Daily Papers

Single-cell RNA sequencing (scRNA-seq) data are often confounded by technical or biological batch effects. Existing deep learning models mitigate these effects but often discard batch-specific information, potentially losing valuable biological insights. We propose a Mixed Effects Deep Learning (MEDL) autoencoder framework that separately models batch-invariant (fixed effects) and batch-specific (random effects) components. By decoupling batch-invariant biological states from batch variations, our framework integrates both into predictive models. Our approach also generates 2D visualizations of how the same cell appears across batches, enhancing interpretability. Retaining both fixed and random effect latent spaces improves classification accuracy. We applied our framework to three datasets spanning the cardiovascular system (Healthy Heart), Autism Spectrum Disorder (ASD), and Acute Myeloid Leukemia (AML). With 147 batches in the Healthy Heart dataset, far exceeding typical numbers, we tested our framework's ability to handle many batches. In the ASD dataset, our approach captured donor heterogeneity between autistic and healthy individuals. In the AML dataset, it distinguished donor heterogeneity despite missing cell types and diseased donors exhibiting both healthy and malignant cells. These results highlight our framework's ability to characterize fixed and random effects, enhance batch effect visualization, and improve prediction accuracy across diverse datasets.

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.

Recent advancements in mixed-modal generative models have enabled flexible integration of information across image-text content. These models have opened new avenues for developing unified biomedical assistants capable of analyzing biomedical images, answering complex questions about them, and predicting the impact of medical procedures on a patient's health. However, existing resources face challenges such as limited data availability, narrow domain coverage, and restricted sources (e.g., medical papers). To address these gaps, we present MedMax, the first large-scale multimodal biomedical instruction-tuning dataset for mixed-modal foundation models. With 1.47 million instances, MedMax encompasses a diverse range of tasks, including multimodal content generation (interleaved image-text data), biomedical image captioning and generation, visual chatting, and report understanding. These tasks span diverse medical domains such as radiology and histopathology. Subsequently, we fine-tune a mixed-modal foundation model on the MedMax dataset, achieving significant performance improvements: a 26% gain over the Chameleon model and an 18.3% improvement over GPT-4o across 12 downstream biomedical visual question-answering tasks. Additionally, we introduce a unified evaluation suite for biomedical tasks, providing a robust framework to guide the development of next-generation mixed-modal biomedical AI assistants.

Deep Learning (DL) has the potential to optimize machine learning in both the scientific and clinical communities. However, greater expertise is required to develop DL algorithms, and the variability of implementations hinders their reproducibility, translation, and deployment. Here we present the community-driven Generally Nuanced Deep Learning Framework (GaNDLF), with the goal of lowering these barriers. GaNDLF makes the mechanism of DL development, training, and inference more stable, reproducible, interpretable, and scalable, without requiring an extensive technical background. GaNDLF aims to provide an end-to-end solution for all DL-related tasks in computational precision medicine. We demonstrate the ability of GaNDLF to analyze both radiology and histology images, with built-in support for k-fold cross-validation, data augmentation, multiple modalities and output classes. Our quantitative performance evaluation on numerous use cases, anatomies, and computational tasks supports GaNDLF as a robust application framework for deployment in clinical workflows.

Predicting multiple heterogeneous biological and medical targets is a challenge for traditional deep learning models. In contrast to single-task learning, in which a separate model is trained for each target, multi-task learning (MTL) optimizes a single model to predict multiple related targets simultaneously. To address this challenge, we propose the Multi-gate Mixture-of-Experts with Exclusivity (MMoEEx). Our work aims to tackle the heterogeneous MTL setting, in which the same model optimizes multiple tasks with different characteristics. Such a scenario can overwhelm current MTL approaches due to the challenges in balancing shared and task-specific representations and the need to optimize tasks with competing optimization paths. Our method makes two key contributions: first, we introduce an approach to induce more diversity among experts, thus creating representations more suitable for highly imbalanced and heterogenous MTL learning; second, we adopt a two-step optimization [6, 11] approach to balancing the tasks at the gradient level. We validate our method on three MTL benchmark datasets, including Medical Information Mart for Intensive Care (MIMIC-III) and PubChem BioAssay (PCBA).

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.

Automated brain structure segmentation is important to many clinical quantitative analysis and diagnoses. In this work, we introduce MixNet, a 2D semantic-wise deep convolutional neural network to segment brain structure in multi-modality MRI images. The network is composed of our modified deep residual learning units. In the unit, we replace the traditional convolution layer with the dilated convolutional layer, which avoids the use of pooling layers and deconvolutional layers, reducing the number of network parameters. Final predictions are made by aggregating information from multiple scales and modalities. A pyramid pooling module is used to capture spatial information of the anatomical structures at the output end. In addition, we test three architectures (MixNetv1, MixNetv2 and MixNetv3) which fuse the modalities differently to see the effect on the results. Our network achieves the state-of-the-art performance. MixNetv2 was submitted to the MRBrainS challenge at MICCAI 2018 and won the 3rd place in the 3-label task. On the MRBrainS2018 dataset, which includes subjects with a variety of pathologies, the overall DSC (Dice Coefficient) of 84.7% (gray matter), 87.3% (white matter) and 83.4% (cerebrospinal fluid) were obtained with only 7 subjects as training data.

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.

Existing open-source multimodal large language models (MLLMs) generally follow a training process involving pre-training and supervised fine-tuning. However, these models suffer from distribution shifts, which limit their multimodal reasoning, particularly in the Chain-of-Thought (CoT) performance. To address this, we introduce a preference optimization (PO) process to enhance the multimodal reasoning capabilities of MLLMs. Specifically, (1) on the data side, we design an automated preference data construction pipeline to create MMPR, a high-quality, large-scale multimodal reasoning preference dataset. and (2) on the model side, we explore integrating PO with MLLMs, developing a simple yet effective method, termed Mixed Preference Optimization (MPO), which boosts multimodal CoT performance. Our approach demonstrates improved performance across multiple benchmarks, particularly in multimodal reasoning tasks. Notably, our model, InternVL2-8B-MPO, achieves an accuracy of 67.0 on MathVista, outperforming InternVL2-8B by 8.7 points and achieving performance comparable to the 10x larger InternVL2-76B. We hope this study could inspire further advancements in MLLMs. Code, data, and model shall be publicly released.

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.

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.

In recent years, Multimodal Large Language Models (MLLM) have achieved notable advancements, demonstrating the feasibility of developing an intelligent biomedical assistant. However, current biomedical MLLMs predominantly focus on image-level understanding and restrict interactions to textual commands, thus limiting their capability boundaries and the flexibility of usage. In this paper, we introduce a novel end-to-end multimodal large language model for the biomedical domain, named MedPLIB, which possesses pixel-level understanding. Excitingly, it supports visual question answering (VQA), arbitrary pixel-level prompts (points, bounding boxes, and free-form shapes), and pixel-level grounding. We propose a novel Mixture-of-Experts (MoE) multi-stage training strategy, which divides MoE into separate training phases for a visual-language expert model and a pixel-grounding expert model, followed by fine-tuning using MoE. This strategy effectively coordinates multitask learning while maintaining the computational cost at inference equivalent to that of a single expert model. To advance the research of biomedical MLLMs, we introduce the Medical Complex Vision Question Answering Dataset (MeCoVQA), which comprises an array of 8 modalities for complex medical imaging question answering and image region understanding. Experimental results indicate that MedPLIB has achieved state-of-the-art outcomes across multiple medical visual language tasks. More importantly, in zero-shot evaluations for the pixel grounding task, MedPLIB leads the best small and large models by margins of 19.7 and 15.6 respectively on the mDice metric. The codes, data, and model checkpoints will be made publicly available at https://github.com/ShawnHuang497/MedPLIB.

In this study, we present MedS-Bench, a comprehensive benchmark designed to evaluate the performance of large language models (LLMs) in clinical contexts. Unlike existing benchmarks that focus on multiple-choice question answering, MedS-Bench spans 11 high-level clinical tasks, including clinical report summarization, treatment recommendations, diagnosis, named entity recognition, and medical concept explanation, among others. We evaluated six leading LLMs, e.g., MEDITRON, Mistral, InternLM 2, Llama 3, GPT-4, and Claude-3.5 using few-shot prompting, and found that even the most sophisticated models struggle with these complex tasks. To address these limitations, we developed MedS-Ins, a large-scale instruction tuning dataset for medicine. MedS-Ins comprises 58 medically oriented language corpora, totaling 13.5 million samples across 122 tasks. To demonstrate the dataset's utility, we conducted a proof-of-concept experiment by performing instruction tuning on a lightweight, open-source medical language model. The resulting model, MMedIns-Llama 3, significantly outperformed existing models across nearly all clinical tasks. To promote further advancements in the application of LLMs to clinical challenges, we have made the MedS-Ins dataset fully accessible and invite the research community to contribute to its expansion.Additionally, we have launched a dynamic leaderboard for MedS-Bench, which we plan to regularly update the test set to track progress and enhance the adaptation of general LLMs to the medical domain. Leaderboard: https://henrychur.github.io/MedS-Bench/. Github: https://github.com/MAGIC-AI4Med/MedS-Ins.

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.

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.

In this paper, we aim to develop an open-source, multilingual language model for medicine, that the benefits a wider, linguistically diverse audience from different regions. In general, we present the contribution from the following aspects: first, for multilingual medical-specific adaptation, we construct a new multilingual medical corpus, that contains approximately 25.5B tokens encompassing 6 main languages, termed as MMedC, that enables auto-regressive training for existing general LLMs. second, to monitor the development of multilingual LLMs in medicine, we propose a new multilingual medical multi-choice question-answering benchmark with rationale, termed as MMedBench; third, we have assessed a number of popular, opensource large language models (LLMs) on our benchmark, along with those further auto-regressive trained on MMedC, as a result, our final model, termed as MMedLM 2, with only 7B parameters, achieves superior performance compared to all other open-source models, even rivaling GPT-4 on MMedBench. We will make the resources publicly available, including code, model weights, and datasets.

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.

Multimodal large language models (MLLMs) have demonstrated impressive performance in vision-language tasks across a broad spectrum of domains. However, the large model scale and associated high computational costs pose significant challenges for training and deploying MLLMs on consumer-grade GPUs or edge devices, thereby hindering their widespread application. In this work, we introduce Mini-InternVL, a series of MLLMs with parameters ranging from 1B to 4B, which achieves 90% of the performance with only 5% of the parameters. This significant improvement in efficiency and effectiveness makes our models more accessible and applicable in various real-world scenarios. To further promote the adoption of our models, we develop a unified adaptation framework for Mini-InternVL, which enables our models to transfer and outperform specialized models in downstream tasks, including autonomous driving, medical images, and remote sensing. We believe that our study can provide valuable insights and resources to advance the development of efficient and effective MLLMs. Code is available at https://github.com/OpenGVLab/InternVL.

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.

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

Mixup data augmentation approaches have been applied for various tasks of deep learning to improve the generalization ability of deep neural networks. Some existing approaches CutMix, SaliencyMix, etc. randomly replace a patch in one image with patches from another to generate the mixed image. Similarly, the corresponding labels are linearly combined by a fixed ratio lambda by l. The objects in two images may be overlapped during the mixing process, so some semantic information is corrupted in the mixed samples. In this case, the mixed image does not match the mixed label information. Besides, such a label may mislead the deep learning model training, which results in poor performance. To solve this problem, we proposed a novel approach named SUMix to learn the mixing ratio as well as the uncertainty for the mixed samples during the training process. First, we design a learnable similarity function to compute an accurate mix ratio. Second, an approach is investigated as a regularized term to model the uncertainty of the mixed samples. We conduct experiments on five image benchmarks, and extensive experimental results imply that our method is capable of improving the performance of classifiers with different cutting-based mixup approaches. The source code is available at https://github.com/JinXins/SUMix.

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.

Artificial Intelligence (AI) has demonstrated significant potential in healthcare, particularly in disease diagnosis and treatment planning. Recent progress in Medical Large Vision-Language Models (Med-LVLMs) has opened up new possibilities for interactive diagnostic tools. However, these models often suffer from factual hallucination, which can lead to incorrect diagnoses. Fine-tuning and retrieval-augmented generation (RAG) have emerged as methods to address these issues. However, the amount of high-quality data and distribution shifts between training data and deployment data limit the application of fine-tuning methods. Although RAG is lightweight and effective, existing RAG-based approaches are not sufficiently general to different medical domains and can potentially cause misalignment issues, both between modalities and between the model and the ground truth. In this paper, we propose a versatile multimodal RAG system, MMed-RAG, designed to enhance the factuality of Med-LVLMs. Our approach introduces a domain-aware retrieval mechanism, an adaptive retrieved contexts selection method, and a provable RAG-based preference fine-tuning strategy. These innovations make the RAG process sufficiently general and reliable, significantly improving alignment when introducing retrieved contexts. Experimental results across five medical datasets (involving radiology, ophthalmology, pathology) on medical VQA and report generation demonstrate that MMed-RAG can achieve an average improvement of 43.8% in the factual accuracy of Med-LVLMs. Our data and code are available in https://github.com/richard-peng-xia/MMed-RAG.

Medical language models (MLMs) have become pivotal in advancing medical natural language processing. However, prior models that rely on pre-training or supervised fine-tuning often exhibit low data efficiency and limited practicality in real-world clinical applications. While OpenAIs O1 highlights test-time scaling in mathematics, attempts to replicate this approach in medicine typically distill responses from GPT-series models to open-source models, focusing primarily on multiple-choice tasks. This strategy, though straightforward, neglects critical concerns like data privacy and realistic deployment in clinical settings. In this work, we present a deployable, small-scale medical language model, \mone, designed for long-chain reasoning in clinical tasks using a self-evolution paradigm. Starting with a seed dataset of around 8,000 instances spanning five domains and 16 datasets, we prompt a base policy model to perform Monte Carlo Tree Search (MCTS) to construct verifiable reasoning chains. Each reasoning step is assigned an evolution rollout value, allowing verified trajectories to train the policy model and the reward model. During inference, the policy model generates multiple responses, and the reward model selects the one with the highest reward score. Experiments on eleven evaluation datasets demonstrate that \mone outperforms prior open-source models by 2 points, with the addition of the reward model further boosting performance (sim13 points), surpassing GPT-4o-mini. Code and data are available at https://github.com/pixas/MedSSS.

As the research of Multimodal Large Language Models (MLLMs) becomes popular, an advancing MLLM model is typically required to handle various textual and visual tasks (e.g., VQA, Detection, OCR, and ChartQA) simultaneously for real-world applications. However, due to the significant differences in representation and distribution among data from various tasks, simply mixing data of all tasks together leads to the well-known``multi-task conflict" issue, resulting in performance degradation across various tasks. To address this issue, we propose Awaker2.5-VL, a Mixture of Experts~(MoE) architecture suitable for MLLM, which acquires the multi-task capabilities through multiple sparsely activated experts. To speed up the training and inference of Awaker2.5-VL, each expert in our model is devised as a low-rank adaptation (LoRA) structure. Extensive experiments on multiple latest benchmarks demonstrate the effectiveness of Awaker2.5-VL. The code and model weight are released in our Project Page: https://github.com/MetabrainAGI/Awaker.

Existing machine learning methods for causal inference usually estimate quantities expressed via the mean of potential outcomes (e.g., average treatment effect). However, such quantities do not capture the full information about the distribution of potential outcomes. In this work, we estimate the density of potential outcomes after interventions from observational data. For this, we propose a novel, fully-parametric deep learning method called Interventional Normalizing Flows. Specifically, we combine two normalizing flows, namely (i) a nuisance flow for estimating nuisance parameters and (ii) a target flow for parametric estimation of the density of potential outcomes. We further develop a tractable optimization objective based on a one-step bias correction for efficient and doubly robust estimation of the target flow parameters. As a result, our Interventional Normalizing Flows offer a properly normalized density estimator. Across various experiments, we demonstrate that our Interventional Normalizing Flows are expressive and highly effective, and scale well with both sample size and high-dimensional confounding. To the best of our knowledge, our Interventional Normalizing Flows are the first proper fully-parametric, deep learning method for density estimation of potential outcomes.

Large Vision-Language Models (LVLMs) are capable of handling diverse data types such as imaging, text, and physiological signals, and can be applied in various fields. In the medical field, LVLMs have a high potential to offer substantial assistance for diagnosis and treatment. Before that, it is crucial to develop benchmarks to evaluate LVLMs' effectiveness in various medical applications. Current benchmarks are often built upon specific academic literature, mainly focusing on a single domain, and lacking varying perceptual granularities. Thus, they face specific challenges, including limited clinical relevance, incomplete evaluations, and insufficient guidance for interactive LVLMs. To address these limitations, we developed the GMAI-MMBench, the most comprehensive general medical AI benchmark with well-categorized data structure and multi-perceptual granularity to date. It is constructed from 285 datasets across 39 medical image modalities, 18 clinical-related tasks, 18 departments, and 4 perceptual granularities in a Visual Question Answering (VQA) format. Additionally, we implemented a lexical tree structure that allows users to customize evaluation tasks, accommodating various assessment needs and substantially supporting medical AI research and applications. We evaluated 50 LVLMs, and the results show that even the advanced GPT-4o only achieves an accuracy of 52%, indicating significant room for improvement. Moreover, we identified five key insufficiencies in current cutting-edge LVLMs that need to be addressed to advance the development of better medical applications. We believe that GMAI-MMBench will stimulate the community to build the next generation of LVLMs toward GMAI. Project Page: https://uni-medical.github.io/GMAI-MMBench.github.io/

Medical Image Analysis (MedIA) has become an essential tool in medicine and healthcare, aiding in disease diagnosis, prognosis, and treatment planning, and recent successes in deep learning (DL) have made significant contributions to its advances. However, DL models for MedIA remain challenging to deploy in real-world situations, failing for generalization under the distributional gap between training and testing samples, known as a distribution shift problem. Researchers have dedicated their efforts to developing various DL methods to adapt and perform robustly on unknown and out-of-distribution data distributions. This paper comprehensively reviews domain generalization studies specifically tailored for MedIA. We provide a holistic view of how domain generalization techniques interact within the broader MedIA system, going beyond methodologies to consider the operational implications on the entire MedIA workflow. Specifically, we categorize domain generalization methods into data-level, feature-level, model-level, and analysis-level methods. We show how those methods can be used in various stages of the MedIA workflow with DL equipped from data acquisition to model prediction and analysis. Furthermore, we include benchmark datasets and applications used to evaluate these approaches and analyze the strengths and weaknesses of various methods, unveiling future research opportunities.

In the field of medical sciences, reliable detection and classification of brain tumors from images remains a formidable challenge due to the rarity of tumors within the population of patients. Therefore, the ability to detect tumors in anomaly scenarios is paramount for ensuring timely interventions and improved patient outcomes. This study addresses the issue by leveraging deep learning (DL) techniques to detect and classify brain tumors in challenging situations. The curated data set from the National Brain Mapping Lab (NBML) comprises 81 patients, including 30 Tumor cases and 51 Normal cases. The detection and classification pipelines are separated into two consecutive tasks. The detection phase involved comprehensive data analysis and pre-processing to modify the number of image samples and the number of patients of each class to anomaly distribution (9 Normal per 1 Tumor) to comply with real world scenarios. Next, in addition to common evaluation metrics for the testing, we employed a novel performance evaluation method called Patient to Patient (PTP), focusing on the realistic evaluation of the model. In the detection phase, we fine-tuned a YOLOv8n detection model to detect the tumor region. Subsequent testing and evaluation yielded competitive performance both in Common Evaluation Metrics and PTP metrics. Furthermore, using the Data Efficient Image Transformer (DeiT) module, we distilled a Vision Transformer (ViT) model from a fine-tuned ResNet152 as a teacher in the classification phase. This approach demonstrates promising strides in reliable tumor detection and classification, offering potential advancements in tumor diagnosis for real-world medical imaging scenarios.

Predicting how different interventions will causally affect a specific individual is important in a variety of domains such as personalized medicine, public policy, and online marketing. There are a large number of methods to predict the effect of an existing intervention based on historical data from individuals who received it. However, in many settings it is important to predict the effects of novel interventions (e.g., a newly invented drug), which these methods do not address. Here, we consider zero-shot causal learning: predicting the personalized effects of a novel intervention. We propose CaML, a causal meta-learning framework which formulates the personalized prediction of each intervention's effect as a task. CaML trains a single meta-model across thousands of tasks, each constructed by sampling an intervention, along with its recipients and nonrecipients. By leveraging both intervention information (e.g., a drug's attributes) and individual features~(e.g., a patient's history), CaML is able to predict the personalized effects of novel interventions that do not exist at the time of training. Experimental results on real world datasets in large-scale medical claims and cell-line perturbations demonstrate the effectiveness of our approach. Most strikingly, CaML's zero-shot predictions outperform even strong baselines trained directly on data from the test interventions.

Large language models (LLM) have recently shown the extraordinary ability to perform unseen tasks based on few-shot examples provided as text, also known as in-context learning (ICL). While recent works have attempted to understand the mechanisms driving ICL, few have explored training strategies that incentivize these models to generalize to multiple tasks. Multi-task learning (MTL) for generalist models is a promising direction that offers transfer learning potential, enabling large parameterized models to be trained from simpler, related tasks. In this work, we investigate the combination of MTL with ICL to build models that efficiently learn tasks while being robust to out-of-distribution examples. We propose several effective curriculum learning strategies that allow ICL models to achieve higher data efficiency and more stable convergence. Our experiments reveal that ICL models can effectively learn difficult tasks by training on progressively harder tasks while mixing in prior tasks, denoted as mixed curriculum in this work. Our code and models are available at https://github.com/harmonbhasin/curriculum_learning_icl .

Mixup is an efficient data augmentation approach that improves the generalization of neural networks by smoothing the decision boundary with mixed data. Recently, dynamic mixup methods have improved previous static policies effectively (e.g., linear interpolation) by maximizing target-related salient regions in mixed samples, but excessive additional time costs are not acceptable. These additional computational overheads mainly come from optimizing the mixed samples according to the mixed labels. However, we found that the extra optimizing step may be redundant because label-mismatched mixed samples are informative hard mixed samples for deep models to localize discriminative features. In this paper, we thus are not trying to propose a more complicated dynamic mixup policy but rather an efficient mixup objective function with a decoupled regularizer named Decoupled Mixup (DM). The primary effect is that DM can adaptively utilize those hard mixed samples to mine discriminative features without losing the original smoothness of mixup. As a result, DM enables static mixup methods to achieve comparable or even exceed the performance of dynamic methods without any extra computation. This also leads to an interesting objective design problem for mixup training that we need to focus on both smoothing the decision boundaries and identifying discriminative features. Extensive experiments on supervised and semi-supervised learning benchmarks across seven datasets validate the effectiveness of DM as a plug-and-play module. Source code and models are available at https://github.com/Westlake-AI/openmixup

Recent artificial intelligence (AI) systems have reached milestones in "grand challenges" ranging from Go to protein-folding. The capability to retrieve medical knowledge, reason over it, and answer medical questions comparably to physicians has long been viewed as one such grand challenge. Large language models (LLMs) have catalyzed significant progress in medical question answering; Med-PaLM was the first model to exceed a "passing" score in US Medical Licensing Examination (USMLE) style questions with a score of 67.2% on the MedQA dataset. However, this and other prior work suggested significant room for improvement, especially when models' answers were compared to clinicians' answers. Here we present Med-PaLM 2, which bridges these gaps by leveraging a combination of base LLM improvements (PaLM 2), medical domain finetuning, and prompting strategies including a novel ensemble refinement approach. Med-PaLM 2 scored up to 86.5% on the MedQA dataset, improving upon Med-PaLM by over 19% and setting a new state-of-the-art. We also observed performance approaching or exceeding state-of-the-art across MedMCQA, PubMedQA, and MMLU clinical topics datasets. We performed detailed human evaluations on long-form questions along multiple axes relevant to clinical applications. In pairwise comparative ranking of 1066 consumer medical questions, physicians preferred Med-PaLM 2 answers to those produced by physicians on eight of nine axes pertaining to clinical utility (p < 0.001). We also observed significant improvements compared to Med-PaLM on every evaluation axis (p < 0.001) on newly introduced datasets of 240 long-form "adversarial" questions to probe LLM limitations. While further studies are necessary to validate the efficacy of these models in real-world settings, these results highlight rapid progress towards physician-level performance in medical question answering.

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.

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.

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.

Accurate medical classification requires a large number of multi-modal data, and in many cases, different feature types. Previous studies have shown promising results when using multi-modal data, outperforming single-modality models when classifying diseases such as Alzheimer's Disease (AD). However, those models are usually not flexible enough to handle missing modalities. Currently, the most common workaround is discarding samples with missing modalities which leads to considerable data under-utilization. Adding to the fact that labeled medical images are already scarce, the performance of data-driven methods like deep learning can be severely hampered. Therefore, a multi-modal method that can handle missing data in various clinical settings is highly desirable. In this paper, we present Multi-Modal Mixing Transformer (3MAT), a disease classification transformer that not only leverages multi-modal data but also handles missing data scenarios. In this work, we test 3MT for AD and Cognitively normal (CN) classification and mild cognitive impairment (MCI) conversion prediction to progressive MCI (pMCI) or stable MCI (sMCI) using clinical and neuroimaging data. The model uses a novel Cascaded Modality Transformer architecture with cross-attention to incorporate multi-modal information for more informed predictions. We propose a novel modality dropout mechanism to ensure an unprecedented level of modality independence and robustness to handle missing data scenarios. The result is a versatile network that enables the mixing of arbitrary numbers of modalities with different feature types and also ensures full data utilization missing data scenarios. The model is trained and evaluated on the ADNI dataset with the SOTRA performance and further evaluated with the AIBL dataset with missing data.

Built on the power of LLMs, numerous multimodal large language models (MLLMs) have recently achieved remarkable performance on various vision-language tasks across multiple benchmarks. However, most existing MLLMs and benchmarks primarily focus on single-image input scenarios, leaving the performance of MLLMs when handling realistic multiple images remain underexplored. Although a few benchmarks consider multiple images, their evaluation dimensions and samples are very limited. Therefore, in this paper, we propose a new benchmark MIBench, to comprehensively evaluate fine-grained abilities of MLLMs in multi-image scenarios. Specifically, MIBench categorizes the multi-image abilities into three scenarios: multi-image instruction (MII), multimodal knowledge-seeking (MKS) and multimodal in-context learning (MIC), and constructs 13 tasks with a total of 13K annotated samples. During data construction, for MII and MKS, we extract correct options from manual annotations and create challenging distractors to obtain multiple-choice questions. For MIC, to enable an in-depth evaluation, we set four sub-tasks and transform the original datasets into in-context learning formats. We evaluate several open-source MLLMs and close-source MLLMs on the proposed MIBench. The results reveal that although current models excel in single-image tasks, they exhibit significant shortcomings when faced with multi-image inputs, such as confused fine-grained perception, limited multi-image reasoning, and unstable in-context learning. The annotated data in MIBench is available at https://huggingface.co/datasets/StarBottle/MIBench.

The increasing interest in developing Artificial Intelligence applications in the medical domain, suffers from the lack of high-quality dataset, mainly due to privacy-related issues. Moreover, the recent rising of Multimodal Large Language Models (MLLM) leads to a need for multimodal medical datasets, where clinical reports and findings are attached to the corresponding CT or MR scans. This paper illustrates the entire workflow for building the data set MedPix 2.0. Starting from the well-known multimodal dataset MedPix\textregistered, mainly used by physicians, nurses and healthcare students for Continuing Medical Education purposes, a semi-automatic pipeline was developed to extract visual and textual data followed by a manual curing procedure where noisy samples were removed, thus creating a MongoDB database. Along with the dataset, we developed a GUI aimed at navigating efficiently the MongoDB instance, and obtaining the raw data that can be easily used for training and/or fine-tuning MLLMs. To enforce this point, we also propose a CLIP-based model trained on MedPix 2.0 for scan classification tasks.

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.

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.

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.

A brain tumour is a mass or cluster of abnormal cells in the brain, which has the possibility of becoming life-threatening because of its ability to invade neighbouring tissues and also form metastases. An accurate diagnosis is essential for successful treatment planning and magnetic resonance imaging is the principal imaging modality for diagnostic of brain tumours and their extent. Deep Learning methods in computer vision applications have shown significant improvement in recent years, most of which can be credited to the fact that a sizeable amount of data is available to train models on, and the improvements in the model architectures yielding better approximations in a supervised setting. Classifying tumours using such deep learning methods has made significant progress with the availability of open datasets with reliable annotations. Typically those methods are either 3D models, which use 3D volumetric MRIs or even 2D models considering each slice separately. However, by treating the slice spatial dimension separately, spatiotemporal models can be employed as spatiospatial models for this task. These models have the capabilities of learning specific spatial and temporal relationship, while reducing computational costs. This paper uses two spatiotemporal models, ResNet (2+1)D and ResNet Mixed Convolution, to classify different types of brain tumours. It was observed that both these models performed superior to the pure 3D convolutional model, ResNet18. Furthermore, it was also observed that pre-training the models on a different, even unrelated dataset before training them for the task of tumour classification improves the performance. Finally, Pre-trained ResNet Mixed Convolution was observed to be the best model in these experiments, achieving a macro F1-score of 0.93 and a test accuracy of 96.98\%, while at the same time being the model with the least computational cost.

While deep learning (DL) is data-hungry and usually relies on extensive labeled data to deliver good performance, Active Learning (AL) reduces labeling costs by selecting a small proportion of samples from unlabeled data for labeling and training. Therefore, Deep Active Learning (DAL) has risen as a feasible solution for maximizing model performance under a limited labeling cost/budget in recent years. Although abundant methods of DAL have been developed and various literature reviews conducted, the performance evaluation of DAL methods under fair comparison settings is not yet available. Our work intends to fill this gap. In this work, We construct a DAL toolkit, DeepAL+, by re-implementing 19 highly-cited DAL methods. We survey and categorize DAL-related works and construct comparative experiments across frequently used datasets and DAL algorithms. Additionally, we explore some factors (e.g., batch size, number of epochs in the training process) that influence the efficacy of DAL, which provides better references for researchers to design their DAL experiments or carry out DAL-related applications.

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.

Deep learning classifiers face significant challenges when dealing with heterogeneous multi-modal and multi-organ biomedical datasets. The low-level feature distinguishability limited to imaging-modality hinders the classifiers' ability to learn high-level semantic relationships, resulting in sub-optimal performance. To address this issue, image augmentation strategies are employed as regularization techniques. While additive noise input during network training is a well-established augmentation as regularization method, modern pipelines often favor more robust techniques such as dropout and weight decay. This preference stems from the observation that combining these established techniques with noise input can adversely affect model performance. In this study, we propose a novel pretraining pipeline that learns to generate conditional noise mask specifically tailored to improve performance on multi-modal and multi-organ datasets. As a reinforcement learning algorithm, our approach employs a dual-component system comprising a very light-weight policy network that learns to sample conditional noise using a differentiable beta distribution as well as a classifier network. The policy network is trained using the reinforce algorithm to generate image-specific noise masks that regularize the classifier during pretraining. A key aspect is that the policy network's role is limited to obtaining an intermediate (or heated) model before fine-tuning. During inference, the policy network is omitted, allowing direct comparison between the baseline and noise-regularized models. We conducted experiments and related analyses on RadImageNet datasets. Results demonstrate that fine-tuning the intermediate models consistently outperforms conventional training algorithms on both classification and generalization to unseen concept tasks.

We present MM1.5, a new family of multimodal large language models (MLLMs) designed to enhance capabilities in text-rich image understanding, visual referring and grounding, and multi-image reasoning. Building upon the MM1 architecture, MM1.5 adopts a data-centric approach to model training, systematically exploring the impact of diverse data mixtures across the entire model training lifecycle. This includes high-quality OCR data and synthetic captions for continual pre-training, as well as an optimized visual instruction-tuning data mixture for supervised fine-tuning. Our models range from 1B to 30B parameters, encompassing both dense and mixture-of-experts (MoE) variants, and demonstrate that careful data curation and training strategies can yield strong performance even at small scales (1B and 3B). Additionally, we introduce two specialized variants: MM1.5-Video, designed for video understanding, and MM1.5-UI, tailored for mobile UI understanding. Through extensive empirical studies and ablations, we provide detailed insights into the training processes and decisions that inform our final designs, offering valuable guidance for future research in MLLM development.

In this paper, we propose an architecture to harness the collective knowledge of multiple trained LLMs to create a new state-of-the-art. At the core of this framework is a LLM-based orchestrator that is adept at picking the right underlying LLM experts for optimal task execution. Inspired by self-play in reinforcement learning, we created a loop of query generation, orchestration, and evaluation to generate training data for the orchestrator. Our evaluation focused on the MMLU benchmark, employing models with 7B, 13B, and 34B parameters available on Hugging Face. The results demonstrate new state-of-the-art open-source models: Our Leeroo orchestrator achieves performance on par with the Mixtral model while incurring only two-thirds of its cost. Moreover, increasing the allowed cost surpasses Mixtral's accuracy by over 5% at the same cost level, reaching an accuracy of 75.9%. Further enhancements were observed when integrating GPT4 into the underlying model pool. The Leeroo orchestrator nearly matches GPT4's performance at half the cost and even exceeds GPT4's results with a 25% cost reduction. These findings illustrate the potential of our architecture in creating state-of-the-art and cost-effective LLMs by optimizing the synergy between multiple LLMs to achieve superior performance outcomes.

Artificial intelligence has significantly impacted medical applications, particularly with the advent of Medical Large Vision Language Models (Med-LVLMs), sparking optimism for the future of automated and personalized healthcare. However, the trustworthiness of Med-LVLMs remains unverified, posing significant risks for future model deployment. In this paper, we introduce CARES and aim to comprehensively evaluate the Trustworthiness of Med-LVLMs across the medical domain. We assess the trustworthiness of Med-LVLMs across five dimensions, including trustfulness, fairness, safety, privacy, and robustness. CARES comprises about 41K question-answer pairs in both closed and open-ended formats, covering 16 medical image modalities and 27 anatomical regions. Our analysis reveals that the models consistently exhibit concerns regarding trustworthiness, often displaying factual inaccuracies and failing to maintain fairness across different demographic groups. Furthermore, they are vulnerable to attacks and demonstrate a lack of privacy awareness. We publicly release our benchmark and code in https://github.com/richard-peng-xia/CARES.

Despite the ever-increasing interest in applying deep learning (DL) models to medical imaging, the typical scarcity and imbalance of medical datasets can severely impact the performance of DL models. The generation of synthetic data that might be freely shared without compromising patient privacy is a well-known technique for addressing these difficulties. Inpainting algorithms are a subset of DL generative models that can alter one or more regions of an input image while matching its surrounding context and, in certain cases, non-imaging input conditions. Although the majority of inpainting techniques for medical imaging data use generative adversarial networks (GANs), the performance of these algorithms is frequently suboptimal due to their limited output variety, a problem that is already well-known for GANs. Denoising diffusion probabilistic models (DDPMs) are a recently introduced family of generative networks that can generate results of comparable quality to GANs, but with diverse outputs. In this paper, we describe a DDPM to execute multiple inpainting tasks on 2D axial slices of brain MRI with various sequences, and present proof-of-concept examples of its performance in a variety of evaluation scenarios. Our model and a public online interface to try our tool are available at: https://github.com/Mayo-Radiology-Informatics-Lab/MBTI

Predicting multiple real-world tasks in a single model often requires a particularly diverse feature space. Multimodal (MM) models aim to extract the synergistic predictive potential of multiple data types to create a shared feature space with aligned semantic meaning across inputs of drastically varying sizes (i.e. images, text, sound). Most current MM architectures fuse these representations in parallel, which not only limits their interpretability but also creates a dependency on modality availability. We present MultiModN, a multimodal, modular network that fuses latent representations in a sequence of any number, combination, or type of modality while providing granular real-time predictive feedback on any number or combination of predictive tasks. MultiModN's composable pipeline is interpretable-by-design, as well as innately multi-task and robust to the fundamental issue of biased missingness. We perform four experiments on several benchmark MM datasets across 10 real-world tasks (predicting medical diagnoses, academic performance, and weather), and show that MultiModN's sequential MM fusion does not compromise performance compared with a baseline of parallel fusion. By simulating the challenging bias of missing not-at-random (MNAR), this work shows that, contrary to MultiModN, parallel fusion baselines erroneously learn MNAR and suffer catastrophic failure when faced with different patterns of MNAR at inference. To the best of our knowledge, this is the first inherently MNAR-resistant approach to MM modeling. In conclusion, MultiModN provides granular insights, robustness, and flexibility without compromising performance.

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.

In this paper, we introduce BiMediX, the first bilingual medical mixture of experts LLM designed for seamless interaction in both English and Arabic. Our model facilitates a wide range of medical interactions in English and Arabic, including multi-turn chats to inquire about additional details such as patient symptoms and medical history, multiple-choice question answering, and open-ended question answering. We propose a semi-automated English-to-Arabic translation pipeline with human refinement to ensure high-quality translations. We also introduce a comprehensive evaluation benchmark for Arabic medical LLMs. Furthermore, we introduce BiMed1.3M, an extensive Arabic-English bilingual instruction set covering 1.3 Million diverse medical interactions, resulting in over 632 million healthcare specialized tokens for instruction tuning. Our BiMed1.3M dataset includes 250k synthesized multi-turn doctor-patient chats and maintains a 1:2 Arabic-to-English ratio. Our model outperforms state-of-the-art Med42 and Meditron by average absolute gains of 2.5% and 4.1%, respectively, computed across multiple medical evaluation benchmarks in English, while operating at 8-times faster inference. Moreover, our BiMediX outperforms the generic Arabic-English bilingual LLM, Jais-30B, by average absolute gains of 10% on our Arabic medical benchmark and 15% on bilingual evaluations across multiple datasets. Our project page with source code and trained model is available at https://github.com/mbzuai-oryx/BiMediX .

Predicting clinical outcomes from preclinical data is essential for identifying safe and effective drug combinations. Current models rely on structural or target-based features to identify high-efficacy, low-toxicity drug combinations. However, these approaches fail to incorporate the multimodal data necessary for accurate, clinically-relevant predictions. Here, we introduce MADRIGAL, a multimodal AI model that learns from structural, pathway, cell viability, and transcriptomic data to predict drug combination effects across 953 clinical outcomes and 21842 compounds, including combinations of approved drugs and novel compounds in development. MADRIGAL uses a transformer bottleneck module to unify preclinical drug data modalities while handling missing data during training and inference--a major challenge in multimodal learning. It outperforms single-modality methods and state-of-the-art models in predicting adverse drug interactions. MADRIGAL performs virtual screening of anticancer drug combinations and supports polypharmacy management for type II diabetes and metabolic dysfunction-associated steatohepatitis (MASH). It identifies transporter-mediated drug interactions. MADRIGAL predicts resmetirom, the first and only FDA-approved drug for MASH, among therapies with the most favorable safety profile. It supports personalized cancer therapy by integrating genomic profiles from cancer patients. Using primary acute myeloid leukemia samples and patient-derived xenograft models, it predicts the efficacy of personalized drug combinations. Integrating MADRIGAL with a large language model allows users to describe clinical outcomes in natural language, improving safety assessment by identifying potential adverse interactions and toxicity risks. MADRIGAL provides a multimodal approach for designing combination therapies with improved predictive accuracy and clinical relevance.

Recent advancements in large language models (LLMs) have shown promise in medical applications such as disease diagnosis and treatment planning. However, most existing medical LLMs struggle with the advanced reasoning required for complex clinical scenarios, such as differential diagnosis or personalized treatment suggestions. We proposed FineMedLM-o1, which leverages high-quality synthetic medical data and long-form reasoning data for Supervised Fine-Tuning (SFT) and Direct Preference Optimization (DPO), enabling advanced dialogue and deep reasoning capabilities. Additionally, we introduced Test-Time Training (TTT) in the medical domain for the first time, facilitating domain adaptation and ensuring reliable, accurate reasoning. Experimental results demonstrate that FineMedLM-o1 achieves a 23% average performance improvement over prior models on key medical benchmarks. Furthermore, the introduction of TTT provides an additional 14% performance boost, highlighting its effectiveness in enhancing medical reasoning capabilities. To support this process, we also proposed a novel method for synthesizing medical dialogue. Compared to other open-source datasets, our dataset stands out as superior in both quality and complexity. The project and data will be released on GitHub.

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.

The integration of large language model (LLM) techniques in the field of medical analysis has brought about significant advancements, yet the scarcity of large, diverse, and well-annotated datasets remains a major challenge. Medical data and tasks, which vary in format, size, and other parameters, require extensive preprocessing and standardization for effective use in training LLMs. To address these challenges, we introduce MedINST, the Meta Dataset of Biomedical Instructions, a novel multi-domain, multi-task instructional meta-dataset. MedINST comprises 133 biomedical NLP tasks and over 7 million training samples, making it the most comprehensive biomedical instruction dataset to date. Using MedINST as the meta dataset, we curate MedINST32, a challenging benchmark with different task difficulties aiming to evaluate LLMs' generalization ability. We fine-tune several LLMs on MedINST and evaluate on MedINST32, showcasing enhanced cross-task generalization.

Multimodal large language models (MLLMs) represent an evolutionary expansion in the capabilities of traditional large language models, enabling them to tackle challenges that surpass the scope of purely text-based applications. It leverages the knowledge previously encoded within these language models, thereby enhancing their applicability and functionality in the reign of multimodal contexts. Recent works investigate the adaptation of MLLMs to predict free-form answers as a generative task to solve medical visual question answering (Med-VQA) tasks. In this paper, we propose a parameter efficient framework for fine-tuning MLLM specifically tailored to Med-VQA applications, and empirically validate it on a public benchmark dataset. To accurately measure the performance, we employ human evaluation and the results reveal that our model achieves an overall accuracy of 81.9%, and outperforms the GPT-4v model by a significant margin of 26% absolute accuracy on closed-ended questions. The code will be available here: https://github.com/jinlHe/PeFoMed.

While deep networks have achieved broad success in analyzing natural images, when applied to medical scans, they often fail in unexcepted situations. We investigate this challenge and focus on model sensitivity to domain shifts, such as data sampled from different hospitals or data confounded by demographic variables such as sex, race, etc, in the context of chest X-rays and skin lesion images. A key finding we show empirically is that existing visual backbones lack an appropriate prior from the architecture for reliable generalization in these settings. Taking inspiration from medical training, we propose giving deep networks a prior grounded in explicit medical knowledge communicated in natural language. To this end, we introduce Knowledge-enhanced Bottlenecks (KnoBo), a class of concept bottleneck models that incorporates knowledge priors that constrain it to reason with clinically relevant factors found in medical textbooks or PubMed. KnoBo uses retrieval-augmented language models to design an appropriate concept space paired with an automatic training procedure for recognizing the concept. We evaluate different resources of knowledge and recognition architectures on a broad range of domain shifts across 20 datasets. In our comprehensive evaluation with two imaging modalities, KnoBo outperforms fine-tuned models on confounded datasets by 32.4% on average. Finally, evaluations reveal that PubMed is a promising resource for making medical models less sensitive to domain shift, outperforming other resources on both diversity of information and final prediction performance.

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.

Building upon our previous investigations of O1 replication (Part 1: Journey Learning [Qin et al., 2024] and Part 2: Distillation [Huang et al., 2024]), this work explores the potential of inference-time scaling in large language models (LLMs) for medical reasoning tasks, ranging from diagnostic decision-making to treatment planning. Through extensive experiments on medical benchmarks of varying complexity (MedQA, Medbullets, and JAMA Clinical Challenges), our investigation reveals several key insights: (1) Increasing inference time does lead to improved performance. With a modest training set of 500 samples, our model yields substantial performance improvements of 6%-11%. (2) Task complexity directly correlates with the required length of reasoning chains, confirming the necessity of extended thought processes for challenging problems. (3) The differential diagnoses generated by our model adhere to the principles of the hypothetico-deductive method, producing a list of potential conditions that may explain a patient's symptoms and systematically narrowing these possibilities by evaluating the evidence. These findings demonstrate the promising synergy between inference-time scaling and journey learning in advancing LLMs' real-world clinical reasoning capabilities.

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.

We present SPHINX, a versatile multi-modal large language model (MLLM) with a joint mixing of model weights, tuning tasks, and visual embeddings. First, for stronger vision-language alignment, we unfreeze the large language model (LLM) during pre-training, and introduce a weight mix strategy between LLMs trained by real-world and synthetic data. By directly integrating the weights from two domains, the mixed LLM can efficiently incorporate diverse semantics with favorable robustness. Then, to enable multi-purpose capabilities, we mix a variety of tasks for joint visual instruction tuning, and design task-specific instructions to avoid inter-task conflict. In addition to the basic visual question answering, we include more challenging tasks such as region-level understanding, caption grounding, document layout detection, and human pose estimation, contributing to mutual enhancement over different scenarios. Additionally, we propose to extract comprehensive visual embeddings from various network architectures, pre-training paradigms, and information granularity, providing language models with more robust image representations. Based on our proposed joint mixing, SPHINX exhibits superior multi-modal understanding capabilities on a wide range of applications. On top of this, we further propose an efficient strategy aiming to better capture fine-grained appearances of high-resolution images. With a mixing of different scales and high-resolution sub-images, SPHINX attains exceptional visual parsing and reasoning performance on existing evaluation benchmarks. We hope our work may cast a light on the exploration of joint mixing in future MLLM research. Code is released at https://github.com/Alpha-VLLM/LLaMA2-Accessory.

Recent research in medical image analysis with deep learning almost exclusively focuses on grid- or voxel-based data representations. We challenge this common choice by introducing MedFuncta, a modality-agnostic continuous data representation based on neural fields. We demonstrate how to scale neural fields from single instances to large datasets by exploiting redundancy in medical signals and by applying an efficient meta-learning approach with a context reduction scheme. We further address the spectral bias in commonly used SIREN activations, by introducing an omega_0-schedule, improving reconstruction quality and convergence speed. We validate our proposed approach on a large variety of medical signals of different dimensions and modalities (1D: ECG; 2D: Chest X-ray, Retinal OCT, Fundus Camera, Dermatoscope, Colon Histopathology, Cell Microscopy; 3D: Brain MRI, Lung CT) and successfully demonstrate that we can solve relevant downstream tasks on these representations. We additionally release a large-scale dataset of > 550k annotated neural fields to promote research in this direction.

Recent Multimodal Large Language Models (MLLMs) have demonstrated significant progress in perceiving and reasoning over multimodal inquiries, ushering in a new research era for foundation models. However, vision-language misalignment in MLLMs has emerged as a critical challenge, where the textual responses generated by these models are not factually aligned with the given text-image inputs. Existing efforts to address vision-language misalignment have focused on developing specialized vision-language connectors or leveraging visual instruction tuning from diverse domains. In this paper, we tackle this issue from a fundamental yet unexplored perspective by revisiting the core architecture of MLLMs. Most MLLMs are typically built on decoder-only LLMs consisting of a causal attention mechanism, which limits the ability of earlier modalities (e.g., images) to incorporate information from later modalities (e.g., text). To address this problem, we propose AKI, a novel MLLM that unlocks causal attention into modality-mutual attention (MMA) to enable image tokens to attend to text tokens. This simple yet effective design allows AKI to achieve superior performance in 12 multimodal understanding benchmarks (+7.2% on average) without introducing additional parameters and increasing training time. Our MMA design is intended to be generic, allowing for application across various modalities, and scalable to accommodate diverse multimodal scenarios. The code is publicly available at https://github.com/sony/aki, and we will release our AKI-4B model to encourage further advancements in MLLMs across various directions.

The ability to accurately interpret complex visual information is a crucial topic of multimodal large language models (MLLMs). Recent work indicates that enhanced visual perception significantly reduces hallucinations and improves performance on resolution-sensitive tasks, such as optical character recognition and document analysis. A number of recent MLLMs achieve this goal using a mixture of vision encoders. Despite their success, there is a lack of systematic comparisons and detailed ablation studies addressing critical aspects, such as expert selection and the integration of multiple vision experts. This study provides an extensive exploration of the design space for MLLMs using a mixture of vision encoders and resolutions. Our findings reveal several underlying principles common to various existing strategies, leading to a streamlined yet effective design approach. We discover that simply concatenating visual tokens from a set of complementary vision encoders is as effective as more complex mixing architectures or strategies. We additionally introduce Pre-Alignment to bridge the gap between vision-focused encoders and language tokens, enhancing model coherence. The resulting family of MLLMs, Eagle, surpasses other leading open-source models on major MLLM benchmarks. Models and code: https://github.com/NVlabs/Eagle

Mixed Integer Linear Programming (MILP) is essential for modeling complex decision-making problems but faces challenges in computational tractability and requires expert formulation. Current deep learning approaches for MILP focus on specific problem classes and do not generalize to unseen classes. To address this shortcoming, we take a foundation model training approach, where we train a single deep learning model on a diverse set of MILP problems to generalize across problem classes. As existing datasets for MILP lack diversity and volume, we introduce MILP-Evolve, a novel LLM-based evolutionary framework that is capable of generating a large set of diverse MILP classes with an unlimited amount of instances. We study our methodology on three key learning tasks that capture diverse aspects of MILP: (1) integrality gap prediction, (2) learning to branch, and (3) a new task of aligning MILP instances with natural language descriptions. Our empirical results show that models trained on the data generated by MILP-Evolve achieve significant improvements on unseen problems, including MIPLIB benchmarks. Our work highlights the potential of moving towards a foundation model approach for MILP that can generalize to a broad range of MILP applications. Our code and data are publicly available at https://github.com/microsoft/OptiGuide.

We present DualFocus, a novel framework for integrating macro and micro perspectives within multi-modal large language models (MLLMs) to enhance vision-language task performance. Current MLLMs typically singularly focus on inputs at a predefined resolution, resulting in deficiencies in detailed questions involving local regions. We introduced a DualFocus mechanism where the model concentrates on the image from a macro perspective, responses to the question, and identifies suitable sub-regions to zoom in for subsequent micro perspective analysis. Via the integration of answers from both macro and micro perspectives, the model is adept at addressing tasks that encompass global, detailed, and combined considerations. To endows the DualFocus mechanism in MLLMs, we curated a tailored dataset derived from the Visual Genome (VG) and adapted it to align with the training regimen of DualFocus. Through comparative studies across different model sizes and benchmarks, we demonstrate DualFocus's superiority in balancing detailed examination with holistic insight, significantly reducing hallucination instances in MLLMs and improving their performance in various vision-language tasks.

LLMs have become increasingly capable at accomplishing a range of specialized-tasks and can be utilized to expand equitable access to medical knowledge. Most medical LLMs have involved extensive fine-tuning, leveraging specialized medical data and significant, thus costly, amounts of computational power. Many of the top performing LLMs are proprietary and their access is limited to very few research groups. However, open-source (OS) models represent a key area of growth for medical LLMs due to significant improvements in performance and an inherent ability to provide the transparency and compliance required in healthcare. We present OpenMedLM, a prompting platform which delivers state-of-the-art (SOTA) performance for OS LLMs on medical benchmarks. We evaluated a range of OS foundation LLMs (7B-70B) on four medical benchmarks (MedQA, MedMCQA, PubMedQA, MMLU medical-subset). We employed a series of prompting strategies, including zero-shot, few-shot, chain-of-thought (random selection and kNN selection), and ensemble/self-consistency voting. We found that OpenMedLM delivers OS SOTA results on three common medical LLM benchmarks, surpassing the previous best performing OS models that leveraged computationally costly extensive fine-tuning. The model delivers a 72.6% accuracy on the MedQA benchmark, outperforming the previous SOTA by 2.4%, and achieves 81.7% accuracy on the MMLU medical-subset, establishing itself as the first OS LLM to surpass 80% accuracy on this benchmark. Our results highlight medical-specific emergent properties in OS LLMs which have not yet been documented to date elsewhere, and showcase the benefits of further leveraging prompt engineering to improve the performance of accessible LLMs for medical applications.

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.

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.

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.

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.

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.

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.

Mixture of Expert Tuning (MoE-Tuning) has effectively enhanced the performance of general MLLMs with fewer parameters, yet its application in resource-limited medical settings has not been fully explored. To address this gap, we developed MoE-TinyMed, a model tailored for medical applications that significantly lowers parameter demands. In evaluations on the VQA-RAD, SLAKE, and Path-VQA datasets, MoE-TinyMed outperformed LLaVA-Med in all Med-VQA closed settings with just 3.6B parameters. Additionally, a streamlined version with 2B parameters surpassed LLaVA-Med's performance in PathVQA, showcasing its effectiveness in resource-limited healthcare settings.

This research paper focuses on the challenges posed by hallucinations in large language models (LLMs), particularly in the context of the medical domain. Hallucination, wherein these models generate plausible yet unverified or incorrect information, can have serious consequences in healthcare applications. We propose a new benchmark and dataset, Med-HALT (Medical Domain Hallucination Test), designed specifically to evaluate and reduce hallucinations. Med-HALT provides a diverse multinational dataset derived from medical examinations across various countries and includes multiple innovative testing modalities. Med-HALT includes two categories of tests reasoning and memory-based hallucination tests, designed to assess LLMs's problem-solving and information retrieval abilities. Our study evaluated leading LLMs, including Text Davinci, GPT-3.5, LlaMa-2, MPT, and Falcon, revealing significant differences in their performance. The paper provides detailed insights into the dataset, promoting transparency and reproducibility. Through this work, we aim to contribute to the development of safer and more reliable language models in healthcare. Our benchmark can be found at medhalt.github.io

Medical knowledge is context-dependent and requires consistent reasoning across various natural language expressions of semantically equivalent phrases. This is particularly crucial for drug names, where patients often use brand names like Advil or Tylenol instead of their generic equivalents. To study this, we create a new robustness dataset, RABBITS, to evaluate performance differences on medical benchmarks after swapping brand and generic drug names using physician expert annotations. We assess both open-source and API-based LLMs on MedQA and MedMCQA, revealing a consistent performance drop ranging from 1-10\%. Furthermore, we identify a potential source of this fragility as the contamination of test data in widely used pre-training datasets. All code is accessible at https://github.com/BittermanLab/RABBITS, and a HuggingFace leaderboard is available at https://huggingface.co/spaces/AIM-Harvard/rabbits-leaderboard.

The remarkable capabilities of large language models (LLMs) in language understanding and generation have not rendered them immune to hallucinations. LLMs can still generate plausible-sounding but factually incorrect or fabricated information. As LLM-empowered chatbots become popular, laypeople may frequently ask health-related queries and risk falling victim to these LLM hallucinations, resulting in various societal and healthcare implications. In this work, we conduct a pioneering study of hallucinations in LLM-generated responses to real-world healthcare queries from patients. We propose MedHalu, a carefully crafted first-of-its-kind medical hallucination dataset with a diverse range of health-related topics and the corresponding hallucinated responses from LLMs with labeled hallucination types and hallucinated text spans. We also introduce MedHaluDetect framework to evaluate capabilities of various LLMs in detecting hallucinations. We also employ three groups of evaluators -- medical experts, LLMs, and laypeople -- to study who are more vulnerable to these medical hallucinations. We find that LLMs are much worse than the experts. They also perform no better than laypeople and even worse in few cases in detecting hallucinations. To fill this gap, we propose expert-in-the-loop approach to improve hallucination detection through LLMs by infusing expert reasoning. We observe significant performance gains for all the LLMs with an average macro-F1 improvement of 6.3 percentage points for GPT-4.

Despite the significant progress in multimodal large language models (MLLMs), their high computational cost remains a barrier to real-world deployment. Inspired by the mixture of depths (MoDs) in natural language processing, we aim to address this limitation from the perspective of ``activated tokens''. Our key insight is that if most tokens are redundant for the layer computation, then can be skipped directly via the MoD layer. However, directly converting the dense layers of MLLMs to MoD layers leads to substantial performance degradation. To address this issue, we propose an innovative MoD adaptation strategy for existing MLLMs called gamma-MoD. In gamma-MoD, a novel metric is proposed to guide the deployment of MoDs in the MLLM, namely rank of attention maps (ARank). Through ARank, we can effectively identify which layer is redundant and should be replaced with the MoD layer. Based on ARank, we further propose two novel designs to maximize the computational sparsity of MLLM while maintaining its performance, namely shared vision-language router and masked routing learning. With these designs, more than 90% dense layers of the MLLM can be effectively converted to the MoD ones. To validate our method, we apply it to three popular MLLMs, and conduct extensive experiments on 9 benchmark datasets. Experimental results not only validate the significant efficiency benefit of gamma-MoD to existing MLLMs but also confirm its generalization ability on various MLLMs. For example, with a minor performance drop, i.e., -1.5%, gamma-MoD can reduce the training and inference time of LLaVA-HR by 31.0% and 53.2%, respectively.

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.

Reasoning is a critical frontier for advancing medical image analysis, where transparency and trustworthiness play a central role in both clinician trust and regulatory approval. Although Medical Visual Language Models (VLMs) show promise for radiological tasks, most existing VLMs merely produce final answers without revealing the underlying reasoning. To address this gap, we introduce MedVLM-R1, a medical VLM that explicitly generates natural language reasoning to enhance transparency and trustworthiness. Instead of relying on supervised fine-tuning (SFT), which often suffers from overfitting to training distributions and fails to foster genuine reasoning, MedVLM-R1 employs a reinforcement learning framework that incentivizes the model to discover human-interpretable reasoning paths without using any reasoning references. Despite limited training data (600 visual question answering samples) and model parameters (2B), MedVLM-R1 boosts accuracy from 55.11% to 78.22% across MRI, CT, and X-ray benchmarks, outperforming larger models trained on over a million samples. It also demonstrates robust domain generalization under out-of-distribution tasks. By unifying medical image analysis with explicit reasoning, MedVLM-R1 marks a pivotal step toward trustworthy and interpretable AI in clinical practice.

Multimodal Large Language Models (MLLMs) have gained significant attention recently, showing remarkable potential in artificial general intelligence. However, assessing the utility of MLLMs presents considerable challenges, primarily due to the absence of multimodal benchmarks that align with human preferences. Drawing inspiration from the concept of LLM-as-a-Judge within LLMs, this paper introduces a novel benchmark, termed MLLM-as-a-Judge, to assess the ability of MLLMs in assisting judges across diverse modalities, encompassing three distinct tasks: Scoring Evaluation, Pair Comparison, and Batch Ranking. Our study reveals that, while MLLMs demonstrate remarkable human-like discernment in Pair Comparison, there is a significant divergence from human preferences in Scoring Evaluation and Batch Ranking. Furthermore, a closer examination reveals persistent challenges in the judgment capacities of LLMs, including diverse biases, hallucinatory responses, and inconsistencies in judgment, even in advanced models such as GPT-4V. These findings emphasize the pressing need for enhancements and further research efforts to be undertaken before regarding MLLMs as fully reliable evaluators. In light of this, we advocate for additional efforts dedicated to supporting the continuous development within the domain of MLLM functioning as judges. The code and dataset are publicly available at our project homepage: https://mllm-judge.github.io/.

Despite the remarkable performance of multimodal large language models (MLLMs) across diverse tasks, the substantial training and inference costs impede their advancement. The majority of computation stems from the overwhelming volume of vision tokens processed by the transformer decoder. In this paper, we propose to build efficient MLLMs by leveraging the Mixture-of-Depths (MoD) mechanism, where each transformer decoder layer selects essential vision tokens to process while skipping redundant ones. However, integrating MoD into MLLMs is non-trivial. To address the challenges of training and inference stability as well as limited training data, we adapt the MoD module with two novel designs: tanh-gated weight normalization (TanhNorm) and symmetric token reweighting (STRing). Moreover, we observe that vision tokens exhibit higher redundancy in deeper layer and thus design a progressive ratio decay (PRD) strategy, which gradually reduces the token retention ratio layer by layer, employing a shifted cosine schedule. This crucial design fully unleashes the potential of MoD, significantly boosting the efficiency and performance of our models. To validate the effectiveness of our approach, we conduct extensive experiments with two baseline models across 14 benchmarks. Our model, p-MoD, matches or even surpasses the performance of the baseline models, with only 55.6% TFLOPs and 53.8% KV cache storage during inference, and 77.7% GPU hours during training.

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.

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.

Solving complex classification tasks using deep neural networks typically requires large amounts of annotated data. However, corresponding class labels are noisy when provided by error-prone annotators, e.g., crowd workers. Training standard deep neural networks leads to subpar performances in such multi-annotator supervised learning settings. We address this issue by presenting a probabilistic training framework named multi-annotator deep learning (MaDL). A ground truth and an annotator performance model are jointly trained in an end-to-end learning approach. The ground truth model learns to predict instances' true class labels, while the annotator performance model infers probabilistic estimates of annotators' performances. A modular network architecture enables us to make varying assumptions regarding annotators' performances, e.g., an optional class or instance dependency. Further, we learn annotator embeddings to estimate annotators' densities within a latent space as proxies of their potentially correlated annotations. Together with a weighted loss function, we improve the learning from correlated annotation patterns. In a comprehensive evaluation, we examine three research questions about multi-annotator supervised learning. Our findings indicate MaDL's state-of-the-art performance and robustness against many correlated, spamming annotators.

This research tests the role of Large Language Models (LLMs) as formal second opinion tools in professional decision-making, particularly focusing on complex medical cases where even experienced physicians seek peer consultation. The work analyzed 183 challenging medical cases from Medscape over a 20-month period, testing multiple LLMs' performance against crowd-sourced physician responses. A key finding was the high overall score possible in the latest foundational models (>80% accuracy compared to consensus opinion), which exceeds most human metrics reported on the same clinical cases (450 pages of patient profiles, test results). The study rates the LLMs' performance disparity between straightforward cases (>81% accuracy) and complex scenarios (43% accuracy), particularly in these cases generating substantial debate among human physicians. The research demonstrates that LLMs may be valuable as generators of comprehensive differential diagnoses rather than as primary diagnostic tools, potentially helping to counter cognitive biases in clinical decision-making, reduce cognitive loads, and thus remove some sources of medical error. The inclusion of a second comparative legal dataset (Supreme Court cases, N=21) provides added empirical context to the AI use to foster second opinions, though these legal challenges proved considerably easier for LLMs to analyze. In addition to the original contributions of empirical evidence for LLM accuracy, the research aggregated a novel benchmark for others to score highly contested question and answer reliability between both LLMs and disagreeing human practitioners. These results suggest that the optimal deployment of LLMs in professional settings may differ substantially from current approaches that emphasize automation of routine tasks.

There is increasing interest in the application large language models (LLMs) to the medical field, in part because of their impressive performance on medical exam questions. While promising, exam questions do not reflect the complexity of real patient-doctor interactions. In reality, physicians' decisions are shaped by many complex factors, such as patient compliance, personal experience, ethical beliefs, and cognitive bias. Taking a step toward understanding this, our hypothesis posits that when LLMs are confronted with clinical questions containing cognitive biases, they will yield significantly less accurate responses compared to the same questions presented without such biases. In this study, we developed BiasMedQA, a benchmark for evaluating cognitive biases in LLMs applied to medical tasks. Using BiasMedQA we evaluated six LLMs, namely GPT-4, Mixtral-8x70B, GPT-3.5, PaLM-2, Llama 2 70B-chat, and the medically specialized PMC Llama 13B. We tested these models on 1,273 questions from the US Medical Licensing Exam (USMLE) Steps 1, 2, and 3, modified to replicate common clinically-relevant cognitive biases. Our analysis revealed varying effects for biases on these LLMs, with GPT-4 standing out for its resilience to bias, in contrast to Llama 2 70B-chat and PMC Llama 13B, which were disproportionately affected by cognitive bias. Our findings highlight the critical need for bias mitigation in the development of medical LLMs, pointing towards safer and more reliable applications in healthcare.

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 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.

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.

Recent studies have demonstrated Large Language Models (LLMs) can extend their zero-shot generalization capabilities to multimodal learning through instruction tuning. As more modalities and downstream tasks are introduced, negative conflicts and interference may have a worse impact on performance. While this phenomenon has been overlooked in previous work, we propose a novel and extensible framework, called Octavius, for comprehensive studies and experimentation on multimodal learning with Multimodal Large Language Models (MLLMs). Specifically, we combine the well-known Mixture-of-Experts (MoE) and one of the representative PEFT techniques, i.e., LoRA, designing a novel LLM-based decoder, called LoRA-MoE, for multimodal learning. To the best of our knowledge, we are one of the pioneering efforts to introduce MoE into MLLMs to address this problem. The experimental results (about 20% improvement) have shown the effectiveness and versatility of our design in various 2D and 3D downstream tasks. Code and datasets are available at https://openlamm.github.io/paper_list/Octavius.

Multiple Instance Learning (MIL) is a sub-domain of classification problems with positive and negative labels and a "bag" of inputs, where the label is positive if and only if a positive element is contained within the bag, and otherwise is negative. Training in this context requires associating the bag-wide label to instance-level information, and implicitly contains a causal assumption and asymmetry to the task (i.e., you can't swap the labels without changing the semantics). MIL problems occur in healthcare (one malignant cell indicates cancer), cyber security (one malicious executable makes an infected computer), and many other tasks. In this work, we examine five of the most prominent deep-MIL models and find that none of them respects the standard MIL assumption. They are able to learn anti-correlated instances, i.e., defaulting to "positive" labels until seeing a negative counter-example, which should not be possible for a correct MIL model. We suspect that enhancements and other works derived from these models will share the same issue. In any context in which these models are being used, this creates the potential for learning incorrect models, which creates risk of operational failure. We identify and demonstrate this problem via a proposed "algorithmic unit test", where we create synthetic datasets that can be solved by a MIL respecting model, and which clearly reveal learning that violates MIL assumptions. The five evaluated methods each fail one or more of these tests. This provides a model-agnostic way to identify violations of modeling assumptions, which we hope will be useful for future development and evaluation of MIL models.

Recent developments in Multimodal Large Language Models (MLLMs) have shown rapid progress, moving towards the goal of creating versatile MLLMs that understand inputs from various modalities. However, existing methods typically rely on joint training with paired multimodal instruction data, which is resource-intensive and challenging to extend to new modalities. In this paper, we propose a new paradigm through the model composition of existing MLLMs to create a new model that retains the modal understanding capabilities of each original model. Our basic implementation, NaiveMC, demonstrates the effectiveness of this paradigm by reusing modality encoders and merging LLM parameters. Furthermore, we introduce DAMC to address parameter interference and mismatch issues during the merging process, thereby enhancing the model performance. To facilitate research in this area, we propose MCUB, a benchmark for assessing ability of MLLMs to understand inputs from diverse modalities. Experiments on this benchmark and four other multimodal understanding tasks show significant improvements over baselines, proving that model composition can create a versatile model capable of processing inputs from multiple modalities.

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.

This paper introduces BiMediX2, a bilingual (Arabic-English) Bio-Medical EXpert Large Multimodal Model (LMM) with a unified architecture that integrates text and visual modalities, enabling advanced image understanding and medical applications. BiMediX2 leverages the Llama3.1 architecture and integrates text and visual capabilities to facilitate seamless interactions in both English and Arabic, supporting text-based inputs and multi-turn conversations involving medical images. The model is trained on an extensive bilingual healthcare dataset consisting of 1.6M samples of diverse medical interactions for both text and image modalities, mixed in Arabic and English. We also propose the first bilingual GPT-4o based medical LMM benchmark named BiMed-MBench. BiMediX2 is benchmarked on both text-based and image-based tasks, achieving state-of-the-art performance across several medical benchmarks. It outperforms recent state-of-the-art models in medical LLM evaluation benchmarks. Our model also sets a new benchmark in multimodal medical evaluations with over 9% improvement in English and over 20% in Arabic evaluations. Additionally, it surpasses GPT-4 by around 9% in UPHILL factual accuracy evaluations and excels in various medical Visual Question Answering, Report Generation, and Report Summarization tasks. The project page including source code and the trained model, is available at https://github.com/mbzuai-oryx/BiMediX2.

This paper considers a novel application of deep AUC maximization (DAM) for multi-instance learning (MIL), in which a single class label is assigned to a bag of instances (e.g., multiple 2D slices of a CT scan for a patient). We address a neglected yet non-negligible computational challenge of MIL in the context of DAM, i.e., bag size is too large to be loaded into {GPU} memory for backpropagation, which is required by the standard pooling methods of MIL. To tackle this challenge, we propose variance-reduced stochastic pooling methods in the spirit of stochastic optimization by formulating the loss function over the pooled prediction as a multi-level compositional function. By synthesizing techniques from stochastic compositional optimization and non-convex min-max optimization, we propose a unified and provable muli-instance DAM (MIDAM) algorithm with stochastic smoothed-max pooling or stochastic attention-based pooling, which only samples a few instances for each bag to compute a stochastic gradient estimator and to update the model parameter. We establish a similar convergence rate of the proposed MIDAM algorithm as the state-of-the-art DAM algorithms. Our extensive experiments on conventional MIL datasets and medical datasets demonstrate the superiority of our MIDAM algorithm.

In recent years, there have been significant breakthroughs in the field of natural language processing, particularly with the development of large language models (LLMs). These LLMs have showcased remarkable capabilities on various benchmarks. In the healthcare field, the exact role LLMs and other future AI models will play remains unclear. There is a potential for these models in the future to be used as part of adaptive physician training, medical co-pilot applications, and digital patient interaction scenarios. The ability of AI models to participate in medical training and patient care will depend in part on their mastery of the knowledge content of specific medical fields. This study investigated the medical knowledge capability of LLMs, specifically in the context of internal medicine subspecialty multiple-choice test-taking ability. We compared the performance of several open-source LLMs (Koala 7B, Falcon 7B, Stable-Vicuna 13B, and Orca Mini 13B), to GPT-4 and Claude 2 on multiple-choice questions in the field of Nephrology. Nephrology was chosen as an example of a particularly conceptually complex subspecialty field within internal medicine. The study was conducted to evaluate the ability of LLM models to provide correct answers to nephSAP (Nephrology Self-Assessment Program) multiple-choice questions. The overall success of open-sourced LLMs in answering the 858 nephSAP multiple-choice questions correctly was 17.1% - 25.5%. In contrast, Claude 2 answered 54.4% of the questions correctly, whereas GPT-4 achieved a score of 73.3%. We show that current widely used open-sourced LLMs do poorly in their ability for zero-shot reasoning when compared to GPT-4 and Claude 2. The findings of this study potentially have significant implications for the future of subspecialty medical training and patient care.

Multimodal large language models (MLLMs) can simultaneously process visual, textual, and auditory data, capturing insights that complement human analysis. However, existing video question-answering (VidQA) benchmarks and datasets often exhibit a bias toward a single modality, despite the goal of requiring advanced reasoning skills that integrate diverse modalities to answer the queries. In this work, we introduce the modality importance score (MIS) to identify such bias. It is designed to assess which modality embeds the necessary information to answer the question. Additionally, we propose an innovative method using state-of-the-art MLLMs to estimate the modality importance, which can serve as a proxy for human judgments of modality perception. With this MIS, we demonstrate the presence of unimodal bias and the scarcity of genuinely multimodal questions in existing datasets. We further validate the modality importance score with multiple ablation studies to evaluate the performance of MLLMs on permuted feature sets. Our results indicate that current models do not effectively integrate information due to modality imbalance in existing datasets. Our proposed MLLM-derived MIS can guide the curation of modality-balanced datasets that advance multimodal learning and enhance MLLMs' capabilities to understand and utilize synergistic relations across modalities.

Recent years have witnessed the rapid development of general multimodal large language models (MLLMs). However, adapting general MLLMs to specific domains, such as scientific fields and industrial applications, remains less explored. This paper systematically investigates domain adaptation of MLLMs through post-training, focusing on data synthesis, training pipelines, and task evaluation. (1) Data Synthesis: Using open-source models, we develop a visual instruction synthesizer that effectively generates diverse visual instruction tasks from domain-specific image-caption pairs. Our synthetic tasks surpass those generated by manual rules, GPT-4, and GPT-4V in enhancing the domain-specific performance of MLLMs. (2) Training Pipeline: While the two-stage training--initially on image-caption pairs followed by visual instruction tasks--is commonly adopted for developing general MLLMs, we apply a single-stage training pipeline to enhance task diversity for domain-specific post-training. (3) Task Evaluation: We conduct experiments in two domains, biomedicine and food, by post-training MLLMs of different sources and scales (e.g., Qwen2-VL-2B, LLaVA-v1.6-8B, Llama-3.2-11B), and then evaluating MLLM performance on various domain-specific tasks. To support further research in MLLM domain adaptation, we will open-source our implementations.

Background: Recent advancements in large language models (LLMs) offer potential benefits in healthcare, particularly in processing extensive patient records. However, existing benchmarks do not fully assess LLMs' capability in handling real-world, lengthy clinical data. Methods: We present the LongHealth benchmark, comprising 20 detailed fictional patient cases across various diseases, with each case containing 5,090 to 6,754 words. The benchmark challenges LLMs with 400 multiple-choice questions in three categories: information extraction, negation, and sorting, challenging LLMs to extract and interpret information from large clinical documents. Results: We evaluated nine open-source LLMs with a minimum of 16,000 tokens and also included OpenAI's proprietary and cost-efficient GPT-3.5 Turbo for comparison. The highest accuracy was observed for Mixtral-8x7B-Instruct-v0.1, particularly in tasks focused on information retrieval from single and multiple patient documents. However, all models struggled significantly in tasks requiring the identification of missing information, highlighting a critical area for improvement in clinical data interpretation. Conclusion: While LLMs show considerable potential for processing long clinical documents, their current accuracy levels are insufficient for reliable clinical use, especially in scenarios requiring the identification of missing information. The LongHealth benchmark provides a more realistic assessment of LLMs in a healthcare setting and highlights the need for further model refinement for safe and effective clinical application. We make the benchmark and evaluation code publicly available.

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.

The integration of Artificial Intelligence (AI), especially Large Language Models (LLMs), into the clinical diagnosis process offers significant potential to improve the efficiency and accessibility of medical care. While LLMs have shown some promise in the medical domain, their application in clinical diagnosis remains underexplored, especially in real-world clinical practice, where highly sophisticated, patient-specific decisions need to be made. Current evaluations of LLMs in this field are often narrow in scope, focusing on specific diseases or specialties and employing simplified diagnostic tasks. To bridge this gap, we introduce CliBench, a novel benchmark developed from the MIMIC IV dataset, offering a comprehensive and realistic assessment of LLMs' capabilities in clinical diagnosis. This benchmark not only covers diagnoses from a diverse range of medical cases across various specialties but also incorporates tasks of clinical significance: treatment procedure identification, lab test ordering and medication prescriptions. Supported by structured output ontologies, CliBench enables a precise and multi-granular evaluation, offering an in-depth understanding of LLM's capability on diverse clinical tasks of desired granularity. We conduct a zero-shot evaluation of leading LLMs to assess their proficiency in clinical decision-making. Our preliminary results shed light on the potential and limitations of current LLMs in clinical settings, providing valuable insights for future advancements in LLM-powered healthcare.

Multimodal Large Language Models (MLLMs) have shown significant promise in various applications, leading to broad interest from researchers and practitioners alike. However, a comprehensive evaluation of their long-context capabilities remains underexplored. To address these gaps, we introduce the MultiModal Needle-in-a-haystack (MMNeedle) benchmark, specifically designed to assess the long-context capabilities of MLLMs. Besides multi-image input, we employ image stitching to further increase the input context length, and develop a protocol to automatically generate labels for sub-image level retrieval. Essentially, MMNeedle evaluates MLLMs by stress-testing their capability to locate a target sub-image (needle) within a set of images (haystack) based on textual instructions and descriptions of image contents. This setup necessitates an advanced understanding of extensive visual contexts and effective information retrieval within long-context image inputs. With this benchmark, we evaluate state-of-the-art MLLMs, encompassing both API-based and open-source models. The findings reveal that GPT-4o consistently surpasses other models in long-context scenarios, but suffers from hallucination problems in negative samples, i.e., when needles are not in the haystacks. Our comprehensive long-context evaluation of MLLMs also sheds lights on the considerable performance gap between API-based and open-source models. All the code, data, and instructions required to reproduce the main results are available at https://github.com/Wang-ML-Lab/multimodal-needle-in-a-haystack.

In this technical report, we propose ChemVLM, the first open-source multimodal large language model dedicated to the fields of chemistry, designed to address the incompatibility between chemical image understanding and text analysis. Built upon the VIT-MLP-LLM architecture, we leverage ChemLLM-20B as the foundational large model, endowing our model with robust capabilities in understanding and utilizing chemical text knowledge. Additionally, we employ InternVIT-6B as a powerful image encoder. We have curated high-quality data from the chemical domain, including molecules, reaction formulas, and chemistry examination data, and compiled these into a bilingual multimodal question-answering dataset. We test the performance of our model on multiple open-source benchmarks and three custom evaluation sets. Experimental results demonstrate that our model achieves excellent performance, securing state-of-the-art results in five out of six involved tasks. Our model can be found at https://huggingface.co/AI4Chem/ChemVLM-26B.

This paper explores the use of unstructured, multimodal data, namely text and images, in causal inference and treatment effect estimation. We propose a neural network architecture that is adapted to the double machine learning (DML) framework, specifically the partially linear model. An additional contribution of our paper is a new method to generate a semi-synthetic dataset which can be used to evaluate the performance of causal effect estimation in the presence of text and images as confounders. The proposed methods and architectures are evaluated on the semi-synthetic dataset and compared to standard approaches, highlighting the potential benefit of using text and images directly in causal studies. Our findings have implications for researchers and practitioners in economics, marketing, finance, medicine and data science in general who are interested in estimating causal quantities using non-traditional data.

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.

Data diversity and volume are crucial to the success of training deep learning models, while in the medical imaging field, the difficulty and cost of data collection and annotation are especially huge. Specifically in robotic surgery, data scarcity and imbalance have heavily affected the model accuracy and limited the design and deployment of deep learning-based surgical applications such as surgical instrument segmentation. Considering this, we rethink the surgical instrument segmentation task and propose a one-to-many data generation solution that gets rid of the complicated and expensive process of data collection and annotation from robotic surgery. In our method, we only utilize a single surgical background tissue image and a few open-source instrument images as the seed images and apply multiple augmentations and blending techniques to synthesize amounts of image variations. In addition, we also introduce the chained augmentation mixing during training to further enhance the data diversities. The proposed approach is evaluated on the real datasets of the EndoVis-2018 and EndoVis-2017 surgical scene segmentation. Our empirical analysis suggests that without the high cost of data collection and annotation, we can achieve decent surgical instrument segmentation performance. Moreover, we also observe that our method can deal with novel instrument prediction in the deployment domain. We hope our inspiring results will encourage researchers to emphasize data-centric methods to overcome demanding deep learning limitations besides data shortage, such as class imbalance, domain adaptation, and incremental learning. Our code is available at https://github.com/lofrienger/Single_SurgicalScene_For_Segmentation.

Medical Vision-Language Pretraining (MedVLP) shows promise in learning generalizable and transferable visual representations from paired and unpaired medical images and reports. MedVLP can provide useful features to downstream tasks and facilitate adapting task-specific models to new setups using fewer examples. However, existing MedVLP methods often differ in terms of datasets, preprocessing, and finetuning implementations. This pose great challenges in evaluating how well a MedVLP method generalizes to various clinically-relevant tasks due to the lack of unified, standardized, and comprehensive benchmark. To fill this gap, we propose BenchX, a unified benchmark framework that enables head-to-head comparison and systematical analysis between MedVLP methods using public chest X-ray datasets. Specifically, BenchX is composed of three components: 1) Comprehensive datasets covering nine datasets and four medical tasks; 2) Benchmark suites to standardize data preprocessing, train-test splits, and parameter selection; 3) Unified finetuning protocols that accommodate heterogeneous MedVLP methods for consistent task adaptation in classification, segmentation, and report generation, respectively. Utilizing BenchX, we establish baselines for nine state-of-the-art MedVLP methods and found that the performance of some early MedVLP methods can be enhanced to surpass more recent ones, prompting a revisiting of the developments and conclusions from prior works in MedVLP. Our code are available at https://github.com/yangzhou12/BenchX.

Large Language Models (LLMs) present immense potential in the medical field, yet concerns over data privacy, regulatory compliance, and model stability restrict their widespread adoption. Although the distillation of high-performing closed-source LLMs has proven effective for general tasks, their application in healthcare is limited due to reduced domain knowledge and remnants of alignment behavior hindering clinical tasks. To address these challenges, we propose Dialogue-Based Knowledge Encoding (DBKE). DBKE enhances models' implicit knowledge base and primes them for conversational recall, augmenting their conversational capabilities and enabling a soft alignment for subsequent use cases. By transforming dense academic source text into synthetic dialogue, DBKE broadens the model's knowledge base and enables a soft alignment that guides downstream behaviours. We present Clinical Camel, an open-source, healthcare-focused conversational model, to showcase the effectiveness of DBKE. Clinical Camel outperforms GPT-3.5 on the United States Medical Licensing Examination (USMLE) Step 1 and Step 3 with scores of 53.2 % and 58.2 %, respectively, compared to GPT-3.5's scores of 36.1 % and 55.7 %. Clinical Camel adeptly handles multi-stage clinical case problems, provides adaptive counseling, and generates clinical notes. However, it is prone to hallucinations, which pose a significant obstacle in safety-critical settings. The performance of Clinical Camel underscores the importance of continued research and development of open-source models for the safe and effective integration of LLMs in healthcare settings.

The rapid advancement of Large Language Models (LLMs) has led to an influx of efforts to extend their capabilities to multimodal tasks. Among them, growing attention has been focused on monolithic Multimodal Large Language Models (MLLMs) that integrate visual encoding and language decoding into a single LLM. Despite the structural simplicity and deployment-friendliness, training a monolithic MLLM with promising performance still remains challenging. In particular, the popular approaches adopt continuous pre-training to extend a pre-trained LLM to a monolithic MLLM, which suffers from catastrophic forgetting and leads to performance degeneration. In this paper, we aim to overcome this limitation from the perspective of delta tuning. Specifically, our core idea is to embed visual parameters into a pre-trained LLM, thereby incrementally learning visual knowledge from massive data via delta tuning, i.e., freezing the LLM when optimizing the visual parameters. Based on this principle, we present Mono-InternVL, a novel monolithic MLLM that seamlessly integrates a set of visual experts via a multimodal mixture-of-experts structure. Moreover, we propose an innovative pre-training strategy to maximize the visual capability of Mono-InternVL, namely Endogenous Visual Pre-training (EViP). In particular, EViP is designed as a progressive learning process for visual experts, which aims to fully exploit the visual knowledge from noisy data to high-quality data. To validate our approach, we conduct extensive experiments on 16 benchmarks. Experimental results not only validate the superior performance of Mono-InternVL compared to the state-of-the-art MLLM on 6 multimodal benchmarks, e.g., +113 points over InternVL-1.5 on OCRBench, but also confirm its better deployment efficiency, with first token latency reduced by up to 67%.

Large Language Models (LLMs) have showcased exceptional performance across a wide array of Natural Language Processing (NLP) tasks. Fine-tuning techniques are commonly utilized to tailor pre-trained models to specific applications. While methods like LoRA have effectively tackled GPU memory constraints during fine-tuning, their applicability is often restricted to limited performance, especially on multi-task. On the other hand, Mix-of-Expert (MoE) models, such as Mixtral 8x7B, demonstrate remarkable performance across multiple NLP tasks while maintaining a reduced parameter count. However, the resource requirements of these MoEs still challenging, particularly for consumer-grade GPUs only have limited VRAM. To address these challenge, we propose MixLoRA, an innovative approach aimed at constructing a resource-efficient sparse MoE model based on LoRA. MixLoRA inserts multiple LoRA-based experts within the feed-forward network block of a frozen pre-trained dense model through fine-tuning, employing a commonly used top-k router. Unlike other LoRA based MoE methods, MixLoRA enhances model performance by utilizing independently configurable attention-layer LoRA adapters, supporting the use of LoRA and its variants for the construction of experts, and applying auxiliary load balance loss to address the imbalance problem of the router. In experiments, MixLoRA achieves commendable performance across all evaluation metrics in both single-task and multi-task learning scenarios. Implemented within the m-LoRA framework, MixLoRA enables parallel fine-tuning of multiple mixture-of-experts models on a single 24GB consumer-grade GPU without quantization, thereby reducing GPU memory consumption by 41\% and latency during the training process by 17\%.

Over the past decade, computer vision applications in minimally invasive surgery have rapidly increased. Despite this growth, the impact of surgical computer vision remains limited compared to other medical fields like pathology and radiology, primarily due to the scarcity of representative annotated data. Whereas transfer learning from large annotated datasets such as ImageNet has been conventionally the norm to achieve high-performing models, recent advancements in self-supervised learning (SSL) have demonstrated superior performance. In medical image analysis, in-domain SSL pretraining has already been shown to outperform ImageNet-based initialization. Although unlabeled data in the field of surgical computer vision is abundant, the diversity within this data is limited. This study investigates the role of dataset diversity in SSL for surgical computer vision, comparing procedure-specific datasets against a more heterogeneous general surgical dataset across three different downstream surgical applications. The obtained results show that using solely procedure-specific data can lead to substantial improvements of 13.8%, 9.5%, and 36.8% compared to ImageNet pretraining. However, extending this data with more heterogeneous surgical data further increases performance by an additional 5.0%, 5.2%, and 2.5%, suggesting that increasing diversity within SSL data is beneficial for model performance. The code and pretrained model weights are made publicly available at https://github.com/TimJaspers0801/SurgeNet.

We introduce InternVL 2.5, an advanced multimodal large language model (MLLM) series that builds upon InternVL 2.0, maintaining its core model architecture while introducing significant enhancements in training and testing strategies as well as data quality. In this work, we delve into the relationship between model scaling and performance, systematically exploring the performance trends in vision encoders, language models, dataset sizes, and test-time configurations. Through extensive evaluations on a wide range of benchmarks, including multi-discipline reasoning, document understanding, multi-image / video understanding, real-world comprehension, multimodal hallucination detection, visual grounding, multilingual capabilities, and pure language processing, InternVL 2.5 exhibits competitive performance, rivaling leading commercial models such as GPT-4o and Claude-3.5-Sonnet. Notably, our model is the first open-source MLLMs to surpass 70% on the MMMU benchmark, achieving a 3.7-point improvement through Chain-of-Thought (CoT) reasoning and showcasing strong potential for test-time scaling. We hope this model contributes to the open-source community by setting new standards for developing and applying multimodal AI systems. HuggingFace demo see https://huggingface.co/spaces/OpenGVLab/InternVL

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

Medical imaging plays a crucial role in modern healthcare by providing non-invasive visualisation of internal structures and abnormalities, enabling early disease detection, accurate diagnosis, and treatment planning. This study aims to explore the application of deep learning models, particularly focusing on the UNet architecture and its variants, in medical image segmentation. We seek to evaluate the performance of these models across various challenging medical image segmentation tasks, addressing issues such as image normalization, resizing, architecture choices, loss function design, and hyperparameter tuning. The findings reveal that the standard UNet, when extended with a deep network layer, is a proficient medical image segmentation model, while the Res-UNet and Attention Res-UNet architectures demonstrate smoother convergence and superior performance, particularly when handling fine image details. The study also addresses the challenge of high class imbalance through careful preprocessing and loss function definitions. We anticipate that the results of this study will provide useful insights for researchers seeking to apply these models to new medical imaging problems and offer guidance and best practices for their implementation.

Objective: We investigate whether deep learning techniques for natural language processing (NLP) can be used efficiently for patient phenotyping. Patient phenotyping is a classification task for determining whether a patient has a medical condition, and is a crucial part of secondary analysis of healthcare data. We assess the performance of deep learning algorithms and compare them with classical NLP approaches. Materials and Methods: We compare convolutional neural networks (CNNs), n-gram models, and approaches based on cTAKES that extract pre-defined medical concepts from clinical notes and use them to predict patient phenotypes. The performance is tested on 10 different phenotyping tasks using 1,610 discharge summaries extracted from the MIMIC-III database. Results: CNNs outperform other phenotyping algorithms in all 10 tasks. The average F1-score of our model is 76 (PPV of 83, and sensitivity of 71) with our model having an F1-score up to 37 points higher than alternative approaches. We additionally assess the interpretability of our model by presenting a method that extracts the most salient phrases for a particular prediction. Conclusion: We show that NLP methods based on deep learning improve the performance of patient phenotyping. Our CNN-based algorithm automatically learns the phrases associated with each patient phenotype. As such, it reduces the annotation complexity for clinical domain experts, who are normally required to develop task-specific annotation rules and identify relevant phrases. Our method performs well in terms of both performance and interpretability, which indicates that deep learning is an effective approach to patient phenotyping based on clinicians' notes.

Vision-Language Models (VLM) can support clinicians by analyzing medical images and engaging in natural language interactions to assist in diagnostic and treatment tasks. However, VLMs often exhibit "hallucinogenic" behavior, generating textual outputs not grounded in contextual multimodal information. This challenge is particularly pronounced in the medical domain, where we do not only require VLM outputs to be accurate in single interactions but also to be consistent with clinical reasoning and diagnostic pathways throughout multi-turn conversations. For this purpose, we propose a new alignment algorithm that uses symbolic representations of clinical reasoning to ground VLMs in medical knowledge. These representations are utilized to (i) generate GPT-4-guided visual instruction tuning data at scale, simulating clinician-VLM conversations with demonstrations of clinical reasoning, and (ii) create an automatic reward function that evaluates the clinical validity of VLM generations throughout clinician-VLM interactions. Our algorithm eliminates the need for human involvement in training data generation or reward model construction, reducing costs compared to standard reinforcement learning with human feedback (RLHF). We apply our alignment algorithm to develop Dr-LLaVA, a conversational VLM finetuned for analyzing bone marrow pathology slides, demonstrating strong performance in multi-turn medical conversations.

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 ten 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 and supervised fine-tuning regimes for medical question-answering (QA). For instance, across all tasks and model pairs we consider in the 3-shot setting, medical LLMs only outperform their base models in 22.7% of cases, reach a (statistical) tie in 36.8% of cases, and are significantly worse than their base models in the remaining 40.5% 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 in zero-/few-shot prompting; 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. Meanwhile, we find that after fine-tuning on specific QA tasks, medical LLMs can show performance improvements, but the benefits do not carry over to tasks based on clinical notes. 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.

Medicine, by its nature, is a multifaceted domain that requires the synthesis of information across various modalities. Medical generative vision-language models (VLMs) make a first step in this direction and promise many exciting clinical applications. However, existing models typically have to be fine-tuned on sizeable down-stream datasets, which poses a significant limitation as in many medical applications data is scarce, necessitating models that are capable of learning from few examples in real-time. Here we propose Med-Flamingo, a multimodal few-shot learner adapted to the medical domain. Based on OpenFlamingo-9B, we continue pre-training on paired and interleaved medical image-text data from publications and textbooks. Med-Flamingo unlocks few-shot generative medical visual question answering (VQA) abilities, which we evaluate on several datasets including a novel challenging open-ended VQA dataset of visual USMLE-style problems. Furthermore, we conduct the first human evaluation for generative medical VQA where physicians review the problems and blinded generations in an interactive app. Med-Flamingo improves performance in generative medical VQA by up to 20\% in clinician's rating and firstly enables multimodal medical few-shot adaptations, such as rationale generation. We release our model, code, and evaluation app under https://github.com/snap-stanford/med-flamingo.

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.

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.

We propose SPHINX-X, an extensive Multimodality Large Language Model (MLLM) series developed upon SPHINX. To improve the architecture and training efficiency, we modify the SPHINX framework by removing redundant visual encoders, bypassing fully-padded sub-images with skip tokens, and simplifying multi-stage training into a one-stage all-in-one paradigm. To fully unleash the potential of MLLMs, we assemble a comprehensive multi-domain and multimodal dataset covering publicly available resources in language, vision, and vision-language tasks. We further enrich this collection with our curated OCR intensive and Set-of-Mark datasets, extending the diversity and generality. By training over different base LLMs including TinyLlama1.1B, InternLM2-7B, LLaMA2-13B, and Mixtral8x7B, we obtain a spectrum of MLLMs that vary in parameter size and multilingual capabilities. Comprehensive benchmarking reveals a strong correlation between the multi-modal performance with the data and parameter scales. Code and models are released at https://github.com/Alpha-VLLM/LLaMA2-Accessory

Commercial large language models (LLMs), like OpenAI's GPT-4 powering ChatGPT and Anthropic's Claude 3 Opus, have dominated natural language processing (NLP) benchmarks across different domains. New competing Open-Source alternatives like Mixtral 8x7B or Llama 3 have emerged and seem to be closing the gap while often offering higher throughput and being less costly to use. Open-Source LLMs can also be self-hosted, which makes them interesting for enterprise and clinical use cases where sensitive data should not be processed by third parties. We participated in the 12th BioASQ challenge, which is a retrieval augmented generation (RAG) setting, and explored the performance of current GPT models Claude 3 Opus, GPT-3.5-turbo and Mixtral 8x7b with in-context learning (zero-shot, few-shot) and QLoRa fine-tuning. We also explored how additional relevant knowledge from Wikipedia added to the context-window of the LLM might improve their performance. Mixtral 8x7b was competitive in the 10-shot setting, both with and without fine-tuning, but failed to produce usable results in the zero-shot setting. QLoRa fine-tuning and Wikipedia context did not lead to measurable performance gains. Our results indicate that the performance gap between commercial and open-source models in RAG setups exists mainly in the zero-shot setting and can be closed by simply collecting few-shot examples for domain-specific use cases. The code needed to rerun these experiments is available through GitHub.

In the quest for artificial general intelligence, Multi-modal Large Language Models (MLLMs) have emerged as a focal point in recent advancements. However, the predominant focus remains on developing their capabilities in static image understanding. The potential of MLLMs in processing sequential visual data is still insufficiently explored, highlighting the absence of a comprehensive, high-quality assessment of their performance. In this paper, we introduce Video-MME, the first-ever full-spectrum, Multi-Modal Evaluation benchmark of MLLMs in Video analysis. Our work distinguishes from existing benchmarks through four key features: 1) Diversity in video types, spanning 6 primary visual domains with 30 subfields to ensure broad scenario generalizability; 2) Duration in temporal dimension, encompassing both short-, medium-, and long-term videos, ranging from 11 seconds to 1 hour, for robust contextual dynamics; 3) Breadth in data modalities, integrating multi-modal inputs besides video frames, including subtitles and audios, to unveil the all-round capabilities of MLLMs; 4) Quality in annotations, utilizing rigorous manual labeling by expert annotators to facilitate precise and reliable model assessment. 900 videos with a total of 256 hours are manually selected and annotated by repeatedly viewing all the video content, resulting in 2,700 question-answer pairs. With Video-MME, we extensively evaluate various state-of-the-art MLLMs, including GPT-4 series and Gemini 1.5 Pro, as well as open-source image models like InternVL-Chat-V1.5 and video models like LLaVA-NeXT-Video. Our experiments reveal that Gemini 1.5 Pro is the best-performing commercial model, significantly outperforming the open-source models. Our dataset along with these findings underscores the need for further improvements in handling longer sequences and multi-modal data. Project Page: https://video-mme.github.io

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.

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.

Large Language Models (LLMs) have demonstrated significant potential in transforming clinical applications. In this study, we investigate the efficacy of four techniques in adapting LLMs for clinical use-cases: continuous pretraining, instruct fine-tuning, NEFTune, and prompt engineering. We employ these methods on Mistral 7B and Mixtral 8x7B models, leveraging a large-scale clinical pretraining dataset of 50 billion tokens and an instruct fine-tuning dataset of 500 million tokens. Our evaluation across various clinical tasks reveals the impact of each technique. While continuous pretraining beyond 250 billion tokens yields marginal improvements on its own, it establishes a strong foundation for instruct fine-tuning. Notably, NEFTune, designed primarily to enhance generation quality, surprisingly demonstrates additional gains on our benchmark. Complex prompt engineering methods further enhance performance. These findings show the importance of tailoring fine-tuning strategies and exploring innovative techniques to optimize LLM performance in the clinical domain.

The rapid evolution of Multimodal Large Language Models (MLLMs) has brought substantial advancements in artificial intelligence, significantly enhancing the capability to understand and generate multimodal content. While prior studies have largely concentrated on model architectures and training methodologies, a thorough analysis of the benchmarks used for evaluating these models remains underexplored. This survey addresses this gap by systematically reviewing 211 benchmarks that assess MLLMs across four core domains: understanding, reasoning, generation, and application. We provide a detailed analysis of task designs, evaluation metrics, and dataset constructions, across diverse modalities. We hope that this survey will contribute to the ongoing advancement of MLLM research by offering a comprehensive overview of benchmarking practices and identifying promising directions for future work. An associated GitHub repository collecting the latest papers is available.

The rapid advancement of large language models (LLMs) has significantly impacted various domains, including healthcare and biomedicine. However, the phenomenon of hallucination, where LLMs generate outputs that deviate from factual accuracy or context, poses a critical challenge, especially in high-stakes domains. This paper conducts a scoping study of existing techniques for mitigating hallucinations in knowledge-based task in general and especially for medical domains. Key methods covered in the paper include Retrieval-Augmented Generation (RAG)-based techniques, iterative feedback loops, supervised fine-tuning, and prompt engineering. These techniques, while promising in general contexts, require further adaptation and optimization for the medical domain due to its unique demands for up-to-date, specialized knowledge and strict adherence to medical guidelines. Addressing these challenges is crucial for developing trustworthy AI systems that enhance clinical decision-making and patient safety as well as accuracy of biomedical scientific research.

Pathology plays a critical role in diagnosing a wide range of diseases, yet existing approaches often rely heavily on task-specific models trained on extensive, well-labeled datasets. These methods face sustainability challenges due to the diversity of pathologies and the labor-intensive nature of data collection. To address these limitations, we highlight the need for universal multimodal embeddings that can support multiple downstream tasks. Previous approaches often involve fine-tuning CLIP-based models, which handle images and text separately, limiting their ability to capture complex multimodal relationships. Additionally, these models are evaluated across diverse datasets without a unified benchmark for assessing multimodal embeddings in pathology. To address these challenges, we propose MLLM4PUE, a novel framework that leverages Multimodal Large Language Models (MLLMs) to generate Pathology Universal Embeddings. The MLLM4PUE framework not only facilitates robust integration of images and text but also enhances understanding and fusion capabilities across various tasks. We further introduce the Pathology Multimodal Embedding Benchmark (PMEB), a comprehensive benchmark designed to assess the quality of pathology multimodal embeddings. PMEB comprises 15 original tasks drawn from 14 datasets, organized into three meta-tasks: retrieval, classification, and composed retrieval. Experimental results demonstrate the superiority of MLLM4PUE, illustrating MLLM-based models can effectively support a wide range of downstream tasks and unify the research direction for foundation models in pathology.

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.

Advancements in Large Language Models (LLMs) and their increasing use in medical question-answering necessitate rigorous evaluation of their reliability. A critical challenge lies in hallucination, where models generate plausible yet factually incorrect outputs. In the medical domain, this poses serious risks to patient safety and clinical decision-making. To address this, we introduce MedHallu, the first benchmark specifically designed for medical hallucination detection. MedHallu comprises 10,000 high-quality question-answer pairs derived from PubMedQA, with hallucinated answers systematically generated through a controlled pipeline. Our experiments show that state-of-the-art LLMs, including GPT-4o, Llama-3.1, and the medically fine-tuned UltraMedical, struggle with this binary hallucination detection task, with the best model achieving an F1 score as low as 0.625 for detecting "hard" category hallucinations. Using bidirectional entailment clustering, we show that harder-to-detect hallucinations are semantically closer to ground truth. Through experiments, we also show incorporating domain-specific knowledge and introducing a "not sure" category as one of the answer categories improves the precision and F1 scores by up to 38% relative to baselines.

Recent advances in generative vision-language models (VLMs) have exciting potential implications for AI in radiology, yet VLMs are also known to produce hallucinations, nonsensical text, and other unwanted behaviors that can waste clinicians' time and cause patient harm. Drawing on recent work on direct preference optimization (DPO), we propose a simple method for modifying the behavior of pretrained VLMs performing radiology report generation by suppressing unwanted types of generations. We apply our method to the prevention of hallucinations of prior exams, addressing a long-established problem behavior in models performing chest X-ray report generation. Across our experiments, we find that DPO fine-tuning achieves a 3.2-4.8x reduction in lines hallucinating prior exams while maintaining model performance on clinical accuracy metrics. Our work is, to the best of our knowledge, the first work to apply DPO to medical VLMs, providing a data- and compute- efficient way to suppress problem behaviors while maintaining overall clinical accuracy.

Backpropagation (BP) is the most successful and widely used algorithm in deep learning. However, the computations required by BP are challenging to reconcile with known neurobiology. This difficulty has stimulated interest in more biologically plausible alternatives to BP. One such algorithm is the inference learning algorithm (IL). IL has close connections to neurobiological models of cortical function and has achieved equal performance to BP on supervised learning and auto-associative tasks. In contrast to BP, however, the mathematical foundations of IL are not well-understood. Here, we develop a novel theoretical framework for IL. Our main result is that IL closely approximates an optimization method known as implicit stochastic gradient descent (implicit SGD), which is distinct from the explicit SGD implemented by BP. Our results further show how the standard implementation of IL can be altered to better approximate implicit SGD. Our novel implementation considerably improves the stability of IL across learning rates, which is consistent with our theory, as a key property of implicit SGD is its stability. We provide extensive simulation results that further support our theoretical interpretations and also demonstrate IL achieves quicker convergence when trained with small mini-batches while matching the performance of BP for large mini-batches.

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.

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.

The recent emergence of Medical Large Vision Language Models (Med-LVLMs) has enhanced medical diagnosis. However, current Med-LVLMs frequently encounter factual issues, often generating responses that do not align with established medical facts. Retrieval-Augmented Generation (RAG), which utilizes external knowledge, can improve the factual accuracy of these models but introduces two major challenges. First, limited retrieved contexts might not cover all necessary information, while excessive retrieval can introduce irrelevant and inaccurate references, interfering with the model's generation. Second, in cases where the model originally responds correctly, applying RAG can lead to an over-reliance on retrieved contexts, resulting in incorrect answers. To address these issues, we propose RULE, which consists of two components. First, we introduce a provably effective strategy for controlling factuality risk through the calibrated selection of the number of retrieved contexts. Second, based on samples where over-reliance on retrieved contexts led to errors, we curate a preference dataset to fine-tune the model, balancing its dependence on inherent knowledge and retrieved contexts for generation. We demonstrate the effectiveness of RULE on three medical VQA datasets, achieving an average improvement of 20.8% in factual accuracy. We publicly release our benchmark and code in https://github.com/richard-peng-xia/RULE.

This paper provides a comprehensive survey of the latest research on multilingual large language models (MLLMs). MLLMs not only are able to understand and generate language across linguistic boundaries, but also represent an important advancement in artificial intelligence. We first discuss the architecture and pre-training objectives of MLLMs, highlighting the key components and methodologies that contribute to their multilingual capabilities. We then discuss the construction of multilingual pre-training and alignment datasets, underscoring the importance of data quality and diversity in enhancing MLLM performance. An important focus of this survey is on the evaluation of MLLMs. We present a detailed taxonomy and roadmap covering the assessment of MLLMs' cross-lingual knowledge, reasoning, alignment with human values, safety, interpretability and specialized applications. Specifically, we extensively discuss multilingual evaluation benchmarks and datasets, and explore the use of LLMs themselves as multilingual evaluators. To enhance MLLMs from black to white boxes, we also address the interpretability of multilingual capabilities, cross-lingual transfer and language bias within these models. Finally, we provide a comprehensive review of real-world applications of MLLMs across diverse domains, including biology, medicine, computer science, mathematics and law. We showcase how these models have driven innovation and improvements in these specialized fields while also highlighting the challenges and opportunities in deploying MLLMs within diverse language communities and application scenarios. We listed the paper related in this survey and publicly available at https://github.com/tjunlp-lab/Awesome-Multilingual-LLMs-Papers.

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

Multiple Instance learning (MIL) models have been extensively used in pathology to predict biomarkers and risk-stratify patients from gigapixel-sized images. Machine learning problems in medical imaging often deal with rare diseases, making it important for these models to work in a label-imbalanced setting. In pathology images, there is another level of imbalance, where given a positively labeled Whole Slide Image (WSI), only a fraction of pixels within it contribute to the positive label. This compounds the severity of imbalance and makes imbalanced classification in pathology challenging. Furthermore, these imbalances can occur in out-of-distribution (OOD) datasets when the models are deployed in the real-world. We leverage the idea that decoupling feature and classifier learning can lead to improved decision boundaries for label imbalanced datasets. To this end, we investigate the integration of supervised contrastive learning with multiple instance learning (SC-MIL). Specifically, we propose a joint-training MIL framework in the presence of label imbalance that progressively transitions from learning bag-level representations to optimal classifier learning. We perform experiments with different imbalance settings for two well-studied problems in cancer pathology: subtyping of non-small cell lung cancer and subtyping of renal cell carcinoma. SC-MIL provides large and consistent improvements over other techniques on both in-distribution (ID) and OOD held-out sets across multiple imbalanced settings.

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.

Large language models (LLM) have achieved impressive performance on medical question-answering benchmarks. However, high benchmark accuracy does not imply that the performance generalizes to real-world clinical settings. Medical question-answering benchmarks rely on assumptions consistent with quantifying LLM performance but that may not hold in the open world of the clinic. Yet LLMs learn broad knowledge that can help the LLM generalize to practical conditions regardless of unrealistic assumptions in celebrated benchmarks. We seek to quantify how well LLM medical question-answering benchmark performance generalizes when benchmark assumptions are violated. Specifically, we present an adversarial method that we call MedFuzz (for medical fuzzing). MedFuzz attempts to modify benchmark questions in ways aimed at confounding the LLM. We demonstrate the approach by targeting strong assumptions about patient characteristics presented in the MedQA benchmark. Successful "attacks" modify a benchmark item in ways that would be unlikely to fool a medical expert but nonetheless "trick" the LLM into changing from a correct to an incorrect answer. Further, we present a permutation test technique that can ensure a successful attack is statistically significant. We show how to use performance on a "MedFuzzed" benchmark, as well as individual successful attacks. The methods show promise at providing insights into the ability of an LLM to operate robustly in more realistic settings.

Recently, rapid advancements in Multi-Modal In-Context Learning (MM-ICL) have achieved notable success, which is capable of achieving superior performance across various tasks without requiring additional parameter tuning. However, the underlying rules for the effectiveness of MM-ICL remain under-explored. To fill this gap, this work aims to investigate the research question: "What factors affect the performance of MM-ICL?'' To this end, we investigate extensive experiments on the three core steps of MM-ICL including demonstration retrieval, demonstration ordering, and prompt construction using 6 vision large language models and 20 strategies. Our findings highlight (1) the necessity of a multi-modal retriever for demonstration retrieval, (2) the importance of intra-demonstration ordering over inter-demonstration ordering, and (3) the enhancement of task comprehension through introductory instructions in prompts. We hope this study can serve as a foundational guide for optimizing MM-ICL strategies in future research.

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.

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.

The emergent abilities of large language models (LLMs) have demonstrated great potential in solving medical questions. They can possess considerable medical knowledge, but may still hallucinate and are inflexible in the knowledge updates. While Retrieval-Augmented Generation (RAG) has been proposed to enhance the medical question-answering capabilities of LLMs with external knowledge bases, it may still fail in complex cases where multiple rounds of information-seeking are required. To address such an issue, we propose iterative RAG for medicine (i-MedRAG), where LLMs can iteratively ask follow-up queries based on previous information-seeking attempts. In each iteration of i-MedRAG, the follow-up queries will be answered by a vanilla RAG system and they will be further used to guide the query generation in the next iteration. Our experiments show the improved performance of various LLMs brought by i-MedRAG compared with vanilla RAG on complex questions from clinical vignettes in the United States Medical Licensing Examination (USMLE), as well as various knowledge tests in the Massive Multitask Language Understanding (MMLU) dataset. Notably, our zero-shot i-MedRAG outperforms all existing prompt engineering and fine-tuning methods on GPT-3.5, achieving an accuracy of 69.68\% on the MedQA dataset. In addition, we characterize the scaling properties of i-MedRAG with different iterations of follow-up queries and different numbers of queries per iteration. Our case studies show that i-MedRAG can flexibly ask follow-up queries to form reasoning chains, providing an in-depth analysis of medical questions. To the best of our knowledge, this is the first-of-its-kind study on incorporating follow-up queries into medical RAG.

Starting from the resurgence of deep learning, vision-language models (VLMs) benefiting from large language models (LLMs) have never been so popular. However, while LLMs can utilize extensive background knowledge and task information with in-context learning, most VLMs still struggle with understanding complex multi-modal prompts with multiple images. The issue can traced back to the architectural design of VLMs or pre-training data. Specifically, the current VLMs primarily emphasize utilizing multi-modal data with a single image some, rather than multi-modal prompts with interleaved multiple images and text. Even though some newly proposed VLMs could handle user prompts with multiple images, pre-training data does not provide more sophisticated multi-modal prompts than interleaved image and text crawled from the web. We propose MMICL to address the issue by considering both the model and data perspectives. We introduce a well-designed architecture capable of seamlessly integrating visual and textual context in an interleaved manner and MIC dataset to reduce the gap between the training data and the complex user prompts in real-world applications, including: 1) multi-modal context with interleaved images and text, 2) textual references for each image, and 3) multi-image data with spatial, logical, or temporal relationships. Our experiments confirm that MMICL achieves new stat-of-the-art zero-shot and few-shot performance on a wide range of general vision-language tasks, especially for complex reasoning benchmarks including MME and MMBench. Our analysis demonstrates that MMICL effectively deals with the challenge of complex multi-modal prompt understanding. The experiments on ScienceQA-IMG also show that MMICL successfully alleviates the issue of language bias in VLMs, which we believe is the reason behind the advanced performance of MMICL.

Preference alignment has become a crucial component in enhancing the performance of Large Language Models (LLMs), yet its impact in Multimodal Large Language Models (MLLMs) remains comparatively underexplored. Similar to language models, MLLMs for image understanding tasks encounter challenges like hallucination. In MLLMs, hallucination can occur not only by stating incorrect facts but also by producing responses that are inconsistent with the image content. A primary objective of alignment for MLLMs is to encourage these models to align responses more closely with image information. Recently, multiple works have introduced preference datasets for MLLMs and examined different alignment methods, including Direct Preference Optimization (DPO) and Proximal Policy Optimization (PPO). However, due to variations in datasets, base model types, and alignment methods, it remains unclear which specific elements contribute most significantly to the reported improvements in these works. In this paper, we independently analyze each aspect of preference alignment in MLLMs. We start by categorizing the alignment algorithms into two groups, offline (such as DPO), and online (such as online-DPO), and show that combining offline and online methods can improve the performance of the model in certain scenarios. We review a variety of published multimodal preference datasets and discuss how the details of their construction impact model performance. Based on these insights, we introduce a novel way of creating multimodal preference data called Bias-Driven Hallucination Sampling (BDHS) that needs neither additional annotation nor external models, and show that it can achieve competitive performance to previously published alignment work for multimodal models across a range of benchmarks.

Artificial intelligence (AI) and large language models (LLMs) in healthcare require advanced clinical skills (CS), yet current benchmarks fail to evaluate these comprehensively. We introduce MedQA-CS, an AI-SCE framework inspired by medical education's Objective Structured Clinical Examinations (OSCEs), to address this gap. MedQA-CS evaluates LLMs through two instruction-following tasks, LLM-as-medical-student and LLM-as-CS-examiner, designed to reflect real clinical scenarios. Our contributions include developing MedQA-CS, a comprehensive evaluation framework with publicly available data and expert annotations, and providing the quantitative and qualitative assessment of LLMs as reliable judges in CS evaluation. Our experiments show that MedQA-CS is a more challenging benchmark for evaluating clinical skills than traditional multiple-choice QA benchmarks (e.g., MedQA). Combined with existing benchmarks, MedQA-CS enables a more comprehensive evaluation of LLMs' clinical capabilities for both open- and closed-source LLMs.

Large Language Models (LLMs) have attained human-level accuracy on medical question-answer (QA) benchmarks. However, their limitations in navigating open-ended clinical scenarios have recently been shown, raising concerns about the robustness and generalizability of LLM reasoning across diverse, real-world medical tasks. To probe potential LLM failure modes in clinical problem-solving, we present the medical abstraction and reasoning corpus (M-ARC). M-ARC assesses clinical reasoning through scenarios designed to exploit the Einstellung effect -- the fixation of thought arising from prior experience, targeting LLM inductive biases toward inflexible pattern matching from their training data rather than engaging in flexible reasoning. We find that LLMs, including current state-of-the-art o1 and Gemini models, perform poorly compared to physicians on M-ARC, often demonstrating lack of commonsense medical reasoning and a propensity to hallucinate. In addition, uncertainty estimation analyses indicate that LLMs exhibit overconfidence in their answers, despite their limited accuracy. The failure modes revealed by M-ARC in LLM medical reasoning underscore the need to exercise caution when deploying these models in clinical settings.

Recently, Large Language Models (LLMs) with Mixture of Experts (MoE) layers have gained significant attention. Currently, state-of-the-art LLMs utilize this architecture. There is a substantial amount of research on how to train such models and how to select hyperparameters for this architecture. However, there is a lack of studies focusing on post-evaluation analysis of MoE layer properties. In this paper, we take a first step toward closing this gap by evaluating expert contributions on the quiz-based MMLU benchmark. We show that most experts were never activated during inference on this benchmark. Additionally, the output distribution of gating networks is much closer to uniform than sparse. Finally, we demonstrate that the average performance of some experts within the same layer varies significantly.

Multimodal Large Language Models (MLLMs) have shown impressive abilities in interacting with visual content with myriad potential downstream tasks. However, even though a list of benchmarks has been proposed, the capabilities and limitations of MLLMs are still not comprehensively understood, due to a lack of a standardized and holistic evaluation framework. To this end, we present the first Comprehensive Evaluation Framework (ChEF) that can holistically profile each MLLM and fairly compare different MLLMs. First, we structure ChEF as four modular components, i.e., Scenario as scalable multimodal datasets, Instruction as flexible instruction retrieving formulae, Inferencer as reliable question answering strategies, and Metric as indicative task-specific score functions. Based on them, ChEF facilitates versatile evaluations in a standardized framework, and new evaluations can be built by designing new Recipes (systematic selection of these four components). Notably, current MLLM benchmarks can be readily summarized as recipes of ChEF. Second, we introduce 6 new recipes to quantify competent MLLMs' desired capabilities (or called desiderata, i.e., calibration, in-context learning, instruction following, language performance, hallucination, and robustness) as reliable agents that can perform real-world multimodal interactions. Third, we conduct a large-scale evaluation of 9 prominent MLLMs on 9 scenarios and 6 desiderata. Our evaluation summarized over 20 valuable observations concerning the generalizability of MLLMs across various scenarios and the composite capability of MLLMs required for multimodal interactions. We will publicly release all the detailed implementations for further analysis, as well as an easy-to-use modular toolkit for the integration of new recipes and models, so that ChEF can be a growing evaluation framework for the MLLM community.

Accurate breast lesion risk estimation can significantly reduce unnecessary biopsies and help doctors decide optimal treatment plans. Most existing computer-aided systems rely solely on mammogram features to classify breast lesions. While this approach is convenient, it does not fully exploit useful information in clinical reports to achieve the optimal performance. Would clinical features significantly improve breast lesion classification compared to using mammograms alone? How to handle missing clinical information caused by variation in medical practice? What is the best way to combine mammograms and clinical features? There is a compelling need for a systematic study to address these fundamental questions. This paper investigates several multimodal deep networks based on feature concatenation, cross-attention, and co-attention to combine mammograms and categorical clinical variables. We show that the proposed architectures significantly increase the lesion classification performance (average area under ROC curves from 0.89 to 0.94). We also evaluate the model when clinical variables are missing.

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.

In an era defined by the explosive growth of data and rapid technological advancements, Multimodal Large Language Models (MLLMs) stand at the forefront of artificial intelligence (AI) systems. Designed to seamlessly integrate diverse data types-including text, images, videos, audio, and physiological sequences-MLLMs address the complexities of real-world applications far beyond the capabilities of single-modality systems. In this paper, we systematically sort out the applications of MLLM in multimodal tasks such as natural language, vision, and audio. We also provide a comparative analysis of the focus of different MLLMs in the tasks, and provide insights into the shortcomings of current MLLMs, and suggest potential directions for future research. Through these discussions, this paper hopes to provide valuable insights for the further development and application of MLLM.

Driven by the remarkable progress in diffusion models, text-to-image generation has made significant strides, creating a pressing demand for automatic quality evaluation of generated images. Current state-of-the-art automatic evaluation methods heavily rely on Multi-modal Large Language Models (MLLMs), particularly powerful commercial models like GPT-4o. While these models are highly effective, their substantial costs limit scalability in large-scale evaluations. Adopting open-source MLLMs is an alternative; however, their performance falls short due to significant limitations in processing multi-modal data compared to commercial MLLMs. To tackle these problems, we first propose a task decomposition evaluation framework based on GPT-4o to automatically construct a new training dataset, where the complex evaluation task is decoupled into simpler sub-tasks, effectively reducing the learning complexity. Based on this dataset, we design innovative training strategies to effectively distill GPT-4o's evaluation capabilities into a 7B open-source MLLM, MiniCPM-V-2.6. Furthermore, to reliably and comprehensively assess prior works and our proposed model, we manually annotate a meta-evaluation benchmark that includes chain-of-thought explanations alongside quality scores for generated images. Experimental results demonstrate that our distilled open-source MLLM significantly outperforms the current state-of-the-art GPT-4o-base baseline, VIEScore, with over 4.6\% improvement in Spearman and Kendall correlations with human judgments.

CutMix is a vital augmentation strategy that determines the performance and generalization ability of vision transformers (ViTs). However, the inconsistency between the mixed images and the corresponding labels harms its efficacy. Existing CutMix variants tackle this problem by generating more consistent mixed images or more precise mixed labels, but inevitably introduce heavy training overhead or require extra information, undermining ease of use. To this end, we propose an novel and effective Self-Motivated image Mixing method (SMMix), which motivates both image and label enhancement by the model under training itself. Specifically, we propose a max-min attention region mixing approach that enriches the attention-focused objects in the mixed images. Then, we introduce a fine-grained label assignment technique that co-trains the output tokens of mixed images with fine-grained supervision. Moreover, we devise a novel feature consistency constraint to align features from mixed and unmixed images. Due to the subtle designs of the self-motivated paradigm, our SMMix is significant in its smaller training overhead and better performance than other CutMix variants. In particular, SMMix improves the accuracy of DeiT-T/S/B, CaiT-XXS-24/36, and PVT-T/S/M/L by more than +1% on ImageNet-1k. The generalization capability of our method is also demonstrated on downstream tasks and out-of-distribution datasets. Our project is anonymously available at https://github.com/ChenMnZ/SMMix.

We introduce DLSIA (Deep Learning for Scientific Image Analysis), a Python-based machine learning library that empowers scientists and researchers across diverse scientific domains with a range of customizable convolutional neural network (CNN) architectures for a wide variety of tasks in image analysis to be used in downstream data processing, or for experiment-in-the-loop computing scenarios. DLSIA features easy-to-use architectures such as autoencoders, tunable U-Nets, and parameter-lean mixed-scale dense networks (MSDNets). Additionally, we introduce sparse mixed-scale networks (SMSNets), generated using random graphs and sparse connections. As experimental data continues to grow in scale and complexity, DLSIA provides accessible CNN construction and abstracts CNN complexities, allowing scientists to tailor their machine learning approaches, accelerate discoveries, foster interdisciplinary collaboration, and advance research in scientific image analysis.

Interleaved multimodal comprehension and generation, enabling models to produce and interpret both images and text in arbitrary sequences, have become a pivotal area in multimodal learning. Despite significant advancements, the evaluation of this capability remains insufficient. Existing benchmarks suffer from limitations in data scale, scope, and evaluation depth, while current evaluation metrics are often costly or biased, lacking in reliability for practical applications. To address these challenges, we introduce MMIE, a large-scale knowledge-intensive benchmark for evaluating interleaved multimodal comprehension and generation in Large Vision-Language Models (LVLMs). MMIE comprises 20K meticulously curated multimodal queries, spanning 3 categories, 12 fields, and 102 subfields, including mathematics, coding, physics, literature, health, and arts. It supports both interleaved inputs and outputs, offering a mix of multiple-choice and open-ended question formats to evaluate diverse competencies. Moreover, we propose a reliable automated evaluation metric, leveraging a scoring model fine-tuned with human-annotated data and systematic evaluation criteria, aimed at reducing bias and improving evaluation accuracy. Extensive experiments demonstrate the effectiveness of our benchmark and metrics in providing a comprehensive evaluation of interleaved LVLMs. Specifically, we evaluate eight LVLMs, revealing that even the best models show significant room for improvement, with most achieving only moderate results. We believe MMIE will drive further advancements in the development of interleaved LVLMs. We publicly release our benchmark and code in https://mmie-bench.github.io/.

Language models (LMs) have demonstrated expert-level reasoning and recall abilities in medicine. However, computational costs and privacy concerns are mounting barriers to wide-scale implementation. We introduce a parsimonious adaptation of phi-3-mini, MedMobile, a 3.8 billion parameter LM capable of running on a mobile device, for medical applications. We demonstrate that MedMobile scores 75.7% on the MedQA (USMLE), surpassing the passing mark for physicians (~60%), and approaching the scores of models 100 times its size. We subsequently perform a careful set of ablations, and demonstrate that chain of thought, ensembling, and fine-tuning lead to the greatest performance gains, while unexpectedly retrieval augmented generation fails to demonstrate significant improvements

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.

Data mixing augmentation has been widely applied to improve the generalization ability of deep neural networks. Recently, offline data mixing augmentation, e.g. handcrafted and saliency information-based mixup, has been gradually replaced by automatic mixing approaches. Through minimizing two sub-tasks, namely, mixed sample generation and mixup classification in an end-to-end way, AutoMix significantly improves accuracy on image classification tasks. However, as the optimization objective is consistent for the two sub-tasks, this approach is prone to generating consistent instead of diverse mixed samples, which results in overfitting for target task training. In this paper, we propose AdAutomixup, an adversarial automatic mixup augmentation approach that generates challenging samples to train a robust classifier for image classification, by alternatively optimizing the classifier and the mixup sample generator. AdAutomixup comprises two modules, a mixed example generator, and a target classifier. The mixed sample generator aims to produce hard mixed examples to challenge the target classifier, while the target classifier's aim is to learn robust features from hard mixed examples to improve generalization. To prevent the collapse of the inherent meanings of images, we further introduce an exponential moving average (EMA) teacher and cosine similarity to train AdAutomixup in an end-to-end way. Extensive experiments on seven image benchmarks consistently prove that our approach outperforms the state of the art in various classification scenarios. The source code is available at https://github.com/JinXins/Adversarial-AutoMixup.

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.

Recent advancements in Multimodal Large Language Models (MLLMs) underscore the significance of scalable models and data to boost performance, yet this often incurs substantial computational costs. Although the Mixture of Experts (MoE) architecture has been employed to efficiently scale large language and image-text models, these efforts typically involve fewer experts and limited modalities. To address this, our work presents the pioneering attempt to develop a unified MLLM with the MoE architecture, named Uni-MoE that can handle a wide array of modalities. Specifically, it features modality-specific encoders with connectors for a unified multimodal representation. We also implement a sparse MoE architecture within the LLMs to enable efficient training and inference through modality-level data parallelism and expert-level model parallelism. To enhance the multi-expert collaboration and generalization, we present a progressive training strategy: 1) Cross-modality alignment using various connectors with different cross-modality data, 2) Training modality-specific experts with cross-modality instruction data to activate experts' preferences, and 3) Tuning the Uni-MoE framework utilizing Low-Rank Adaptation (LoRA) on mixed multimodal instruction data. We evaluate the instruction-tuned Uni-MoE on a comprehensive set of multimodal datasets. The extensive experimental results demonstrate Uni-MoE's principal advantage of significantly reducing performance bias in handling mixed multimodal datasets, alongside improved multi-expert collaboration and generalization. Our findings highlight the substantial potential of MoE frameworks in advancing MLLMs and the code is available at https://github.com/HITsz-TMG/UMOE-Scaling-Unified-Multimodal-LLMs.

We train a suite of multimodal foundation models (MMFM) using the popular LLaVA framework with the recently released Gemma family of large language models (LLMs). Of particular interest is the 2B parameter Gemma model, which provides opportunities to construct capable small-scale MMFMs. In line with findings from other papers in this space, we test the effect of ablating three design features: pretraining the connector, utilizing a more powerful image backbone, and increasing the size of the language backbone. The resulting models, which we call LLaVA-Gemma, exhibit moderate performance on an array of evaluations, but fail to improve past the current comparably sized SOTA models. Closer analysis of performance shows mixed effects; skipping pretraining tends to reduce performance, larger vision models sometimes improve performance, and increasing language model size has inconsistent effects. We publicly release training recipes, code and weights for our models for the LLaVA-Gemma models.

The soft Dice loss (SDL) has taken a pivotal role in numerous automated segmentation pipelines in the medical imaging community. Over the last years, some reasons behind its superior functioning have been uncovered and further optimizations have been explored. However, there is currently no implementation that supports its direct utilization in scenarios involving soft labels. Hence, a synergy between the use of SDL and research leveraging the use of soft labels, also in the context of model calibration, is still missing. In this work, we introduce Dice semimetric losses (DMLs), which (i) are by design identical to SDL in a standard setting with hard labels, but (ii) can be employed in settings with soft labels. Our experiments on the public QUBIQ, LiTS and KiTS benchmarks confirm the potential synergy of DMLs with soft labels (e.g.\ averaging, label smoothing, and knowledge distillation) over hard labels (e.g.\ majority voting and random selection). As a result, we obtain superior Dice scores and model calibration, which supports the wider adoption of DMLs in practice. The code is available at https://github.com/zifuwanggg/JDTLosses{https://github.com/zifuwanggg/JDTLosses}.

The global cost of drug discovery and development exceeds $200 billion annually. The main results of drug discovery and development are the outcomes of clinical trials, which directly influence the regulatory approval of new drug candidates and ultimately affect patient outcomes. Despite their significance, large-scale, high-quality clinical trial outcome data are not readily available to the public. Suppose a large clinical trial outcome dataset is provided; machine learning researchers can potentially develop accurate prediction models using past trials and outcome labels, which could help prioritize and optimize therapeutic programs, ultimately benefiting patients. This paper introduces Clinical Trial Outcome (CTO) dataset, the largest trial outcome dataset with around 479K clinical trials, aggregating outcomes from multiple sources of weakly supervised labels, minimizing the noise from individual sources, and eliminating the need for human annotation. These sources include large language model (LLM) decisions on trial-related documents, news headline sentiments, stock prices of trial sponsors, trial linkages across phases, and other signals such as patient dropout rates and adverse events. CTO's labels show unprecedented agreement with supervised clinical trial outcome labels from test split of the supervised TOP dataset, with a 91 F1.

Deep learning (DL) has proven to be a highly effective approach for developing models in diverse contexts, including visual perception, speech recognition, and machine translation. However, the end-to-end process for applying DL is not trivial. It requires grappling with problem formulation and context understanding, data engineering, model development, deployment, continuous monitoring and maintenance, and so on. Moreover, each of these steps typically relies heavily on humans, in terms of both knowledge and interactions, which impedes the further advancement and democratization of DL. Consequently, in response to these issues, a new field has emerged over the last few years: automated deep learning (AutoDL). This endeavor seeks to minimize the need for human involvement and is best known for its achievements in neural architecture search (NAS), a topic that has been the focus of several surveys. That stated, NAS is not the be-all and end-all of AutoDL. Accordingly, this review adopts an overarching perspective, examining research efforts into automation across the entirety of an archetypal DL workflow. In so doing, this work also proposes a comprehensive set of ten criteria by which to assess existing work in both individual publications and broader research areas. These criteria are: novelty, solution quality, efficiency, stability, interpretability, reproducibility, engineering quality, scalability, generalizability, and eco-friendliness. Thus, ultimately, this review provides an evaluative overview of AutoDL in the early 2020s, identifying where future opportunities for progress may exist.

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.

Medical image analysis continues to hold interesting challenges given the subtle characteristics of certain diseases and the significant overlap in appearance between diseases. In this work, we explore the concept of self-attention for tackling such subtleties in and between diseases. To this end, we introduce MEDUSA, a multi-scale encoder-decoder self-attention mechanism tailored for medical image analysis. While self-attention deep convolutional neural network architectures in existing literature center around the notion of multiple isolated lightweight attention mechanisms with limited individual capacities being incorporated at different points in the network architecture, MEDUSA takes a significant departure from this notion by possessing a single, unified self-attention mechanism with significantly higher capacity with multiple attention heads feeding into different scales in the network architecture. To the best of the authors' knowledge, this is the first "single body, multi-scale heads" realization of self-attention and enables explicit global context amongst selective attention at different levels of representational abstractions while still enabling differing local attention context at individual levels of abstractions. With MEDUSA, we obtain state-of-the-art performance on multiple challenging medical image analysis benchmarks including COVIDx, RSNA RICORD, and RSNA Pneumonia Challenge when compared to previous work. Our MEDUSA model is publicly available.

Exploiting activation sparsity is a promising approach to significantly accelerating the inference process of large language models (LLMs) without compromising performance. However, activation sparsity is determined by activation functions, and commonly used ones like SwiGLU and GeGLU exhibit limited sparsity. Simply replacing these functions with ReLU fails to achieve sufficient sparsity. Moreover, inadequate training data can further increase the risk of performance degradation. To address these challenges, we propose a novel dReLU function, which is designed to improve LLM activation sparsity, along with a high-quality training data mixture ratio to facilitate effective sparsification. Additionally, we leverage sparse activation patterns within the Feed-Forward Network (FFN) experts of Mixture-of-Experts (MoE) models to further boost efficiency. By applying our neuron sparsification method to the Mistral and Mixtral models, only 2.5 billion and 4.3 billion parameters are activated per inference iteration, respectively, while achieving even more powerful model performance. Evaluation results demonstrate that this sparsity achieves a 2-5x decoding speedup. Remarkably, on mobile phones, our TurboSparse-Mixtral-47B achieves an inference speed of 11 tokens per second. Our models are available at https://huggingface.co/PowerInfer

Pretraining data of large language models composes multiple domains (e.g., web texts, academic papers, codes), whose mixture proportions crucially impact the competence of outcome models. While existing endeavors rely on heuristics or qualitative strategies to tune the proportions, we discover the quantitative predictability of model performance regarding the mixture proportions in function forms, which we refer to as the data mixing laws. Fitting such functions on sample mixtures unveils model performance on unseen mixtures before actual runs, thus guiding the selection of an ideal data mixture. Furthermore, we propose nested use of the scaling laws of training steps, model sizes, and our data mixing law to enable predicting the performance of large models trained on massive data under various mixtures with only small-scale training. Moreover, experimental results verify that our method effectively optimizes the training mixture of a 1B model trained for 100B tokens in RedPajama, reaching a performance comparable to the one trained for 48% more steps on the default mixture. Extending the application of data mixing laws to continual training accurately predicts the critical mixture proportion that avoids catastrophic forgetting and outlooks the potential for dynamic data schedules

Data mixing strategies (e.g., CutMix) have shown the ability to greatly improve the performance of convolutional neural networks (CNNs). They mix two images as inputs for training and assign them with a mixed label with the same ratio. While they are shown effective for vision transformers (ViTs), we identify a token fluctuation phenomenon that has suppressed the potential of data mixing strategies. We empirically observe that the contributions of input tokens fluctuate as forward propagating, which might induce a different mixing ratio in the output tokens. The training target computed by the original data mixing strategy can thus be inaccurate, resulting in less effective training. To address this, we propose a token-label alignment (TL-Align) method to trace the correspondence between transformed tokens and the original tokens to maintain a label for each token. We reuse the computed attention at each layer for efficient token-label alignment, introducing only negligible additional training costs. Extensive experiments demonstrate that our method improves the performance of ViTs on image classification, semantic segmentation, objective detection, and transfer learning tasks. Code is available at: https://github.com/Euphoria16/TL-Align.

Interventions on model-internal states are fundamental operations in many areas of AI, including model editing, steering, robustness, and interpretability. To facilitate such research, we introduce pyvene, an open-source Python library that supports customizable interventions on a range of different PyTorch modules. pyvene supports complex intervention schemes with an intuitive configuration format, and its interventions can be static or include trainable parameters. We show how pyvene provides a unified and extensible framework for performing interventions on neural models and sharing the intervened upon models with others. We illustrate the power of the library via interpretability analyses using causal abstraction and knowledge localization. We publish our library through Python Package Index (PyPI) and provide code, documentation, and tutorials at https://github.com/stanfordnlp/pyvene.

Inspire therapy is an FDA-approved internal neurostimulation treatment for obstructive sleep apnea. However, not all patients respond to this therapy, posing a challenge even for experienced otolaryngologists to determine candidacy. This paper makes the first attempt to leverage both machine learning and deep learning techniques in discerning patient responsiveness to Inspire therapy using medical data and videos captured through Drug-Induced Sleep Endoscopy (DISE), an essential procedure for Inspire therapy. To achieve this, we gathered and annotated three datasets from 127 patients. Two of these datasets comprise endoscopic videos focused on the Base of the Tongue and Velopharynx. The third dataset composes the patient's clinical information. By utilizing these datasets, we benchmarked and compared the performance of six deep learning models and five classical machine learning algorithms. The results demonstrate the potential of employing machine learning and deep learning techniques to determine a patient's eligibility for Inspire therapy, paving the way for future advancements in this field.

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.

Despite the recent advancements in Multi-modal Large Language Models (MLLMs), understanding inter-object relations, i.e., interactions or associations between distinct objects, remains a major challenge for such models. This issue significantly hinders their advanced reasoning capabilities and is primarily due to the lack of large-scale, high-quality, and diverse multi-modal data essential for training and evaluating MLLMs. In this paper, we provide a taxonomy of inter-object relations and introduce Multi-Modal Relation Understanding (MMRel), a comprehensive dataset designed to bridge this gap by providing large-scale, high-quality and diverse data for studying inter-object relations with MLLMs. MMRel features three distinctive attributes: (i) It includes over 15K question-answer pairs, which are sourced from three distinct domains, ensuring large scale and high diversity; (ii) It contains a subset featuring highly unusual relations, on which MLLMs often fail due to hallucinations, thus are very challenging; (iii) It provides manually verified high-quality labels for inter-object relations. Thanks to these features, MMRel is ideal for evaluating MLLMs on relation understanding, as well as being used to fine-tune MLLMs to enhance relation understanding and even benefit overall performance in various vision-language tasks. Extensive experiments on various popular MLLMs validate the effectiveness of MMRel. Both MMRel dataset and the complete labeling scripts have been made publicly available.