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Abstract Background Vaccines have revolutionized public health by providing protection against infectious diseases. They stimulate the immune system and generate memory cells to defend against targeted diseases. Clinical trials evaluate vaccine performance, including dosage, administration routes, and potential side effects. ClinicalTrials.gov is a valuable repository of clinical trial information, but the vaccine data in them lacks standardization, leading to challenges in automatic concept mapping, vaccine-related knowledge development, evidence-based decision-making, and vaccine surveillance. Results In this study, we developed a cascaded framework that capitalized on multiple domain knowledge sources, including clinical trials, the Unified Medical Language System (UMLS), and the Vaccine Ontology (VO), to enhance the performance of domain-specific language models for automated mapping of VO from clinical trials. The Vaccine Ontology (VO) is a community-based ontology that was developed to promote vaccine data standardization, integration, and computer-assisted reasoning. Our methodology involved extracting and annotating data from various sources. We then performed pre-training on the PubMedBERT model, leading to the development of CTPubMedBERT. Subsequently, we enhanced CTPubMedBERT by incorporating SAPBERT, which was pretrained using the UMLS, resulting in CTPubMedBERT + SAPBERT. Further refinement was accomplished through fine-tuning using the Vaccine Ontology corpus and vaccine data from clinical trials, yielding the CTPubMedBERT + SAPBERT + VO model. Finally, we utilized a collection of pre-trained models, along with the weighted rule-based ensemble approach, to normalize the vaccine corpus and improve the accuracy of the process. The ranking process in concept normalization involves prioritizing and ordering potential concepts to identify the most suitable match for a given context. We conducted a ranking of the Top 10 concepts, and our experimental results demonstrate that our proposed cascaded framework consistently outperformed existing effective baselines on vaccine mapping, achieving 71.8% on top 1 candidate’s accuracy and 90.0% on top 10 candidate’s accuracy. Conclusion This study provides a detailed insight into a cascaded framework of fine-tuned domain-specific language models improving mapping of VO from clinical trials. By effectively leveraging domain-specific information and applying weighted rule-based ensembles of different pre-trained BERT models, our framework can significantly enhance the mapping of VO from clinical trials.

Objective: To validate deep learning models’ ability to predict post-transplantation major adverse cardiovascular events (MACE) in patients undergoing liver transplantation (LT). Patients and Methods: We used data from Optum’s de-identified Clinformatics Data Mart Database to identify liver transplant recipients between January 2007 and March 2020. To predict post-transplantation MACE risk, we considered patients’ demographics characteristics, diagnoses, medications, and procedural data recorded back to 3 years before the LT procedure date (index date). MACE is predicted using the bidirectional gated recurrent units (BiGRU) deep learning model in different prediction interval lengths up to 5 years after the index date. In total, 18,304 liver transplant recipients (mean age, 57.4 years [SD, 12.76]; 7158 [39.1%] women) were used to develop and test the deep learning model’s performance against other baseline machine learning models. Models were optimized using 5-fold cross-validation on 80% of the cohort, and model performance was evaluated on the remaining 20% using the area under the receiver operating characteristic curve (AUC-ROC) and the area under the precision-recall curve (AUC-PR). Results: Using different prediction intervals after the index date, the top-performing model was the deep learning model, BiGRU, and achieved an AUC-ROC of 0.841 (95% CI, 0.822-0.862) and AUC-PR of 0.578 (95% CI, 0.537-0.621) for a 30-day prediction interval after LT. Conclusion: Using longitudinal claims data, deep learning models can efficiently predict MACE after LT, assisting clinicians in identifying high-risk candidates for further risk stratification or other management strategies to improve transplant outcomes based on important features identified by the model.

Abstract Background In this era of big data, data harmonization is an important step to ensure reproducible, scalable, and collaborative research. Thus, terminology mapping is a necessary step to harmonize heterogeneous data. Take the Medical Dictionary for Regulatory Activities (MedDRA) and International Classification of Diseases (ICD) for example, the mapping between them is essential for drug safety and pharmacovigilance research. Our main objective is to provide a quantitative and qualitative analysis of the mapping status between MedDRA and ICD. We focus on evaluating the current mapping status between MedDRA and ICD through the Unified Medical Language System (UMLS) and Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We summarized the current mapping statistics and evaluated the quality of the current MedDRA-ICD mapping; for unmapped terms, we used our self-developed algorithm to rank the best possible mapping candidates for additional mapping coverage. Results The identified MedDRA-ICD mapped pairs cover 27.23% of the overall MedDRA preferred terms (PT). The systematic quality analysis demonstrated that, among the mapped pairs provided by UMLS, only 51.44% are considered an exact match. For the 2400 sampled unmapped terms, 56 of the 2400 MedDRA Preferred Terms (PT) could have exact match terms from ICD. Conclusion Some of the mapped pairs between MedDRA and ICD are not exact matches due to differences in granularity and focus. For 72% of the unmapped PT terms, the identified exact match pairs illustrate the possibility of identifying additional mapped pairs. Referring to its own mapping standard, some of the unmapped terms should qualify for the expansion of MedDRA to ICD mapping in UMLS.

BackgroundThe COVID-19 pandemic, caused by SARS-CoV-2, has had a profound impact worldwide, leading to widespread morbidity and mortality. Vaccination against COVID-19 is a critical tool in controlling the spread of the virus and reducing the severity of the disease. However, the rapid development and deployment of COVID-19 vaccines have raised concerns about potential adverse events following immunization (AEFIs). Understanding the temporal and spatial patterns of these AEFIs is crucial for an effective public health response and vaccine safety monitoring. ObjectiveThis study aimed to analyze the temporal and spatial characteristics of AEFIs associated with COVID-19 vaccines in the United States reported to the Vaccine Adverse Event Reporting System (VAERS), thereby providing insights into the patterns and distributions of the AEFIs, the safety profile of COVID-19 vaccines, and potential risk factors associated with the AEFIs. MethodsWe conducted a retrospective analysis of administration data from the Centers for Disease Control and Prevention (n=663,822,575) and reports from the surveillance system VAERS (n=900,522) between 2020 and 2022. To gain a broader understanding of postvaccination AEFIs reported, we categorized them into system organ classes (SOCs) according to the Medical Dictionary for Regulatory Activities. Additionally, we performed temporal analysis to examine the trends of AEFIs in all VAERS reports, those related to Pfizer-BioNTech and Moderna, and the top 10 AEFI trends in serious reports. We also compared the similarity of symptoms across various regions within the United States. ResultsOur findings revealed that the most frequently reported symptoms following COVID-19 vaccination were headache (n=141,186, 15.68%), pyrexia (n=122,120, 13.56%), and fatigue (n=121,910, 13.54%). The most common symptom combination was chills and pyrexia (n=56,954, 6.32%). Initially, general disorders and administration site conditions (SOC 22) were the most prevalent class reported. Moderna exhibited a higher reporting rate of AEFIs compared to Pfizer-BioNTech. Over time, we observed a decreasing reporting rate of AEFIs associated with COVID-19 vaccines. In addition, the overall rates of AEFIs between the Pfizer-BioNTech and Moderna vaccines were comparable. In terms of spatial analysis, the middle and north regions of the United States displayed a higher reporting rate of AEFIs associated with COVID-19 vaccines, while the southeast and south-central regions showed notable similarity in symptoms reported. ConclusionsThis study provides valuable insights into the temporal and spatial patterns of AEFIs associated with COVID-19 vaccines in the United States. The findings underscore the critical need for increasing vaccination coverage, as well as ongoing surveillance and monitoring of AEFIs. Implementing targeted monitoring programs can facilitate the effective and efficient management of AEFIs, enhancing public confidence in future COVID-19 vaccine campaigns.

BackgroundAlzheimer disease and related dementias (ADRD) rank as the sixth leading cause of death in the United States, underlining the importance of accurate ADRD risk prediction. While recent advancements in ADRD risk prediction have primarily relied on imaging analysis, not all patients undergo medical imaging before an ADRD diagnosis. Merging machine learning with claims data can reveal additional risk factors and uncover interconnections among diverse medical codes. ObjectiveThe study aims to use graph neural networks (GNNs) with claim data for ADRD risk prediction. Addressing the lack of human-interpretable reasons behind these predictions, we introduce an innovative, self-explainable method to evaluate relationship importance and its influence on ADRD risk prediction. MethodsWe used a variationally regularized encoder-decoder GNN (variational GNN [VGNN]) integrated with our proposed relation importance method for estimating ADRD likelihood. This self-explainable method can provide a feature-important explanation in the context of ADRD risk prediction, leveraging relational information within a graph. Three scenarios with 1-year, 2-year, and 3-year prediction windows were created to assess the model’s efficiency, respectively. Random forest (RF) and light gradient boost machine (LGBM) were used as baselines. By using this method, we further clarify the key relationships for ADRD risk prediction. ResultsIn scenario 1, the VGNN model showed area under the receiver operating characteristic (AUROC) scores of 0.7272 and 0.7480 for the small subset and the matched cohort data set. It outperforms RF and LGBM by 10.6% and 9.1%, respectively, on average. In scenario 2, it achieved AUROC scores of 0.7125 and 0.7281, surpassing the other models by 10.5% and 8.9%, respectively. Similarly, in scenario 3, AUROC scores of 0.7001 and 0.7187 were obtained, exceeding 10.1% and 8.5% than the baseline models, respectively. These results clearly demonstrate the significant superiority of the graph-based approach over the tree-based models (RF and LGBM) in predicting ADRD. Furthermore, the integration of the VGNN model and our relation importance interpretation could provide valuable insight into paired factors that may contribute to or delay ADRD progression. ConclusionsUsing our innovative self-explainable method with claims data enhances ADRD risk prediction and provides insights into the impact of interconnected medical code relationships. This methodology not only enables ADRD risk modeling but also shows potential for other image analysis predictions using claims data.

BackgroundDermoscopy is a growing field that uses microscopy to allow dermatologists and primary care physicians to identify skin lesions. For a given skin lesion, a wide variety of differential diagnoses exist, which may be challenging for inexperienced users to name and understand. ObjectiveIn this study, we describe the creation of the dermoscopy differential diagnosis explorer (D3X), an ontology linking dermoscopic patterns to differential diagnoses. MethodsExisting ontologies that were incorporated into D3X include the elements of visuals ontology and dermoscopy elements of visuals ontology, which connect visual features to dermoscopic patterns. A list of differential diagnoses for each pattern was generated from the literature and in consultation with domain experts. Open-source images were incorporated from DermNet, Dermoscopedia, and open-access research papers. ResultsD3X was encoded in the OWL 2 web ontology language and includes 3041 logical axioms, 1519 classes, 103 object properties, and 20 data properties. We compared D3X with publicly available ontologies in the dermatology domain using a semiotic theory–driven metric to measure the innate qualities of D3X with others. The results indicate that D3X is adequately comparable with other ontologies of the dermatology domain. ConclusionsThe D3X ontology is a resource that can link and integrate dermoscopic differential diagnoses and supplementary information with existing ontology-based resources. Future directions include developing a web application based on D3X for dermoscopy education and clinical practice.

Abstract BackgroundIndividuals from minoritized racial and ethnic backgrounds experience pernicious and pervasive health disparities that have emerged, in part, from clinician bias. ObjectiveWe used a natural language processing approach to examine whether linguistic markers in electronic health record (EHR) notes differ based on the race and ethnicity of the patient. To validate this methodological approach, we also assessed the extent to which clinicians perceive linguistic markers to be indicative of bias. MethodsIn this cross-sectional study, we extracted EHR notes for patients who were aged 18 years or older; had more than 5 years of diabetes diagnosis codes; and received care between 2006 and 2014 from family physicians, general internists, or endocrinologists practicing in an urban, academic network of clinics. The race and ethnicity of patients were defined as White non-HispanicBlack non-HispanicHispanic or Latino ResultsWe examined EHR notes (n=12,905) of Black non-Hispanic, White non-Hispanic, and Hispanic or Latino patients (n=1562), who were seen by 281 physicians. A total of 27 clinicians participated in the validation study. In terms of bias, participants rated negative adjectives as 8.63 (SD 2.06), fear and disgust words as 8.11 (SD 2.15), and positive adjectives as 7.93 (SD 2.46) on a scale of 1 to 10, with 10 being extremely indicative of bias. Notes for Black non-Hispanic patients contained significantly more negative adjectives (coefficient 0.07, SE 0.02) and significantly more fear and disgust words (coefficient 0.007, SE 0.002) than those for White non-Hispanic patients. The notes for Hispanic or Latino patients included significantly fewer positive adjectives (coefficient −0.02, SE 0.007), trust verbs (coefficient −0.009, SE 0.004), and joy words (coefficient −0.03, SE 0.01) than those for White non-Hispanic patients. ConclusionsThis approach may enable physicians and researchers to identify and mitigate bias in medical interactions, with the goal of reducing health disparities stemming from bias.

Abstract Background Vaccine Adverse Events ReportingSystem (VAERS) is a promising resource of tracking adverse events following immunization. Medical Dictionary for Regulatory Activities (MedDRA) terminology used for coding adverse events in VAERS reports has several limitations. We focus on developing an automated system for semantic extraction of adverse events following vaccination and their temporal relationships for a better understanding of VAERS data and its integration into other applications. The aim of the present studyis to summarize the lessons learned during the initial phase of this project in annotating adverse events following influenza vaccination and related to Guillain-Barré syndrome (GBS). We emphasize on identifying the limitations of VAERS and MedDRA. Results We collected 282 VAERS reports documented between 1990 and 2016 and shortlisted those with at least 1,100 characters in the report. We used a subset of 50 reports for the preliminary investigation and annotated all adverse events following influenza vaccination by mapping to representative MedDRA terms. Associated time expressions were annotated when available. We used 16 System Organ Class (SOC) level MedDRA terms to map GBS related adverse events and expanded some SOC terms to Lowest Level Terms (LLT) for granular representation. We annotated three broad categories of events such as problems, clinical investigations, and treatments/procedures. The inter-annotator agreement of events achieved was 86%. Incomplete reports, typographical errors, lack of clarity and coherence, repeated texts, unavailability of associated temporal information, difficulty to interpret due to incorrect grammar, use of generalized terms to describe adverse events / symptoms, uncommon abbreviations, difficulty annotating multiple events with a conjunction / common phrase, irrelevant historical events and coexisting events were some of the challenges encountered. Some of the limitations we noted are in agreement with previous reports. Conclusions We reported the challenges encountered and lessons learned during annotation of adverse events in VAERS reports following influenza vaccination and related to GBS. Though the challenges may be due to the inevitable limitations of public reporting systems and widely reported limitations of MedDRA, we emphasize the need to understand these limitations and extraction of other supportive information for a better understanding of adverse events following vaccination.

Abstract Background With more clinical trials are offering optional participation in the collection of bio-specimens for biobanking comes the increasing complexity of requirements of informed consent forms. The aim of this study is to develop an automatic natural language processing (NLP) tool to annotate informed consent documents to promote biorepository data regulation, sharing, and decision support. We collected informed consent documents from several publicly available sources, then manually annotated them, covering sentences containing permission information about the sharing of either bio-specimens or donor data, or conducting genetic research or future research using bio-specimens or donor data. Results We evaluated a variety of machine learning algorithms including random forest (RF) and support vector machine (SVM) for the automatic identification of these sentences. 120 informed consent documents containing 29,204 sentences were annotated, of which 1250 sentences (4.28%) provide answers to a permission question. A support vector machine (SVM) model achieved a F-1 score of 0.95 on classifying the sentences when using a gold standard, which is a prefiltered corpus containing all relevant sentences. Conclusions This study provides the feasibility of using machine learning tools to classify permission-related sentences in informed consent documents.

BackgroundSocial determinants of health (SDoH) have been described by the World Health Organization as the conditions in which individuals are born, live, work, and age. These conditions can be grouped into 3 interrelated levels known as macrolevel (societal), mesolevel (community), and microlevel (individual) determinants. The scope of SDoH expands beyond the biomedical level, and there remains a need to connect other areas such as economics, public policy, and social factors. ObjectiveProviding a computable artifact that can link health data to concepts involving the different levels of determinants may improve our understanding of the impact SDoH have on human populations. Modeling SDoH may help to reduce existing gaps in the literature through explicit links between the determinants and biological factors. This in turn can allow researchers and clinicians to make better sense of data and discover new knowledge through the use of semantic links. MethodsAn experimental ontology was developed to represent knowledge of the social and economic characteristics of SDoH. Information from 27 literature sources was analyzed to gather concepts and encoded using Web Ontology Language, version 2 (OWL2) and Protégé. Four evaluators independently reviewed the ontology axioms using natural language translation. The analyses from the evaluations and selected terminologies from the Basic Formal Ontology were used to create a revised ontology with a broad spectrum of knowledge concepts ranging from the macrolevel to the microlevel determinants. ResultsThe literature search identified several topics of discussion for each determinant level. Publications for the macrolevel determinants centered around health policy, income inequality, welfare, and the environment. Articles relating to the mesolevel determinants discussed work, work conditions, psychosocial factors, socioeconomic position, outcomes, food, poverty, housing, and crime. Finally, sources found for the microlevel determinants examined gender, ethnicity, race, and behavior. Concepts were gathered from the literature and used to produce an ontology consisting of 383 classes, 109 object properties, and 748 logical axioms. A reasoning test revealed no inconsistent axioms. ConclusionsThis ontology models heterogeneous social and economic concepts to represent aspects of SDoH. The scope of SDoH is expansive, and although the ontology is broad, it is still in its early stages. To our current understanding, this ontology represents the first attempt to concentrate on knowledge concepts that are currently not covered by existing ontologies. Future direction will include further expanding the ontology to link with other biomedical ontologies, including alignment for granular semantics.

Background The rapid evolution of artificial intelligence (AI) in conjunction with recent updates in dual antiplatelet therapy (DAPT) management guidelines emphasizes the necessity for innovative models to predict ischemic or bleeding events after drug‐eluting stent implantation. Leveraging AI for dynamic prediction has the potential to revolutionize risk stratification and provide personalized decision support for DAPT management. Methods and Results We developed and validated a new AI‐based pipeline using retrospective data of drug‐eluting stent‐treated patients, sourced from the Cerner Health Facts data set (n=98 236) and Optum's de‐identified Clinformatics Data Mart Database (n=9978). The 36 months following drug‐eluting stent implantation were designated as our primary forecasting interval, further segmented into 6 sequential prediction windows. We evaluated 5 distinct AI algorithms for their precision in predicting ischemic and bleeding risks. Model discriminative accuracy was assessed using the area under the receiver operating characteristic curve, among other metrics. The weighted light gradient boosting machine stood out as the preeminent model, thus earning its place as our AI‐DAPT model. The AI‐DAPT demonstrated peak accuracy in the 30 to 36 months window, charting an area under the receiver operating characteristic curve of 90% [95% CI, 88%–92%] for ischemia and 84% [95% CI, 82%–87%] for bleeding predictions. Conclusions Our AI‐DAPT excels in formulating iterative, refined dynamic predictions by assimilating ongoing updates from patients' clinical profiles, holding value as a novel smart clinical tool to facilitate optimal DAPT duration management with high accuracy and adaptability.

Plasmonic waveguides have attracted tremendous interest due to efficiently confining photons on the subwavelength spatial scale to be beating the propagation diffraction limit. Transition metal molybdenum (Mo) exhibits outstanding properties in light trapping and electromagnetic field confining, making it potentially valuable in 1.55 μm plasmonic waveguide applications. However, the reliable fabrication of high-quality Mo plasmonic waveguides is a significant challenge. A real-space micro-imaging study of the surface plasmon on Mo structures is still absent. In this study, we successfully prepared a single-crystalline Mo microrod waveguide structure and fabricated subwavelength gratings on it. The diffraction gratings were designed, optimized, and etched to excite the surface plasmon polariton behaviour of Mo for the first time. The grating-optimized Mo microrod single-crystal reveals highly efficient waveguide performance around near-infrared spectroscopy, exhibiting a long propagation length of 32 μm and a low transmission loss of 0.067 dB μm−1. The results provide an alternative to advanced materials research and optical device applications of plasmonic waveguide systems.

Abstract Background The utilization of dermoscopic analysis is becoming increasingly critical for diagnosing skin diseases by physicians and even artificial intelligence. With the expansion of dermoscopy, its vocabulary has proliferated, but the rapid evolution of the vocabulary of dermoscopy without standardized control is counterproductive. We aimed to develop a domain-specific ontology to formally represent knowledge for certain dermoscopic features. Methods The first phase involved creating a fundamental-level ontology that covers the fundamental aspects and elements in describing visualizations, such as shapes and colors. The second phase involved creating a domain ontology that harnesses the fundamental-level ontology to formalize the definitions of dermoscopic metaphorical terms. Results The Dermoscopy Elements of Visuals Ontology (DEVO) contains 1047 classes, 47 object properties, and 16 data properties. It has a better semiotic score compared to similar ontologies of the same domain. Three human annotators also examined the consistency, complexity, and future application of the ontology. Conclusions The proposed ontology was able to harness the definitions of metaphoric terms by decomposing them into their visual elements. Future applications include providing education for trainees and diagnostic support for dermatologists, with the goal of generating responses to queries about dermoscopic features and integrating these features to diagnose skin diseases.

Abstract Background In the United States, the National Alzheimer’s Coordinating Center (NACC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) are two major data sharing resources for Alzheimer’s Disease (AD) research. NACC and ADNI strive to make their data more FAIR (findable, interoperable, accessible and reusable) for the broader research community. However, there is limited work harmonizing and supporting cross-cohort interoperability of the two resources. Method In this paper, we leverage an ontology-based approach to harmonize data elements in the two resources and develop a web-based query system to search patient cohorts across the two resources. We first mapped data elements across NACC and ADNI, and performed value harmonization for the mapped data elements with inconsistent permissible values. Then we built an Alzheimer’s Disease Data Element Ontology (ADEO) to model the mapped data elements in NACC and ADNI. We further developed a prototype cross-cohort query system to search patient cohorts across NACC and ADNI. Results After manual review, we found 172 mappings between NACC and ADNI. These 172 mappings were further used to construct common concepts in ADEO. Our data element mapping and harmonization resulted in five files storing common concepts, variables in NACC and ADNI, mappings between variables and common concepts, permissible values of categorical type data elements, and coding inconsistency harmonization, respectively. Our cross-cohort query system consists of three core architectural elements: a web-based interface, an advanced query engine, and a backend MongoDB database. Conclusions In this work, ADEO has been specifically designed to facilitate data harmonization and cross-cohort query of NACC and ADNI data resources. Although our prototype cross-cohort query system was developed for exploring NACC and ADNI, its backend and frontend framework has been designed and implemented to be generally applicable to other domains for querying patient cohorts from multiple heterogeneous data sources.

Though Vaccines are instrumental in global health, mitigating infectious diseases and pandemic outbreaks, they can occasionally lead to adverse events (AEs). Recently, Large Language Models (LLMs) have shown promise in effectively identifying and cataloging AEs within clinical reports. Utilizing data from the Vaccine Adverse Event Reporting System (VAERS) from 1990 to 2016, this study particularly focuses on AEs to evaluate LLMs' capability for AE extraction. A variety of prevalent LLMs, including GPT-2, GPT-3 variants, GPT-4, and Llama2, were evaluated using Influenza vaccine as a use case. The fine-tuned GPT 3.5 model (AE-GPT) stood out with a 0.704 averaged micro F1 score for strict match and 0.816 for relaxed match. The encouraging performance of the AE-GPT underscores LLMs' potential in processing medical data, indicating a significant stride towards advanced AE detection, thus presumably generalizable to other AE extraction tasks.

BackgroundReminiscence, a therapy that uses stimulating materials such as old photos and videos to stimulate long-term memory, can improve the emotional well-being and life satisfaction of older adults, including those who are cognitively intact. However, providing personalized reminiscence therapy can be challenging for caregivers and family members. ObjectiveThis study aimed to achieve three objectives: (1) design and develop the GoodTimes app, an interactive multimodal photo album that uses artificial intelligence (AI) to engage users in personalized conversations and storytelling about their pictures, encompassing family, friends, and special moments; (2) examine the app’s functionalities in various scenarios using use-case studies and assess the app’s usability and user experience through the user study; and (3) investigate the app’s potential as a supplementary tool for reminiscence therapy among cognitively intact older adults, aiming to enhance their psychological well-being by facilitating the recollection of past experiences. MethodsWe used state-of-the-art AI technologies, including image recognition, natural language processing, knowledge graph, logic, and machine learning, to develop GoodTimes. First, we constructed a comprehensive knowledge graph that models the information required for effective communication, including photos, people, locations, time, and stories related to the photos. Next, we developed a voice assistant that interacts with users by leveraging the knowledge graph and machine learning techniques. Then, we created various use cases to examine the functions of the system in different scenarios. Finally, to evaluate GoodTimes’ usability, we conducted a study with older adults (N=13; age range 58-84, mean 65.8 years). The study period started from January to March 2023. ResultsThe use-case tests demonstrated the performance of GoodTimes in handling a variety of scenarios, highlighting its versatility and adaptability. For the user study, the feedback from our participants was highly positive, with 92% (12/13) reporting a positive experience conversing with GoodTimes. All participants mentioned that the app invoked pleasant memories and aided in recollecting loved ones, resulting in a sense of happiness for the majority (11/13, 85%). Additionally, a significant majority found GoodTimes to be helpful (11/13, 85%) and user-friendly (12/13, 92%). Most participants (9/13, 69%) expressed a desire to use the app frequently, although some (4/13, 31%) indicated a need for technical support to navigate the system effectively. ConclusionsOur AI-based interactive photo album, GoodTimes, was able to engage users in browsing their photos and conversing about them. Preliminary evidence supports GoodTimes’ usability and benefits cognitively intact older adults. Future work is needed to explore its potential positive effects among older adults with cognitive impairment.

Abstract Background To date, there are no effective treatments for most neurodegenerative diseases. Knowledge graphs can provide comprehensive and semantic representation for heterogeneous data, and have been successfully leveraged in many biomedical applications including drug repurposing. Our objective is to construct a knowledge graph from literature to study the relations between Alzheimer’s disease (AD) and chemicals, drugs and dietary supplements in order to identify opportunities to prevent or delay neurodegenerative progression. We collected biomedical annotations and extracted their relations using SemRep via SemMedDB. We used both a BERT-based classifier and rule-based methods during data preprocessing to exclude noise while preserving most AD-related semantic triples. The 1,672,110 filtered triples were used to train with knowledge graph completion algorithms (i.e., TransE, DistMult, and ComplEx) to predict candidates that might be helpful for AD treatment or prevention. Results Among three knowledge graph completion models, TransE outperformed the other two (MR = 10.53, Hits@1 = 0.28). We leveraged the time-slicing technique to further evaluate the prediction results. We found supporting evidence for most highly ranked candidates predicted by our model which indicates that our approach can inform reliable new knowledge. Conclusion This paper shows that our graph mining model can predict reliable new relationships between AD and other entities (i.e., dietary supplements, chemicals, and drugs). The knowledge graph constructed can facilitate data-driven knowledge discoveries and the generation of novel hypotheses.

Abstract Background The Vaccine Ontology (VO) is a biomedical ontology that standardizes vaccine annotation. Errors in VO will affect a multitude of applications that it is being used in. Quality assurance of VO is imperative to ensure that it provides accurate domain knowledge to these downstream tasks. Manual review to identify and fix quality issues (such as missing hierarchical is-a relations) is challenging given the complexity of the ontology. Automated approaches are highly desirable to facilitate the quality assurance of VO. Methods We developed an automated lexical approach that identifies potentially missing is-a relations in VO. First, we construct two types of VO concept-pairs: (1) linked; and (2) unlinked. Each concept-pair further derives an Acquired Term Pair (ATP) based on their lexical features. If the same ATP is obtained by a linked concept-pair and an unlinked concept-pair, this is considered to indicate a potentially missing is-a relation between the unlinked pair of concepts. Results Applying this approach on the 1.1.192 version of VO, we were able to identify 232 potentially missing is-a relations. A manual review by a VO domain expert on a random sample of 70 potentially missing is-a relations revealed that 65 of the cases were valid missing is-a relations in VO (a precision of 92.86%). Conclusions The results indicate that our approach is highly effective in identifying missing is-a relation in VO.

Abstract Background Model card reports aim to provide informative and transparent description of machine learning models to stakeholders. This report document is of interest to the National Institutes of Health’s Bridge2AI initiative to address the FAIR challenges with artificial intelligence-based machine learning models for biomedical research. We present our early undertaking in developing an ontology for capturing the conceptual-level information embedded in model card reports. Results Sourcing from existing ontologies and developing the core framework, we generated the Model Card Report Ontology. Our development efforts yielded an OWL2-based artifact that represents and formalizes model card report information. The current release of this ontology utilizes standard concepts and properties from OBO Foundry ontologies. Also, the software reasoner indicated no logical inconsistencies with the ontology. With sample model cards of machine learning models for bioinformatics research (HIV social networks and adverse outcome prediction for stent implantation), we showed the coverage and usefulness of our model in transforming static model card reports to a computable format for machine-based processing. Conclusions The benefit of our work is that it utilizes expansive and standard terminologies and scientific rigor promoted by biomedical ontologists, as well as, generating an avenue to make model cards machine-readable using semantic web technology. Our future goal is to assess the veracity of our model and later expand the model to include additional concepts to address terminological gaps. We discuss tools and software that will utilize our ontology for potential application services.

Abstract Severe adverse events (AEs) after COVID-19 vaccination are not well studied in randomized controlled trials (RCTs) due to rarity and short follow-up. To monitor the safety of COVID-19 vaccines (“Pfizer” vaccine dose 1 and 2, “Moderna” vaccine dose 1 and 2, and “Janssen” vaccine single dose) in the U.S., especially regarding severe AEs, we compare the relative rankings of these vaccines using both RCT and the Vaccine Adverse Event Reporting System (VAERS) data. The risks of local and systemic AEs were assessed from the three pivotal COVID-19 vaccine trials and also calculated in the VAERS cohort consisting of 559,717 reports between December 14, 2020 and September 17, 2021. AE rankings of the five vaccine groups calculated separately by RCT and VAERS were consistent, especially for systemic AEs. For severe AEs reported in VAERS, the reported risks of thrombosis and GBS after Janssen vaccine were highest. The reported risk of shingles after the first dose of Moderna vaccine was highest, followed by the second dose of the Moderna vaccine. The reported risk of myocarditis was higher after the second dose of Pfizer and Moderna vaccines. The reported risk of anaphylaxis was higher after the first dose of Pfizer vaccine. Limitations of this study are the inherent biases of the spontaneous reporting system data, and only including three pivotal RCTs and no comparison with other active vaccine safety surveillance systems.

Background Existing studies on cardiovascular diseases (CVDs) often focus on individual‐level behavioral risk factors, but research examining social determinants is limited. This study applies a novel machine learning approach to identify the key predictors of county‐level care costs and prevalence of CVDs (including atrial fibrillation, acute myocardial infarction, congestive heart failure, and ischemic heart disease). Methods and Results We applied the extreme gradient boosting machine learning approach to a total of 3137 counties. Data are from the Interactive Atlas of Heart Disease and Stroke and a variety of national data sets. We found that although demographic composition (eg, percentages of Black people and older adults) and risk factors (eg, smoking and physical inactivity) are among the most important predictors for inpatient care costs and CVD prevalence, contextual factors such as social vulnerability and racial and ethnic segregation are particularly important for the total and outpatient care costs. Poverty and income inequality are the major contributors to the total care costs for counties that are in nonmetro areas or have high segregation or social vulnerability levels. Racial and ethnic segregation is particularly important in shaping the total care costs for counties with low poverty rates or social vulnerability level. Demographic composition, education, and social vulnerability are consistently important across different scenarios. Conclusions The findings highlight the differences in predictors for different types of CVD cost outcomes and the importance of social determinants. Interventions directed toward areas that have been economically and socially marginalized may aid in reducing the impact of CVDs.

Complex forms of diabetes are the ultimate common pathway involving multiple genetic variations and multiple environmental factors. Type 2 diabetes (T2DM) is classified as complex diabetes. Varying degrees of insulin deficiency and tissue insulin resistance are two key links to T2DM. The islet β cell dysfunction plays a crucial role in the pathogenesis of T2DM. The decompensation of the islet β cell to insulin resistance is a common mechanism leading to the pathogenesis of T2DM. Available data show that genetic factors mainly affect cell function. At present, a number of susceptibility genes related to T2DM have been reported at home and abroad. In this study, the diabetes-related genes in the case of early-onset diabetes with a significant family history were examined, and our results showed the presence of the intron mutations of catalase (CAT) gene and hepatocyte nuclear factor 1β (HNF1β) gene. The patient enrolled in this study was observed and analyzed, thus, increasing further understanding of the genes associated with diabetes and exploring the pathogenesis of diabetes from the molecular level. This is significant for guiding the prevention, treatment, and prognosis evaluation of diabetes.

The weight-loading swimming assay, liver glycogen and serum urea nitrogen tests in mice were used to evaluate the alleviating physical fatigue effects of Lijiang and Peru Maca. The mouse mating assay, sperm quantity, survival rate and gonadal organ index tests were used to observe the improving sexual function between them. The acute toxicity test was used to evaluate the safety of two samples. The result showed that compared with the blank control group, Lijiang and Peru Maca can significantly increase the swimming time and the level of liver glycogen, as well as reduce the level of urea nitrogen in mice. Compared with the blank control group, Lijiang and Peru Maca can obviously improve the mating ability, sperm quantity and testis index in mice, but it has no obvious effect on sperm viability, seminal vesicles and Foreskin gland index. Compared with the Peru Maca group, there was no significant difference in the activity of anti-fatigue and improving sexual function. The acute toxicity test showed that the maximum dose of Lijiang and Peru Maca was 17.48g/kg. There was no toxicity or death after administration.

Abstract Background Fast food with its abundance and availability to consumers may have health consequences due to the high calorie intake which is a major contributor to life threatening diseases. Providing nutritional information has some impact on consumer decisions to self regulate and promote healthier diets, and thus, government regulations have mandated the publishing of nutritional content to assist consumers, including for fast food. However, fast food nutritional information is fragmented, and we realize a benefit to collate nutritional data to synthesize knowledge for individuals. Methods We developed the ontology of fast food facts as an opportunity to standardize knowledge of fast food and link nutritional data that could be analyzed and aggregated for the information needs of consumers and experts. The ontology is based on metadata from 21 fast food establishment nutritional resources and authored in OWL2 using Protégé. Results Three evaluators reviewed the logical structure of the ontology through natural language translation of the axioms. While there is majority agreement (76.1% pairwise agreement) of the veracity of the ontology, we identified 103 out of the 430 statements that were erroneous. We revised the ontology and publicably published the initial release of the ontology. The ontology has 413 classes, 21 object properties, 13 data properties, and 494 logical axioms. Conclusion With the initial release of the ontology of fast food facts we discuss some future visions with the continued evolution of this knowledge base, and the challenges we plan to address, like the management and publication of voluminous amount of semantically linked fast food nutritional data.

BackgroundAutomatic skin lesion recognition has shown to be effective in increasing access to reliable dermatology evaluation; however, most existing algorithms rely solely on images. Many diagnostic rules, including the 3-point checklist, are not considered by artificial intelligence algorithms, which comprise human knowledge and reflect the diagnosis process of human experts. ObjectiveIn this paper, we aimed to develop a semisupervised model that can not only integrate the dermoscopic features and scoring rule from the 3-point checklist but also automate the feature-annotation process. MethodsWe first trained the semisupervised model on a small, annotated data set with disease and dermoscopic feature labels and tried to improve the classification accuracy by integrating the 3-point checklist using ranking loss function. We then used a large, unlabeled data set with only disease label to learn from the trained algorithm to automatically classify skin lesions and features. ResultsAfter adding the 3-point checklist to our model, its performance for melanoma classification improved from a mean of 0.8867 (SD 0.0191) to 0.8943 (SD 0.0115) under 5-fold cross-validation. The trained semisupervised model can automatically detect 3 dermoscopic features from the 3-point checklist, with best performances of 0.80 (area under the curve [AUC] 0.8380), 0.89 (AUC 0.9036), and 0.76 (AUC 0.8444), in some cases outperforming human annotators. ConclusionsOur proposed semisupervised learning framework can help with the automatic diagnosis of skin disease based on its ability to detect dermoscopic features and automate the label-annotation process. The framework can also help combine semantic knowledge with a computer algorithm to arrive at a more accurate and more interpretable diagnostic result, which can be applied to broader use cases.

Abstract Deep learning (DL)-based predictive models from electronic health records (EHRs) deliver impressive performance in many clinical tasks. Large training cohorts, however, are often required by these models to achieve high accuracy, hindering the adoption of DL-based models in scenarios with limited training data. Recently, bidirectional encoder representations from transformers (BERT) and related models have achieved tremendous successes in the natural language processing domain. The pretraining of BERT on a very large training corpus generates contextualized embeddings that can boost the performance of models trained on smaller datasets. Inspired by BERT, we propose Med-BERT, which adapts the BERT framework originally developed for the text domain to the structured EHR domain. Med-BERT is a contextualized embedding model pretrained on a structured EHR dataset of 28,490,650 patients. Fine-tuning experiments showed that Med-BERT substantially improves the prediction accuracy, boosting the area under the receiver operating characteristics curve (AUC) by 1.21–6.14% in two disease prediction tasks from two clinical databases. In particular, pretrained Med-BERT obtains promising performances on tasks with small fine-tuning training sets and can boost the AUC by more than 20% or obtain an AUC as high as a model trained on a training set ten times larger, compared with deep learning models without Med-BERT. We believe that Med-BERT will benefit disease prediction studies with small local training datasets, reduce data collection expenses, and accelerate the pace of artificial intelligence aided healthcare.

Abstract Background Dyadic-based social networks analyses have been effective in a variety of behavioral- and health-related research areas. We introduce an ontology-driven approach towards social network analysis through encoding social data and inferring new information from the data. Methods The Friend of a Friend (FOAF) ontology is a lightweight social network ontology. We enriched FOAF by deriving social interaction data and relationships from social data to extend its domain scope. Results Our effort produced Friend of a Friend with Benefits (FOAF+) ontology that aims to support the spectrum of human interaction. A preliminary semiotic evaluation revealed a semantically rich and comprehensive knowledge base to represent complex social network relationships. With Semantic Web Rules Language, we demonstrated FOAF+ potential to infer social network ties between individual data. Conclusion Using logical rules, we defined interpersonal dyadic social connections, which can create inferred linked dyadic social representations of individuals, represent complex behavioral information, help machines interpret some of the concepts and relationships involving human interaction, query network data, and contribute methods for analytical and disease surveillance.

Abstract In this introduction, we first summarize the Fourth International Workshop on Semantics-Powered Data Mining and Analytics (SEPDA 2019) held on October 26, 2019 in conjunction with the 18th International Semantic Web Conference (ISWC 2019) in Auckland, New Zealand, and then briefly introduce seven research articles included in this supplement issue, covering the topics on Knowledge Graph, Ontology-Powered Analytics, and Deep Learning.

Abstract Background Semantic web technology has been applied widely in the biomedical informatics field. Large numbers of biomedical datasets are available online in the resource description framework (RDF) format. Semantic relationship mining among genes, disorders, and drugs is widely used in, for example, precision medicine and drug repositioning. However, most of the existing studies focused on a single dataset. It is not easy to find the most current relationships among disorder-gene-drug relationships since the relationships are distributed in heterogeneous datasets. How to mine their semantic relationships from different biomedical datasets is an important issue. Methods First, a variety of biomedical datasets were converted into RDF triple data; then, multisource biomedical datasets were integrated into a storage system using a data integration algorithm. Second, nine query patterns among genes, disorders, and drugs from different biomedical datasets were designed. Third, the gene-disorder-drug semantic relationship mining algorithm is presented. This algorithm can query the relationships among various entities from different datasets. Results and conclusions We focused on mining the putative and the most current disorder-gene-drug relationships about Parkinson’s disease (PD). The results demonstrate that our method has significant advantages in mining and integrating multisource heterogeneous biomedical datasets. Twenty-five new relationships among the genes, disorders, and drugs were mined from four different datasets. The query results showed that most of them came from different datasets. The precision of the method increased by 2.51% compared to that of the multisource linked open data fusion method presented in the 4th International Workshop on Semantics-Powered Data Mining and Analytics (SEPDA 2019). Moreover, the number of query results increased by 7.7%, and the number of correct queries increased by 9.5%.

Abstract Background Previously, we introduced our Patient Health Information Dialogue Ontology (PHIDO) that manages the dialogue and contextual information of the session between an agent and a health consumer. In this study, we take the next step and introduce the Conversational Ontology Operator (COO), the software engine harnessing PHIDO. We also developed a question-answering subsystem called Frankenstein Ontology Question-Answering for User-centric Systems (FOQUS) to support the dialogue interaction. Methods We tested both the dialogue engine and the question-answering system using application-based competency questions and questions furnished from our previous Wizard of OZ simulation trials. Results Our results revealed that the dialogue engine is able to perform the core tasks of communicating health information and conversational flow. Inter-rater agreement and accuracy scores among four reviewers indicated perceived, acceptable responses to the questions asked by participants from the simulation studies, yet the composition of the responses was deemed mediocre by our evaluators. Conclusions Overall, we present some preliminary evidence of a functioning ontology-based system to manage dialogue and consumer questions. Future plans for this work will involve deploying this system in a speech-enabled agent to assess its usage with potential health consumer users.

BackgroundIdentifying the key factors of Guillain-Barré syndrome (GBS) and predicting its occurrence are vital for improving the prognosis of patients with GBS. However, there are scarcely any publications on a forewarning model of GBS. A Bayesian network (BN) model, which is known to be an accurate, interpretable, and interaction-sensitive graph model in many similar domains, is worth trying in GBS risk prediction. ObjectiveThe aim of this study is to determine the most significant factors of GBS and further develop and validate a BN model for predicting GBS risk. MethodsLarge-scale influenza vaccine postmarketing surveillance data, including 79,165 US (obtained from the Vaccine Adverse Event Reporting System between 1990 and 2017) and 12,495 European (obtained from the EudraVigilance system between 2003 and 2016) adverse events (AEs) reports, were extracted for model development and validation. GBS, age, gender, and the top 50 prevalent AEs were included for initial BN construction using the R package bnlearn. ResultsAge, gender, and 10 AEs were identified as the most significant factors of GBS. The posttest probability of GBS suggested that male vaccinees aged 50-64 years and without erythema should be on the alert or be warned by clinicians about an increased risk of GBS, especially when they also experience symptoms of asthenia, hypesthesia, muscular weakness, or paresthesia. The established BN model achieved an area under the receiver operating characteristic curve of 0.866 (95% CI 0.865-0.867), sensitivity of 0.752 (95% CI 0.749-0.756), specificity of 0.882 (95% CI 0.879-0.885), and accuracy of 0.882 (95% CI 0.879-0.884) for predicting GBS risk during the internal validation and obtained values of 0.829, 0.673, 0.854, and 0.843 for area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy, respectively, during the external validation. ConclusionsThe findings of this study illustrated that a BN model can effectively identify the most significant factors of GBS, improve understanding of the complex interactions among different postvaccination symptoms through its graphical representation, and accurately predict the risk of GBS. The established BN model could further assist clinical decision-making by providing an estimated risk of GBS for a specific vaccinee or be developed into an open-access platform for vaccinees’ self-monitoring.

BackgroundUnderstanding consumers’ health information needs across all stages of the pregnancy trajectory is crucial to the development of mechanisms that allow them to retrieve high-quality, customized, and layperson-friendly health information. ObjectiveThe objective of this study was to identify research gaps in pregnancy-related consumer information needs and available information from different sources. MethodsWe conducted a systematic review of CINAHL, Cochrane, PubMed, and Web of Science for relevant articles that were published from 2009 to 2019. The quality of the included articles was assessed using the Critical Appraisal Skills Program. A descriptive data analysis was performed on these articles. Based on the review result, we developed the Pregnancy Information Needs Ontology (PINO) and made it publicly available in GitHub and BioPortal. ResultsA total of 33 articles from 9 countries met the inclusion criteria for this review, of which the majority were published no earlier than 2016. Most studies were either descriptive (9/33, 27%), interviews (7/33, 21%), or surveys/questionnaires (7/33, 21%); 20 articles mentioned consumers’ pregnancy-related information needs. Half (9/18, 50%) of the human-subject studies were conducted in the United States. More than a third (13/33, 39%) of all studies focused on during-pregnancy stage; only one study (1/33, 3%) was about all stages of pregnancy. The most frequent consumer information needs were related to labor delivery (9/20, 45%), medication in pregnancy (6/20, 30%), newborn care (5/20, 25%), and lab tests (6/20, 30%). The most frequently available source of information was the internet (15/24, 63%). PINO consists of 267 classes, 555 axioms, and 271 subclass relationships. ConclusionsOnly a few articles assessed the barriers to access to pregnancy-related information and the quality of each source of information; further work is needed. Future work is also needed to address the gaps between the information needed and the information available.

Abstract. Background. Diagnoses of Skin diseases are frequently delayed in China due to lack of dermatologists. A deep learning-based diagnosis supporting system can facilitate pre-screening patients to prioritize dermatologists’ efforts. We aimed to evaluate the classification sensitivity and specificity of deep learning models to classify skin tumors and psoriasis for Chinese population with a modest number of dermoscopic images. Methods. We developed a convolutional neural network (CNN) based on two datasets from a consecutive series of patients who underwent the dermoscopy in the clinic of the Department of Dermatology, Peking Union Medical College Hospital, between 2016 and 2018, prospectively. In order to evaluate the feasibility of the algorithm, we used two datasets. Dataset I consisted of 7192 dermoscopic images for a multi-class model to differentiate three most common skin tumors and other diseases. Dataset II consisted of 3115 dermoscopic images for a two-class model to classify psoriasis from other inflammatory diseases. We compared the performance of CNN with 164 dermatologists in a reader study with 130 dermoscopic images. The experts’ consensus was used as the reference standard except for the cases of basal cell carcinoma (BCC), which were all confirmed by histopathology. Results. The accuracies of multi-class and two-class models were 81.49% ± 0.88% and 77.02% ± 1.81%, respectively. In the reader study, for the multi-class tasks, the diagnosis sensitivity and specificity of 164 dermatologists were 0.770 and 0.962 for BCC, 0.807 and 0.897 for melanocytic nevus, 0.624 and 0.976 for seborrheic keratosis, 0.939 and 0.875 for the “others” group, respectively; the diagnosis sensitivity and specificity of multi-class CNN were 0.800 and 1.000 for BCC, 0.800 and 0.840 for melanocytic nevus, 0.850 and 0.940 for seborrheic keratosis, 0.750 and 0.940 for the “others” group, respectively. For the two-class tasks, the sensitivity and specificity of dermatologists and CNN for classifying psoriasis were 0.872 and 0.838, 1.000 and 0.605, respectively. Both the dermatologists and CNN achieved at least moderate consistency with the reference standard, and there was no significant difference in Kappa coefficients between them (P > 0.05). Conclusions. The performance of CNN developed with relatively modest number of dermoscopic images of skin tumors and psoriasis for Chinese population is comparable with 164 dermatologists. These two models could be used for screening in patients suspected with skin tumors and psoriasis respectively in primary care hospital.

Abstract This Editorial first introduces the background of the vaccine and drug relations and how biomedical terminologies and ontologies have been used to support their studies. The history of the seven workshops, initially named VDOSME, and then named VDOS, is also summarized and introduced. Then the 7th International Workshop on Vaccine and Drug Ontology Studies (VDOS 2018), held on August 10th, 2018, Corvallis, Oregon, USA, is introduced in detail. These VDOS workshops have greatly supported the development, applications, and discussion of vaccine- and drug-related terminology and drug studies.

Abstract Background In the United States and parts of the world, the human papillomavirus vaccine uptake is below the prescribed coverage rate for the population. Some research have noted that dialogue that communicates the risks and benefits, as well as patient concerns, can improve the uptake levels. In this paper, we introduce an application ontology for health information dialogue called Patient Health Information Dialogue Ontology for patient-level human papillomavirus vaccine counseling and potentially for any health-related counseling. Results The ontology’s class level hierarchy is segmented into 4 basic levels - Discussion, Goal, Utterance, and Speech Task. The ontology also defines core low-level utterance interaction for communicating human papillomavirus health information. We discuss the design of the ontology and the execution of the utterance interaction. Conclusion With an ontology that represents patient-centric dialogue to communicate health information, we have an application-driven model that formalizes the structure for the communication of health information, and a reusable scaffold that can be integrated for software agents. Our next step will to be develop the software engine that will utilize the ontology and automate the dialogue interaction of a software agent.

BackgroundThe rapid growth of social media as an information channel has made it possible to quickly spread inaccurate or false vaccine information, thus creating obstacles for vaccine promotion. ObjectiveThe aim of this study is to develop and evaluate an intelligent automated protocol for identifying and classifying human papillomavirus (HPV) vaccine misinformation on social media using machine learning (ML)–based methods. MethodsReddit posts (from 2007 to 2017, N=28,121) that contained keywords related to HPV vaccination were compiled. A random subset (2200/28,121, 7.82%) was manually labeled for misinformation and served as the gold standard corpus for evaluation. A total of 5 ML-based algorithms, including a support vector machine, logistic regression, extremely randomized trees, a convolutional neural network, and a recurrent neural network designed to identify vaccine misinformation, were evaluated for identification performance. Topic modeling was applied to identify the major categories associated with HPV vaccine misinformation. ResultsA convolutional neural network model achieved the highest area under the receiver operating characteristic curve of 0.7943. Of the 28,121 Reddit posts, 7207 (25.63%) were classified as vaccine misinformation, with discussions about general safety issues identified as the leading type of misinformed posts (2666/7207, 36.99%). ConclusionsML-based approaches are effective in the identification and classification of HPV vaccine misinformation on Reddit and may be generalizable to other social media platforms. ML-based methods may provide the capacity and utility to meet the challenge involved in intelligent automated monitoring and classification of public health misinformation on social media platforms. The timely identification of vaccine misinformation on the internet is the first step in misinformation correction and vaccine promotion.

Abstract Background The existing community-wide bodies of biomedical ontologies are known to contain quality and content problems. Past research has revealed various errors related to their semantics and logical structure. Automated tools may help to ease the ontology construction, maintenance, assessment and quality assurance processes. However, there are relatively few tools that exist that can provide this support to knowledge engineers. Method We introduce OntoKeeper as a web-based tool that can automate quality scoring for ontology developers. We enlisted 5 experienced ontologists to test the tool and then administered the System Usability Scale to measure their assessment. Results In this paper, we present usability results from 5 ontologists revealing high system usability of OntoKeeper, and use-cases that demonstrate its capabilities in previous published biomedical ontology research. Conclusion To the best of our knowledge, OntoKeeper is the first of a few ontology evaluation tools that can help provide ontology evaluation functionality for knowledge engineers with good usability.

Abstract Background Hepatitis C affects about 3 % of the world’s population. In the United States, about 3.5 million have chronic hepatitis C, and it is the leading cause of liver cancer and the most common indication for liver transplantation. In the last decades, new advances in therapy have substantially increased the cure rate of hepatitis C to more than 95% with the use of antiviral agents. However, drug safety of the new treatments remains one of the major concerns. Data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the Electronic Health Record (EHR) systems provide crucial post-market information to evaluate drug safety. Currently, quantitative evidence of drug safety of hepatitis C treatments based on post-market data are still limited, and there is also a lack of a standard statistical procedure to systematically compare drug safety across multiple drugs using FAERS and EHR. Method In this study, we presented a statistical procedure to compare the difference in adverse events (AE) across multiple hepatitis C drugs using data from FAERS and EHR, and to assess the consistency of results from two data bases. Through three major steps, including descriptive comparison, testing for difference among groups, and quantification of association, the proposed method can provide a quantitative comparison on safety of multiple drugs. Specifically, we compared drugs that were approved by FDA to treat hepatitis C before 2011versus those approved after 2013. We used spontaneous AE reports submitted between 2004 to 2015 from FAERS data base and medical records between 1999 to 2015 from the Cerner health facts data base to estimate and compare the rate of AE after drug use. Result We studied 30 most frequently reported AEs after treatment of hepatitis C, comparing the difference between drugs approved before 2011versus those approved after 2013. Our results showed that there was difference in rate of AE between the two groups of treatment. We reported the AEs that have significant statistical difference, and estimate the difference attributable to variation of age and gender between the two groups of drug users. Our findings are consistent with results in existing literature. Moreover, we compared the results obtained from FAERS data and EHR data, and evaluated the consistency of evidence. Conclusion The proposed procedure is a general and standardized pipeline that can be used to compare and visualize drug safety among multiple drugs to support regulatory decision-makings using post-market data. We showed that there was statistically significant difference in AE rates between the new and old therapies for hepatitis C. We showed that both FAERS and EHR contained large information for research of post-market drug safety, but each has its own strength and limitations. Cautions should be taken when combining evidence from the two data resources and there is a need of more sophisticated informatics and statistical tools for evidence synthesis.

Abstract Background Learning distributional representation of clinical concepts (e.g., diseases, drugs, and labs) is an important research area of deep learning in the medical domain. However, many existing relevant methods do not consider temporal dependencies along the longitudinal sequence of a patient’s records, which may lead to incorrect selection of contexts. Methods To address this issue, we extended three popular concept embedding learning methods: word2vec, positive pointwise mutual information (PPMI) and FastText, to consider time-sensitive information. We then trained them on a large electronic health records (EHR) database containing about 50 million patients to generate concept embeddings and evaluated them for both intrinsic evaluations focusing on concept similarity measure and an extrinsic evaluation to assess the use of generated concept embeddings in the task of predicting disease onset. Results Our experiments show that embeddings learned from information within one visit (time window zero) improve performance on the concept similarity measure and the FastText algorithm usually had better performance than the other two algorithms. For the predictive modeling task, the optimal result was achieved by word2vec embeddings with a 30-day sliding window. Conclusions Considering time constraints are important in training clinical concept embeddings. We expect they can benefit a series of downstream applications.

Abstract Background Existing functional description of genes are categorical, discrete, and mostly through manual process. In this work, we explore the idea of gene embedding, distributed representation of genes, in the spirit of word embedding. Results From a pure data-driven fashion, we trained a 200-dimension vector representation of all human genes, using gene co-expression patterns in 984 data sets from the GEO databases. These vectors capture functional relatedness of genes in terms of recovering known pathways - the average inner product (similarity) of genes within a pathway is 1.52X greater than that of random genes. Using t-SNE, we produced a gene co-expression map that shows local concentrations of tissue specific genes. We also illustrated the usefulness of the embedded gene vectors, laden with rich information on gene co-expression patterns, in tasks such as gene-gene interaction prediction. Conclusions We proposed a machine learning method that utilizes transcriptome-wide gene co-expression to generate a distributed representation of genes. We further demonstrated the utility of our distribution by predicting gene-gene interaction based solely on gene names. The distributed representation of genes could be useful for more bioinformatics applications.

Abstract Background Disease comorbidity is very common and has significant impact on disease treatment. Revealing the associations among diseases may help to understand the mechanisms of diseases, improve the prevention and treatment of diseases, and support the discovery of new drugs or new uses of existing drugs. Methods In this paper, we introduced a mathematical model to represent gene related diseases with a series of associated genes based on the overrepresentation of genes and diseases in PubMed literature. We also illustrated an efficient way to reveal the implicit connections between COPD and other diseases based on this model. Results We applied this approach to analyze the relationships between Chronic Obstructive Pulmonary Disease (COPD) and other diseases under the Lung diseases branch in the Medical subject heading index system and detected 4 novel diseases relevant to COPD. As judged by domain experts, the F score of our approach is up to 77.6%. Conclusions The results demonstrate the effectiveness of the gene fingerprint model for diseases on the basis of medical literature.

The Sanchahe iron-gold deposit in western Shandong province is located in the southeast of the North China Craton. The skarn type of iron-gold deposit (without copper) is located in the contact belt between pyroxene diorites and Ordovician limestone xenoliths. The zircon U-Pb age of pyroxene diorites is 138.4 ± 1.2 Ma belonging to the Early Cretaceous. Pyroxene diorites (Rittmann index σ = 2.2~2.5) belong to the calc-alkaline series and the SiO2 content is 55~59%. Furthermore, pyroxene diorites are characterized by high Mg and Na contents and high contents of Sc, Cr, Co, and Ni, indicating that it has a geochemical affinity with mantle-derived magma. All of the samples are enriched in light rare earth elements (LREEs) and depleted in heavy rare earth elements (HREEs), with a weak Eu-negative anomaly. They are also enriched in Cs, Ba and Sr and depleted in high field strength elements (HFSEs) (Nb, Ta, Zr), indicating the involvement of some crustal materials. The whole-rock (87Sr/86Sr)I values are 0.70824~0.70891, and the εNd(t) values are from −8.1 to −12.5. Two-stage model ages of TDM2 are 1591~1928 Ma. The εHf(t) values range from −7.0 to −17.4, and the two-stage model ages of TDM2 range from 1629 to 2297 Ma, indicating that the magma was derived from Mesoproterozoic to Neoarchean crusts. Combined with Pb isotopic characteristics, pyroxene diorites may be generated by the partial melting of the enriched lithospheric mantle, which had been metasomatized by the ancient lower crust materials of the North China Craton and formed in the strong extensional tectonic setting linked with lithospheric thinning, which may be caused by the rollback of the Pacific plate after subduction.

Abstract Introduction A large volume of clinical care data has been generated for managing agitation in dementia. However, the valuable information in these data has not been used effectively to generate insights for improving the quality of care. Application of artificial intelligence technologies offers us enormous opportunities to reuse these data. For health data science to achieve this, this study focuses on using ontology to coding clinical knowledge for non‐pharmacological treatment of agitation in a machine‐readable format. Methods The resultant ontology—Dementia‐Related Agitation Non‐Pharmacological Treatment Ontology (DRANPTO)—was developed using a method adopted from the NeOn methodology. Results DRANPTO consisted of 569 concepts and 48 object properties. It meets the standards for biomedical ontology. Discussion DRANPTO is the first comprehensive semantic representation of non‐pharmacological management for agitation in dementia in the long‐term care setting. As a knowledge base, it will play a vital role to facilitate the development of intelligent systems for managing agitation in dementia.

The human papillomavirus (HPV) vaccine protects adolescents and young adults from 9 high-risk HPV virus types that cause 90% of cervical and anal cancers and 70% of oropharyngeal cancers. This study extends our previous research analyzing online content concerning the HPV vaccination in social media platforms used by young adults, in which we used Pathfinder network scaling and methods of distributional semantics to characterize differences in knowledge organization reflected in consumer- and expert-generated online content. The current study extends this approach to evaluate HPV vaccine perceptions among young adults who populate Reddit, a major social media platform. We derived Pathfinder networks from estimates of semantic relatedness obtained by learning word embeddings from Reddit posts and compared these to networks derived from human expert estimation of the relationship between key concepts. Results revealed that users of Reddit, predominantly comprising young adults in the vaccine catch up age-group 18 through 26 years of age, perceived the HPV vaccine domain from a virus-framed perspective that could impact their lifestyle choices and that their awareness of the HPV vaccine for cancer prevention is also lacking. Further differences in knowledge structures were elucidated, with implications for future health communication initiatives.

Abstract Background In this paper, we discuss the design and development of a formal ontology to describe misinformation about vaccines. Vaccine misinformation is one of the drivers leading to vaccine hesitancy in patients. While there are various levels of vaccine hesitancy to combat and specific interventions to address those levels, it is important to have tools that help researchers understand this problem. With an ontology, not only can we collect and analyze varied misunderstandings about vaccines, but we can also develop tools that can provide informatics solutions. Results We developed the Vaccine Misinformation Ontology (VAXMO) that extends the Misinformation Ontology and links to the nanopublication Resource Description Framework (RDF) model for false assertions of vaccines. Preliminary assessment using semiotic evaluation metrics indicated adequate quality for our ontology. We outlined and demonstrated proposed uses of the ontology to detect and understand anti-vaccine information. Conclusion We surmised that VAXMO and its proposed use cases can support tools and technology that can pave the way for vaccine misinformation detection and analysis. Using an ontology, we can formally structure knowledge for machines and software to better understand the vaccine misinformation domain.

Abstract Background The emergence of the deep convolutional neural network (CNN) greatly improves the quality of computer-aided supporting systems. However, due to the challenges of generating reliable and timely results, clinical adoption of computer-aided diagnosis systems is still limited. Recent informatics research indicates that machine learning algorithms need to be combined with sufficient clinical expertise in order to achieve an optimal result. Methods In this research, we used deep learning algorithms to help diagnose four common cutaneous diseases based on dermoscopic images. In order to facilitate decision-making and improve the accuracy of our algorithm, we summarized classification/diagnosis scenarios based on domain expert knowledge and semantically represented them in a hierarchical structure. Results Our algorithm achieved an accuracy of 87.25 ± 2.24% in our test dataset with 1067 images. The semantic summarization of diagnosis scenarios can help further improve the algorithm to facilitate future computer-aided decision support. Conclusions In this paper, we applied deep neural network algorithm to classify dermoscopic images of four common skin diseases and archived promising results. Based on the results, we further summarized the diagnosis/classification scenarios, which reflect the importance of combining the efforts of both human expertise and computer algorithms in dermatologic diagnoses.

Abstract Background Healthcare services, particularly in patient-provider interaction, often involve highly emotional situations, and it is important for physicians to understand and respond to their patients’ emotions to best ensure their well-being. Methods In order to model the emotion domain, we have created the Visualized Emotion Ontology (VEO) to provide a semantic definition of 25 emotions based on established models, as well as visual representations of emotions utilizing shapes, lines, and colors. Results As determined by ontology evaluation metrics, VEO exhibited better machine-readability (z=1.12), linguistic quality (z=0.61), and domain coverage (z=0.39) compared to a sample of cognitive ontologies. Additionally, a survey of 1082 participants through Amazon Mechanical Turk revealed that a significantly higher proportion of people agree than disagree with 17 out of our 25 emotion images, validating the majority of our visualizations. Conclusion From the development, evaluation, and serialization of the VEO, we have defined a set of 25 emotions using OWL that linked surveyed visualizations to each emotion. In the future, we plan to use the VEO in patient-facing software tools, such as embodied conversational agents, to enhance interactions between patients and providers in a clinical environment.