Diagnosis prediction is a critical task in healthcare, where timely and accurate identification of medical conditions can significantly impact patient outcomes. Traditional machine learning and deep learning models have achieved notable success in this domain but often lack interpretability which is a crucial requirement in clinical settings. In this study, we explore the use of neuro-symbolic methods, specifically Logical Neural Networks (LNNs), to develop explainable models for diagnosis prediction. Essentially, we design and implement LNN-based models that integrate domain-specific knowledge through logical rules with learnable thresholds. Our models, particularly $M_{\text{multi-pathway}}$ and $M_{\text{comprehensive}}$, demonstrate superior performance over traditional models such as Logistic Regression, SVM, and Random Forest, achieving higher accuracy (up to 80.52\%) and AUROC scores (up to 0.8457) in the case study of diabetes prediction. The learned weights and thresholds within the LNN models provide direct insights into feature contributions, enhancing interpretability without compromising predictive power. These findings highlight the potential of neuro-symbolic approaches in bridging the gap between accuracy and explainability in healthcare AI applications. By offering transparent and adaptable diagnostic models, our work contributes to the advancement of precision medicine and supports the development of equitable healthcare solutions. Future research will focus on extending these methods to larger and more diverse datasets to further validate their applicability across different medical conditions and populations.

Accurate identification and categorization of suicidal events can yield better suicide precautions, reducing operational burden, and improving care quality in high-acuity psychiatric settings. Pre-trained language models offer promise for identifying suicidality from unstructured clinical narratives. We evaluated the performance of four BERT-based models using two fine-tuning strategies (multiple single-label and single multi-label) for detecting coexisting suicidal events from 500 annotated psychiatric evaluation notes. The notes were labeled for suicidal ideation (SI), suicide attempts (SA), exposure to suicide (ES), and non-suicidal self-injury (NSSI). RoBERTa outperformed other models using multiple single-label classification strategy (acc=0.86, F1=0.78). MentalBERT (acc=0.83, F1=0.74) also exceeded BioClinicalBERT (acc=0.82, F1=0.72) which outperformed BERT (acc=0.80, F1=0.70). RoBERTa fine-tuned with single multi-label classification further improved the model performance (acc=0.88, F1=0.81). The findings highlight that the model optimization, pretraining with domain-relevant data, and the single multi-label classification strategy enhance the model performance of suicide phenotyping. Keywords: EHR-based Phenotyping; Natural Language Processing; Secondary Use of EHR Data; Suicide Classification; BERT-based Model; Psychiatry; Mental Health

Large Language Models (LLMs) have revolutionized various sectors, including healthcare where they are employed in diverse applications. Their utility is particularly significant in the context of rare diseases, where data scarcity, complexity, and specificity pose considerable challenges. In the clinical domain, Named Entity Recognition (NER) stands out as an essential task and it plays a crucial role in extracting relevant information from clinical texts. Despite the promise of LLMs, current research mostly concentrates on document-level NER, identifying entities in a more general context across entire documents, without extracting their precise location. Additionally, efforts have been directed towards adapting ChatGPT for token-level NER. However, there is a significant research gap when it comes to employing token-level NER for clinical texts, especially with the use of local open-source LLMs. This study aims to bridge this gap by investigating the effectiveness of both proprietary and local LLMs in token-level clinical NER. Essentially, we delve into the capabilities of these models through a series of experiments involving zero-shot prompting, few-shot prompting, retrieval-augmented generation (RAG), and instruction-fine-tuning. Our exploration reveals the inherent challenges LLMs face in token-level NER, particularly in the context of rare diseases, and suggests possible improvements for their application in healthcare. This research contributes to narrowing a significant gap in healthcare informatics and offers insights that could lead to a more refined application of LLMs in the healthcare sector.

Medical Large Language Models (LLMs) such as ClinicalCamel 70B, Llama3-OpenBioLLM 70B have demonstrated impressive performance on a wide variety of medical NLP task.However, there still lacks a large language model (LLM) specifically designed for cancer domain. Moreover, these LLMs typically have billions of parameters, making them computationally expensive for healthcare systems.Thus, in this study, we propose CancerLLM, a model with 7 billion parameters and a Mistral-style architecture, pre-trained on 2,676,642 clinical notes and 515,524 pathology reports covering 17 cancer types, followed by fine-tuning on three cancer-relevant tasks, including cancer phenotypes extraction, cancer diagnosis generation, and cancer treatment plan generation. Our evaluation demonstrated that CancerLLM achieves state-of-the-art results compared to other existing LLMs, with an average F1 score improvement of 8.1\%. Additionally, CancerLLM outperforms other models on two proposed robustness testbeds. This illustrates that CancerLLM can be effectively applied to clinical AI systems, enhancing clinical research and healthcare delivery in the field of cancer.

Conventional task- and modality-specific artificial intelligence (AI) models are inflexible in real-world deployment and maintenance for biomedicine. At the same time, the growing availability of biomedical data, coupled with the advancements in modern multi-modal multi-task AI techniques, has paved the way for the emergence of generalist biomedical AI solutions. These solutions hold the potential to interpret different medical modalities and produce expressive outputs such as free-text reports or disease diagnosis. Here, we propose BiomedGPT, the first open-source and generalist visual language AI for diverse biomedical tasks. BiomedGPT achieved 16 state-of-the-art results across five clinically significant tasks on 26 datasets. Notably, it outperformed OpenAI's GPT-4 with vision (GPT-4V) in radiology human evaluation and surpassed Google's Med-PaLM M (12B) in breast cancer diagnosis and medical visual question answering. Moreover, BiomedGPT facilitates zero-shot transfer learning, greatly enhancing its utility as a biomedical assistant, similar to ChatGPT. Our method demonstrates effective training with diverse datasets can lead to more practical biomedical AI.

Background: Accurate risk prediction models for individual level endpoint (e.g., death), or time-to-endpoint are highly desirable in clinical practice. Methods: We propose a novel predictive modeling approach, GRU-D-Weibull, which models Weibull distribution leveraging gated recurrent units with decay (GRU-D), for real-time individualized endpoint prediction and population level risk management using electronic health records (EHRs). Experiments: We systematically evaluated the performance and showcased the clinical utility of the proposed approach through individual level endpoint prediction using a cohort of patients with chronic kidney disease stage 4 (CKD4). A total of 536 features including ICD/CPT codes, medications, lab tests, vital measurements, and demographics were retrieved for 6,879 CKD4 patients. The performance metrics including C-index, L1-loss, Parkes' error, and predicted survival probability at time of event were compared between GRU-D-Weibull and other alternative approaches including accelerated failure time model (AFT), XGBoost(AFT), random survival forest (RSF), and Nnet-survival. Both in-process and post-process calibrations were experimented on GRU-D-Weibull generated survival probabilities. Results: GRU-D-Weibull demonstrated C-index of ~0.7 at index date, which increased to ~0.77 at 4.3 years of follow-up, comparable to that of RSF. GRU-D-Weibull achieved absolute L1-loss of ~1.1 years (sd 0.95) at CKD4 index date, and a minimum of ~0.45 year (sd 0.3) at 4 years of follow-up, comparing to second-ranked RSF of ~1.4 years (sd 1.1) at index date and ~0.64 years (sd 0.26) at 4 years. Both significantly outperform competing approaches. GRU-D-Weibull constrained predicted survival probability at time of event to a remarkably smaller and more fixed range than competing models throughout follow-up.

Objective: The generalizability of clinical large language models is usually ignored during the model development process. This study evaluated the generalizability of BERT-based clinical NLP models across different clinical settings through a breast cancer phenotype extraction task. Materials and Methods: Two clinical corpora of breast cancer patients were collected from the electronic health records from the University of Minnesota and the Mayo Clinic, and annotated following the same guideline. We developed three types of NLP models (i.e., conditional random field, bi-directional long short-term memory and CancerBERT) to extract cancer phenotypes from clinical texts. The models were evaluated for their generalizability on different test sets with different learning strategies (model transfer vs. locally trained). The entity coverage score was assessed with their association with the model performances. Results: We manually annotated 200 and 161 clinical documents at UMN and MC, respectively. The corpora of the two institutes were found to have higher similarity between the target entities than the overall corpora. The CancerBERT models obtained the best performances among the independent test sets from two clinical institutes and the permutation test set. The CancerBERT model developed in one institute and further fine-tuned in another institute achieved reasonable performance compared to the model developed on local data (micro-F1: 0.925 vs 0.932). Conclusions: The results indicate the CancerBERT model has the best learning ability and generalizability among the three types of clinical NLP models. The generalizability of the models was found to be correlated with the similarity of the target entities between the corpora.

Background: Extractive question-answering (EQA) is a useful natural language processing (NLP) application for answering patient-specific questions by locating answers in their clinical notes. Realistic clinical EQA can have multiple answers to a single question and multiple focus points in one question, which are lacking in the existing datasets for development of artificial intelligence solutions. Objective: Create a dataset for developing and evaluating clinical EQA systems that can handle natural multi-answer and multi-focus questions. Methods: We leveraged the annotated relations from the 2018 National NLP Clinical Challenges (n2c2) corpus to generate an EQA dataset. Specifically, the 1-to-N, M-to-1, and M-to-N drug-reason relations were included to form the multi-answer and multi-focus QA entries, which represent more complex and natural challenges in addition to the basic one-drug-one-reason cases. A baseline solution was developed and tested on the dataset. Results: The derived RxWhyQA dataset contains 96,939 QA entries. Among the answerable questions, 25% require multiple answers, and 2% ask about multiple drugs within one question. There are frequent cues observed around the answers in the text, and 90% of the drug and reason terms occur within the same or an adjacent sentence. The baseline EQA solution achieved a best f1-measure of 0.72 on the entire dataset, and on specific subsets, it was: 0.93 on the unanswerable questions, 0.48 on single-drug questions versus 0.60 on multi-drug questions, 0.54 on the single-answer questions versus 0.43 on multi-answer questions. Discussion: The RxWhyQA dataset can be used to train and evaluate systems that need to handle multi-answer and multi-focus questions. Specifically, multi-answer EQA appears to be challenging and therefore warrants more investment in research.

Depression is a widespread mental health issue, affecting an estimated 3.8% of the global population. It is also one of the main contributors to disability worldwide. Recently it is becoming popular for individuals to use social media platforms (e.g., Reddit) to express their difficulties and health issues (e.g., depression) and seek support from other users in online communities. It opens great opportunities to automatically identify social media users with depression by parsing millions of posts for potential interventions. Deep learning methods have begun to dominate in the field of machine learning and natural language processing (NLP) because of their ease of use, efficient processing, and state-of-the-art results on many NLP tasks. In this work, we propose a hybrid deep learning model which combines a pretrained sentence BERT (SBERT) and convolutional neural network (CNN) to detect individuals with depression with their Reddit posts. The sentence BERT is used to learn the meaningful representation of semantic information in each post. CNN enables the further transformation of those embeddings and the temporal identification of behavioral patterns of users. We trained and evaluated the model performance to identify Reddit users with depression by utilizing the Self-reported Mental Health Diagnoses (SMHD) data. The hybrid deep learning model achieved an accuracy of 0.86 and an F1 score of 0.86 and outperformed the state-of-the-art documented result (F1 score of 0.79) by other machine learning models in the literature. The results show the feasibility of the hybrid model to identify individuals with depression. Although the hybrid model is validated to detect depression with Reddit posts, it can be easily tuned and applied to other text classification tasks and different clinical applications.

Real-time individual endpoint prediction has always been a challenging task but of great clinic utility for both patients and healthcare providers. GRU-D-Weibull has a maximum C-index of 0.77 at 4.3 years of follow-up, compared to 0.68 achieved by competing models. The average absolute L1-loss of GRU-D-Weibull is around one year, with a minimum of 40% Parkes' serious error after index date. GRU-D-Weibull is not calibrated and significantly underestimates true survival probability. Feature importance tests indicate blood pressure becomes increasingly important during follow-up, while eGFR and blood albumin are less important. Most continuous features have non-linear/parabola impact on predicted survival time, and the results are generally consistent with existing knowledge. GRU-D-Weibull as a semi-parametric temporal model shows advantages in built-in parameterization of missingness, native support for asynchronously arrived measurement, capability of output both probability and point estimates at arbitrary time point for arbitrary prediction horizon, improved discrimination and point estimate accuracy after incorporating newly arrived data. Further research on its performance with more comprehensive input features, in-process or post-process calibration are warranted to benefit CKD4 or alike terminally-ill patients. Author Contribution: XR performed data analysis and manuscript writing. LW performed data extraction, curation, and proof-reading. CT and WC provided expert opinion on selection of study population, explanation of observations, and proof-reading.