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Large language models (LLMs) represent a transformative class of AI tools capable of revolutionizing various aspects of healthcare by generating human-like responses across diverse contexts and adapting to novel tasks following human instructions. Their potential application spans a broad range of medical tasks, such as clinical documentation, matching patients to clinical trials, and answering medical questions. In this primer paper, we propose an actionable guideline to help healthcare professionals more efficiently utilize LLMs in their work, along with a set of best practices. This approach consists of several main phases, including formulating the task, choosing LLMs, prompt engineering, fine-tuning, and deployment. We start with the discussion of critical considerations in identifying healthcare tasks that align with the core capabilities of LLMs and selecting models based on the selected task and data, performance requirements, and model interface. We then review the strategies, such as prompt engineering and fine-tuning, to adapt standard LLMs to specialized medical tasks. Deployment considerations, including regulatory compliance, ethical guidelines, and continuous monitoring for fairness and bias, are also discussed. By providing a structured step-by-step methodology, this tutorial aims to equip healthcare professionals with the tools necessary to effectively integrate LLMs into clinical practice, ensuring that these powerful technologies are applied in a safe, reliable, and impactful manner., Competing Interests: Disclosures The recommendations in this article are those of the authors and do not necessarily represent the official position of the National Institutes of Health.

Expert curation is essential to capture knowledge of enzyme functions from the scientific literature in FAIR open knowledgebases but cannot keep pace with the rate of new discoveries and new publications. In this work we present EnzChemRED, for Enzyme Chemistry Relation Extraction Dataset, a new training and benchmarking dataset to support the development of Natural Language Processing (NLP) methods such as (large) language models that can assist enzyme curation. EnzChemRED consists of 1,210 expert curated PubMed abstracts where enzymes and the chemical reactions they catalyze are annotated using identifiers from the protein knowledgebase UniProtKB and the chemical ontology ChEBI. We show that fine-tuning language models with EnzChemRED significantly boosts their ability to identify proteins and chemicals in text (86.30% F 1 score) and to extract the chemical conversions (86.66% F 1 score) and the enzymes that catalyze those conversions (83.79% F 1 score). We apply our methods to abstracts at PubMed scale to create a draft map of enzyme functions in literature to guide curation efforts in UniProtKB and the reaction knowledgebase Rhea., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

PubTator 3.0 (https://www.ncbi.nlm.nih.gov/research/pubtator3/) is a biomedical literature resource using state-of-the-art AI techniques to offer semantic and relation searches for key concepts like proteins, genetic variants, diseases and chemicals. It currently provides over one billion entity and relation annotations across approximately 36 million PubMed abstracts and 6 million full-text articles from the PMC open access subset, updated weekly. PubTator 3.0's online interface and API utilize these precomputed entity relations and synonyms to provide advanced search capabilities and enable large-scale analyses, streamlining many complex information needs. We showcase the retrieval quality of PubTator 3.0 using a series of entity pair queries, demonstrating that PubTator 3.0 retrieves a greater number of articles than either PubMed or Google Scholar, with higher precision in the top 20 results. We further show that integrating ChatGPT (GPT-4) with PubTator APIs dramatically improves the factuality and verifiability of its responses. In summary, PubTator 3.0 offers a comprehensive set of features and tools that allow researchers to navigate the ever-expanding wealth of biomedical literature, expediting research and unlocking valuable insights for scientific discovery., (Published by Oxford University Press on behalf of Nucleic Acids Research 2024.)

Biomedical research yields vast information, much of which is only accessible through the literature. Consequently, literature search is crucial for healthcare and biomedicine. Recent improvements in artificial intelligence (AI) have expanded functionality beyond keywords, but they might be unfamiliar to clinicians and researchers. In response, we present an overview of over 30 literature search tools tailored to common biomedical use cases, aiming at helping readers efficiently fulfill their information needs. We first discuss recent improvements and continued challenges of the widely used PubMed. Then, we describe AI-based literature search tools catering to five specific information needs: 1. Evidence-based medicine. 2. Precision medicine and genomics. 3. Searching by meaning, including questions. 4. Finding related articles with literature recommendation. 5. Discovering hidden associations through literature mining. Finally, we discuss the impacts of recent developments of large language models such as ChatGPT on biomedical information seeking., Competing Interests: Declaration of interests None declared., (Published by Elsevier B.V.)

Motivation: Biomedical named entity recognition (BioNER) seeks to automatically recognize biomedical entities in natural language text, serving as a necessary foundation for downstream text mining tasks and applications such as information extraction and question answering. Manually labeling training data for the BioNER task is costly, however, due to the significant domain expertise required for accurate annotation. The resulting data scarcity causes current BioNER approaches to be prone to overfitting, to suffer from limited generalizability, and to address a single entity type at a time (e.g. gene or disease)., Results: We therefore propose a novel all-in-one (AIO) scheme that uses external data from existing annotated resources to enhance the accuracy and stability of BioNER models. We further present AIONER, a general-purpose BioNER tool based on cutting-edge deep learning and our AIO schema. We evaluate AIONER on 14 BioNER benchmark tasks and show that AIONER is effective, robust, and compares favorably to other state-of-the-art approaches such as multi-task learning. We further demonstrate the practical utility of AIONER in three independent tasks to recognize entity types not previously seen in training data, as well as the advantages of AIONER over existing methods for processing biomedical text at a large scale (e.g. the entire PubMed data)., Availability and Implementation: The source code, trained models and data for AIONER are freely available at https://github.com/ncbi/AIONER., (Published by Oxford University Press 2023.)

The BioCreative National Library of Medicine (NLM)-Chem track calls for a community effort to fine-tune automated recognition of chemical names in the biomedical literature. Chemicals are one of the most searched biomedical entities in PubMed, and-as highlighted during the coronavirus disease 2019 pandemic-their identification may significantly advance research in multiple biomedical subfields. While previous community challenges focused on identifying chemical names mentioned in titles and abstracts, the full text contains valuable additional detail. We, therefore, organized the BioCreative NLM-Chem track as a community effort to address automated chemical entity recognition in full-text articles. The track consisted of two tasks: (i) chemical identification and (ii) chemical indexing. The chemical identification task required predicting all chemicals mentioned in recently published full-text articles, both span [i.e. named entity recognition (NER)] and normalization (i.e. entity linking), using Medical Subject Headings (MeSH). The chemical indexing task required identifying which chemicals reflect topics for each article and should therefore appear in the listing of MeSH terms for the document in the MEDLINE article indexing. This manuscript summarizes the BioCreative NLM-Chem track and post-challenge experiments. We received a total of 85 submissions from 17 teams worldwide. The highest performance achieved for the chemical identification task was 0.8672 F-score (0.8759 precision and 0.8587 recall) for strict NER performance and 0.8136 F-score (0.8621 precision and 0.7702 recall) for strict normalization performance. The highest performance achieved for the chemical indexing task was 0.6073 F-score (0.7417 precision and 0.5141 recall). This community challenge demonstrated that (i) the current substantial achievements in deep learning technologies can be utilized to improve automated prediction accuracy further and (ii) the chemical indexing task is substantially more challenging. We look forward to further developing biomedical text-mining methods to respond to the rapid growth of biomedical literature. The NLM-Chem track dataset and other challenge materials are publicly available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BC7-NLM-Chem-track/. Database URL https://ftp.ncbi.nlm.nih.gov/pub/lu/BC7-NLM-Chem-track/., (Published by Oxford University Press 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

A significant percentage of COVID-19 survivors experience ongoing multisystemic symptoms that often affect daily living, a condition known as Long Covid or post-acute-sequelae of SARS-CoV-2 infection. However, identifying scientific articles relevant to Long Covid is challenging since there is no standardized or consensus terminology. We developed an iterative human-in-the-loop machine learning framework combining data programming with active learning into a robust ensemble model, demonstrating higher specificity and considerably higher sensitivity than other methods. Analysis of the Long Covid Collection shows that (1) most Long Covid articles do not refer to Long Covid by any name, (2) when the condition is named, the name used most frequently in the literature is Long Covid, and (3) Long Covid is associated with disorders in a wide variety of body systems. The Long Covid Collection is updated weekly and is searchable online at the LitCovid portal: https://www.ncbi.nlm.nih.gov/research/coronavirus/docsum?filters=e_condition.LongCovid., Competing Interests: The authors declare no competing interests.

LitCovid (https://www.ncbi.nlm.nih.gov/research/coronavirus/)-first launched in February 2020-is a first-of-its-kind literature hub for tracking up-to-date published research on COVID-19. The number of articles in LitCovid has increased from 55 000 to ∼300 000 over the past 2.5 years, with a consistent growth rate of ∼10 000 articles per month. In addition to the rapid literature growth, the COVID-19 pandemic has evolved dramatically. For instance, the Omicron variant has now accounted for over 98% of new infections in the United States. In response to the continuing evolution of the COVID-19 pandemic, this article describes significant updates to LitCovid over the last 2 years. First, we introduced the long Covid collection consisting of the articles on COVID-19 survivors experiencing ongoing multisystemic symptoms, including respiratory issues, cardiovascular disease, cognitive impairment, and profound fatigue. Second, we provided new annotations on the latest COVID-19 strains and vaccines mentioned in the literature. Third, we improved several existing features with more accurate machine learning algorithms for annotating topics and classifying articles relevant to COVID-19. LitCovid has been widely used with millions of accesses by users worldwide on various information needs and continues to play a critical role in collecting, curating and standardizing the latest knowledge on the COVID-19 literature., (Published by Oxford University Press on behalf of Nucleic Acids Research 2022.)

The automatic recognition of chemical names and their corresponding database identifiers in biomedical text is an important first step for many downstream text-mining applications. The task is even more challenging when considering the identification of these entities in the article's full text and, furthermore, the identification of candidate substances for that article's metadata [Medical Subject Heading (MeSH) article indexing]. The National Library of Medicine (NLM)-Chem track at BioCreative VII aimed to foster the development of algorithms that can predict with high quality the chemical entities in the biomedical literature and further identify the chemical substances that are candidates for article indexing. As a result of this challenge, the NLM-Chem track produced two comprehensive, manually curated corpora annotated with chemical entities and indexed with chemical substances: the chemical identification corpus and the chemical indexing corpus. The NLM-Chem BioCreative VII (NLM-Chem-BC7) Chemical Identification corpus consists of 204 full-text PubMed Central (PMC) articles, fully annotated for chemical entities by 12 NLM indexers for both span (i.e. named entity recognition) and normalization (i.e. entity linking) using MeSH. This resource was used for the training and testing of the Chemical Identification task to evaluate the accuracy of algorithms in predicting chemicals mentioned in recently published full-text articles. The NLM-Chem-BC7 Chemical Indexing corpus consists of 1333 recently published PMC articles, equipped with chemical substance indexing by manual experts at the NLM. This resource was used for the evaluation of the Chemical Indexing task, which evaluated the accuracy of algorithms in predicting the chemicals that should be indexed, i.e. appear in the listing of MeSH terms for the document. This set was further enriched after the challenge in two ways: (i) 11 NLM indexers manually verified each of the candidate terms appearing in the prediction results of the challenge participants, but not in the MeSH indexing, and the chemical indexing terms appearing in the MeSH indexing list, but not in the prediction results, and (ii) the challenge organizers algorithmically merged the chemical entity annotations in the full text for all predicted chemical entities and used a statistical approach to keep those with the highest degree of confidence. As a result, the NLM-Chem-BC7 Chemical Indexing corpus is a gold-standard corpus for chemical indexing of journal articles and a silver-standard corpus for chemical entity identification in full-text journal articles. Together, these resources are currently the most comprehensive resources for chemical entity recognition, and we demonstrate improvements in the chemical entity recognition algorithms. We detail the characteristics of these novel resources and make them available for the community. Database URL: https://ftp.ncbi.nlm.nih.gov/pub/lu/NLM-Chem-BC7-corpus/., (Published by Oxford University Press 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The coronavirus disease 2019 (COVID-19) pandemic has been severely impacting global society since December 2019. The related findings such as vaccine and drug development have been reported in biomedical literature-at a rate of about 10 000 articles on COVID-19 per month. Such rapid growth significantly challenges manual curation and interpretation. For instance, LitCovid is a literature database of COVID-19-related articles in PubMed, which has accumulated more than 200 000 articles with millions of accesses each month by users worldwide. One primary curation task is to assign up to eight topics (e.g. Diagnosis and Treatment) to the articles in LitCovid. The annotated topics have been widely used for navigating the COVID literature, rapidly locating articles of interest and other downstream studies. However, annotating the topics has been the bottleneck of manual curation. Despite the continuing advances in biomedical text-mining methods, few have been dedicated to topic annotations in COVID-19 literature. To close the gap, we organized the BioCreative LitCovid track to call for a community effort to tackle automated topic annotation for COVID-19 literature. The BioCreative LitCovid dataset-consisting of over 30 000 articles with manually reviewed topics-was created for training and testing. It is one of the largest multi-label classification datasets in biomedical scientific literature. Nineteen teams worldwide participated and made 80 submissions in total. Most teams used hybrid systems based on transformers. The highest performing submissions achieved 0.8875, 0.9181 and 0.9394 for macro-F1-score, micro-F1-score and instance-based F1-score, respectively. Notably, these scores are substantially higher (e.g. 12%, higher for macro F1-score) than the corresponding scores of the state-of-art multi-label classification method. The level of participation and results demonstrate a successful track and help close the gap between dataset curation and method development. The dataset is publicly available via https://ftp.ncbi.nlm.nih.gov/pub/lu/LitCovid/biocreative/ for benchmarking and further development. Database URL https://ftp.ncbi.nlm.nih.gov/pub/lu/LitCovid/biocreative/., (Published by Oxford University Press 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)