Yikuan Li

Yikuan Li, Ramsey M. Wehbe, Faraz S. Ahmad et al.

Objective: Clinical knowledge enriched transformer models (e.g., ClinicalBERT) have state-of-the-art results on clinical NLP (natural language processing) tasks. One of the core limitations of these transformer models is the substantial memory consumption due to their full self-attention mechanism, which leads to the performance degradation in long clinical texts. To overcome this, we propose to leverage long-sequence transformer models (e.g., Longformer and BigBird), which extend the maximum input sequence length from 512 to 4096, to enhance the ability to model long-term dependencies in long clinical texts. Materials and Methods: Inspired by the success of long sequence transformer models and the fact that clinical notes are mostly long, we introduce two domain enriched language models, Clinical-Longformer and Clinical-BigBird, which are pre-trained on a large-scale clinical corpus. We evaluate both language models using 10 baseline tasks including named entity recognition, question answering, natural language inference, and document classification tasks. Results: The results demonstrate that Clinical-Longformer and Clinical-BigBird consistently and significantly outperform ClinicalBERT and other short-sequence transformers in all 10 downstream tasks and achieve new state-of-the-art results. Discussion: Our pre-trained language models provide the bedrock for clinical NLP using long texts. We have made our source code available at https://github.com/luoyuanlab/Clinical-Longformer, and the pre-trained models available for public download at: https://huggingface.co/yikuan8/Clinical-Longformer. Conclusion: This study demonstrates that clinical knowledge enriched long-sequence transformers are able to learn long-term dependencies in long clinical text. Our methods can also inspire the development of other domain-enriched long-sequence transformers.

Zheng Yu, Yikuan Li, Joseph Kim et al.

Dynamic diagnosis is desirable when medical tests are costly or time-consuming. In this work, we use reinforcement learning (RL) to find a dynamic policy that selects lab test panels sequentially based on previous observations, ensuring accurate testing at a low cost. Clinical diagnostic data are often highly imbalanced; therefore, we aim to maximize the $F_1$ score instead of the error rate. However, optimizing the non-concave $F_1$ score is not a classic RL problem, thus invalidates standard RL methods. To remedy this issue, we develop a reward shaping approach, leveraging properties of the $F_1$ score and duality of policy optimization, to provably find the set of all Pareto-optimal policies for budget-constrained $F_1$ score maximization. To handle the combinatorially complex state space, we propose a Semi-Model-based Deep Diagnosis Policy Optimization (SM-DDPO) framework that is compatible with end-to-end training and online learning. SM-DDPO is tested on diverse clinical tasks: ferritin abnormality detection, sepsis mortality prediction, and acute kidney injury diagnosis. Experiments with real-world data validate that SM-DDPO trains efficiently and identifies all Pareto-front solutions. Across all tasks, SM-DDPO is able to achieve state-of-the-art diagnosis accuracy (in some cases higher than conventional methods) with up to $85\%$ reduction in testing cost. The code is available at [https://github.com/Zheng321/Deep-Reinforcement-Learning-for-Cost-Effective-Medical-Diagnosis].

Adrienne Kline, Hanyin Wang, Yikuan Li et al.

As machine learning and artificial intelligence are more frequently being leveraged to tackle problems in the health sector, there has been increased interest in utilizing them in clinical decision-support. This has historically been the case in single modal data such as electronic health record data. Attempts to improve prediction and resemble the multimodal nature of clinical expert decision-making this has been met in the computational field of machine learning by a fusion of disparate data. This review was conducted to summarize this field and identify topics ripe for future research. We conducted this review in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) extension for Scoping Reviews to characterize multi-modal data fusion in health. We used a combination of content analysis and literature searches to establish search strings and databases of PubMed, Google Scholar, and IEEEXplore from 2011 to 2021. A final set of 125 articles were included in the analysis. The most common health areas utilizing multi-modal methods were neurology and oncology. However, there exist a wide breadth of current applications. The most common form of information fusion was early fusion. Notably, there was an improvement in predictive performance performing heterogeneous data fusion. Lacking from the papers were clear clinical deployment strategies and pursuit of FDA-approved tools. These findings provide a map of the current literature on multimodal data fusion as applied to health diagnosis/prognosis problems. Multi-modal machine learning, while more robust in its estimations over unimodal methods, has drawbacks in its scalability and the time-consuming nature of information concatenation.

Chengsheng Mao, Jie Xu, Luke Rasmussen et al.

Objective: We develop a deep learning framework based on the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model using unstructured clinical notes from electronic health records (EHRs) to predict the risk of disease progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Materials and Methods: We identified 3657 patients diagnosed with MCI together with their progress notes from Northwestern Medicine Enterprise Data Warehouse (NMEDW) between 2000-2020. The progress notes no later than the first MCI diagnosis were used for the prediction. We first preprocessed the notes by deidentification, cleaning and splitting, and then pretrained a BERT model for AD (AD-BERT) based on the publicly available Bio+Clinical BERT on the preprocessed notes. The embeddings of all the sections of a patient's notes processed by AD-BERT were combined by MaxPooling to compute the probability of MCI-to-AD progression. For replication, we conducted a similar set of experiments on 2563 MCI patients identified at Weill Cornell Medicine (WCM) during the same timeframe. Results: Compared with the 7 baseline models, the AD-BERT model achieved the best performance on both datasets, with Area Under receiver operating characteristic Curve (AUC) of 0.8170 and F1 score of 0.4178 on NMEDW dataset and AUC of 0.8830 and F1 score of 0.6836 on WCM dataset. Conclusion: We developed a deep learning framework using BERT models which provide an effective solution for prediction of MCI-to-AD progression using clinical note analysis.

Yikuan Li, Chengsheng Mao, Kaixuan Huang et al.

Scarcity of health care resources could result in the unavoidable consequence of rationing. For example, ventilators are often limited in supply, especially during public health emergencies or in resource-constrained health care settings, such as amid the pandemic of COVID-19. Currently, there is no universally accepted standard for health care resource allocation protocols, resulting in different governments prioritizing patients based on various criteria and heuristic-based protocols. In this study, we investigate the use of reinforcement learning for critical care resource allocation policy optimization to fairly and effectively ration resources. We propose a transformer-based deep Q-network to integrate the disease progression of individual patients and the interaction effects among patients during the critical care resource allocation. We aim to improve both fairness of allocation and overall patient outcomes. Our experiments demonstrate that our method significantly reduces excess deaths and achieves a more equitable distribution under different levels of ventilator shortage, when compared to existing severity-based and comorbidity-based methods in use by different governments. Our source code is included in the supplement and will be released on Github upon publication.

Hanyin Wang, Meghan R. Hutch, Yikuan Li et al.

Over 12 billion doses of COVID-19 vaccines have been administered at the time of writing. However, public perceptions of vaccines have been complex. We analyzed COVID-19 vaccine-related tweets to understand the evolving perceptions of COVID-19 vaccines. We finetuned a deep learning classifier using a state-of-the-art model, XLNet, to detect each tweet's sentiment automatically. We employed validated methods to extract the users' race or ethnicity, gender, age, and geographical locations from user profiles. Incorporating multiple data sources, we assessed the sentiment patterns among subpopulations and juxtaposed them against vaccine uptake data to unravel their interactive patterns. 11,211,672 COVID-19 vaccine-related tweets corresponding to 2,203,681 users over two years were analyzed. The finetuned model for sentiment classification yielded an accuracy of 0.92 on testing set. Users from various demographic groups demonstrated distinct patterns in sentiments towards COVID-19 vaccines. User sentiments became more positive over time, upon which we observed subsequent upswing in the population-level vaccine uptake. Surrounding dates where positive sentiments crest, we detected encouraging news or events regarding vaccine development and distribution. Positive sentiments in pregnancy-related tweets demonstrated a delayed pattern compared with trends in general population, with postponed vaccine uptake trends. Distinctive patterns across subpopulations suggest the need of tailored strategies. Global news and events profoundly involved in shaping users' thoughts on social media. Populations with additional concerns, such as pregnancy, demonstrated more substantial hesitancy since lack of timely recommendations. Feature analysis revealed hesitancies of various subpopulations stemmed from clinical trial logics, risks and complications, and urgency of scientific evidence.

Yikuan Li, Hanyin Wang, Halid Yerebakan et al.

In this study, we investigated the ability of the large language model (LLM) to enhance healthcare data interoperability. We leveraged the LLM to convert clinical texts into their corresponding FHIR resources. Our experiments, conducted on 3,671 snippets of clinical text, demonstrated that the LLM not only streamlines the multi-step natural language processing and human calibration processes but also achieves an exceptional accuracy rate of over 90% in exact matches when compared to human annotations.

Yikuan Li, Ramsey M. Wehbe, Faraz S. Ahmad et al.

Transformers-based models, such as BERT, have dramatically improved the performance for various natural language processing tasks. The clinical knowledge enriched model, namely ClinicalBERT, also achieved state-of-the-art results when performed on clinical named entity recognition and natural language inference tasks. One of the core limitations of these transformers is the substantial memory consumption due to their full self-attention mechanism. To overcome this, long sequence transformer models, e.g. Longformer and BigBird, were proposed with the idea of sparse attention mechanism to reduce the memory usage from quadratic to the sequence length to a linear scale. These models extended the maximum input sequence length from 512 to 4096, which enhanced the ability of modeling long-term dependency and consequently achieved optimal results in a variety of tasks. Inspired by the success of these long sequence transformer models, we introduce two domain enriched language models, namely Clinical-Longformer and Clinical-BigBird, which are pre-trained from large-scale clinical corpora. We evaluate both pre-trained models using 10 baseline tasks including named entity recognition, question answering, and document classification tasks. The results demonstrate that Clinical-Longformer and Clinical-BigBird consistently and significantly outperform ClinicalBERT as well as other short-sequence transformers in all downstream tasks. We have made our source code available at [https://github.com/luoyuanlab/Clinical-Longformer] the pre-trained models available for public download at: [https://huggingface.co/yikuan8/Clinical-Longformer].

Hanyin Wang, Yikuan Li, Andrew Naidech et al.

Background Sepsis is one of the most life-threatening circumstances for critically ill patients in the US, while a standardized criteria for sepsis identification is still under development. Disparities in social determinants of sepsis patients can interfere with the risk prediction performances using machine learning. Methods Disparities in social determinants, including race, gender, marital status, insurance types and languages, among patients identified by six available sepsis criteria were revealed by forest plots. Sixteen machine learning classifiers were trained to predict in-hospital mortality for sepsis patients. The performance of the trained model was tested on the entire randomly conducted test set and each sub-population built based on each of the following social determinants: race, gender, marital status, insurance type, and language. Results We analyzed a total of 11,791 critical care patients from the MIMIC-III database. Within the population identified by each sepsis identification method, significant differences were observed among sub-populations regarding race, marital status, insurance type, and language. On the 5,783 sepsis patients identified by the Sepsis-3 criteria statistically significant performance decreases for mortality prediction were observed when applying the trained machine learning model on Asian and Hispanic patients. With pairwise comparison, we detected performance discrepancies in mortality prediction between Asian and White patients, Asians and patients of other races, as well as English-speaking and Spanish-speaking patients. Conclusions Disparities in proportions of patients identified by various sepsis criteria were detected among the different social determinant groups. To achieve accurate diagnosis, a versatile diagnostic system for sepsis is needed to overcome the social determinant disparities of patients.

Jiyoung Shin, Yikuan Li, Yuan Luo

Sepsis is an important cause of mortality, especially in intensive care unit (ICU) patients. Developing novel methods to identify early mortality is critical for improving survival outcomes in sepsis patients. Using the MIMIC-III database, we integrated demographic data, physiological measurements and clinical notes. We built and applied several machine learning models to predict the risk of hospital mortality and 30-day mortality in sepsis patients. From the clinical notes, we generated clinically meaningful word representations and embeddings. Supervised learning classifiers and a deep learning architecture were used to construct prediction models. The configurations that utilized both structured and unstructured clinical features yielded competitive F-measure of 0.512. Our results showed that the approaches integrating both structured and unstructured clinical features can be effectively applied to assist clinicians in identifying the risk of mortality in sepsis patients upon admission to the ICU.

Yikuan Li, Hanyin Wang, Yuan Luo

Joint image-text embedding extracted from medical images and associated contextual reports is the bedrock for most biomedical vision-and-language (V+L) tasks, including medical visual question answering, clinical image-text retrieval, clinical report auto-generation. In this study, we adopt four pre-trained V+L models: LXMERT, VisualBERT, UNIER and PixelBERT to learn multimodal representation from MIMIC-CXR radiographs and associated reports. The extrinsic evaluation on OpenI dataset shows that in comparison to the pioneering CNN-RNN model, the joint embedding learned by pre-trained V+L models demonstrate performance improvement in the thoracic findings classification task. We conduct an ablation study to analyze the contribution of certain model components and validate the advantage of joint embedding over text-only embedding. We also visualize attention maps to illustrate the attention mechanism of V+L models.

Abdelaali Hassaine, Dexter Canoy, Jose Roberto Ayala Solares et al.

Multimorbidity, or the presence of several medical conditions in the same individual, has been increasing in the population, both in absolute and relative terms. However, multimorbidity remains poorly understood, and the evidence from existing research to describe its burden, determinants and consequences has been limited. Previous studies attempting to understand multimorbidity patterns are often cross-sectional and do not explicitly account for multimorbidity patterns' evolution over time; some of them are based on small datasets and/or use arbitrary and narrow age ranges; and those that employed advanced models, usually lack appropriate benchmarking and validations. In this study, we (1) introduce a novel approach for using Non-negative Matrix Factorisation (NMF) for temporal phenotyping (i.e., simultaneously mining disease clusters and their trajectories); (2) provide quantitative metrics for the evaluation of disease clusters from such studies; and (3) demonstrate how the temporal characteristics of the disease clusters that result from our model can help mine multimorbidity networks and generate new hypotheses for the emergence of various multimorbidity patterns over time. We trained and evaluated our models on one of the world's largest electronic health records (EHR), with 7 million patients, from which over 2 million where relevant to this study.

Yikuan Li, Yajie Zhu

Deep Bayesian neural network has aroused a great attention in recent years since it combines the benefits of deep neural network and probability theory. Because of this, the network can make predictions and quantify the uncertainty of the predictions at the same time, which is important in many life-threatening areas. However, most of the recent researches are mainly focusing on making the Bayesian neural network easier to train, and proposing methods to estimate the uncertainty. I notice there are very few works that properly discuss the ways to measure the performance of the Bayesian neural network. Although accuracy and average uncertainty are commonly used for now, they are too general to provide any insight information about the model. In this paper, we would like to introduce more specific criteria and propose several metrics to measure the model performance from different perspectives, which include model calibration measurement, data rejection ability and uncertainty divergence for samples from the same and different distributions.

Yikuan Li, Liang Yao, Chengsheng Mao et al.

Acute kidney injury (AKI) in critically ill patients is associated with significant morbidity and mortality. Development of novel methods to identify patients with AKI earlier will allow for testing of novel strategies to prevent or reduce the complications of AKI. We developed data-driven prediction models to estimate the risk of new AKI onset. We generated models from clinical notes within the first 24 hours following intensive care unit (ICU) admission extracted from Medical Information Mart for Intensive Care III (MIMIC-III). From the clinical notes, we generated clinically meaningful word and concept representations and embeddings, respectively. Five supervised learning classifiers and knowledge-guided deep learning architecture were used to construct prediction models. The best configuration yielded a competitive AUC of 0.779. Our work suggests that natural language processing of clinical notes can be applied to assist clinicians in identifying the risk of incident AKI onset in critically ill patients upon admission to the ICU.