Large language models for biomedicine: foundations, opportunities, challenges, and best practices.

Abstract. Large language models (LLMs) have revolutionized the field of natural language processing (NLP), demonstrating remarkable capabilities in understanding, generating, and manipulating human language. This comprehensive review explores the development, applications, optimizations, and challenges of LLMs. This paper begin by tracing the evolution of these models and their foundational architectures, such as the Transformer, GPT, and BERT. We then delve into the applications of LLMs in natural language understanding tasks, including sentiment analysis, named entity recognition, question answering, and text summarization, highlighting real-world use cases. Next, we examine the role of LLMs in natural language generation, covering areas such as content creation, language translation, personalized recommendations, and automated responses. We further discuss LLM applications in other NLP tasks like text style transfer, text correction, and language model pre-training. Subsequently, we explore techniques for optimizing and improving LLMs, including model compression, explainability, robustness, and security. Finally, we address the challenges posed by the significant computational requirements, sample inefficiency, and ethical considerations surrounding LLMs. We conclude by discussing potential future research directions, such as efficient architectures, few-shot learning, bias mitigation, and privacy-preserving techniques, which will shape the ongoing development and responsible deployment of LLMs in NLP.

Background and Aims Large language models (LLMs) have gained significant attention in the field of natural language processing (NLP), marking a shift from traditional techniques like Term Frequency-Inverse Document Frequency (TF-IDF). We developed a traditional NLP model to predict arteriovenous fistula (AVF) failure within next 30 days using clinical notes. The goal of this analysis was to investigate whether LLMs would outperform traditional NLP techniques, specifically in the context of predicting AVF failure within the next 30 days using clinical notes. Method We defined AVF failure as the change in status from active to permanently unusable status or temporarily unusable status. We used data from a large kidney care network from January 2021 to December 2021. Two models were created using LLMs and traditional TF-IDF technique. We used “distilbert-base-uncased”, a distilled version of BERT base model [1], and compared its performance with traditional TF-IDF-based NLP techniques. The dataset was randomly divided into 60% training, 20% validation and 20% test dataset. The test data, comprising of unseen patients’ data was used to evaluate the performance of the model. Both models were evaluated using metrics such as area under the receiver operating curve (AUROC), accuracy, sensitivity, and specificity. Results The incidence of 30 days AVF failure rate was 2.3% in the population. Both LLMs and traditional showed similar overall performance as summarized in Table 1. Notably, LLMs showed marginally better performance in certain evaluation metrics. Both models had same AUROC of 0.64 on test data. The accuracy and balanced accuracy for LLMs were 72.9% and 59.7%, respectively, compared to 70.9% and 59.6% for the traditional TF-IDF approach. In terms of specificity, LLMs scored 73.2%, slightly higher than the 71.2% observed for traditional NLP methods. However, LLMs had a lower sensitivity of 46.1% compared to 48% for traditional NLP. However, it is worth noting that training on LLMs took considerably longer than TF-IDF. Moreover, it also used higher computational resources such as utilization of graphics processing units (GPU) instances in cloud-based services, leading to higher cost. Conclusion In our study, we discovered that advanced LLMs perform comparably to traditional TF-IDF modeling techniques in predicting the failure of AVF. Both models demonstrated identical AUROC. While specificity was higher in LLMs compared to traditional NLP, sensitivity was higher in traditional NLP compared to LLMs. LLM was fine-tuned with a limited dataset, which could have influenced its performance to be similar to that of traditional NLP methods. This finding suggests that while LLMs may excel in certain scenarios, such as performing in-depth sentiment analysis of patient data for complex tasks, their effectiveness is highly dependent on the specific use case. It is crucial to weigh the benefits against the resources required for LLMs, as they can be significantly more resource-intensive and costly compared to traditional TF-IDF methods. This highlights the importance of a use-case-driven approach in selecting the appropriate NLP technique for healthcare applications.

Large Language Models (LLMs) have been the cutting-edge technology in natural language processing (NLP) in recent years, making machine-generated text indistinguishable from human-generated text. On the other hand, “rule-based” Natural Language Generation (NLG) and Natural Language Understanding (NLU) algorithms were developed in earlier years, and they have performed well in certain areas of Natural Language Processing (NLP). Today, an arduous task that arises is how to estimate the quality of the produced text. This process depends on the aspects of text that you need to assess, varying from correct grammar and syntax to more intriguing aspects such as coherence and semantical fluency. Although the performance of LLMs is high, the challenge is whether LLMs can cooperate with rule-based NLG/NLU technology by leveraging their assets to overcome LLMs’ weak points. This paper presents the basics of these two families of technologies and the applications, strengths, and weaknesses of each approach, analyzes the different ways of evaluating a machine-generated text, and, lastly, focuses on a first-level approach of possible combinations of these two approaches to enhance performance in specific tasks.

Evaluating gpt-4 for zero-shot classification of bleeding and clotting events: Can large language models serve as second reviewers?

Extracting information from unstructured and semi-structured geoscience literature is a crucial step in conducting geological research. The traditional machine learning extraction paradigm requires a substantial amount of high-quality manually annotated data for model training, which is time-consuming, labor-intensive, and not easily transferable to new fields. Recently, large language models (LLMs) (e.g., ChatGPT, GPT-4, and LLaMA), have shown great performance in various natural language processing (NLP) tasks, such as question answering, machine translation, and text generation. A substantial body of work has demonstrated that LLMs possess strong in-context learning (ICL) and even zero-shot learning capabilities to solve downstream tasks without specifically designed supervised fine-tuning. In this paper, we propose utilizing LLMs for geoscience literature information extraction. Specifically, we design a hierarchical PDF parsing pipeline and an automated knowledge extraction process, which can significantly reduce the need for manual data annotation, assisting geoscientists in literature data mining. For the hierarchical PDF parsing pipeline, firstly, a document layout detection model fine-tuned on geoscience literature is employed for layout detection, obtaining layout detection information for the document. Secondly, based on the document layout information, an optical character content parsing model is used for content parsing, obtaining the text structure and plain text corresponding to the content. Finally, the text structure and plain text are combined and reconstructed to ultimately obtain the parsed structured data. For the automated knowledge extraction process, firstly, the parsed long text is segmented into paragraphs to adapt to the input length limit of LLMs. Subsequently, a few-shot prompting method is employed for structured knowledge extraction, encompassing two tasks: attribute value extraction and triplet extraction. In attribute value extraction, prompts are generated automatically by the LLMs based on the subdomain and attribute names, facilitating the location and extraction of values related to subdomain attribute names in the text. For triplet extraction, the LLMs employ a procedural approach to entity extraction, entity type extraction, and relation extraction, following the knowledge graph structure pattern. Finally, the extracted structured knowledge is stored in the form of knowledge graphs, facilitating further analysis and integration of various types of knowledge from the literature. Our proposed approach turns out to be simple, flexible, and highly effective in geoscience literature information extraction. Demonstrations of information extraction in subdomains such as radiolarian fossils and fluvial facies have yielded satisfactory results. The extraction efficiency has significantly improved, and feedback from domain experts indicates a relatively high level of accuracy in the extraction process. The extracted results can be used to construct a foundational knowledge graph for geoscience literature, supporting the comprehensive construction and efficient application of a geoscience knowledge graph.

Detecting biases in natural language understanding (NLU) for African American Vernacular English (AAVE) is crucial to developing inclusive natural language processing (NLP) systems.To address dialectinduced performance discrepancies, we introduce AAVENUE (AAVE Natural Language Understanding Evaluation), a benchmark for evaluating large language model (LLM) performance on NLU tasks in AAVE and Standard American English (SAE).AAVENUE builds upon and extends existing benchmarks like VALUE, replacing deterministic syntactic and morphological transformations with a more flexible methodology leveraging LLMbased translation with few-shot prompting, improving performance across several evaluation metrics when translating key tasks from the GLUE and SuperGLUE benchmarks.We compare AAVENUE and VALUE translations using five popular LLMs and a comprehensive set of metrics including fluency, BARTScore, quality, coherence, and understandability.Additionally, the fluency of AAVENUE is validated by annotations from AAVE speakers.Our evaluations reveal that LLMs consistently perform better on SAE tasks than AAVEtranslated versions, underscoring inherent biases and highlighting the need for more inclusive NLP models.We have open-sourced our source code on GitHub and created a website to showcase our work at https://aavenue.live.

BackgroundA large language model (LLM) is a machine learning model inferred from text data that captures subtle patterns of language use in context. Modern LLMs are based on neural network architectures that incorporate transformer methods. They allow the model to relate words together through attention to multiple words in a text sequence. LLMs have been shown to be highly effective for a range of tasks in natural language processing (NLP), including classification and information extraction tasks and generative applications.ObjectiveThe aim of this adapted Delphi study was to collect researchers’ opinions on how LLMs might influence health care and on the strengths, weaknesses, opportunities, and threats of LLM use in health care.MethodsWe invited researchers in the fields of health informatics, nursing informatics, and medical NLP to share their opinions on LLM use in health care. We started the first round with open questions based on our strengths, weaknesses, opportunities, and threats framework. In the second and third round, the participants scored these items.ResultsThe first, second, and third rounds had 28, 23, and 21 participants, respectively. Almost all participants (26/28, 93% in round 1 and 20/21, 95% in round 3) were affiliated with academic institutions. Agreement was reached on 103 items related to use cases, benefits, risks, reliability, adoption aspects, and the future of LLMs in health care. Participants offered several use cases, including supporting clinical tasks, documentation tasks, and medical research and education, and agreed that LLM-based systems will act as health assistants for patient education. The agreed-upon benefits included increased efficiency in data handling and extraction, improved automation of processes, improved quality of health care services and overall health outcomes, provision of personalized care, accelerated diagnosis and treatment processes, and improved interaction between patients and health care professionals. In total, 5 risks to health care in general were identified: cybersecurity breaches, the potential for patient misinformation, ethical concerns, the likelihood of biased decision-making, and the risk associated with inaccurate communication. Overconfidence in LLM-based systems was recognized as a risk to the medical profession. The 6 agreed-upon privacy risks included the use of unregulated cloud services that compromise data security, exposure of sensitive patient data, breaches of confidentiality, fraudulent use of information, vulnerabilities in data storage and communication, and inappropriate access or use of patient data.ConclusionsFuture research related to LLMs should not only focus on testing their possibilities for NLP-related tasks but also consider the workflows the models could contribute to and the requirements regarding quality, integration, and regulations needed for successful implementation in practice.

Large language models (LLMs) are increasingly adopted in educational contexts to provide personalized support to students and teachers. The unprecedented capacity of LLM‐based applications to understand and generate natural language can potentially improve instructional effectiveness and learning outcomes, but the integration of LLMs in education technology has renewed concerns over algorithmic bias, which may exacerbate educational inequalities. Building on prior work that mapped the traditional machine learning life cycle, we provide a framework of the LLM life cycle from the initial development of LLMs to customizing pre‐trained models for various applications in educational settings. We explain each step in the LLM life cycle and identify potential sources of bias that may arise in the context of education. We discuss why current measures of bias from traditional machine learning fail to transfer to LLM‐generated text (eg, tutoring conversations) because text encodings are high‐dimensional, there can be multiple correct responses, and tailoring responses may be pedagogically desirable rather than unfair. The proposed framework clarifies the complex nature of bias in LLM applications and provides practical guidance for their evaluation to promote educational equity. Practitioner notes What is already known about this topic The life cycle of traditional machine learning (ML) applications which focus on predicting labels is well understood. Biases are known to enter in traditional ML applications at various points in the life cycle, and methods to measure and mitigate these biases have been developed and tested. Large language models (LLMs) and other forms of generative artificial intelligence (GenAI) are increasingly adopted in education technologies (EdTech), but current evaluation approaches are not specific to the domain of education. What this paper adds A holistic perspective of the LLM life cycle with domain‐specific examples in education to highlight opportunities and challenges for incorporating natural language understanding (NLU) and natural language generation (NLG) into EdTech. Potential sources of bias are identified in each step of the LLM life cycle and discussed in the context of education. A framework for understanding where to expect potential harms of LLMs for students, teachers, and other users of GenAI technology in education, which can guide approaches to bias measurement and mitigation. Implications for practice and/or policy Education practitioners and policymakers should be aware that biases can originate from a multitude of steps in the LLM life cycle, and the life cycle perspective offers them a heuristic for asking technology developers to explain each step to assess the risk of bias. Measuring the biases of systems that use LLMs in education is more complex than with traditional ML, in large part because the evaluation of natural language generation is highly context‐dependent (eg, what counts as good feedback on an assignment varies). EdTech developers can play an important role in collecting and curating datasets for the evaluation and benchmarking of LLM applications moving forward.

Plagiarism, the unauthorized reuse of text, fueled by the ease of access to online content, is a pressing concern for academia, publishers, and authors. Paraphrasing, a common tactic in textual plagiarism, compounds the problem further. The automatic detection of paraphrased plagiarism in text documents is a fundamental task in Natural Language Processing (NLP), crucial for maintaining academic integrity and authenticity. This paper presents an extensive investigation into Urdu sentential paraphrased plagiarism detection leveraging advanced Deep Neural Networks (DNNs) and Large Language Models (LLMs). The study builds upon the foundational work and proposes modifications to the Deep Text Reuse and Paraphrased Plagiarism Detection (D-TRaPPD) architecture to incorporate state-of-the-art pre-trained LLMs. The proposed approach, SELLM-D-TRaPPD, integrates various language models, including contextualized sentence embedding-based LLMs, language-agnostic and multilingual transformer-based LLMs, and multilingual knowledge-distilled transformer-based LLMs. We evaluated these models against three benchmark Urdu sentential paraphrase corpora—Urdu Sentential Paraphrase Corpus, Urdu Short Text Reuse Corpus, and Semi-automatic Urdu Sentential Paraphrase Corpus. The results demonstrate the effectiveness of SELLM-D-TRaPPD with LLMs, achieving F1 scores of 92.09%, 96.70%, and 98.23%, respectively. A comparative analysis with existing state-of-the-art methods shows significant performance improvements, establishing SELLM-D-TRaPPD as the new leading approach for Urdu sentential paraphrased plagiarism detection. These findings highlight the value of leveraging advanced neural network architectures and pre-trained LLMs in improving the accuracy and effectiveness of paraphrased plagiarism detection in Urdu, addressing a crucial gap in Urdu NLP research.

Large Language Models (LLMs) recently demonstrated extraordinary capability, including natural language processing (NLP), language translation, text generation, question answering, etc. Moreover, LLMs are a new and essential part of computerized language processing, having the ability to understand complex verbal patterns and generate coherent and appropriate replies for the situation. Though this success of LLMs has prompted a substantial increase in research contributions, rapid growth has made it difficult to understand the overall impact of these improvements. Since a lot of new research on LLMs is coming out quickly, it is getting tough to get an overview of all of them in a short note. Consequently, the research community would benefit from a short but thorough review of the recent changes in this area. This article thoroughly overviews LLMs, including their history, architectures, transformers, resources, training methods, applications, impacts, challenges, etc. This paper begins by discussing the fundamental concepts of LLMs with its traditional pipeline of the LLMs training phase. It then provides an overview of the existing works, the history of LLMs, their evolution over time, the architecture of transformers in LLMs, the different resources of LLMs, and the different training methods that have been used to train them. It also demonstrated the datasets utilized in the studies. After that, the paper discusses the wide range of applications of LLMs, including biomedical and healthcare, education, social, business, and agriculture. It also illustrates how LLMs create an impact on society and shape the future of AI and how they can be used to solve real-world problems. Then it also explores open issues and challenges to deploying LLMs in real-world scenario. Our review paper aims to help practitioners, researchers, and experts thoroughly understand the evolution of LLMs, pre-trained architectures, applications, challenges, and future goals.

Accurate syntactic parsing is fundamental to natural language processing (NLP) applications such as machine translation, text summarization, and sentiment analysis. Traditional rule-based and statistical parsing methods often struggle with complex sentence structures, ambiguities, and cross-linguistic variations. Recent advances in large language models (LLMs) have shown remarkable capabilities in understanding linguistic patterns, offering new opportunities to enhance syntactic parsing accuracy and efficiency. This paper proposes an optimized syntactic structure parsing framework based on LLMs, integrating self-attention mechanisms and fine-tuned transformer architectures to improve parsing precision and generalization. The framework incorporates a hybrid training approach that combines supervised learning with reinforcement learning from human feedback (RLHF) to refine parsing decisions. Experimental evaluations on benchmark datasets demonstrate that the proposed method outperforms conventional dependency and constituency parsers in accuracy, robustness, and adaptability to complex sentence structures. These findings highlight the potential of LLM-driven syntactic parsing for advancing NLP applications.

Work orders, equipment information, technical records and best practices documents contain within them a wealth of insights related to Equipment Maintenance which can be unlocked with Natural Language Processing tasks like classification, clustering, named entity recognition or part of speech tagging. But obtaining large enough labelled data sets in Equipment Maintenance domain manually is prohibitive and very expensive. This lack of labeled Equipment Maintenance data can be overcome with Large Language Models (LLMs) such as GPT-3, BERT that are pretrained transformer networks, considered state-of-the-art when it comes to Natural Language Processing (NLP) tasks. However, the vocabulary understood by these LLMs are mostly from English Language and need to be fine-tuned to understand industry and organization specific vocabulary and acronyms. This paper explores the potential of a domain specific LLM model for oil and gas industries. Data that are of good quality and that provide a comprehensive overview of industry are collected. This corpus of text contains documents like work orders, equipment data and technical documents. A custom tokenizer is trained on this data to identify domain specific terminology. A comparative study is done with other off-the-shelf tokenizers: BERT and RoBERTa, to compare the effectiveness of the tokenization. With millions of work orders and equipment documents, training pipelines had to parallelized so that training can occur on multiple GPUs. A comprehensive study of multiple training methods is done in this paper. Model and tokenizer developed were packaged and archived to be consumed in machine learning pipelines to specific use-cases across the organization. For an organization adopting digital transformation, the availability of an organization specific LLM is an enabler to extract insights from millions of documents containing free text. The applicability of such models spans across multiple disciplines like Maintenance, Reliability, Safety etc. and streamlines the development of highly accurate and robust text analytics.

This chapter introduces essential systems and tools for leveraging various natural language processing (NLP) tasks and large language models (LLMs) in qualitative analysis, emphasizing accessibility for noncoders. It begins with an overview of the Python programming language and introduces tools such as the Pandas library, integrated development environments (IDEs), Jupyter notebooks, and application programming interfaces (APIs) for accessing LLMs. A second section provides a hands-on guide for setting up a computer environment, with step-by-step code examples designed to familiarize readers with NLP libraries and LLMs. It emphasizes the acquisition of programming skills to better adapt and utilize LLM capabilities for qualitative data analysis while providing multiple resources for further learning.

BackgroundDisease name recognition is a fundamental task in clinical natural language processing, enabling the extraction of critical patient information from electronic health records. While recent advances in large language models (LLMs) have shown promise, most evaluations have focused on English, and little is known about their robustness in low-resource languages such as Japanese. In particular, whether these models can perform reliably on previously unseen in-hospital data, which differs from training data in writing styles and clinical contexts, has not been thoroughly investigated.ObjectiveThis study evaluated the robustness of fine-tuned LLMs for disease name recognition in Japanese clinical notes, with a particular focus on their performance on in-hospital data that was not included during training.MethodsWe used two corpora for this study: (1) a publicly available set of Japanese case reports denoted as CR, and (2) a newly constructed corpus of progress notes, denoted as PN, written by ten physicians to capture stylistic variations of in-hospital clinical notes. To reflect real-world deployment scenarios, we first fine-tuned models on CR. Specifically, we compared a LLM and a baseline-masked language model (MLM). These models were then evaluated under two conditions: (1) on CR, representing the in-domain (ID) setting with the same document type, similar to training, and (2) on PN, representing the out-of-domain (OOD) setting with a different document type. Robustness was assessed by calculating the performance gap (ie, the performance drop from in-domain to out-of-domain settings).ResultsThe LLM demonstrated greater robustness, with a smaller performance gap in F1-scores (ID–OOD = −8.6) compared to the MLM baseline performance (ID–OOD = −13.9). This indicated more stable performance across ID and OOD settings, highlighting the effectiveness of fine-tuned LLMs for reliable use in diverse clinical settings.ConclusionsFine-tuned LLMs demonstrate superior robustness for disease name recognition in Japanese clinical notes, with a smaller performance gap. These findings highlight the potential of LLMs as reliable tools for clinical natural language processing in low-resource language settings and support their deployment in real-world health care applications, where diversity in documentation is inevitable.

With the rapid development of large language models (LLMs) in natural language processing and generation tasks, researchers are continuously validating their application potential in the field of medical artificial intelligence (AI). Generative Pre-trained Transformer 5 (GPT-5), Pathways Language Model 2 (PaLM-2), Large Language Model Meta AI 3 (Llama-3), Gemini-2.5, and various medical vertical models have demonstrated excellent performance in many medical and health-related tasks. However, LLMs still face key bottlenecks in real-world medical scenarios, including “illusions” slow knowledge updates, and a lack of interpretability. These problems severely restrict the safe deployment of large language models in high-risk medical scenarios and have become a major obstacle to the transition of medical artificial intelligence from research to clinical application. Retrieval-augmented generation (RAG) technology has therefore become an important solution for improving the credibility of medical LLMs. RAG significantly reduces the risk of information errors by retrieving authoritative medical knowledge before generation while maintaining knowledge updates without retraining. A review of research progress on RAG in the medical field is of great theoretical value and practical significance for promoting the design, evaluation, and standardized application of trustworthy medical AI. This review aims to systematically summarize the research progress of RAG in medical scenarios, including the technical frameworks, typical applications, and development trends of three types of methods—naive RAG, advanced RAG, and modular RAG—and further discuss their significance in medical reliability, health equity, and personalized medicine. The naive RAG architecture, through a standard “index-retrieval-generation” process, transforms external knowledge bases into a structured vector space that can be queried by an LLM, achieving positive results in electronic medical record (EMR) summary, preoperative assessment, and medical question answering (QA). However, naive RAG still has limitations in retrieval accuracy and cross-modal processing. To address these shortcomings, advanced RAG methods have been devised that significantly improve the model’s decision-making capabilities by improving retrieval strategies, enhancing inference chains, and introducing self-reflection mechanisms. Furthermore, modular RAG design offers composable, multi-module systems to support multi-source knowledge integration and complex task decomposition. In terms of application value, RAG’s contributions to the healthcare field are primarily reflected in these aspects. On the one hand, it significantly improves the reliability of medical AI by introducing traceable knowledge to reduce illusions. On the other hand, it helps promote healthcare equity by driving a shift toward a patient-centered healthcare model through localized knowledge bases and multilingual support. However, the deployment of RAG in medical scenarios still faces many challenges, such as data privacy risks. Future research should focus on improving self-supervised reflection capabilities and developing cross-modal knowledge fusion technologies. As research develops, RAG is expected to become a core foundational capability of future intelligent healthcare systems, further promoting the development of safe and efficient intelligent healthcare.