Hongfang Liu

Ziwen Kan, Yishuo Chen, Kecheng Li et al.

Time series foundation models (TS-FMs) aim to learn generalizable temporal representations that can be adapted to a wide range of downstream tasks. In real-world multimodal settings, time series are frequently affected by temporal misalignment and partial modality missingness, where different modalities are observed at heterogeneous time scales or are partially absent. Existing approaches typically rely on naive imputation or masking strategies, which fail to account for cross-modal dependencies and often lead to misaligned or degraded representations. We propose TRACE, a conditional estimation paradigm for multimodal time series foundation model pipelines under missingness and irregular sampling, allowing incomplete target modalities to be systematically inferred from available auxiliary modalities. We evaluate TRACE on diverse multimodal benchmarks spanning healthcare and affective computing, including the MIMIC-IV clinical dataset and the CMU-MOSI and CMU-MOSEI benchmarks for multimodal sentiment analysis. Across a range of downstream prediction tasks and missing-modality settings, TRACE consistently outperforms prior multimodal fusion approaches, demonstrating improved robustness to severe modality missingness and more reliable cross-modal representations.

Xiaoyang Ruan, Liwei Wang, Charat Thongprayoon et al.

Accurate prediction models for individual-level endpoints and time-to-endpoints are crucial in clinical practice. In this study, we propose a novel approach, GRU-D-Weibull, which combines gated recurrent units with decay (GRU-D) to model the Weibull distribution. Our method enables real-time individualized endpoint prediction and population-level risk management. Using a cohort of 6,879 patients with stage 4 chronic kidney disease (CKD4), we evaluated the performance of GRU-D-Weibull in endpoint prediction. The C-index of GRU-D-Weibull was ~0.7 at the index date and increased to ~0.77 after 4.3 years of follow-up, similar to random survival forest. Our approach achieved an absolute L1-loss of ~1.1 years (SD 0.95) at the CKD4 index date and a minimum of ~0.45 years (SD0.3) at 4 years of follow-up, outperforming competing methods significantly. GRU-D-Weibull consistently constrained the predicted survival probability at the time of an event within a smaller and more fixed range compared to other models throughout the follow-up period. We observed significant correlations between the error in point estimates and missing proportions of input features at the index date (correlations from ~0.1 to ~0.3), which diminished within 1 year as more data became available. By post-training recalibration, we successfully aligned the predicted and observed survival probabilities across multiple prediction horizons at different time points during follow-up. Our findings demonstrate the considerable potential of GRU-D-Weibull as the next-generation architecture for endpoint risk management, capable of generating various endpoint estimates for real-time monitoring using clinical data.

Sicheng Zhou, Nan Wang, Liwei Wang et al.

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.

Ziyi Chen, Ren Yang, Sunyang Fu et al.

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.

Xiaoyang Ruan, Liwei Wang, Michelle Mai et al.

Real-time individual endpoint prediction has always been a challenging task but of great clinic utility for both patients and healthcare providers. With 6,879 chronic kidney disease stage 4 (CKD4) patients as a use case, we explored the feasibility and performance of gated recurrent units with decay that models Weibull probability density function (GRU-D-Weibull) as a semi-parametric longitudinal model for real-time individual endpoint prediction. 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 L1-loss of GRU-D-Weibull is ~66% of XGB(AFT), ~60% of MTLR, and ~30% of AFT model at CKD4 index date. 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 missing, 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.

Zehan Li, Yan Hu, Scott Lane et al.

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

Yao Yan, Thomas Yu, Kathleen Muenzen et al.

Objective The evaluation of natural language processing (NLP) models for clinical text de-identification relies on the availability of clinical notes, which is often restricted due to privacy concerns. The NLP Sandbox is an approach for alleviating the lack of data and evaluation frameworks for NLP models by adopting a federated, model-to-data approach. This enables unbiased federated model evaluation without the need for sharing sensitive data from multiple institutions. Materials and Methods We leveraged the Synapse collaborative framework, containerization software, and OpenAPI generator to build the NLP Sandbox (nlpsandbox.io). We evaluated two state-of-the-art NLP de-identification focused annotation models, Philter and NeuroNER, using data from three institutions. We further validated model performance using data from an external validation site. Results We demonstrated the usefulness of the NLP Sandbox through de-identification clinical model evaluation. The external developer was able to incorporate their model into the NLP Sandbox template and provide user experience feedback. Discussion We demonstrated the feasibility of using the NLP Sandbox to conduct a multi-site evaluation of clinical text de-identification models without the sharing of data. Standardized model and data schemas enable smooth model transfer and implementation. To generalize the NLP Sandbox, work is required on the part of data owners and model developers to develop suitable and standardized schemas and to adapt their data or model to fit the schemas. Conclusions The NLP Sandbox lowers the barrier to utilizing clinical data for NLP model evaluation and facilitates federated, multi-site, unbiased evaluation of NLP models.

Rui Yang, Huitao Li, Weihao Xuan et al.

Despite continuous advances in medical technology, the global distribution of health care resources remains uneven. The development of large language models (LLMs) has transformed the landscape of medicine and holds promise for improving health care quality and expanding access to medical information globally. However, existing LLMs are primarily trained on high-resource languages, limiting their applicability in global medical scenarios. To address this gap, we constructed GlobMed, a large multilingual medical dataset, containing over 500,000 entries spanning 12 languages, including four low-resource languages. Building on this, we established GlobMed-Bench, which systematically assesses 56 state-of-the-art proprietary and open-weight LLMs across multiple multilingual medical tasks, revealing significant performance disparities across languages, particularly for low-resource languages. Additionally, we introduced GlobMed-LLMs, a suite of multilingual medical LLMs trained on GlobMed, with parameters ranging from 1.7B to 8B. GlobMed-LLMs achieved an average performance improvement of over 40% relative to baseline models, with a more than threefold increase in performance on low-resource languages. Together, these resources provide an important foundation for advancing the equitable development and application of LLMs globally, enabling broader language communities to benefit from technological advances.

Qiuhao Lu, Rui Li, Andrew Wen et al.

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.

Kai Zhang, Rong Zhou, Eashan Adhikarla et al.

Traditional biomedical artificial intelligence (AI) models, designed for specific tasks or modalities, often exhibit limited flexibility in real-world deployment and struggle to utilize holistic information. Generalist AI holds the potential to address these limitations due to its versatility in interpreting different data types and generating tailored outputs for diverse needs. However, existing biomedical generalist AI solutions are typically heavyweight and closed source to researchers, practitioners, and patients. Here, we propose BiomedGPT, the first open-source and lightweight vision-language foundation model, designed as a generalist capable of performing various biomedical tasks. BiomedGPT achieved state-of-the-art results in 16 out of 25 experiments while maintaining a computing-friendly model scale. We also conducted human evaluations to assess the capabilities of BiomedGPT in radiology visual question answering, report generation, and summarization. BiomedGPT exhibits robust prediction ability with a low error rate of 3.8% in question answering, satisfactory performance with an error rate of 8.3% in writing complex radiology reports, and competitive summarization ability with a nearly equivalent preference score to human experts. Our method demonstrates that effective training with diverse data can lead to more practical biomedical AI for improving diagnosis and workflow efficiency.

Yanshan Wang, Hongfang Liu

Probabilistic language models are widely used in Information Retrieval (IR) to rank documents by the probability that they generate the query. However, the implementation of the probabilistic representations with programming languages that favor matrix calculations is challenging. In this paper, we utilize matrix representations to reformulate the probabilistic language models. The matrix representation is a superstructure for the probabilistic language models to organize the calculated probabilities and a potential formalism for standardization of language models and for further mathematical analysis. It facilitates implementations by matrix friendly programming languages. In this paper, we consider the matrix formulation of conventional language model with Dirichlet smoothing, and two language models based on Latent Dirichlet Allocation (LDA), i.e., LBDM and LDI. We release a Java software package--MatLM--implementing the proposed models. Code is available at: https://github.com/yanshanwang/JGibbLDA-v.1.0-MatLM.

Kurt Miller, Qiuhao Lu, William Hersh et al.

Clinical document metadata, such as document type, structure, author role, medical specialty, and encounter setting, is essential for accurate interpretation of information captured in clinical documents. However, vast documentation heterogeneity and drift over time challenge harmonization of document metadata. Automated extraction methods have emerged to coalesce metadata from disparate practices into target schema. This scoping review aims to catalog research on clinical document metadata extraction, identify methodological trends and applications, and highlight gaps. We followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines to identify articles that perform clinical document metadata extraction. We initially found and screened 266 articles published between January 2011 and August 2025, then comprehensively reviewed 67 we deemed relevant to our study. Among the articles included, 45 were methodological, 17 used document metadata as features in a downstream application, and 5 analyzed document metadata composition. We observe myriad purposes for methodological study and application types. Available labelled public data remains sparse except for structural section datasets. Methods for extracting document metadata have progressed from largely rule-based and traditional machine learning with ample feature engineering to transformer-based architectures with minimal feature engineering. The emergence of large language models has enabled broader exploration of generalizability across tasks and datasets, allowing the possibility of advanced clinical text processing systems. We anticipate that research will continue to expand into richer document metadata representations and integrate further into clinical applications and workflows.

Cheng Peng, Kai Zhang, Mengxian Lyu et al.

To advance biomedical vison-language model capabilities through scaling up, fine-tuning, and instruction tuning, develop vision-language models with improved performance in handling long text, explore strategies to efficiently adopt vision language models for diverse multi-modal biomedical tasks, and examine the zero-shot learning performance. We developed two biomedical vision language models, BiomedGPT-Large and BiomedGPT-XLarge, based on an encoder-decoder-based transformer architecture. We fine-tuned the two models on 23 benchmark datasets from 6 multi-modal biomedical tasks including one image-only task (image classification), three language-only tasks (text understanding, text summarization and question answering), and two vision-language tasks (visual question answering and image captioning). We compared the developed scaled models with our previous BiomedGPT-Base model and existing prestigious models reported in the literature. We instruction-tuned the two models using a large-scale multi-modal biomedical instruction-tuning dataset and assessed the zero-shot learning performance and alignment accuracy.

Jaerong Ahn, Andrew Wen, Nan Wang et al.

The Observational Medical Outcomes Partnership (OMOP) common data model (CDM) provides a standardized representation of heterogeneous health data to support large-scale, multi-institutional research. One critical step in data standardization using OMOP CDM is the mapping of source medical terms to OMOP standard concepts, a procedure that is resource-intensive and error-prone. While large language models (LLMs) have the potential to facilitate this process, their tendency toward hallucination makes them unsuitable for clinical deployment without training and expert validation. Here, we developed a zero-training, hallucination-preventive mapping system based on the Model Context Protocol (MCP), a standardized and secure framework allowing LLMs to interact with external resources and tools. The system enables explainable mapping and significantly improves efficiency and accuracy with minimal effort. It provides real-time vocabulary lookups and structured reasoning outputs suitable for immediate use in both exploratory and production environments.

Ming Huang, Zehan Li, Yan Hu et al.

Suicide remains a pressing global health crisis, with over 720,000 deaths annually and millions more affected by suicide ideation (SI) and suicide attempts (SA). Early identification of suicidality-related factors (SrFs), including SI, SA, exposure to suicide (ES), and non-suicidal self-injury (NSSI), is critical for timely intervention. While prior studies have applied AI to detect SrFs in clinical notes, most treat suicidality as a binary classification task, overlooking the complexity of cooccurring risk factors. This study explores the use of generative large language models (LLMs), specifically GPT-3.5 and GPT-4.5, for multi-label classification (MLC) of SrFs from psychiatric electronic health records (EHRs). We present a novel end to end generative MLC pipeline and introduce advanced evaluation methods, including label set level metrics and a multilabel confusion matrix for error analysis. Finetuned GPT-3.5 achieved top performance with 0.94 partial match accuracy and 0.91 F1 score, while GPT-4.5 with guided prompting showed superior performance across label sets, including rare or minority label sets, indicating a more balanced and robust performance. Our findings reveal systematic error patterns, such as the conflation of SI and SA, and highlight the models tendency toward cautious over labeling. This work not only demonstrates the feasibility of using generative AI for complex clinical classification tasks but also provides a blueprint for structuring unstructured EHR data to support large scale clinical research and evidence based medicine.

Mingchen Li, Jiatan Huang, Jeremy Yeung et al.

Medical Large Language Models (LLMs) have demonstrated impressive performance on a wide variety of medical NLP tasks; however, there still lacks a LLM specifically designed for phenotyping identification and diagnosis in cancer domain. Moreover, these LLMs typically have several 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 nearly 2.7M clinical notes and over 515K pathology reports covering 17 cancer types, followed by fine-tuning on two cancer-relevant tasks, including cancer phenotypes extraction and cancer diagnosis generation. Our evaluation demonstrated that the CancerLLM achieves state-of-the-art results with F1 score of 91.78% on phenotyping extraction and 86.81% on disganois generation. It outperformed existing LLMs, with an average F1 score improvement of 9.23%. Additionally, the CancerLLM demonstrated its efficiency on time and GPU usage, and robustness comparing with other LLMs. We demonstrated that CancerLLM can potentially provide an effective and robust solution to advance clinical research and practice in cancer domain

Sungrim Moon, Huan He, Hongfang Liu et al.

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.

Sijia Liu, Andrew Wen, Liwei Wang et al.

While we pay attention to the latest advances in clinical natural language processing (NLP), we can notice some resistance in the clinical and translational research community to adopt NLP models due to limited transparency, interpretability, and usability. In this study, we proposed an open natural language processing development framework. We evaluated it through the implementation of NLP algorithms for the National COVID Cohort Collaborative (N3C). Based on the interests in information extraction from COVID-19 related clinical notes, our work includes 1) an open data annotation process using COVID-19 signs and symptoms as the use case, 2) a community-driven ruleset composing platform, and 3) a synthetic text data generation workflow to generate texts for information extraction tasks without involving human subjects. The corpora were derived from texts from three different institutions (Mayo Clinic, University of Kentucky, University of Minnesota). The gold standard annotations were tested with a single institution's (Mayo) ruleset. This resulted in performances of 0.876, 0.706, and 0.694 in F-scores for Mayo, Minnesota, and Kentucky test datasets, respectively. The study as a consortium effort of the N3C NLP subgroup demonstrates the feasibility of creating a federated NLP algorithm development and benchmarking platform to enhance multi-institution clinical NLP study and adoption. Although we use COVID-19 as a use case in this effort, our framework is general enough to be applied to other domains of interest in clinical NLP.

Sicheng Zhou, Liwei Wang, Nan Wang et al.

Accurate extraction of breast cancer patients' phenotypes is important for clinical decision support and clinical research. Current models do not take full advantage of cancer domain-specific corpus, whether pre-training Bidirectional Encoder Representations from Transformer model on cancer-specific corpus could improve the performances of extracting breast cancer phenotypes from texts data remains to be explored. The objective of this study is to develop and evaluate the CancerBERT model for extracting breast cancer phenotypes from clinical texts in electronic health records. This data used in the study included 21,291 breast cancer patients diagnosed from 2010 to 2020, patients' clinical notes and pathology reports were collected from the University of Minnesota Clinical Data Repository (UMN). Results: About 3 million clinical notes and pathology reports in electronic health records for 21,291 breast cancer patients were collected to train the CancerBERT model. 200 pathology reports and 50 clinical notes of breast cancer patients that contain 9,685 sentences and 221,356 tokens were manually annotated by two annotators. 20% of the annotated data was used as a test set. Our CancerBERT model achieved the best performance with macro F1 scores equal to 0.876 (95% CI, 0.896-0.902) for exact match and 0.904 (95% CI, 0.896-0.902) for the lenient match. The NER models we developed would facilitate the automated information extraction from clinical texts to further help clinical decision support. Conclusions and Relevance: In this study, we focused on the breast cancer-related concepts extraction from EHR data and obtained a comprehensive annotated dataset that contains 7 types of breast cancer-related concepts. The CancerBERT model with customized vocabulary could significantly improve the performance for extracting breast cancer phenotypes from clinical texts.

Greg M. Silverman, Raymond L. Finzel, Michael V. Heinz et al.

Our objective in this study is to investigate the behavior of Boolean operators on combining annotation output from multiple Natural Language Processing (NLP) systems across multiple corpora and to assess how filtering by aggregation of Unified Medical Language System (UMLS) Metathesaurus concepts affects system performance for Named Entity Recognition (NER) of UMLS concepts. We used three corpora annotated for UMLS concepts: 2010 i2b2 VA challenge set (31,161 annotations), Multi-source Integrated Platform for Answering Clinical Questions (MiPACQ) corpus (17,457 annotations including UMLS concept unique identifiers), and Fairview Health Services corpus (44,530 annotations). Our results showed that for UMLS concept matching, Boolean ensembling of the MiPACQ corpus trended towards higher performance over individual systems. Use of an approximate grid-search can help optimize the precision-recall tradeoff and can provide a set of heuristics for choosing an optimal set of ensembles.

David Oniani, Chen Wang, Yiqing Zhao et al.

Cancer is responsible for millions of deaths worldwide every year. Although significant progress has been achieved in cancer medicine, many issues remain to be addressed for improving cancer therapy. Appropriate cancer patient stratification is the prerequisite for selecting appropriate treatment plan, as cancer patients are of known heterogeneous genetic make-ups and phenotypic differences. In this study, built upon deep phenotypic characterizations extractable from Mayo Clinic electronic health records (EHRs) and genetic test reports for a collection of cancer patients, we developed a system leveraging a joint of phenotypic and genetic features for cancer patient subgrouping. The workflow is roughly divided into three parts: feature preprocessing, cancer patient classification, and cancer patient clustering based. In feature preprocessing step, we performed filtering, retaining the most relevant features. In cancer patient classification, we utilized joint categorical features to build a patient-feature matrix and applied nine different machine learning models, Random Forests (RF), Decision Tree (DT), Support Vector Machine (SVM), Naive Bayes (NB), Logistic Regression (LR), Multilayer Perceptron (MLP), Gradient Boosting (GB), Convolutional Neural Network (CNN), and Feedforward Neural Network (FNN), for classification purposes. Finally, in the cancer patient clustering step, we leveraged joint embeddings features and patient-feature associations to build an undirected feature graph and then trained the cancer feature node embeddings.

David Oniani, Chen Wang, Yiqing Zhao et al.

Cancer is responsible for millions of deaths worldwide every year. Although significant progress hasbeen achieved in cancer medicine, many issues remain to be addressed for improving cancer therapy.Appropriate cancer patient stratification is the prerequisite for selecting appropriate treatment plan, ascancer patients are of known heterogeneous genetic make-ups and phenotypic differences. In thisstudy, built upon deep phenotypic characterizations extractable from Mayo Clinic electronic healthrecords (EHRs) and genetic test reports for a collection of cancer patients, we evaluated variousgraph neural networks (GNNs) leveraging a joint of phenotypic and genetic features for cancer typeclassification. Models were applied and fine-tuned on the Mayo Clinic cancer disease dataset. Theassessment was done through the reported accuracy, precision, recall, and F1 values as well as throughF1 scores based on the disease class. Per our evaluation results, GNNs on average outperformed thebaseline models with mean statistics always being higher that those of the baseline models (0.849 vs0.772 for accuracy, 0.858 vs 0.794 for precision, 0.843 vs 0.759 for recall, and 0.843 vs 0.855 for F1score). Among GNNs, ChebNet, GraphSAGE, and TAGCN showed the best performance, while GATshowed the worst. We applied and compared eight GNN models including AGNN, ChebNet, GAT,GCN, GIN, GraphSAGE, SGC, and TAGCN on the Mayo Clinic cancer disease dataset and assessedtheir performance as well as compared them with each other and with more conventional machinelearning models such as decision tree, gradient boosting, multi-layer perceptron, naive bayes, andrandom forest which we used as the baselines.

Sunyang Fu, David Chen, Huan He et al.

Background Concept extraction, a subdomain of natural language processing (NLP) with a focus on extracting concepts of interest, has been adopted to computationally extract clinical information from text for a wide range of applications ranging from clinical decision support to care quality improvement. Objectives In this literature review, we provide a methodology review of clinical concept extraction, aiming to catalog development processes, available methods and tools, and specific considerations when developing clinical concept extraction applications. Methods Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search was conducted for retrieving EHR-based information extraction articles written in English and published from January 2009 through June 2019 from Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, Web of Science, and the ACM Digital Library. Results A total of 6,686 publications were retrieved. After title and abstract screening, 228 publications were selected. The methods used for developing clinical concept extraction applications were discussed in this review.

Krishna B. Soundararajan, Sunyang Fu, Luke A. Carlson et al.

Alzheimer's Disease (AD) is the most common type of dementia, comprising 60-80% of cases. There were an estimated 5.8 million Americans living with Alzheimer's dementia in 2019, and this number will almost double every 20 years. The total lifetime cost of care for someone with dementia is estimated to be $350,174 in 2018, 70% of which is associated with family-provided care. Most family caregivers face emotional, financial and physical difficulties. As a medium to relieve this burden, online communities in social media websites such as Twitter, Reddit, and Yahoo! Answers provide potential venues for caregivers to search relevant questions and answers, or post questions and seek answers from other members. However, there are often a limited number of relevant questions and responses to search from, and posted questions are rarely answered immediately. Due to recent advancement in Artificial Intelligence (AI), particularly Natural Language Processing (NLP), we propose to utilize AI to automatically generate answers to AD-related consumer questions posted by caregivers and evaluate how good AI is at answering those questions. To the best of our knowledge, this is the first study in the literature applying and evaluating AI models designed to automatically answer consumer questions related to AD.

Jun Jiang, Shumao Pang, Xia Zhao et al.

Text classification is a fundamental task for text data mining. In order to train a generalizable model, a large volume of text must be collected. To address data insufficiency, cross-lingual data may occasionally be necessary. Cross-lingual data sources may however suffer from data incompatibility, as text written in different languages can hold distinct word sequences and semantic patterns. Machine translation and word embedding alignment provide an effective way to transform and combine data for cross-lingual data training. To the best of our knowledge, there has been little work done on evaluating how the methodology used to conduct semantic space transformation and data combination affects the performance of classification models trained from cross-lingual resources. In this paper, we systematically evaluated the performance of two commonly used CNN (Convolutional Neural Network) and RNN (Recurrent Neural Network) text classifiers with differing data transformation and combination strategies. Monolingual models were trained from English and French alongside their translated and aligned embeddings. Our results suggested that semantic space transformation may conditionally promote the performance of monolingual models. Bilingual models were trained from a combination of both English and French. Our results indicate that a cross-lingual classification model can significantly benefit from cross-lingual data by learning from translated or aligned embedding spaces.

Yanshan Wang, Yiqing Zhao, Terry M. Therneau et al.

Machine learning has become ubiquitous and a key technology on mining electronic health records (EHRs) for facilitating clinical research and practice. Unsupervised machine learning, as opposed to supervised learning, has shown promise in identifying novel patterns and relations from EHRs without using human created labels. In this paper, we investigate the application of unsupervised machine learning models in discovering latent disease clusters and patient subgroups based on EHRs. We utilized Latent Dirichlet Allocation (LDA), a generative probabilistic model, and proposed a novel model named Poisson Dirichlet Model (PDM), which extends the LDA approach using a Poisson distribution to model patients' disease diagnoses and to alleviate age and sex factors by considering both observed and expected observations. In the empirical experiments, we evaluated LDA and PDM on three patient cohorts with EHR data retrieved from the Rochester Epidemiology Project (REP), for the discovery of latent disease clusters and patient subgroups. We compared the effectiveness of LDA and PDM in identifying latent disease clusters through the visualization of disease representations learned by two approaches. We also tested the performance of LDA and PDM in differentiating patient subgroups through survival analysis, as well as statistical analysis. The experimental results show that the proposed PDM could effectively identify distinguished disease clusters by alleviating the impact of age and sex, and that LDA could stratify patients into more differentiable subgroups than PDM in terms of p-values. However, the subgroups discovered by PDM might imply the underlying patterns of diseases of greater interest in epidemiology research due to the alleviation of age and sex. Both unsupervised machine learning approaches could be leveraged to discover patient subgroups using EHRs but with different foci.

Sijia Liu, Yanshan Wang, Andrew Wen et al.

Background: Widespread adoption of electronic health records (EHRs) has enabled secondary use of EHR data for clinical research and healthcare delivery. Natural language processing (NLP) techniques have shown promise in their capability to extract the embedded information in unstructured clinical data, and information retrieval (IR) techniques provide flexible and scalable solutions that can augment the NLP systems for retrieving and ranking relevant records. Methods: In this paper, we present the implementation of Cohort Retrieval Enhanced by Analysis of Text from EHRs (CREATE), a cohort retrieval system that can execute textual cohort selection queries on both structured and unstructured EHR data. CREATE is a proof-of-concept system that leverages a combination of structured queries and IR techniques on NLP results to improve cohort retrieval performance while adopting the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to enhance model portability. The NLP component empowered by cTAKES is used to extract CDM concepts from textual queries. We design a hierarchical index in Elasticsearch to support CDM concept search utilizing IR techniques and frameworks. Results: Our case study on 5 cohort identification queries evaluated using the IR metric, P@5 (Precision at 5) at both the patient-level and document-level, demonstrates that CREATE achieves an average P@5 of 0.90, which outperforms systems using only structured data or only unstructured data with average P@5s of 0.54 and 0.74, respectively.

Yanshan Wang, Naveed Afzal, Sunyang Fu et al.

The wide adoption of electronic health records (EHRs) has enabled a wide range of applications leveraging EHR data. However, the meaningful use of EHR data largely depends on our ability to efficiently extract and consolidate information embedded in clinical text where natural language processing (NLP) techniques are essential. Semantic textual similarity (STS) that measures the semantic similarity between text snippets plays a significant role in many NLP applications. In the general NLP domain, STS shared tasks have made available a huge collection of text snippet pairs with manual annotations in various domains. In the clinical domain, STS can enable us to detect and eliminate redundant information that may lead to a reduction in cognitive burden and an improvement in the clinical decision-making process. This paper elaborates our efforts to assemble a resource for STS in the medical domain, MedSTS. It consists of a total of 174,629 sentence pairs gathered from a clinical corpus at Mayo Clinic. A subset of MedSTS (MedSTS_ann) containing 1,068 sentence pairs was annotated by two medical experts with semantic similarity scores of 0-5 (low to high similarity). We further analyzed the medical concepts in the MedSTS corpus, and tested four STS systems on the MedSTS_ann corpus. In the future, we will organize a shared task by releasing the MedSTS_ann corpus to motivate the community to tackle the real world clinical problems.

Yanshan Wang, Sunghwan Sohn, Sijia Liu et al.

Objective: To automatically create large labeled training datasets and reduce the efforts of feature engineering for training accurate machine learning models for clinical information extraction. Materials and Methods: We propose a distant supervision paradigm empowered by deep representation for extracting information from clinical text. In this paradigm, the rule-based NLP algorithms are utilized to generate weak labels and create large training datasets automatically. Additionally, we use pre-trained word embeddings as deep representation to eliminate the need of task-specific feature engineering for machine learning. We evaluated the effectiveness of the proposed paradigm on two clinical information extraction tasks: smoking status extraction and proximal femur (hip) fracture extraction. We tested three prevalent machine learning models, namely, Convolutional Neural Networks (CNN), Support Vector Machine (SVM), and Random Forrest (RF). Results: The results indicate that CNN is the best fit to the proposed distant supervision paradigm. It outperforms the rule-based NLP algorithms given large datasets by capturing additional extraction patterns. We also verified the advantage of word embedding feature representation in the paradigm over term frequency-inverse document frequency (tf-idf) and topic modeling representations. Discussion: In the clinical domain, the limited amount of labeled data is always a bottleneck for applying machine learning. Additionally, the performance of machine learning approaches highly depends on task-specific feature engineering. The proposed paradigm could alleviate those problems by leveraging rule-based NLP algorithms to automatically assign weak labels and eliminating the need of task-specific feature engineering using word embedding feature representation.

Feichen Shen, David W Larson, James M. Naessens et al.

Postsurgical complications (PSCs) are known as a deviation from the normal postsurgical course and categorized by severity and treatment requirements. Surgical site infection (SSI) is one of major PSCs and the most common healthcare-associated infection, resulting in increased length of hospital stay and cost. In this work, we assessed an automated way to generate lexicon (i.e., keyword features) from clinical narratives using sublanguage analysis with heuristics to detect SSI and evaluated these keywords with medical experts. To further validate our approach, we also conducted decision tree algorithm on cohort using automatically generated keywords. The results show that our framework was able to identify SSI keywords from clinical narratives and to support search-based natural language processing (NLP) approaches by augmenting search queries.

Yanshan Wang, Sijia Liu, Naveed Afzal et al.

Word embeddings have been widely used in biomedical Natural Language Processing (NLP) applications as they provide vector representations of words capturing the semantic properties of words and the linguistic relationship between words. Many biomedical applications use different textual resources (e.g., Wikipedia and biomedical articles) to train word embeddings and apply these word embeddings to downstream biomedical applications. However, there has been little work on evaluating the word embeddings trained from these resources.In this study, we provide an empirical evaluation of word embeddings trained from four different resources, namely clinical notes, biomedical publications, Wikipedia, and news. We performed the evaluation qualitatively and quantitatively. For the qualitative evaluation, we manually inspected five most similar medical words to a given set of target medical words, and then analyzed word embeddings through the visualization of those word embeddings. For the quantitative evaluation, we conducted both intrinsic and extrinsic evaluation. Based on the evaluation results, we can draw the following conclusions. First, the word embeddings trained on clinical notes and biomedical publications can capture the semantics of medical terms better, and find more relevant similar medical terms, and are closer to human experts' judgments, compared to these trained on Wikipedia and news. Second, there does not exist a consistent global ranking of word embedding quality for downstream biomedical NLP applications. However, adding word embeddings as extra features will improve results on most downstream tasks. Finally, the word embeddings trained on biomedical domain corpora do not necessarily have better performance than those trained on other general domain corpora for any downstream biomedical NLP tasks.

Yanshan Wang, In-Chan Choi, Hongfang Liu

A generalized ensemble model (gEnM) for document ranking is proposed in this paper. The gEnM linearly combines basis document retrieval models and tries to retrieve relevant documents at high positions. In order to obtain the optimal linear combination of multiple document retrieval models or rankers, an optimization program is formulated by directly maximizing the mean average precision. Both supervised and unsupervised learning algorithms are presented to solve this program. For the supervised scheme, two approaches are considered based on the data setting, namely batch and online setting. In the batch setting, we propose a revised Newton's algorithm, gEnM.BAT, by approximating the derivative and Hessian matrix. In the online setting, we advocate a stochastic gradient descent (SGD) based algorithm---gEnM.ON. As for the unsupervised scheme, an unsupervised ensemble model (UnsEnM) by iteratively co-learning from each constituent ranker is presented. Experimental study on benchmark data sets verifies the effectiveness of the proposed algorithms. Therefore, with appropriate algorithms, the gEnM is a viable option in diverse practical information retrieval applications.