arXiv subjects

Hongfang Liu

Publications and source records attributed to Hongfang Liu.

At least 37 records · Page 2Linked to original sources

arXiv2023

GRU-D-Weibull: A Novel Real-Time Individualized Endpoint Prediction

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.

cs.LG↗

arXiv2023

Systematic Design and Evaluation of Social Determinants of Health Ontology (SDoHO)

Social determinants of health (SDoH) have a significant impact on health outcomes and well-being. Addressing SDoH is the key to reducing healthcare inequalities and transforming a "sick care" system into a "health promoting" system. To address the SDOH terminology gap and better embed relevant elements in advanced biomedical informatics, we propose an SDoH ontology (SDoHO), which represents fundamental SDoH factors and their relationships in a standardized and measurable way. The ontology formally models classes, relationships, and constraints based on multiple SDoH-related resources. Expert review and coverage evaluation, using clinical notes data and a national survey, showed satisfactory results. SDoHO could potentially play an essential role in providing a foundation for a comprehensive understanding of the associations between SDoH and health outcomes and providing a path toward health equity across populations.

cs.CY↗

arXiv2023

A Cross-institutional Evaluation on Breast Cancer Phenotyping NLP Algorithms on Electronic Health Records

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.

cs.CL↗

arXiv2023

Development of an Extractive Clinical Question Answering Dataset with Multi-Answer and Multi-Focus Questions

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.

cs.CL↗

arXiv2022

Discrimination, calibration, and point estimate accuracy of GRU-D-Weibull architecture for real-time individualized endpoint prediction

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.

cs.LG↗

arXiv2022

Modified Generalized-Brillouin-Zone Theory with On-site Disorders

We study the characterization of the non-Hermitian skin effect (NHSE) in non-Hermitian systems with on-site disorder. We extend the application of generalized-Brillouin-zone (GBZ) theory to these systems. By proposing a modified GBZ theory, we give a faithfully description of the NHSE. For applications, we obtain a unified $β$ for system with long-range hopping, and explain the conventional-GBZ irrelevance of the magnetic suppression of the NHSE in the previous study.

cond-mat.dis-nn↗

arXiv2022

Bulk-Bulk Correspondence in Disordered Non-Hermitian Systems

The consistency between eigenvalues calculated under open and periodic boundary conditions, named as {\it bulk-bulk correspondence} ($\mathcal{BBC}$), can be destroyed in systems with non-Hermitian skin effect (NHSE). In spite of the great success of the generalized Brillouin zone (GBZ) theory in clean non-Hermitian systems, the applicability of GBZ theory is questionable when the translational symmetry is broken. Thus, it is of great value to rebuild the $\mathcal{BBC}$ for disorder samples, which extends the application of GBZ theory in non-Hermitian systems. Here, we propose a scheme reconstructing $\mathcal{BBC}$, which can be regarded as the solution of an optimization problem. By solving this optimization problem analytically, we reconstruct the $\mathcal{BBC}$ and obtain the modified GBZ theory in several prototypical disordered non-Hermitian models. The modified GBZ theory gives a precise description of NHSE, which predicts the intriguing disorder-enhanced and disorder-irrelevant NHSEs.

cond-mat.dis-nn↗

arXiv2022

The NLP Sandbox: an efficient model-to-data system to enable federated and unbiased evaluation of clinical NLP models

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.

cs.CL↗

arXiv2022

An Open Natural Language Processing Development Framework for EHR-based Clinical Research: A case demonstration using the National COVID Cohort Collaborative (N3C)

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.

cs.CL↗

arXiv2022

CancerBERT: a BERT model for Extracting Breast Cancer Phenotypes from Electronic Health Records

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.

cs.IR↗

arXiv2021

An Empirical Study of UMLS Concept Extraction from Clinical Notes using Boolean Combination Ensembles

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.

cs.CL↗

arXiv2021

A Hierarchical Bayesian Model for Stochastic Spatiotemporal SIR Modeling and Prediction of COVID-19 Cases and Hospitalizations

Most COVID-19 predictive modeling efforts use statistical or mathematical models to predict national- and state-level COVID-19 cases or deaths in the future. These approaches assume parameters such as reproduction time, test positivity rate, hospitalization rate, and social intervention effectiveness (masking, distancing, and mobility) are constant. However, the one certainty with the COVID-19 pandemic is that these parameters change over time, as well as vary across counties and states. In fact, the rate of spread over region, hospitalization rate, hospital length of stay and mortality rate, the proportion of the population that is susceptible, test positivity rate, and social behaviors can all change significantly over time. Thus, the quantification of uncertainty becomes critical in making meaningful and accurate forecasts of the future. Bayesian approaches are a natural way to fully represent this uncertainty in mathematical models and have become particularly popular in physics and engineering models. The explicit integration time varying parameters and uncertainty quantification into a hierarchical Bayesian forecast model differentiates the Mayo COVID-19 model from other forecasting models. By accounting for all sources of uncertainty in both parameter estimation as well as future trends with a Bayesian approach, the Mayo COVID-19 model accurately forecasts future cases and hospitalizations, as well as the degree of uncertainty. This approach has been remarkably accurate and a linchpin in Mayo Clinic's response to managing the COVID-19 pandemic. The model accurately predicted timing and extent of the summer and fall surges at Mayo Clinic sites, allowing hospital leadership to manage resources effectively to provide a successful pandemic response. This model has also proven to be very useful to the state of Minnesota to help guide difficult policy decisions.

stat.AP↗

arXiv2021

Leveraging a Joint of Phenotypic and Genetic Features on Cancer Patient Subgrouping

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.

cs.LG↗

arXiv2021

Real space topological invariant and higher-order topological Anderson insulator in two-dimensional non-Hermitian systems

We study the characterization and realization of higher-order topological Anderson insulator (HOTAI) in non-Hermitian systems, where the non-Hermitian mechanism ensures extra symmetries as well as gain and loss disorder.We illuminate that the quadrupole moment $Q_{xy}$ can be used as the real space topological invariant of non-Hermitian higher-order topological insulator (HOTI). Based on the biorthogonal bases and non-Hermitian symmetries, we prove that $Q_{xy}$ can be quantized to $0$ or $0.5$. Considering the disorder effect, we find the disorder-induced phase transition from normal insulator to non-Hermitian HOTAI. Furthermore, we elucidate that the real space topological invariant $Q_{xy}$ is also applicable for systems with the non-Hermitian skin effect. Our work enlightens the study of the combination of disorder and non-Hermitian HOTI.

cond-mat.dis-nn↗

arXiv2021

Comparisons of Graph Neural Networks on Cancer Classification Leveraging a Joint of Phenotypic and Genetic Features

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.

cs.LG↗

arXiv2020

Digital pathology-based study of cell- and tissue-level morphologic features in serous borderline ovarian tumor and high-grade serous ovarian cancer

Serous borderline ovarian tumor (SBOT) and high-grade serous ovarian cancer (HGSOC) are two distinct subtypes of epithelial ovarian tumors, with markedly different biologic background, behavior, prognosis, and treatment. However, the histologic diagnosis of serous ovarian tumors can be subjectively variable and labor-intensive as multiple tumor slides/blocks need to be thoroughly examined to search for these features. In this study, we aimed to evaluate technical feasibility of using digital pathological approaches to facilitate objective and scalable diagnosis screening for SBOT and HGSOC. Based on Groovy scripts and QuPath, a novel informatics system was developed to facilitate interactive annotation and imaging data exchange for machine learning purposes. Through this developed system, cellular boundaries were detected and expanded set of cellular features were extracted to represent cell- and tissue-level characteristics. According to our evaluation, cell-level classification was accurately achieved for both tumor and stroma cells with greater than 90% accuracy. Upon further re-examinations, 44.2% of the misclassified cells were due to over-/under-segmentations or low-quality of imaging areas. For a total number of 6,485 imaging patches with sufficient tumor and stroma cells (ten of each at least), we achieved 91-95% accuracy to differentiate HGSOC v. SBOT. When all the patches were considered for a WSI to make consensus prediction, 97% accuracy was achieved for accurately classifying all patients, indicating that cellular features digitally extracted from pathological images can be used for cell classification and SBOT v. HGSOC differentiation. Introducing digital pathology into ovarian cancer research could be beneficial to discover potential clinical implications.

eess.IV↗

arXiv2020

Clinical Concept Extraction: a Methodology Review

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.

cs.IR↗

arXiv2020

How Good is Artificial Intelligence at Automatically Answering Consumer Questions Related to Alzheimer's Disease?

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.

cs.IR↗