BACKGROUND: Acupuncture, a key modality in traditional Chinese medicine, is gaining global recognition as a complementary therapy and a subject of increasing scientific interest. However, fragmented and unstructured acupuncture knowledge spread across diverse sources poses challenges for semantic retrieval, reasoning, and in-depth analysis. To address this gap, we developed AcuKG, a comprehensive knowledge graph that systematically organizes acupuncture-related knowledge to support sharing, discovery, and artificial intelligence-driven innovation in the field. METHODS: AcuKG integrates data from multiple sources, including online resources, guidelines, PubMed literature, ClinicalTrials.gov, and multiple ontologies (SNOMED CT, UBERON, and MeSH). We employed entity recognition, relation extraction, and ontology mapping to establish AcuKG, with human-in-the-loop to ensure data quality. Two cases evaluated AcuKG's usability: (1) how AcuKG advances acupuncture research for obesity and (2) how AcuKG enhances large language model (LLM) application on acupuncture question-answering. RESULTS: AcuKG comprises 1839 entities and 11 527 relations, mapped to 1836 standard concepts in 3 ontologies. Two use cases demonstrated AcuKG's effectiveness and potential in advancing acupuncture research and supporting LLM applications. In the obesity use case, AcuKG identified highly relevant acupoints (eg, ST25, ST36) and uncovered novel research insights based on evidence from clinical trials and literature. When applied to LLMs in answering acupuncture-related questions, integrating AcuKG with GPT-4o and LLaMA 3 significantly improved accuracy (GPT-4o: 46% → 54%, P = .03; LLaMA 3: 17% → 28%, P = .01). CONCLUSION: AcuKG is an open dataset that provides a structured and computational framework for acupuncture applications, bridging traditional practices with acupuncture research and cutting-edge LLM technologies.

OBJECTIVES: Precise literature recommendation and summarization are crucial for biomedical professionals. While the latest iteration of generative pretrained transformer (GPT) incorporates 2 distinct modes-real-time search and pretrained model utilization-it encounters challenges in dealing with these tasks. Specifically, the real-time search can pinpoint some relevant articles but occasionally provides fabricated papers, whereas the pretrained model excels in generating well-structured summaries but struggles to cite specific sources. In response, this study introduces RefAI, an innovative retrieval-augmented generative tool designed to synergize the strengths of large language models (LLMs) while overcoming their limitations. MATERIALS AND METHODS: RefAI utilized PubMed for systematic literature retrieval, employed a novel multivariable algorithm for article recommendation, and leveraged GPT-4 turbo for summarization. Ten queries under 2 prevalent topics ("cancer immunotherapy and target therapy" and "LLMs in medicine") were chosen as use cases and 3 established counterparts (ChatGPT-4, ScholarAI, and Gemini) as our baselines. The evaluation was conducted by 10 domain experts through standard statistical analyses for performance comparison. RESULTS: The overall performance of RefAI surpassed that of the baselines across 5 evaluated dimensions-relevance and quality for literature recommendation, accuracy, comprehensiveness, and reference integration for summarization, with the majority exhibiting statistically significant improvements (P-values <.05). DISCUSSION: RefAI demonstrated substantial improvements in literature recommendation and summarization over existing tools, addressing issues like fabricated papers, metadata inaccuracies, restricted recommendations, and poor reference integration. CONCLUSION: By augmenting LLM with external resources and a novel ranking algorithm, RefAI is uniquely capable of recommending high-quality literature and generating well-structured summaries, holding the potential to meet the critical needs of biomedical professionals in navigating and synthesizing vast amounts of scientific literature.

Brain computer interface (BCI) systems used for clinical assistance purposes such as wheelchair control require decoding of streaming brain signals i.e. electroencephalography (EEG) signals over a long period of time with subject shift in the middle. Numerous challenges arise during this online continual brain signal decoding process: 1) the EEG decoder needs to deal with streaming EEG signals from sequentially arriving subjects, with no data available beforehand for large-scale pretraining; 2) the EEG decoder should avoid catastrophic forgetting on previous subjects after learning on a new subject; 3) the EEG decoder should perform well on noisy signals with high variance across subjects. We proposed a principled replay-based approach for this general decoding scenario, forming a bi-level optimization framework with stochastic neural transformation for dynamic memory evolution, making them representative in feature space and encouraging the model to generalize well. The evolved signal segments are stored and replayed during later decoding stages to achieve optimal model performance on all previous subjects. The stochastic neural transformation performed in inner sup of bi-level optimization significantly enhances the diversity of stored signal segments and improves model robustness during online continual decoding. We perform detailed theoretical analysis on model’s generalization ability in addition to the empirical evaluations. We construct multiple new benchmarks to mimic real-world online sequential EEG decoding scenarios with underlying subject shifts. The extensive evaluation of the proposed approach shows it outperforms related strong baselines by a large margin.

Recently, deep learning has shown to be effective for Electroencephalography (EEG) decoding tasks. Yet, its performance can be negatively influenced by two key factors: 1) the high variance and different types of corruption that are inherent in the signal, 2) the EEG datasets are usually relatively small given the acquisition cost, annotation cost and amount of effort needed. Data augmentation approaches for alleviation of this problem have been empirically studied, with augmentation operations on spatial domain, time domain or frequency domain handcrafted based on expertise of domain knowledge. In this work, we propose a principled approach to perform dynamic evolution on the data for improvement of decoding robustness. The approach is based on distributionally robust optimization and achieves robustness by optimizing on a family of evolved data distributions instead of the single training data distribution. We derived a general data evolution framework based on Wasserstein gradient flow (WGF) and provides two different forms of evolution within the framework. Intuitively, the evolution process helps the EEG decoder to learn more robust and diverse features. It is worth mentioning that the proposed approach can be readily integrated with other data augmentation approaches for further improvements. We performed extensive experiments on the proposed approach and tested its performance on different types of corrupted EEG signals. The model significantly outperforms competitive baselines on challenging decoding scenarios.

OBJECTIVE: Social determinants of health (SDoH) play critical roles in health outcomes and well-being. Understanding the interplay of SDoH and health outcomes is critical to reducing healthcare inequalities and transforming a "sick care" system into a "health-promoting" system. To address the SDOH terminology gap and better embed relevant elements in advanced biomedical informatics, we propose an SDoH ontology (SDoHO), which represents fundamental SDoH factors and their relationships in a standardized and measurable way. MATERIAL AND METHODS: Drawing on the content of existing ontologies relevant to certain aspects of SDoH, we used a top-down approach to formally model classes, relationships, and constraints based on multiple SDoH-related resources. Expert review and coverage evaluation, using a bottom-up approach employing clinical notes data and a national survey, were performed. RESULTS: We constructed the SDoHO with 708 classes, 106 object properties, and 20 data properties, with 1,561 logical axioms and 976 declaration axioms in the current version. Three experts achieved 0.967 agreement in the semantic evaluation of the ontology. A comparison between the coverage of the ontology and SDOH concepts in 2 sets of clinical notes and a national survey instrument also showed satisfactory results. DISCUSSION: SDoHO could potentially play an essential role in providing a foundation for a comprehensive understanding of the associations between SDoH and health outcomes and paving the way for health equity across populations. CONCLUSION: SDoHO has well-designed hierarchies, practical objective properties, and versatile functionalities, and the comprehensive semantic and coverage evaluation achieved promising performance compared to the existing ontologies relevant to SDoH.

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.

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.

OBJECTIVE: The goal of this study is to develop a robust Time Event Ontology (TEO), which can formally represent and reason both structured and unstructured temporal information. MATERIALS AND METHODS: Using our previous Clinical Narrative Temporal Relation Ontology 1.0 and 2.0 as a starting point, we redesigned concept primitives (clinical events and temporal expressions) and enriched temporal relations. Specifically, 2 sets of temporal relations (Allen's interval algebra and a novel suite of basic time relations) were used to specify qualitative temporal order relations, and a Temporal Relation Statement was designed to formalize quantitative temporal relations. Moreover, a variety of data properties were defined to represent diversified temporal expressions in clinical narratives. RESULTS: TEO has a rich set of classes and properties (object, data, and annotation). When evaluated with real electronic health record data from the Mayo Clinic, it could faithfully represent more than 95% of the temporal expressions. Its reasoning ability was further demonstrated on a sample drug adverse event report annotated with respect to TEO. The results showed that our Java-based TEO reasoner could answer a set of frequently asked time-related queries, demonstrating that TEO has a strong capability of reasoning complex temporal relations. CONCLUSION: TEO can support flexible temporal relation representation and reasoning. Our next step will be to apply TEO to the natural language processing field to facilitate automated temporal information annotation, extraction, and timeline reasoning to better support time-based clinical decision-making.