures or modalities. This limitation restricts their broader clinical use. In this paper, we introduce SAM-Med3D for general-purpose segmentation on volumetric medical images. Given only a few 3D prompt points, SAM-Med3D can accurately segment diverse anatomical structures and lesions across various modalities. To achieve this, we gather and process a large-scale 3D medical image dataset, SA-Med3D-140K, from a blend of public sources and licensed private datasets. This dataset includes 22K 3D images and 143K corresponding 3D masks. Then SAM-Med3D, a promptable segmentation model characterized by the fully learnable 3D structure, is trained on this dataset using a two-stage procedure and exhibits impressive performance on both seen and unseen segmentation targets. We comprehensively evaluate SAM-Med3D on 16 datasets covering diverse medical scenarios, including different anatomical structures, modalities, targets, and zero-shot transferability to new/unseen tasks. The evaluation shows the efficiency and efficacy of SAM-Med3D, as well as its promising application to diverse downstream tasks as a pre-trained model. Our approach demonstrates that substantial medical resources can be utilized to develop a general-purpose medical AI for various potential applications. Our dataset, code, and models are available at https://github.com/uni-medical/SAM-Med3D.

Segment Anything Model (SAM) has achieved impressive results for natural image segmentation with input prompts such as points and bounding boxes. Its success largely owes to massive labeled training data. However, directly applying SAM to medical image segmentation cannot perform well because SAM lacks medical knowledge -- it does not use medical images for training. To incorporate medical knowledge into SAM, we introduce SA-Med2D-20M, a large-scale segmentation dataset of 2D medical images built upon numerous public and private datasets. It consists of 4.6 million 2D medical images and 19.7 million corresponding masks, covering almost the whole body and showing significant diversity. This paper describes all the datasets collected in SA-Med2D-20M and details how to process these datasets. Furthermore, comprehensive statistics of SA-Med2D-20M are presented to facilitate the better use of our dataset, which can help the researchers build medical vision foundation models or apply their models to downstream medical applications. We hope that the large scale and diversity of SA-Med2D-20M can be leveraged to develop medical artificial intelligence for enhancing diagnosis, medical image analysis, knowledge sharing, and education. The data with the redistribution license is publicly available at https://github.com/OpenGVLab/SAM-Med2D.

In this paper, we introduce DRR-RATE, a large-scale synthetic chest X-ray dataset derived from the recently released CT-RATE dataset. DRR-RATE comprises of 50,188 frontal Digitally Reconstructed Radiographs (DRRs) from 21,304 unique patients. Each image is paired with a corresponding radiology text report and binary labels for 18 pathology classes. Given the controllable nature of DRR generation, it facilitates the inclusion of lateral view images and images from any desired viewing position. This opens up avenues for research into new and novel multimodal applications involving paired CT, X-ray images from various views, text, and binary labels. We demonstrate the applicability of DRR-RATE alongside existing large-scale chest X-ray resources, notably the CheXpert dataset and CheXnet model. Experiments demonstrate that CheXnet, when trained and tested on the DRR-RATE dataset, achieves sufficient to high AUC scores for the six common pathologies cited in common literature: Atelectasis, Cardiomegaly, Consolidation, Lung Lesion, Lung Opacity, and Pleural Effusion. Additionally, CheXnet trained on the CheXpert dataset can accurately identify several pathologies, even when operating out of distribution. This confirms that the generated DRR images effectively capture the essential pathology features from CT images. The dataset and labels are publicly accessible at https://huggingface.co/datasets/farrell236/DRR-RATE.

Developing generalist foundation model has recently attracted tremendous attention among researchers in the field of AI for Medicine (AI4Medicine). A pivotal insight in developing these models is their reliance on dataset scaling, which emphasizes the requirements on developing open-source medical image datasets that incorporate diverse supervision signals across various imaging modalities. In this paper, we introduce RadGenome-Chest CT, a comprehensive, large-scale, region-guided 3D chest CT interpretation dataset based on CT-RATE. Specifically, we leverage the latest powerful universal segmentation and large language models, to extend the original datasets (over 25,692 non-contrast 3D chest CT volume and reports from 20,000 patients) from the following aspects: (i) organ-level segmentation masks covering 197 categories, which provide intermediate reasoning visual clues for interpretation; (ii) 665 K multi-granularity grounded reports, where each sentence of the report is linked to the corresponding anatomical region of CT volume in the form of a segmentation mask; (iii) 1.3 M grounded VQA pairs, where questions and answers are all linked with reference segmentation masks, enabling models to associate visual evidence with textual explanations. All grounded reports and VQA pairs in the validation set have gone through manual verification to ensure dataset quality. We believe that RadGenome-Chest CT can significantly advance the development of multimodal medical foundation models, by training to generate texts based on given segmentation regions, which is unattainable with previous relevant datasets. We will release all segmentation masks, grounded reports, and VQA pairs to facilitate further research and development in this field.

Large Language Models (LLMs) have demonstrated remarkable versatility in recent years, offering potential applications across specialized domains such as healthcare and medicine. Despite the availability of various open-source LLMs tailored for health contexts, adapting general-purpose LLMs to the medical domain presents significant challenges. In this paper, we introduce BioMistral, an open-source LLM tailored for the biomedical domain, utilizing Mistral as its foundation model and further pre-trained on PubMed Central. We conduct a comprehensive evaluation of BioMistral on a benchmark comprising 10 established medical question-answering (QA) tasks in English. We also explore lightweight models obtained through quantization and model merging approaches. Our results demonstrate BioMistral's superior performance compared to existing open-source medical models and its competitive edge against proprietary counterparts. Finally, to address the limited availability of data beyond English and to assess the multilingual generalization of medical LLMs, we automatically translated and evaluated this benchmark into 7 other languages. This marks the first large-scale multilingual evaluation of LLMs in the medical domain. Datasets, multilingual evaluation benchmarks, scripts, and all the models obtained during our experiments are freely released.

Recent large language models (LLMs) such as ChatGPT and LLaMA have shown great promise in many AI applications. However, their performance on medical tasks is suboptimal and can be improved by training on extensive domain-specific datasets. This study introduces Me LLaMA, a medical LLM family that includes foundation models - Me LLaMA 13/70B, along with their chat-enhanced versions - Me LLaMA 13/70B-chat, developed through continual pre-training and instruction tuning of LLaMA2 using large medical datasets. Our domain-specific data suite for training and evaluation includes a large-scale, continual pre-training dataset with 129B tokens, an instruction tuning dataset with 214k samples, and a new medical evaluation benchmark (MIBE) across six tasks with 12 datasets. Our extensive evaluation using the MIBE shows that Me LLaMA models achieve overall better performance than existing open-source medical LLMs in zero-shot, few-shot and supervised learning abilities. Their zero-shot performance is comparable with ChatGPT across 7 out of 8 datasets, with a slight variance of within 3%, and yet falls short when compared to GPT-4. In addition, we investigated the catastrophic forgetting problem, and our results show that Me LLaMA models outperform other open-source medical LLMs in mitigating this issue. Me LLaMA is one of the largest open-source medical foundation LLMs that use both biomedical and clinical data. It exhibits superior performance across both general and medical tasks compared to other open-source medical LLMs, rendering it an attractive choice for medical AI applications. We release our models, datasets, and evaluation scripts at: https://github.com/BIDS-Xu-Lab/Me-LLaMA.

Medical images are acquired at high resolutions with large fields of view in order to capture fine-grained features necessary for clinical decision-making. Consequently, training deep learning models on medical images can incur large computational costs. In this work, we address the challenge of downsizing medical images in order to improve downstream computational efficiency while preserving clinically-relevant features. We introduce MedVAE, a family of six large-scale 2D and 3D autoencoders capable of encoding medical images as downsized latent representations and decoding latent representations back to high-resolution images. We train MedVAE autoencoders using a novel two-stage training approach with 1,052,730 medical images. Across diverse tasks obtained from 20 medical image datasets, we demonstrate that (1) utilizing MedVAE latent representations in place of high-resolution images when training downstream models can lead to efficiency benefits (up to 70x improvement in throughput) while simultaneously preserving clinically-relevant features and (2) MedVAE can decode latent representations back to high-resolution images with high fidelity. Our work demonstrates that large-scale, generalizable autoencoders can help address critical efficiency challenges in the medical domain. Our code is available at https://github.com/StanfordMIMI/MedVAE.

Background: Recent advances in large language models highlight the need for high-quality multilingual medical datasets. While Japan leads globally in CT scanner deployment and utilization, the lack of large-scale Japanese radiology datasets has hindered the development of specialized language models for medical imaging analysis. Objective: To develop a comprehensive Japanese CT report dataset through machine translation and establish a specialized language model for structured finding classification. Additionally, to create a rigorously validated evaluation dataset through expert radiologist review. Methods: We translated the CT-RATE dataset (24,283 CT reports from 21,304 patients) into Japanese using GPT-4o mini. The training dataset consisted of 22,778 machine-translated reports, while the validation dataset included 150 radiologist-revised reports. We developed CT-BERT-JPN based on "tohoku-nlp/bert-base-japanese-v3" architecture for extracting 18 structured findings from Japanese radiology reports. Results: Translation metrics showed strong performance with BLEU scores of 0.731 and 0.690, and ROUGE scores ranging from 0.770 to 0.876 for Findings and from 0.748 to 0.857 for Impression sections. CT-BERT-JPN demonstrated superior performance compared to GPT-4o in 11 out of 18 conditions, including lymphadenopathy (+14.2%), interlobular septal thickening (+10.9%), and atelectasis (+7.4%). The model maintained F1 scores exceeding 0.95 in 14 out of 18 conditions and achieved perfect scores in four conditions. Conclusions: Our study establishes a robust Japanese CT report dataset and demonstrates the effectiveness of a specialized language model for structured finding classification. The hybrid approach of machine translation and expert validation enables the creation of large-scale medical datasets while maintaining high quality.

Large-scale language models (LLMs), such as ChatGPT, are capable of generating human-like responses for various downstream tasks, such as task-oriented dialogues and question answering. However, applying LLMs to medical domains remains challenging due to their inability to leverage domain-specific knowledge. In this study, we present the Large-scale Language Models Augmented with Medical Textbooks (LLM-AMT), which integrates authoritative medical textbooks as the cornerstone of its design, enhancing its proficiency in the specialized domain through plug-and-play modules, comprised of a Hybrid Textbook Retriever, supplemented by the Query Augmenter and the LLM Reader. Experimental evaluation on three open-domain medical question-answering tasks reveals a substantial enhancement in both the professionalism and accuracy of the LLM responses when utilizing LLM-AMT, exhibiting an improvement ranging from 11.4% to 13.2%. Despite being 100 times smaller, we found that medical textbooks as the retrieval corpus serves as a more valuable external knowledge source than Wikipedia in the medical domain. Our experiments show that textbook augmentation results in a performance improvement ranging from 9.7% to 12.2% over Wikipedia augmentation.

Due to privacy restrictions, there's a shortage of publicly available speech recognition datasets in the medical domain. In this work, we present VietMed - a Vietnamese speech recognition dataset in the medical domain comprising 16h of labeled medical speech, 1000h of unlabeled medical speech and 1200h of unlabeled general-domain speech. To our best knowledge, VietMed is by far the world's largest public medical speech recognition dataset in 7 aspects: total duration, number of speakers, diseases, recording conditions, speaker roles, unique medical terms and accents. VietMed is also by far the largest public Vietnamese speech dataset in terms of total duration. Additionally, we are the first to present a medical ASR dataset covering all ICD-10 disease groups and all accents within a country. Moreover, we release the first public large-scale pre-trained models for Vietnamese ASR, w2v2-Viet and XLSR-53-Viet, along with the first public large-scale fine-tuned models for medical ASR. Even without any medical data in unsupervised pre-training, our best pre-trained model XLSR-53-Viet generalizes very well to the medical domain by outperforming state-of-the-art XLSR-53, from 51.8% to 29.6% WER on test set (a relative reduction of more than 40%). All code, data and models are made publicly available here: https://github.com/leduckhai/MultiMed.

Foundation models, often pre-trained with large-scale data, have achieved paramount success in jump-starting various vision and language applications. Recent advances further enable adapting foundation models in downstream tasks efficiently using only a few training samples, e.g., in-context learning. Yet, the application of such learning paradigms in medical image analysis remains scarce due to the shortage of publicly accessible data and benchmarks. In this paper, we aim at approaches adapting the foundation models for medical image classification and present a novel dataset and benchmark for the evaluation, i.e., examining the overall performance of accommodating the large-scale foundation models downstream on a set of diverse real-world clinical tasks. We collect five sets of medical imaging data from multiple institutes targeting a variety of real-world clinical tasks (22,349 images in total), i.e., thoracic diseases screening in X-rays, pathological lesion tissue screening, lesion detection in endoscopy images, neonatal jaundice evaluation, and diabetic retinopathy grading. Results of multiple baseline methods are demonstrated using the proposed dataset from both accuracy and cost-effective perspectives.

High-quality, large-scale data is essential for robust deep learning models in medical applications, particularly ultrasound image analysis. Diffusion models facilitate high-fidelity medical image generation, reducing the costs associated with acquiring and annotating new images. This paper utilizes recent vision-language models to produce diverse and realistic synthetic echocardiography image data, preserving key features of the original images guided by textual and semantic label maps. Specifically, we investigate three potential avenues: unconditional generation, generation guided by text, and a hybrid approach incorporating both textual and semantic supervision. We show that the rich contextual information present in the synthesized data potentially enhances the accuracy and interpretability of downstream tasks, such as echocardiography segmentation and classification with improved metrics and faster convergence. Our implementation with checkpoints, prompts, and the created synthetic dataset will be publicly available at https://github.com/Pooria90/DiffEcho{GitHub}.

Pretraining with large-scale 3D volumes has a potential for improving the segmentation performance on a target medical image dataset where the training images and annotations are limited. Due to the high cost of acquiring pixel-level segmentation annotations on the large-scale pretraining dataset, pretraining with unannotated images is highly desirable. In this work, we propose a novel self-supervised learning strategy named Volume Fusion (VF) for pretraining 3D segmentation models. It fuses several random patches from a foreground sub-volume to a background sub-volume based on a predefined set of discrete fusion coefficients, and forces the model to predict the fusion coefficient of each voxel, which is formulated as a self-supervised segmentation task without manual annotations. Additionally, we propose a novel network architecture based on parallel convolution and transformer blocks that is suitable to be transferred to different downstream segmentation tasks with various scales of organs and lesions. The proposed model was pretrained with 110k unannotated 3D CT volumes, and experiments with different downstream segmentation targets including head and neck organs, thoracic/abdominal organs showed that our pretrained model largely outperformed training from scratch and several state-of-the-art self-supervised training methods and segmentation models. The code and pretrained model are available at https://github.com/openmedlab/MIS-FM.

Large Vision-Language Models (LVLMs) have demonstrated remarkable capabilities in various multimodal tasks. However, their potential in the medical domain remains largely unexplored. A significant challenge arises from the scarcity of diverse medical images spanning various modalities and anatomical regions, which is essential in real-world medical applications. To solve this problem, in this paper, we introduce OmniMedVQA, a novel comprehensive medical Visual Question Answering (VQA) benchmark. This benchmark is collected from 75 different medical datasets, including 12 different modalities and covering more than 20 distinct anatomical regions. Importantly, all images in this benchmark are sourced from authentic medical scenarios, ensuring alignment with the requirements of the medical field and suitability for evaluating LVLMs. Through our extensive experiments, we have found that existing LVLMs struggle to address these medical VQA problems effectively. Moreover, what surprises us is that medical-specialized LVLMs even exhibit inferior performance to those general-domain models, calling for a more versatile and robust LVLM in the biomedical field. The evaluation results not only reveal the current limitations of LVLM in understanding real medical images but also highlight our dataset's significance. Our dataset will be made publicly available.

Tracking biosignals is crucial for monitoring wellness and preempting the development of severe medical conditions. Today, wearable devices can conveniently record various biosignals, creating the opportunity to monitor health status without disruption to one's daily routine. Despite widespread use of wearable devices and existing digital biomarkers, the absence of curated data with annotated medical labels hinders the development of new biomarkers to measure common health conditions. In fact, medical datasets are usually small in comparison to other domains, which is an obstacle for developing neural network models for biosignals. To address this challenge, we have employed self-supervised learning using the unlabeled sensor data collected under informed consent from the large longitudinal Apple Heart and Movement Study (AHMS) to train foundation models for two common biosignals: photoplethysmography (PPG) and electrocardiogram (ECG) recorded on Apple Watch. We curated PPG and ECG datasets from AHMS that include data from ~141K participants spanning ~3 years. Our self-supervised learning framework includes participant level positive pair selection, stochastic augmentation module and a regularized contrastive loss optimized with momentum training, and generalizes well to both PPG and ECG modalities. We show that the pre-trained foundation models readily encode information regarding participants' demographics and health conditions. To the best of our knowledge, this is the first study that builds foundation models using large-scale PPG and ECG data collected via wearable consumer devices x2013 prior works have commonly used smaller-size datasets collected in clinical and experimental settings. We believe PPG and ECG foundation models can enhance future wearable devices by reducing the reliance on labeled data and hold the potential to help the users improve their health.

The cross-domain text-to-SQL task aims to build a system that can parse user questions into SQL on complete unseen databases, and the single-domain text-to-SQL task evaluates the performance on identical databases. Both of these setups confront unavoidable difficulties in real-world applications. To this end, we introduce the cross-schema text-to-SQL task, where the databases of evaluation data are different from that in the training data but come from the same domain. Furthermore, we present CSS, a large-scale CrosS-Schema Chinese text-to-SQL dataset, to carry on corresponding studies. CSS originally consisted of 4,340 question/SQL pairs across 2 databases. In order to generalize models to different medical systems, we extend CSS and create 19 new databases along with 29,280 corresponding dataset examples. Moreover, CSS is also a large corpus for single-domain Chinese text-to-SQL studies. We present the data collection approach and a series of analyses of the data statistics. To show the potential and usefulness of CSS, benchmarking baselines have been conducted and reported. Our dataset is publicly available at https://huggingface.co/datasets/zhanghanchong/css.

Prior to the deep learning era, shape was commonly used to describe the objects. Nowadays, state-of-the-art (SOTA) algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from numerous shape-related publications in premier vision conferences as well as the growing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models). For the medical domain, we present a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D models of surgical instrument, called MedShapeNet, created to facilitate the translation of data-driven vision algorithms to medical applications and to adapt SOTA vision algorithms to medical problems. As a unique feature, we directly model the majority of shapes on the imaging data of real patients. As of today, MedShapeNet includes 23 dataset with more than 100,000 shapes that are paired with annotations (ground truth). Our data is freely accessible via a web interface and a Python application programming interface (API) and can be used for discriminative, reconstructive, and variational benchmarks as well as various applications in virtual, augmented, or mixed reality, and 3D printing. Exemplary, we present use cases in the fields of classification of brain tumors, facial and skull reconstructions, multi-class anatomy completion, education, and 3D printing. In future, we will extend the data and improve the interfaces. The project pages are: https://medshapenet.ikim.nrw/ and https://github.com/Jianningli/medshapenet-feedback

Driven by the recent advances in deep learning methods and, in particular, by the development of modern self-supervised learning algorithms, increased interest and efforts have been devoted to build foundation models (FMs) for medical images. In this work, we present our scalable training pipeline for large pathology imaging data, and a comprehensive analysis of various hyperparameter choices and training techniques for building pathology FMs. We release and make publicly available the first batch of our pathology FMs (https://github.com/kaiko-ai/towards_large_pathology_fms) trained on open-access TCGA whole slide images, a commonly used collection of pathology images. The experimental evaluation shows that our models reach state-of-the-art performance on various patch-level downstream tasks, ranging from breast cancer subtyping to colorectal nuclear segmentation. Finally, to unify the evaluation approaches used in the field and to simplify future comparisons of different FMs, we present an open-source framework (https://github.com/kaiko-ai/eva) designed for the consistent evaluation of pathology FMs across various downstream tasks.

This paper introduces MedMCQA, a new large-scale, Multiple-Choice Question Answering (MCQA) dataset designed to address real-world medical entrance exam questions. More than 194k high-quality AIIMS \& NEET PG entrance exam MCQs covering 2.4k healthcare topics and 21 medical subjects are collected with an average token length of 12.77 and high topical diversity. Each sample contains a question, correct answer(s), and other options which requires a deeper language understanding as it tests the 10+ reasoning abilities of a model across a wide range of medical subjects \& topics. A detailed explanation of the solution, along with the above information, is provided in this study.

Medical Visual Question Answering (Med-VQA) combines computer vision and natural language processing to automatically answer clinical inquiries about medical images. However, current Med-VQA datasets exhibit two significant limitations: (1) they often lack visual and textual explanations for answers, hindering comprehension for patients and junior doctors; (2) they typically offer a narrow range of question formats, inadequately reflecting the diverse requirements in practical scenarios. These limitations pose significant challenges to the development of a reliable and user-friendly Med-VQA system. To address these challenges, we introduce a large-scale, Groundable, and Explainable Medical VQA benchmark for chest X-ray diagnosis (GEMeX), featuring several innovative components: (1) a multi-modal explainability mechanism that offers detailed visual and textual explanations for each question-answer pair, thereby enhancing answer comprehensibility; (2) four question types, open-ended, closed-ended, single-choice, and multiple-choice, to better reflect practical needs. With 151,025 images and 1,605,575 questions, GEMeX is the currently largest chest X-ray VQA dataset. Evaluation of 12 representative large vision language models (LVLMs) on GEMeX reveals suboptimal performance, underscoring the dataset's complexity. Meanwhile, we propose a strong model by fine-tuning an existing LVLM on the GEMeX training set. The substantial performance improvement showcases the dataset's effectiveness. The benchmark is available at https://www.med-vqa.com/GEMeX.

Multilingual speech translation (ST) in the medical domain enhances patient care by enabling efficient communication across language barriers, alleviating specialized workforce shortages, and facilitating improved diagnosis and treatment, particularly during pandemics. In this work, we present the first systematic study on medical ST, to our best knowledge, by releasing MultiMed-ST, a large-scale ST dataset for the medical domain, spanning all translation directions in five languages: Vietnamese, English, German, French, Traditional Chinese and Simplified Chinese, together with the models. With 290,000 samples, our dataset is the largest medical machine translation (MT) dataset and the largest many-to-many multilingual ST among all domains. Secondly, we present the most extensive analysis study in ST research to date, including: empirical baselines, bilingual-multilingual comparative study, end-to-end vs. cascaded comparative study, task-specific vs. multi-task sequence-to-sequence (seq2seq) comparative study, code-switch analysis, and quantitative-qualitative error analysis. All code, data, and models are available online: https://github.com/leduckhai/MultiMed-ST.

Medical image analysis is essential to clinical diagnosis and treatment, which is increasingly supported by multi-modal large language models (MLLMs). However, previous research has primarily focused on 2D medical images, leaving 3D images under-explored, despite their richer spatial information. This paper aims to advance 3D medical image analysis with MLLMs. To this end, we present a large-scale 3D multi-modal medical dataset, M3D-Data, comprising 120K image-text pairs and 662K instruction-response pairs specifically tailored for various 3D medical tasks, such as image-text retrieval, report generation, visual question answering, positioning, and segmentation. Additionally, we propose M3D-LaMed, a versatile multi-modal large language model for 3D medical image analysis. Furthermore, we introduce a new 3D multi-modal medical benchmark, M3D-Bench, which facilitates automatic evaluation across eight tasks. Through comprehensive evaluation, our method proves to be a robust model for 3D medical image analysis, outperforming existing solutions. All code, data, and models are publicly available at: https://github.com/BAAI-DCAI/M3D.

Test-time scaling has emerged as a powerful technique for enhancing the reasoning capabilities of large language models. However, its effectiveness in medical reasoning remains uncertain, as the medical domain fundamentally differs from mathematical tasks in terms of knowledge representation and decision-making processes. In this paper, we provide the first comprehensive investigation of test-time scaling for medical reasoning and present m1, a simple yet effective approach that increases a model's medical reasoning capability at inference. Our evaluation across diverse medical tasks demonstrates that test-time scaling consistently enhances medical reasoning, enabling lightweight fine-tuned models under 10B parameters to establish new state-of-the-art performance, while our 32B model rivals previous 70B-scale medical LLMs. However, we identify an optimal reasoning token budget of approximately 4K, beyond which performance may degrade due to overthinking. Budget forcing, which extends test-time computation through iterative prompts, helps models double-check answers but does not necessarily improve the overall medical QA performance and, in some cases, even introduces errors into previously correct responses. Our case-by-case analysis identifies insufficient medical knowledge as a key bottleneck that prevents further performance gains through test-time scaling. We find that increasing data scale, improving data quality, and expanding model capacity consistently enhance medical knowledge grounding, enabling continued performance improvements, particularly on challenging medical benchmarks where smaller models reach saturation. These findings underscore fundamental differences between medical and mathematical reasoning in LLMs, highlighting that enriched medical knowledge, other than increased reasoning depth alone, is essential for realizing the benefits of test-time scaling.

Large-scale Vision-Language Models (LVLMs) have significantly advanced with text-aligned vision inputs. They have made remarkable progress in computer vision tasks by aligning text modality with vision inputs. There are also endeavors to incorporate multi-vision sensors beyond RGB, including thermal, depth, and medical X-ray images. However, we observe that current LVLMs view images taken from multi-vision sensors as if they were in the same RGB domain without considering the physical characteristics of multi-vision sensors. They fail to convey the fundamental multi-vision sensor information from the dataset and the corresponding contextual knowledge properly. Consequently, alignment between the information from the actual physical environment and the text is not achieved correctly, making it difficult to answer complex sensor-related questions that consider the physical environment. In this paper, we aim to establish a multi-vision Sensor Perception And Reasoning benchmarK called SPARK that can reduce the fundamental multi-vision sensor information gap between images and multi-vision sensors. We generated 6,248 vision-language test samples automatically to investigate multi-vision sensory perception and multi-vision sensory reasoning on physical sensor knowledge proficiency across different formats, covering different types of sensor-related questions. We utilized these samples to assess ten leading LVLMs. The results showed that most models displayed deficiencies in multi-vision sensory reasoning to varying extents. Codes and data are available at https://github.com/top-yun/SPARK

Open domain question answering (OpenQA) tasks have been recently attracting more and more attention from the natural language processing (NLP) community. In this work, we present the first free-form multiple-choice OpenQA dataset for solving medical problems, MedQA, collected from the professional medical board exams. It covers three languages: English, simplified Chinese, and traditional Chinese, and contains 12,723, 34,251, and 14,123 questions for the three languages, respectively. We implement both rule-based and popular neural methods by sequentially combining a document retriever and a machine comprehension model. Through experiments, we find that even the current best method can only achieve 36.7\%, 42.0\%, and 70.1\% of test accuracy on the English, traditional Chinese, and simplified Chinese questions, respectively. We expect MedQA to present great challenges to existing OpenQA systems and hope that it can serve as a platform to promote much stronger OpenQA models from the NLP community in the future.

Pretraining a deep learning model on large image datasets is a standard step before fine-tuning the model on small targeted datasets. The large dataset is usually general images (e.g. imagenet2012) while the small dataset can be specialized datasets that have different distributions from the large dataset. However, this 'large-to-small' strategy is not well-validated when the large dataset is specialized and has a similar distribution to small datasets. We newly compiled three hematoxylin and eosin-stained image datasets, one large (PTCGA200) and two magnification-adjusted small datasets (PCam200 and segPANDA200). Major deep learning models were trained with supervised and self-supervised learning methods and fine-tuned on the small datasets for tumor classification and tissue segmentation benchmarks. ResNet50 pretrained with MoCov2, SimCLR, and BYOL on PTCGA200 was better than imagenet2012 pretraining when fine-tuned on PTCGA200 (accuracy of 83.94%, 86.41%, 84.91%, and 82.72%, respectively). ResNet50 pre-trained on PTCGA200 with MoCov2 exceeded the COCOtrain2017-pretrained baseline and was the best in ResNet50 for the tissue segmentation benchmark (mIoU of 63.53% and 63.22%). We found re-training imagenet-pretrained models (ResNet50, BiT-M-R50x1, and ViT-S/16) on PTCGA200 improved downstream benchmarks.

This paper presents an annotated dataset of brain MRI images designed to advance the field of brain symmetry study. Magnetic resonance imaging (MRI) has gained interest in analyzing brain symmetry in neonatal infants, and challenges remain due to the vast size differences between fetal and adult brains. Classification methods for brain structural MRI use scales and visual cues to assess hemisphere symmetry, which can help diagnose neonatal patients by comparing hemispheres and anatomical regions of interest in the brain. Using the Developing Human Connectome Project dataset, this work presents a dataset comprising cerebral images extracted as slices across selected portions of interest for clinical evaluation . All the extracted images are annotated with the brain's midline. All the extracted images are annotated with the brain's midline. From the assumption that a decrease in symmetry is directly related to possible clinical pathologies, the dataset can contribute to a more precise diagnosis because it can be used to train deep learning model application in neonatal cerebral MRI anomaly detection from postnatal infant scans thanks to computer vision. Such models learn to identify and classify anomalies by identifying potential asymmetrical patterns in medical MRI images. Furthermore, this dataset can contribute to the research and development of methods using the relative symmetry of the two brain hemispheres for crucial diagnosis and treatment planning.

Vision-Language Models (VLMs) have shown promise in various 2D visual tasks, yet their readiness for 3D clinical diagnosis remains unclear due to stringent demands for recognition precision, reasoning ability, and domain knowledge. To systematically evaluate these dimensions, we present DeepTumorVQA, a diagnostic visual question answering (VQA) benchmark targeting abdominal tumors in CT scans. It comprises 9,262 CT volumes (3.7M slices) from 17 public datasets, with 395K expert-level questions spanning four categories: Recognition, Measurement, Visual Reasoning, and Medical Reasoning. DeepTumorVQA introduces unique challenges, including small tumor detection and clinical reasoning across 3D anatomy. Benchmarking four advanced VLMs (RadFM, M3D, Merlin, CT-CHAT), we find current models perform adequately on measurement tasks but struggle with lesion recognition and reasoning, and are still not meeting clinical needs. Two key insights emerge: (1) large-scale multimodal pretraining plays a crucial role in DeepTumorVQA testing performance, making RadFM stand out among all VLMs. (2) Our dataset exposes critical differences in VLM components, where proper image preprocessing and design of vision modules significantly affect 3D perception. To facilitate medical multimodal research, we have released DeepTumorVQA as a rigorous benchmark: https://github.com/Schuture/DeepTumorVQA.

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.

Recent advancements in Large Language Models (LLMs) have demonstrated their potential in delivering accurate answers to questions about world knowledge. Despite this, existing benchmarks for evaluating LLMs in healthcare predominantly focus on medical doctors, leaving other critical healthcare professions underrepresented. To fill this research gap, we introduce the Examinations for Medical Personnel in Chinese (EMPEC), a pioneering large-scale healthcare knowledge benchmark in traditional Chinese. EMPEC consists of 157,803 exam questions across 124 subjects and 20 healthcare professions, including underrepresented occupations like Optometrists and Audiologists. Each question is tagged with its release time and source, ensuring relevance and authenticity. We conducted extensive experiments on 17 LLMs, including proprietary, open-source models, general domain models and medical specific models, evaluating their performance under various settings. Our findings reveal that while leading models like GPT-4 achieve over 75\% accuracy, they still struggle with specialized fields and alternative medicine. Surprisingly, general-purpose LLMs outperformed medical-specific models, and incorporating EMPEC's training data significantly enhanced performance. Additionally, the results on questions released after the models' training cutoff date were consistent with overall performance trends, suggesting that the models' performance on the test set can predict their effectiveness in addressing unseen healthcare-related queries. The transition from traditional to simplified Chinese characters had a negligible impact on model performance, indicating robust linguistic versatility. Our study underscores the importance of expanding benchmarks to cover a broader range of healthcare professions to better assess the applicability of LLMs in real-world healthcare scenarios.

Large language models (LLMs), such as GPT-4, PaLM, and LLaMa, have been shown to achieve remarkable performance across a variety of natural language tasks. Recent advancements in instruction tuning bring LLMs with ability in following user's instructions and producing human-like responses. However, the high costs associated with training and implementing LLMs pose challenges to academic research. Furthermore, the availability of pretrained LLMs and instruction-tune datasets for Vietnamese language is limited. To tackle these concerns, we leverage large-scale instruction-following datasets from open-source projects, namely Alpaca, GPT4All, and Chat-Doctor, which cover general domain and specific medical domain. To the best of our knowledge, these are the first instructional dataset for Vietnamese. Subsequently, we utilize parameter-efficient tuning through Low-Rank Adaptation (LoRA) on two open LLMs: Bloomz (Multilingual) and GPTJ-6B (Vietnamese), resulting four models: Bloomz-Chat, Bloomz-Doctor, GPTJ-Chat, GPTJ-Doctor.Finally, we assess the effectiveness of our methodology on a per-sample basis, taking into consideration the helpfulness, relevance, accuracy, level of detail in their responses. This evaluation process entails the utilization of GPT-4 as an automated scoring mechanism. Despite utilizing a low-cost setup, our method demonstrates about 20-30\% improvement over the original models in our evaluation tasks.

Krylov subspace, which is generated by multiplying a given vector by the matrix of a linear transformation and its successive powers, has been extensively studied in classical optimization literature to design algorithms that converge quickly for large linear inverse problems. For example, the conjugate gradient method (CG), one of the most popular Krylov subspace methods, is based on the idea of minimizing the residual error in the Krylov subspace. However, with the recent advancement of high-performance diffusion solvers for inverse problems, it is not clear how classical wisdom can be synergistically combined with modern diffusion models. In this study, we propose a novel and efficient diffusion sampling strategy that synergistically combines the diffusion sampling and Krylov subspace methods. Specifically, we prove that if the tangent space at a denoised sample by Tweedie's formula forms a Krylov subspace, then the CG initialized with the denoised data ensures the data consistency update to remain in the tangent space. This negates the need to compute the manifold-constrained gradient (MCG), leading to a more efficient diffusion sampling method. Our method is applicable regardless of the parametrization and setting (i.e., VE, VP). Notably, we achieve state-of-the-art reconstruction quality on challenging real-world medical inverse imaging problems, including multi-coil MRI reconstruction and 3D CT reconstruction. Moreover, our proposed method achieves more than 80 times faster inference time than the previous state-of-the-art method. Code is available at https://github.com/HJ-harry/DDS

We present ReXGradient-160K, representing the largest publicly available chest X-ray dataset to date in terms of the number of patients. This dataset contains 160,000 chest X-ray studies with paired radiological reports from 109,487 unique patients across 3 U.S. health systems (79 medical sites). This comprehensive dataset includes multiple images per study and detailed radiology reports, making it particularly valuable for the development and evaluation of AI systems for medical imaging and automated report generation models. The dataset is divided into training (140,000 studies), validation (10,000 studies), and public test (10,000 studies) sets, with an additional private test set (10,000 studies) reserved for model evaluation on the ReXrank benchmark. By providing this extensive dataset, we aim to accelerate research in medical imaging AI and advance the state-of-the-art in automated radiological analysis. Our dataset will be open-sourced at https://huggingface.co/datasets/rajpurkarlab/ReXGradient-160K.

Widely deployed large language models (LLMs) can produce convincing yet incorrect outputs, potentially misleading users who may rely on them as if they were correct. To reduce such overreliance, there have been calls for LLMs to communicate their uncertainty to end users. However, there has been little empirical work examining how users perceive and act upon LLMs' expressions of uncertainty. We explore this question through a large-scale, pre-registered, human-subject experiment (N=404) in which participants answer medical questions with or without access to responses from a fictional LLM-infused search engine. Using both behavioral and self-reported measures, we examine how different natural language expressions of uncertainty impact participants' reliance, trust, and overall task performance. We find that first-person expressions (e.g., "I'm not sure, but...") decrease participants' confidence in the system and tendency to agree with the system's answers, while increasing participants' accuracy. An exploratory analysis suggests that this increase can be attributed to reduced (but not fully eliminated) overreliance on incorrect answers. While we observe similar effects for uncertainty expressed from a general perspective (e.g., "It's not clear, but..."), these effects are weaker and not statistically significant. Our findings suggest that using natural language expressions of uncertainty may be an effective approach for reducing overreliance on LLMs, but that the precise language used matters. This highlights the importance of user testing before deploying LLMs at scale.

The paper describes the open Russian medical language understanding benchmark covering several task types (classification, question answering, natural language inference, named entity recognition) on a number of novel text sets. Given the sensitive nature of the data in healthcare, such a benchmark partially closes the problem of Russian medical dataset absence. We prepare the unified format labeling, data split, and evaluation metrics for new tasks. The remaining tasks are from existing datasets with a few modifications. A single-number metric expresses a model's ability to cope with the benchmark. Moreover, we implement several baseline models, from simple ones to neural networks with transformer architecture, and release the code. Expectedly, the more advanced models yield better performance, but even a simple model is enough for a decent result in some tasks. Furthermore, for all tasks, we provide a human evaluation. Interestingly the models outperform humans in the large-scale classification tasks. However, the advantage of natural intelligence remains in the tasks requiring more knowledge and reasoning.

Pre-training large-scale neural language models on raw texts has made a significant contribution to improving transfer learning in natural language processing (NLP). With the introduction of transformer-based language models, such as bidirectional encoder representations from transformers (BERT), the performance of information extraction from a free text by NLP has significantly improved for both the general domain and medical domain; however, it is difficult to train specific BERT models that perform well for domains in which there are few publicly available databases of high quality and large size. We hypothesized that this problem can be addressed by up-sampling a domain-specific corpus and using it for pre-training with a larger corpus in a balanced manner. Our proposed method consists of a single intervention with one option: simultaneous pre-training after up-sampling and amplified vocabulary. We conducted three experiments and evaluated the resulting products. We confirmed that our Japanese medical BERT outperformed conventional baselines and the other BERT models in terms of the medical document classification task and that our English BERT pre-trained using both the general and medical-domain corpora performed sufficiently well for practical use in terms of the biomedical language understanding evaluation (BLUE) benchmark. Moreover, our enhanced biomedical BERT model, in which clinical notes were not used during pre-training, showed that both the clinical and biomedical scores of the BLUE benchmark were 0.3 points above that of the ablation model trained without our proposed method. Well-balanced pre-training by up-sampling instances derived from a corpus appropriate for the target task allows us to construct a high-performance BERT model.

Computed Tomography (CT) is one of the most popular modalities for medical imaging. By far, CT images have contributed to the largest publicly available datasets for volumetric medical segmentation tasks, covering full-body anatomical structures. Large amounts of full-body CT images provide the opportunity to pre-train powerful models, e.g., STU-Net pre-trained in a supervised fashion, to segment numerous anatomical structures. However, it remains unclear in which conditions these pre-trained models can be transferred to various downstream medical segmentation tasks, particularly segmenting the other modalities and diverse targets. To address this problem, a large-scale benchmark for comprehensive evaluation is crucial for finding these conditions. Thus, we collected 87 public datasets varying in modality, target, and sample size to evaluate the transfer ability of full-body CT pre-trained models. We then employed a representative model, STU-Net with multiple model scales, to conduct transfer learning across modalities and targets. Our experimental results show that (1) there may be a bottleneck effect concerning the dataset size in fine-tuning, with more improvement on both small- and large-scale datasets than medium-size ones. (2) Models pre-trained on full-body CT demonstrate effective modality transfer, adapting well to other modalities such as MRI. (3) Pre-training on the full-body CT not only supports strong performance in structure detection but also shows efficacy in lesion detection, showcasing adaptability across target tasks. We hope that this large-scale open evaluation of transfer learning can direct future research in volumetric medical image segmentation.

Multimodal Large Language Models (MLLMs) have demonstrated impressive capabilities in understanding common visual elements, largely due to their large-scale datasets and advanced training strategies. However, their effectiveness in medical applications remains limited due to the inherent discrepancies between data and tasks in medical scenarios and those in the general domain. Concretely, existing medical MLLMs face the following critical limitations: (1) limited coverage of medical knowledge beyond imaging, (2) heightened susceptibility to hallucinations due to suboptimal data curation processes, (3) lack of reasoning capabilities tailored for complex medical scenarios. To address these challenges, we first propose a comprehensive data curation procedure that (1) efficiently acquires rich medical knowledge data not only from medical imaging but also from extensive medical texts and general-domain data; and (2) synthesizes accurate medical captions, visual question answering (VQA), and reasoning samples. As a result, we build a multimodal dataset enriched with extensive medical knowledge. Building on the curated data, we introduce our medical-specialized MLLM: Lingshu. Lingshu undergoes multi-stage training to embed medical expertise and enhance its task-solving capabilities progressively. Besides, we preliminarily explore the potential of applying reinforcement learning with verifiable rewards paradigm to enhance Lingshu's medical reasoning ability. Additionally, we develop MedEvalKit, a unified evaluation framework that consolidates leading multimodal and textual medical benchmarks for standardized, fair, and efficient model assessment. We evaluate the performance of Lingshu on three fundamental medical tasks, multimodal QA, text-based QA, and medical report generation. The results show that Lingshu consistently outperforms the existing open-source multimodal models on most tasks ...

Image registration is fundamental in medical imaging, enabling precise alignment of anatomical structures for diagnosis, treatment planning, image-guided treatment or longitudinal monitoring. This work introduces IMPACT (Image Metric with Pretrained model-Agnostic Comparison for Transmodality registration), a generic semantic similarity metric designed for seamless integration into diverse image registration frameworks (such as Elastix and Voxelmorph). It compares deep learning-based features extracted from medical images without requiring task-specific training, ensuring broad applicability across various modalities. By leveraging the features of the large-scale pretrained TotalSegmentator models and the ability to integrate Segment Anything Model (SAM) and other large-scale segmentation networks, this approach offers significant advantages. It provides robust, scalable, and efficient solutions for multimodal image registration. The IMPACT loss was evaluated on five challenging registration tasks involving thoracic CT/CBCT, and pelvic MR/CT datasets. Quantitative metrics, such as Target Registration Error and Dice Similarity Coefficient, demonstrated significant improvements in anatomical alignment compared to baseline methods. Qualitative analyses further confirmed the increased robustness of the proposed metric in the face of noise, artifacts, and modality variations. IMPACT's versatility and efficiency make it a valuable tool for advancing registration performance in clinical and research applications, addressing critical challenges in multimodal medical imaging.

This study is dedicated to exploring the application of prompt learning methods to advance Named Entity Recognition (NER) within the medical domain. In recent years, the emergence of large-scale models has driven significant progress in NER tasks, particularly with the introduction of the BioBERT language model, which has greatly enhanced NER capabilities in medical texts. Our research introduces the Prompt-bioMRC model, which integrates both hard template and soft prompt designs aimed at refining the precision and efficiency of medical entity recognition. Through extensive experimentation across diverse medical datasets, our findings consistently demonstrate that our approach surpasses traditional models. This enhancement not only validates the efficacy of our methodology but also highlights its potential to provide reliable technological support for applications like intelligent diagnosis systems. By leveraging advanced NER techniques, this study contributes to advancing automated medical data processing, facilitating more accurate medical information extraction, and supporting efficient healthcare decision-making processes.

Recent "segment anything" efforts show promise by learning from large-scale data, but adapting such models directly to medical images remains challenging due to the complexity of medical data, noisy annotations, and continual learning requirements across diverse modalities and anatomical structures. In this work, we propose SAMed-2, a new foundation model for medical image segmentation built upon the SAM-2 architecture. Specifically, we introduce a temporal adapter into the image encoder to capture image correlations and a confidence-driven memory mechanism to store high-certainty features for later retrieval. This memory-based strategy counters the pervasive noise in large-scale medical datasets and mitigates catastrophic forgetting when encountering new tasks or modalities. To train and evaluate SAMed-2, we curate MedBank-100k, a comprehensive dataset spanning seven imaging modalities and 21 medical segmentation tasks. Our experiments on both internal benchmarks and 10 external datasets demonstrate superior performance over state-of-the-art baselines in multi-task scenarios. The code is available at: https://github.com/ZhilingYan/Medical-SAM-Bench.

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

Recent work has investigated the distributions of learned convolution filters through a large-scale study containing hundreds of heterogeneous image models. Surprisingly, on average, the distributions only show minor drifts in comparisons of various studied dimensions including the learned task, image domain, or dataset. However, among the studied image domains, medical imaging models appeared to show significant outliers through "spikey" distributions, and, therefore, learn clusters of highly specific filters different from other domains. Following this observation, we study the collected medical imaging models in more detail. We show that instead of fundamental differences, the outliers are due to specific processing in some architectures. Quite the contrary, for standardized architectures, we find that models trained on medical data do not significantly differ in their filter distributions from similar architectures trained on data from other domains. Our conclusions reinforce previous hypotheses stating that pre-training of imaging models can be done with any kind of diverse image data.

We present MedHal, a novel large-scale dataset specifically designed to evaluate if models can detect hallucinations in medical texts. Current hallucination detection methods face significant limitations when applied to specialized domains like medicine, where they can have disastrous consequences. Existing medical datasets are either too small, containing only a few hundred samples, or focus on a single task like Question Answering or Natural Language Inference. MedHal addresses these gaps by: (1) incorporating diverse medical text sources and tasks; (2) providing a substantial volume of annotated samples suitable for training medical hallucination detection models; and (3) including explanations for factual inconsistencies to guide model learning. We demonstrate MedHal's utility by training and evaluating a baseline medical hallucination detection model, showing improvements over general-purpose hallucination detection approaches. This resource enables more efficient evaluation of medical text generation systems while reducing reliance on costly expert review, potentially accelerating the development of medical AI research.

Interactive Medical Image Segmentation (IMIS) has long been constrained by the limited availability of large-scale, diverse, and densely annotated datasets, which hinders model generalization and consistent evaluation across different models. In this paper, we introduce the IMed-361M benchmark dataset, a significant advancement in general IMIS research. First, we collect and standardize over 6.4 million medical images and their corresponding ground truth masks from multiple data sources. Then, leveraging the strong object recognition capabilities of a vision foundational model, we automatically generated dense interactive masks for each image and ensured their quality through rigorous quality control and granularity management. Unlike previous datasets, which are limited by specific modalities or sparse annotations, IMed-361M spans 14 modalities and 204 segmentation targets, totaling 361 million masks-an average of 56 masks per image. Finally, we developed an IMIS baseline network on this dataset that supports high-quality mask generation through interactive inputs, including clicks, bounding boxes, text prompts, and their combinations. We evaluate its performance on medical image segmentation tasks from multiple perspectives, demonstrating superior accuracy and scalability compared to existing interactive segmentation models. To facilitate research on foundational models in medical computer vision, we release the IMed-361M and model at https://github.com/uni-medical/IMIS-Bench.

Vision-language pre-training for chest X-rays has made significant strides, primarily by utilizing paired radiographs and radiology reports. However, existing approaches often face challenges in encoding medical knowledge effectively. While radiology reports provide insights into the current disease manifestation, medical definitions (as used by contemporary methods) tend to be overly abstract, creating a gap in knowledge. To address this, we propose DeViDe, a novel transformer-based method that leverages radiographic descriptions from the open web. These descriptions outline general visual characteristics of diseases in radiographs, and when combined with abstract definitions and radiology reports, provide a holistic snapshot of knowledge. DeViDe incorporates three key features for knowledge-augmented vision language alignment: First, a large-language model-based augmentation is employed to homogenise medical knowledge from diverse sources. Second, this knowledge is aligned with image information at various levels of granularity. Third, a novel projection layer is proposed to handle the complexity of aligning each image with multiple descriptions arising in a multi-label setting. In zero-shot settings, DeViDe performs comparably to fully supervised models on external datasets and achieves state-of-the-art results on three large-scale datasets. Additionally, fine-tuning DeViDe on four downstream tasks and six segmentation tasks showcases its superior performance across data from diverse distributions.

Under the pandemic of COVID-19, people experiencing COVID19-related symptoms or exposed to risk factors have a pressing need to consult doctors. Due to hospital closure, a lot of consulting services have been moved online. Because of the shortage of medical professionals, many people cannot receive online consultations timely. To address this problem, we aim to develop a medical dialogue system that can provide COVID19-related consultations. We collected two dialogue datasets -- CovidDialog -- (in English and Chinese respectively) containing conversations between doctors and patients about COVID-19. On these two datasets, we train several dialogue generation models based on Transformer, GPT, and BERT-GPT. Since the two COVID-19 dialogue datasets are small in size, which bear high risk of overfitting, we leverage transfer learning to mitigate data deficiency. Specifically, we take the pretrained models of Transformer, GPT, and BERT-GPT on dialog datasets and other large-scale texts, then finetune them on our CovidDialog tasks. We perform both automatic and human evaluation of responses generated by these models. The results show that the generated responses are promising in being doctor-like, relevant to the conversation history, and clinically informative. The data and code are available at https://github.com/UCSD-AI4H/COVID-Dialogue.

Recent advancements in artificial intelligence (AI) have precipitated significant breakthroughs in healthcare, particularly in refining diagnostic procedures. However, previous studies have often been constrained to limited functionalities. This study introduces MiniGPT-Med, a vision-language model derived from large-scale language models and tailored for medical applications. MiniGPT-Med demonstrates remarkable versatility across various imaging modalities, including X-rays, CT scans, and MRIs, enhancing its utility. The model is capable of performing tasks such as medical report generation, visual question answering (VQA), and disease identification within medical imagery. Its integrated processing of both image and textual clinical data markedly improves diagnostic accuracy. Our empirical assessments confirm MiniGPT-Med's superior performance in disease grounding, medical report generation, and VQA benchmarks, representing a significant step towards reducing the gap in assisting radiology practice. Furthermore, it achieves state-of-the-art performance on medical report generation, higher than the previous best model by 19\% accuracy. MiniGPT-Med promises to become a general interface for radiology diagnoses, enhancing diagnostic efficiency across a wide range of medical imaging applications.

In this review, we explore the potential applications of Artificial General Intelligence (AGI) models in healthcare, focusing on foundational Large Language Models (LLMs), Large Vision Models, and Large Multimodal Models. We emphasize the importance of integrating clinical expertise, domain knowledge, and multimodal capabilities into AGI models. In addition, we lay out key roadmaps that guide the development and deployment of healthcare AGI models. Throughout the review, we provide critical perspectives on the potential challenges and pitfalls associated with deploying large-scale AGI models in the medical field. This comprehensive review aims to offer insights into the future implications of AGI in medical imaging, healthcare and beyond.

Recently, Large Language Models (LLMs) have showcased remarkable capabilities in natural language understanding. While demonstrating proficiency in everyday conversations and question-answering situations, these models frequently struggle in domains that require precision, such as medical applications, due to their lack of domain-specific knowledge. In this paper, we describe the procedure for building a powerful, open-source language model specifically designed for medicine applications, termed as PMC-LLaMA. Our contributions are threefold: (i) we systematically investigate the process of adapting a general-purpose foundation language model towards medical domain, this involves data-centric knowledge injection through the integration of 4.8M biomedical academic papers and 30K medical textbooks, as well as comprehensive fine-tuning for alignment with domain-specific instructions; (ii) we contribute a large-scale, comprehensive dataset for instruction tuning. This dataset encompasses medical question-answering (QA), rationale for reasoning, and conversational dialogues, comprising a total of 202M tokens; (iii) we conduct thorough ablation studies to demonstrate the effectiveness of each proposed component. While evaluating on various public medical question-answering benchmarks, our lightweight PMCLLaMA, which consists of only 13 billion parameters, exhibits superior performance, even surpassing ChatGPT. All models, codes, datasets can be found in https://github.com/chaoyi-wu/PMC-LLaMA.

In the field of medical imaging, the scarcity of large-scale datasets due to privacy restrictions stands as a significant barrier to develop large models for medical. To address this issue, we introduce SynFundus-1M, a high-quality synthetic dataset with over 1 million retinal fundus images and extensive disease and pathologies annotations, which is generated by a Denoising Diffusion Probabilistic Model. The SynFundus-Generator and SynFundus-1M achieve superior Frechet Inception Distance (FID) scores compared to existing methods on main-stream public real datasets. Furthermore, the ophthalmologists evaluation validate the difficulty in discerning these synthetic images from real ones, confirming the SynFundus-1M's authenticity. Through extensive experiments, we demonstrate that both CNN and ViT can benifit from SynFundus-1M by pretraining or training directly. Compared to datasets like ImageNet or EyePACS, models train on SynFundus-1M not only achieve better performance but also faster convergence on various downstream tasks.

Generative modeling has experienced substantial progress in recent years, particularly in text-to-image and text-to-video synthesis. However, the medical field has not yet fully exploited the potential of large-scale foundational models for synthetic data generation. In this paper, we introduce GenerateCT, the first method for text-conditional computed tomography (CT) generation, addressing the limitations in 3D medical imaging research and making our entire framework open-source. GenerateCT consists of a pre-trained large language model, a transformer-based text-conditional 3D chest CT generation architecture, and a text-conditional spatial super-resolution diffusion model. We also propose CT-ViT, which efficiently compresses CT volumes while preserving auto-regressiveness in-depth, enabling the generation of 3D CT volumes with variable numbers of axial slices. Our experiments demonstrate that GenerateCT can produce realistic, high-resolution, and high-fidelity 3D chest CT volumes consistent with medical language text prompts. We further investigate the potential of GenerateCT by training a model using generated CT volumes for multi-abnormality classification of chest CT volumes. Our contributions provide a valuable foundation for future research in text-conditional 3D medical image generation and have the potential to accelerate advancements in medical imaging research. Our code, pre-trained models, and generated data are available at https://github.com/ibrahimethemhamamci/GenerateCT.

Medical image segmentation has recently demonstrated impressive progress with deep neural networks, yet the heterogeneous modalities and scarcity of mask annotations limit the development of segmentation models on unannotated modalities. This paper investigates a new paradigm for leveraging generative models in medical applications: controllably synthesizing data for unannotated modalities, without requiring registered data pairs. Specifically, we make the following contributions in this paper: (i) we collect and curate a large-scale radiology image-text dataset, MedGen-1M, comprising modality labels, attributes, region, and organ information, along with a subset of organ mask annotations, to support research in controllable medical image generation; (ii) we propose a diffusion-based data engine, termed MRGen, which enables generation conditioned on text prompts and masks, synthesizing MR images for diverse modalities lacking mask annotations, to train segmentation models on unannotated modalities; (iii) we conduct extensive experiments across various modalities, illustrating that our data engine can effectively synthesize training samples and extend MRI segmentation towards unannotated modalities.

The rapid development of multimodal large language models (MLLMs), such as GPT-4V, has led to significant advancements. However, these models still face challenges in medical multimodal capabilities due to limitations in the quantity and quality of medical vision-text data, stemming from data privacy concerns and high annotation costs. While pioneering approaches utilize PubMed's large-scale, de-identified medical image-text pairs to address these limitations, they still fall short due to inherent data noise. To tackle this, we refined medical image-text pairs from PubMed and employed MLLMs (GPT-4V) in an 'unblinded' capacity to denoise and reformat the data, resulting in the creation of the PubMedVision dataset with 1.3 million medical VQA samples. Our validation demonstrates that: (1) PubMedVision can significantly enhance the medical multimodal capabilities of current MLLMs, showing significant improvement in benchmarks including the MMMU Health & Medicine track; (2) manual checks by medical experts and empirical results validate the superior data quality of our dataset compared to other data construction methods. Using PubMedVision, we train a 34B medical MLLM HuatuoGPT-Vision, which shows superior performance in medical multimodal scenarios among open-source MLLMs.

Foundation vision-language models are currently transforming computer vision, and are on the rise in medical imaging fueled by their very promising generalization capabilities. However, the initial attempts to transfer this new paradigm to medical imaging have shown less impressive performances than those observed in other domains, due to the significant domain shift and the complex, expert domain knowledge inherent to medical-imaging tasks. Motivated by the need for domain-expert foundation models, we present FLAIR, a pre-trained vision-language model for universal retinal fundus image understanding. To this end, we compiled 37 open-access, mostly categorical fundus imaging datasets from various sources, with up to 97 different target conditions and 284,660 images. We integrate the expert's domain knowledge in the form of descriptive textual prompts, during both pre-training and zero-shot inference, enhancing the less-informative categorical supervision of the data. Such a textual expert's knowledge, which we compiled from the relevant clinical literature and community standards, describes the fine-grained features of the pathologies as well as the hierarchies and dependencies between them. We report comprehensive evaluations, which illustrate the benefit of integrating expert knowledge and the strong generalization capabilities of FLAIR under difficult scenarios with domain shifts or unseen categories. When adapted with a lightweight linear probe, FLAIR outperforms fully-trained, dataset-focused models, more so in the few-shot regimes. Interestingly, FLAIR outperforms by a large margin more generalist, larger-scale image-language models, which emphasizes the potential of embedding experts' domain knowledge and the limitations of generalist models in medical imaging.

The rapid advancement of large models, driven by their exceptional abilities in learning and generalization through large-scale pre-training, has reshaped the landscape of Artificial Intelligence (AI). These models are now foundational to a wide range of applications, including conversational AI, recommendation systems, autonomous driving, content generation, medical diagnostics, and scientific discovery. However, their widespread deployment also exposes them to significant safety risks, raising concerns about robustness, reliability, and ethical implications. This survey provides a systematic review of current safety research on large models, covering Vision Foundation Models (VFMs), Large Language Models (LLMs), Vision-Language Pre-training (VLP) models, Vision-Language Models (VLMs), Diffusion Models (DMs), and large-model-based Agents. Our contributions are summarized as follows: (1) We present a comprehensive taxonomy of safety threats to these models, including adversarial attacks, data poisoning, backdoor attacks, jailbreak and prompt injection attacks, energy-latency attacks, data and model extraction attacks, and emerging agent-specific threats. (2) We review defense strategies proposed for each type of attacks if available and summarize the commonly used datasets and benchmarks for safety research. (3) Building on this, we identify and discuss the open challenges in large model safety, emphasizing the need for comprehensive safety evaluations, scalable and effective defense mechanisms, and sustainable data practices. More importantly, we highlight the necessity of collective efforts from the research community and international collaboration. Our work can serve as a useful reference for researchers and practitioners, fostering the ongoing development of comprehensive defense systems and platforms to safeguard AI models.

Large language models (LLMs) have demonstrated impressive capabilities in natural language understanding and generation, but the quality bar for medical and clinical applications is high. Today, attempts to assess models' clinical knowledge typically rely on automated evaluations on limited benchmarks. There is no standard to evaluate model predictions and reasoning across a breadth of tasks. To address this, we present MultiMedQA, a benchmark combining six existing open question answering datasets spanning professional medical exams, research, and consumer queries; and HealthSearchQA, a new free-response dataset of medical questions searched online. We propose a framework for human evaluation of model answers along multiple axes including factuality, precision, possible harm, and bias. In addition, we evaluate PaLM (a 540-billion parameter LLM) and its instruction-tuned variant, Flan-PaLM, on MultiMedQA. Using a combination of prompting strategies, Flan-PaLM achieves state-of-the-art accuracy on every MultiMedQA multiple-choice dataset (MedQA, MedMCQA, PubMedQA, MMLU clinical topics), including 67.6% accuracy on MedQA (US Medical License Exam questions), surpassing prior state-of-the-art by over 17%. However, human evaluation reveals key gaps in Flan-PaLM responses. To resolve this we introduce instruction prompt tuning, a parameter-efficient approach for aligning LLMs to new domains using a few exemplars. The resulting model, Med-PaLM, performs encouragingly, but remains inferior to clinicians. We show that comprehension, recall of knowledge, and medical reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal important limitations of today's models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLM models for clinical applications.

Large-scale medical imaging datasets have accelerated development of artificial intelligence tools for clinical decision support. However, the large size of these datasets is a bottleneck for users with limited storage and bandwidth. Many users may not even require such large datasets as AI models are often trained on lower resolution images. If users could directly download at their desired resolution, storage and bandwidth requirements would significantly decrease. However, it is impossible to anticipate every users' requirements and impractical to store the data at multiple resolutions. What if we could store images at a single resolution but send them at different ones? We propose MIST, an open-source framework to operationalize progressive resolution for streaming medical images at multiple resolutions from a single high-resolution copy. We demonstrate that MIST can dramatically reduce imaging infrastructure inefficiencies for hosting and streaming medical images by >90%, while maintaining diagnostic quality for deep learning applications.

There is an increasing interest in developing artificial intelligence (AI) systems to process and interpret electronic health records (EHRs). Natural language processing (NLP) powered by pretrained language models is the key technology for medical AI systems utilizing clinical narratives. However, there are few clinical language models, the largest of which trained in the clinical domain is comparatively small at 110 million parameters (compared with billions of parameters in the general domain). It is not clear how large clinical language models with billions of parameters can help medical AI systems utilize unstructured EHRs. In this study, we develop from scratch a large clinical language model - GatorTron - using >90 billion words of text (including >82 billion words of de-identified clinical text) and systematically evaluate it on 5 clinical NLP tasks including clinical concept extraction, medical relation extraction, semantic textual similarity, natural language inference (NLI), and medical question answering (MQA). We examine how (1) scaling up the number of parameters and (2) scaling up the size of the training data could benefit these NLP tasks. GatorTron models scale up the clinical language model from 110 million to 8.9 billion parameters and improve 5 clinical NLP tasks (e.g., 9.6% and 9.5% improvement in accuracy for NLI and MQA), which can be applied to medical AI systems to improve healthcare delivery. The GatorTron models are publicly available at: https://catalog.ngc.nvidia.com/orgs/nvidia/teams/clara/models/gatortron_og.

While Large Language Models (LLMs) excel in world knowledge understanding, adapting them to specific subfields requires precise adjustments. Due to the model's vast scale, traditional global fine-tuning methods for large models can be computationally expensive and impact generalization. To address this challenge, a range of innovative Parameters-Efficient Fine-Tuning (PEFT) methods have emerged and achieved remarkable success in both LLMs and Large Vision-Language Models (LVLMs). In the medical domain, fine-tuning a medical Vision-Language Pretrained (VLP) model is essential for adapting it to specific tasks. Can the fine-tuning methods for large models be transferred to the medical field to enhance transfer learning efficiency? In this paper, we delve into the fine-tuning methods of LLMs and conduct extensive experiments to investigate the impact of fine-tuning methods for large models on the existing multimodal model in the medical domain from the training data level and the model structure level. We show the different impacts of fine-tuning methods for large models on medical VLMs and develop the most efficient ways to fine-tune medical VLP models. We hope this research can guide medical domain researchers in optimizing VLMs' training costs, fostering the broader application of VLMs in healthcare fields. The code and dataset have been released at https://github.com/TIMMY-CHAN/MILE.

Contrastive Language-Image Pre-training (CLIP) demonstrates strong potential in medical image analysis but requires substantial data and computational resources. Due to these restrictions, existing CLIP applications in medical imaging focus mainly on modalities like chest X-rays that have abundant image-report data available, leaving many other important modalities underexplored. Here, we propose one of the first adaptations of the full CLIP model to mammography, which presents significant challenges due to labeled data scarcity, high-resolution images with small regions of interest, and class-wise imbalance. We first develop a specialized supervision framework for mammography that leverages its multi-view nature. Furthermore, we design a symmetric local alignment module to better focus on detailed features in high-resolution images. Lastly, we incorporate a parameter-efficient fine-tuning approach for large language models pre-trained with medical knowledge to address data limitations. Our multi-view and multi-scale alignment (MaMA) method outperforms state-of-the-art baselines for three different tasks on two large real-world mammography datasets, EMBED and RSNA-Mammo, with only 52% model size compared with the largest baseline. The code is available at https://github.com/XYPB/MaMA

Recently, large language model (LLM) based artificial intelligence (AI) systems have demonstrated remarkable capabilities in natural language understanding and generation. However, these models face a significant challenge when it comes to sensitive applications, such as reasoning over medical knowledge and answering medical questions in a physician-like manner. Prior studies attempted to overcome this challenge by increasing the model size (>100B) to learn more general medical knowledge, while there is still room for improvement in LLMs with smaller-scale model sizes (<100B). In this work, we start from a pre-trained general LLM model (AntGLM-10B) and fine-tune it from a medical beginner towards a medical expert (called AntGLM-Med-10B), which leverages a 3-stage optimization procedure, i.e., general medical knowledge injection, medical domain instruction tuning, and specific medical task adaptation. Our contributions are threefold: (1) We specifically investigate how to adapt a pre-trained general LLM in medical domain, especially for a specific medical task. (2) We collect and construct large-scale medical datasets for each stage of the optimization process. These datasets encompass various data types and tasks, such as question-answering, medical reasoning, multi-choice questions, and medical conversations. (3) Specifically for multi-choice questions in the medical domain, we propose a novel Verification-of-Choice approach for prompting engineering, which significantly enhances the reasoning ability of LLMs. Remarkably, by combining the above approaches, our AntGLM-Med-10B model can outperform the most of LLMs on PubMedQA, including both general and medical LLMs, even when these LLMs have larger model size.

Deep learning-based point cloud modeling has been widely investigated as an indispensable component of general shape analysis. Recently, transformer and state space model (SSM) have shown promising capacities in point cloud learning. However, limited research has been conducted on medical point clouds, which have great potential in disease diagnosis and treatment. This paper presents an SSM-based hierarchical feature learning framework for medical point cloud understanding. Specifically, we down-sample input into multiple levels through the farthest point sampling. At each level, we perform a series of k-nearest neighbor (KNN) queries to aggregate multi-scale structural information. To assist SSM in processing point clouds, we introduce coordinate-order and inside-out scanning strategies for efficient serialization of irregular points. Point features are calculated progressively from short neighbor sequences and long point sequences through vanilla and group Point SSM blocks, to capture both local patterns and long-range dependencies. To evaluate the proposed method, we build a large-scale medical point cloud dataset named MedPointS for anatomy classification, completion, and segmentation. Extensive experiments conducted on MedPointS demonstrate that our method achieves superior performance across all tasks. The dataset is available at https://flemme-docs.readthedocs.io/en/latest/medpoints.html. Code is merged to a public medical imaging platform: https://github.com/wlsdzyzl/flemme.

Advances in deep learning have significantly enhanced medical image analysis, yet the availability of large-scale medical datasets remains constrained by patient privacy concerns. We present EchoFlow, a novel framework designed to generate high-quality, privacy-preserving synthetic echocardiogram images and videos. EchoFlow comprises four key components: an adversarial variational autoencoder for defining an efficient latent representation of cardiac ultrasound images, a latent image flow matching model for generating accurate latent echocardiogram images, a latent re-identification model to ensure privacy by filtering images anatomically, and a latent video flow matching model for animating latent images into realistic echocardiogram videos conditioned on ejection fraction. We rigorously evaluate our synthetic datasets on the clinically relevant task of ejection fraction regression and demonstrate, for the first time, that downstream models trained exclusively on EchoFlow-generated synthetic datasets achieve performance parity with models trained on real datasets. We release our models and synthetic datasets, enabling broader, privacy-compliant research in medical ultrasound imaging at https://huggingface.co/spaces/HReynaud/EchoFlow.

In this study, we aim to initiate the development of Radiology Foundation Model, termed as RadFM.We consider the construction of foundational models from the perspectives of data, model design, and evaluation thoroughly. Our contribution can be concluded as follows: (i), we construct a large-scale Medical Multi-modal Dataset, MedMD, consisting of 16M 2D and 3D medical scans. To the best of our knowledge, this is the first multi-modal dataset containing 3D medical scans. (ii), We propose an architecture that enables visually conditioned generative pre-training, allowing for the integration of text input interleaved with 2D or 3D medical scans to generate response for diverse radiologic tasks. The model was initially pre-trained on MedMD and subsequently domain-specific fine-tuned on RadMD, a radiologic cleaned version of MedMD, containing 3M radiologic visual-language pairs. (iii), we propose a new evaluation benchmark that comprises five tasks, aiming to comprehensively assess the capability of foundation models in handling practical clinical problems. Our experimental results confirm that RadFM significantly outperforms existing multi-modal foundation models. The codes, data, and model checkpoint will all be made publicly available to promote further research and development in the field.

The Segment Anything Model (SAM) represents a state-of-the-art research advancement in natural image segmentation, achieving impressive results with input prompts such as points and bounding boxes. However, our evaluation and recent research indicate that directly applying the pretrained SAM to medical image segmentation does not yield satisfactory performance. This limitation primarily arises from significant domain gap between natural images and medical images. To bridge this gap, we introduce SAM-Med2D, the most comprehensive studies on applying SAM to medical 2D images. Specifically, we first collect and curate approximately 4.6M images and 19.7M masks from public and private datasets, constructing a large-scale medical image segmentation dataset encompassing various modalities and objects. Then, we comprehensively fine-tune SAM on this dataset and turn it into SAM-Med2D. Unlike previous methods that only adopt bounding box or point prompts as interactive segmentation approach, we adapt SAM to medical image segmentation through more comprehensive prompts involving bounding boxes, points, and masks. We additionally fine-tune the encoder and decoder of the original SAM to obtain a well-performed SAM-Med2D, leading to the most comprehensive fine-tuning strategies to date. Finally, we conducted a comprehensive evaluation and analysis to investigate the performance of SAM-Med2D in medical image segmentation across various modalities, anatomical structures, and organs. Concurrently, we validated the generalization capability of SAM-Med2D on 9 datasets from MICCAI 2023 challenge. Overall, our approach demonstrated significantly superior performance and generalization capability compared to SAM.

The generation of medical images presents significant challenges due to their high-resolution and three-dimensional nature. Existing methods often yield suboptimal performance in generating high-quality 3D medical images, and there is currently no universal generative framework for medical imaging. In this paper, we introduce the 3D Medical Diffusion (3D MedDiffusion) model for controllable, high-quality 3D medical image generation. 3D MedDiffusion incorporates a novel, highly efficient Patch-Volume Autoencoder that compresses medical images into latent space through patch-wise encoding and recovers back into image space through volume-wise decoding. Additionally, we design a new noise estimator to capture both local details and global structure information during diffusion denoising process. 3D MedDiffusion can generate fine-detailed, high-resolution images (up to 512x512x512) and effectively adapt to various downstream tasks as it is trained on large-scale datasets covering CT and MRI modalities and different anatomical regions (from head to leg). Experimental results demonstrate that 3D MedDiffusion surpasses state-of-the-art methods in generative quality and exhibits strong generalizability across tasks such as sparse-view CT reconstruction, fast MRI reconstruction, and data augmentation.

Medical image segmentation remains a formidable challenge due to the label scarcity. Pre-training Vision Transformer (ViT) through masked image modeling (MIM) on large-scale unlabeled medical datasets presents a promising solution, providing both computational efficiency and model generalization for various downstream tasks. However, current ViT-based MIM pre-training frameworks predominantly emphasize local aggregation representations in output layers and fail to exploit the rich representations across different ViT layers that better capture fine-grained semantic information needed for more precise medical downstream tasks. To fill the above gap, we hereby present Hierarchical Encoder-driven MAE (Hi-End-MAE), a simple yet effective ViT-based pre-training solution, which centers on two key innovations: (1) Encoder-driven reconstruction, which encourages the encoder to learn more informative features to guide the reconstruction of masked patches; and (2) Hierarchical dense decoding, which implements a hierarchical decoding structure to capture rich representations across different layers. We pre-train Hi-End-MAE on a large-scale dataset of 10K CT scans and evaluated its performance across seven public medical image segmentation benchmarks. Extensive experiments demonstrate that Hi-End-MAE achieves superior transfer learning capabilities across various downstream tasks, revealing the potential of ViT in medical imaging applications. The code is available at: https://github.com/FengheTan9/Hi-End-MAE

Deep learning presents novel opportunities for the auto-segmentation of gross tumor volume (GTV) in head and neck cancer (HNC), yet fully automatic methods usually necessitate significant manual refinement. This study investigates the Segment Anything Model (SAM), recognized for requiring minimal human prompting and its zero-shot generalization ability across natural images. We specifically examine MedSAM, a version of SAM fine-tuned with large-scale public medical images. Despite its progress, the integration of multi-modality images (CT, PET, MRI) for effective GTV delineation remains a challenge. Focusing on SAM's application in HNC GTV segmentation, we assess its performance in both zero-shot and fine-tuned scenarios using single (CT-only) and fused multi-modality images. Our study demonstrates that fine-tuning SAM significantly enhances its segmentation accuracy, building upon the already effective zero-shot results achieved with bounding box prompts. These findings open a promising avenue for semi-automatic HNC GTV segmentation.

We have released Sina-BERT, a language model pre-trained on BERT (Devlin et al., 2018) to address the lack of a high-quality Persian language model in the medical domain. SINA-BERT utilizes pre-training on a large-scale corpus of medical contents including formal and informal texts collected from a variety of online resources in order to improve the performance on health-care related tasks. We employ SINA-BERT to complete following representative tasks: categorization of medical questions, medical sentiment analysis, and medical question retrieval. For each task, we have developed Persian annotated data sets for training and evaluation and learnt a representation for the data of each task especially complex and long medical questions. With the same architecture being used across tasks, SINA-BERT outperforms BERT-based models that were previously made available in the Persian language.

Medical image segmentation involves partitioning medical images into meaningful regions, with a focus on identifying anatomical structures and lesions. It has broad applications in healthcare, and deep learning methods have enabled significant advancements in automating this process. Recently, the introduction of the Segmentation Anything Model (SAM), the first foundation model for segmentation task, has prompted researchers to adapt it for the medical domain to improve performance across various tasks. However, SAM's large model size and high GPU requirements hinder its scalability and development in the medical domain. In this work, we propose MCP-MedSAM, a powerful and lightweight medical SAM model designed to be trainable on a single A100 GPU with 40GB of memory within one day while delivering superior segmentation performance. Recognizing the significant internal differences between modalities and the need for direct segmentation target information within bounding boxes, we introduce two kinds of prompts: the modality prompt and the content prompt. After passing through the prompt encoder, their embedding representations can further improve the segmentation performance by incorporating more relevant information without adding significant training overhead. Additionally, we adopt an effective modality-based data sampling strategy to address data imbalance between modalities, ensuring more balanced performance across all modalities. Our method was trained and evaluated using a large-scale challenge dataset, compared to top-ranking methods on the challenge leaderboard, MCP-MedSAM achieved superior performance while requiring only one day of training on a single GPU. The code is publicly available at blue{https://github.com/dong845/MCP-MedSAM}.}

Artificial Intelligence (AI) has the potential to revolutionize diagnosis and segmentation in medical imaging. However, development and clinical implementation face multiple challenges including limited data availability, lack of generalizability, and the necessity to incorporate multi-modal data effectively. A foundation model, which is a large-scale pre-trained AI model, offers a versatile base that can be adapted to a variety of specific tasks and contexts. Here, we present a novel foundation model, VISION-MAE, specifically designed for medical imaging. Specifically, VISION-MAE is trained on a dataset of 2.5 million unlabeled images from various modalities (CT, MR, PET, X-rays, and ultrasound), using self-supervised learning techniques. It is then adapted to classification and segmentation tasks using explicit labels. VISION-MAE has high label efficiency, outperforming several benchmark models in both in-domain and out-of-domain applications, and achieves high performance even with reduced availability of labeled data. This model represents a significant advancement in medical imaging AI, offering a generalizable and robust solution for improving segmentation and classification tasks while reducing the data annotation workload.

Self-supervised learning has emerged as a highly effective approach in the fields of natural language processing and computer vision. It is also applicable to brain signals such as electroencephalography (EEG) data, given the abundance of available unlabeled data that exist in a wide spectrum of real-world medical applications ranging from seizure detection to wave analysis. The existing works leveraging self-supervised learning on EEG modeling mainly focus on pretraining upon each individual dataset corresponding to a single downstream task, which cannot leverage the power of abundant data, and they may derive sub-optimal solutions with a lack of generalization. Moreover, these methods rely on end-to-end model learning which is not easy for humans to understand. In this paper, we present a novel EEG foundation model, namely EEGFormer, pretrained on large-scale compound EEG data. The pretrained model cannot only learn universal representations on EEG signals with adaptable performance on various downstream tasks but also provide interpretable outcomes of the useful patterns within the data. To validate the effectiveness of our model, we extensively evaluate it on various downstream tasks and assess the performance under different transfer settings. Furthermore, we demonstrate how the learned model exhibits transferable anomaly detection performance and provides valuable interpretability of the acquired patterns via self-supervised learning.

Whole-heart segmentation from CT and MRI scans is crucial for cardiovascular disease analysis, yet existing methods struggle with modality-specific biases and the need for extensive labeled datasets. To address these challenges, we propose a foundation model for whole-heart segmentation using a self-supervised learning (SSL) framework based on a student-teacher architecture. Our model is pretrained on a large, unlabeled dataset of CT and MRI scans, leveraging the xLSTM backbone to capture long-range spatial dependencies and complex anatomical structures in 3D medical images. By incorporating multi-modal pretraining, our approach ensures strong generalization across both CT and MRI modalities, mitigating modality-specific variations and improving segmentation accuracy in diverse clinical settings. The use of large-scale unlabeled data significantly reduces the dependency on manual annotations, enabling robust performance even with limited labeled data. We further introduce an xLSTM-UNet-based architecture for downstream whole-heart segmentation tasks, demonstrating its effectiveness on few-label CT and MRI datasets. Our results validate the robustness and adaptability of the proposed model, highlighting its potential for advancing automated whole-heart segmentation in medical imaging.

Interpretability can improve the safety, transparency and trust of AI models, which is especially important in healthcare applications where decisions often carry significant consequences. Mechanistic interpretability, particularly through the use of sparse autoencoders (SAEs), offers a promising approach for uncovering human-interpretable features within large transformer-based models. In this study, we apply Matryoshka-SAE to the radiology-specialised multimodal large language model, MAIRA-2, to interpret its internal representations. Using large-scale automated interpretability of the SAE features, we identify a range of clinically relevant concepts - including medical devices (e.g., line and tube placements, pacemaker presence), pathologies such as pleural effusion and cardiomegaly, longitudinal changes and textual features. We further examine the influence of these features on model behaviour through steering, demonstrating directional control over generations with mixed success. Our results reveal practical and methodological challenges, yet they offer initial insights into the internal concepts learned by MAIRA-2 - marking a step toward deeper mechanistic understanding and interpretability of a radiology-adapted multimodal large language model, and paving the way for improved model transparency. We release the trained SAEs and interpretations: https://huggingface.co/microsoft/maira-2-sae.

Fairness or equity in machine learning is profoundly important for societal well-being, but limited public datasets hinder its progress, especially in the area of medicine. It is undeniable that fairness in medicine is one of the most important areas for fairness learning's applications. Currently, no large-scale public medical datasets with 3D imaging data for fairness learning are available, while 3D imaging data in modern clinics are standard tests for disease diagnosis. In addition, existing medical fairness datasets are actually repurposed datasets, and therefore they typically have limited demographic identity attributes with at most three identity attributes of age, gender, and race for fairness modeling. To address this gap, we introduce our Eye Fairness dataset with 30,000 subjects (Harvard-EF) covering three major eye diseases including age-related macular degeneration, diabetic retinopathy, and glaucoma affecting 380 million patients globally. Our Harvard-EF dataset includes both 2D fundus photos and 3D optical coherence tomography scans with six demographic identity attributes including age, gender, race, ethnicity, preferred language, and marital status. We also propose a fair identity scaling (FIS) approach combining group and individual scaling together to improve model fairness. Our FIS approach is compared with various state-of-the-art fairness learning methods with superior performance in the racial, gender, and ethnicity fairness tasks with 2D and 3D imaging data, which demonstrate the utilities of our Harvard-EF dataset for fairness learning. To facilitate fairness comparisons between different models, we propose performance-scaled disparity measures, which can be used to compare model fairness accounting for overall performance levels. The dataset and code are publicly accessible via https://ophai.hms.harvard.edu/datasets/harvard-ef30k.

Pre-trained large language models(LLMs) have attracted increasing attention in biomedical domains due to their success in natural language processing. However, the complex traits and heterogeneity of multi-sources genomics data pose significant challenges when adapting these models to the bioinformatics and biomedical field. To address these challenges, we present GP-GPT, the first specialized large language model for genetic-phenotype knowledge representation and genomics relation analysis. Our model is fine-tuned in two stages on a comprehensive corpus composed of over 3,000,000 terms in genomics, proteomics, and medical genetics, derived from multiple large-scale validated datasets and scientific publications. GP-GPT demonstrates proficiency in accurately retrieving medical genetics information and performing common genomics analysis tasks, such as genomics information retrieval and relationship determination. Comparative experiments across domain-specific tasks reveal that GP-GPT outperforms state-of-the-art LLMs, including Llama2, Llama3 and GPT-4. These results highlight GP-GPT's potential to enhance genetic disease relation research and facilitate accurate and efficient analysis in the fields of genomics and medical genetics. Our investigation demonstrated the subtle changes of bio-factor entities' representations in the GP-GPT, which suggested the opportunities for the application of LLMs to advancing gene-phenotype research.

Trustworthiness is essential for the precise and interpretable application of artificial intelligence (AI) in medical imaging. Traditionally, precision and interpretability have been addressed as separate tasks, namely medical image analysis and explainable AI, each developing its own models independently. In this study, for the first time, we investigate the development of a unified medical vision-language pre-training model that can achieve both accurate analysis and interpretable understanding of medical images across various modalities. To build the model, we construct MedConcept-23M, a large-scale dataset comprising 23 million medical image-text pairs extracted from 6.2 million scientific articles, enriched with concepts from the Unified Medical Language System (UMLS). Based on MedConcept-23M, we introduce ConceptCLIP, a medical AI model utilizing concept-enhanced contrastive language-image pre-training. The pre-training of ConceptCLIP involves two primary components: image-text alignment learning (IT-Align) and patch-concept alignment learning (PC-Align). This dual alignment strategy enhances the model's capability to associate specific image regions with relevant concepts, thereby improving both the precision of analysis and the interpretability of the AI system. We conducted extensive experiments on 5 diverse types of medical image analysis tasks, spanning 51 subtasks across 10 image modalities, with the broadest range of downstream tasks. The results demonstrate the effectiveness of the proposed vision-language pre-training model. Further explainability analysis across 6 modalities reveals that ConceptCLIP achieves superior performance, underscoring its robust ability to advance explainable AI in medical imaging. These findings highlight ConceptCLIP's capability in promoting trustworthy AI in the field of medicine.

In this paper, we focus on the problem of Medical Visual Question Answering (MedVQA), which is crucial in efficiently interpreting medical images with vital clinic-relevant information. Firstly, we reframe the problem of MedVQA as a generation task that naturally follows the human-machine interaction, we propose a generative-based model for medical visual understanding by aligning visual information from a pre-trained vision encoder with a large language model. Secondly, we establish a scalable pipeline to construct a large-scale medical visual question-answering dataset, named PMC-VQA, which contains 227k VQA pairs of 149k images that cover various modalities or diseases. Thirdly, we pre-train our proposed model on PMC-VQA and then fine-tune it on multiple public benchmarks, e.g., VQA-RAD and SLAKE, outperforming existing work by a large margin. Additionally, we propose a test set that has undergone manual verification, which is significantly more challenging, even the best models struggle to solve.

Convolutional Neural Networks (CNNs) have advanced existing medical systems for automatic disease diagnosis. However, there are still concerns about the reliability of deep medical diagnosis systems against the potential threats of adversarial attacks since inaccurate diagnosis could lead to disastrous consequences in the safety realm. In this study, we propose a highly robust yet efficient CNN-Transformer hybrid model which is equipped with the locality of CNNs as well as the global connectivity of vision Transformers. To mitigate the high quadratic complexity of the self-attention mechanism while jointly attending to information in various representation subspaces, we construct our attention mechanism by means of an efficient convolution operation. Moreover, to alleviate the fragility of our Transformer model against adversarial attacks, we attempt to learn smoother decision boundaries. To this end, we augment the shape information of an image in the high-level feature space by permuting the feature mean and variance within mini-batches. With less computational complexity, our proposed hybrid model demonstrates its high robustness and generalization ability compared to the state-of-the-art studies on a large-scale collection of standardized MedMNIST-2D datasets.

Chest X-rays (CXRs) are the most frequently performed imaging test in clinical practice. Recent advances in the development of vision-language foundation models (FMs) give rise to the possibility of performing automated CXR interpretation, which can assist physicians with clinical decision-making and improve patient outcomes. However, developing FMs that can accurately interpret CXRs is challenging due to the (1) limited availability of large-scale vision-language datasets in the medical image domain, (2) lack of vision and language encoders that can capture the complexities of medical data, and (3) absence of evaluation frameworks for benchmarking the abilities of FMs on CXR interpretation. In this work, we address these challenges by first introducing CheXinstruct - a large-scale instruction-tuning dataset curated from 28 publicly-available datasets. We then present CheXagent - an instruction-tuned FM capable of analyzing and summarizing CXRs. To build CheXagent, we design a clinical large language model (LLM) for parsing radiology reports, a vision encoder for representing CXR images, and a network to bridge the vision and language modalities. Finally, we introduce CheXbench - a novel benchmark designed to systematically evaluate FMs across 8 clinically-relevant CXR interpretation tasks. Extensive quantitative evaluations and qualitative reviews with five expert radiologists demonstrate that CheXagent outperforms previously-developed general- and medical-domain FMs on CheXbench tasks. Furthermore, in an effort to improve model transparency, we perform a fairness evaluation across factors of sex, race and age to highlight potential performance disparities. Our project is at https://stanford-aimi.github.io/chexagent.html.

There is enormous enthusiasm and concerns in using large language models (LLMs) in healthcare, yet current assumptions are all based on general-purpose LLMs such as ChatGPT. This study develops a clinical generative LLM, GatorTronGPT, using 277 billion words of mixed clinical and English text with a GPT-3 architecture of 20 billion parameters. GatorTronGPT improves biomedical natural language processing for medical research. Synthetic NLP models trained using GatorTronGPT generated text outperform NLP models trained using real-world clinical text. Physicians Turing test using 1 (worst) to 9 (best) scale shows that there is no significant difference in linguistic readability (p = 0.22; 6.57 of GatorTronGPT compared with 6.93 of human) and clinical relevance (p = 0.91; 7.0 of GatorTronGPT compared with 6.97 of human) and that physicians cannot differentiate them (p < 0.001). This study provides insights on the opportunities and challenges of LLMs for medical research and healthcare.

State Space Models (SSMs), especially Mamba, have shown great promise in medical image segmentation due to their ability to model long-range dependencies with linear computational complexity. However, accurate medical image segmentation requires the effective learning of both multi-scale detailed feature representations and global contextual dependencies. Although existing works have attempted to address this issue by integrating CNNs and SSMs to leverage their respective strengths, they have not designed specialized modules to effectively capture multi-scale feature representations, nor have they adequately addressed the directional sensitivity problem when applying Mamba to 2D image data. To overcome these limitations, we propose a Multi-Scale Vision Mamba UNet model for medical image segmentation, termed MSVM-UNet. Specifically, by introducing multi-scale convolutions in the VSS blocks, we can more effectively capture and aggregate multi-scale feature representations from the hierarchical features of the VMamba encoder and better handle 2D visual data. Additionally, the large kernel patch expanding (LKPE) layers achieve more efficient upsampling of feature maps by simultaneously integrating spatial and channel information. Extensive experiments on the Synapse and ACDC datasets demonstrate that our approach is more effective than some state-of-the-art methods in capturing and aggregating multi-scale feature representations and modeling long-range dependencies between pixels.

Large Language Models (LLMs), known for their versatility in textual data, are increasingly being explored for their potential to enhance medical image segmentation, a crucial task for accurate diagnostic imaging. This study explores enhancing Vision Transformers (ViTs) for medical image segmentation by integrating pre-trained LLM transformer blocks. Our approach, which incorporates a frozen LLM transformer block into the encoder of a ViT-based model, leads to substantial improvements in segmentation performance across various medical imaging modalities. We propose a Hybrid Attention Mechanism that combines global and local feature learning with a Multi-Scale Fusion Block for aggregating features across different scales. The enhanced model shows significant performance gains, including an average Dice score increase from 0.74 to 0.79 and improvements in accuracy, precision, and the Jaccard Index. These results demonstrate the effectiveness of LLM-based transformers in refining medical image segmentation, highlighting their potential to significantly boost model accuracy and robustness. The source code and our implementation are available at: https://bit.ly/3zf2CVs

We introduce MedAgentGYM, the first publicly available training environment designed to enhance coding-based medical reasoning capabilities in large language model (LLM) agents. MedAgentGYM comprises 72,413 task instances across 129 categories derived from authentic real-world biomedical scenarios. Tasks are encapsulated within executable coding environments, each featuring detailed task descriptions, interactive feedback mechanisms, verifiable ground-truth annotations, and scalable training trajectory generation. Extensive benchmarking of over 30 LLMs reveals a notable performance disparity between commercial API-based models and open-source counterparts. Leveraging MedAgentGYM, Med-Copilot-7B achieves substantial performance gains through supervised fine-tuning (+36.44%) and continued reinforcement learning (+42.47%), emerging as an affordable and privacy-preserving alternative competitive with gpt-4o. By offering both a comprehensive benchmark and accessible, expandable training resources within unified execution environments, MedAgentGYM delivers an integrated platform to develop LLM-based coding assistants for advanced biomedical research and practice.

The previous advancements in pathology image understanding primarily involved developing models tailored to specific tasks. Recent studies has demonstrated that the large vision-language model can enhance the performance of various downstream tasks in medical image understanding. In this study, we developed a domain-specific large language-vision assistant (PA-LLaVA) for pathology image understanding. Specifically, (1) we first construct a human pathology image-text dataset by cleaning the public medical image-text data for domain-specific alignment; (2) Using the proposed image-text data, we first train a pathology language-image pretraining (PLIP) model as the specialized visual encoder for pathology image, and then we developed scale-invariant connector to avoid the information loss caused by image scaling; (3) We adopt two-stage learning to train PA-LLaVA, first stage for domain alignment, and second stage for end to end visual question \& answering (VQA) task. In experiments, we evaluate our PA-LLaVA on both supervised and zero-shot VQA datasets, our model achieved the best overall performance among multimodal models of similar scale. The ablation experiments also confirmed the effectiveness of our design. We posit that our PA-LLaVA model and the datasets presented in this work can promote research in field of computational pathology. All codes are available at: https://github.com/ddw2AIGROUP2CQUPT/PA-LLaVA}{https://github.com/ddw2AIGROUP2CQUPT/PA-LLaVA

Medical image analysis is a fundamental component. As deep learning progresses, the focus has shifted from single-task applications, such as classification and segmentation, to more complex multimodal tasks, including medical visual question answering and report generation. Traditional shallow and task-specific models are increasingly limited in addressing the complexity and scalability required in clinical practice. The emergence of large language models (LLMs) has driven the development of medical Large Vision-Language Models (LVLMs), offering a unified solution for diverse vision-language tasks. In this study, we investigate various architectural designs for medical LVLMs based on the widely adopted LLaVA framework, which follows an encoder-connector-LLM paradigm. We construct two distinct models targeting 2D and 3D modalities, respectively. These models are designed to support both general-purpose medical tasks and domain-specific fine-tuning, thereby serving as effective foundation models. To facilitate reproducibility and further research, we develop a modular and extensible codebase, MedM-VL, and release two LVLM variants: MedM-VL-2D for 2D medical image analysis and MedM-VL-CT-Chest for 3D CT-based applications. The code and models are available at: https://github.com/MSIIP/MedM-VL

The scaling laws and extraordinary performance of large foundation models motivate the development and utilization of such models in biomedicine. However, despite early promising results on some biomedical benchmarks, there are still major challenges that need to be addressed before these models can be used in real-world clinics. Frontier general-domain models such as GPT-4V still have significant performance gaps in multimodal biomedical applications. More importantly, less-acknowledged pragmatic issues, including accessibility, model cost, and tedious manual evaluation make it hard for clinicians to use state-of-the-art large models directly on private patient data. Here, we explore training open-source small multimodal models (SMMs) to bridge competency gaps for unmet clinical needs in radiology. To maximize data efficiency, we adopt a modular approach by incorporating state-of-the-art pre-trained models for image and text modalities, and focusing on training a lightweight adapter to ground each modality to the text embedding space, as exemplified by LLaVA-Med. For training, we assemble a large dataset of over 697 thousand radiology image-text pairs. For evaluation, we propose CheXprompt, a GPT-4-based metric for factuality evaluation, and demonstrate its parity with expert evaluation. For best practice, we conduct a systematic ablation study on various choices in data engineering and multimodal training. The resulting LlaVA-Rad (7B) model attains state-of-the-art results on standard radiology tasks such as report generation and cross-modal retrieval, even outperforming much larger models such as GPT-4V and Med-PaLM M (84B). The inference of LlaVA-Rad is fast and can be performed on a single V100 GPU in private settings, offering a promising state-of-the-art tool for real-world clinical applications.

Large language models (LLMs) represent a transformative class of AI tools capable of revolutionizing various aspects of healthcare by generating human-like responses across diverse contexts and adapting to novel tasks following human instructions. Their potential application spans a broad range of medical tasks, such as clinical documentation, matching patients to clinical trials, and answering medical questions. In this primer paper, we propose an actionable guideline to help healthcare professionals more efficiently utilize LLMs in their work, along with a set of best practices. This approach consists of several main phases, including formulating the task, choosing LLMs, prompt engineering, fine-tuning, and deployment. We start with the discussion of critical considerations in identifying healthcare tasks that align with the core capabilities of LLMs and selecting models based on the selected task and data, performance requirements, and model interface. We then review the strategies, such as prompt engineering and fine-tuning, to adapt standard LLMs to specialized medical tasks. Deployment considerations, including regulatory compliance, ethical guidelines, and continuous monitoring for fairness and bias, are also discussed. By providing a structured step-by-step methodology, this tutorial aims to equip healthcare professionals with the tools necessary to effectively integrate LLMs into clinical practice, ensuring that these powerful technologies are applied in a safe, reliable, and impactful manner.

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.

The integration of Large Language Models (LLMs) into healthcare promises to transform medical diagnostics, research, and patient care. Yet, the progression of medical LLMs faces obstacles such as complex training requirements, rigorous evaluation demands, and the dominance of proprietary models that restrict academic exploration. Transparent, comprehensive access to LLM resources is essential for advancing the field, fostering reproducibility, and encouraging innovation in healthcare AI. We present Hippocrates, an open-source LLM framework specifically developed for the medical domain. In stark contrast to previous efforts, it offers unrestricted access to its training datasets, codebase, checkpoints, and evaluation protocols. This open approach is designed to stimulate collaborative research, allowing the community to build upon, refine, and rigorously evaluate medical LLMs within a transparent ecosystem. Also, we introduce Hippo, a family of 7B models tailored for the medical domain, fine-tuned from Mistral and LLaMA2 through continual pre-training, instruction tuning, and reinforcement learning from human and AI feedback. Our models outperform existing open medical LLMs models by a large-margin, even surpassing models with 70B parameters. Through Hippocrates, we aspire to unlock the full potential of LLMs not just to advance medical knowledge and patient care but also to democratize the benefits of AI research in healthcare, making them available across the globe.

Large Language Models (LLMs) hold great promise to revolutionize current clinical systems for their superior capacities on medical text processing tasks and medical licensing exams. Meanwhile, traditional ML models such as SVM and XGBoost have still been mainly adopted in clinical prediction tasks. An emerging question is Can LLMs beat traditional ML models in clinical prediction? Thus, we build a new benchmark ClinicalBench to comprehensively study the clinical predictive modeling capacities of both general-purpose and medical LLMs, and compare them with traditional ML models. ClinicalBench embraces three common clinical prediction tasks, two databases, 14 general-purpose LLMs, 8 medical LLMs, and 11 traditional ML models. Through extensive empirical investigation, we discover that both general-purpose and medical LLMs, even with different model scales, diverse prompting or fine-tuning strategies, still cannot beat traditional ML models in clinical prediction yet, shedding light on their potential deficiency in clinical reasoning and decision-making. We call for caution when practitioners adopt LLMs in clinical applications. ClinicalBench can be utilized to bridge the gap between LLMs' development for healthcare and real-world clinical practice.

Large Language Models (LLMs) have gained significant attention in the medical domain for their human-level capabilities, leading to increased efforts to explore their potential in various healthcare applications. However, despite such a promising future, there are multiple challenges and obstacles that remain for their real-world uses in practical settings. This work discusses key challenges for LLMs in medical applications from four unique aspects: operational vulnerabilities, ethical and social considerations, performance and assessment difficulties, and legal and regulatory compliance. Addressing these challenges is crucial for leveraging LLMs to their full potential and ensuring their responsible integration into healthcare.

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.

Large Language Model (LLM)-based agents have demonstrated strong capabilities across a wide range of tasks, and their application in the medical domain holds particular promise due to the demand for high generalizability and reliance on interdisciplinary knowledge. However, existing medical agent systems often rely on static, manually crafted workflows that lack the flexibility to accommodate diverse diagnostic requirements and adapt to emerging clinical scenarios. Motivated by the success of automated machine learning (AutoML), this paper introduces a novel framework for the automated design of medical agent architectures. Specifically, we define a hierarchical and expressive agent search space that enables dynamic workflow adaptation through structured modifications at the node, structural, and framework levels. Our framework conceptualizes medical agents as graph-based architectures composed of diverse, functional node types and supports iterative self-improvement guided by diagnostic feedback. Experimental results on skin disease diagnosis tasks demonstrate that the proposed method effectively evolves workflow structures and significantly enhances diagnostic accuracy over time. This work represents the first fully automated framework for medical agent architecture design and offers a scalable, adaptable foundation for deploying intelligent agents in real-world clinical environments.

Large language models (LLMs) hold great promise for medical applications and are evolving rapidly, with new models being released at an accelerated pace. However, current evaluations of LLMs in clinical contexts remain limited. Most existing benchmarks rely on medical exam-style questions or PubMed-derived text, failing to capture the complexity of real-world electronic health record (EHR) data. Others focus narrowly on specific application scenarios, limiting their generalizability across broader clinical use. To address this gap, we present BRIDGE, a comprehensive multilingual benchmark comprising 87 tasks sourced from real-world clinical data sources across nine languages. We systematically evaluated 52 state-of-the-art LLMs (including DeepSeek-R1, GPT-4o, Gemini, and Llama 4) under various inference strategies. With a total of 13,572 experiments, our results reveal substantial performance variation across model sizes, languages, natural language processing tasks, and clinical specialties. Notably, we demonstrate that open-source LLMs can achieve performance comparable to proprietary models, while medically fine-tuned LLMs based on older architectures often underperform versus updated general-purpose models. The BRIDGE and its corresponding leaderboard serve as a foundational resource and a unique reference for the development and evaluation of new LLMs in real-world clinical text understanding.

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.

Large Language Models (LLMs) have demonstrated significant potential in handling specialized tasks, including medical problem-solving. However, most studies predominantly focus on English-language contexts. This study introduces a novel benchmark dataset based on Polish medical licensing and specialization exams (LEK, LDEK, PES) taken by medical doctor candidates and practicing doctors pursuing specialization. The dataset was web-scraped from publicly available resources provided by the Medical Examination Center and the Chief Medical Chamber. It comprises over 24,000 exam questions, including a subset of parallel Polish-English corpora, where the English portion was professionally translated by the examination center for foreign candidates. By creating a structured benchmark from these existing exam questions, we systematically evaluate state-of-the-art LLMs, including general-purpose, domain-specific, and Polish-specific models, and compare their performance against human medical students. Our analysis reveals that while models like GPT-4o achieve near-human performance, significant challenges persist in cross-lingual translation and domain-specific understanding. These findings underscore disparities in model performance across languages and medical specialties, highlighting the limitations and ethical considerations of deploying LLMs in clinical practice.

Large Language Models (LLMs) have introduced a new era of proficiency in comprehending complex healthcare and biomedical topics. However, there is a noticeable lack of models in languages other than English and models that can interpret multi-modal input, which is crucial for global healthcare accessibility. In response, this study introduces Qilin-Med-VL, the first Chinese large vision-language model designed to integrate the analysis of textual and visual data. Qilin-Med-VL combines a pre-trained Vision Transformer (ViT) with a foundational LLM. It undergoes a thorough two-stage curriculum training process that includes feature alignment and instruction tuning. This method enhances the model's ability to generate medical captions and answer complex medical queries. We also release ChiMed-VL, a dataset consisting of more than 1M image-text pairs. This dataset has been carefully curated to enable detailed and comprehensive interpretation of medical data using various types of images.

Med42-v2 introduces a suite of clinical large language models (LLMs) designed to address the limitations of generic models in healthcare settings. These models are built on Llama3 architecture and fine-tuned using specialized clinical data. They underwent multi-stage preference alignment to effectively respond to natural prompts. While generic models are often preference-aligned to avoid answering clinical queries as a precaution, Med42-v2 is specifically trained to overcome this limitation, enabling its use in clinical settings. Med42-v2 models demonstrate superior performance compared to the original Llama3 models in both 8B and 70B parameter configurations and GPT-4 across various medical benchmarks. These LLMs are developed to understand clinical queries, perform reasoning tasks, and provide valuable assistance in clinical environments. The models are now publicly available at https://huggingface.co/m42-health{https://huggingface.co/m42-health}.

Recent large language models (LLMs) in the general domain, such as ChatGPT, have shown remarkable success in following instructions and producing human-like responses. However, such language models have not been learned individually and carefully for the medical domain, resulting in poor diagnostic accuracy and inability to give correct recommendations for medical diagnosis, medications, etc. To address this issue, we collected more than 700 diseases and their corresponding symptoms, recommended medications, and required medical tests, and then generated 5K doctor-patient conversations. By fine-tuning models of doctor-patient conversations, these models emerge with great potential to understand patients' needs, provide informed advice, and offer valuable assistance in a variety of medical-related fields. The integration of these advanced language models into healthcare can revolutionize the way healthcare professionals and patients communicate, ultimately improving the overall quality of care and patient outcomes. In addition, we will open all source code, datasets and model weights to advance the further development of dialogue models in the medical field. In addition, the training data, code, and weights of this project are available at: https://github.com/Kent0n-Li/ChatDoctor.

Multimodal Large Language Models (MLLMs) have tremendous potential to improve the accuracy, availability, and cost-effectiveness of healthcare by providing automated solutions or serving as aids to medical professionals. Despite promising first steps in developing medical MLLMs in the past few years, their capabilities and limitations are not well-understood. Recently, many benchmark datasets have been proposed that test the general medical knowledge of such models across a variety of medical areas. However, the systematic failure modes and vulnerabilities of such models are severely underexplored with most medical benchmarks failing to expose the shortcomings of existing models in this safety-critical domain. In this paper, we introduce MediConfusion, a challenging medical Visual Question Answering (VQA) benchmark dataset, that probes the failure modes of medical MLLMs from a vision perspective. We reveal that state-of-the-art models are easily confused by image pairs that are otherwise visually dissimilar and clearly distinct for medical experts. Strikingly, all available models (open-source or proprietary) achieve performance below random guessing on MediConfusion, raising serious concerns about the reliability of existing medical MLLMs for healthcare deployment. We also extract common patterns of model failure that may help the design of a new generation of more trustworthy and reliable MLLMs in healthcare.

Recently, the increasing demand for superior medical services has highlighted the discrepancies in the medical infrastructure. With big data, especially texts, forming the foundation of medical services, there is an exigent need for effective natural language processing (NLP) solutions tailored to the healthcare domain. Conventional approaches leveraging pre-trained models present promising results in this domain and current large language models (LLMs) offer advanced foundation for medical text processing. However, most medical LLMs are trained only with supervised fine-tuning (SFT), even though it efficiently empowers LLMs to understand and respond to medical instructions but is ineffective in learning domain knowledge and aligning with human preference. Another engineering barrier that prevents current medical LLM from better text processing ability is their restricted context length (e.g., 2,048 tokens), making it hard for the LLMs to process long context, which is frequently required in the medical domain. In this work, we propose ChiMed-GPT, a new benchmark LLM designed explicitly for Chinese medical domain, with enlarged context length to 4,096 tokens and undergoes a comprehensive training regime with pre-training, SFT, and RLHF. Evaluations on real-world tasks including information extraction, question answering, and dialogue generation demonstrate ChiMed-GPT's superior performance over general domain LLMs. Furthermore, we analyze possible biases through prompting ChiMed-GPT to perform attitude scales regarding discrimination of patients, so as to contribute to further responsible development of LLMs in the medical domain. The code and model are released at https://github.com/synlp/ChiMed-GPT.

The emergence of large language models (LLMs) has significantly influenced numerous fields, including healthcare, by enhancing the capabilities of automated systems to process and generate human-like text. However, despite their advancements, the reliability and accuracy of LLMs in medical contexts remain critical concerns. Current evaluation methods often lack robustness and fail to provide a comprehensive assessment of LLM performance, leading to potential risks in clinical settings. In this work, we propose Med-CoDE, a specifically designed evaluation framework for medical LLMs to address these challenges. The framework leverages a critique-based approach to quantitatively measure the degree of disagreement between model-generated responses and established medical ground truths. This framework captures both accuracy and reliability in medical settings. The proposed evaluation framework aims to fill the existing gap in LLM assessment by offering a systematic method to evaluate the quality and trustworthiness of medical LLMs. Through extensive experiments and case studies, we illustrate the practicality of our framework in providing a comprehensive and reliable evaluation of medical LLMs.

The performance on deep learning is significantly affected by volume of training data. Models pre-trained from massive dataset such as ImageNet become a powerful weapon for speeding up training convergence and improving accuracy. Similarly, models based on large dataset are important for the development of deep learning in 3D medical images. However, it is extremely challenging to build a sufficiently large dataset due to difficulty of data acquisition and annotation in 3D medical imaging. We aggregate the dataset from several medical challenges to build 3DSeg-8 dataset with diverse modalities, target organs, and pathologies. To extract general medical three-dimension (3D) features, we design a heterogeneous 3D network called Med3D to co-train multi-domain 3DSeg-8 so as to make a series of pre-trained models. We transfer Med3D pre-trained models to lung segmentation in LIDC dataset, pulmonary nodule classification in LIDC dataset and liver segmentation on LiTS challenge. Experiments show that the Med3D can accelerate the training convergence speed of target 3D medical tasks 2 times compared with model pre-trained on Kinetics dataset, and 10 times compared with training from scratch as well as improve accuracy ranging from 3% to 20%. Transferring our Med3D model on state-the-of-art DenseASPP segmentation network, in case of single model, we achieve 94.6\% Dice coefficient which approaches the result of top-ranged algorithms on the LiTS challenge.

The integration of Large Language Models (LLMs) into healthcare holds significant potential to enhance diagnostic accuracy and support medical treatment planning. These AI-driven systems can analyze vast datasets, assisting clinicians in identifying diseases, recommending treatments, and predicting patient outcomes. This study evaluates the performance of a range of contemporary LLMs, including both open-source and closed-source models, on the 2024 Portuguese National Exam for medical specialty access (PNA), a standardized medical knowledge assessment. Our results highlight considerable variation in accuracy and cost-effectiveness, with several models demonstrating performance exceeding human benchmarks for medical students on this specific task. We identify leading models based on a combined score of accuracy and cost, discuss the implications of reasoning methodologies like Chain-of-Thought, and underscore the potential for LLMs to function as valuable complementary tools aiding medical professionals in complex clinical decision-making.

Large Language Models (LLMs), despite their remarkable progress across various general domains, encounter significant barriers in medicine and healthcare. This field faces unique challenges such as domain-specific terminologies and the reasoning over specialized knowledge. To address these obstinate issues, we propose a novel Multi-disciplinary Collaboration (MC) framework for the medical domain that leverages role-playing LLM-based agents who participate in a collaborative multi-round discussion, thereby enhancing LLM proficiency and reasoning capabilities. This training-free and interpretable framework encompasses five critical steps: gathering domain experts, proposing individual analyses, summarising these analyses into a report, iterating over discussions until a consensus is reached, and ultimately making a decision. Our work particularly focuses on the zero-shot scenario, our results on nine data sets (MedQA, MedMCQA, PubMedQA, and six subtasks from MMLU) establish that our proposed MC framework excels at mining and harnessing the medical expertise in LLMs, as well as extending its reasoning abilities. Based on these outcomes, we further conduct a human evaluation to pinpoint and categorize common errors within our method, as well as ablation studies aimed at understanding the impact of various factors on overall performance. Our code can be found at https://github.com/gersteinlab/MedAgents.

Large language models (LLMs) have recently demonstrated their potential in clinical applications, providing valuable medical knowledge and advice. For example, a large dialog LLM like ChatGPT has successfully passed part of the US medical licensing exam. However, LLMs currently have difficulty processing images, making it challenging to interpret information from medical images, which are rich in information that supports clinical decisions. On the other hand, computer-aided diagnosis (CAD) networks for medical images have seen significant success in the medical field by using advanced deep-learning algorithms to support clinical decision-making. This paper presents a method for integrating LLMs into medical-image CAD networks. The proposed framework uses LLMs to enhance the output of multiple CAD networks, such as diagnosis networks, lesion segmentation networks, and report generation networks, by summarizing and reorganizing the information presented in natural language text format. The goal is to merge the strengths of LLMs' medical domain knowledge and logical reasoning with the vision understanding capability of existing medical-image CAD models to create a more user-friendly and understandable system for patients compared to conventional CAD systems. In the future, LLM's medical knowledge can be also used to improve the performance of vision-based medical-image CAD models.

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/

Large Language Models (LLMs) provide a possibility to make a great breakthrough in medicine. The establishment of a standardized medical benchmark becomes a fundamental cornerstone to measure progression. However, medical environments in different regions have their local characteristics, e.g., the ubiquity and significance of traditional Chinese medicine within China. Therefore, merely translating English-based medical evaluation may result in contextual incongruities to a local region. To solve the issue, we propose a localized medical benchmark called CMB, a Comprehensive Medical Benchmark in Chinese, designed and rooted entirely within the native Chinese linguistic and cultural framework. While traditional Chinese medicine is integral to this evaluation, it does not constitute its entirety. Using this benchmark, we have evaluated several prominent large-scale LLMs, including ChatGPT, GPT-4, dedicated Chinese LLMs, and LLMs specialized in the medical domain. It is worth noting that our benchmark is not devised as a leaderboard competition but as an instrument for self-assessment of model advancements. We hope this benchmark could facilitate the widespread adoption and enhancement of medical LLMs within China. Check details in https://cmedbenchmark.llmzoo.com/.

The rapid development of Large Language Models (LLMs) for healthcare applications has spurred calls for holistic evaluation beyond frequently-cited benchmarks like USMLE, to better reflect real-world performance. While real-world assessments are valuable indicators of utility, they often lag behind the pace of LLM evolution, likely rendering findings obsolete upon deployment. This temporal disconnect necessitates a comprehensive upfront evaluation that can guide model selection for specific clinical applications. We introduce MEDIC, a framework assessing LLMs across five critical dimensions of clinical competence: medical reasoning, ethics and bias, data and language understanding, in-context learning, and clinical safety. MEDIC features a novel cross-examination framework quantifying LLM performance across areas like coverage and hallucination detection, without requiring reference outputs. We apply MEDIC to evaluate LLMs on medical question-answering, safety, summarization, note generation, and other tasks. Our results show performance disparities across model sizes, baseline vs medically finetuned models, and have implications on model selection for applications requiring specific model strengths, such as low hallucination or lower cost of inference. MEDIC's multifaceted evaluation reveals these performance trade-offs, bridging the gap between theoretical capabilities and practical implementation in healthcare settings, ensuring that the most promising models are identified and adapted for diverse healthcare applications.

Multi-Modal Large Language Models (MLLMs), despite being successful, exhibit limited generality and often fall short when compared to specialized models. Recently, LLM-based agents have been developed to address these challenges by selecting appropriate specialized models as tools based on user inputs. However, such advancements have not been extensively explored within the medical domain. To bridge this gap, this paper introduces the first agent explicitly designed for the medical field, named Multi-modal Medical Agent (MMedAgent). We curate an instruction-tuning dataset comprising six medical tools solving seven tasks across five modalities, enabling the agent to choose the most suitable tools for a given task. Comprehensive experiments demonstrate that MMedAgent achieves superior performance across a variety of medical tasks compared to state-of-the-art open-source methods and even the closed-source model, GPT-4o. Furthermore, MMedAgent exhibits efficiency in updating and integrating new medical tools. Codes and models are all available.

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.

Multimodal large language models (MLLMs) have demonstrated promising prospects in healthcare, particularly for addressing complex medical tasks, supporting multidisciplinary treatment (MDT), and enabling personalized precision medicine. However, their practical deployment faces critical challenges in resource efficiency, diagnostic accuracy, clinical considerations, and ethical privacy. To address these limitations, we propose Infi-Med, a comprehensive framework for medical MLLMs that introduces three key innovations: (1) a resource-efficient approach through curating and constructing high-quality supervised fine-tuning (SFT) datasets with minimal sample requirements, with a forward-looking design that extends to both pretraining and posttraining phases; (2) enhanced multimodal reasoning capabilities for cross-modal integration and clinical task understanding; and (3) a systematic evaluation system that assesses model performance across medical modalities and task types. Our experiments demonstrate that Infi-Med achieves state-of-the-art (SOTA) performance in general medical reasoning while maintaining rapid adaptability to clinical scenarios. The framework establishes a solid foundation for deploying MLLMs in real-world healthcare settings by balancing model effectiveness with operational constraints.

We aim to present a comprehensive overview of the latest advancements in utilizing Large Language Models (LLMs) within the healthcare sector, emphasizing their transformative impact across various medical domains. LLMs have become pivotal in supporting healthcare, including physicians, healthcare providers, and patients. Our review provides insight into the applications of Large Language Models (LLMs) in healthcare, specifically focusing on diagnostic and treatment-related functionalities. We shed light on how LLMs are applied in cancer care, dermatology, dental care, neurodegenerative disorders, and mental health, highlighting their innovative contributions to medical diagnostics and patient care. Throughout our analysis, we explore the challenges and opportunities associated with integrating LLMs in healthcare, recognizing their potential across various medical specialties despite existing limitations. Additionally, we offer an overview of handling diverse data types within the medical field.

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.

Pathological diagnosis remains the definitive standard for identifying tumors. The rise of multimodal large models has simplified the process of integrating image analysis with textual descriptions. Despite this advancement, the substantial costs associated with training and deploying these complex multimodal models, together with a scarcity of high-quality training datasets, create a significant divide between cutting-edge technology and its application in the clinical setting. We had meticulously compiled a dataset of approximately 45,000 cases, covering over 6 different tasks, including the classification of organ tissues, generating pathology report descriptions, and addressing pathology-related questions and answers. We have fine-tuned multimodal large models, specifically LLaVA, Qwen-VL, InternLM, with this dataset to enhance instruction-based performance. We conducted a qualitative assessment of the capabilities of the base model and the fine-tuned model in performing image captioning and classification tasks on the specific dataset. The evaluation results demonstrate that the fine-tuned model exhibits proficiency in addressing typical pathological questions. We hope that by making both our models and datasets publicly available, they can be valuable to the medical and research communities.

Large language models (LLMs) have been applied to tasks in healthcare, ranging from medical exam questions to responding to patient questions. With increasing institutional partnerships between companies producing LLMs and healthcare systems, real world clinical application is coming closer to reality. As these models gain traction, it is essential for healthcare practitioners to understand what LLMs are, their development, their current and potential applications, and the associated pitfalls when utilized in medicine. This review and accompanying tutorial aim to give an overview of these topics to aid healthcare practitioners in understanding the rapidly changing landscape of LLMs as applied to medicine.

Multimodal large language models (MLLMs) hold significant potential in medical applications, including disease diagnosis and clinical decision-making. However, these tasks require highly accurate, context-sensitive, and professionally aligned responses, making reliable reward models and judges critical. Despite their importance, medical reward models (MRMs) and judges remain underexplored, with no dedicated benchmarks addressing clinical requirements. Existing benchmarks focus on general MLLM capabilities or evaluate models as solvers, neglecting essential evaluation dimensions like diagnostic accuracy and clinical relevance. To address this, we introduce Med-RewardBench, the first benchmark specifically designed to evaluate MRMs and judges in medical scenarios. Med-RewardBench features a multimodal dataset spanning 13 organ systems and 8 clinical departments, with 1,026 expert-annotated cases. A rigorous three-step process ensures high-quality evaluation data across six clinically critical dimensions. We evaluate 32 state-of-the-art MLLMs, including open-source, proprietary, and medical-specific models, revealing substantial challenges in aligning outputs with expert judgment. Additionally, we develop baseline models that demonstrate substantial performance improvements through fine-tuning.

Although recent advances in scaling large language models (LLMs) have resulted in improvements on many NLP tasks, it remains unclear whether these models trained primarily with general web text are the right tool in highly specialized, safety critical domains such as clinical text. Recent results have suggested that LLMs encode a surprising amount of medical knowledge. This raises an important question regarding the utility of smaller domain-specific language models. With the success of general-domain LLMs, is there still a need for specialized clinical models? To investigate this question, we conduct an extensive empirical analysis of 12 language models, ranging from 220M to 175B parameters, measuring their performance on 3 different clinical tasks that test their ability to parse and reason over electronic health records. As part of our experiments, we train T5-Base and T5-Large models from scratch on clinical notes from MIMIC III and IV to directly investigate the efficiency of clinical tokens. We show that relatively small specialized clinical models substantially outperform all in-context learning approaches, even when finetuned on limited annotated data. Further, we find that pretraining on clinical tokens allows for smaller, more parameter-efficient models that either match or outperform much larger language models trained on general text. We release the code and the models used under the PhysioNet Credentialed Health Data license and data use agreement.

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.

Open-source, multilingual medical large language models (LLMs) have the potential to serve linguistically diverse populations across different regions. Adapting generic LLMs for healthcare often requires continual pretraining, but this approach is computationally expensive and sometimes impractical. Instruction fine-tuning on a specific task may not always guarantee optimal performance due to the lack of broader domain knowledge that the model needs to understand and reason effectively in diverse scenarios. To address these challenges, we introduce two multilingual instruction fine-tuning datasets, MMed-IFT and MMed-IFT-MC, containing over 200k high-quality medical samples in six languages. We propose a two-stage training paradigm: the first stage injects general medical knowledge using MMed-IFT, while the second stage fine-tunes task-specific multiple-choice questions with MMed-IFT-MC. Our method achieves competitive results on both English and multilingual benchmarks, striking a balance between computational efficiency and performance. We plan to make our dataset and model weights public at https://github.com/SpassMed/Med-Llama3 in the future.

The increasing use of tools and solutions based on Large Language Models (LLMs) for various tasks in the medical domain has become a prominent trend. Their use in this highly critical and sensitive domain has thus raised important questions about their robustness, especially in response to variations in input, and the reliability of the generated outputs. This study addresses these questions by constructing a textual dataset based on the ICD-10-CM code descriptions, widely used in US hospitals and containing many clinical terms, and their easily reproducible rephrasing. We then benchmarked existing embedding models, either generalist or specialized in the clinical domain, in a semantic search task where the goal was to correctly match the rephrased text to the original description. Our results showed that generalist models performed better than clinical models, suggesting that existing clinical specialized models are more sensitive to small changes in input that confuse them. The highlighted problem of specialized models may be due to the fact that they have not been trained on sufficient data, and in particular on datasets that are not diverse enough to have a reliable global language understanding, which is still necessary for accurate handling of medical documents.

Accurate and efficient question-answering systems are essential for delivering high-quality patient care in the medical field. While Large Language Models (LLMs) have made remarkable strides across various domains, they continue to face significant challenges in medical question answering, particularly in understanding domain-specific terminologies and performing complex reasoning. These limitations undermine their effectiveness in critical medical applications. To address these issues, we propose a novel approach incorporating similar case generation within a multi-agent medical question-answering (MedQA) system. Specifically, we leverage the Llama3.1:70B model, a state-of-the-art LLM, in a multi-agent architecture to enhance performance on the MedQA dataset using zero-shot learning. Our method capitalizes on the model's inherent medical knowledge and reasoning capabilities, eliminating the need for additional training data. Experimental results show substantial performance gains over existing benchmark models, with improvements of 7% in both accuracy and F1-score across various medical QA tasks. Furthermore, we examine the model's interpretability and reliability in addressing complex medical queries. This research not only offers a robust solution for medical question answering but also establishes a foundation for broader applications of LLMs in the medical domain.

The rapid expansion of medical literature presents growing challenges for structuring and integrating domain knowledge at scale. Knowledge Graphs (KGs) offer a promising solution by enabling efficient retrieval, automated reasoning, and knowledge discovery. However, current KG construction methods often rely on supervised pipelines with limited generalizability or naively aggregate outputs from Large Language Models (LLMs), treating biomedical corpora as static and ignoring the temporal dynamics and contextual uncertainty of evolving knowledge. To address these limitations, we introduce MedKGent, a LLM agent framework for constructing temporally evolving medical KGs. Leveraging over 10 million PubMed abstracts published between 1975 and 2023, we simulate the emergence of biomedical knowledge via a fine-grained daily time series. MedKGent incrementally builds the KG in a day-by-day manner using two specialized agents powered by the Qwen2.5-32B-Instruct model. The Extractor Agent identifies knowledge triples and assigns confidence scores via sampling-based estimation, which are used to filter low-confidence extractions and inform downstream processing. The Constructor Agent incrementally integrates the retained triples into a temporally evolving graph, guided by confidence scores and timestamps to reinforce recurring knowledge and resolve conflicts. The resulting KG contains 156,275 entities and 2,971,384 relational triples. Quality assessments by two SOTA LLMs and three domain experts demonstrate an accuracy approaching 90%, with strong inter-rater agreement. To evaluate downstream utility, we conduct RAG across seven medical question answering benchmarks using five leading LLMs, consistently observing significant improvements over non-augmented baselines. Case studies further demonstrate the KG's value in literature-based drug repurposing via confidence-aware causal inference.

Large language models (LLMs) offer a promising pre-screening tool, improving early disease detection and providing enhanced healthcare access for underprivileged communities. The early diagnosis of various diseases continues to be a significant challenge in healthcare, primarily due to the nonspecific nature of early symptoms, the shortage of expert medical practitioners, and the need for prolonged clinical evaluations, all of which can delay treatment and adversely affect patient outcomes. With impressive accuracy in prediction across a range of diseases, LLMs have the potential to revolutionize clinical pre-screening and decision-making for various medical conditions. In this work, we study the diagnostic capability of LLMs for Rheumatoid Arthritis (RA) with real world patients data. Patient data was collected alongside diagnoses from medical experts, and the performance of LLMs was evaluated in comparison to expert diagnoses for RA disease prediction. We notice an interesting pattern in disease diagnosis and find an unexpected misalignment between prediction and explanation. We conduct a series of multi-round analyses using different LLM agents. The best-performing model accurately predicts rheumatoid arthritis (RA) diseases approximately 95\% of the time. However, when medical experts evaluated the reasoning generated by the model, they found that nearly 68\% of the reasoning was incorrect. This study highlights a clear misalignment between LLMs high prediction accuracy and its flawed reasoning, raising important questions about relying on LLM explanations in clinical settings. LLMs provide incorrect reasoning to arrive at the correct answer for RA disease diagnosis.

Building trusted datasets is critical for transparent and responsible Medical AI (MAI) research, but creating even small, high-quality datasets can take years of effort from multidisciplinary teams. This process often delays AI benefits, as human-centric data creation and AI-centric model development are treated as separate, sequential steps. To overcome this, we propose ScaleMAI, an agent of AI-integrated data curation and annotation, allowing data quality and AI performance to improve in a self-reinforcing cycle and reducing development time from years to months. We adopt pancreatic tumor detection as an example. First, ScaleMAI progressively creates a dataset of 25,362 CT scans, including per-voxel annotations for benign/malignant tumors and 24 anatomical structures. Second, through progressive human-in-the-loop iterations, ScaleMAI provides Flagship AI Model that can approach the proficiency of expert annotators (30-year experience) in detecting pancreatic tumors. Flagship Model significantly outperforms models developed from smaller, fixed-quality datasets, with substantial gains in tumor detection (+14%), segmentation (+5%), and classification (72%) on three prestigious benchmarks. In summary, ScaleMAI transforms the speed, scale, and reliability of medical dataset creation, paving the way for a variety of impactful, data-driven applications.

Foundation models are becoming valuable tools in medicine. Yet despite their promise, the best way to leverage Large Language Models (LLMs) in complex medical tasks remains an open question. We introduce a novel multi-agent framework, named Medical Decision-making Agents (MDAgents) that helps address this gap by automatically assigning a collaboration structure to a team of LLMs. The assigned solo or group collaboration structure is tailored to the medical task at hand, emulating real-world medical decision-making processes adapted to tasks of varying complexities. We evaluate our framework and baseline methods using state-of-the-art LLMs across a suite of real-world medical knowledge and medical diagnosis benchmarks, including a comparison of LLMs' medical complexity classification against human physicians. MDAgents achieved the best performance in seven out of ten benchmarks on tasks requiring an understanding of medical knowledge and multi-modal reasoning, showing a significant improvement of up to 4.2% (p < 0.05) compared to previous methods' best performances. Ablation studies reveal that MDAgents effectively determines medical complexity to optimize for efficiency and accuracy across diverse medical tasks. Notably, the combination of moderator review and external medical knowledge in group collaboration resulted in an average accuracy improvement of 11.8%. Our code can be found at https://github.com/mitmedialab/MDAgents.

Medical image and video segmentation is a critical task for precision medicine, which has witnessed considerable progress in developing task or modality-specific and generalist models for 2D images. However, there have been limited studies on building general-purpose models for 3D images and videos with comprehensive user studies. Here, we present MedSAM2, a promptable segmentation foundation model for 3D image and video segmentation. The model is developed by fine-tuning the Segment Anything Model 2 on a large medical dataset with over 455,000 3D image-mask pairs and 76,000 frames, outperforming previous models across a wide range of organs, lesions, and imaging modalities. Furthermore, we implement a human-in-the-loop pipeline to facilitate the creation of large-scale datasets resulting in, to the best of our knowledge, the most extensive user study to date, involving the annotation of 5,000 CT lesions, 3,984 liver MRI lesions, and 251,550 echocardiogram video frames, demonstrating that MedSAM2 can reduce manual costs by more than 85%. MedSAM2 is also integrated into widely used platforms with user-friendly interfaces for local and cloud deployment, making it a practical tool for supporting efficient, scalable, and high-quality segmentation in both research and healthcare environments.

In recent years, the application of Large Language Models (LLMs) in healthcare has shown significant promise in improving the accessibility and dissemination of medical knowledge. This paper presents a detailed study of various LLMs trained on the MedQuAD medical question-answering dataset, with a focus on identifying the most effective model for providing accurate medical information. Among the models tested, the Sentence-t5 combined with Mistral 7B demonstrated superior performance, achieving a precision score of 0.762. This model's enhanced capabilities are attributed to its advanced pretraining techniques, robust architecture, and effective prompt construction methodologies. By leveraging these strengths, the Sentence-t5 + Mistral 7B model excels in understanding and generating precise medical answers. Our findings highlight the potential of integrating sophisticated LLMs in medical contexts to facilitate efficient and accurate medical knowledge retrieval, thus significantly enhancing patient education and support.

The successes of foundation models such as ChatGPT and AlphaFold have spurred significant interest in building similar models for electronic medical records (EMRs) to improve patient care and hospital operations. However, recent hype has obscured critical gaps in our understanding of these models' capabilities. We review over 80 foundation models trained on non-imaging EMR data (i.e. clinical text and/or structured data) and create a taxonomy delineating their architectures, training data, and potential use cases. We find that most models are trained on small, narrowly-scoped clinical datasets (e.g. MIMIC-III) or broad, public biomedical corpora (e.g. PubMed) and are evaluated on tasks that do not provide meaningful insights on their usefulness to health systems. In light of these findings, we propose an improved evaluation framework for measuring the benefits of clinical foundation models that is more closely grounded to metrics that matter in healthcare.

Large language models (LLMs) have shown substantial progress in natural language understanding and generation, proving valuable especially in the medical field. Despite advancements, challenges persist due to the complexity and diversity inherent in medical tasks, which can be categorized as knowledge-intensive tasks and alignment-required tasks. Previous approaches either ignore the latter task or focus on a minority of tasks and hence lose generalization. To address these drawbacks, we propose a progressive fine-tuning pipeline. This pipeline employs a Knowledge Aggregator and a Noise aggregator to encode diverse knowledge in the first stage and filter out detrimental information. In the second stage, we drop the Noise Aggregator to avoid the interference of suboptimal representation and leverage an additional alignment module optimized towards an orthogonal direction to the knowledge space to mitigate knowledge forgetting. Based on this two-stage paradigm, we proposed a Medical LLM through decoupling Clinical Alignment and Knowledge Aggregation (MedCare), which is designed to achieve state-of-the-art (SOTA) performance on over 20 medical tasks, as well as SOTA results on specific medical alignment tasks. Various model sizes of MedCare (1.8B, 7B, 14B) all demonstrate significant improvements over existing models with similar model sizes.

Models such as GPT-4 and Med-PaLM 2 have demonstrated impressive performance on a wide variety of biomedical NLP tasks. However, these models have hundreds of billions of parameters, are computationally expensive to run, require users to send their input data over the internet, and are trained on unknown data sources. Can smaller, more targeted models compete? To address this question, we build and release BioMedLM, a 2.7 billion parameter GPT-style autoregressive model trained exclusively on PubMed abstracts and full articles. When fine-tuned, BioMedLM can produce strong multiple-choice biomedical question-answering results competitive with much larger models, such as achieving a score of 57.3% on MedMCQA (dev) and 69.0% on the MMLU Medical Genetics exam. BioMedLM can also be fine-tuned to produce useful answers to patient questions on medical topics. This demonstrates that smaller models can potentially serve as transparent, privacy-preserving, economical and environmentally friendly foundations for particular NLP applications, such as in biomedicine. The model is available on the Hugging Face Hub: https://huggingface.co/stanford-crfm/BioMedLM.

Large language models (LLMs) have shown potential in biomedical applications, leading to efforts to fine-tune them on domain-specific data. However, the effectiveness of this approach remains unclear. This study evaluates the performance of biomedically fine-tuned LLMs against their general-purpose counterparts on a variety of clinical tasks. We evaluated their performance on clinical case challenges from the New England Journal of Medicine (NEJM) and the Journal of the American Medical Association (JAMA) and on several clinical tasks (e.g., information extraction, document summarization, and clinical coding). Using benchmarks specifically chosen to be likely outside the fine-tuning datasets of biomedical models, we found that biomedical LLMs mostly perform inferior to their general-purpose counterparts, especially on tasks not focused on medical knowledge. While larger models showed similar performance on case tasks (e.g., OpenBioLLM-70B: 66.4% vs. Llama-3-70B-Instruct: 65% on JAMA cases), smaller biomedical models showed more pronounced underperformance (e.g., OpenBioLLM-8B: 30% vs. Llama-3-8B-Instruct: 64.3% on NEJM cases). Similar trends were observed across the CLUE (Clinical Language Understanding Evaluation) benchmark tasks, with general-purpose models often performing better on text generation, question answering, and coding tasks. Our results suggest that fine-tuning LLMs to biomedical data may not provide the expected benefits and may potentially lead to reduced performance, challenging prevailing assumptions about domain-specific adaptation of LLMs and highlighting the need for more rigorous evaluation frameworks in healthcare AI. Alternative approaches, such as retrieval-augmented generation, may be more effective in enhancing the biomedical capabilities of LLMs without compromising their general knowledge.

As the capabilities of Large Language Models (LLMs) in healthcare and medicine continue to advance, there is a growing need for competitive open-source models that can safeguard public interest. With the increasing availability of highly competitive open base models, the impact of continued pre-training is increasingly uncertain. In this work, we explore the role of instruct tuning, model merging, alignment, red teaming and advanced inference schemes, as means to improve current open models. To that end, we introduce the Aloe family, a set of open medical LLMs highly competitive within its scale range. Aloe models are trained on the current best base models (Mistral, LLaMA 3), using a new custom dataset which combines public data sources improved with synthetic Chain of Thought (CoT). Aloe models undergo an alignment phase, becoming one of the first few policy-aligned open healthcare LLM using Direct Preference Optimization, setting a new standard for ethical performance in healthcare LLMs. Model evaluation expands to include various bias and toxicity datasets, a dedicated red teaming effort, and a much-needed risk assessment for healthcare LLMs. Finally, to explore the limits of current LLMs in inference, we study several advanced prompt engineering strategies to boost performance across benchmarks, yielding state-of-the-art results for open healthcare 7B LLMs, unprecedented at this scale.

Medical systematic reviews can be very costly and resource intensive. We explore how Large Language Models (LLMs) can support and be trained to perform literature screening when provided with a detailed set of selection criteria. Specifically, we instruction tune LLaMA and Guanaco models to perform abstract screening for medical systematic reviews. Our best model, Bio-SIEVE, outperforms both ChatGPT and trained traditional approaches, and generalises better across medical domains. However, there remains the challenge of adapting the model to safety-first scenarios. We also explore the impact of multi-task training with Bio-SIEVE-Multi, including tasks such as PICO extraction and exclusion reasoning, but find that it is unable to match single-task Bio-SIEVE's performance. We see Bio-SIEVE as an important step towards specialising LLMs for the biomedical systematic review process and explore its future developmental opportunities. We release our models, code and a list of DOIs to reconstruct our dataset for reproducibility.

Large Language Models (LLMs), although powerful in general domains, often perform poorly on domain-specific tasks like medical question answering (QA). Moreover, they tend to function as "black-boxes," making it challenging to modify their behavior. Addressing this, our study delves into model editing utilizing in-context learning, aiming to improve LLM responses without the need for fine-tuning or retraining. Specifically, we propose a comprehensive retrieval strategy to extract medical facts from an external knowledge base, and then we incorporate them into the query prompt for the LLM. Focusing on medical QA using the MedQA-SMILE dataset, we evaluate the impact of different retrieval models and the number of facts provided to the LLM. Notably, our edited Vicuna model exhibited an accuracy improvement from 44.46% to 48.54%. This work underscores the potential of model editing to enhance LLM performance, offering a practical approach to mitigate the challenges of black-box LLMs.

In this study, we investigate the potential of Large Language Models to complement biomedical knowledge graphs in the training of semantic models for the biomedical and clinical domains. Drawing on the wealth of the UMLS knowledge graph and harnessing cutting-edge Large Language Models, we propose a new state-of-the-art approach for obtaining high-fidelity representations of biomedical concepts and sentences, consisting of three steps: an improved contrastive learning phase, a novel self-distillation phase, and a weight averaging phase. Through rigorous evaluations via the extensive BioLORD testing suite and diverse downstream tasks, we demonstrate consistent and substantial performance improvements over the previous state of the art (e.g. +2pts on MedSTS, +2.5pts on MedNLI-S, +6.1pts on EHR-Rel-B). Besides our new state-of-the-art biomedical model for English, we also distill and release a multilingual model compatible with 50+ languages and finetuned on 7 European languages. Many clinical pipelines can benefit from our latest models. Our new multilingual model enables a range of languages to benefit from our advancements in biomedical semantic representation learning, opening a new avenue for bioinformatics researchers around the world. As a result, we hope to see BioLORD-2023 becoming a precious tool for future biomedical applications.

This study presents a comprehensive analysis and comparison of two predominant fine-tuning methodologies - full-parameter fine-tuning and parameter-efficient tuning - within the context of medical Large Language Models (LLMs). We developed and refined a series of LLMs, based on the Llama-2 architecture, specifically designed to enhance medical knowledge retrieval, reasoning, and question-answering capabilities. Our experiments systematically evaluate the effectiveness of these tuning strategies across various well-known medical benchmarks. Notably, our medical LLM Med42 showed an accuracy level of 72% on the US Medical Licensing Examination (USMLE) datasets, setting a new standard in performance for openly available medical LLMs. Through this comparative analysis, we aim to identify the most effective and efficient method for fine-tuning LLMs in the medical domain, thereby contributing significantly to the advancement of AI-driven healthcare applications.

Large language models exhibit promising general capabilities but often lack specialized knowledge for domain-specific tasks. Developing domain experts from a base model enables a range of applications without prohibitive training costs. This work demonstrates a method using continuous training and instruction fine-tuning to rapidly adapt Llama 2 base models to the Chinese medical domain. We first conduct continuous training on 1B tokens from Chinese medical references to teach relevant vocabulary and knowledge. The models are then fine-tuned on 54K examples sourced from the Chinese National Medical Licensing Examination. Experiments on Chinese medical data confirm the effectiveness of this approach, producing a model comparable to GPT-3.5-turbo while using way less computational resource. The resulting domain-specific model could be useful for various Chinese medical applications. More broadly, this provides a template for domain-specific training of large language models in areas where pre-trained models lack the required expertise, such as law, science, and engineering.

Medicine is inherently multimodal, with rich data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence (AI) systems that flexibly encode, integrate, and interpret this data at scale can potentially enable impactful applications ranging from scientific discovery to care delivery. To enable the development of these models, we first curate MultiMedBench, a new multimodal biomedical benchmark. MultiMedBench encompasses 14 diverse tasks such as medical question answering, mammography and dermatology image interpretation, radiology report generation and summarization, and genomic variant calling. We then introduce Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system. Med-PaLM M is a large multimodal generative model that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. Med-PaLM M reaches performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. We also report examples of zero-shot generalization to novel medical concepts and tasks, positive transfer learning across tasks, and emergent zero-shot medical reasoning. To further probe the capabilities and limitations of Med-PaLM M, we conduct a radiologist evaluation of model-generated (and human) chest X-ray reports and observe encouraging performance across model scales. In a side-by-side ranking on 246 retrospective chest X-rays, clinicians express a pairwise preference for Med-PaLM M reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility. While considerable work is needed to validate these models in real-world use cases, our results represent a milestone towards the development of generalist biomedical AI systems.

While recent advancements in commercial large language models (LM) have shown promising results in medical tasks, their closed-source nature poses significant privacy and security concerns, hindering their widespread use in the medical field. Despite efforts to create open-source models, their limited parameters often result in insufficient multi-step reasoning capabilities required for solving complex medical problems. To address this, we introduce Meerkat-7B, a novel medical AI system with 7 billion parameters. Meerkat-7B was trained using our new synthetic dataset consisting of high-quality chain-of-thought reasoning paths sourced from 18 medical textbooks, along with diverse instruction-following datasets. Our system achieved remarkable accuracy across seven medical benchmarks, surpassing GPT-3.5 by 13.1%, as well as outperforming the previous best 7B models such as MediTron-7B and BioMistral-7B by 13.4% and 9.8%, respectively. Notably, it surpassed the passing threshold of the United States Medical Licensing Examination (USMLE) for the first time for a 7B-parameter model. Additionally, our system offered more detailed free-form responses to clinical queries compared to existing 7B and 13B models, approaching the performance level of GPT-3.5. This significantly narrows the performance gap with large LMs, showcasing its effectiveness in addressing complex medical challenges.

Large language models (LLMs), such as GPT-4, have demonstrated remarkable capabilities across a wide range of tasks, including health applications. In this paper, we study how LLMs can be used to scale biomedical knowledge curation. We find that while LLMs already possess decent competency in structuring biomedical text, by distillation into a task-specific student model through self-supervised learning, substantial gains can be attained over out-of-box LLMs, with additional advantages such as cost, efficiency, and white-box model access. We conduct a case study on adverse drug event (ADE) extraction, which is an important area for improving care. On standard ADE extraction evaluation, a GPT-3.5 distilled PubMedBERT model attained comparable accuracy as supervised state-of-the-art models without using any labeled data. Despite being over 1,000 times smaller, the distilled model outperformed its teacher GPT-3.5 by over 6 absolute points in F1 and GPT-4 by over 5 absolute points. Ablation studies on distillation model choice (e.g., PubMedBERT vs BioGPT) and ADE extraction architecture shed light on best practice for biomedical knowledge extraction. Similar gains were attained by distillation for other standard biomedical knowledge extraction tasks such as gene-disease associations and protected health information, further illustrating the promise of this approach.

Medical question-answering (QA) is a critical task for evaluating how effectively large language models (LLMs) encode clinical knowledge and assessing their potential applications in medicine. Despite showing promise on multiple-choice tests, LLMs frequently struggle with open-ended medical questions, producing responses with dangerous hallucinations or lacking comprehensive coverage of critical aspects. Existing approaches attempt to address these challenges through domain-specific fine-tuning, but this proves resource-intensive and difficult to scale across models. To improve the comprehensiveness and factuality of medical responses, we propose a novel approach utilizing structured medical reasoning. Our method guides LLMs through an seven-step cognitive process inspired by clinical diagnosis, enabling more accurate and complete answers without additional training. Experiments on the MedLFQA benchmark demonstrate that our approach achieves the highest Factuality Score of 85.8, surpassing fine-tuned models. Notably, this improvement transfers to smaller models, highlighting the method's efficiency and scalability. Our code and datasets are available.

Despite the success of Large Language Models (LLMs) in general image tasks, a gap persists in the medical field for a multimodal large model adept at handling the nuanced diversity of medical images. Addressing this, we propose MedXChat, a unified multimodal large model designed for seamless interactions between medical assistants and users. MedXChat encompasses three key functionalities: CXR(Chest X-ray)-to-Report generation, CXR-based visual question-answering (VQA), and Text-to-CXR synthesis. Our contributions are as follows. Firstly, our model showcases exceptional cross-task adaptability, displaying adeptness across all three defined tasks and outperforming the benchmark models on the MIMIC dataset in medical multimodal applications. Secondly, we introduce an innovative Text-to-CXR synthesis approach that utilizes instruction-following capabilities within the Stable Diffusion (SD) architecture. This technique integrates smoothly with the existing model framework, requiring no extra parameters, thereby maintaining the SD's generative strength while also bestowing upon it the capacity to render fine-grained medical images with high fidelity. Comprehensive experiments validate MedXChat's synergistic enhancement across all tasks. Our instruction data and model will be open-sourced.

We introduce SoftTiger, a clinical large language model (CLaM) designed as a foundation model for healthcare workflows. The narrative and unstructured nature of clinical notes is a major obstacle for healthcare intelligentization. We address a critical problem of structuring clinical notes into clinical data, according to international interoperability standards. We collect and annotate data for three subtasks, namely, international patient summary, clinical impression and medical encounter. We then supervised fine-tuned a state-of-the-art LLM using public and credentialed clinical data. The training is orchestrated in a way that the target model can first support basic clinical tasks such as abbreviation expansion and temporal information extraction, and then learn to perform more complex downstream clinical tasks. Moreover, we address several modeling challenges in the healthcare context, e.g., extra long context window. Our blind pairwise evaluation shows that SoftTiger outperforms other popular open-source models and GPT-3.5, comparable to Gemini-pro, with a mild gap from GPT-4. We believe that LLMs may become a step-stone towards healthcare digitalization and democratization. Therefore, we publicly release SoftTiger models at scales of 13 billion and 70 billion parameters, as well as datasets and code for our innovative scalable evaluation, hopefully, making a significant contribution to the healthcare industry.

The accelerating development of general medical artificial intelligence (GMAI), powered by multimodal large language models (MLLMs), offers transformative potential for addressing persistent healthcare challenges, including workforce deficits and escalating costs. The parallel development of systematic evaluation benchmarks emerges as a critical imperative to enable performance assessment and provide technological guidance. Meanwhile, as an invaluable knowledge source, the potential of medical textbooks for benchmark development remains underexploited. Here, we present MedBookVQA, a systematic and comprehensive multimodal benchmark derived from open-access medical textbooks. To curate this benchmark, we propose a standardized pipeline for automated extraction of medical figures while contextually aligning them with corresponding medical narratives. Based on this curated data, we generate 5,000 clinically relevant questions spanning modality recognition, disease classification, anatomical identification, symptom diagnosis, and surgical procedures. A multi-tier annotation system categorizes queries through hierarchical taxonomies encompassing medical imaging modalities (42 categories), body anatomies (125 structures), and clinical specialties (31 departments), enabling nuanced analysis across medical subdomains. We evaluate a wide array of MLLMs, including proprietary, open-sourced, medical, and reasoning models, revealing significant performance disparities across task types and model categories. Our findings highlight critical capability gaps in current GMAI systems while establishing textbook-derived multimodal benchmarks as essential evaluation tools. MedBookVQA establishes textbook-derived benchmarking as a critical paradigm for advancing clinical AI, exposing limitations in GMAI systems while providing anatomically structured performance metrics across specialties.

Many large language models (LLMs) for medicine have largely been evaluated on short texts, and their ability to handle longer sequences such as a complete electronic health record (EHR) has not been systematically explored. Assessing these models on long sequences is crucial since prior work in the general domain has demonstrated performance degradation of LLMs on longer texts. Motivated by this, we introduce LongBoX, a collection of seven medical datasets in text-to-text format, designed to investigate model performance on long sequences. Preliminary experiments reveal that both medical LLMs (e.g., BioGPT) and strong general domain LLMs (e.g., FLAN-T5) struggle on this benchmark. We further evaluate two techniques designed for long-sequence handling: (i) local-global attention, and (ii) Fusion-in-Decoder (FiD). Our results demonstrate mixed results with long-sequence handling - while scores on some datasets increase, there is substantial room for improvement. We hope that LongBoX facilitates the development of more effective long-sequence techniques for the medical domain. Data and source code are available at https://github.com/Mihir3009/LongBoX.

Large Language Models (LLMs) constitute a breakthrough state-of-the-art Artificial Intelligence (AI) technology which is rapidly evolving and promises to aid in medical diagnosis either by assisting doctors or by simulating a doctor's workflow in more advanced and complex implementations. In this technical paper, we outline Cognitive Network Evaluation Toolkit for Medical Domains (COGNET-MD), which constitutes a novel benchmark for LLM evaluation in the medical domain. Specifically, we propose a scoring-framework with increased difficulty to assess the ability of LLMs in interpreting medical text. The proposed framework is accompanied with a database of Multiple Choice Quizzes (MCQs). To ensure alignment with current medical trends and enhance safety, usefulness, and applicability, these MCQs have been constructed in collaboration with several associated medical experts in various medical domains and are characterized by varying degrees of difficulty. The current (first) version of the database includes the medical domains of Psychiatry, Dentistry, Pulmonology, Dermatology and Endocrinology, but it will be continuously extended and expanded to include additional medical domains.

Large Language Models (LLMs) are at the forefront of NLP achievements but fall short in dealing with shortcut learning, factual inconsistency, and vulnerability to adversarial inputs.These shortcomings are especially critical in medical contexts, where they can misrepresent actual model capabilities. Addressing this, we present SemEval-2024 Task 2: Safe Biomedical Natural Language Inference for ClinicalTrials. Our contributions include the refined NLI4CT-P dataset (i.e., Natural Language Inference for Clinical Trials - Perturbed), designed to challenge LLMs with interventional and causal reasoning tasks, along with a comprehensive evaluation of methods and results for participant submissions. A total of 106 participants registered for the task contributing to over 1200 individual submissions and 25 system overview papers. This initiative aims to advance the robustness and applicability of NLI models in healthcare, ensuring safer and more dependable AI assistance in clinical decision-making. We anticipate that the dataset, models, and outcomes of this task can support future research in the field of biomedical NLI. The dataset, competition leaderboard, and website are publicly available.

Large-scale multi-modal deep learning models have revolutionized domains such as healthcare, highlighting the importance of computational power. However, in resource-constrained regions like Low and Middle-Income Countries (LMICs), limited access to GPUs and data poses significant challenges, often leaving CPUs as the sole resource. To address this, we advocate for leveraging vector embeddings to enable flexible and efficient computational methodologies, democratizing multimodal deep learning across diverse contexts. Our paper investigates the efficiency and effectiveness of using vector embeddings from single-modal foundation models and multi-modal Vision-Language Models (VLMs) for multimodal deep learning in low-resource environments, particularly in healthcare. Additionally, we propose a simple yet effective inference-time method to enhance performance by aligning image-text embeddings. Comparing these approaches with traditional methods, we assess their impact on computational efficiency and model performance using metrics like accuracy, F1-score, inference time, training time, and memory usage across three medical modalities: BRSET (ophthalmology), HAM10000 (dermatology), and SatelliteBench (public health). Our findings show that embeddings reduce computational demands without compromising model performance. Furthermore, our alignment method improves performance in medical tasks. This research promotes sustainable AI practices by optimizing resources in constrained environments, highlighting the potential of embedding-based approaches for efficient multimodal learning. Vector embeddings democratize multimodal deep learning in LMICs, particularly in healthcare, enhancing AI adaptability in varied use cases.

In this study, we investigated the ability of the large language model (LLM) to enhance healthcare data interoperability. We leveraged the LLM to convert clinical texts into their corresponding FHIR resources. Our experiments, conducted on 3,671 snippets of clinical text, demonstrated that the LLM not only streamlines the multi-step natural language processing and human calibration processes but also achieves an exceptional accuracy rate of over 90% in exact matches when compared to human annotations.

This study evaluates the performance of large language models (LLMs) as medical agents in Portuguese, aiming to develop a reliable and relevant virtual assistant for healthcare professionals. The HealthCareMagic-100k-en and MedQuAD datasets, translated from English using GPT-3.5, were used to fine-tune the ChatBode-7B model using the PEFT-QLoRA method. The InternLM2 model, with initial training on medical data, presented the best overall performance, with high precision and adequacy in metrics such as accuracy, completeness and safety. However, DrBode models, derived from ChatBode, exhibited a phenomenon of catastrophic forgetting of acquired medical knowledge. Despite this, these models performed frequently or even better in aspects such as grammaticality and coherence. A significant challenge was low inter-rater agreement, highlighting the need for more robust assessment protocols. This work paves the way for future research, such as evaluating multilingual models specific to the medical field, improving the quality of training data, and developing more consistent evaluation methodologies for the medical field.

Large language models (LLMs), such as ChatGPT, have received substantial attention due to their impressive human language understanding and generation capabilities. Therefore, the application of LLMs in medicine to assist physicians and patient care emerges as a promising research direction in both artificial intelligence and clinical medicine. To reflect this trend, this survey provides a comprehensive overview of the principles, applications, and challenges faced by LLMs in medicine. Specifically, we aim to address the following questions: 1) How can medical LLMs be built? 2) What are the downstream performances of medical LLMs? 3) How can medical LLMs be utilized in real-world clinical practice? 4) What challenges arise from the use of medical LLMs? and 5) How can we better construct and utilize medical LLMs? As a result, this survey aims to provide insights into the opportunities and challenges of LLMs in medicine and serve as a valuable resource for constructing practical and effective medical LLMs. A regularly updated list of practical guides on medical LLMs can be found at https://github.com/AI-in-Health/MedLLMsPracticalGuide.

Recent breakthroughs in large language models (LLMs) offer unprecedented natural language understanding and generation capabilities. However, existing surveys on LLMs in biomedicine often focus on specific applications or model architectures, lacking a comprehensive analysis that integrates the latest advancements across various biomedical domains. This review, based on an analysis of 484 publications sourced from databases including PubMed, Web of Science, and arXiv, provides an in-depth examination of the current landscape, applications, challenges, and prospects of LLMs in biomedicine, distinguishing itself by focusing on the practical implications of these models in real-world biomedical contexts. Firstly, we explore the capabilities of LLMs in zero-shot learning across a broad spectrum of biomedical tasks, including diagnostic assistance, drug discovery, and personalized medicine, among others, with insights drawn from 137 key studies. Then, we discuss adaptation strategies of LLMs, including fine-tuning methods for both uni-modal and multi-modal LLMs to enhance their performance in specialized biomedical contexts where zero-shot fails to achieve, such as medical question answering and efficient processing of biomedical literature. Finally, we discuss the challenges that LLMs face in the biomedicine domain including data privacy concerns, limited model interpretability, issues with dataset quality, and ethics due to the sensitive nature of biomedical data, the need for highly reliable model outputs, and the ethical implications of deploying AI in healthcare. To address these challenges, we also identify future research directions of LLM in biomedicine including federated learning methods to preserve data privacy and integrating explainable AI methodologies to enhance the transparency of LLMs.

Multimodal large language models (MLLMs) have made significant strides, yet they face challenges in the medical domain due to limited specialized knowledge. While recent medical MLLMs demonstrate strong performance in lab settings, they often struggle in real-world applications, highlighting a substantial gap between research and practice. In this paper, we seek to address this gap at various stages of the end-to-end learning pipeline, including data collection, model fine-tuning, and evaluation. At the data collection stage, we introduce SemiHVision, a dataset that combines human annotations with automated augmentation techniques to improve both medical knowledge representation and diagnostic reasoning. For model fine-tuning, we trained PMC-Cambrian-8B-AN over 2400 H100 GPU hours, resulting in performance that surpasses public medical models like HuatuoGPT-Vision-34B (79.0% vs. 66.7%) and private general models like Claude3-Opus (55.7%) on traditional benchmarks such as SLAKE and VQA-RAD. In the evaluation phase, we observed that traditional benchmarks cannot accurately reflect realistic clinical task capabilities. To overcome this limitation and provide more targeted guidance for model evaluation, we introduce the JAMA Clinical Challenge, a novel benchmark specifically designed to evaluate diagnostic reasoning. On this benchmark, PMC-Cambrian-AN achieves state-of-the-art performance with a GPT-4 score of 1.29, significantly outperforming HuatuoGPT-Vision-34B (1.13) and Claude3-Opus (1.17), demonstrating its superior diagnostic reasoning abilities.

The integration of Large Language Models (LLMs) into healthcare applications offers promising advancements in medical diagnostics, treatment recommendations, and patient care. However, the susceptibility of LLMs to adversarial attacks poses a significant threat, potentially leading to harmful outcomes in delicate medical contexts. This study investigates the vulnerability of LLMs to two types of adversarial attacks in three medical tasks. Utilizing real-world patient data, we demonstrate that both open-source and proprietary LLMs are susceptible to manipulation across multiple tasks. This research further reveals that domain-specific tasks demand more adversarial data in model fine-tuning than general domain tasks for effective attack execution, especially for more capable models. We discover that while integrating adversarial data does not markedly degrade overall model performance on medical benchmarks, it does lead to noticeable shifts in fine-tuned model weights, suggesting a potential pathway for detecting and countering model attacks. This research highlights the urgent need for robust security measures and the development of defensive mechanisms to safeguard LLMs in medical applications, to ensure their safe and effective deployment in healthcare settings.

We present Shap-MeD, a text-to-3D object generative model specialized in the biomedical domain. The objective of this study is to develop an assistant that facilitates the 3D modeling of medical objects, thereby reducing development time. 3D modeling in medicine has various applications, including surgical procedure simulation and planning, the design of personalized prosthetic implants, medical education, the creation of anatomical models, and the development of research prototypes. To achieve this, we leverage Shap-e, an open-source text-to-3D generative model developed by OpenAI, and fine-tune it using a dataset of biomedical objects. Our model achieved a mean squared error (MSE) of 0.089 in latent generation on the evaluation set, compared to Shap-e's MSE of 0.147. Additionally, we conducted a qualitative evaluation, comparing our model with others in the generation of biomedical objects. Our results indicate that Shap-MeD demonstrates higher structural accuracy in biomedical object generation.

Current Large Language Models (LLMs) exhibit significant limitations, notably in structured, interpretable, and verifiable medical reasoning, alongside practical deployment challenges related to computational resources and data privacy. This report focused on the development of WiNGPT-3.0, the 32-billion parameter LLMs, engineered with the objective of enhancing its capacity for medical reasoning and exploring its potential for effective integration within healthcare IT infrastructures. The broader aim is to advance towards clinically applicable models. The approach involved a multi-stage training pipeline tailored for general, medical, and clinical reasoning. This pipeline incorporated supervised fine-tuning (SFT) and reinforcement learning (RL), leveraging curated Long Chain-of-Thought (CoT) datasets, auxiliary reward models, and an evidence-based diagnostic chain simulation. WiNGPT-3.0 demonstrated strong performance: specific model variants achieved scores of 66.6 on MedCalc and 87.1 on MedQA-USMLE. Furthermore, targeted training improved performance on a clinical reasoning task from a baseline score of 58.1 to 62.5. These findings suggest that reinforcement learning, even when applied with a limited dataset of only a few thousand examples, can enhance medical reasoning accuracy. Crucially, this demonstration of RL's efficacy with limited data and computation paves the way for more trustworthy and practically deployable LLMs within clinical workflows and health information infrastructures.

Multimodal large language models (MLLMs) hold significant potential in the medical field, but their capabilities are often limited by insufficient data in certain medical domains, highlighting the need for understanding what kinds of images can be used by MLLMs for generalization. Current research suggests that multi-task training outperforms single-task as different tasks can benefit each other, but they often overlook the internal relationships within these tasks, providing limited guidance on selecting datasets to enhance specific tasks. To analyze this phenomenon, we attempted to employ compositional generalization (CG)-the ability of models to understand novel combinations by recombining learned elements-as a guiding framework. Since medical images can be precisely defined by Modality, Anatomical area, and Task, naturally providing an environment for exploring CG. Therefore, we assembled 106 medical datasets to create Med-MAT for comprehensive experiments. The experiments confirmed that MLLMs can use CG to understand unseen medical images and identified CG as one of the main drivers of the generalization observed in multi-task training. Additionally, further studies demonstrated that CG effectively supports datasets with limited data and delivers consistent performance across different backbones, highlighting its versatility and broad applicability. Med-MAT is publicly available at https://github.com/FreedomIntelligence/Med-MAT.

Large-language models have recently demonstrated impressive zero-shot capabilities in a variety of natural language tasks such as summarization, dialogue generation, and question-answering. Despite many promising applications in clinical medicine, adoption of these models in real-world settings has been largely limited by their tendency to generate incorrect and sometimes even toxic statements. In this study, we develop Almanac, a large language model framework augmented with retrieval capabilities for medical guideline and treatment recommendations. Performance on a novel dataset of clinical scenarios (n = 130) evaluated by a panel of 5 board-certified and resident physicians demonstrates significant increases in factuality (mean of 18% at p-value < 0.05) across all specialties, with improvements in completeness and safety. Our results demonstrate the potential for large language models to be effective tools in the clinical decision-making process, while also emphasizing the importance of careful testing and deployment to mitigate their shortcomings.

Large Language Models (LLMs) have great potential in the field of health care, yet they face great challenges in adapting to rapidly evolving medical knowledge. This can lead to outdated or contradictory treatment suggestions. This study investigated how LLMs respond to evolving clinical guidelines, focusing on concept drift and internal inconsistencies. We developed the DriftMedQA benchmark to simulate guideline evolution and assessed the temporal reliability of various LLMs. Our evaluation of seven state-of-the-art models across 4,290 scenarios demonstrated difficulties in rejecting outdated recommendations and frequently endorsing conflicting guidance. Additionally, we explored two mitigation strategies: Retrieval-Augmented Generation and preference fine-tuning via Direct Preference Optimization. While each method improved model performance, their combination led to the most consistent and reliable results. These findings underscore the need to improve LLM robustness to temporal shifts to ensure more dependable applications in clinical practice.

Diabetes is a chronic disease that poses a significant global health burden, and optimizing diabetes management requires multi-stakeholder collaboration. Large language models (LLMs) have shown promise in various healthcare scenarios, but their effectiveness across a diverse range of diabetes tasks remains unproven. In this study, we introduced a framework to train and validate diabetes-specific LLMs. We first developed a comprehensive data processing pipeline that includes data collection, filtering, augmentation and refinement. This approach contributes to creating a high-quality, diabetes-specific dataset, and several evaluation benchmarks entirely from scratch. Utilizing the collected training dataset, we fine-tuned a diabetes-specific LLM family that demonstrated state-of-the-art proficiency in understanding and processing various diabetes tasks compared to other LLMs. Furthermore, clinical studies showed the potential applications of our models in diabetes care, including providing personalized healthcare, assisting medical education, and streamlining clinical tasks. In conclusion, our study introduced a framework to develop and evaluate a diabetes-specific LLM family, and highlighted its potential to enhance clinical practice and provide personalized, data-driven support for diabetes support when facing different end users. The code is provided via GitHub at https://github.com/waltonfuture/Diabetica.

Despite the vast repository of global medical knowledge predominantly being in English, local languages are crucial for delivering tailored healthcare services, particularly in areas with limited medical resources. To extend the reach of medical AI advancements to a broader population, we aim to develop medical LLMs across the six most widely spoken languages, encompassing a global population of 6.1 billion. This effort culminates in the creation of the ApolloCorpora multilingual medical dataset and the XMedBench benchmark. In the multilingual medical benchmark, the released Apollo models, at various relatively-small sizes (i.e., 0.5B, 1.8B, 2B, 6B, and 7B), achieve the best performance among models of equivalent size. Especially, Apollo-7B is the state-of-the-art multilingual medical LLMs up to 70B. Additionally, these lite models could be used to improve the multi-lingual medical capabilities of larger models without fine-tuning in a proxy-tuning fashion. We will open-source training corpora, code, model weights and evaluation benchmark.

Recent advances in generative AI have brought incredible breakthroughs in several areas, including medical imaging. These generative models have tremendous potential not only to help safely share medical data via synthetic datasets but also to perform an array of diverse applications, such as anomaly detection, image-to-image translation, denoising, and MRI reconstruction. However, due to the complexity of these models, their implementation and reproducibility can be difficult. This complexity can hinder progress, act as a use barrier, and dissuade the comparison of new methods with existing works. In this study, we present MONAI Generative Models, a freely available open-source platform that allows researchers and developers to easily train, evaluate, and deploy generative models and related applications. Our platform reproduces state-of-art studies in a standardised way involving different architectures (such as diffusion models, autoregressive transformers, and GANs), and provides pre-trained models for the community. We have implemented these models in a generalisable fashion, illustrating that their results can be extended to 2D or 3D scenarios, including medical images with different modalities (like CT, MRI, and X-Ray data) and from different anatomical areas. Finally, we adopt a modular and extensible approach, ensuring long-term maintainability and the extension of current applications for future features.

The remarkable capabilities of Large Language Models (LLMs) make them increasingly compelling for adoption in real-world healthcare applications. However, the risks associated with using LLMs in medical applications have not been systematically characterized. We propose using five key principles for safe and trustworthy medical AI: Truthfulness, Resilience, Fairness, Robustness, and Privacy, along with ten specific aspects. Under this comprehensive framework, we introduce a novel MedGuard benchmark with 1,000 expert-verified questions. Our evaluation of 11 commonly used LLMs shows that the current language models, regardless of their safety alignment mechanisms, generally perform poorly on most of our benchmarks, particularly when compared to the high performance of human physicians. Despite recent reports indicate that advanced LLMs like ChatGPT can match or even exceed human performance in various medical tasks, this study underscores a significant safety gap, highlighting the crucial need for human oversight and the implementation of AI safety guardrails.

Since the emergence of the Transformer architecture, language model development has increased, driven by their promising potential. However, releasing these models into production requires properly understanding their behavior, particularly in sensitive domains such as medicine. Despite this need, the medical literature still lacks technical assessments of pre-trained language models, which are especially valuable in resource-constrained settings in terms of computational power or limited budget. To address this gap, we provide a comprehensive survey of language models in the medical domain. In addition, we selected a subset of these models for thorough evaluation, focusing on classification and text generation tasks. Our subset encompasses 53 models, ranging from 110 million to 13 billion parameters, spanning the three families of Transformer-based models and from diverse knowledge domains. This study employs a series of approaches for text classification together with zero-shot prompting instead of model training or fine-tuning, which closely resembles the limited resource setting in which many users of language models find themselves. Encouragingly, our findings reveal remarkable performance across various tasks and datasets, underscoring the latent potential of certain models to contain medical knowledge, even without domain specialization. Consequently, our study advocates for further exploration of model applications in medical contexts, particularly in resource-constrained settings. The code is available on https://github.com/anpoc/Language-models-in-medicine.

Foundation models are rapidly being developed for computational pathology applications. However, it remains an open question which factors are most important for downstream performance with data scale and diversity, model size, and training algorithm all playing a role. In this work, we present the result of scaling both data and model size, surpassing previous studies in both dimensions, and introduce two new models: Virchow 2, a 632M parameter vision transformer, and Virchow 2G, a 1.85B parameter vision transformer, each trained with 3.1M histopathology whole slide images. To support this scale, we propose domain-inspired adaptations to the DINOv2 training algorithm, which is quickly becoming the default method in self-supervised learning for computational pathology. We achieve state of the art performance on twelve tile-level tasks, as compared to the top performing competing models. Our results suggest that data diversity and domain-specific training can outperform models that only scale in the number of parameters, but, on average, performance benefits from domain-tailoring, data scale, and model scale.

Recent researches of large language models(LLM), which is pre-trained on massive general-purpose corpora, have achieved breakthroughs in responding human queries. However, these methods face challenges including limited data insufficiency to support extensive pre-training and can not align responses with users' instructions. To address these issues, we introduce a medical instruction dataset, CMedINS, containing six medical instructions derived from actual medical tasks, which effectively fine-tunes LLM in conjunction with other data. Subsequently, We launch our medical model, IIMedGPT, employing an efficient preference alignment method, Direct preference Optimization(DPO). The results show that our final model outperforms existing medical models in medical dialogue.Datsets, Code and model checkpoints will be released upon acceptance.

Large Language Models (LLMs) have demonstrated significant enhancements in instruction-following abilities through instruction tuning, achieving notable performances across various tasks. Previous research has focused on fine-tuning medical domain-specific LLMs using an extensive array of medical-specific data, incorporating millions of pieces of biomedical literature to augment their medical capabilities. However, existing medical instruction-tuned LLMs have been constrained by the limited scope of tasks and instructions available, restricting the efficacy of instruction tuning and adversely affecting performance in the general domain. In this paper, we fine-tune LLaMA-series models using 52k diverse, machine-generated, medical instruction-following data, MedInstruct-52k, resulting in the model AlpaCare. Comprehensive experimental results on both general and medical-specific domain free-form instruction evaluations showcase AlpaCare's strong medical proficiency and generalizability compared to previous instruction-tuned models in both medical and general domains. We provide public access to our MedInstruct-52k dataset and a clinician-crafted free-form instruction test set, MedInstruct-test, along with our codebase, to foster further research and development. Our project page is available at https://github.com/XZhang97666/AlpaCare.

Large language models (LLMs) have exhibited remarkable capabilities across various domains and tasks, pushing the boundaries of our knowledge in learning and cognition. The latest model, OpenAI's o1, stands out as the first LLM with an internalized chain-of-thought technique using reinforcement learning strategies. While it has demonstrated surprisingly strong capabilities on various general language tasks, its performance in specialized fields such as medicine remains unknown. To this end, this report provides a comprehensive exploration of o1 on different medical scenarios, examining 3 key aspects: understanding, reasoning, and multilinguality. Specifically, our evaluation encompasses 6 tasks using data from 37 medical datasets, including two newly constructed and more challenging question-answering (QA) tasks based on professional medical quizzes from the New England Journal of Medicine (NEJM) and The Lancet. These datasets offer greater clinical relevance compared to standard medical QA benchmarks such as MedQA, translating more effectively into real-world clinical utility. Our analysis of o1 suggests that the enhanced reasoning ability of LLMs may (significantly) benefit their capability to understand various medical instructions and reason through complex clinical scenarios. Notably, o1 surpasses the previous GPT-4 in accuracy by an average of 6.2% and 6.6% across 19 datasets and two newly created complex QA scenarios. But meanwhile, we identify several weaknesses in both the model capability and the existing evaluation protocols, including hallucination, inconsistent multilingual ability, and discrepant metrics for evaluation. We release our raw data and model outputs at https://ucsc-vlaa.github.io/o1_medicine/ for future research.

Large Language Models (LLMs) have rapidly become important tools in Biomedical and Health Informatics (BHI), enabling new ways to analyze data, treat patients, and conduct research. This bibliometric review aims to provide a panoramic view of how LLMs have been used in BHI by examining research articles and collaboration networks from 2022 to 2023. It further explores how LLMs can improve Natural Language Processing (NLP) applications in various BHI areas like medical diagnosis, patient engagement, electronic health record management, and personalized medicine. To do this, our bibliometric review identifies key trends, maps out research networks, and highlights major developments in this fast-moving field. Lastly, it discusses the ethical concerns and practical challenges of using LLMs in BHI, such as data privacy and reliable medical recommendations. Looking ahead, we consider how LLMs could further transform biomedical research as well as healthcare delivery and patient outcomes. This bibliometric review serves as a resource for stakeholders in healthcare, including researchers, clinicians, and policymakers, to understand the current state and future potential of LLMs in BHI.

Large Language Models (LLMs) have the potential of facilitating the development of Artificial Intelligence technology to assist medical experts for interactive decision support, which has been demonstrated by their competitive performances in Medical QA. However, while impressive, the required quality bar for medical applications remains far from being achieved. Currently, LLMs remain challenged by outdated knowledge and by their tendency to generate hallucinated content. Furthermore, most benchmarks to assess medical knowledge lack reference gold explanations which means that it is not possible to evaluate the reasoning of LLMs predictions. Finally, the situation is particularly grim if we consider benchmarking LLMs for languages other than English which remains, as far as we know, a totally neglected topic. In order to address these shortcomings, in this paper we present MedExpQA, the first multilingual benchmark based on medical exams to evaluate LLMs in Medical Question Answering. To the best of our knowledge, MedExpQA includes for the first time reference gold explanations written by medical doctors which can be leveraged to establish various gold-based upper-bounds for comparison with LLMs performance. Comprehensive multilingual experimentation using both the gold reference explanations and Retrieval Augmented Generation (RAG) approaches show that performance of LLMs still has large room for improvement, especially for languages other than English. Furthermore, and despite using state-of-the-art RAG methods, our results also demonstrate the difficulty of obtaining and integrating readily available medical knowledge that may positively impact results on downstream evaluations for Medical Question Answering. So far the benchmark is available in four languages, but we hope that this work may encourage further development to other languages.

Tumor documentation in Germany is largely done manually, requiring reading patient records and entering data into structured databases. Large language models (LLMs) could potentially enhance this process by improving efficiency and reliability. This evaluation tests eleven different open source LLMs with sizes ranging from 1-70 billion model parameters on three basic tasks of the tumor documentation process: identifying tumor diagnoses, assigning ICD-10 codes, and extracting the date of first diagnosis. For evaluating the LLMs on these tasks, a dataset of annotated text snippets based on anonymized doctors' notes from urology was prepared. Different prompting strategies were used to investigate the effect of the number of examples in few-shot prompting and to explore the capabilities of the LLMs in general. The models Llama 3.1 8B, Mistral 7B, and Mistral NeMo 12 B performed comparably well in the tasks. Models with less extensive training data or having fewer than 7 billion parameters showed notably lower performance, while larger models did not display performance gains. Examples from a different medical domain than urology could also improve the outcome in few-shot prompting, which demonstrates the ability of LLMs to handle tasks needed for tumor documentation. Open source LLMs show a strong potential for automating tumor documentation. Models from 7-12 billion parameters could offer an optimal balance between performance and resource efficiency. With tailored fine-tuning and well-designed prompting, these models might become important tools for clinical documentation in the future. The code for the evaluation is available from https://github.com/stefan-m-lenz/UroLlmEval. We also release the dataset as a new valuable resource that addresses the shortage of authentic and easily accessible benchmarks in German-language medical NLP.

Large Language Models (LLMs) have demonstrated impressive capabilities across natural language processing tasks. However, their application to specialized domains such as medicine and biology requires further optimization to ensure factual accuracy, reliability, and contextual depth. We introduce MedBioLM, a domain-adapted biomedical question-answering model designed to enhance both short-form and long-form queries. By integrating fine-tuning and retrieval-augmented generation (RAG), MedBioLM dynamically incorporates domain-specific knowledge, improving reasoning abilities and factual accuracy. To evaluate its effectiveness, we fine-tuned the model on diverse biomedical QA datasets, covering structured multiple-choice assessments and complex clinical reasoning tasks. Fine-tuning significantly improves accuracy on benchmark datasets, while RAG enhances factual consistency. These results highlight the potential of domain-optimized LLMs in advancing biomedical research, medical education, and clinical decision support.

Recent advances in generative models, including large language models (LLMs), vision language models (VLMs), and diffusion models, have accelerated the field of natural language and image processing in medicine and marked a significant paradigm shift in how biomedical models can be developed and deployed. While these models are highly adaptable to new tasks, scaling and evaluating their usage presents new challenges not addressed in previous frameworks. In particular, the ability of these models to produce useful outputs with little to no specialized training data ("zero-" or "few-shot" approaches), as well as the open-ended nature of their outputs, necessitate the development of new guidelines for robust reporting of clinical generative model research. In response to gaps in standards and best practices for the development of clinical AI tools identified by US Executive Order 141103 and several emerging national networks for clinical AI evaluation, we begin to formalize some of these guidelines by building on the original MI-CLAIM checklist. The new checklist, MI-CLAIM-GEN (Table 1), aims to address differences in training, evaluation, interpretability, and reproducibility of new generative models compared to non-generative ("predictive") AI models. This MI-CLAIM-GEN checklist also seeks to clarify cohort selection reporting with unstructured clinical data and adds additional items on alignment with ethical standards for clinical AI research.

The current generation of large language models (LLMs) is typically designed for broad, general-purpose applications, while domain-specific LLMs, especially in vertical fields like medicine, remain relatively scarce. In particular, the development of highly efficient and practical LLMs for the medical domain is challenging due to the complexity of medical knowledge and the limited availability of high-quality data. To bridge this gap, we introduce Baichuan-M1, a series of large language models specifically optimized for medical applications. Unlike traditional approaches that simply continue pretraining on existing models or apply post-training to a general base model, Baichuan-M1 is trained from scratch with a dedicated focus on enhancing medical capabilities. Our model is trained on 20 trillion tokens and incorporates a range of effective training methods that strike a balance between general capabilities and medical expertise. As a result, Baichuan-M1 not only performs strongly across general domains such as mathematics and coding but also excels in specialized medical fields. We have open-sourced Baichuan-M1-14B, a mini version of our model, which can be accessed through the following links.

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.

The recent success of Large Language Models (LLMs) has had a significant impact on the healthcare field, providing patients with medical advice, diagnostic information, and more. However, due to a lack of professional medical knowledge, patients are easily misled by generated erroneous information from LLMs, which may result in serious medical problems. To address this issue, we focus on tuning the LLMs to be medical assistants who collaborate with more experienced doctors. We first conduct a two-stage survey by inspiration-feedback to gain a broad understanding of the real needs of doctors for medical assistants. Based on this, we construct a Chinese medical dataset called DoctorFLAN to support the entire workflow of doctors, which includes 92K Q\&A samples from 22 tasks and 27 specialists. Moreover, we evaluate LLMs in doctor-oriented scenarios by constructing the DoctorFLAN-test containing 550 single-turn Q\&A and DotaBench containing 74 multi-turn conversations. The evaluation results indicate that being a medical assistant still poses challenges for existing open-source models, but DoctorFLAN can help them significantly. It demonstrates that the doctor-oriented dataset and benchmarks we construct can complement existing patient-oriented work and better promote medical LLMs research.

Data science plays a critical role in clinical research, but it requires professionals with expertise in coding and medical data analysis. Large language models (LLMs) have shown great potential in supporting medical tasks and performing well in general coding tests. However, these tests do not assess LLMs' ability to handle data science tasks in medicine, nor do they explore their practical utility in clinical research. To address this, we developed a dataset consisting of 293 real-world data science coding tasks, based on 39 published clinical studies, covering 128 tasks in Python and 165 tasks in R. This dataset simulates realistic clinical research scenarios using patient data. Our findings reveal that cutting-edge LLMs struggle to generate perfect solutions, frequently failing to follow input instructions, understand target data, and adhere to standard analysis practices. Consequently, LLMs are not yet ready to fully automate data science tasks. We benchmarked advanced adaptation methods and found two to be particularly effective: chain-of-thought prompting, which provides a step-by-step plan for data analysis, which led to a 60% improvement in code accuracy; and self-reflection, enabling LLMs to iteratively refine their code, yielding a 38% accuracy improvement. Building on these insights, we developed a platform that integrates LLMs into the data science workflow for medical professionals. In a user study with five medical doctors, we found that while LLMs cannot fully automate coding tasks, they significantly streamline the programming process. We found that 80% of their submitted code solutions were incorporated from LLM-generated code, with up to 96% reuse in some cases. Our analysis highlights the potential of LLMs, when integrated into expert workflows, to enhance data science efficiency in clinical research.

The rapid progress in Large Language Models (LLMs) has prompted the creation of numerous benchmarks to evaluate their capabilities.This study focuses on the Comprehensive Medical Benchmark in Chinese (CMB), showcasing how dataset diversity and distribution in supervised fine-tuning (SFT) may enhance LLM performance.Remarkably, We successfully trained a smaller base model to achieve scores comparable to larger models, indicating that a diverse and well-distributed dataset can optimize performance regardless of model size.This study suggests that even smaller models may reach high performance levels with carefully curated and varied datasets.By integrating a wide range of instructional content, our approach addresses potential issues such as data quality inconsistencies. Our results imply that a broader spectrum of training data may enhance a model's ability to generalize and perform effectively across different medical scenarios, highlighting the importance of dataset quality and diversity in fine-tuning processes.

Security concerns related to Large Language Models (LLMs) have been extensively explored, yet the safety implications for Multimodal Large Language Models (MLLMs), particularly in medical contexts (MedMLLMs), remain insufficiently studied. This paper delves into the underexplored security vulnerabilities of MedMLLMs, especially when deployed in clinical environments where the accuracy and relevance of question-and-answer interactions are critically tested against complex medical challenges. By combining existing clinical medical data with atypical natural phenomena, we redefine two types of attacks: mismatched malicious attack (2M-attack) and optimized mismatched malicious attack (O2M-attack). Using our own constructed voluminous 3MAD dataset, which covers a wide range of medical image modalities and harmful medical scenarios, we conduct a comprehensive analysis and propose the MCM optimization method, which significantly enhances the attack success rate on MedMLLMs. Evaluations with this dataset and novel attack methods, including white-box attacks on LLaVA-Med and transfer attacks on four other state-of-the-art models, indicate that even MedMLLMs designed with enhanced security features are vulnerable to security breaches. Our work underscores the urgent need for a concerted effort to implement robust security measures and enhance the safety and efficacy of open-source MedMLLMs, particularly given the potential severity of jailbreak attacks and other malicious or clinically significant exploits in medical settings. For further research and replication, anonymous access to our code is available at https://github.com/dirtycomputer/O2M_attack. Warning: Medical large model jailbreaking may generate content that includes unverified diagnoses and treatment recommendations. Always consult professional medical advice.

High computation costs and latency of large language models such as GPT-4 have limited their deployment in clinical settings. Small language models (SLMs) offer a cost-effective alternative, but their limited capacity requires biomedical domain adaptation, which remains challenging. An additional bottleneck is the unavailability and high sensitivity of clinical data. To address these challenges, we propose a novel framework for adapting SLMs into high-performing clinical models. We introduce the MediPhi collection of 3.8B-parameter SLMs developed with our novel framework: pre-instruction tuning of experts on relevant medical and clinical corpora (PMC, Medical Guideline, MedWiki, etc.), model merging, and clinical-tasks alignment. To cover most clinical tasks, we extended the CLUE benchmark to CLUE+, doubling its size. Our expert models deliver relative improvements on this benchmark over the base model without any task-specific fine-tuning: 64.3% on medical entities, 49.5% on radiology reports, and 44% on ICD-10 coding (outperforming GPT-4-0125 by 14%). We unify the expert models into MediPhi via model merging, preserving gains across benchmarks. Furthermore, we built the MediFlow collection, a synthetic dataset of 2.5 million high-quality instructions on 14 medical NLP tasks, 98 fine-grained document types, and JSON format support. Alignment of MediPhi using supervised fine-tuning and direct preference optimization achieves further gains of 18.9% on average.

This paper investigates the challenges of developing large language models (LLMs) proficient in both multilingual understanding and medical knowledge. We demonstrate that simply translating medical data does not guarantee strong performance on clinical tasks in the target language. Our experiments reveal that the optimal language mix in training data varies significantly across different medical tasks. We find that larger models with carefully calibrated language ratios achieve superior performance on native-language clinical tasks. Furthermore, our results suggest that relying solely on fine-tuning may not be the most effective approach for incorporating new language knowledge into LLMs. Instead, data and computationally intensive pretraining methods may still be necessary to achieve optimal performance in multilingual medical settings. These findings provide valuable guidance for building effective and inclusive medical AI systems for diverse linguistic communities.

Several medical Multimodal Large Languange Models (MLLMs) have been developed to address tasks involving visual images with textual instructions across various medical modalities, achieving impressive results. Most current medical generalist models are region-agnostic, treating the entire image as a holistic representation. However, they struggle to identify which specific regions they are focusing on when generating a sentence. To mimic the behavior of doctors, who typically begin by reviewing the entire image before concentrating on specific regions for a thorough evaluation, we aim to enhance the capability of medical MLLMs in understanding anatomical regions within entire medical scans. To achieve it, we first formulate Region-Centric tasks and construct a large-scale dataset, MedRegInstruct, to incorporate regional information into training. Combining our collected dataset with other medical multimodal corpora for training, we propose a Region-Aware medical MLLM, MedRegA, which is the first bilingual generalist medical AI system to simultaneously handle image-level and region-level medical vision-language tasks across a broad range of modalities. Our MedRegA not only enables three region-centric tasks, but also achieves the best performance for visual question answering, report generation and medical image classification over 8 modalities, showcasing significant versatility. Experiments demonstrate that our model can not only accomplish powerful performance across various medical vision-language tasks in bilingual settings, but also recognize and detect structures in multimodal medical scans, boosting the interpretability and user interactivity of medical MLLMs. Our project page is https://medrega.github.io.

Large foundation models, including large language models (LLMs), vision transformers (ViTs), diffusion, and LLM-based multimodal models, are revolutionizing the entire machine learning lifecycle, from training to deployment. However, the substantial advancements in versatility and performance these models offer come at a significant cost in terms of hardware resources. To support the growth of these large models in a scalable and environmentally sustainable way, there has been a considerable focus on developing resource-efficient strategies. This survey delves into the critical importance of such research, examining both algorithmic and systemic aspects. It offers a comprehensive analysis and valuable insights gleaned from existing literature, encompassing a broad array of topics from cutting-edge model architectures and training/serving algorithms to practical system designs and implementations. The goal of this survey is to provide an overarching understanding of how current approaches are tackling the resource challenges posed by large foundation models and to potentially inspire future breakthroughs in this field.

Several recent works seek to develop foundation models specifically for medical applications, adapting general-purpose large language models (LLMs) and vision-language models (VLMs) via continued pretraining on publicly available biomedical corpora. These works typically claim that such domain-adaptive pretraining (DAPT) improves performance on downstream medical tasks, such as answering medical licensing exam questions. In this paper, we compare seven public "medical" LLMs and two VLMs against their corresponding base models, arriving at a different conclusion: all medical VLMs and nearly all medical LLMs fail to consistently improve over their base models in the zero-/few-shot prompting regime for medical question-answering (QA) tasks. For instance, across the tasks and model pairs we consider in the 3-shot setting, medical LLMs only outperform their base models in 12.1% of cases, reach a (statistical) tie in 49.8% of cases, and are significantly worse than their base models in the remaining 38.2% of cases. Our conclusions are based on (i) comparing each medical model head-to-head, directly against the corresponding base model; (ii) optimizing the prompts for each model separately; and (iii) accounting for statistical uncertainty in comparisons. While these basic practices are not consistently adopted in the literature, our ablations show that they substantially impact conclusions. Our findings suggest that state-of-the-art general-domain models may already exhibit strong medical knowledge and reasoning capabilities, and offer recommendations to strengthen the conclusions of future studies.

Addressing the imminent shortfall of 10 million health workers by 2030, predominantly in Low- and Middle-Income Countries (LMICs), this paper introduces an innovative approach that harnesses the power of Large Language Models (LLMs) integrated with machine translation models. This solution is engineered to meet the unique needs of Community Health Workers (CHWs), overcoming language barriers, cultural sensitivities, and the limited availability of medical dialog datasets. I have crafted a model that not only boasts superior translation capabilities but also undergoes rigorous fine-tuning on open-source datasets to ensure medical accuracy and is equipped with comprehensive safety features to counteract the risks of misinformation. Featuring a modular design, this approach is specifically structured for swift adaptation across various linguistic and cultural contexts, utilizing open-source components to significantly reduce healthcare operational costs. This strategic innovation markedly improves the accessibility and quality of healthcare services by providing CHWs with contextually appropriate medical knowledge and diagnostic tools. This paper highlights the transformative impact of this context-aware LLM, underscoring its crucial role in addressing the global healthcare workforce deficit and propelling forward healthcare outcomes in LMICs.

The deployment of large language models (LLMs) within the healthcare sector has sparked both enthusiasm and apprehension. These models exhibit the remarkable capability to provide proficient responses to free-text queries, demonstrating a nuanced understanding of professional medical knowledge. This comprehensive survey delves into the functionalities of existing LLMs designed for healthcare applications, elucidating the trajectory of their development, starting from traditional Pretrained Language Models (PLMs) to the present state of LLMs in healthcare sector. First, we explore the potential of LLMs to amplify the efficiency and effectiveness of diverse healthcare applications, particularly focusing on clinical language understanding tasks. These tasks encompass a wide spectrum, ranging from named entity recognition and relation extraction to natural language inference, multi-modal medical applications, document classification, and question-answering. Additionally, we conduct an extensive comparison of the most recent state-of-the-art LLMs in the healthcare domain, while also assessing the utilization of various open-source LLMs and highlighting their significance in healthcare applications. Furthermore, we present the essential performance metrics employed to evaluate LLMs in the biomedical domain, shedding light on their effectiveness and limitations. Finally, we summarize the prominent challenges and constraints faced by large language models in the healthcare sector, offering a holistic perspective on their potential benefits and shortcomings. This review provides a comprehensive exploration of the current landscape of LLMs in healthcare, addressing their role in transforming medical applications and the areas that warrant further research and development.

Large language models (LLMs) have demonstrated remarkable capabilities in natural language understanding and generation across various domains, including medicine. We present a comprehensive evaluation of GPT-4, a state-of-the-art LLM, on medical competency examinations and benchmark datasets. GPT-4 is a general-purpose model that is not specialized for medical problems through training or engineered to solve clinical tasks. Our analysis covers two sets of official practice materials for the USMLE, a three-step examination program used to assess clinical competency and grant licensure in the United States. We also evaluate performance on the MultiMedQA suite of benchmark datasets. Beyond measuring model performance, experiments were conducted to investigate the influence of test questions containing both text and images on model performance, probe for memorization of content during training, and study probability calibration, which is of critical importance in high-stakes applications like medicine. Our results show that GPT-4, without any specialized prompt crafting, exceeds the passing score on USMLE by over 20 points and outperforms earlier general-purpose models (GPT-3.5) as well as models specifically fine-tuned on medical knowledge (Med-PaLM, a prompt-tuned version of Flan-PaLM 540B). In addition, GPT-4 is significantly better calibrated than GPT-3.5, demonstrating a much-improved ability to predict the likelihood that its answers are correct. We also explore the behavior of the model qualitatively through a case study that shows the ability of GPT-4 to explain medical reasoning, personalize explanations to students, and interactively craft new counterfactual scenarios around a medical case. Implications of the findings are discussed for potential uses of GPT-4 in medical education, assessment, and clinical practice, with appropriate attention to challenges of accuracy and safety.

Recent advances in AI foundation models have significant potential for lightening the clinical workload by mimicking the comprehensive and multi-faceted approaches used by medical professionals. In the field of radiation oncology, the integration of multiple modalities holds great importance, so the opportunity of foundational model is abundant. Inspired by this, here we present RO-LMM, a multi-purpose, comprehensive large multimodal model (LMM) tailored for the field of radiation oncology. This model effectively manages a series of tasks within the clinical workflow, including clinical context summarization, radiation treatment plan suggestion, and plan-guided target volume segmentation by leveraging the capabilities of LMM. In particular, to perform consecutive clinical tasks without error accumulation, we present a novel Consistency Embedding Fine-Tuning (CEFTune) technique, which boosts LMM's robustness to noisy inputs while preserving the consistency of handling clean inputs. We further extend this concept to LMM-driven segmentation framework, leading to a novel Consistency Embedding Segmentation~(CESEG) techniques. Experimental results including multi-centre validation confirm that our RO-LMM with CEFTune and CESEG results in promising performance for multiple clinical tasks with generalization capabilities.

Large language models have exhibited exceptional performance on various Natural Language Processing (NLP) tasks, leveraging techniques such as the pre-training, and instruction fine-tuning. Despite these advances, their effectiveness in medical applications is limited, due to challenges such as factual inaccuracies, reasoning abilities, and lack grounding in real-world experience. In this study, we present ClinicalGPT, a language model explicitly designed and optimized for clinical scenarios. By incorporating extensive and diverse real-world data, such as medical records, domain-specific knowledge, and multi-round dialogue consultations in the training process, ClinicalGPT is better prepared to handle multiple clinical task. Furthermore, we introduce a comprehensive evaluation framework that includes medical knowledge question-answering, medical exams, patient consultations, and diagnostic analysis of medical records. Our results demonstrate that ClinicalGPT significantly outperforms other models in these tasks, highlighting the effectiveness of our approach in adapting large language models to the critical domain of healthcare.

Large language models (LLMs) hold great promise in summarizing medical evidence. Most recent studies focus on the application of proprietary LLMs. Using proprietary LLMs introduces multiple risk factors, including a lack of transparency and vendor dependency. While open-source LLMs allow better transparency and customization, their performance falls short compared to proprietary ones. In this study, we investigated to what extent fine-tuning open-source LLMs can further improve their performance in summarizing medical evidence. Utilizing a benchmark dataset, MedReview, consisting of 8,161 pairs of systematic reviews and summaries, we fine-tuned three broadly-used, open-sourced LLMs, namely PRIMERA, LongT5, and Llama-2. Overall, the fine-tuned LLMs obtained an increase of 9.89 in ROUGE-L (95% confidence interval: 8.94-10.81), 13.21 in METEOR score (95% confidence interval: 12.05-14.37), and 15.82 in CHRF score (95% confidence interval: 13.89-16.44). The performance of fine-tuned LongT5 is close to GPT-3.5 with zero-shot settings. Furthermore, smaller fine-tuned models sometimes even demonstrated superior performance compared to larger zero-shot models. The above trends of improvement were also manifested in both human and GPT4-simulated evaluations. Our results can be applied to guide model selection for tasks demanding particular domain knowledge, such as medical evidence summarization.

Advances in large language models (LLMs) provide new opportunities in healthcare for improved patient care, clinical decision-making, and enhancement of physician and administrator workflows. However, the potential of these models importantly depends on their ability to generalize effectively across clinical environments and populations, a challenge often underestimated in early development. To better understand reasons for these challenges and inform mitigation approaches, we evaluated ClinicLLM, an LLM trained on [HOSPITAL]'s clinical notes, analyzing its performance on 30-day all-cause readmission prediction focusing on variability across hospitals and patient characteristics. We found poorer generalization particularly in hospitals with fewer samples, among patients with government and unspecified insurance, the elderly, and those with high comorbidities. To understand reasons for lack of generalization, we investigated sample sizes for fine-tuning, note content (number of words per note), patient characteristics (comorbidity level, age, insurance type, borough), and health system aspects (hospital, all-cause 30-day readmission, and mortality rates). We used descriptive statistics and supervised classification to identify features. We found that, along with sample size, patient age, number of comorbidities, and the number of words in notes are all important factors related to generalization. Finally, we compared local fine-tuning (hospital specific), instance-based augmented fine-tuning and cluster-based fine-tuning for improving generalization. Among these, local fine-tuning proved most effective, increasing AUC by 0.25% to 11.74% (most helpful in settings with limited data). Overall, this study provides new insights for enhancing the deployment of large language models in the societally important domain of healthcare, and improving their performance for broader populations.

Despite significant progress in applying large language models (LLMs) to the medical domain, several limitations still prevent them from practical applications. Among these are the constraints on model size and the lack of cohort-specific labeled datasets. In this work, we investigated the potential of improving a lightweight LLM, such as Llama 3.1-8B, through fine-tuning with datasets using synthetic labels. Two tasks are jointly trained by combining their respective instruction datasets. When the quality of the task-specific synthetic labels is relatively high (e.g., generated by GPT4- o), Llama 3.1-8B achieves satisfactory performance on the open-ended disease detection task, with a micro F1 score of 0.91. Conversely, when the quality of the task-relevant synthetic labels is relatively low (e.g., from the MIMIC-CXR dataset), fine-tuned Llama 3.1-8B is able to surpass its noisy teacher labels (micro F1 score of 0.67 v.s. 0.63) when calibrated against curated labels, indicating the strong inherent underlying capability of the model. These findings demonstrate the potential of fine-tuning LLMs with synthetic labels, offering a promising direction for future research on LLM specialization in the medical domain.

Developing artificial intelligence (AI) for vertical domains requires a solid data foundation for both training and evaluation. In this work, we introduce TrialPanorama, a large-scale, structured database comprising 1,657,476 clinical trial records aggregated from 15 global sources. The database captures key aspects of trial design and execution, including trial setups, interventions, conditions, biomarkers, and outcomes, and links them to standard biomedical ontologies such as DrugBank and MedDRA. This structured and ontology-grounded design enables TrialPanorama to serve as a unified, extensible resource for a wide range of clinical trial tasks, including trial planning, design, and summarization. To demonstrate its utility, we derive a suite of benchmark tasks directly from the TrialPanorama database. The benchmark spans eight tasks across two categories: three for systematic review (study search, study screening, and evidence summarization) and five for trial design (arm design, eligibility criteria, endpoint selection, sample size estimation, and trial completion assessment). The experiments using five state-of-the-art large language models (LLMs) show that while general-purpose LLMs exhibit some zero-shot capability, their performance is still inadequate for high-stakes clinical trial workflows. We release TrialPanorama database and the benchmark to facilitate further research on AI for clinical trials.

Large Language Models (LLMs) have demonstrated remarkable capabilities across various domains and are moving towards more specialized areas. Recent advanced proprietary models such as GPT-4 and Gemini have achieved significant advancements in biomedicine, which have also raised privacy and security challenges. The construction of specialized generalists hinges largely on high-quality datasets, enhanced by techniques like supervised fine-tuning and reinforcement learning from human or AI feedback, and direct preference optimization. However, these leading technologies (e.g., preference learning) are still significantly limited in the open source community due to the scarcity of specialized data. In this paper, we present the UltraMedical collections, which consist of high-quality manual and synthetic datasets in the biomedicine domain, featuring preference annotations across multiple advanced LLMs. By utilizing these datasets, we fine-tune a suite of specialized medical models based on Llama-3 series, demonstrating breathtaking capabilities across various medical benchmarks. Moreover, we develop powerful reward models skilled in biomedical and general reward benchmark, enhancing further online preference learning within the biomedical LLM community.

Large Language Models (LLMs) have been widely applied in various professional fields. By fine-tuning the models using domain specific question and answer datasets, the professional domain knowledge and Q\&A abilities of these models have significantly improved, for example, medical professional LLMs that use fine-tuning of doctor-patient Q\&A data exhibit extraordinary disease diagnostic abilities. However, we observed that despite improvements in specific domain knowledge, the performance of medical LLM in long-context understanding has significantly declined, especially compared to general language models with similar parameters. The purpose of this study is to investigate the phenomenon of reduced performance in understanding long-context in medical LLM. We designed a series of experiments to conduct open-book professional knowledge exams on all models to evaluate their ability to read long-context. By adjusting the proportion and quantity of general data and medical data in the process of fine-tuning, we can determine the best data composition to optimize the professional model and achieve a balance between long-context performance and specific domain knowledge.

Histopathology plays a central role in clinical medicine and biomedical research. While artificial intelligence shows promising results on many pathological tasks, generalization and dealing with rare diseases, where training data is scarce, remains a challenge. Distilling knowledge from unlabeled data into a foundation model before learning from, potentially limited, labeled data provides a viable path to address these challenges. In this work, we extend the state of the art of foundation models for digital pathology whole slide images by semi-automated data curation and incorporating pathologist domain knowledge. Specifically, we combine computational and pathologist domain knowledge (1) to curate a diverse dataset of 103k slides corresponding to 750 million image patches covering data from different fixation, staining, and scanning protocols as well as data from different indications and labs across the EU and US, (2) for grouping semantically similar slides and tissue patches, and (3) to augment the input images during training. We evaluate the resulting model on a set of public and internal benchmarks and show that although our foundation model is trained with an order of magnitude less slides, it performs on par or better than competing models. We expect that scaling our approach to more data and larger models will further increase its performance and capacity to deal with increasingly complex real world tasks in diagnostics and biomedical research.

Medical open-domain question answering demands substantial access to specialized knowledge. Recent efforts have sought to decouple knowledge from model parameters, counteracting architectural scaling and allowing for training on common low-resource hardware. The retrieve-then-read paradigm has become ubiquitous, with model predictions grounded on relevant knowledge pieces from external repositories such as PubMed, textbooks, and UMLS. An alternative path, still under-explored but made possible by the advent of domain-specific large language models, entails constructing artificial contexts through prompting. As a result, "to generate or to retrieve" is the modern equivalent of Hamlet's dilemma. This paper presents MedGENIE, the first generate-then-read framework for multiple-choice question answering in medicine. We conduct extensive experiments on MedQA-USMLE, MedMCQA, and MMLU, incorporating a practical perspective by assuming a maximum of 24GB VRAM. MedGENIE sets a new state-of-the-art (SOTA) in the open-book setting of each testbed, even allowing a small-scale reader to outcompete zero-shot closed-book 175B baselines while using up to 706times fewer parameters. Overall, our findings reveal that generated passages are more effective than retrieved counterparts in attaining higher accuracy.

Purpose: With advancements in Large Language Models (LLMs) for healthcare, the need arises for competitive open-source models to protect the public interest. This work contributes to the field of open medical LLMs by optimizing key stages of data preprocessing and training, while showing how to improve model safety (through DPO) and efficacy (through RAG). The evaluation methodology used, which includes four different types of tests, defines a new standard for the field. The resultant models, shown to be competitive with the best private alternatives, are released with a permisive license. Methods: Building on top of strong base models like Llama 3.1 and Qwen 2.5, Aloe Beta uses a custom dataset to enhance public data with synthetic Chain of Thought examples. The models undergo alignment with Direct Preference Optimization, emphasizing ethical and policy-aligned performance in the presence of jailbreaking attacks. Evaluation includes close-ended, open-ended, safety and human assessments, to maximize the reliability of results. Results: Recommendations are made across the entire pipeline, backed by the solid performance of the Aloe Family. These models deliver competitive performance across healthcare benchmarks and medical fields, and are often preferred by healthcare professionals. On bias and toxicity, the Aloe Beta models significantly improve safety, showing resilience to unseen jailbreaking attacks. For a responsible release, a detailed risk assessment specific to healthcare is attached to the Aloe Family models. Conclusion: The Aloe Beta models, and the recipe that leads to them, are a significant contribution to the open-source medical LLM field, offering top-of-the-line performance while maintaining high ethical requirements. This work sets a new standard for developing and reporting aligned LLMs in healthcare.

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.

Large Language Models (LLMs) have shown promising results on machine translation for high resource language pairs and domains. However, in specialised domains (e.g. medical) LLMs have shown lower performance compared to standard neural machine translation models. The consistency in the machine translation of terminology is crucial for users, researchers, and translators in specialised domains. In this study, we compare the performance between baseline LLMs and instruction-tuned LLMs in the medical domain. In addition, we introduce terminology from specialised medical dictionaries into the instruction formatted datasets for fine-tuning LLMs. The instruction-tuned LLMs significantly outperform the baseline models with automatic metrics.

The entry of large language models (LLMs) into research and commercial spaces has led to a trend of ever-larger models, with initial promises of generalisability, followed by a widespread desire to downsize and create specialised models without the need for complete fine-tuning, using Parameter Efficient Fine-tuning (PEFT) methods. We present an investigation into the suitability of different PEFT methods to clinical decision-making tasks, across a range of model sizes, including extremely small models with as few as 25 million parameters. Our analysis shows that the performance of most PEFT approaches varies significantly from one task to another, with the exception of LoRA, which maintains relatively high performance across all model sizes and tasks, typically approaching or matching full fine-tuned performance. The effectiveness of PEFT methods in the clinical domain is evident, particularly for specialised models which can operate on low-cost, in-house computing infrastructure. The advantages of these models, in terms of speed and reduced training costs, dramatically outweighs any performance gain from large foundation LLMs. Furthermore, we highlight how domain-specific pre-training interacts with PEFT methods and model size, and discuss how these factors interplay to provide the best efficiency-performance trade-off. Full code available at: tbd.

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

Artificial intelligence has significantly advanced healthcare, particularly through large language models (LLMs) that excel in medical question answering benchmarks. However, their real-world clinical application remains limited due to the complexities of doctor-patient interactions. To address this, we introduce AI Hospital, a multi-agent framework simulating dynamic medical interactions between Doctor as player and NPCs including Patient, Examiner, Chief Physician. This setup allows for realistic assessments of LLMs in clinical scenarios. We develop the Multi-View Medical Evaluation (MVME) benchmark, utilizing high-quality Chinese medical records and NPCs to evaluate LLMs' performance in symptom collection, examination recommendations, and diagnoses. Additionally, a dispute resolution collaborative mechanism is proposed to enhance diagnostic accuracy through iterative discussions. Despite improvements, current LLMs exhibit significant performance gaps in multi-turn interactions compared to one-step approaches. Our findings highlight the need for further research to bridge these gaps and improve LLMs' clinical diagnostic capabilities. Our data, code, and experimental results are all open-sourced at https://github.com/LibertFan/AI_Hospital.

As the performance of large language models (LLMs) continues to advance, their adoption is expanding across a wide range of domains, including the medical field. The integration of LLMs into medical applications raises critical safety concerns, particularly due to their use by users with diverse roles, e.g. patients and clinicians, and the potential for model's outputs to directly affect human health. Despite the domain-specific capabilities of medical LLMs, prior safety evaluations have largely focused only on general safety benchmarks. In this paper, we introduce a safety evaluation protocol tailored to the medical domain in both patient user and clinician user perspectives, alongside general safety assessments and quantitatively analyze the safety of medical LLMs. We bridge a gap in the literature by building the PatientSafetyBench containing 466 samples over 5 critical categories to measure safety from the perspective of the patient. We apply our red-teaming protocols on the MediPhi model collection as a case study. To our knowledge, this is the first work to define safety evaluation criteria for medical LLMs through targeted red-teaming taking three different points of view - patient, clinician, and general user - establishing a foundation for safer deployment in medical domains.

Large language models (LLMs) hold immense promise to serve complex health information needs but also have the potential to introduce harm and exacerbate health disparities. Reliably evaluating equity-related model failures is a critical step toward developing systems that promote health equity. In this work, we present resources and methodologies for surfacing biases with potential to precipitate equity-related harms in long-form, LLM-generated answers to medical questions and then conduct an empirical case study with Med-PaLM 2, resulting in the largest human evaluation study in this area to date. Our contributions include a multifactorial framework for human assessment of LLM-generated answers for biases, and EquityMedQA, a collection of seven newly-released datasets comprising both manually-curated and LLM-generated questions enriched for adversarial queries. Both our human assessment framework and dataset design process are grounded in an iterative participatory approach and review of possible biases in Med-PaLM 2 answers to adversarial queries. Through our empirical study, we find that the use of a collection of datasets curated through a variety of methodologies, coupled with a thorough evaluation protocol that leverages multiple assessment rubric designs and diverse rater groups, surfaces biases that may be missed via narrower evaluation approaches. Our experience underscores the importance of using diverse assessment methodologies and involving raters of varying backgrounds and expertise. We emphasize that while our framework can identify specific forms of bias, it is not sufficient to holistically assess whether the deployment of an AI system promotes equitable health outcomes. We hope the broader community leverages and builds on these tools and methods towards realizing a shared goal of LLMs that promote accessible and equitable healthcare for all.

Integrating Large Language Models (LLMs) in healthcare diagnosis demands systematic frameworks that can handle complex medical scenarios while maintaining specialized expertise. We present KG4Diagnosis, a novel hierarchical multi-agent framework that combines LLMs with automated knowledge graph construction, encompassing 362 common diseases across medical specialties. Our framework mirrors real-world medical systems through a two-tier architecture: a general practitioner (GP) agent for initial assessment and triage, coordinating with specialized agents for in-depth diagnosis in specific domains. The core innovation lies in our end-to-end knowledge graph generation methodology, incorporating: (1) semantic-driven entity and relation extraction optimized for medical terminology, (2) multi-dimensional decision relationship reconstruction from unstructured medical texts, and (3) human-guided reasoning for knowledge expansion. KG4Diagnosis serves as an extensible foundation for specialized medical diagnosis systems, with capabilities to incorporate new diseases and medical knowledge. The framework's modular design enables seamless integration of domain-specific enhancements, making it valuable for developing targeted medical diagnosis systems. We provide architectural guidelines and protocols to facilitate adoption across medical contexts.

As large language models (LLMs) like OpenAI's GPT series continue to make strides, we witness the emergence of artificial intelligence applications in an ever-expanding range of fields. In medicine, these LLMs hold considerable promise for improving medical workflows, diagnostics, patient care, and education. Yet, there is an urgent need for open-source models that can be deployed on-premises to safeguard patient privacy. In our work, we present an innovative dataset consisting of over 160,000 entries, specifically crafted to fine-tune LLMs for effective medical applications. We investigate the impact of fine-tuning these datasets on publicly accessible pre-trained LLMs, and subsequently, we juxtapose the performance of pre-trained-only models against the fine-tuned models concerning the examinations that future medical doctors must pass to achieve certification.

Solving the inverse problem is the key step in evaluating the capacity of a physical model to describe real phenomena. In medical image computing, it aligns with the classical theme of image-based model personalization. Traditionally, a solution to the problem is obtained by performing either sampling or variational inference based methods. Both approaches aim to identify a set of free physical model parameters that results in a simulation best matching an empirical observation. When applied to brain tumor modeling, one of the instances of image-based model personalization in medical image computing, the overarching drawback of the methods is the time complexity for finding such a set. In a clinical setting with limited time between imaging and diagnosis or even intervention, this time complexity may prove critical. As the history of quantitative science is the history of compression, we align in this paper with the historical tendency and propose a method compressing complex traditional strategies for solving an inverse problem into a simple database query task. We evaluated different ways of performing the database query task assessing the trade-off between accuracy and execution time. On the exemplary task of brain tumor growth modeling, we prove that the proposed method achieves one order speed-up compared to existing approaches for solving the inverse problem. The resulting compute time offers critical means for relying on more complex and, hence, realistic models, for integrating image preprocessing and inverse modeling even deeper, or for implementing the current model into a clinical workflow.

Providing effective treatment and making informed clinical decisions are essential goals of modern medicine and clinical care. We are interested in simulating disease dynamics for clinical decision-making, leveraging recent advances in large generative models. To this end, we introduce the Medical World Model (MeWM), the first world model in medicine that visually predicts future disease states based on clinical decisions. MeWM comprises (i) vision-language models to serve as policy models, and (ii) tumor generative models as dynamics models. The policy model generates action plans, such as clinical treatments, while the dynamics model simulates tumor progression or regression under given treatment conditions. Building on this, we propose the inverse dynamics model that applies survival analysis to the simulated post-treatment tumor, enabling the evaluation of treatment efficacy and the selection of the optimal clinical action plan. As a result, the proposed MeWM simulates disease dynamics by synthesizing post-treatment tumors, with state-of-the-art specificity in Turing tests evaluated by radiologists. Simultaneously, its inverse dynamics model outperforms medical-specialized GPTs in optimizing individualized treatment protocols across all metrics. Notably, MeWM improves clinical decision-making for interventional physicians, boosting F1-score in selecting the optimal TACE protocol by 13%, paving the way for future integration of medical world models as the second readers.