Translational Medical Research Commons^™

Isolation Of Therapeutic Antibodies Against Microseminoprotien To Potentially Overcome Resistance To Anti-Angiogenic Therapy, Mason Ruiz

Dissertations and Theses (Open Access)

High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. Angiogenesis is a vital function for both wound healing and oxygen homeostasis and is one of the hallmarks of cancer in solid tumors. To combat the formation of tumors, an anti-VEGF drug, bevacizumab, is used to starve tumors of blood that provide essential nutrients. While platinum-taxane doublet therapy in addition to cytoreductive surgery has been the gold standard treatment for patients with ovarian cancer, greater than 70% of patients will develop relapsed disease and be burdened with a terminal …

Brief Report: Clinical Response, Toxicity, And Resistance Mechanisms To Osimertinib Plus Met Inhibitors In Patients With Egfr-Mutant Met-Amplified Nsclc, Kaiwen Wang, Robyn Du, Sinchita Roy-Chowdhuri, Ziping T Li, Lingzhi Hong, Natalie Vokes, Yasir Y Elamin, Celyne Bueno Hume, Ferdinandos Skoulidis, Carl M Gay, George Blumenschein, Frank V Fossella, Anne Tsao, Jianjun Zhang, Niki Karachaliou, Aurora O'Brate, Claudia-Nanette Gann, Jeff Lewis, Waree Rinsurongkawong, J Jack Lee, Don Lynn Gibbons, Ara A Vaporciyan, John V Heymach, Mehmet Altan, Xiuning Le

Faculty, Staff and Student Publications

INTRODUCTION:MET amplification is a known resistance mechanism to EGFR tyrosine kinase inhibitor (TKI) treatment in EGFR-mutant NSCLC. Dual EGFR-MET inhibition has been reported with success in overcoming such resistance and inducing clinical benefit. Resistance mechanisms to dual EGFR-MET inhibition require further investigation and characterization.

METHODS: Patients with NSCLC with both MET amplification and EGFR mutation who have received crizotinib, capmatinib, savolitinib, or tepotinib plus osimertinib (OSI) after progression on OSI at MD Anderson Cancer Center were included in this study. Molecular profiling was completed by means of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). Radiological response …

Machine Learning For Ecg Diagnosis And Risk Stratification Of Occlusion Myocardial Infarction, Salah S Al-Zaiti, Christian Martin-Gill, Jessica K Zègre-Hemsey, Zeineb Bouzid, Ziad Faramand, Mohammad O Alrawashdeh, Richard E Gregg, Stephanie Helman, Nathan T Riek, Karina Kraevsky-Phillips, Gilles Clermont, Murat Akcakaya, Susan M Sereika, Peter Van Dam, Stephen W Smith, Yochai Birnbaum, Samir Saba, Ervin Sejdic, Clifton W Callaway

Faculty, Staff and Students Publications

Patients with occlusion myocardial infarction (OMI) and no ST-elevation on presenting electrocardiogram (ECG) are increasing in numbers. These patients have a poor prognosis and would benefit from immediate reperfusion therapy, but, currently, there are no accurate tools to identify them during initial triage. Here we report, to our knowledge, the first observational cohort study to develop machine learning models for the ECG diagnosis of OMI. Using 7,313 consecutive patients from multiple clinical sites, we derived and externally validated an intelligent model that outperformed practicing clinicians and other widely used commercial interpretation systems, substantially boosting both precision and sensitivity. Our derived …

Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li

Dissertations and Theses (Open Access)

Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted the transfer of the CAR-cognate-antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their targets, (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen expressing NK cells (NK^TROG+) and NK cell hyporesponsiveness. This phenomenon could be offset by a dual-CAR system incorporating both …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations and Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Umbilical Cord Blood Transplantation: Connecting Its Origin To Its Future, Gabriela Sanchez-Petitto, Katayoun Rezvani, May Daher, Hind Rafei, Partow Kebriaei, Elizabeth J Shpall, Amanda Olson

Faculty, Staff and Student Publications

Transplantation of umbilical cord blood (UCB) is an attractive alternative source of hematopoietic stem cells (HSCs). The unique properties of cord blood and its distinct immune tolerance and engraftment kinetics compared to bone marrow (BM) and peripheral blood progenitor cells, permit a wider disparity in human leukocyte antigen levels between a cord blood donor and recipient after an unrelated umbilical cord blood transplant (UCBT). In addition, it is readily available and has a lowered risk of graft-versus-host disease (GvHD), with similar long-term clinical outcomes, compared to BM transplants. However, the relatively low number of cells administered by UCB units, as …

Narrative Review Of Single Ventricle: Where Are We After 40 Years?, Antonio F Corno, Tina O Findley, Jorge D Salazar

Faculty, Staff and Student Publications

Background and objective: Key medical and surgical advances have been made in the longitudinal management of patients with "functionally" single ventricle physiology, with the principles of Fontan circulation applied to other complex congenital heart defects. The purpose of this article is to review all of the innovations, starting from fetal life, that led to a change of strategy for single ventricle.

Methods: Our literature review included all full articles published in English language on the Cochrane, MedLine, and Embase with references to "single ventricle" and "univentricular hearts", including the initial history of the treatments for this congenital heart defects as …

Efficient Federated Kinship Relationship Identification, Xinyue Wang, Leonard Dervishi, Wentao Li, Xiaoqian Jiang, Erman Ayday, Jaideep Vaidya

Faculty, Staff and Student Publications

Kinship relationship estimation plays a significant role in today's genome studies. Since genetic data are mostly stored and protected in different silos, retrieving the desirable kinship relationships across federated data warehouses is a non-trivial problem. The ability to identify and connect related individuals is important for both research and clinical applications. In this work, we propose a new privacy-preserving kinship relationship estimation framework: Incremental Update Kinship Identification (INK). The proposed framework includes three key components that allow us to control the balance between privacy and accuracy (of kinship estimation): an incremental process coupled with the use of auxiliary information and …

Sensitive Data Detection With High-Throughput Machine Learning Models In Electrical Health Records, Kai Zhang, Xiaoqian Jiang

Faculty, Staff and Student Publications

In the era of big data, there is an increasing need for healthcare providers, communities, and researchers to share data and collaborate to improve health outcomes, generate valuable insights, and advance research. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) is a federal law designed to protect sensitive health information by defining regulations for protected health information (PHI). However, it does not provide efficient tools for detecting or removing PHI before data sharing. One of the challenges in this area of research is the heterogeneous nature of PHI fields in data across different parties. This variability makes rule-based …

Large Language Models For Healthcare Data Augmentation: An Example On Patient-Trial Matching, Jiayi Yuan, Ruixiang Tang, Xiaoqian Jiang, Xia Hu

Faculty, Staff and Student Publications

The process of matching patients with suitable clinical trials is essential for advancing medical research and providing optimal care. However, current approaches face challenges such as data standardization, ethical considerations, and a lack of interoperability between Electronic Health Records (EHRs) and clinical trial criteria. In this paper, we explore the potential of large language models (LLMs) to address these challenges by leveraging their advanced natural language generation capabilities to improve compatibility between EHRs and clinical trial descriptions. We propose an innovative privacy-aware data augmentation approach for LLM-based patient-trial matching (LLM-PTM), which balances the benefits of LLMs while ensuring the security …

N-Of-1 Trials: The Epitome Of Personalized Medicine?, Joyce P Samuel, Susan H Wootton, Jon E Tyson

Faculty, Staff and Student Publications

Observational studies are notoriously susceptible to bias, and parallel-group randomized trials are important to identify the best overall treatment for eligible patients. Yet, such trials can be expected to be a misleading indicator of the best treatment for some subgroups or individual patients. In selected circumstances, patients can be treated in n-of-1 trials to address the inherent heterogeneity of treatment response in clinical populations. Such trials help to accomplish the ultimate goal of all biomedical research, to optimize the care of individual patients.

Triple Blockade Of Ido-1, Pd-L1 And Mek As A Potential Therapeutic Strategy In Nsclc, Carminia Maria Della Corte, Vincenza Ciaramella, Kavya Ramkumar, Giovanni Vicidomini, Alfonso Fiorelli, Valerio Nardone, Salvatore Cappabianca, Immacolata Cozzolino, Federica Zito Marino, Gaetano Di Guida, Qi Wang, Robert Cardnell, Carl Michael Gay, Davide Ciardiello, Erika Martinelli, Teresa Troiani, Giulia Martini, Stefania Napolitano, Jing Wang, Lauren Averett Byers, Fortunato Ciardiello, Floriana Morgillo

Faculty, Staff and Student Publications

BACKGROUND: Despite the recent progress in the treatment and outcome of Non Small Cell Lung Cancer (NSCLC), immunotherapy has still significant limitations reporting a significant proportion of patients not benefiting from therapy, even in patients with high PD-L1 expression. We have previously demonstrated that the combined inhibition of MEK and PD-L1 in NSCLC patients derived three dimensional cultures exerted significant synergistic effect in terms of immune-dependent cancer cell death. However, subsequent experiments analyzing the expression of Indoleamine 2,3-dioxygenase-1 (Ido-1) gene expression demonstrated that Ido-1 resulted unaffected by the MEK inhibition and even increased after the combined inhibition of MEK and …

A Population-Based Meta-Analysis Of Circulating Gfap For Cognition And Dementia Risk, Mitzi M Gonzales, Crystal Wiedner, Chen-Pin Wang, Qianqian Liu, Joshua C Bis, Zhiguang Li, Jayandra J Himali, Saptaparni Ghosh, Emy A Thomas, Danielle M Parent, Tiffany F Kautz, Matthew P Pase, Hugo J Aparicio, Luc Djoussé, Kenneth J Mukamal, Bruce M Psaty, William T Longstreth, Thomas H Mosley, Vilmundur Gudnason, Djass Mbangdadji, Oscar L Lopez, Kristine Yaffe, Stephen Sidney, R Nick Bryan, Ilya M Nasrallah, Charles S Decarli, Alexa S Beiser, Lenore J Launer, Myriam Fornage, Russell P Tracy, Sudha Seshadri, Claudia L Satizabal

Faculty, Staff and Student Publications

Objective: Expression of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis, colocalizes with neuropathology in the brain. Blood levels of GFAP have been associated with cognitive decline and dementia status. However, further examinations at a population-based level are necessary to broaden generalizability to community settings.

Methods: Circulating GFAP levels were assayed using a Simoa HD-1 analyzer in 4338 adults without prevalent dementia from four longitudinal community-based cohort studies. The associations between GFAP levels with general cognition, total brain volume, and hippocampal volume were evaluated with separate linear regression models in each cohort with adjustment for age, sex, education, …

A Microfluidics-Based Approach For Isolation Of Antigen-Specific Cd8+ T Cells, Meredith Frank

Dissertations and Theses (Open Access)

Cancer is a global epidemic: there are predicted to be 200 million new cases this year alone. Almost a quarter of all cancer-related deaths are caused by lung cancer, for which 5-year survival rates are just above 20%. 85% of lung cancer diagnoses are classified as non-small cell lung cancer (NSCLC) for which 5-year survival rates in metastatic disease are less than 10%. Early detection and targeted therapies have improved prognoses, yet relapse is still common among patients.

Immunotherapies that leverage tumor-specific CD8⁺ cytotoxic T cells have shown great promise for the treatment of NSCLC. However, although highly promising, …

Absolute Quantification Of Tc-99m Activity Distributions Using A Planar Molecular Breast Imaging Commercial System, Benjamin P. Lopez

Dissertations and Theses (Open Access)

Molecular breast imaging (MBI) uses two dedicated-breast semiconductor detectors to visualize the preferential uptake of technetium-99m-sestamibi (^99mTc-sestamibi) by breast cancer cells relative to surrounding benign breast tissues. Clinically, MBI is used primarily as a supplementary tool to standard-of-care mammography because of its improved detection of breast cancers, especially in women with mammographically-dense breasts. Because of a lack of image corrections, MBI applications are currently limited to qualitative evaluations of relative pixel intensities between image regions with suspected lesions and normal tissue.

The objective of this dissertation was to use Monte Carlo simulations to better characterize the MBI imaging …

Unraveling The Effects Of Aerobic Exercise And Erk5 Signaling In The Solid Tumor Microenvironment Using Murine Models, Hannah Savage

Dissertations and Theses (Open Access)

Solid tumors are comprised of multiple cell types which communicate and work together to promote tumor progression. Advances in the treatment of solid tumors have armed clinicians with more efficacious pharmacologic agents and combinations. However, a focus on drug adjuvants in the treatment of solid cancer has left gaps in knowledge regarding non-pharmacologic treatment adjuvants, like aerobic exercise. The current dissertation investigates pharmacologic and non-pharmacologic based approaches to remodel the solid tumor microenvironment landscape and alter therapeutic efficacy. We disassemble compartments of the tumor microenvironment, including tumor vasculature and immune infiltrate, using mouse models and single cell techniques, to elucidate …

Bhlhe40: Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery Salmon, Avery J. Salmon

Dissertations and Theses (Open Access)

Advancements in immunotherapy treatments have become essential in the treatment of various cancers, such as those with high tumor burden like melanoma(Brahmer et al., 2012; Hodi et al., 2010). Immunotherapy, specifically immune checkpoint therapy (ICT) provides antagonist effect on specific immune checkpoints to control effector T cell functions(Pardoll, 2012). This therapy allows for the modulation of anti-tumor responses through the use of monoclonal antibodies, such as anti-CTLA-4 or anti-PD-1 that block the receptors from binding with their ligands, thus allowing for CD4⁺ and CD8⁺ T cell priming and activation(Wei et al., 2017). However, the required epigenetic and transcriptional …

Cell-Free Dna Sequencing In Multiple Myeloma, Russell Irwin

Dissertations and Theses (Open Access)

Multiple myeloma (MM) is an incurable plasma cell dyscrasia. Recent advances in MM therapy, including CAR-T therapy, have increased survival and shown the value of assessing treatment response with great sensitivity, both in acute and long-term settings. Cell-free DNA, DNA fragments which are released into circulation as a part of normal cellular turnover, is a useful and dynamic biomarker in cancer patients due to the presence of circulating tumor DNA (ctDNA), which is readily identified using next generation sequencing. Here we report the analytical sensitivity, applicability, consistency, and prognostic ability of M5Seq, a novel hybrid capture panel designed for MM …

Prognostic Serum Biomarkers In Cancer Patients With Covid-19: A Systematic Review, Te-An Lee, Shih-Han Wang, Chun-Tse Kuo, Chia-Wei Li, Louise D Mccullough, Dhimiter Bello, Yun-Ju Lai

Faculty, Staff and Student Publications

Purpose: Cancer patients with COVID-19 likely express biomarker changes in circulation. However, the biomarkers used in SARS-CoV-2 infected cancer patients for COVID-19 severity and prognosis are largely unclear. Therefore, this systematic review aims to determine what biomarkers were measured in cancer patients with COVID-19 and their prognostic utility.

Methods: A systematic literature review in PubMed, Embase, and Scopus was performed on June 16th, 2021. The search keywords coronavirus, neoplasm, biomarkers, and disease progression were used to filter out 17 eligible studies, which were then carefully evaluated.

Results: A total of 4,168 patients, 16 types of cancer, and 60 biomarkers were …

Neoadjuvant Immunotherapy Across Cancers: Meeting Report From The Immunotherapy Bridge-December 1st–2nd, 2021, Elizabeth M Burton, Rodabe N Amaria, Tina Cascone, Myriam Chalabi, Neil D Gross, Elizabeth A Mittendorf, Richard A Scolyer, Padmanee Sharma, Paolo A Ascierto

Faculty, Staff and Student Publications

After the success of immunotherapy in the treatment of advanced metastatic cancer, further evaluation in earlier settings, including high-risk, surgically-resectable disease is underway. Potential benefits of a neoadjuvant immunotherapeutic approach include presurgical tumor shrinkage, reduced surgical morbidity, early eradication of micrometastases and prevention of distant disease, and greater antigen-specific T cell response. For some cancers, pathologic response has been established as a surrogate measure for long-term outcomes, therefore offering the ability for early and objective assessment of treatment efficacy and the potential to inform and personalize adjuvant treatment clinical decision-making. Leveraging the neoadjuvant treatment setting offers the ability to deeply …

Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin

Dissertations and Theses (Open Access)

One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test …

Spatial Transcriptomics Of Dorsal Root Ganglia Identifies Molecular Signatures Of Human Nociceptors, Diana Tavares-Ferreira, Stephanie Shiers, Pradipta R Ray, Andi Wangzhou, Vivekanand Jeevakumar, Ishwarya Sankaranarayanan, Anna M Cervantes, Jeffrey C Reese, Alexander Chamessian, Bryan A Copits, Patrick M Dougherty, Robert W Gereau, Michael D Burton, Gregory Dussor, Theodore J Price

Faculty, Staff and Student Publications

Nociceptors are specialized sensory neurons that detect damaging or potentially damaging stimuli and are found in the dorsal root ganglia (DRG) and trigeminal ganglia. These neurons are critical for the generation of neuronal signals that ultimately create the perception of pain. Nociceptors are also primary targets for treating acute and chronic pain. Single-cell transcriptomics on mouse nociceptors has transformed our understanding of pain mechanisms. We sought to generate equivalent information for human nociceptors with the goal of identifying transcriptomic signatures of nociceptors, identifying species differences and potential drug targets. We used spatial transcriptomics to molecularly characterize transcriptomes of single DRG …

Medical Management Of Infants With Supraventricular Tachycardia: Results From A Registry And Review Of The Literature, Nathan Wei, Avani Lamba, Sonia Franciosi, Ian H Law, Luis A Ochoa, Christopher L Johnsrude, Sit Yee Kwok, Teng Hong Tan, Santokh S Dhillon, Anne Fournier, Stephen P Seslar, Elizabeth A Stephenson, Andrew D Blaufox, Michel Cabrera Ortega, Jeffrey N Bone, Ash Sandhu, Carolina A Escudero, Shubhayan Sanatani

Faculty, Staff and Student Publications

BACKGROUND: Several medication choices are available for acute and prophylactic treatment of refractory supraventricular tachycardia (SVT) in infants. There are almost no controlled trials, and medication choices are not necessarily evidence based. Our objective was to report the effectiveness of management strategies for infant SVT.

METHODS: A registry of infants admitted to hospital with re-entrant SVT and no haemodynamically significant heart disease were prospectively followed at 11 international tertiary care centres. In addition, a systematic review of studies on infant re-entrant SVT in MEDLINE and EMBASE was conducted. Data on demographics, symptoms, acute and maintenance treatments, and outcomes were collected. …

Improving Pharmacovigilance Signal Detection From Clinical Notes With Locality Sensitive Neural Concept Embeddings, Justin Mower, Elmer Bernstam, Hua Xu, Sahiti Myneni, Devika Subramanian, Trevor Cohen

Faculty, Staff and Student Publications

Although pharmaceutical products undergo clinical trials to profile efficacy and safety, some adverse drug reactions (ADRs) are only discovered after release to market. Post-market drug safety surveillance - pharmacovigilance - leverages information from various sources to proactively identify such ADRs. Clinical notes are one source of observational data that could assist this process, but their inherent complexity can obfuscate possible ADR signals. In previous research, embeddings trained on observational reports have improved detection of such signals over commonly used statistical measures. Moreover, neural embedding methods which further encode juxtapositional information have shown promise on analogical retrieval tasks, suggesting proximity-based alternatives …

Temporal Cohort Logic, Guo-Qiang Zhang, Xiaojin Li, Yan Huang, Licong Cui

Faculty, Staff and Student Publications

We introduce a new logic, called Temporal Cohort Logic (TCL), for cohort specification and discovery in clinical and population health research. TCL is created to fill a conceptual gap in formalizing temporal reasoning in biomedicine, in a similar role that temporal logics play for computer science and its applications. We provide formal syntax and semantics for TCL and illustrate the various logical constructs using examples related to human health. Relationships and distinctions with existing temporal logical frameworks are discussed. Applications in electronic health record (EHR) and in neurophysiological data resource are provided. Our approach differs from existing temporal logics, in …

Modulating Immunometabolism To Improve The Activity Of Car-Nk Cells Targeting Cd70 In Renal Cell Carcinoma, Hind Rafei

Dissertations and Theses (Open Access)

Despite the approval of several therapies for metastatic clear cell renal cell carcinoma (ccRCC), disease resistance and relapse are common, and therapies with novel mechanisms of action are urgently needed. Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable responses in hematologic malignancies, but many obstacles hinder success in solid tumors including the paucity of highly specific targets and the hostility of the tumor microenvironment (TME). Moreover, the limitations of generating an autologous cell product, such as cost of manufacture, and the challenges of toxicity with CAR-T cells highlight the need to develop new cell therapy products that are at …

Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra

Dissertations and Theses (Open Access)

Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …

A Fully-Automated, Deep Learning-Based Framework For Ct-Based Localization, Segmentation, Verification And Planning Of Metastatic Vertebrae, Tucker Netherton, Tucker James Netherton

Dissertations and Theses (Open Access)

Palliative radiotherapy is an effective treatment for the palliation of symptoms caused by vertebral metastases. Visible evidence of disease is localized on medical images as part of the treatment planning process. However, complicating factors such as time pressures, anatomic variants in the spine, and similarities in adjacent vertebrae are associated with wrong level treatments of the spine. In addition, erroneous manual contouring of anatomic structures is a major failure mode in radiotherapy treatment planning.

The purpose of this study is to mitigate the challenges associated with treatment planning of the spine by automating the treatment planning process for three-dimensional conformal …

A Comparison Of Exhaustive And Non-Lattice-Based Methods For Auditing Hierarchical Relations In Gene Ontology, Rashmie Abeysinghe, Fengbo Zheng, Licong Cui

Faculty, Staff and Student Publications

Uncovering and fixing errors in biomedical terminologies is essential so that they provide accurate knowledge to downstream applications that rely on them. Non-lattice-based methods have been applied to identify various kinds of inconsistencies in different biomedical terminologies. In previous work, we have introduced two inference-based approaches that were applied in an exhaustive manner to audit hierarchical relations in the Gene Ontology: (1) Lexical-based inference framework, and (2) Subsumption-based sub-term inference framework. However, it is unclear how effective these exhaustive approaches perform compared with their corresponding non-lattice-based approaches. Therefore, in this paper, we implement the non-lattice versions of these two exhaustive …

Identifying Sleep-Related Factors Associated With Cognitive Function In A Hispanics/Latinos Cohort: A Dual Random Forest Approach, Li Xiaojin, Cui Licong, Wang Fei, Paul E Schulz, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Disordered sleep is associated with poor cognitive function and cognitive decline. However, little is known regarding the association of sleep-related factors with cognitive function in underrepresented cohorts such as the Hispanic/Latino population. Leveraging the National Sleep Research Resource, one of the most comprehensive collections of sleep studies, we identified a Hispanic/Latino cohort of 1,031 lower cognitive function cases and 2,062 normal controls. We developed a novel dual random forest (DRF) approach to discriminate cases against controls for estimating the potential impact of sleep-related variables related to the decline of cognitive function. Several important sleep-related factors were identified which may be …