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Abstract Background To advance new therapies into clinical care, clinical trials must recruit enough participants. Yet, many trials fail to do so, leading to delays, early trial termination, and wasted resources. Under-enrolling trials make it impossible to draw conclusions about the efficacy of new therapies. An oft-cited reason for insufficient enrollment is lack of study team and provider awareness about patient eligibility. Automating clinical trial eligibility surveillance and study team and provider notification could offer a solution. Methods To address this need for an automated solution, we conducted an observational pilot study of our TAES (TriAl Eligibility Surveillance) system. We tested the hypothesis that an automated system based on natural language processing and machine learning algorithms could detect patients eligible for specific clinical trials by linking the information extracted from trial descriptions to the corresponding clinical information in the electronic health record (EHR). To evaluate the TAES information extraction and matching prototype (i.e., TAES prototype), we selected five open cardiovascular and cancer trials at the Medical University of South Carolina and created a new reference standard of 21,974 clinical text notes from a random selection of 400 patients (including at least 100 enrolled in the selected trials), with a small subset of 20 notes annotated in detail. We also developed a simple web interface for a new database that stores all trial eligibility criteria, corresponding clinical information, and trial-patient match characteristics using the Observational Medical Outcomes Partnership (OMOP) common data model. Finally, we investigated options for integrating an automated clinical trial eligibility system into the EHR and for notifying health care providers promptly of potential patient eligibility without interrupting their clinical workflow. Results Although the rapidly implemented TAES prototype achieved only moderate accuracy (recall up to 0.778; precision up to 1.000), it enabled us to assess options for integrating an automated system successfully into the clinical workflow at a healthcare system. Conclusions Once optimized, the TAES system could exponentially enhance identification of patients potentially eligible for clinical trials, while simultaneously decreasing the burden on research teams of manual EHR review. Through timely notifications, it could also raise physician awareness of patient eligibility for clinical trials.

Abstract Background Visit-to-visit body weight variability (BWV), pulse rate variability (PRV), and blood pressure variability (BPV) have been respectively linked to multiple health outcomes. The associations of the combination of long-term variability in physiological measures with mortality and epigenetic age acceleration (EAA) remain largely unknown. Methods We constructed a composite score of physiological variability (0-3) of large variability in BWV, PRV, and BPV (the top tertiles) in 2006/2008–2014/2016 in the Health and Retirement Study (HRS) and 2011–2015 in the China Health and Retirement Longitudinal Study (CHARLS). All-cause mortality was documented through 2018. EAA was calculated using thirteen DNA methylation-based epigenetic clocks among 1047 participants in a substudy of the HRS. We assessed the relation of the composite score to the risk of mortality among 6566 participants in the HRS and 6906 participants in the CHARLS by Cox proportional models and then investigated its association with EAA using linear regression models. Results A higher score of variability was associated with higher mortality risk in both cohorts (pooled hazard ratio [HR] per one-point increment, 1.27; 95% confidence interval [CI], 1.18, 1.39; P-heterogeneity = 0.344), after adjustment for multiple confounders and baseline physiological measures. Specifically, each SD increment in BWV, PRV, and BPV was related to 21% (95% CI: 15%, 28%), 6% (0%, 13%), and 12% (4%, 19%) higher hazard of mortality, respectively. The composite score was significantly related to EAA in second-generation clocks trained on health outcomes (e.g., standardized coefficient = 0.126 in the Levine clock, 95% CI: 0.055, 0.196) but not in most first-generation clocks trained on chronological age. Conclusions Larger variability in physiological measures was associated with a higher risk of mortality and faster EAA.

Abstract Background Visium Spatial Gene Expression (ST) is a method combining histological spatial information with transcriptomics profiles directly from tissue sections. The use of spatial information has made it possible to discover new modes of gene expression regulations. However, in the ST experiment, the nucleus size of cells may exceed the thickness of a tissue slice. This may, in turn, negatively affect comprehensive capturing the transcriptomics profile in a single slice, especially for tissues having large differences in the size of nuclei. Methods Here, we defined the effect of Consecutive Slices Data Integration (CSDI) on unveiling accurate spot clustering and deconvolution of spatial transcriptomic spots in human postmortem brains. By considering the histological information as reference, we assessed the improvement of unsupervised clustering and single nuclei RNA-seq and ST data integration before and after CSDI. Results Apart from the escalated number of defined clusters representing neuronal layers, the pattern of clusters in consecutive sections was concordant only after CSDI. Besides, the assigned cell labels to spots matches the histological pattern of tissue sections after CSDI. Conclusion CSDI can be applied to investigate consecutive sections studied with ST in the human cerebral cortex, avoiding misinterpretation of spot clustering and annotation, increasing accuracy of cell recognition as well as improvement in uncovering the layers of grey matter in the human brain.

Abstract Background Dietary supplements (DS) have been widely used by consumers, but the information around the efficacy and safety of DS is disparate or incomplete, thus creating barriers for consumers to find information effectively. Conversational agent (CA) systems have been applied to healthcare domain, but there is no such system to answer consumers regarding DS use, although widespread use of DS. In this study, we develop the first CA system for DS use. Methods Our CA system for DS use developed on the MindMeld framework, consists of three components: question understanding, DS knowledge base, and answer generation. We collected and annotated 1509 questions to develop a natural language understanding module (e.g., question type classifier, named entity recognizer) which was then integrated into MindMeld framework. CA then queries the DS knowledge base (i.e., iDISK) and generates answers using rule-based slot filling techniques. We evaluated the algorithms of each component and the CA system as a whole. Results CNN is the best question classifier with an F1 score of 0.81, and CRF is the best named entity recognizer with an F1 score of 0.87. The system achieves an overall accuracy of 81% and an average score of 1.82 with succ@3 + score of 76.2% and succ@2 + of 66% approximately. Conclusion This study develops the first CA system for DS use using the MindMeld framework and iDISK domain knowledge base.

Abstract Background Finite element modelling the material behavior of bone in-silico is a powerful tool to predict the best suited surgical treatment for individual patients. Results We demonstrate the development and use of a pre-processing plug-in program with a 3D modelling image processing software suite (Synopsys Simpleware, ScanIP) to assist with identifying, isolating, and defining cortical and trabecular bone material properties from patient specific computed tomography scans. The workflow starts by calibrating grayscale values of each constituent element with a phantom – a standardized object with defined densities. Using an established power law equation, we convert the apparent density value per voxel to a Young’s Modulus. The resulting “calibrated” scan can be used for modeling and in-silico experimentation with Finite Element Analysis. Conclusions This process allows for the creation of realistic and personalized simulations to inform a surgeon’s decision-making. We have made this plug-in program open and accessible as a supplemental file.

This is the data that was used for a paper titled 'Altered basal ganglia output during self-restraint.' Format and organization is written in the ReadMe.txt file. Files will be continued to be uploaded until 10/30/22.

Abstract Background There is progress to be made in building artificially intelligent systems to detect abnormalities that are not only accurate but can handle the true breadth of findings that radiologists encounter in body (chest, abdomen, and pelvis) computed tomography (CT). Currently, the major bottleneck for developing multi-disease classifiers is a lack of manually annotated data. The purpose of this work was to develop high throughput multi-label annotators for body CT reports that can be applied across a variety of abnormalities, organs, and disease states thereby mitigating the need for human annotation. Methods We used a dictionary approach to develop rule-based algorithms (RBA) for extraction of disease labels from radiology text reports. We targeted three organ systems (lungs/pleura, liver/gallbladder, kidneys/ureters) with four diseases per system based on their prevalence in our dataset. To expand the algorithms beyond pre-defined keywords, attention-guided recurrent neural networks (RNN) were trained using the RBA-extracted labels to classify reports as being positive for one or more diseases or normal for each organ system. Alternative effects on disease classification performance were evaluated using random initialization or pre-trained embedding as well as different sizes of training datasets. The RBA was tested on a subset of 2158 manually labeled reports and performance was reported as accuracy and F-score. The RNN was tested against a test set of 48,758 reports labeled by RBA and performance was reported as area under the receiver operating characteristic curve (AUC), with 95% CIs calculated using the DeLong method. Results Manual validation of the RBA confirmed 91–99% accuracy across the 15 different labels. Our models extracted disease labels from 261,229 radiology reports of 112,501 unique subjects. Pre-trained models outperformed random initialization across all diseases. As the training dataset size was reduced, performance was robust except for a few diseases with a relatively small number of cases. Pre-trained classification AUCs reached > 0.95 for all four disease outcomes and normality across all three organ systems. Conclusions Our label-extracting pipeline was able to encompass a variety of cases and diseases in body CT reports by generalizing beyond strict rules with exceptional accuracy. The method described can be easily adapted to enable automated labeling of hospital-scale medical data sets for training image-based disease classifiers.

Abstract Background Adverse events induced by drug-drug interactions are a major concern in the United States. Current research is moving toward using electronic health record (EHR) data, including for adverse drug events discovery. One of the first steps in EHR-based studies is to define a phenotype for establishing a cohort of patients. However, phenotype definitions are not readily available for all phenotypes. One of the first steps of developing automated text mining tools is building a corpus. Therefore, this study aimed to develop annotation guidelines and a gold standard corpus to facilitate building future automated approaches for mining phenotype definitions contained in the literature. Furthermore, our aim is to improve the understanding of how these published phenotype definitions are presented in the literature and how we annotate them for future text mining tasks. Results Two annotators manually annotated the corpus on a sentence-level for the presence of evidence for phenotype definitions. Three major categories (inclusion, intermediate, and exclusion) with a total of ten dimensions were proposed characterizing major contextual patterns and cues for presenting phenotype definitions in published literature. The developed annotation guidelines were used to annotate the corpus that contained 3971 sentences: 1923 out of 3971 (48.4%) for the inclusion category, 1851 out of 3971 (46.6%) for the intermediate category, and 2273 out of 3971 (57.2%) for exclusion category. The highest number of annotated sentences was 1449 out of 3971 (36.5%) for the “Biomedical & Procedure” dimension. The lowest number of annotated sentences was 49 out of 3971 (1.2%) for “The use of NLP”. The overall percent inter-annotator agreement was 97.8%. Percent and Kappa statistics also showed high inter-annotator agreement across all dimensions. Conclusions The corpus and annotation guidelines can serve as a foundational informatics approach for annotating and mining phenotype definitions in literature, and can be used later for text mining applications.