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OBJECTIVES: 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. MATERIALS AND METHODS: We created the BioInstruct, comprising 25 005 instructions to instruction-tune LLMs (LLaMA 1 and 2, 7B and 13B version). The instructions were created by prompting the GPT-4 language model with 3-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 3 major categories: question answering (QA), information extraction (IE), and text generation (GEN). We also examined whether categories (eg, QA, IE, and generation) of instructions impact model performance. RESULTS AND DISCUSSION: Comparing with LLMs without instruction-tuned, our instruction-tuned LLMs demonstrated marked performance gains: 17.3% in QA on average accuracy metric, 5.7% in IE on average F1 metric, and 96% in Generation tasks on average GPT-4 score metric. 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 2 tasks. CONCLUSION: The BioInstruct dataset serves as a valuable resource and instruction tuned LLMs lead to the best performing BioNLP applications.

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Automatic International Classification of Diseases (ICD) coding aims to assign multiple ICD codes to a medical note with an average of 3,000+ tokens. This task is challenging due to the high-dimensional space of multi-label assignment (155,000+ ICD code candidates) and the long-tail challenge - Many ICD codes are infrequently assigned yet infrequent ICD codes are important clinically. This study addresses the long-tail challenge by transforming this multi-label classification task into an autoregressive generation task. Specifically, we first introduce a novel pretraining objective to generate free text diagnoses and procedures using the SOAP structure, the medical logic physicians use for note documentation. Second, instead of directly predicting the high dimensional space of ICD codes, our model generates the lower dimension of text descriptions, which then infers ICD codes. Third, we designed a novel prompt template for multi-label classification. We evaluate our Generation with Prompt (GPsoap) model with the benchmark of all code assignment (MIMIC-III-full) and few shot ICD code assignment evaluation benchmark (MIMIC-III-few). Experiments on MIMIC-III-few show that our model performs with a marco F130.2, which substantially outperforms the previous MIMIC-III-full SOTA model (marco F1 4.3) and the model specifically designed for few/zero shot setting (marco F1 18.7). Finally, we design a novel ensemble learner, a cross-attention reranker with prompts, to integrate previous SOTA and our best few-shot coding predictions. Experiments on MIMIC-III-full show that our ensemble learner substantially improves both macro and micro F1, from 10.4 to 14.6 and from 58.2 to 59.1, respectively.

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Pretrained language models (PLMs) have motivated research on what kinds of knowledge these models learn. Fill-in-the-blanks problem (e.g., cloze tests) is a natural approach for gauging such knowledge. BioLAMA generates prompts for biomedical factual knowledge triples and uses the Top-k accuracy metric to evaluate different PLMs' knowledge. However, existing research has shown that such prompt-based knowledge probing methods can only probe a lower bound of knowledge. Many factors like prompt-based probing biases make the LAMA benchmark unreliable and unstable. This problem is more prominent in BioLAMA. The severe long-tailed distribution in vocabulary and large-N-M relation make the performance gap between LAMA and BioLAMA remain notable. To address these, we introduced context variance into the prompt generation and proposed a new rank-change-based evaluation metric. Different from the previous known-unknown evaluation criteria, we proposed the concept of "Misunderstand" in LAMA for the first time. Through experiments on 12 PLMs, we showed that our context variance prompts and Understand-Confuse-Misunderstand (UCM) metric make BioLAMA more friendly to large-N-M relations and rare relations. We also conducted a set of control experiments to disentangle "understand" from just "read and copy".

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OBJECTIVE: Evictions are important social and behavioral determinants of health. Evictions are associated with a cascade of negative events that can lead to unemployment, housing insecurity/homelessness, long-term poverty, and mental health problems. In this study, we developed a natural language processing system to automatically detect eviction status from electronic health record (EHR) notes. MATERIALS AND METHODS: We first defined eviction status (eviction presence and eviction period) and then annotated eviction status in 5000 EHR notes from the Veterans Health Administration (VHA). We developed a novel model, KIRESH, that has shown to substantially outperform other state-of-the-art models such as fine-tuning pretrained language models like BioBERT and Bio_ClinicalBERT. Moreover, we designed a novel prompt to further improve the model performance by using the intrinsic connection between the 2 subtasks of eviction presence and period prediction. Finally, we used the Temperature Scaling-based Calibration on our KIRESH-Prompt method to avoid overconfidence issues arising from the imbalance dataset. RESULTS: KIRESH-Prompt substantially outperformed strong baseline models including fine-tuning the Bio_ClinicalBERT model to achieve 0.74672 MCC, 0.71153 Macro-F1, and 0.83396 Micro-F1 in predicting eviction period and 0.66827 MCC, 0.62734 Macro-F1, and 0.7863 Micro-F1 in predicting eviction presence. We also conducted additional experiments on a benchmark social determinants of health (SBDH) dataset to demonstrate the generalizability of our methods. CONCLUSION AND FUTURE WORK: KIRESH-Prompt has substantially improved eviction status classification. We plan to deploy KIRESH-Prompt to the VHA EHRs as an eviction surveillance system to help address the US Veterans' housing insecurity.

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This paper proposes a new natural language processing (NLP) application for identifying medical jargon terms potentially difficult for patients to comprehend from electronic health record (EHR) notes. We first present a novel and publicly available dataset with expert-annotated medical jargon terms from 18K+ EHR note sentences (MedJ). Then, we introduce a novel medical jargon extraction (MedJEx) model which has been shown to outperform existing state-of-the-art NLP models. First, MedJEx improved the overall performance when it was trained on an auxiliary Wikipedia hyperlink span dataset, where hyperlink spans provide additional Wikipedia articles to explain the spans (or terms), and then fine-tuned on the annotated MedJ data. Secondly, we found that a contextualized masked language model score was beneficial for detecting domain-specific unfamiliar jargon terms. Moreover, our results show that training on the auxiliary Wikipedia hyperlink span datasets improved six out of eight biomedical named entity recognition benchmark datasets. Both MedJ and MedJEx are publicly available.

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Language Models (LMs) have performed well on biomedical natural language processing applications. In this study, we conducted some experiments to use prompt methods to extract knowledge from LMs as new knowledge Bases (LMs as KBs). However, prompting can only be used as a low bound for knowledge extraction, and perform particularly poorly on biomedical domain KBs. In order to make LMs as KBs more in line with the actual application scenarios of the biomedical domain, we specifically add EHR notes as context to the prompt to improve the low bound in the biomedical domain. We design and validate a series of experiments for our Dynamic-Context-BioLAMA task. Our experiments show that the knowledge possessed by those language models can distinguish the correct knowledge from the noise knowledge in the EHR notes, and such distinguishing ability can also be used as a new metric to evaluate the amount of knowledge possessed by the model.

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