Daily Papers

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.

Medical image segmentation and video object segmentation are essential for diagnosing and analyzing diseases by identifying and measuring biological structures. Recent advances in natural domain have been driven by foundation models like the Segment Anything Model 2 (SAM 2). To explore the performance of SAM 2 in biomedical applications, we designed two evaluation pipelines for single-frame image segmentation and multi-frame video segmentation with varied prompt designs, revealing SAM 2's limitations in medical contexts. Consequently, we developed BioSAM 2, an enhanced foundation model optimized for biomedical data based on SAM 2. Our experiments show that BioSAM 2 not only surpasses the performance of existing state-of-the-art foundation models but also matches or even exceeds specialist models, demonstrating its efficacy and potential in the medical domain.

Semantic segmentation is crucial for various biomedical applications, yet its reliance on large annotated datasets presents a bottleneck due to the high cost and specialized expertise required for manual labeling. Active Learning (AL) aims to mitigate this challenge by querying only the most informative samples, thereby reducing annotation effort. However, in the domain of 3D biomedical imaging, there is no consensus on whether AL consistently outperforms Random sampling. Four evaluation pitfalls hinder the current methodological assessment. These are (1) restriction to too few datasets and annotation budgets, (2) using 2D models on 3D images without partial annotations, (3) Random baseline not being adapted to the task, and (4) measuring annotation cost only in voxels. In this work, we introduce nnActive, an open-source AL framework that overcomes these pitfalls by (1) means of a large scale study spanning four biomedical imaging datasets and three label regimes, (2) extending nnU-Net by using partial annotations for training with 3D patch-based query selection, (3) proposing Foreground Aware Random sampling strategies tackling the foreground-background class imbalance of medical images and (4) propose the foreground efficiency metric, which captures the low annotation cost of background-regions. We reveal the following findings: (A) while all AL methods outperform standard Random sampling, none reliably surpasses an improved Foreground Aware Random sampling; (B) benefits of AL depend on task specific parameters; (C) Predictive Entropy is overall the best performing AL method, but likely requires the most annotation effort; (D) AL performance can be improved with more compute intensive design choices. As a holistic, open-source framework, nnActive can serve as a catalyst for research and application of AL in 3D biomedical imaging. Code is at: https://github.com/MIC-DKFZ/nnActive

Developing effective biomedical retrieval models is important for excelling at knowledge-intensive biomedical tasks but still challenging due to the deficiency of sufficient publicly annotated biomedical data and computational resources. We present BMRetriever, a series of dense retrievers for enhancing biomedical retrieval via unsupervised pre-training on large biomedical corpora, followed by instruction fine-tuning on a combination of labeled datasets and synthetic pairs. Experiments on 5 biomedical tasks across 11 datasets verify BMRetriever's efficacy on various biomedical applications. BMRetriever also exhibits strong parameter efficiency, with the 410M variant outperforming baselines up to 11.7 times larger, and the 2B variant matching the performance of models with over 5B parameters. The training data and model checkpoints are released at https://huggingface.co/BMRetriever to ensure transparency, reproducibility, and application to new domains.

Electronic health records (EHR) contain narrative notes that provide extensive details on the medical condition and management of patients. Natural language processing (NLP) of clinical notes can use observed frequencies of clinical terms as predictive features for downstream applications such as clinical decision making and patient trajectory prediction. However, due to the vast number of highly similar and related clinical concepts, a more effective modeling strategy is to represent clinical terms as semantic embeddings via representation learning and use the low dimensional embeddings as feature vectors for predictive modeling. To achieve efficient representation, fine-tuning pretrained language models with biomedical knowledge graphs may generate better embeddings for biomedical terms than those from standard language models alone. These embeddings can effectively discriminate synonymous pairs of from those that are unrelated. However, they often fail to capture different degrees of similarity or relatedness for concepts that are hierarchical in nature. To overcome this limitation, we propose HiPrBERT, a novel biomedical term representation model trained on additionally complied data that contains hierarchical structures for various biomedical terms. We modify an existing contrastive loss function to extract information from these hierarchies. Our numerical experiments demonstrate that HiPrBERT effectively learns the pair-wise distance from hierarchical information, resulting in a substantially more informative embeddings for further biomedical applications

Self-supervised learning in vision-language processing exploits semantic alignment between imaging and text modalities. Prior work in biomedical VLP has mostly relied on the alignment of single image and report pairs even though clinical notes commonly refer to prior images. This does not only introduce poor alignment between the modalities but also a missed opportunity to exploit rich self-supervision through existing temporal content in the data. In this work, we explicitly account for prior images and reports when available during both training and fine-tuning. Our approach, named BioViL-T, uses a CNN-Transformer hybrid multi-image encoder trained jointly with a text model. It is designed to be versatile to arising challenges such as pose variations and missing input images across time. The resulting model excels on downstream tasks both in single- and multi-image setups, achieving state-of-the-art performance on (I) progression classification, (II) phrase grounding, and (III) report generation, whilst offering consistent improvements on disease classification and sentence-similarity tasks. We release a novel multi-modal temporal benchmark dataset, MS-CXR-T, to quantify the quality of vision-language representations in terms of temporal semantics. Our experimental results show the advantages of incorporating prior images and reports to make most use of the data.

Large language models (LLM) hold significant potential for applications in biomedicine, but they struggle with hallucinations and outdated knowledge. While retrieval-augmented generation (RAG) is generally employed to address these issues, it also has its own set of challenges: (1) LLMs are vulnerable to irrelevant or incorrect context, (2) medical queries are often not well-targeted for helpful information, and (3) retrievers are prone to bias toward the specific source corpus they were trained on. In this study, we present RAG^2 (RAtionale-Guided RAG), a new framework for enhancing the reliability of RAG in biomedical contexts. RAG^2 incorporates three key innovations: a small filtering model trained on perplexity-based labels of rationales, which selectively augments informative snippets of documents while filtering out distractors; LLM-generated rationales as queries to improve the utility of retrieved snippets; a structure designed to retrieve snippets evenly from a comprehensive set of four biomedical corpora, effectively mitigating retriever bias. Our experiments demonstrate that RAG^2 improves the state-of-the-art LLMs of varying sizes, with improvements of up to 6.1\%, and it outperforms the previous best medical RAG model by up to 5.6\% across three medical question-answering benchmarks. Our code is available at https://github.com/dmis-lab/RAG2.

Accurate extraction of heart rate from photoplethysmography (PPG) signals remains challenging due to motion artifacts and signal degradation. Although deep learning methods trained as a data-driven inference problem offer promising solutions, they often underutilize existing knowledge from the medical and signal processing community. In this paper, we address three shortcomings of deep learning models: motion artifact removal, degradation assessment, and physiologically plausible analysis of the PPG signal. We propose KID-PPG, a knowledge-informed deep learning model that integrates expert knowledge through adaptive linear filtering, deep probabilistic inference, and data augmentation. We evaluate KID-PPG on the PPGDalia dataset, achieving an average mean absolute error of 2.85 beats per minute, surpassing existing reproducible methods. Our results demonstrate a significant performance improvement in heart rate tracking through the incorporation of prior knowledge into deep learning models. This approach shows promise in enhancing various biomedical applications by incorporating existing expert knowledge in deep learning models.

Pocket representations play a vital role in various biomedical applications, such as druggability estimation, ligand affinity prediction, and de novo drug design. While existing geometric features and pretrained representations have demonstrated promising results, they usually treat pockets independent of ligands, neglecting the fundamental interactions between them. However, the limited pocket-ligand complex structures available in the PDB database (less than 100 thousand non-redundant pairs) hampers large-scale pretraining endeavors for interaction modeling. To address this constraint, we propose a novel pocket pretraining approach that leverages knowledge from high-resolution atomic protein structures, assisted by highly effective pretrained small molecule representations. By segmenting protein structures into drug-like fragments and their corresponding pockets, we obtain a reasonable simulation of ligand-receptor interactions, resulting in the generation of over 5 million complexes. Subsequently, the pocket encoder is trained in a contrastive manner to align with the representation of pseudo-ligand furnished by some pretrained small molecule encoders. Our method, named ProFSA, achieves state-of-the-art performance across various tasks, including pocket druggability prediction, pocket matching, and ligand binding affinity prediction. Notably, ProFSA surpasses other pretraining methods by a substantial margin. Moreover, our work opens up a new avenue for mitigating the scarcity of protein-ligand complex data through the utilization of high-quality and diverse protein structure databases.

Detecting and segmenting object instances is a common task in biomedical applications. Examples range from detecting lesions on functional magnetic resonance images, to the detection of tumours in histopathological images and extracting quantitative single-cell information from microscopy imagery, where cell segmentation is a major bottleneck. Attention-based transformers are state-of-the-art in a range of deep learning fields. They have recently been proposed for segmentation tasks where they are beginning to outperforming other methods. We present a novel attention-based cell detection transformer (Cell-DETR) for direct end-to-end instance segmentation. While the segmentation performance is on par with a state-of-the-art instance segmentation method, Cell-DETR is simpler and faster. We showcase the method's contribution in a the typical use case of segmenting yeast in microstructured environments, commonly employed in systems or synthetic biology. For the specific use case, the proposed method surpasses the state-of-the-art tools for semantic segmentation and additionally predicts the individual object instances. The fast and accurate instance segmentation performance increases the experimental information yield for a posteriori data processing and makes online monitoring of experiments and closed-loop optimal experimental design feasible.

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

Segmenting cells and tracking their motion over time is a common task in biomedical applications. However, predicting accurate instance-wise segmentation and cell motions from microscopy imagery remains a challenging task. Using microstructured environments for analyzing single cells in a constant flow of media adds additional complexity. While large-scale labeled microscopy datasets are available, we are not aware of any large-scale dataset, including both cells and microstructures. In this paper, we introduce the trapped yeast cell (TYC) dataset, a novel dataset for understanding instance-level semantics and motions of cells in microstructures. We release 105 dense annotated high-resolution brightfield microscopy images, including about 19k instance masks. We also release 261 curated video clips composed of 1293 high-resolution microscopy images to facilitate unsupervised understanding of cell motions and morphology. TYC offers ten times more instance annotations than the previously largest dataset, including cells and microstructures. Our effort also exceeds previous attempts in terms of microstructure variability, resolution, complexity, and capturing device (microscopy) variability. We facilitate a unified comparison on our novel dataset by introducing a standardized evaluation strategy. TYC and evaluation code are publicly available under CC BY 4.0 license.

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

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

Computational microscopy, in which hardware and algorithms of an imaging system are jointly designed, shows promise for making imaging systems that cost less, perform more robustly, and collect new types of information. Often, the performance of computational imaging systems, especially those that incorporate machine learning, is sample-dependent. Thus, standardized datasets are an essential tool for comparing the performance of different approaches. Here, we introduce the Berkeley Single Cell Computational Microscopy (BSCCM) dataset, which contains over ~12,000,000 images of 400,000 of individual white blood cells. The dataset contains images captured with multiple illumination patterns on an LED array microscope and fluorescent measurements of the abundance of surface proteins that mark different cell types. We hope this dataset will provide a valuable resource for the development and testing of new algorithms in computational microscopy and computer vision with practical biomedical applications.

Text-to-SQL systems allow non-SQL experts to interact with relational databases using natural language. However, their tendency to generate executable SQL for ambiguous, out-of-scope, or unanswerable queries introduces a hidden risk, as outputs may be misinterpreted as correct. This risk is especially serious in biomedical contexts, where precision is critical. We therefore present Query Carefully, a pipeline that integrates LLM-based SQL generation with explicit detection and handling of unanswerable inputs. Building on the OncoMX component of ScienceBenchmark, we construct OncoMX-NAQ (No-Answer Questions), a set of 80 no-answer questions spanning 8 categories (non-SQL, out-of-schema/domain, and multiple ambiguity types). Our approach employs llama3.3:70b with schema-aware prompts, explicit No-Answer Rules (NAR), and few-shot examples drawn from both answerable and unanswerable questions. We evaluate SQL exact match, result accuracy, and unanswerable-detection accuracy. On the OncoMX dev split, few-shot prompting with answerable examples increases result accuracy, and adding unanswerable examples does not degrade performance. On OncoMX-NAQ, balanced prompting achieves the highest unanswerable-detection accuracy (0.8), with near-perfect results for structurally defined categories (non-SQL, missing columns, out-of-domain) but persistent challenges for missing-value queries (0.5) and column ambiguity (0.3). A lightweight user interface surfaces interim SQL, execution results, and abstentions, supporting transparent and reliable text-to-SQL in biomedical applications.

Fluorescence Lifetime Imaging (FLI) is a critical molecular imaging modality that provides unique information about the tissue microenvironment, which is invaluable for biomedical applications. FLI operates by acquiring and analyzing photon time-of-arrival histograms to extract quantitative parameters associated with temporal fluorescence decay. These histograms are influenced by the intrinsic properties of the fluorophore, instrument parameters, time-of-flight distributions associated with pixel-wise variations in the topographic and optical characteristics of the sample. Recent advancements in Deep Learning (DL) have enabled improved fluorescence lifetime parameter estimation. However, existing models are primarily designed for planar surface samples, limiting their applicability in translational scenarios involving complex surface profiles, such as in-vivo whole-animal or imaged guided surgical applications. To address this limitation, we present MFliNet (Macroscopic FLI Network), a novel DL architecture that integrates the Instrument Response Function (IRF) as an additional input alongside experimental photon time-of-arrival histograms. Leveraging the capabilities of a Differential Transformer encoder-decoder architecture, MFliNet effectively focuses on critical input features, such as variations in photon time-of-arrival distributions. We evaluate MFliNet using rigorously designed tissue-mimicking phantoms and preclinical in-vivo cancer xenograft models. Our results demonstrate the model's robustness and suitability for complex macroscopic FLI applications, offering new opportunities for advanced biomedical imaging in diverse and challenging settings.

The objective of personalized medicine is to tailor interventions to an individual patient's unique characteristics. A key technology for this purpose involves medical digital twins, computational models of human biology that can be personalized and dynamically updated to incorporate patient-specific data collected over time. Certain aspects of human biology, such as the immune system, are not easily captured with physics-based models, such as differential equations. Instead, they are often multi-scale, stochastic, and hybrid. This poses a challenge to existing model-based control and optimization approaches that cannot be readily applied to such models. Recent advances in automatic differentiation and neural-network control methods hold promise in addressing complex control problems. However, the application of these approaches to biomedical systems is still in its early stages. This work introduces dynamics-informed neural-network controllers as an alternative approach to control of medical digital twins. As a first use case for this method, the focus is on agent-based models, a versatile and increasingly common modeling platform in biomedicine. The effectiveness of the proposed neural-network control method is illustrated and benchmarked against other methods with two widely-used agent-based model types. The relevance of the method introduced here extends beyond medical digital twins to other complex dynamical systems.

Advances in peptide identification are revolutionizing our ability to decipher protein functions and accelerate therapeutic discovery. We present PDeepPP, a deep learning framework that integrates pretrained protein language models with parallel transformer-CNN architectures, achieving state-of-the-art performance in peptide characterization tasks. The model's hybrid architecture demonstrates unique capabilities in capturing both local sequence motifs and global structural features, as evidenced by 29% improved cluster separation in UMAP visualizations compared to conventional approaches. Evaluated across 33 biological recognition tasks - including post-translational modification site prediction and bioactive peptide identification - PDeepPP outperformed existing methods in 25 tasks with average AUC improvements of 4.2%. Notably, it achieved 0.9726 accuracy with PR AUC 0.9977 in antimicrobial peptide detection while reducing false negatives by 37.5% in antimalarial recognition scenarios. This framework enables accurate large-scale peptide analysis, achieving 218* acceleration over sequence-alignment-based methods while maintaining 99.5% specificity in critical glycosylation site detection.PDeepPP establishes a new paradigm for computational peptide analysis through its synergistic architecture design, enabling rapid yet precise functional annotation that bridges molecular pattern recognition with translational biomedical applications.We have made our implementation, including code, data, and pretrained models, publicly available via GitHub (https://github.com/fondress/PDeepPP) and Hugging Face (https://huggingface.co/fondress/PDeppPP).

Motivation: A perennial challenge for biomedical researchers and clinical practitioners is to stay abreast with the rapid growth of publications and medical notes. Natural language processing (NLP) has emerged as a promising direction for taming information overload. In particular, large neural language models facilitate transfer learning by pretraining on unlabeled text, as exemplified by the successes of BERT models in various NLP applications. However, fine-tuning such models for an end task remains challenging, especially with small labeled datasets, which are common in biomedical NLP. Results: We conduct a systematic study on fine-tuning stability in biomedical NLP. We show that finetuning performance may be sensitive to pretraining settings, especially in low-resource domains. Large models have potential to attain better performance, but increasing model size also exacerbates finetuning instability. We thus conduct a comprehensive exploration of techniques for addressing fine-tuning instability. We show that these techniques can substantially improve fine-tuning performance for lowresource biomedical NLP applications. Specifically, freezing lower layers is helpful for standard BERT-BASE models, while layerwise decay is more effective for BERT-LARGE and ELECTRA models. For low-resource text similarity tasks such as BIOSSES, reinitializing the top layer is the optimal strategy. Overall, domainspecific vocabulary and pretraining facilitate more robust models for fine-tuning. Based on these findings, we establish new state of the art on a wide range of biomedical NLP applications. Availability and implementation: To facilitate progress in biomedical NLP, we release our state-of-the-art pretrained and fine-tuned models: https://aka.ms/BLURB.

Pre-trained language models (PLMs) have been the de facto paradigm for most natural language processing (NLP) tasks. This also benefits biomedical domain: researchers from informatics, medicine, and computer science (CS) communities propose various PLMs trained on biomedical datasets, e.g., biomedical text, electronic health records, protein, and DNA sequences for various biomedical tasks. However, the cross-discipline characteristics of biomedical PLMs hinder their spreading among communities; some existing works are isolated from each other without comprehensive comparison and discussions. It expects a survey that not only systematically reviews recent advances of biomedical PLMs and their applications but also standardizes terminology and benchmarks. In this paper, we summarize the recent progress of pre-trained language models in the biomedical domain and their applications in biomedical downstream tasks. Particularly, we discuss the motivations and propose a taxonomy of existing biomedical PLMs. Their applications in biomedical downstream tasks are exhaustively discussed. At last, we illustrate various limitations and future trends, which we hope can provide inspiration for the future research of the research community.

Deep learning time-series processing often relies on convolutional neural networks with overlapping windows. This overlap allows the network to produce an output faster than the window length. However, it introduces additional computations. This work explores the potential to optimize computational efficiency during inference by exploiting convolution's shift-invariance properties to skip the calculation of layer activations between successive overlapping windows. Although convolutions are shift-invariant, zero-padding and pooling operations, widely used in such networks, are not efficient and complicate efficient streaming inference. We introduce StreamiNNC, a strategy to deploy Convolutional Neural Networks for online streaming inference. We explore the adverse effects of zero padding and pooling on the accuracy of streaming inference, deriving theoretical error upper bounds for pooling during streaming. We address these limitations by proposing signal padding and pooling alignment and provide guidelines for designing and deploying models for StreamiNNC. We validate our method in simulated data and on three real-world biomedical signal processing applications. StreamiNNC achieves a low deviation between streaming output and normal inference for all three networks (2.03 - 3.55% NRMSE). This work demonstrates that it is possible to linearly speed up the inference of streaming CNNs processing overlapping windows, negating the additional computation typically incurred by overlapping windows.

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.

A promising application of AI to healthcare is the retrieval of information from electronic health records (EHRs), e.g. to aid clinicians in finding relevant information for a consultation or to recruit suitable patients for a study. This requires search capabilities far beyond simple string matching, including the retrieval of concepts (diagnoses, symptoms, medications, etc.) related to the one in question. The suitability of AI methods for such applications is tested by predicting the relatedness of concepts with known relatedness scores. However, all existing biomedical concept relatedness datasets are notoriously small and consist of hand-picked concept pairs. We open-source a novel concept relatedness benchmark overcoming these issues: it is six times larger than existing datasets and concept pairs are chosen based on co-occurrence in EHRs, ensuring their relevance for the application of interest. We present an in-depth analysis of our new dataset and compare it to existing ones, highlighting that it is not only larger but also complements existing datasets in terms of the types of concepts included. Initial experiments with state-of-the-art embedding methods show that our dataset is a challenging new benchmark for testing concept relatedness models.

Constructing large-scaled medical knowledge graphs can significantly boost healthcare applications for medical surveillance, bring much attention from recent research. An essential step in constructing large-scale MKG is extracting information from medical reports. Recently, information extraction techniques have been proposed and show promising performance in biomedical information extraction. However, these methods only consider limited types of entity and relation due to the noisy biomedical text data with complex entity correlations. Thus, they fail to provide enough information for constructing MKGs and restrict the downstream applications. To address this issue, we propose Biomedical Information Extraction, a hybrid neural network to extract relations from biomedical text and unstructured medical reports. Our model utilizes a multi-head attention enhanced graph convolutional network to capture the complex relations and context information while resisting the noise from the data. We evaluate our model on two major biomedical relationship extraction tasks, chemical-disease relation and chemical-protein interaction, and a cross-hospital pan-cancer pathology report corpus. The results show that our method achieves superior performance than baselines. Furthermore, we evaluate the applicability of our method under a transfer learning setting and show that BioIE achieves promising performance in processing medical text from different formats and writing styles.

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

There has been an influx of biomedical domain-specific language models, showing language models pre-trained on biomedical text perform better on biomedical domain benchmarks than those trained on general domain text corpora such as Wikipedia and Books. Yet, most works do not study the factors affecting each domain language application deeply. Additionally, the study of model size on domain-specific models has been mostly missing. We empirically study and evaluate several factors that can affect performance on domain language applications, such as the sub-word vocabulary set, model size, pre-training corpus, and domain transfer. We show consistent improvements on benchmarks with our larger BioMegatron model trained on a larger domain corpus, contributing to our understanding of domain language model applications. We demonstrate noticeable improvements over the previous state-of-the-art (SOTA) on standard biomedical NLP benchmarks of named entity recognition, relation extraction, and question answering. Model checkpoints and code are available at [https://ngc.nvidia.com] and [https://github.com/NVIDIA/NeMo].

This paper presents the development of a prototype Automatic Speech Recognition (ASR) system specifically designed for Bengali biomedical data. Recent advancements in Bengali ASR are encouraging, but a lack of domain-specific data limits the creation of practical healthcare ASR models. This project bridges this gap by developing an ASR system tailored for Bengali medical terms like symptoms, severity levels, and diseases, encompassing two major dialects: Bengali and Sylheti. We train and evaluate two popular ASR frameworks on a comprehensive 46-hour Bengali medical corpus. Our core objective is to create deployable health-domain ASR systems for digital health applications, ultimately increasing accessibility for non-technical users in the healthcare sector.

Automated relation extraction (RE) from biomedical literature is critical for many downstream text mining applications in both research and real-world settings. However, most existing benchmarking datasets for bio-medical RE only focus on relations of a single type (e.g., protein-protein interactions) at the sentence level, greatly limiting the development of RE systems in biomedicine. In this work, we first review commonly used named entity recognition (NER) and RE datasets. Then we present BioRED, a first-of-its-kind biomedical RE corpus with multiple entity types (e.g., gene/protein, disease, chemical) and relation pairs (e.g., gene-disease; chemical-chemical) at the document level, on a set of 600 PubMed abstracts. Further, we label each relation as describing either a novel finding or previously known background knowledge, enabling automated algorithms to differentiate between novel and background information. We assess the utility of BioRED by benchmarking several existing state-of-the-art methods, including BERT-based models, on the NER and RE tasks. Our results show that while existing approaches can reach high performance on the NER task (F-score of 89.3%), there is much room for improvement for the RE task, especially when extracting novel relations (F-score of 47.7%). Our experiments also demonstrate that such a rich dataset can successfully facilitate the development of more accurate, efficient, and robust RE systems for biomedicine. The BioRED dataset and annotation guideline are freely available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BioRED/.

This work presents biomedical and clinical language models for Spanish by experimenting with different pretraining choices, such as masking at word and subword level, varying the vocabulary size and testing with domain data, looking for better language representations. Interestingly, in the absence of enough clinical data to train a model from scratch, we applied mixed-domain pretraining and cross-domain transfer approaches to generate a performant bio-clinical model suitable for real-world clinical data. We evaluated our models on Named Entity Recognition (NER) tasks for biomedical documents and challenging hospital discharge reports. When compared against the competitive mBERT and BETO models, we outperform them in all NER tasks by a significant margin. Finally, we studied the impact of the model's vocabulary on the NER performances by offering an interesting vocabulary-centric analysis. The results confirm that domain-specific pretraining is fundamental to achieving higher performances in downstream NER tasks, even within a mid-resource scenario. To the best of our knowledge, we provide the first biomedical and clinical transformer-based pretrained language models for Spanish, intending to boost native Spanish NLP applications in biomedicine. Our best models are freely available in the HuggingFace hub: https://huggingface.co/BSC-TeMU.

The increasing depth of parametric domain knowledge in large language models (LLMs) is fueling their rapid deployment in real-world applications. Understanding model vulnerabilities in high-stakes and knowledge-intensive tasks is essential for quantifying the trustworthiness of model predictions and regulating their use. The recent discovery of named entities as adversarial examples (i.e. adversarial entities) in natural language processing tasks raises questions about their potential impact on the knowledge robustness of pre-trained and finetuned LLMs in high-stakes and specialized domains. We examined the use of type-consistent entity substitution as a template for collecting adversarial entities for billion-parameter LLMs with biomedical knowledge. To this end, we developed an embedding-space attack based on powerscaled distance-weighted sampling to assess the robustness of their biomedical knowledge with a low query budget and controllable coverage. Our method has favorable query efficiency and scaling over alternative approaches based on random sampling and blackbox gradient-guided search, which we demonstrated for adversarial distractor generation in biomedical question answering. Subsequent failure mode analysis uncovered two regimes of adversarial entities on the attack surface with distinct characteristics and we showed that entity substitution attacks can manipulate token-wise Shapley value explanations, which become deceptive in this setting. Our approach complements standard evaluations for high-capacity models and the results highlight the brittleness of domain knowledge in LLMs.

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.

Biomedical image analysis is fundamental for biomedical discovery in cell biology, pathology, radiology, and many other biomedical domains. Holistic image analysis comprises interdependent subtasks such as segmentation, detection, and recognition of relevant objects. Here, we propose BiomedParse, a biomedical foundation model for imaging parsing that can jointly conduct segmentation, detection, and recognition for 82 object types across 9 imaging modalities. Through joint learning, we can improve accuracy for individual tasks and enable novel applications such as segmenting all relevant objects in an image through a text prompt, rather than requiring users to laboriously specify the bounding box for each object. We leveraged readily available natural-language labels or descriptions accompanying those datasets and use GPT-4 to harmonize the noisy, unstructured text information with established biomedical object ontologies. We created a large dataset comprising over six million triples of image, segmentation mask, and textual description. On image segmentation, we showed that BiomedParse is broadly applicable, outperforming state-of-the-art methods on 102,855 test image-mask-label triples across 9 imaging modalities (everything). On object detection, which aims to locate a specific object of interest, BiomedParse again attained state-of-the-art performance, especially on objects with irregular shapes (everywhere). On object recognition, which aims to identify all objects in a given image along with their semantic types, we showed that BiomedParse can simultaneously segment and label all biomedical objects in an image (all at once). In summary, BiomedParse is an all-in-one tool for biomedical image analysis by jointly solving segmentation, detection, and recognition for all major biomedical image modalities, paving the path for efficient and accurate image-based biomedical discovery.

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

Recent advances in context optimization (CoOp) guided by large language model (LLM)-distilled medical semantic priors offer a scalable alternative to manual prompt engineering and full fine-tuning for adapting biomedical CLIP-based vision-language models (VLMs). However, prompt learning in this context is challenged by semantic misalignment between LLMs and CLIP variants due to divergent training corpora and model architectures; it further lacks scalability across continuously evolving families of foundation models. More critically, pairwise multimodal alignment via conventional Euclidean-space optimization lacks the capacity to model unified representations or apply localized geometric constraints, which tends to amplify modality gaps in complex biomedical imaging and destabilize few-shot adaptation. In this work, we propose vMFCoOp, a framework that inversely estimates von Mises-Fisher (vMF) distributions on a shared Hyperspherical Manifold, aligning semantic biases between arbitrary LLMs and CLIP backbones via Unified Semantic Anchors to achieve robust biomedical prompting and superior few-shot classification. Grounded in three complementary constraints, vMFCoOp demonstrates consistent improvements across 14 medical datasets, 12 medical imaging modalities, and 13 anatomical regions, outperforming state-of-the-art methods in accuracy, generalization, and clinical applicability. This work aims to continuously expand to encompass more downstream applications, and the corresponding resources are intended to be shared through https://github.com/VinyehShaw/UniEqui.

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

Recent advancements in vision-language models (VLMs), such as CLIP, have demonstrated substantial success in self-supervised representation learning for vision tasks. However, effectively adapting VLMs to downstream applications remains challenging, as their accuracy often depends on time-intensive and expertise-demanding prompt engineering, while full model fine-tuning is costly. This is particularly true for biomedical images, which, unlike natural images, typically suffer from limited annotated datasets, unintuitive image contrasts, and nuanced visual features. Recent prompt learning techniques, such as Context Optimization (CoOp) intend to tackle these issues, but still fall short in generalizability. Meanwhile, explorations in prompt learning for biomedical image analysis are still highly limited. In this work, we propose BiomedCoOp, a novel prompt learning framework that enables efficient adaptation of BiomedCLIP for accurate and highly generalizable few-shot biomedical image classification. Our approach achieves effective prompt context learning by leveraging semantic consistency with average prompt ensembles from Large Language Models (LLMs) and knowledge distillation with a statistics-based prompt selection strategy. We conducted comprehensive validation of our proposed framework on 11 medical datasets across 9 modalities and 10 organs against existing state-of-the-art methods, demonstrating significant improvements in both accuracy and generalizability. The code is publicly available at https://github.com/HealthX-Lab/BiomedCoOp.

The development of domain-specific language models has significantly advanced natural language processing applications in various specialized fields, particularly in biomedicine. However, the focus has largely been on English-language models, leaving a gap for less-resourced languages such as Italian. This paper introduces Igea, the first decoder-only language model designed explicitly for biomedical text generation in Italian. Built on the Minerva model and continually pretrained on a diverse corpus of Italian medical texts, Igea is available in three model sizes: 350 million, 1 billion, and 3 billion parameters. The models aim to balance computational efficiency and performance, addressing the challenges of managing the peculiarities of medical terminology in Italian. We evaluate Igea using a mix of in-domain biomedical corpora and general-purpose benchmarks, highlighting its efficacy and retention of general knowledge even after the domain-specific training. This paper discusses the model's development and evaluation, providing a foundation for future advancements in Italian biomedical NLP.

Single-task models have proven pivotal in solving specific tasks; however, they have limitations in real-world applications where multi-tasking is necessary and domain shifts are exhibited. Recently, instructional prompts have shown significant improvement towards multi-task generalization; however, the effect of instructional prompts and Multi-Task Learning (MTL) has not been systematically studied in the biomedical domain. Motivated by this, this paper explores the impact of instructional prompts for biomedical MTL. We introduce the BoX, a collection of 32 instruction tasks for Biomedical NLP across (X) various categories. Using this meta-dataset, we propose a unified model termed In-BoXBART, that can jointly learn all tasks of the BoX without any task-specific modules. To the best of our knowledge, this is the first attempt to propose a unified model in the biomedical domain and use instructions to achieve generalization across several biomedical tasks. Experimental results indicate that the proposed model: 1) outperforms the single-task baseline by ~3% and multi-task (without instruction) baseline by ~18% on an average, and 2) shows ~23% improvement compared to the single-task baseline in few-shot learning (i.e., 32 instances per task) on an average. Our analysis indicates that there is significant room for improvement across tasks in the BoX, implying the scope for future research direction.

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

To enhance the performance of large language models (LLMs) in biomedical natural language processing (BioNLP) by introducing a domain-specific instruction dataset and examining its impact when combined with multi-task learning principles. We created the BioInstruct, comprising 25,005 instructions to instruction-tune LLMs(LLaMA 1 & 2, 7B & 13B version). The instructions were created by prompting the GPT-4 language model with three-seed samples randomly drawn from an 80 human curated instructions. We employed Low-Rank Adaptation(LoRA) for parameter-efficient fine-tuning. We then evaluated these instruction-tuned LLMs on several BioNLP tasks, which can be grouped into three major categories: question answering(QA), information extraction(IE), and text generation(GEN). We also examined whether categories(e.g., QA, IE, and generation) of instructions impact model performance. Comparing with LLMs without instruction-tuned, our instruction-tuned LLMs demonstrated marked performance gains: 17.3% in QA, 5.7% in IE, and 96% in Generation tasks. Our 7B-parameter instruction-tuned LLaMA 1 model was competitive or even surpassed other LLMs in the biomedical domain that were also fine-tuned from LLaMA 1 with vast domain-specific data or a variety of tasks. Our results also show that the performance gain is significantly higher when instruction fine-tuning is conducted with closely related tasks. Our findings align with the observations of multi-task learning, suggesting the synergies between two tasks. The BioInstruct dataset serves as a valuable resource and instruction tuned LLMs lead to the best performing BioNLP applications.

Pretrained language models such as Bidirectional Encoder Representations from Transformers (BERT) have achieved state-of-the-art performance in natural language processing (NLP) tasks. Recently, BERT has been adapted to the biomedical domain. Despite the effectiveness, these models have hundreds of millions of parameters and are computationally expensive when applied to large-scale NLP applications. We hypothesized that the number of parameters of the original BERT can be dramatically reduced with minor impact on performance. In this study, we present Bioformer, a compact BERT model for biomedical text mining. We pretrained two Bioformer models (named Bioformer8L and Bioformer16L) which reduced the model size by 60% compared to BERTBase. Bioformer uses a biomedical vocabulary and was pre-trained from scratch on PubMed abstracts and PubMed Central full-text articles. We thoroughly evaluated the performance of Bioformer as well as existing biomedical BERT models including BioBERT and PubMedBERT on 15 benchmark datasets of four different biomedical NLP tasks: named entity recognition, relation extraction, question answering and document classification. The results show that with 60% fewer parameters, Bioformer16L is only 0.1% less accurate than PubMedBERT while Bioformer8L is 0.9% less accurate than PubMedBERT. Both Bioformer16L and Bioformer8L outperformed BioBERTBase-v1.1. In addition, Bioformer16L and Bioformer8L are 2-3 fold as fast as PubMedBERT/BioBERTBase-v1.1. Bioformer has been successfully deployed to PubTator Central providing gene annotations over 35 million PubMed abstracts and 5 million PubMed Central full-text articles. We make Bioformer publicly available via https://github.com/WGLab/bioformer, including pre-trained models, datasets, and instructions for downstream use.

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

Large Language Models (LLMs) have achieved remarkable success in natural language processing through strong semantic understanding and generation. However, their black-box nature limits structured and multi-hop reasoning. In contrast, Text-Attributed Graphs (TAGs) provide explicit relational structures enriched with textual context, yet often lack semantic depth. Recent research shows that combining LLMs and TAGs yields complementary benefits: enhancing TAG representation learning and improving the reasoning and interpretability of LLMs. This survey provides the first systematic review of LLM--TAG integration from an orchestration perspective. We introduce a novel taxonomy covering two fundamental directions: LLM for TAG, where LLMs enrich graph-based tasks, and TAG for LLM, where structured graphs improve LLM reasoning. We categorize orchestration strategies into sequential, parallel, and multi-module frameworks, and discuss advances in TAG-specific pretraining, prompting, and parameter-efficient fine-tuning. Beyond methodology, we summarize empirical insights, curate available datasets, and highlight diverse applications across recommendation systems, biomedical analysis, and knowledge-intensive question answering. Finally, we outline open challenges and promising research directions, aiming to guide future work at the intersection of language and graph learning.

Geometric alignment appears in a variety of applications, ranging from domain adaptation, optimal transport, and normalizing flows in machine learning; optical flow and learned augmentation in computer vision and deformable registration within biomedical imaging. A recurring challenge is the alignment of domains whose topology is not the same; a problem that is routinely ignored, potentially introducing bias in downstream analysis. As a first step towards solving such alignment problems, we propose an unsupervised algorithm for the detection of changes in image topology. The model is based on a conditional variational auto-encoder and detects topological changes between two images during the registration step. We account for both topological changes in the image under spatial variation and unexpected transformations. Our approach is validated on two tasks and datasets: detection of topological changes in microscopy images of cells, and unsupervised anomaly detection brain imaging.

Large language models and autonomous AI agents have evolved rapidly, resulting in a diverse array of evaluation benchmarks, frameworks, and collaboration protocols. However, the landscape remains fragmented and lacks a unified taxonomy or comprehensive survey. Therefore, we present a side-by-side comparison of benchmarks developed between 2019 and 2025 that evaluate these models and agents across multiple domains. In addition, we propose a taxonomy of approximately 60 benchmarks that cover general and academic knowledge reasoning, mathematical problem-solving, code generation and software engineering, factual grounding and retrieval, domain-specific evaluations, multimodal and embodied tasks, task orchestration, and interactive assessments. Furthermore, we review AI-agent frameworks introduced between 2023 and 2025 that integrate large language models with modular toolkits to enable autonomous decision-making and multi-step reasoning. Moreover, we present real-world applications of autonomous AI agents in materials science, biomedical research, academic ideation, software engineering, synthetic data generation, chemical reasoning, mathematical problem-solving, geographic information systems, multimedia, healthcare, and finance. We then survey key agent-to-agent collaboration protocols, namely the Agent Communication Protocol (ACP), the Model Context Protocol (MCP), and the Agent-to-Agent Protocol (A2A). Finally, we discuss recommendations for future research, focusing on advanced reasoning strategies, failure modes in multi-agent LLM systems, automated scientific discovery, dynamic tool integration via reinforcement learning, integrated search capabilities, and security vulnerabilities in agent protocols.

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.

Medical text embedding models are foundational to a wide array of healthcare applications, ranging from clinical decision support and biomedical information retrieval to medical question answering, yet they remain hampered by two critical shortcomings. First, most models are trained on a narrow slice of medical and biological data, beside not being up to date in terms of methodology, making them ill suited to capture the diversity of terminology and semantics encountered in practice. Second, existing evaluations are often inadequate: even widely used benchmarks fail to generalize across the full spectrum of real world medical tasks. To address these gaps, we leverage MEDTE, a GTE model extensively fine-tuned on diverse medical corpora through self-supervised contrastive learning across multiple data sources, to deliver robust medical text embeddings. Alongside this model, we propose a comprehensive benchmark suite of 51 tasks spanning classification, clustering, pair classification, and retrieval modeled on the Massive Text Embedding Benchmark (MTEB) but tailored to the nuances of medical text. Our results demonstrate that this combined approach not only establishes a robust evaluation framework but also yields embeddings that consistently outperform state of the art alternatives in different tasks.

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.

Large Vision-Language Models (LVLMs) have demonstrated remarkable performance in performing complex multimodal tasks. However, they are still plagued by object hallucination: the misidentification or misclassification of objects present in images. To this end, we propose HALLUCINOGEN, a novel visual question answering (VQA) object hallucination attack benchmark that utilizes diverse contextual reasoning prompts to evaluate object hallucination in state-of-the-art LVLMs. We design a series of contextual reasoning hallucination prompts to evaluate LVLMs' ability to accurately identify objects in a target image while asking them to perform diverse visual-language tasks such as identifying, locating or performing visual reasoning around specific objects. Further, we extend our benchmark to high-stakes medical applications and introduce MED-HALLUCINOGEN, hallucination attacks tailored to the biomedical domain, and evaluate the hallucination performance of LVLMs on medical images, a critical area where precision is crucial. Finally, we conduct extensive evaluations of eight LVLMs and two hallucination mitigation strategies across multiple datasets to show that current generic and medical LVLMs remain susceptible to hallucination attacks.

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.

Accurate and efficient dense depth reconstruction from light field imagery remains a central challenge in computer vision, underpinning applications such as augmented reality, biomedical imaging, and 3D scene reconstruction. Existing deep convolutional approaches, while effective, often incur high computational overhead and are sensitive to noise and disparity inconsistencies in real-world scenarios. This paper introduces a novel Deep Spectral Epipolar Representation (DSER) framework for dense light field reconstruction, which unifies deep spectral feature learning with epipolar-domain regularization. The proposed approach exploits frequency-domain correlations across epipolar plane images to enforce global structural coherence, thereby mitigating artifacts and enhancing depth accuracy. Unlike conventional supervised models, DSER operates efficiently with limited training data while maintaining high reconstruction fidelity. Comprehensive experiments on the 4D Light Field Benchmark and a diverse set of real-world datasets demonstrate that DSER achieves superior performance in terms of precision, structural consistency, and computational efficiency compared to state-of-the-art methods. These results highlight the potential of integrating spectral priors with epipolar geometry for scalable and noise-resilient dense light field depth estimation, establishing DSER as a promising direction for next-generation high-dimensional vision systems.

The semantic capabilities of large language models (LLMs) have the potential to enable rich analytics and reasoning over vast knowledge corpora. Unfortunately, existing systems either empirically optimize expensive LLM-powered operations with no performance guarantees, or serve a limited set of row-wise LLM operations, providing limited robustness, expressiveness and usability. We introduce semantic operators, the first formalism for declarative and general-purpose AI-based transformations based on natural language specifications (e.g., filtering, sorting, joining or aggregating records using natural language criteria). Each operator opens a rich space for execution plans, similar to relational operators. Our model specifies the expected behavior of each operator with a high-quality gold algorithm, and we develop an optimization framework that reduces cost, while providing accuracy guarantees with respect to a gold algorithm. Using this approach, we propose several novel optimizations to accelerate semantic filtering, joining, group-by and top-k operations by up to 1,000times. We implement semantic operators in the LOTUS system and demonstrate LOTUS' effectiveness on real, bulk-semantic processing applications, including fact-checking, biomedical multi-label classification, search, and topic analysis. We show that the semantic operator model is expressive, capturing state-of-the-art AI pipelines in a few operator calls, and making it easy to express new pipelines that match or exceed quality of recent LLM-based analytic systems by up to 170%, while offering accuracy guarantees. Overall, LOTUS programs match or exceed the accuracy of state-of-the-art AI pipelines for each task while running up to 3.6times faster than the highest-quality baselines. LOTUS is publicly available at https://github.com/lotus-data/lotus.

Machine learning force fields (MLFF) have been proposed to accelerate molecular dynamics (MD) simulation, which finds widespread applications in chemistry and biomedical research. Even for the most data-efficient MLFFs, reaching chemical accuracy can require hundreds of frames of force and energy labels generated by expensive quantum mechanical algorithms, which may scale as O(n^3) to O(n^7), with n proportional to the number of basis functions. To address this issue, we propose a multi-stage computational framework -- ASTEROID, which lowers the data cost of MLFFs by leveraging a combination of cheap inaccurate data and expensive accurate data. The motivation behind ASTEROID is that inaccurate data, though incurring large bias, can help capture the sophisticated structures of the underlying force field. Therefore, we first train a MLFF model on a large amount of inaccurate training data, employing a bias-aware loss function to prevent the model from overfitting tahe potential bias of this data. We then fine-tune the obtained model using a small amount of accurate training data, which preserves the knowledge learned from the inaccurate training data while significantly improving the model's accuracy. Moreover, we propose a variant of ASTEROID based on score matching for the setting where the inaccurate training data are unlabeled. Extensive experiments on MD datasets and downstream tasks validate the efficacy of ASTEROID. Our code and data are available at https://github.com/abukharin3/asteroid.

This study leverages the data representation capability of fuzzy based membership-mappings for practical secure distributed deep learning using fully homomorphic encryption. The impracticality issue of secure machine (deep) learning with fully homomorphic encrypted data, arising from large computational overhead, is addressed via applying fuzzy attributes. Fuzzy attributes are induced by globally convergent and robust variational membership-mappings based local deep models. Fuzzy attributes combine the local deep models in a robust and flexible manner such that the global model can be evaluated homomorphically in an efficient manner using a boolean circuit composed of bootstrapped binary gates. The proposed method, while preserving privacy in a distributed learning scenario, remains accurate, practical, and scalable. The method is evaluated through numerous experiments including demonstrations through MNIST dataset and Freiburg Groceries Dataset. Further, a biomedical application related to mental stress detection on individuals is considered.

In order to develop machine learning and deep learning models that take into account the guidelines and principles of trustworthy AI, a novel information theoretic trustworthy AI framework is introduced. A unified approach to "privacy-preserving interpretable and transferable learning" is considered for studying and optimizing the tradeoffs between privacy, interpretability, and transferability aspects. A variational membership-mapping Bayesian model is used for the analytical approximations of the defined information theoretic measures for privacy-leakage, interpretability, and transferability. The approach consists of approximating the information theoretic measures via maximizing a lower-bound using variational optimization. The study presents a unified information theoretic approach to study different aspects of trustworthy AI in a rigorous analytical manner. The approach is demonstrated through numerous experiments on benchmark datasets and a real-world biomedical application concerned with the detection of mental stress on individuals using heart rate variability analysis.

Large language models (LLM) have demonstrated remarkable capabilities in various biomedical natural language processing (NLP) tasks, leveraging the demonstration within the input context to adapt to new tasks. However, LLM is sensitive to the selection of demonstrations. To address the hallucination issue inherent in LLM, retrieval-augmented LLM (RAL) offers a solution by retrieving pertinent information from an established database. Nonetheless, existing research work lacks rigorous evaluation of the impact of retrieval-augmented large language models on different biomedical NLP tasks. This deficiency makes it challenging to ascertain the capabilities of RAL within the biomedical domain. Moreover, the outputs from RAL are affected by retrieving the unlabeled, counterfactual, or diverse knowledge that is not well studied in the biomedical domain. However, such knowledge is common in the real world. Finally, exploring the self-awareness ability is also crucial for the RAL system. So, in this paper, we systematically investigate the impact of RALs on 5 different biomedical tasks (triple extraction, link prediction, classification, question answering, and natural language inference). We analyze the performance of RALs in four fundamental abilities, including unlabeled robustness, counterfactual robustness, diverse robustness, and negative awareness. To this end, we proposed an evaluation framework to assess the RALs' performance on different biomedical NLP tasks and establish four different testbeds based on the aforementioned fundamental abilities. Then, we evaluate 3 representative LLMs with 3 different retrievers on 5 tasks over 9 datasets.

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.

Biomedical text mining is becoming increasingly important as the number of biomedical documents rapidly grows. With the progress in natural language processing (NLP), extracting valuable information from biomedical literature has gained popularity among researchers, and deep learning has boosted the development of effective biomedical text mining models. However, directly applying the advancements in NLP to biomedical text mining often yields unsatisfactory results due to a word distribution shift from general domain corpora to biomedical corpora. In this article, we investigate how the recently introduced pre-trained language model BERT can be adapted for biomedical corpora. We introduce BioBERT (Bidirectional Encoder Representations from Transformers for Biomedical Text Mining), which is a domain-specific language representation model pre-trained on large-scale biomedical corpora. With almost the same architecture across tasks, BioBERT largely outperforms BERT and previous state-of-the-art models in a variety of biomedical text mining tasks when pre-trained on biomedical corpora. While BERT obtains performance comparable to that of previous state-of-the-art models, BioBERT significantly outperforms them on the following three representative biomedical text mining tasks: biomedical named entity recognition (0.62% F1 score improvement), biomedical relation extraction (2.80% F1 score improvement) and biomedical question answering (12.24% MRR improvement). Our analysis results show that pre-training BERT on biomedical corpora helps it to understand complex biomedical texts. We make the pre-trained weights of BioBERT freely available at https://github.com/naver/biobert-pretrained, and the source code for fine-tuning BioBERT available at https://github.com/dmis-lab/biobert.

This study evaluated the effect of BioBERT in medical text processing for the task of medical named entity recognition. Through comparative experiments with models such as BERT, ClinicalBERT, SciBERT, and BlueBERT, the results showed that BioBERT achieved the best performance in both precision and F1 score, verifying its applicability and superiority in the medical field. BioBERT enhances its ability to understand professional terms and complex medical texts through pre-training on biomedical data, providing a powerful tool for medical information extraction and clinical decision support. The study also explored the privacy and compliance challenges of BioBERT when processing medical data, and proposed future research directions for combining other medical-specific models to improve generalization and robustness. With the development of deep learning technology, the potential of BioBERT in application fields such as intelligent medicine, personalized treatment, and disease prediction will be further expanded. Future research can focus on the real-time and interpretability of the model to promote its widespread application in the medical field.

The advancement of natural language processing (NLP) in biology hinges on models' ability to interpret intricate biomedical literature. Traditional models often struggle with the complex and domain-specific language in this field. In this paper, we present BioMamba, a pre-trained model specifically designed for biomedical text mining. BioMamba builds upon the Mamba architecture and is pre-trained on an extensive corpus of biomedical literature. Our empirical studies demonstrate that BioMamba significantly outperforms models like BioBERT and general-domain Mamba across various biomedical tasks. For instance, BioMamba achieves a 100 times reduction in perplexity and a 4 times reduction in cross-entropy loss on the BioASQ test set. We provide an overview of the model architecture, pre-training process, and fine-tuning techniques. Additionally, we release the code and trained model to facilitate further research.

Biomedical text mining is becoming increasingly important as the number of biomedical documents and web data rapidly grows. Recently, word representation models such as BERT has gained popularity among researchers. However, it is difficult to estimate their performance on datasets containing biomedical texts as the word distributions of general and biomedical corpora are quite different. Moreover, the medical domain has long-tail concepts and terminologies that are difficult to be learned via language models. For the Chinese biomedical text, it is more difficult due to its complex structure and the variety of phrase combinations. In this paper, we investigate how the recently introduced pre-trained language model BERT can be adapted for Chinese biomedical corpora and propose a novel conceptualized representation learning approach. We also release a new Chinese Biomedical Language Understanding Evaluation benchmark (ChineseBLUE). We examine the effectiveness of Chinese pre-trained models: BERT, BERT-wwm, RoBERTa, and our approach. Experimental results on the benchmark show that our approach could bring significant gain. We release the pre-trained model on GitHub: https://github.com/alibaba-research/ChineseBLUE.

Biomedical text mining and question-answering are essential yet highly demanding tasks, particularly in the face of the exponential growth of biomedical literature. In this work, we present our participation in the 13th edition of the BioASQ challenge, which involves biomedical semantic question-answering for Task 13b and biomedical question-answering for developing topics for the Synergy task. We deploy a selection of open-source large language models (LLMs) as retrieval-augmented generators to answer biomedical questions. Various models are used to process the questions. A majority voting system combines their output to determine the final answer for Yes/No questions, while for list and factoid type questions, the union of their answers in used. We evaluated 13 state-of-the-art open source LLMs, exploring all possible model combinations to contribute to the final answer, resulting in tailored LLM pipelines for each question type. Our findings provide valuable insight into which combinations of LLMs consistently produce superior results for specific question types. In the four rounds of the 2025 BioASQ challenge, our system achieved notable results: in the Synergy task, we secured 1st place for ideal answers and 2nd place for exact answers in round 2, as well as two shared 1st places for exact answers in round 3 and 4.

Information retrieval (IR) is essential in biomedical knowledge acquisition and clinical decision support. While recent progress has shown that language model encoders perform better semantic retrieval, training such models requires abundant query-article annotations that are difficult to obtain in biomedicine. As a result, most biomedical IR systems only conduct lexical matching. In response, we introduce BioCPT, a first-of-its-kind Contrastively Pre-trained Transformer model for zero-shot biomedical IR. To train BioCPT, we collected an unprecedented scale of 255 million user click logs from PubMed. With such data, we use contrastive learning to train a pair of closely-integrated retriever and re-ranker. Experimental results show that BioCPT sets new state-of-the-art performance on five biomedical IR tasks, outperforming various baselines including much larger models such as GPT-3-sized cpt-text-XL. In addition, BioCPT also generates better biomedical article and sentence representations for semantic evaluations. As such, BioCPT can be readily applied to various real-world biomedical IR tasks. BioCPT API and code are publicly available at https://github.com/ncbi/BioCPT.

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.

Biomedical researchers increasingly rely on large-scale structured databases for complex analytical tasks. However, current text-to-SQL systems often struggle to map qualitative scientific questions into executable SQL, particularly when implicit domain reasoning is required. We introduce BiomedSQL, the first benchmark explicitly designed to evaluate scientific reasoning in text-to-SQL generation over a real-world biomedical knowledge base. BiomedSQL comprises 68,000 question/SQL query/answer triples grounded in a harmonized BigQuery knowledge base that integrates gene-disease associations, causal inference from omics data, and drug approval records. Each question requires models to infer domain-specific criteria, such as genome-wide significance thresholds, effect directionality, or trial phase filtering, rather than rely on syntactic translation alone. We evaluate a range of open- and closed-source LLMs across prompting strategies and interaction paradigms. Our results reveal a substantial performance gap: GPT-o3-mini achieves 59.0% execution accuracy, while our custom multi-step agent, BMSQL, reaches 62.6%, both well below the expert baseline of 90.0%. BiomedSQL provides a new foundation for advancing text-to-SQL systems capable of supporting scientific discovery through robust reasoning over structured biomedical knowledge bases. Our dataset is publicly available at https://huggingface.co/datasets/NIH-CARD/BiomedSQL, and our code is open-source at https://github.com/NIH-CARD/biomedsql.

Keeping track of scientific challenges, advances and emerging directions is a fundamental part of research. However, researchers face a flood of papers that hinders discovery of important knowledge. In biomedicine, this directly impacts human lives. To address this problem, we present a novel task of extraction and search of scientific challenges and directions, to facilitate rapid knowledge discovery. We construct and release an expert-annotated corpus of texts sampled from full-length papers, labeled with novel semantic categories that generalize across many types of challenges and directions. We focus on a large corpus of interdisciplinary work relating to the COVID-19 pandemic, ranging from biomedicine to areas such as AI and economics. We apply a model trained on our data to identify challenges and directions across the corpus and build a dedicated search engine. In experiments with 19 researchers and clinicians using our system, we outperform a popular scientific search engine in assisting knowledge discovery. Finally, we show that models trained on our resource generalize to the wider biomedical domain and to AI papers, highlighting its broad utility. We make our data, model and search engine publicly available. https://challenges.apps.allenai.org/

Named entity recognition (NER) stands as a fundamental and pivotal task within the realm of Natural Language Processing. Particularly within the domain of Biomedical Method NER, this task presents notable challenges, stemming from the continual influx of domain-specific terminologies in scholarly literature. Current research in Biomedical Method (BioMethod) NER suffers from a scarcity of resources, primarily attributed to the intricate nature of methodological concepts, which necessitate a profound understanding for precise delineation. In this study, we propose a novel dataset for biomedical method entity recognition, employing an automated BioMethod entity recognition and information retrieval system to assist human annotation. Furthermore, we comprehensively explore a range of conventional and contemporary open-domain NER methodologies, including the utilization of cutting-edge large-scale language models (LLMs) customised to our dataset. Our empirical findings reveal that the large parameter counts of language models surprisingly inhibit the effective assimilation of entity extraction patterns pertaining to biomedical methods. Remarkably, the approach, leveraging the modestly sized ALBERT model (only 11MB), in conjunction with conditional random fields (CRF), achieves state-of-the-art (SOTA) performance.

Recent advancements in biological research leverage the integration of molecules, proteins, and natural language to enhance drug discovery. However, current models exhibit several limitations, such as the generation of invalid molecular SMILES, underutilization of contextual information, and equal treatment of structured and unstructured knowledge. To address these issues, we propose BioT5, a comprehensive pre-training framework that enriches cross-modal integration in biology with chemical knowledge and natural language associations. BioT5 utilizes SELFIES for 100% robust molecular representations and extracts knowledge from the surrounding context of bio-entities in unstructured biological literature. Furthermore, BioT5 distinguishes between structured and unstructured knowledge, leading to more effective utilization of information. After fine-tuning, BioT5 shows superior performance across a wide range of tasks, demonstrating its strong capability of capturing underlying relations and properties of bio-entities. Our code is available at https://github.com/QizhiPei/BioT5{Github}.

This paper presents the formal release of MedMentions, a new manually annotated resource for the recognition of biomedical concepts. What distinguishes MedMentions from other annotated biomedical corpora is its size (over 4,000 abstracts and over 350,000 linked mentions), as well as the size of the concept ontology (over 3 million concepts from UMLS 2017) and its broad coverage of biomedical disciplines. In addition to the full corpus, a sub-corpus of MedMentions is also presented, comprising annotations for a subset of UMLS 2017 targeted towards document retrieval. To encourage research in Biomedical Named Entity Recognition and Linking, data splits for training and testing are included in the release, and a baseline model and its metrics for entity linking are also described.

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

Foundation models (FMs) have exhibited remarkable performance across a wide range of downstream tasks in many domains. Nevertheless, general-purpose FMs often face challenges when confronted with domain-specific problems, due to their limited access to the proprietary training data in a particular domain. In biomedicine, there are various biological modalities, such as molecules, proteins, and cells, which are encoded by the language of life and exhibit significant modality gaps with human natural language. In this paper, we introduce BioMedGPT, an open multimodal generative pre-trained transformer (GPT) for biomedicine, to bridge the gap between the language of life and human natural language. BioMedGPT allows users to easily ``communicate'' with diverse biological modalities through free text, which is the first of its kind. BioMedGPT aligns different biological modalities with natural language via a large generative language model, namely, BioMedGPT-LM. We publish BioMedGPT-10B, which unifies the feature spaces of molecules, proteins, and natural language via encoding and alignment. Through fine-tuning, BioMedGPT-10B outperforms or is on par with human and significantly larger general-purpose foundation models on the biomedical QA task. It also demonstrates promising performance in the molecule QA and protein QA tasks, which could greatly accelerate the discovery of new drugs and therapeutic targets. In addition, BioMedGPT-LM-7B is the first large generative language model based on Llama2 in the biomedical domain, therefore is commercial friendly. Both BioMedGPT-10B and BioMedGPT-LM-7B are open-sourced to the research community. In addition, we publish the datasets that are meticulously curated for the alignment of multi-modalities, i.e., PubChemQA and UniProtQA. All the models, codes, and datasets are available at https://github.com/PharMolix/OpenBioMed.

Scientific discovery relies on scientists generating novel hypotheses that undergo rigorous experimental validation. To augment this process, we introduce an AI co-scientist, a multi-agent system built on Gemini 2.0. The AI co-scientist is intended to help uncover new, original knowledge and to formulate demonstrably novel research hypotheses and proposals, building upon prior evidence and aligned to scientist-provided research objectives and guidance. The system's design incorporates a generate, debate, and evolve approach to hypothesis generation, inspired by the scientific method and accelerated by scaling test-time compute. Key contributions include: (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling; (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute, improving hypothesis quality. While general purpose, we focus development and validation in three biomedical areas: drug repurposing, novel target discovery, and explaining mechanisms of bacterial evolution and anti-microbial resistance. For drug repurposing, the system proposes candidates with promising validation findings, including candidates for acute myeloid leukemia that show tumor inhibition in vitro at clinically applicable concentrations. For novel target discovery, the AI co-scientist proposed new epigenetic targets for liver fibrosis, validated by anti-fibrotic activity and liver cell regeneration in human hepatic organoids. Finally, the AI co-scientist recapitulated unpublished experimental results via a parallel in silico discovery of a novel gene transfer mechanism in bacterial evolution. These results, detailed in separate, co-timed reports, demonstrate the potential to augment biomedical and scientific discovery and usher an era of AI empowered scientists.

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

With the advent of artificial intelligence (AI), many researchers are attempting to extract structured information from document-level biomedical literature by fine-tuning large language models (LLMs). However, they face significant challenges such as the need for expensive hardware, like high-performance GPUs and the high labor costs associated with annotating training datasets, especially in biomedical realm. Recent research on LLMs, such as GPT-4 and Llama3, has shown promising performance in zero-shot settings, inspiring us to explore a novel approach to achieve the same results from unannotated full documents using general LLMs with lower hardware and labor costs. Our approach combines two major stages: named entity recognition (NER) and relation extraction (RE). NER identifies chemical, disease and gene entities from the document with synonym and hypernym extraction using an LLM with a crafted prompt. RE extracts relations between entities based on predefined relation schemas and prompts. To enhance the effectiveness of prompt, we propose a five-part template structure and a scenario-based prompt design principles, along with evaluation method to systematically assess the prompts. Finally, we evaluated our approach against fine-tuning and pre-trained models on two biomedical datasets: ChemDisGene and CDR. The experimental results indicate that our proposed method can achieve comparable accuracy levels to fine-tuning and pre-trained models but with reduced human and hardware expenses.

Computing in the life sciences has undergone a transformative evolution, from early computational models in the 1950s to the applications of artificial intelligence (AI) and machine learning (ML) seen today. This paper highlights key milestones and technological advancements through the historical development of computing in the life sciences. The discussion includes the inception of computational models for biological processes, the advent of bioinformatics tools, and the integration of AI/ML in modern life sciences research. Attention is given to AI-enabled tools used in the life sciences, such as scientific large language models and bio-AI tools, examining their capabilities, limitations, and impact to biological risk. This paper seeks to clarify and establish essential terminology and concepts to ensure informed decision-making and effective communication across disciplines.

Biomedical research is growing at such an exponential pace that scientists, researchers, and practitioners are no more able to cope with the amount of published literature in the domain. The knowledge presented in the literature needs to be systematized in such a way that claims and hypotheses can be easily found, accessed, and validated. Knowledge graphs can provide such a framework for semantic knowledge representation from literature. However, in order to build a knowledge graph, it is necessary to extract knowledge as relationships between biomedical entities and normalize both entities and relationship types. In this paper, we present and compare few rule-based and machine learning-based (Naive Bayes, Random Forests as examples of traditional machine learning methods and DistilBERT, PubMedBERT, T5 and SciFive-based models as examples of modern deep learning transformers) methods for scalable relationship extraction from biomedical literature, and for the integration into the knowledge graphs. We examine how resilient are these various methods to unbalanced and fairly small datasets. Our experiments show that transformer-based models handle well both small (due to pre-training on a large dataset) and unbalanced datasets. The best performing model was the PubMedBERT-based model fine-tuned on balanced data, with a reported F1-score of 0.92. DistilBERT-based model followed with F1-score of 0.89, performing faster and with lower resource requirements. BERT-based models performed better then T5-based generative models.

Large Language Models (LLMs) demonstrate remarkable versatility in various NLP tasks but encounter distinct challenges in biomedical due to the complexities of language and data scarcity. This paper investigates LLMs application in the biomedical domain by exploring strategies to enhance their performance for the NER task. Our study reveals the importance of meticulously designed prompts in the biomedical. Strategic selection of in-context examples yields a marked improvement, offering ~15-20\% increase in F1 score across all benchmark datasets for biomedical few-shot NER. Additionally, our results indicate that integrating external biomedical knowledge via prompting strategies can enhance the proficiency of general-purpose LLMs to meet the specialized needs of biomedical NER. Leveraging a medical knowledge base, our proposed method, DiRAG, inspired by Retrieval-Augmented Generation (RAG), can boost the zero-shot F1 score of LLMs for biomedical NER. Code is released at https://github.com/masoud-monajati/LLM_Bio_NER

Language models pre-trained on biomedical corpora, such as BioBERT, have recently shown promising results on downstream biomedical tasks. Many existing pre-trained models, on the other hand, are resource-intensive and computationally heavy owing to factors such as embedding size, hidden dimension, and number of layers. The natural language processing (NLP) community has developed numerous strategies to compress these models utilising techniques such as pruning, quantisation, and knowledge distillation, resulting in models that are considerably faster, smaller, and subsequently easier to use in practice. By the same token, in this paper we introduce six lightweight models, namely, BioDistilBERT, BioTinyBERT, BioMobileBERT, DistilBioBERT, TinyBioBERT, and CompactBioBERT which are obtained either by knowledge distillation from a biomedical teacher or continual learning on the Pubmed dataset via the Masked Language Modelling (MLM) objective. We evaluate all of our models on three biomedical tasks and compare them with BioBERT-v1.1 to create efficient lightweight models that perform on par with their larger counterparts. All the models will be publicly available on our Huggingface profile at https://huggingface.co/nlpie and the codes used to run the experiments will be available at https://github.com/nlpie-research/Compact-Biomedical-Transformers.

This work introduces BioLORD, a new pre-training strategy for producing meaningful representations for clinical sentences and biomedical concepts. State-of-the-art methodologies operate by maximizing the similarity in representation of names referring to the same concept, and preventing collapse through contrastive learning. However, because biomedical names are not always self-explanatory, it sometimes results in non-semantic representations. BioLORD overcomes this issue by grounding its concept representations using definitions, as well as short descriptions derived from a multi-relational knowledge graph consisting of biomedical ontologies. Thanks to this grounding, our model produces more semantic concept representations that match more closely the hierarchical structure of ontologies. BioLORD establishes a new state of the art for text similarity on both clinical sentences (MedSTS) and biomedical concepts (MayoSRS).

Understanding the biological mechanism of disease is critical for medicine, and in particular drug discovery. AI-powered analysis of genome-scale biological data hold great potential in this regard. The increasing availability of single-cell RNA sequencing data has enabled the development of large foundation models for disease biology. However, existing foundation models either do not improve or only modestly improve over task-specific models in downstream applications. Here, we explored two avenues for improving the state-of-the-art. First, we scaled the pre-training dataset to 116 million cells, which is larger than those used by previous models. Second, we leveraged the availability of large-scale biological annotations as a form of supervision during pre-training. We trained the TEDDY family of models comprising six transformer-based state-of-the-art single-cell foundation models with 70 million, 160 million, and 400 million parameters. We vetted our models on two downstream evaluation tasks -- identifying the underlying disease state of held-out donors not seen during training and distinguishing healthy cells from diseased ones for disease conditions and donors not seen during training. Scaling experiments showed that performance improved predictably with both data volume and parameter count. Our models showed substantial improvement over existing work on the first task and more muted improvements on the second.

Biomedical knowledge graphs (BioMedKGs) are essential infrastructures for biomedical and healthcare big data and artificial intelligence (AI), facilitating natural language processing, model development, and data exchange. For decades, these knowledge graphs have been developed via expert curation; however, this method can no longer keep up with today's AI development, and a transition to algorithmically generated BioMedKGs is necessary. In this work, we introduce the Biomedical Informatics Ontology System (BIOS), the first large-scale publicly available BioMedKG generated completely by machine learning algorithms. BIOS currently contains 4.1 million concepts, 7.4 million terms in two languages, and 7.3 million relation triplets. We present the methodology for developing BIOS, including the curation of raw biomedical terms, computational identification of synonymous terms and aggregation of these terms to create concept nodes, semantic type classification of the concepts, relation identification, and biomedical machine translation. We provide statistics on the current BIOS content and perform preliminary assessments of term quality, synonym grouping, and relation extraction. The results suggest that machine learning-based BioMedKG development is a viable alternative to traditional expert curation.

Foundation models (FMs) are able to leverage large volumes of unlabeled data to demonstrate superior performance across a wide range of tasks. However, FMs developed for biomedical domains have largely remained unimodal, i.e., independently trained and used for tasks on protein sequences alone, small molecule structures alone, or clinical data alone. To overcome this limitation of biomedical FMs, we present BioBridge, a novel parameter-efficient learning framework, to bridge independently trained unimodal FMs to establish multimodal behavior. BioBridge achieves it by utilizing Knowledge Graphs (KG) to learn transformations between one unimodal FM and another without fine-tuning any underlying unimodal FMs. Our empirical results demonstrate that BioBridge can beat the best baseline KG embedding methods (on average by around 76.3%) in cross-modal retrieval tasks. We also identify BioBridge demonstrates out-of-domain generalization ability by extrapolating to unseen modalities or relations. Additionally, we also show that BioBridge presents itself as a general purpose retriever that can aid biomedical multimodal question answering as well as enhance the guided generation of novel drugs.

Medical research generates a large number of publications with the PubMed database already containing >35 million research articles. Integration of the knowledge scattered across this large body of literature could provide key insights into physiological mechanisms and disease processes leading to novel medical interventions. However, it is a great challenge for researchers to utilize this information in full since the scale and complexity of the data greatly surpasses human processing abilities. This becomes especially problematic in cases of extreme urgency like the COVID-19 pandemic. Automated text mining can help extract and connect information from the large body of medical research articles. The first step in text mining is typically the identification of specific classes of keywords (e.g., all protein or disease names), so called Named Entity Recognition (NER). Here we present an end-to-end pipeline for NER of typical entities found in medical research articles, including diseases, cells, chemicals, genes/proteins, and species. The pipeline can access and process large medical research article collections (PubMed, CORD-19) or raw text and incorporates a series of deep learning models fine-tuned on the HUNER corpora collection. In addition, the pipeline can perform dictionary-based NER related to COVID-19 and other medical topics. Users can also load their own NER models and dictionaries to include additional entities. The output consists of publication-ready ranked lists and graphs of detected entities and files containing the annotated texts. An associated script allows rapid inspection of the results for specific entities of interest. As model use cases, the pipeline was deployed on two collections of autophagy-related abstracts from PubMed and on the CORD19 dataset, a collection of 764 398 research article abstracts related to COVID-19.

This paper presents several BERT-based models for Russian language biomedical text mining (RuBioBERT, RuBioRoBERTa). The models are pre-trained on a corpus of freely available texts in the Russian biomedical domain. With this pre-training, our models demonstrate state-of-the-art results on RuMedBench - Russian medical language understanding benchmark that covers a diverse set of tasks, including text classification, question answering, natural language inference, and named entity recognition.

Recent advancements in large language models (LLMs) have shown promising results across a variety of natural language processing (NLP) tasks. The application of LLMs to specific domains, such as biomedicine, has achieved increased attention. However, most biomedical LLMs focus on enhancing performance in monolingual biomedical question answering and conversation tasks. To further investigate the effectiveness of the LLMs on diverse biomedical NLP tasks in different languages, we present Taiyi, a bilingual (English and Chinese) fine-tuned LLM for diverse biomedical tasks. In this work, we first curated a comprehensive collection of 140 existing biomedical text mining datasets across over 10 task types. Subsequently, a two-stage strategy is proposed for supervised fine-tuning to optimize the model performance across varied tasks. Experimental results on 13 test sets covering named entity recognition, relation extraction, text classification, question answering tasks demonstrate Taiyi achieves superior performance compared to general LLMs. The case study involving additional biomedical NLP tasks further shows Taiyi's considerable potential for bilingual biomedical multi-tasking. The source code, datasets, and model for Taiyi are freely available at https://github.com/DUTIR-BioNLP/Taiyi-LLM.

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

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

The development of vision-language models (VLMs) is driven by large-scale and diverse multimodal datasets. However, progress toward generalist biomedical VLMs is limited by the lack of annotated, publicly accessible datasets across biology and medicine. Existing efforts are restricted to narrow domains, missing the full diversity of biomedical knowledge encoded in scientific literature. To address this gap, we introduce BIOMEDICA, a scalable, open-source framework to extract, annotate, and serialize the entirety of the PubMed Central Open Access subset into an easy-to-use, publicly accessible dataset.Our framework produces a comprehensive archive with over 24 million unique image-text pairs from over 6 million articles. Metadata and expert-guided annotations are also provided. We demonstrate the utility and accessibility of our resource by releasing BMCA-CLIP, a suite of CLIP-style models continuously pre-trained on the BIOMEDICA dataset via streaming, eliminating the need to download 27 TB of data locally.On average, our models achieve state-of-the-art performance across 40 tasks - spanning pathology, radiology, ophthalmology, dermatology, surgery, molecular biology, parasitology, and cell biology - excelling in zero-shot classification with a 6.56% average improvement (as high as 29.8% and 17.5% in dermatology and ophthalmology, respectively), and stronger image-text retrieval, all while using 10x less compute. To foster reproducibility and collaboration, we release our codebase and dataset for the broader research community.

Using language models (LMs) pre-trained in a self-supervised setting on large corpora and then fine-tuning for a downstream task has helped to deal with the problem of limited label data for supervised learning tasks such as Named Entity Recognition (NER). Recent research in biomedical language processing has offered a number of biomedical LMs pre-trained using different methods and techniques that advance results on many BioNLP tasks, including NER. However, there is still a lack of a comprehensive comparison of pre-training approaches that would work more optimally in the biomedical domain. This paper aims to investigate different pre-training methods, such as pre-training the biomedical LM from scratch and pre-training it in a continued fashion. We compare existing methods with our proposed pre-training method of initializing weights for new tokens by distilling existing weights from the BERT model inside the context where the tokens were found. The method helps to speed up the pre-training stage and improve performance on NER. In addition, we compare how masking rate, corruption strategy, and masking strategies impact the performance of the biomedical LM. Finally, using the insights from our experiments, we introduce a new biomedical LM (BIOptimus), which is pre-trained using Curriculum Learning (CL) and contextualized weight distillation method. Our model sets new states of the art on several biomedical Named Entity Recognition (NER) tasks. We release our code and all pre-trained models

The integration of biomolecular modeling with natural language (BL) has emerged as a promising interdisciplinary area at the intersection of artificial intelligence, chemistry and biology. This approach leverages the rich, multifaceted descriptions of biomolecules contained within textual data sources to enhance our fundamental understanding and enable downstream computational tasks such as biomolecule property prediction. The fusion of the nuanced narratives expressed through natural language with the structural and functional specifics of biomolecules described via various molecular modeling techniques opens new avenues for comprehensively representing and analyzing biomolecules. By incorporating the contextual language data that surrounds biomolecules into their modeling, BL aims to capture a holistic view encompassing both the symbolic qualities conveyed through language as well as quantitative structural characteristics. In this review, we provide an extensive analysis of recent advancements achieved through cross modeling of biomolecules and natural language. (1) We begin by outlining the technical representations of biomolecules employed, including sequences, 2D graphs, and 3D structures. (2) We then examine in depth the rationale and key objectives underlying effective multi-modal integration of language and molecular data sources. (3) We subsequently survey the practical applications enabled to date in this developing research area. (4) We also compile and summarize the available resources and datasets to facilitate future work. (5) Looking ahead, we identify several promising research directions worthy of further exploration and investment to continue advancing the field. The related resources and contents are updating in https://github.com/QizhiPei/Awesome-Biomolecule-Language-Cross-Modeling.

Biomedical question-answering (QA) systems require effective retrieval and generation components to ensure accuracy, efficiency, and scalability. This study systematically examines a Retrieval-Augmented Generation (RAG) system for biomedical QA, evaluating retrieval strategies and response time trade-offs. We first assess state-of-the-art retrieval methods, including BM25, BioBERT, MedCPT, and a hybrid approach, alongside common data stores such as Elasticsearch, MongoDB, and FAISS, on a ~10% subset of PubMed (2.4M documents) to measure indexing efficiency, retrieval latency, and retriever performance in the end-to-end RAG system. Based on these insights, we deploy the final RAG system on the full 24M PubMed corpus, comparing different retrievers' impact on overall performance. Evaluations of the retrieval depth show that retrieving 50 documents with BM25 before reranking with MedCPT optimally balances accuracy (0.90), recall (0.90), and response time (1.91s). BM25 retrieval time remains stable (82ms), while MedCPT incurs the main computational cost. These results highlight previously not well-known trade-offs in retrieval depth, efficiency, and scalability for biomedical QA. With open-source code, the system is fully reproducible and extensible.

Recent research trends in computational biology have increasingly focused on integrating text and bio-entity modeling, especially in the context of molecules and proteins. However, previous efforts like BioT5 faced challenges in generalizing across diverse tasks and lacked a nuanced understanding of molecular structures, particularly in their textual representations (e.g., IUPAC). This paper introduces BioT5+, an extension of the BioT5 framework, tailored to enhance biological research and drug discovery. BioT5+ incorporates several novel features: integration of IUPAC names for molecular understanding, inclusion of extensive bio-text and molecule data from sources like bioRxiv and PubChem, the multi-task instruction tuning for generality across tasks, and a novel numerical tokenization technique for improved processing of numerical data. These enhancements allow BioT5+ to bridge the gap between molecular representations and their textual descriptions, providing a more holistic understanding of biological entities, and largely improving the grounded reasoning of bio-text and bio-sequences. The model is pre-trained and fine-tuned with a large number of experiments, including 3 types of problems (classification, regression, generation), 15 kinds of tasks, and 21 total benchmark datasets, demonstrating the remarkable performance and state-of-the-art results in most cases. BioT5+ stands out for its ability to capture intricate relationships in biological data, thereby contributing significantly to bioinformatics and computational biology. Our code is available at https://github.com/QizhiPei/BioT5.

Biomedical text embeddings have primarily been developed using research literature from PubMed, yet clinical cardiology practice relies heavily on procedural knowledge and specialized terminology found in comprehensive textbooks rather than research abstracts. This research practice gap limits the effectiveness of existing embedding models for clinical applications incardiology. This study trained CardioEmbed, a domain-specialized embedding model based on Qwen3-Embedding-8B, using contrastive learning on a curated corpus of seven comprehensive cardiology textbooks totaling approximately 150,000 sentences after deduplication. The model employs InfoNCE loss with in-batch negatives and achieves 99.60% retrieval accuracy on cardiac-specific semantic retrieval tasks, a +15.94 percentage point improvement over MedTE, the current state-of-the-art medical embedding model. On MTEB medical benchmarks, the model obtained BIOSSES 0.77 Spearman and SciFact 0.61 NDCG@10, indicating competitive performance on related biomedical domains. Domain-specialized training on comprehensive clinical textbooks yields near-perfect cardiology retrieval (99.60% Acc@1), improving over MedTE by +15.94 percentage points.

Artificial intelligence (AI) has significant potential in healthcare applications, but its training and deployment faces challenges due to healthcare's diverse data, complex tasks, and the need to preserve privacy. Foundation models that perform well on medical tasks and require less task-specific tuning data are critical to accelerate the development of healthcare AI applications. We introduce MedGemma, a collection of medical vision-language foundation models based on Gemma 3 4B and 27B. MedGemma demonstrates advanced medical understanding and reasoning on images and text, significantly exceeding the performance of similar-sized generative models and approaching the performance of task-specific models, while maintaining the general capabilities of the Gemma 3 base models. For out-of-distribution tasks, MedGemma achieves 2.6-10% improvement on medical multimodal question answering, 15.5-18.1% improvement on chest X-ray finding classification, and 10.8% improvement on agentic evaluations compared to the base models. Fine-tuning MedGemma further improves performance in subdomains, reducing errors in electronic health record information retrieval by 50% and reaching comparable performance to existing specialized state-of-the-art methods for pneumothorax classification and histopathology patch classification. We additionally introduce MedSigLIP, a medically-tuned vision encoder derived from SigLIP. MedSigLIP powers the visual understanding capabilities of MedGemma and as an encoder achieves comparable or better performance than specialized medical image encoders. Taken together, the MedGemma collection provides a strong foundation of medical image and text capabilities, with potential to significantly accelerate medical research and development of downstream applications. The MedGemma collection, including tutorials and model weights, can be found at https://goo.gle/medgemma.

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

Molecules play a crucial role in biomedical research and discovery, particularly in the field of small molecule drug development. Given the rapid advancements in large language models, especially the recent emergence of reasoning models, it is natural to explore how a general-purpose language model can be efficiently adapted for molecular science applications. In this work, we introduce BioMedGPT-Mol, a molecular language model designed to support molecular understanding and generation tasks. By curating and unifying existing public instruction datasets, we have assembled a large-scale, comprehensive, and high-quality training dataset. The model is then fine-tuned through a meticulously designed multi-task learning framework. On a consolidated benchmark derived from LlaSMol, TOMG-Bench, and MuMOInstruct, BioMedGPT-Mol achieves remarkable performance. Our experimental results demonstrate that a general-purpose reasoning model can be effectively and efficiently post-trained into a professional molecular language model through a well-structured multi-task curriculum. Leveraging these capabilities, we further apply the model to multi-step retrosynthetic planning, achieving state-of-the-art performance on RetroBench and demonstrating its superior efficacy as an end-to-end retrosynthetic planner. We anticipate that our approach can be extended to other biomedical scientific domains.

Contrastive pretraining on parallel image-text data has attained great success in vision-language processing (VLP), as exemplified by CLIP and related methods. However, prior explorations tend to focus on general domains in the web. Biomedical images and text are rather different, but publicly available datasets are small and skew toward chest X-ray, thus severely limiting progress. In this paper, we conducted by far the largest study on biomedical VLP, using 15 million figure-caption pairs extracted from biomedical research articles in PubMed Central. Our dataset (PMC-15M) is two orders of magnitude larger than existing biomedical image-text datasets such as MIMIC-CXR, and spans a diverse range of biomedical images. The standard CLIP method is suboptimal for the biomedical domain. We propose BiomedCLIP with domain-specific adaptations tailored to biomedical VLP. We conducted extensive experiments and ablation studies on standard biomedical imaging tasks from retrieval to classification to visual question-answering (VQA). BiomedCLIP established new state of the art in a wide range of standard datasets, substantially outperformed prior VLP approaches. Surprisingly, BiomedCLIP even outperformed radiology-specific state-of-the-art models such as BioViL on radiology-specific tasks such as RSNA pneumonia detection, thus highlighting the utility in large-scale pretraining across all biomedical image types. We will release our models at https://aka.ms/biomedclip to facilitate future research in biomedical VLP.

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

With the development of computer-assisted techniques, research communities including biochemistry and deep learning have been devoted into the drug discovery field for over a decade. Various applications of deep learning have drawn great attention in drug discovery, such as molecule generation, molecular property prediction, retrosynthesis prediction, and reaction prediction. While most existing surveys only focus on one of the applications, limiting the view of researchers in the community. In this paper, we present a comprehensive review on the aforementioned four aspects, and discuss the relationships among different applications. The latest literature and classical benchmarks are presented for better understanding the development of variety of approaches. We commence by summarizing the molecule representation format in these works, followed by an introduction of recent proposed approaches for each of the four tasks. Furthermore, we review a variety of commonly used datasets and evaluation metrics and compare the performance of deep learning-based models. Finally, we conclude by identifying remaining challenges and discussing the future trend for deep learning methods in drug discovery.

Drug discovery typically consists of multiple steps, including identifying a target protein key to a disease's etiology, validating that interacting with this target could prevent symptoms or cure the disease, discovering a small molecule or biologic therapeutic to interact with it, and optimizing the candidate molecule through a complex landscape of required properties. Drug discovery related tasks often involve prediction and generation while considering multiple entities that potentially interact, which poses a challenge for typical AI models. For this purpose we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a method that we applied to create a versatile multi-task foundation model ibm/biomed.omics.bl.sm.ma-ted-458m that learns from large-scale biological datasets (2 billion samples) across diverse modalities, including proteins, small molecules, and genes. We introduce a prompt syntax that supports a wide range of classification, regression, and generation tasks. It allows combining different modalities and entity types as inputs and/or outputs. Our model handles combinations of tokens and scalars and enables the generation of small molecules and proteins, property prediction, and transcriptomic lab test predictions. We evaluated the model on 11 diverse downstream tasks spanning different steps within a typical drug discovery pipeline, where it reaches new SOTA in 9 tasks and is comparable to SOTA in 2 tasks. This performance is achieved while using a unified architecture serving all tasks, in contrast to the original SOTA performance achieved using tailored architectures. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m.

Modern life sciences research is increasingly relying on artificial intelligence approaches to model biological systems, primarily centered around the use of machine learning (ML) models. Although ML is undeniably useful for identifying patterns in large, complex data sets, its widespread application in biological sciences represents a significant deviation from traditional methods of scientific inquiry. As such, the interplay between these models and scientific understanding in biology is a topic with important implications for the future of scientific research, yet it is a subject that has received little attention. Here, we draw from an epistemological toolkit to contextualize recent applications of ML in biological sciences under modern philosophical theories of understanding, identifying general principles that can guide the design and application of ML systems to model biological phenomena and advance scientific knowledge. We propose that conceptions of scientific understanding as information compression, qualitative intelligibility, and dependency relation modelling provide a useful framework for interpreting ML-mediated understanding of biological systems. Through a detailed analysis of two key application areas of ML in modern biological research - protein structure prediction and single cell RNA-sequencing - we explore how these features have thus far enabled ML systems to advance scientific understanding of their target phenomena, how they may guide the development of future ML models, and the key obstacles that remain in preventing ML from achieving its potential as a tool for biological discovery. Consideration of the epistemological features of ML applications in biology will improve the prospects of these methods to solve important problems and advance scientific understanding of living systems.

In the era of digital healthcare, the huge volumes of textual information generated every day in hospitals constitute an essential but underused asset that could be exploited with task-specific, fine-tuned biomedical language representation models, improving patient care and management. For such specialized domains, previous research has shown that fine-tuning models stemming from broad-coverage checkpoints can largely benefit additional training rounds over large-scale in-domain resources. However, these resources are often unreachable for less-resourced languages like Italian, preventing local medical institutions to employ in-domain adaptation. In order to reduce this gap, our work investigates two accessible approaches to derive biomedical language models in languages other than English, taking Italian as a concrete use-case: one based on neural machine translation of English resources, favoring quantity over quality; the other based on a high-grade, narrow-scoped corpus natively written in Italian, thus preferring quality over quantity. Our study shows that data quantity is a harder constraint than data quality for biomedical adaptation, but the concatenation of high-quality data can improve model performance even when dealing with relatively size-limited corpora. The models published from our investigations have the potential to unlock important research opportunities for Italian hospitals and academia. Finally, the set of lessons learned from the study constitutes valuable insights towards a solution to build biomedical language models that are generalizable to other less-resourced languages and different domain settings.

Pre-trained language models have attracted increasing attention in the biomedical domain, inspired by their great success in the general natural language domain. Among the two main branches of pre-trained language models in the general language domain, i.e., BERT (and its variants) and GPT (and its variants), the first one has been extensively studied in the biomedical domain, such as BioBERT and PubMedBERT. While they have achieved great success on a variety of discriminative downstream biomedical tasks, the lack of generation ability constrains their application scope. In this paper, we propose BioGPT, a domain-specific generative Transformer language model pre-trained on large scale biomedical literature. We evaluate BioGPT on six biomedical NLP tasks and demonstrate that our model outperforms previous models on most tasks. Especially, we get 44.98%, 38.42% and 40.76% F1 score on BC5CDR, KD-DTI and DDI end-to-end relation extraction tasks respectively, and 78.2% accuracy on PubMedQA, creating a new record. Our larger model BioGPT-Large achieves 81.0% on PubMedQA. Our case study on text generation further demonstrates the advantage of BioGPT on biomedical literature to generate fluent descriptions for biomedical terms. Code is available at https://github.com/microsoft/BioGPT.

We introduce Biomed-Enriched, a biomedical text dataset constructed from PubMed via a two-stage annotation process. In the first stage, a large language model annotates 400K paragraphs from PubMed scientific articles, assigning scores for their type (review, study, clinical case, other), domain (clinical, biomedical, other), and educational quality. The educational quality score (rated 1 to 5) estimates how useful a paragraph is for college-level learning. These annotations are then used to fine-tune a small language model, which propagates the labels across the full PMC-OA corpus. The resulting metadata allows us to extract refined subsets, including 2M clinical case paragraphs with over 450K high-quality ones from articles with commercial-use licenses, and to construct several variants via quality filtering and domain upsampling. Clinical text is typically difficult to access due to privacy constraints, as hospital records cannot be publicly shared. Hence, our dataset provides an alternative large-scale, openly available collection of clinical cases from PubMed, making it a valuable resource for biomedical and clinical NLP. Preliminary continual-pretraining experiments with OLMo2 suggest these curated subsets enable targeted improvements, with clinical upsampling boosting performance by ~5% on MMLU ProfMed and educational quality filtering improving MedQA and MedMCQA by ~1%. Combinations of these techniques led to faster convergence, reaching same performance with a third of training tokens, indicating potential for more efficient and effective biomedical pretraining strategies.

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

Introduction: The scientific publishing landscape is expanding rapidly, creating challenges for researchers to stay up-to-date with the evolution of the literature. Natural Language Processing (NLP) has emerged as a potent approach to automating knowledge extraction from this vast amount of publications and preprints. Tasks such as Named-Entity Recognition (NER) and Named-Entity Linking (NEL), in conjunction with context-dependent semantic interpretation, offer promising and complementary approaches to extracting structured information and revealing key concepts. Results: We present the SourceData-NLP dataset produced through the routine curation of papers during the publication process. A unique feature of this dataset is its emphasis on the annotation of bioentities in figure legends. We annotate eight classes of biomedical entities (small molecules, gene products, subcellular components, cell lines, cell types, tissues, organisms, and diseases), their role in the experimental design, and the nature of the experimental method as an additional class. SourceData-NLP contains more than 620,000 annotated biomedical entities, curated from 18,689 figures in 3,223 papers in molecular and cell biology. We illustrate the dataset's usefulness by assessing BioLinkBERT and PubmedBERT, two transformers-based models, fine-tuned on the SourceData-NLP dataset for NER. We also introduce a novel context-dependent semantic task that infers whether an entity is the target of a controlled intervention or the object of measurement. Conclusions: SourceData-NLP's scale highlights the value of integrating curation into publishing. Models trained with SourceData-NLP will furthermore enable the development of tools able to extract causal hypotheses from the literature and assemble them into knowledge graphs.

Recent proprietary large language models (LLMs), such as GPT-4, have achieved a milestone in tackling diverse challenges in the biomedical domain, ranging from multiple-choice questions to long-form generations. To address challenges that still cannot be handled with the encoded knowledge of LLMs, various retrieval-augmented generation (RAG) methods have been developed by searching documents from the knowledge corpus and appending them unconditionally or selectively to the input of LLMs for generation. However, when applying existing methods to different domain-specific problems, poor generalization becomes apparent, leading to fetching incorrect documents or making inaccurate judgments. In this paper, we introduce Self-BioRAG, a framework reliable for biomedical text that specializes in generating explanations, retrieving domain-specific documents, and self-reflecting generated responses. We utilize 84k filtered biomedical instruction sets to train Self-BioRAG that can assess its generated explanations with customized reflective tokens. Our work proves that domain-specific components, such as a retriever, domain-related document corpus, and instruction sets are necessary for adhering to domain-related instructions. Using three major medical question-answering benchmark datasets, experimental results of Self-BioRAG demonstrate significant performance gains by achieving a 7.2% absolute improvement on average over the state-of-the-art open-foundation model with a parameter size of 7B or less. Overall, we analyze that Self-BioRAG finds the clues in the question, retrieves relevant documents if needed, and understands how to answer with information from retrieved documents and encoded knowledge as a medical expert does. We release our data and code for training our framework components and model weights (7B and 13B) to enhance capabilities in biomedical and clinical domains.

Understanding and designing biomolecules, such as proteins and small molecules, is central to advancing drug discovery, synthetic biology, and enzyme engineering. Recent breakthroughs in Artificial Intelligence (AI) have revolutionized biomolecular research, achieving remarkable accuracy in biomolecular prediction and design. However, a critical gap remains between AI's computational power and researchers' intuition, using natural language to align molecular complexity with human intentions. Large Language Models (LLMs) have shown potential to interpret human intentions, yet their application to biomolecular research remains nascent due to challenges including specialized knowledge requirements, multimodal data integration, and semantic alignment between natural language and biomolecules. To address these limitations, we present InstructBioMol, a novel LLM designed to bridge natural language and biomolecules through a comprehensive any-to-any alignment of natural language, molecules, and proteins. This model can integrate multimodal biomolecules as input, and enable researchers to articulate design goals in natural language, providing biomolecular outputs that meet precise biological needs. Experimental results demonstrate InstructBioMol can understand and design biomolecules following human instructions. Notably, it can generate drug molecules with a 10% improvement in binding affinity and design enzymes that achieve an ESP Score of 70.4, making it the only method to surpass the enzyme-substrate interaction threshold of 60.0 recommended by the ESP developer. This highlights its potential to transform real-world biomolecular research.

The challenge of replicating research results has posed a significant impediment to the field of molecular biology. The advent of modern intelligent systems has led to notable progress in various domains. Consequently, we embarked on an investigation of intelligent monitoring systems as a means of tackling the issue of the reproducibility crisis. Specifically, we first curate a comprehensive multimodal dataset, named ProBio, as an initial step towards this objective. This dataset comprises fine-grained hierarchical annotations intended for the purpose of studying activity understanding in BioLab. Next, we devise two challenging benchmarks, transparent solution tracking and multimodal action recognition, to emphasize the unique characteristics and difficulties associated with activity understanding in BioLab settings. Finally, we provide a thorough experimental evaluation of contemporary video understanding models and highlight their limitations in this specialized domain to identify potential avenues for future research. We hope ProBio with associated benchmarks may garner increased focus on modern AI techniques in the realm of molecular biology.

Nanorobots are a promising development in targeted drug delivery and the treatment of neurological disorders, with potential for crossing the blood-brain barrier (BBB). These small devices leverage advancements in nanotechnology and bioengineering for precise navigation and targeted payload delivery, particularly for conditions like brain tumors, Alzheimer's disease, and Parkinson's disease. Recent progress in artificial intelligence (AI) and machine learning (ML) has improved the navigation and effectiveness of nanorobots, allowing them to detect and interact with cancer cells through biomarker analysis. This study presents a new reinforcement learning (RL) framework for optimizing nanorobot navigation in complex biological environments, focusing on cancer cell detection by analyzing the concentration gradients of surrounding biomarkers. We utilize a computer simulation model to explore the behavior of nanorobots in a three-dimensional space with cancer cells and biological barriers. The proposed method uses Q-learning to refine movement strategies based on real-time biomarker concentration data, enabling nanorobots to autonomously navigate to cancerous tissues for targeted drug delivery. This research lays the groundwork for future laboratory experiments and clinical applications, with implications for personalized medicine and less invasive cancer treatments. The integration of intelligent nanorobots could revolutionize therapeutic strategies, reducing side effects and enhancing treatment effectiveness for cancer patients. Further research will investigate the practical deployment of these technologies in medical settings, aiming to unlock the full potential of nanorobotics in healthcare.

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

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

Generative models hold promise for revolutionizing medical education, robot-assisted surgery, and data augmentation for medical AI development. Diffusion models can now generate realistic images from text prompts, while recent advancements have demonstrated their ability to create diverse, high-quality videos. However, these models often struggle with generating accurate representations of medical procedures and detailed anatomical structures. This paper introduces Bora, the first spatio-temporal diffusion probabilistic model designed for text-guided biomedical video generation. Bora leverages Transformer architecture and is pre-trained on general-purpose video generation tasks. It is fine-tuned through model alignment and instruction tuning using a newly established medical video corpus, which includes paired text-video data from various biomedical fields. To the best of our knowledge, this is the first attempt to establish such a comprehensive annotated biomedical video dataset. Bora is capable of generating high-quality video data across four distinct biomedical domains, adhering to medical expert standards and demonstrating consistency and diversity. This generalist video generative model holds significant potential for enhancing medical consultation and decision-making, particularly in resource-limited settings. Additionally, Bora could pave the way for immersive medical training and procedure planning. Extensive experiments on distinct medical modalities such as endoscopy, ultrasound, MRI, and cell tracking validate the effectiveness of our model in understanding biomedical instructions and its superior performance across subjects compared to state-of-the-art generation models.

Pretrained language models have served as important backbones for natural language processing. Recently, in-domain pretraining has been shown to benefit various domain-specific downstream tasks. In the biomedical domain, natural language generation (NLG) tasks are of critical importance, while understudied. Approaching natural language understanding (NLU) tasks as NLG achieves satisfying performance in the general domain through constrained language generation or language prompting. We emphasize the lack of in-domain generative language models and the unsystematic generative downstream benchmarks in the biomedical domain, hindering the development of the research community. In this work, we introduce the generative language model BioBART that adapts BART to the biomedical domain. We collate various biomedical language generation tasks including dialogue, summarization, entity linking, and named entity recognition. BioBART pretrained on PubMed abstracts has enhanced performance compared to BART and set strong baselines on several tasks. Furthermore, we conduct ablation studies on the pretraining tasks for BioBART and find that sentence permutation has negative effects on downstream tasks.

Medication Extraction and Mining play an important role in healthcare NLP research due to its practical applications in hospital settings, such as their mapping into standard clinical knowledge bases (SNOMED-CT, BNF, etc.). In this work, we investigate state-of-the-art LLMs in text mining tasks on medications and their related attributes such as dosage, route, strength, and adverse effects. In addition, we explore different ensemble learning methods (Stack-Ensemble and Voting-Ensemble) to augment the model performances from individual LLMs. Our ensemble learning result demonstrated better performances than individually fine-tuned base models BERT, RoBERTa, RoBERTa-L, BioBERT, BioClinicalBERT, BioMedRoBERTa, ClinicalBERT, and PubMedBERT across general and specific domains. Finally, we build up an entity linking function to map extracted medical terminologies into the SNOMED-CT codes and the British National Formulary (BNF) codes, which are further mapped to the Dictionary of Medicines and Devices (dm+d), and ICD. Our model's toolkit and desktop applications are publicly available at https://github.com/HECTA-UoM/ensemble-NER.

Biomedical named entity recognition (NER) presents unique challenges due to specialized vocabularies, the sheer volume of entities, and the continuous emergence of novel entities. Traditional NER models, constrained by fixed taxonomies and human annotations, struggle to generalize beyond predefined entity types or efficiently adapt to emerging concepts. To address these issues, we introduce GLiNER-biomed, a domain-adapted suite of Generalist and Lightweight Model for NER (GLiNER) models specifically tailored for biomedical NER. In contrast to conventional approaches, GLiNER uses natural language descriptions to infer arbitrary entity types, enabling zero-shot recognition. Our approach first distills the annotation capabilities of large language models (LLMs) into a smaller, more efficient model, enabling the generation of high-coverage synthetic biomedical NER data. We subsequently train two GLiNER architectures, uni- and bi-encoder, at multiple scales to balance computational efficiency and recognition performance. Evaluations on several biomedical datasets demonstrate that GLiNER-biomed outperforms state-of-the-art GLiNER models in both zero- and few-shot scenarios, achieving 5.96% improvement in F1-score over the strongest baseline. Ablation studies highlight the effectiveness of our synthetic data generation strategy and emphasize the complementary benefits of synthetic biomedical pre-training combined with fine-tuning on high-quality general-domain annotations. All datasets, models, and training pipelines are publicly available at https://github.com/ds4dh/GLiNER-biomed.

Large multimodal models (LMMs) have demonstrated significant potential in providing innovative solutions for various biomedical tasks, including pathology analysis, radiology report generation, and biomedical assistance. However, the existing multimodal biomedical AI is typically based on foundation LLMs, thus hindering the understanding of intricate medical concepts with limited medical training data. Moreover, recent LLaVA-induced medical LMMs struggle to effectively capture the intricate relationship between the texts and the images. Therefore, we introduce Doctor Sun, a large multimodal generative model specialized in medicine, developed to encode, integrate, and interpret diverse biomedical data modalities such as text and images. In particular, Doctor Sun integrates a pre-trained vision encoder with a medical LLM and conducts two-stage training on various medical datasets, focusing on feature alignment and instruction tuning. Moreover, we release SunMed-VL, a wide-range bilingual medical multimodal dataset, along with all associated models, code, and resources, to freely support the advancement of biomedical multimodal research.

Two key obstacles in biomedical relation extraction (RE) are the scarcity of annotations and the prevalence of instances without explicitly pre-defined labels due to low annotation coverage. Existing approaches, which treat biomedical RE as a multi-class classification task, often result in poor generalization in low-resource settings and do not have the ability to make selective prediction on unknown cases but give a guess from seen relations, hindering the applicability of those approaches. We present NBR, which converts biomedical RE as natural language inference formulation through indirect supervision. By converting relations to natural language hypotheses, NBR is capable of exploiting semantic cues to alleviate annotation scarcity. By incorporating a ranking-based loss that implicitly calibrates abstinent instances, NBR learns a clearer decision boundary and is instructed to abstain on uncertain instances. Extensive experiments on three widely-used biomedical RE benchmarks, namely ChemProt, DDI and GAD, verify the effectiveness of NBR in both full-set and low-resource regimes. Our analysis demonstrates that indirect supervision benefits biomedical RE even when a domain gap exists, and combining NLI knowledge with biomedical knowledge leads to the best performance gains.