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Mar 14

Exploring the Effectiveness of Instruction Tuning in Biomedical Language Processing

Large Language Models (LLMs), particularly those similar to ChatGPT, have significantly influenced the field of Natural Language Processing (NLP). While these models excel in general language tasks, their performance in domain-specific downstream tasks such as biomedical and clinical Named Entity Recognition (NER), Relation Extraction (RE), and Medical Natural Language Inference (NLI) is still evolving. In this context, our study investigates the potential of instruction tuning for biomedical language processing, applying this technique to two general LLMs of substantial scale. We present a comprehensive, instruction-based model trained on a dataset that consists of approximately 200,000 instruction-focused samples. This dataset represents a carefully curated compilation of existing data, meticulously adapted and reformatted to align with the specific requirements of our instruction-based tasks. This initiative represents an important step in utilising such models to achieve results on par with specialised encoder-only models like BioBERT and BioClinicalBERT for various classical biomedical NLP tasks. Our work includes an analysis of the dataset's composition and its impact on model performance, providing insights into the intricacies of instruction tuning. By sharing our codes, models, and the distinctively assembled instruction-based dataset, we seek to encourage ongoing research and development in this area.

Domain-Specific Language Model Pretraining for Biomedical Natural Language Processing

Pretraining large neural language models, such as BERT, has led to impressive gains on many natural language processing (NLP) tasks. However, most pretraining efforts focus on general domain corpora, such as newswire and Web. A prevailing assumption is that even domain-specific pretraining can benefit by starting from general-domain language models. In this paper, we challenge this assumption by showing that for domains with abundant unlabeled text, such as biomedicine, pretraining language models from scratch results in substantial gains over continual pretraining of general-domain language models. To facilitate this investigation, we compile a comprehensive biomedical NLP benchmark from publicly-available datasets. Our experiments show that domain-specific pretraining serves as a solid foundation for a wide range of biomedical NLP tasks, leading to new state-of-the-art results across the board. Further, in conducting a thorough evaluation of modeling choices, both for pretraining and task-specific fine-tuning, we discover that some common practices are unnecessary with BERT models, such as using complex tagging schemes in named entity recognition (NER). To help accelerate research in biomedical NLP, we have released our state-of-the-art pretrained and task-specific models for the community, and created a leaderboard featuring our BLURB benchmark (short for Biomedical Language Understanding & Reasoning Benchmark) at https://aka.ms/BLURB.

BioBERT: a pre-trained biomedical language representation model for biomedical text mining

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.

BIOptimus: Pre-training an Optimal Biomedical Language Model with Curriculum Learning for Named Entity Recognition

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

Fine-Tuning Large Neural Language Models for Biomedical Natural Language Processing

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.

Large-Scale Domain-Specific Pretraining for Biomedical Vision-Language Processing

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.

Making the Most of Text Semantics to Improve Biomedical Vision--Language Processing

Multi-modal data abounds in biomedicine, such as radiology images and reports. Interpreting this data at scale is essential for improving clinical care and accelerating clinical research. Biomedical text with its complex semantics poses additional challenges in vision--language modelling compared to the general domain, and previous work has used insufficiently adapted models that lack domain-specific language understanding. In this paper, we show that principled textual semantic modelling can substantially improve contrastive learning in self-supervised vision--language processing. We release a language model that achieves state-of-the-art results in radiology natural language inference through its improved vocabulary and novel language pretraining objective leveraging semantics and discourse characteristics in radiology reports. Further, we propose a self-supervised joint vision--language approach with a focus on better text modelling. It establishes new state of the art results on a wide range of publicly available benchmarks, in part by leveraging our new domain-specific language model. We release a new dataset with locally-aligned phrase grounding annotations by radiologists to facilitate the study of complex semantic modelling in biomedical vision--language processing. A broad evaluation, including on this new dataset, shows that our contrastive learning approach, aided by textual-semantic modelling, outperforms prior methods in segmentation tasks, despite only using a global-alignment objective.

BioInstruct: Instruction Tuning of Large Language Models for Biomedical Natural Language Processing

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.

Benchmarking Retrieval-Augmented Large Language Models in Biomedical NLP: Application, Robustness, and Self-Awareness

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.

Large Language Models and Control Mechanisms Improve Text Readability of Biomedical Abstracts

Biomedical literature often uses complex language and inaccessible professional terminologies. That is why simplification plays an important role in improving public health literacy. Applying Natural Language Processing (NLP) models to automate such tasks allows for quick and direct accessibility for lay readers. In this work, we investigate the ability of state-of-the-art large language models (LLMs) on the task of biomedical abstract simplification, using the publicly available dataset for plain language adaptation of biomedical abstracts (PLABA). The methods applied include domain fine-tuning and prompt-based learning (PBL) on: 1) Encoder-decoder models (T5, SciFive, and BART), 2) Decoder-only GPT models (GPT-3.5 and GPT-4) from OpenAI and BioGPT, and 3) Control-token mechanisms on BART-based models. We used a range of automatic evaluation metrics, including BLEU, ROUGE, SARI, and BERTscore, and also conducted human evaluations. BART-Large with Control Token (BART-L-w-CT) mechanisms reported the highest SARI score of 46.54 and T5-base reported the highest BERTscore 72.62. In human evaluation, BART-L-w-CTs achieved a better simplicity score over T5-Base (2.9 vs. 2.2), while T5-Base achieved a better meaning preservation score over BART-L-w-CTs (3.1 vs. 2.6). We also categorised the system outputs with examples, hoping this will shed some light for future research on this task. Our code, fine-tuned models, and data splits are available at https://github.com/HECTA-UoM/PLABA-MU

Bioformer: an efficient transformer language model for biomedical text mining

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.

Lightweight Transformers for Clinical Natural Language Processing

Specialised pre-trained language models are becoming more frequent in NLP since they can potentially outperform models trained on generic texts. BioBERT and BioClinicalBERT are two examples of such models that have shown promise in medical NLP tasks. Many of these models are overparametrised and resource-intensive, but thanks to techniques like Knowledge Distillation (KD), it is possible to create smaller versions that perform almost as well as their larger counterparts. In this work, we specifically focus on development of compact language models for processing clinical texts (i.e. progress notes, discharge summaries etc). We developed a number of efficient lightweight clinical transformers using knowledge distillation and continual learning, with the number of parameters ranging from 15 million to 65 million. These models performed comparably to larger models such as BioBERT and ClinicalBioBERT and significantly outperformed other compact models trained on general or biomedical data. Our extensive evaluation was done across several standard datasets and covered a wide range of clinical text-mining tasks, including Natural Language Inference, Relation Extraction, Named Entity Recognition, and Sequence Classification. To our knowledge, this is the first comprehensive study specifically focused on creating efficient and compact transformers for clinical NLP tasks. The models and code used in this study can be found on our Huggingface profile at https://huggingface.co/nlpie and Github page at https://github.com/nlpie-research/Lightweight-Clinical-Transformers, respectively, promoting reproducibility of our results.

Hierarchical Pretraining for Biomedical Term Embeddings

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

Pre-training technique to localize medical BERT and enhance biomedical BERT

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

Can Open-Source LLMs Compete with Commercial Models? Exploring the Few-Shot Performance of Current GPT Models in Biomedical Tasks

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

Label Dependent Attention Model for Disease Risk Prediction Using Multimodal Electronic Health Records

Disease risk prediction has attracted increasing attention in the field of modern healthcare, especially with the latest advances in artificial intelligence (AI). Electronic health records (EHRs), which contain heterogeneous patient information, are widely used in disease risk prediction tasks. One challenge of applying AI models for risk prediction lies in generating interpretable evidence to support the prediction results while retaining the prediction ability. In order to address this problem, we propose the method of jointly embedding words and labels whereby attention modules learn the weights of words from medical notes according to their relevance to the names of risk prediction labels. This approach boosts interpretability by employing an attention mechanism and including the names of prediction tasks in the model. However, its application is only limited to the handling of textual inputs such as medical notes. In this paper, we propose a label dependent attention model LDAM to 1) improve the interpretability by exploiting Clinical-BERT (a biomedical language model pre-trained on a large clinical corpus) to encode biomedically meaningful features and labels jointly; 2) extend the idea of joint embedding to the processing of time-series data, and develop a multi-modal learning framework for integrating heterogeneous information from medical notes and time-series health status indicators. To demonstrate our method, we apply LDAM to the MIMIC-III dataset to predict different disease risks. We evaluate our method both quantitatively and qualitatively. Specifically, the predictive power of LDAM will be shown, and case studies will be carried out to illustrate its interpretability.

The Minimum Information about CLinical Artificial Intelligence Checklist for Generative Modeling Research (MI-CLAIM-GEN)

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

A Survey for Large Language Models in Biomedicine

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.

Biomedical Language Models are Robust to Sub-optimal Tokenization

As opposed to general English, many concepts in biomedical terminology have been designed in recent history by biomedical professionals with the goal of being precise and concise. This is often achieved by concatenating meaningful biomedical morphemes to create new semantic units. Nevertheless, most modern biomedical language models (LMs) are pre-trained using standard domain-specific tokenizers derived from large scale biomedical corpus statistics without explicitly leveraging the agglutinating nature of biomedical language. In this work, we first find that standard open-domain and biomedical tokenizers are largely unable to segment biomedical terms into meaningful components. Therefore, we hypothesize that using a tokenizer which segments biomedical terminology more accurately would enable biomedical LMs to improve their performance on downstream biomedical NLP tasks, especially ones which involve biomedical terms directly such as named entity recognition (NER) and entity linking. Surprisingly, we find that pre-training a biomedical LM using a more accurate biomedical tokenizer does not improve the entity representation quality of a language model as measured by several intrinsic and extrinsic measures such as masked language modeling prediction (MLM) accuracy as well as NER and entity linking performance. These quantitative findings, along with a case study which explores entity representation quality more directly, suggest that the biomedical pre-training process is quite robust to instances of sub-optimal tokenization.

Large language models in healthcare and medical domain: A review

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.

EasyNER: A Customizable Easy-to-Use Pipeline for Deep Learning- and Dictionary-based Named Entity Recognition from Medical Text

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.

Improving Medical Reasoning through Retrieval and Self-Reflection with Retrieval-Augmented Large Language Models

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.

A Biomedical Entity Extraction Pipeline for Oncology Health Records in Portuguese

Textual health records of cancer patients are usually protracted and highly unstructured, making it very time-consuming for health professionals to get a complete overview of the patient's therapeutic course. As such limitations can lead to suboptimal and/or inefficient treatment procedures, healthcare providers would greatly benefit from a system that effectively summarizes the information of those records. With the advent of deep neural models, this objective has been partially attained for English clinical texts, however, the research community still lacks an effective solution for languages with limited resources. In this paper, we present the approach we developed to extract procedures, drugs, and diseases from oncology health records written in European Portuguese. This project was conducted in collaboration with the Portuguese Institute for Oncology which, besides holding over 10 years of duly protected medical records, also provided oncologist expertise throughout the development of the project. Since there is no annotated corpus for biomedical entity extraction in Portuguese, we also present the strategy we followed in annotating the corpus for the development of the models. The final models, which combined a neural architecture with entity linking, achieved F_1 scores of 88.6, 95.0, and 55.8 per cent in the mention extraction of procedures, drugs, and diseases, respectively.

Biomedical Large Languages Models Seem not to be Superior to Generalist Models on Unseen Medical Data

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

The SourceData-NLP dataset: integrating curation into scientific publishing for training large language models

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.

BioRED: A Rich Biomedical Relation Extraction Dataset

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/.

Medical mT5: An Open-Source Multilingual Text-to-Text LLM for The Medical Domain

Research on language technology for the development of medical applications is currently a hot topic in Natural Language Understanding and Generation. Thus, a number of large language models (LLMs) have recently been adapted to the medical domain, so that they can be used as a tool for mediating in human-AI interaction. While these LLMs display competitive performance on automated medical texts benchmarks, they have been pre-trained and evaluated with a focus on a single language (English mostly). This is particularly true of text-to-text models, which typically require large amounts of domain-specific pre-training data, often not easily accessible for many languages. In this paper, we address these shortcomings by compiling, to the best of our knowledge, the largest multilingual corpus for the medical domain in four languages, namely English, French, Italian and Spanish. This new corpus has been used to train Medical mT5, the first open-source text-to-text multilingual model for the medical domain. Additionally, we present two new evaluation benchmarks for all four languages with the aim of facilitating multilingual research in this domain. A comprehensive evaluation shows that Medical mT5 outperforms both encoders and similarly sized text-to-text models for the Spanish, French, and Italian benchmarks, while being competitive with current state-of-the-art LLMs in English.

Localising In-Domain Adaptation of Transformer-Based Biomedical Language Models

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.

Comparison of biomedical relationship extraction methods and models for knowledge graph creation

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.

Biomedical and Clinical Language Models for Spanish: On the Benefits of Domain-Specific Pretraining in a Mid-Resource Scenario

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.

Evaluation of Language Models in the Medical Context Under Resource-Constrained Settings

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

Distilling Large Language Models for Biomedical Knowledge Extraction: A Case Study on Adverse Drug Events

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.

ClinLinker: Medical Entity Linking of Clinical Concept Mentions in Spanish

Advances in natural language processing techniques, such as named entity recognition and normalization to widely used standardized terminologies like UMLS or SNOMED-CT, along with the digitalization of electronic health records, have significantly advanced clinical text analysis. This study presents ClinLinker, a novel approach employing a two-phase pipeline for medical entity linking that leverages the potential of in-domain adapted language models for biomedical text mining: initial candidate retrieval using a SapBERT-based bi-encoder and subsequent re-ranking with a cross-encoder, trained by following a contrastive-learning strategy to be tailored to medical concepts in Spanish. This methodology, focused initially on content in Spanish, substantially outperforming multilingual language models designed for the same purpose. This is true even for complex scenarios involving heterogeneous medical terminologies and being trained on a subset of the original data. Our results, evaluated using top-k accuracy at 25 and other top-k metrics, demonstrate our approach's performance on two distinct clinical entity linking Gold Standard corpora, DisTEMIST (diseases) and MedProcNER (clinical procedures), outperforming previous benchmarks by 40 points in DisTEMIST and 43 points in MedProcNER, both normalized to SNOMED-CT codes. These findings highlight our approach's ability to address language-specific nuances and set a new benchmark in entity linking, offering a potent tool for enhancing the utility of digital medical records. The resulting system is of practical value, both for large scale automatic generation of structured data derived from clinical records, as well as for exhaustive extraction and harmonization of predefined clinical variables of interest.

PMC-LLaMA: Towards Building Open-source Language Models for Medicine

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

Cross-lingual Argument Mining in the Medical Domain

Nowadays the medical domain is receiving more and more attention in applications involving Artificial Intelligence. Clinicians have to deal with an enormous amount of unstructured textual data to make a conclusion about patients' health in their everyday life. Argument mining helps to provide a structure to such data by detecting argumentative components in the text and classifying the relations between them. However, as it is the case for many tasks in Natural Language Processing in general and in medical text processing in particular, the large majority of the work on computational argumentation has been done only for English. This is also the case with the only dataset available for argumentation in the medical domain, namely, the annotated medical data of abstracts of Randomized Controlled Trials (RCT) from the MEDLINE database. In order to mitigate the lack of annotated data for other languages, we empirically investigate several strategies to perform argument mining and classification in medical texts for a language for which no annotated data is available. This project shows that automatically translating and project annotations from English to a target language (Spanish) is an effective way to generate annotated data without manual intervention. Furthermore, our experiments demonstrate that the translation and projection approach outperforms zero-shot cross-lingual approaches using a large masked multilingual language model. Finally, we show how the automatically generated data in Spanish can also be used to improve results in the original English evaluation setting.

Towards Evaluating and Building Versatile Large Language Models for Medicine

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

ChiMed-GPT: A Chinese Medical Large Language Model with Full Training Regime and Better Alignment to Human Preferences

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

Large Language Models as Biomedical Hypothesis Generators: A Comprehensive Evaluation

The rapid growth of biomedical knowledge has outpaced our ability to efficiently extract insights and generate novel hypotheses. Large language models (LLMs) have emerged as a promising tool to revolutionize knowledge interaction and potentially accelerate biomedical discovery. In this paper, we present a comprehensive evaluation of LLMs as biomedical hypothesis generators. We construct a dataset of background-hypothesis pairs from biomedical literature, carefully partitioned into training, seen, and unseen test sets based on publication date to mitigate data contamination. Using this dataset, we assess the hypothesis generation capabilities of top-tier instructed models in zero-shot, few-shot, and fine-tuning settings. To enhance the exploration of uncertainty, a crucial aspect of scientific discovery, we incorporate tool use and multi-agent interactions in our evaluation framework. Furthermore, we propose four novel metrics grounded in extensive literature review to evaluate the quality of generated hypotheses, considering both LLM-based and human assessments. Our experiments yield two key findings: 1) LLMs can generate novel and validated hypotheses, even when tested on literature unseen during training, and 2) Increasing uncertainty through multi-agent interactions and tool use can facilitate diverse candidate generation and improve zero-shot hypothesis generation performance. However, we also observe that the integration of additional knowledge through few-shot learning and tool use may not always lead to performance gains, highlighting the need for careful consideration of the type and scope of external knowledge incorporated. These findings underscore the potential of LLMs as powerful aids in biomedical hypothesis generation and provide valuable insights to guide further research in this area.

Contrastive Learning and Mixture of Experts Enables Precise Vector Embeddings

The advancement of transformer neural networks has significantly elevated the capabilities of sentence similarity models, particularly in creating effective vector representations of natural language inputs. However, these models face notable challenges in domain-specific contexts, especially in highly specialized scientific sub-fields. Traditional methods often struggle in this regime, either overgeneralizing similarities within a niche or being overly sensitive to minor differences, resulting in inaccurate text classification and subpar vector representation. In an era where retrieval augmentation and search are increasingly crucial, precise and concise numerical representations are essential. In this paper, we target this issue by assembling niche datasets using co-citations as a similarity metric, focusing on biomedical domains. We employ two key strategies for fine-tuning state-of-the-art models: 1. Domain-specific Fine-Tuning, which tailors pretrained models to a single domain, and 2. Universal Applicability with Mixture of Experts (MoE), adapting pretrained models with enforced routing for multiple domains simultaneously. Our training approach emphasizes the use of abstracts for faster training, incorporating Multiple Negative Rankings loss for efficient contrastive learning. Notably, our MoE variants, equipped with N experts, achieve the efficacy of N individual models, heralding a new era of versatile, One-Size-Fits-All transformer networks for various tasks. This methodology marks significant advancements in scientific text classification metrics and holds promise for enhancing vector database search and compilation.

Summarizing Patients Problems from Hospital Progress Notes Using Pre-trained Sequence-to-Sequence Models

Automatically summarizing patients' main problems from daily progress notes using natural language processing methods helps to battle against information and cognitive overload in hospital settings and potentially assists providers with computerized diagnostic decision support. Problem list summarization requires a model to understand, abstract, and generate clinical documentation. In this work, we propose a new NLP task that aims to generate a list of problems in a patient's daily care plan using input from the provider's progress notes during hospitalization. We investigate the performance of T5 and BART, two state-of-the-art seq2seq transformer architectures, in solving this problem. We provide a corpus built on top of progress notes from publicly available electronic health record progress notes in the Medical Information Mart for Intensive Care (MIMIC)-III. T5 and BART are trained on general domain text, and we experiment with a data augmentation method and a domain adaptation pre-training method to increase exposure to medical vocabulary and knowledge. Evaluation methods include ROUGE, BERTScore, cosine similarity on sentence embedding, and F-score on medical concepts. Results show that T5 with domain adaptive pre-training achieves significant performance gains compared to a rule-based system and general domain pre-trained language models, indicating a promising direction for tackling the problem summarization task.

Explanatory Argument Extraction of Correct Answers in Resident Medical Exams

Developing the required technology to assist medical experts in their everyday activities is currently a hot topic in the Artificial Intelligence research field. Thus, a number of large language models (LLMs) and automated benchmarks have recently been proposed with the aim of facilitating information extraction in Evidence-Based Medicine (EBM) using natural language as a tool for mediating in human-AI interaction. The most representative benchmarks are limited to either multiple-choice or long-form answers and are available only in English. In order to address these shortcomings, in this paper we present a new dataset which, unlike previous work: (i) includes not only explanatory arguments for the correct answer, but also arguments to reason why the incorrect answers are not correct; (ii) the explanations are written originally by medical doctors to answer questions from the Spanish Residency Medical Exams. Furthermore, this new benchmark allows us to setup a novel extractive task which consists of identifying the explanation of the correct answer written by medical doctors. An additional benefit of our setting is that we can leverage the extractive QA paradigm to automatically evaluate performance of LLMs without resorting to costly manual evaluation by medical experts. Comprehensive experimentation with language models for Spanish shows that sometimes multilingual models fare better than monolingual ones, even outperforming models which have been adapted to the medical domain. Furthermore, results across the monolingual models are mixed, with supposedly smaller and inferior models performing competitively. In any case, the obtained results show that our novel dataset and approach can be an effective technique to help medical practitioners in identifying relevant evidence-based explanations for medical questions.

PhenoTagger: A Hybrid Method for Phenotype Concept Recognition using Human Phenotype Ontology

Automatic phenotype concept recognition from unstructured text remains a challenging task in biomedical text mining research. Previous works that address the task typically use dictionary-based matching methods, which can achieve high precision but suffer from lower recall. Recently, machine learning-based methods have been proposed to identify biomedical concepts, which can recognize more unseen concept synonyms by automatic feature learning. However, most methods require large corpora of manually annotated data for model training, which is difficult to obtain due to the high cost of human annotation. In this paper, we propose PhenoTagger, a hybrid method that combines both dictionary and machine learning-based methods to recognize Human Phenotype Ontology (HPO) concepts in unstructured biomedical text. We first use all concepts and synonyms in HPO to construct a dictionary, which is then used to automatically build a distantly supervised training dataset for machine learning. Next, a cutting-edge deep learning model is trained to classify each candidate phrase (n-gram from input sentence) into a corresponding concept label. Finally, the dictionary and machine learning-based prediction results are combined for improved performance. Our method is validated with two HPO corpora, and the results show that PhenoTagger compares favorably to previous methods. In addition, to demonstrate the generalizability of our method, we retrained PhenoTagger using the disease ontology MEDIC for disease concept recognition to investigate the effect of training on different ontologies. Experimental results on the NCBI disease corpus show that PhenoTagger without requiring manually annotated training data achieves competitive performance as compared with state-of-the-art supervised methods.

PMC-Patients: A Large-scale Dataset of Patient Notes and Relations Extracted from Case Reports in PubMed Central

Objective: Data unavailability has been one of the biggest barriers in clinical natural language processing. This paper is aimed at providing a large-scale and publicly available patient note dataset, named PMC-Patients, with relevant articles and similar patients annotations. The ultimate goal of PMC-Patients is to facilitate the development of retrieval-based clinical decision support systems. Materials and Methods: To collect PMC-Patients, we extract patient notes from case reports in PubMed Central by recognizing certain section patterns. Patient-article relevance and patient-patient similarity are annotated by citation relationships in PubMed. In addition, we perform three tasks with PMC-Patients to demonstrate its utility in providing clinical decision support for a given patient, including (1) classifying whether another patient is similar, (2) retrieving similar patients in PMC-Patients, and (3) retrieving relevant articles in PubMed. Results: We collect and release PMC-Patients under the CC BY-NC-SA license, which becomes the largest publicly available patient note dataset so far. PMC-Patients contains 167k patient notes that are annotated with 3.1M relevant articles and 293k similar patients. Qualitative and quantitative analyses reveal the high quality and richness of our dataset. Experiments show that classifying the similarity of patient pairs is relatively easy, but it is hard to retrieve similar patients or relevant articles for a given patient from a large set of candidates. Conclusion: We present PMC-Patients, a large-scale dataset of patient notes with high quality, easy access, diverse conditions, and rich annotations. The proposed dataset can also serve as a hard benchmark for evaluating retrieval-based clinical decision support systems.

BioMedGPT: Open Multimodal Generative Pre-trained Transformer for BioMedicine

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.

Using the Tsetlin Machine to Learn Human-Interpretable Rules for High-Accuracy Text Categorization with Medical Applications

Medical applications challenge today's text categorization techniques by demanding both high accuracy and ease-of-interpretation. Although deep learning has provided a leap ahead in accuracy, this leap comes at the sacrifice of interpretability. To address this accuracy-interpretability challenge, we here introduce, for the first time, a text categorization approach that leverages the recently introduced Tsetlin Machine. In all brevity, we represent the terms of a text as propositional variables. From these, we capture categories using simple propositional formulae, such as: if "rash" and "reaction" and "penicillin" then Allergy. The Tsetlin Machine learns these formulae from a labelled text, utilizing conjunctive clauses to represent the particular facets of each category. Indeed, even the absence of terms (negated features) can be used for categorization purposes. Our empirical comparison with Na\"ive Bayes, decision trees, linear support vector machines (SVMs), random forest, long short-term memory (LSTM) neural networks, and other techniques, is quite conclusive. The Tsetlin Machine either performs on par with or outperforms all of the evaluated methods on both the 20 Newsgroups and IMDb datasets, as well as on a non-public clinical dataset. On average, the Tsetlin Machine delivers the best recall and precision scores across the datasets. Finally, our GPU implementation of the Tsetlin Machine executes 5 to 15 times faster than the CPU implementation, depending on the dataset. We thus believe that our novel approach can have a significant impact on a wide range of text analysis applications, forming a promising starting point for deeper natural language understanding with the Tsetlin Machine.

LLMs-in-the-loop Part-1: Expert Small AI Models for Bio-Medical Text Translation

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

A Survey of Large Language Models for Healthcare: from Data, Technology, and Applications to Accountability and Ethics

The utilization of large language models (LLMs) in the Healthcare domain has generated both excitement and concern due to their ability to effectively respond to freetext queries with certain professional knowledge. This survey outlines the capabilities of the currently developed LLMs for Healthcare and explicates their development process, with the aim of providing an overview of the development roadmap from traditional Pretrained Language Models (PLMs) to LLMs. Specifically, we first explore the potential of LLMs to enhance the efficiency and effectiveness of various Healthcare applications highlighting both the strengths and limitations. Secondly, we conduct a comparison between the previous PLMs and the latest LLMs, as well as comparing various LLMs with each other. Then we summarize related Healthcare training data, training methods, optimization strategies, and usage. Finally, the unique concerns associated with deploying LLMs in Healthcare settings are investigated, particularly regarding fairness, accountability, transparency and ethics. Our survey provide a comprehensive investigation from perspectives of both computer science and Healthcare specialty. Besides the discussion about Healthcare concerns, we supports the computer science community by compiling a collection of open source resources, such as accessible datasets, the latest methodologies, code implementations, and evaluation benchmarks in the Github. Summarily, we contend that a significant paradigm shift is underway, transitioning from PLMs to LLMs. This shift encompasses a move from discriminative AI approaches to generative AI approaches, as well as a shift from model-centered methodologies to datacentered methodologies.

Towards Efficient Methods in Medical Question Answering using Knowledge Graph Embeddings

In Natural Language Processing (NLP), Machine Reading Comprehension (MRC) is the task of answering a question based on a given context. To handle questions in the medical domain, modern language models such as BioBERT, SciBERT and even ChatGPT are trained on vast amounts of in-domain medical corpora. However, in-domain pre-training is expensive in terms of time and resources. In this paper, we propose a resource-efficient approach for injecting domain knowledge into a model without relying on such domain-specific pre-training. Knowledge graphs are powerful resources for accessing medical information. Building on existing work, we introduce a method using Multi-Layer Perceptrons (MLPs) for aligning and integrating embeddings extracted from medical knowledge graphs with the embedding spaces of pre-trained language models (LMs). The aligned embeddings are fused with open-domain LMs BERT and RoBERTa that are fine-tuned for two MRC tasks, span detection (COVID-QA) and multiple-choice questions (PubMedQA). We compare our method to prior techniques that rely on a vocabulary overlap for embedding alignment and show how our method circumvents this requirement to deliver better performance. On both datasets, our method allows BERT/RoBERTa to either perform on par (occasionally exceeding) with stronger domain-specific models or show improvements in general over prior techniques. With the proposed approach, we signal an alternative method to in-domain pre-training to achieve domain proficiency.

Medical Graph RAG: Towards Safe Medical Large Language Model via Graph Retrieval-Augmented Generation

We introduce a novel graph-based Retrieval-Augmented Generation (RAG) framework specifically designed for the medical domain, called MedGraphRAG, aimed at enhancing Large Language Model (LLM) capabilities and generating evidence-based results, thereby improving safety and reliability when handling private medical data. Our comprehensive pipeline begins with a hybrid static-semantic approach to document chunking, significantly improving context capture over traditional methods. Extracted entities are used to create a three-tier hierarchical graph structure, linking entities to foundational medical knowledge sourced from medical papers and dictionaries. These entities are then interconnected to form meta-graphs, which are merged based on semantic similarities to develop a comprehensive global graph. This structure supports precise information retrieval and response generation. The retrieval process employs a U-retrieve method to balance global awareness and indexing efficiency of the LLM. Our approach is validated through a comprehensive ablation study comparing various methods for document chunking, graph construction, and information retrieval. The results not only demonstrate that our hierarchical graph construction method consistently outperforms state-of-the-art models on multiple medical Q\&A benchmarks, but also confirms that the responses generated include source documentation, significantly enhancing the reliability of medical LLMs in practical applications. Code will be at: https://github.com/MedicineToken/Medical-Graph-RAG/tree/main

Biomedical knowledge graph-optimized prompt generation for large language models

Large Language Models (LLMs) are being adopted at an unprecedented rate, yet still face challenges in knowledge-intensive domains like biomedicine. Solutions such as pre-training and domain-specific fine-tuning add substantial computational overhead, requiring further domain expertise. Here, we introduce a token-optimized and robust Knowledge Graph-based Retrieval Augmented Generation (KG-RAG) framework by leveraging a massive biomedical KG (SPOKE) with LLMs such as Llama-2-13b, GPT-3.5-Turbo and GPT-4, to generate meaningful biomedical text rooted in established knowledge. Compared to the existing RAG technique for Knowledge Graphs, the proposed method utilizes minimal graph schema for context extraction and uses embedding methods for context pruning. This optimization in context extraction results in more than 50% reduction in token consumption without compromising the accuracy, making a cost-effective and robust RAG implementation on proprietary LLMs. KG-RAG consistently enhanced the performance of LLMs across diverse biomedical prompts by generating responses rooted in established knowledge, accompanied by accurate provenance and statistical evidence (if available) to substantiate the claims. Further benchmarking on human curated datasets, such as biomedical true/false and multiple-choice questions (MCQ), showed a remarkable 71% boost in the performance of the Llama-2 model on the challenging MCQ dataset, demonstrating the framework's capacity to empower open-source models with fewer parameters for domain specific questions. Furthermore, KG-RAG enhanced the performance of proprietary GPT models, such as GPT-3.5 and GPT-4. In summary, the proposed framework combines explicit and implicit knowledge of KG and LLM in a token optimized fashion, thus enhancing the adaptability of general-purpose LLMs to tackle domain-specific questions in a cost-effective fashion.

Question-Answering Model for Schizophrenia Symptoms and Their Impact on Daily Life using Mental Health Forums Data

In recent years, there is strong emphasis on mining medical data using machine learning techniques. A common problem is to obtain a noiseless set of textual documents, with a relevant content for the research question, and developing a Question Answering (QA) model for a specific medical field. The purpose of this paper is to present a new methodology for building a medical dataset and obtain a QA model for analysis of symptoms and impact on daily life for a specific disease domain. The ``Mental Health'' forum was used, a forum dedicated to people suffering from schizophrenia and different mental disorders. Relevant posts of active users, who regularly participate, were extrapolated providing a new method of obtaining low-bias content and without privacy issues. Furthermore, it is shown how to pre-process the dataset to convert it into a QA dataset. The Bidirectional Encoder Representations from Transformers (BERT), DistilBERT, RoBERTa, and BioBERT models were fine-tuned and evaluated via F1-Score, Exact Match, Precision and Recall. Accurate empirical experiments demonstrated the effectiveness of the proposed method for obtaining an accurate dataset for QA model implementation. By fine-tuning the BioBERT QA model, we achieved an F1 score of 0.885, showing a considerable improvement and outperforming the state-of-the-art model for mental disorders domain.

BiomedParse: a biomedical foundation model for image parsing of everything everywhere all at once

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.

A New Data Representation Based on Training Data Characteristics to Extract Drug Named-Entity in Medical Text

One essential task in information extraction from the medical corpus is drug name recognition. Compared with text sources come from other domains, the medical text is special and has unique characteristics. In addition, the medical text mining poses more challenges, e.g., more unstructured text, the fast growing of new terms addition, a wide range of name variation for the same drug. The mining is even more challenging due to the lack of labeled dataset sources and external knowledge, as well as multiple token representations for a single drug name that is more common in the real application setting. Although many approaches have been proposed to overwhelm the task, some problems remained with poor F-score performance (less than 0.75). This paper presents a new treatment in data representation techniques to overcome some of those challenges. We propose three data representation techniques based on the characteristics of word distribution and word similarities as a result of word embedding training. The first technique is evaluated with the standard NN model, i.e., MLP (Multi-Layer Perceptrons). The second technique involves two deep network classifiers, i.e., DBN (Deep Belief Networks), and SAE (Stacked Denoising Encoders). The third technique represents the sentence as a sequence that is evaluated with a recurrent NN model, i.e., LSTM (Long Short Term Memory). In extracting the drug name entities, the third technique gives the best F-score performance compared to the state of the art, with its average F-score being 0.8645.

Enhancing Health Information Retrieval with RAG by Prioritizing Topical Relevance and Factual Accuracy

The exponential surge in online health information, coupled with its increasing use by non-experts, highlights the pressing need for advanced Health Information Retrieval models that consider not only topical relevance but also the factual accuracy of the retrieved information, given the potential risks associated with health misinformation. To this aim, this paper introduces a solution driven by Retrieval-Augmented Generation (RAG), which leverages the capabilities of generative Large Language Models (LLMs) to enhance the retrieval of health-related documents grounded in scientific evidence. In particular, we propose a three-stage model: in the first stage, the user's query is employed to retrieve topically relevant passages with associated references from a knowledge base constituted by scientific literature. In the second stage, these passages, alongside the initial query, are processed by LLMs to generate a contextually relevant rich text (GenText). In the last stage, the documents to be retrieved are evaluated and ranked both from the point of view of topical relevance and factual accuracy by means of their comparison with GenText, either through stance detection or semantic similarity. In addition to calculating factual accuracy, GenText can offer a layer of explainability for it, aiding users in understanding the reasoning behind the retrieval. Experimental evaluation of our model on benchmark datasets and against baseline models demonstrates its effectiveness in enhancing the retrieval of both topically relevant and factually accurate health information, thus presenting a significant step forward in the health misinformation mitigation problem.

An analysis of full-size Russian complexly NER labelled corpus of Internet user reviews on the drugs based on deep learning and language neural nets

We present the full-size Russian complexly NER-labeled corpus of Internet user reviews, along with an evaluation of accuracy levels reached on this corpus by a set of advanced deep learning neural networks to extract the pharmacologically meaningful entities from Russian texts. The corpus annotation includes mentions of the following entities: Medication (33005 mentions), Adverse Drug Reaction (1778), Disease (17403), and Note (4490). Two of them - Medication and Disease - comprise a set of attributes. A part of the corpus has the coreference annotation with 1560 coreference chains in 300 documents. Special multi-label model based on a language model and the set of features is developed, appropriate for presented corpus labeling. The influence of the choice of different modifications of the models: word vector representations, types of language models pre-trained for Russian, text normalization styles, and other preliminary processing are analyzed. The sufficient size of our corpus allows to study the effects of particularities of corpus labeling and balancing entities in the corpus. As a result, the state of the art for the pharmacological entity extraction problem for Russian is established on a full-size labeled corpus. In case of the adverse drug reaction (ADR) recognition, it is 61.1 by the F1-exact metric that, as our analysis shows, is on par with the accuracy level for other language corpora with similar characteristics and the ADR representativnes. The evaluated baseline precision of coreference relation extraction on the corpus is 71, that is higher the results reached on other Russian corpora.

Do We Still Need Clinical Language Models?

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

LongHealth: A Question Answering Benchmark with Long Clinical Documents

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

BioT5+: Towards Generalized Biological Understanding with IUPAC Integration and Multi-task Tuning

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.

Extraction of Medication and Temporal Relation from Clinical Text using Neural Language Models

Clinical texts, represented in electronic medical records (EMRs), contain rich medical information and are essential for disease prediction, personalised information recommendation, clinical decision support, and medication pattern mining and measurement. Relation extractions between medication mentions and temporal information can further help clinicians better understand the patients' treatment history. To evaluate the performances of deep learning (DL) and large language models (LLMs) in medication extraction and temporal relations classification, we carry out an empirical investigation of MedTem project using several advanced learning structures including BiLSTM-CRF and CNN-BiLSTM for a clinical domain named entity recognition (NER), and BERT-CNN for temporal relation extraction (RE), in addition to the exploration of different word embedding techniques. Furthermore, we also designed a set of post-processing roles to generate structured output on medications and the temporal relation. Our experiments show that CNN-BiLSTM slightly wins the BiLSTM-CRF model on the i2b2-2009 clinical NER task yielding 75.67, 77.83, and 78.17 for precision, recall, and F1 scores using Macro Average. BERT-CNN model also produced reasonable evaluation scores 64.48, 67.17, and 65.03 for P/R/F1 using Macro Avg on the temporal relation extraction test set from i2b2-2012 challenges. Code and Tools from MedTem will be hosted at https://github.com/HECTA-UoM/MedTem