Medicine and Health Sciences Commons^™

Correction: Exploiting Prmt5 As A Target For Combination Therapy In Mantle Cell Lymphoma Characterized By Frequent Atm And Tp53 Mutations, Yijing Li, Wei Wang, Lixin Rui, Michael Wang

Faculty, Staff and Student Publications

No abstract provided.

An Artificial Intelligence Optimized Hepatic Differentiation Unveils Nr5a2 And Ap-1 Transcriptional Regulation In Hepatic Maturation, Ruoyu Wang, Tara N Tavakol, Mikal Kizilbash, Megan E Fisher, Yu-Wen Huang, Dandan Zhu, Trinh T T Phan, Rachel Shoemaker, Ya-Wen Chen, Yang Zhang, Chad D Huff, Shih-Yu Chen, Tien-Jen Liu, Haipeng Xiao, Dung-Fang Lee, Ruiying Zhao

Faculty, Staff and Student Publications

The generation of hepatocyte-like cells (HLCs) from human pluripotent stem cells (hPSCs) holds great promise for drug discovery and cell-based therapy for liver disease. However, current differentiation protocols are complicated and unstable, and the underlying gene regulatory mechanisms of hepatic differentiation remain incompletely defined. Here, we developed a machine learning-based artificial intelligence (AI) tool using phase-contrast images of hepatic progenitor cells (HPCs), which are essential for generating HLCs. The AI tool significantly improves the success rate of hepatic differentiation without the need for immunostaining or lineage tracing. By optimizing the methodology, we achieved an impressive purity of 90-95% for HLCs …

Integration Of Aged Brain Multi-Omics Reveals Cross-System Mechanisms Underlying Alzheimer’S Disease Heterogeneity, Philip L De Jager, Julie A Schneider, Aron S Buchman, Yanling Wang, Shinya Tasaki, Roberto T Raittz, David A Bennett, Ricardo A Vialle

Faculty, Staff and Student Publications

The molecular correlates of Alzheimer's disease (AD) are increasingly being defined by multi-omics. However, findings from different data types are often difficult to reconcile. Here, we apply a data-driven multi-omics framework integrating seven omics layers from up to 1,358 aged human brain samples from the Religious Orders Study and Rush Memory and Aging Project. We demonstrate sprawling cross-omics biological factors relating to AD phenotypes. The strongest AD-associated factor (factor 8) is characterized by elevated immune activity at the epigenetic level, decreased heat shock gene expression in the transcriptome, and disrupted energy metabolism and cytoskeletal dynamics in the proteome. Unsupervised clustering …

Lgr5: From Stem Cell Marker To Therapeutic Target

Faculty, Staff and Student Publications

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is an established marker of normal and cancer stemlike cells. LGR5 has been implicated in promoting cancer cell plasticity that drives tumorigenesis, metastasis, and therapeutic resistance. LGR5 rapidly and constitutively internalizes and potentiates Wnt (Wingless/Int-1)/β-catenin and adhesion signaling pathways, though its precise mechanisms and interacting partners remain unresolved. An improved understanding of LGR5 signaling may provide invaluable insight into its intricate and important functions in cancer progression. Moreover, several LGR5-targeting therapies, including peptibody- and antibody-drug conjugates and bispecific antibodies, are showing promising efficacy and tolerability in colorectal cancer and other tumor types. This …

Data Science In Medicine: Bridging The Statistics & Research Skills Education Gap Through Multi-Platform Bootcamps, Marta Haireek, Muhammad Idrees, Yiannos Demetriou, Laura Benjamins, Alan Dombkowski

Medical Student Research Symposium

Background

Presently, there is great emphasis on medical students' research output and demand for healthcare practitioners with skills in data appraisal, research methodologies, and evidence interpretation; however, medical students do not receive formal training in research and data science. This presents a major gap in medical education as curriculums focus on USMLE preparation without exposure to statistical software or analytical thinking required for productive research outcomes or evidence appraisal. Accordingly, the “Data Science Research Bootcamp” addressed this gap through workshops focused on Python, R, and SPSS.

Methods

WSUSOM students attended Python (n=22), R (n=9), and SPSS (upcoming) workshops to learn …

Bdcd: A Comprehensive Brain Disease Cell-Cell Communication Database, Andi Liu, Chia-Hao Tung, Zhongming Zhao

Faculty, Staff and Student Publications

Dysregulated cell–cell communication (CCC) is increasingly recognized as a driver of brain disease pathology, contributing to neuroinflammation, synaptic dysfunction, and neurodegeneration. Nevertheless, existing resources remain limited in brain specificity, regional coverage, and functional annotation. To address this gap, we develop the Brain Disease Cell-cell communication Database (BDCD), the first comprehensive resource focused on CCC networks across major brain diseases. BDCD integrates 38 manually curated datasets, comprising 8 519 425 single cells from single-cell RNA-seq studies and 140 744 spots from spatial transcriptomic maps, spanning 14 brain regions and 13 canonical cell types covering Alzheimer’s disease, Parkinson’s disease, schizophrenia, bipolar disorder, …

Deep Learning-Based Automated Pneumonia Detection From Chest X-Rays: A Comparative Study Of Custom Cnn And Transfer Learning Architectures, Ahmed Sajim

Honors Theses

Pneumonia is a leading global cause of mortality, claiming approximately 2.5 million lives an-nually and placing exceptional diagnostic pressure on radiologists in resource-limited settings. Manual interpretation of chest X-ray (CXR) images is time-consuming, subject to inter-observer variability, and limited by radiologist availability. This thesis presents a systematic investiga-tion into deep learning-based automated pneumonia detection comparing five convolutional neural network (CNN) architectures: a custom-designed 2D CNN and four pretrained transfer learning models—ResNet, DenseNet, MobileNet, and VGG19.

A targeted data augmentation pipeline addresses the severe class imbalance in the Kag-gle Chest X-Ray Pneumonia dataset, expanding the Normal class from 1,583 to 9,495 …

Deep Learning Based Approaches For Low Cost Defense Detection, Adele J. Noel-Rickert

All NMU Master's Theses

Pulmonary fibrosis is a progressive interstitial lung disease characterized by the accumulation of fibrotic tissue within the lungs, leading to impaired respiratory function and reduced quality of life. Early detection is important for disease management; however, accurate diagnosis often relies on high-resolution computed tomography (CT), which may not be accessible in all clinical settings. Chest radiography provides a lower-cost and widely available imaging modality, but interpretation of chest X-rays for fibrotic disease can be challenging due to subtle radiographic patterns and overlapping anatomical structures. This thesis investigates the use of multimodal deep learning techniques to assist in pul- monary fibrosis …

A Patient-Centric Chatbot For Improving Clinical Trial Accessibility, Yumeng Yang

Dissertations and Theses (Open Access)

Clinical trial enrollment remains a major challenge, and low accrual continues to delay study completion, increase research costs, and slow the development of new therapies. A barrier is the scale of the trial-matching problem: patients and clinicians must search through a large and growing number of studies, while each trial contains complex eligibility criteria that may overlap only partially with other trials. Although public registries such as ClinicalTrials.gov make trial information available, they do not adequately help patients identify which studies are most relevant to their clinical profile. This dissertation addresses that information problem by developing and evaluating a patient-centric …

A Computational Framework For Quantifying Dysregulation And Mapping Pathways Using Transcriptomic And Molecular Data And Its Application In O-Glcnacylation, Rastko Stojsin

Dissertations and Theses (Open Access)

Post-translational modifications (PTMs) are chemical modifications that occur on proteins after synthesis and play an essential role in regulating protein function. Dysregulation of biologically critical PTMs has been widely implicated in many disease phenotypes primarily through effects on complex downstream protein networks. Measurement of PTMs—particularly abundant and rapidly cycling modifications—is often limited to technically challenging and low-throughput biochemical assays. As a result, large-scale clinical datasets rarely contain direct measurements of PTM activity. These limitations restrict current research to expensive, small-scale, hypothesis-driven laboratory studies often focused on an individual disease and pathway. This dissertation presents a data-driven biomedical informatics framework for …

Graph And Language Models For Biomedical Inference Across Networks And Text, Evan Yu

Dissertations and Theses (Open Access)

Biomedical research increasingly relies on large and heterogeneous data sources to support scientific inference. However, relevant evidence is often distributed across environments that differ substantially in structure, reliability, and scale. Biomedical evidence may be represented in relational networks that encode interactions among entities and in large-scale text corpora that contain unstructured knowledge and discourse. Developing computational approaches capable of extracting reliable and interpretable signals from these diverse data environments remains a central challenge. This dissertation investigates how graph and language models can support robust biomedical inference across three evidence environments: relational epidemiologic networks, large-scale social media discourse, and biomedical scientific …

Using Artificial Intelligence Agents To Improve Identification Of Patients With Diabetic Retinopathy For Population Health Management, Mary H. Stanfill

Translational Projects (Open Access)

Population health management of patients in risk-adjusted payment plans requires new tools and techniques to control costs, enhance care, and ultimately improve patient outcomes. Effective population health management of risk-adjusted patients with complications of chronic conditions first requires identifying all the risk-adjusted patients with such complications, but common structured data sources in the electronic health record (EHR) to identify such patients are notoriously inaccurate. Thus, the mechanisms used today, based only on structured data to retrieve patients with complications of a chronic condition, are prone to problems. This makes current information retrieval (IR) approaches inadequate to support population health management …

Standardizing Anticoagulant Hold Orders In Computerized Provider Order Entry, Alicia Beebe

Translational Projects (Open Access)

Medication safety remains a persistent challenge, particularly for high-risk anticoagulants where even minor communication failures can result in catastrophic bleeding or thromboembolic events. This translational project aimed to address the systemic risks associated with temporary medication holds in the electronic health record of a 10-hospital health system. The project used a phased approach combining quantitative chart audits, qualitative clinician interviews, and workflow and cause mapping to examine anticoagulant medication hold processes. Findings revealed design limitations, fragmented workflows, and usability challenges. Additionally, baseline analysis of September 2024 data revealed a substantial safety gap: Communication hold orders had a 15.05% medication error …

Building A Monitoring And Tracking System To Optimize Radiation Quality In Clinical Trials, Andrea Molineu

Translational Projects (Open Access)

Imaging Radiation Oncology Core (IROC) is funded by a grant from the National Cancer Institute (NCI). One of the grant requirements is that IROC provides an annual remote independent verification of radiation output for all institutions participating in NCI-sponsored clinical trials. This involves shipping acrylic blocks that hold dosimeters to each of the institutions. Each institution is assigned a month to receive a shipment. However, mailing is often delayed. The goal of sending 100% of the shipments in the month they are scheduled has not been reached. This delays the institutions' independent dose verification. The delay is detrimental because it …

Making Value Visible: A Translational Informatics Study Of Independent Primary Care, Julia Pulliam

Translational Projects (Open Access)

The transition to Value-Based Care (VBC) challenges independent rural primary care practices due to heavy administrative burdens, interoperability barriers, and a reliance on claims data that often undervalues care. This project aimed to improve clinical data reporting to Medicare Advantage Quality Incentive Programs (QIPs) at Oregon City Family Practice (OCFP). By focusing on colon cancer screening metrics, the project sought to demonstrate how automating semantic interoperability can accurately reflect care quality, reduce manual waste, and increase revenue. Guided by the Johns Hopkins Evidence-Based Practice (JHEBP) framework, Plan-Do Study-Act (PDSA) cycles were used to design a transition from manual reporting to …

Natural Language Generation In Healthcare: A Review Of Methods And Applications, Cheng Peng, Sankalp Talankar, Yonghui Wu

Faculty, Staff and Student Publications

Objective: This study presents a systematic review of natural language generation (NLG) methods and applications in the medical domain, providing quantitative and qualitative analyses to answer four key research questions regarding methods, evaluation, applications, and challenges of NLG in healthcare.

Methods: We searched PubMed, ACM Digital Library, Web of Science, Science Direct, Scopus, Embase, and ACL Anthology for NLG-related studies in healthcare from 2018 to 2024. Out of 3,988 research articles, 113 met the inclusion criteria and were analyzed across data modality, model architecture, evaluation metrics, and application domain.

Results and conclusion: NLG in healthcare has grown substantially, with annual …

A Topic Modeling Analysis Of Stigma Dimensions, Social, And Related Behavioral Circumstances In Clinical Notes Among Patients With Hiv, Robert L Cook, Jiang Bian, Yi Guo, Yonghui Wu

Faculty, Staff and Student Publications

Objective: To characterize stigma dimensions, social, and related behavioral circumstances in people living with HIV (PLWHs) seeking care, using natural language processing methods applied to a large collection of electronic health record (EHR) clinical notes from a large integrated health system in the southeast United States.

Methods: We identified a cohort of PLWHs from the University of Florida (UF) Health Integrated Data Repository and performed topic modeling analysis using Latent Dirichlet Allocation (LDA) to uncover stigma-related dimensions and related social and behavioral contexts. Domain experts created a seed list of HIV-related stigma keywords, then applied a snowball strategy to iteratively …

Feasibility Of Identifying Factors Related To Alzheimer’S Disease And Related Dementia In Real-World Data, Yu-Neng Chuang, Xia Hu, Serena Jingchuan Guo, Xing He, Yijiang Pang, Jiayu Zhou, Yonghui Wu, Yi Guo, Jiang Bian

Faculty, Staff and Student Publications

Objective: This study aimed to provide a comprehensive understanding of factors associated with Alzheimer's disease (AD) and AD-related dementias (AD/ADRD), which could aid in studies to develop new treatments for AD/ADRD patients and identify high-risk populations for prevention.

Scope and method: In our study, we summarized the risk factors for AD/ADRD by reviewing existing meta-analyses and review articles on risk and preventive factors for AD/ADRD. From this literature review and the identified AD/ADRD factors, we examined the accessibility of these risk and preventive factors in both structured and unstructured Electronic Health Records (EHRs) data.

Results: In total, we extracted 401 …

Baseline Parp-1 Pet Imaging In Patients With Advanced Solid Tumors With Dna Damage Response Mutations, Tarek Daoud, Jiansong Chen, Peng Wei, Franklin Wong, Timothy A Yap

Faculty, Staff and Student Publications

Purpose: Inhibitors of poly(ADP-ribose) polymerase (PARP), an enzyme with numerous roles in DNA damage response signaling, represent a class of anti-cancer drugs approved for treating solid tumors with defects in the DNA damage response. However, additional methods for identifying patients who would benefit from the use of PARP inhibitors are urgently needed. We evaluated a novel radiotracer, 18F-FluorThanatrace ([18F]-FTT), to noninvasively assess PARP activity with PET/CT before treatment and determine associations between uptake, tumor mutation status, and prior receipt of therapy including PARP inhibitors.

Methods: Fifty-two patients with solid tumors underwent whole-body (skull base to thigh) [18F]-FTT PET/CT scans before …

Gompertz Growth With A Shared Carrying Capacity Optimally Simulates Primary And Metastatic Tumor Growth Dynamics, Pirmin Schlicke, Preethi Korangath, Xiaoxi Pan, Caner Ercan, Kathleen Gabrielson, Yinyin Yuan, Robert Ivkov, Heiko Enderling

Faculty, Staff and Student Publications

Background: Cancer is a systemic disease with most deaths attributed to metastatic burden. Primary and metastatic tumors, albeit at different anatomic locations, are interconnected through multiple biological processes. Pre-clinical and clinical observations of growth acceleration of metastases after surgery, or abscopal effects outside the radiation field are widely reported, yet reliably triggering favorable and avoiding unfavorable systemic responses remains an unmet clinical need. Understanding local and systemic tumor interaction dynamics will help guide future treatments.

Methods: We analyze the data of multiple in vivo tumor models. We formalize the systemic interplay of tumors as mathematical differential equation and calibrate parameters …

Unraveling The Nexus: Tumor Mutational Burden, Pd-L1 Expression, And Oncogenic Alterations In Non-Small Cell Lung Cancer Cytology Specimens, Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Asif Rashid, Mark J Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.

Methods: Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.

Results: …

Structural-Functional Analyses Of The Huntingtin/Hap40 Complex In Drosophila And Humans, Stephen M Farmer, Amanda Solbach, Shiyu Xu, Beatriz Rios, Xin Ye, Daniela Covarrubias, Lili Ye, Vicky Chuong, Erin Furr Stimming, Haiqing Zhao, Sheng Zhang

Faculty, Staff and Student Publications

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal CAG expansion in the Huntingtin (HTT) gene. Given its simple genetic cause but complex pathogenic mechanisms, interest in targeting HTT for HD treatment is growing, necessitating a clear understanding of HTT regulation. HTT protein primarily exists in a core complex with HAP40, forming a highly ordered structure with two large globular domains connected by a bridge. We previously demonstrated that HAP40 is conserved in

Multiparametric Mri To Predict Response To Irreversible Electroporation Plus Anti-Pd-1 Immunotherapy In Pancreatic Ductal Adenocarcinoma, Qizhen Cao, Mark D Pagel, Charles V Kingsley, Jingfei Ma, James P Long, Seth T Gammon, Sanaz Javadi, Chun Li

Faculty, Staff and Student Publications

Purpose: To investigate contrast-enhanced T1-weighted MRI and diffusion-weighted magnetic resonance imaging (DWI) for early prediction of tumor response to combined irreversible electroporation (IRE) and anti-PD-1 immunotherapy.

Methods: Murine pancreatic ductal adenocarcinoma (PDAC) cells KRAS* were inoculated into the pancreas of C57BL/6 mice. IRE was performed when tumors became palpable. After IRE, mice received six intraperitoneal injections of anti-PD-1 over 2 weeks. T2-weighted MRI, T1-weighted MRI with macromolecular contrast agent poly(L-glutamic acid)-conjugated gadolinium (PG-Gd), and DWI were performed before and after IRE. Survival was analyzed using Kaplan-Meier curves. Mice surviving at least 100 days without recurrence after IRE were considered complete …

Identifying Sorafenib Benefit Among Patients With Hepatocellular Carcinoma: A Transcriptomic And Genomic Approach, Sun Young Yim, Hayeon Kim, Tae Hyung Kim, Sang-Hee Kang, Youngwoo Lee, Yang Jae Yoo, Young-Sun Lee, Young Kul Jung, Yeon Seok Seo, Hyung Joon Yim, Jong Eun Yeon, Kyung Suk Yang, Yitao Tang, Bowha Sohn, Yun Seong Jeong, Hyewon Park, Han Liang, Ju-Seog Lee, Ji Hoon Kim

Faculty, Staff and Student Publications

Background & aims: Sorafenib has been a cornerstone of hepatocellular carcinoma (HCC) therapy; however, its efficacy is limited, and identifying patients who will benefit from sorafenib is challenging. We aimed to identify predictive biomarkers of sorafenib benefit in patients with HCC.

Methods: Gene expression data from 33 HCC tumors treated with sorafenib were analyzed to construct a prediction model aimed at identifying patients with greater benefit from sorafenib treatment. The robustness of the predictor was validated using gene expression data from two phase III clinical trials, IMbrave150 and STORM.

Results: The analysis of transcriptome data revealed a 50-gene signature, the …

Neutrophil-Microglia Interaction Drives Motor Dysfunction In A Neuromyelitis Optica Model Induced By Subarachnoid Aqp4-Igg, Fangfang Qi, Vanda A Lennon, Shunyi Zhao, Yong Guo, Husheng Ding, Whitney M Bartley, Claudia F Lucchinetti, Long-Jun Wu

Faculty, Staff and Student Publications

Neutrophils and neutrophil extracellular traps (NETs) contribute to early neuromyelitis optica (NMO) histopathology initiated by IgG targeting astrocytic aquaporin-4 (AQP4) water channels. Yet, the mechanisms underlying neutrophil recruitment and their pathogenic roles in disease progression remain unclear. To investigate molecular-cellular events preceding classical complement cascade activation in a mouse NMO model, we continuously infused, via spinal subarachnoid route, a non-complement-activating mouse monoclonal AQP4-IgG. Parenchymal infiltration of netting neutrophils containing C5a ensued with microglial activation and motor impairment but no blood-brain barrier leakage. Motor impairment and neuronal dysfunction both reversed when AQP4-IgG infusion stopped. Two-photon microscopy and electron microscopy-based reconstructions revealed …

Tumor Flare Reaction With Brentuximab-Vedotin In Mycosis Fungoides, Rishabh Lohray, Seda Purnak, Samruddhi Arkatkar, Madeleine Duvic, Victor Prieto, Auris Huen

Faculty, Staff and Student Publications

No abstract provided.

Axillary Management After Neoadjuvant Endocrine Therapy (Net), Laura Leonard, Min Yi, Emma Wingate, Puneet Singh, Abigail Caudle, Isabelle Bedrosian, Jennifer Litton, Nuhad Ibrahim, Kelly K Hunt

Faculty, Staff and Student Publications

BACKGROUND: In patients with hormone receptor-positive (HR

PATIENTS AND METHODS: We performed a retrospective review of patients with clinical stage I-III, HR

RESULTS: A total of 230 patients were included; 120 (52.2%) were clinically node-negative (cN0), while 110 (47.8%) were clinically node-positive (cN+). In the cN+ group, 7.3% (8/110) had a nodal pathologic complete response (pCR). In total, 76.4% (84/110) in the cN+ group underwent axillary lymph node dissection (ALND) as the initial axillary procedure, and 90.9% (100/110) underwent ALND overall. In total, 98.3% (118/120) with cN0 disease underwent sentinel lymph node dissection (SLND), and 28 (23.7%) had positive nodes. …

56-Year-Old Man With Dyspnea And Volume Overload

Faculty, Staff and Student Publications

No abstract provided.

Carotid Endarterectomy Remains A Feasible Bailout For Progressive Disease After Transcarotid Artery Revascularization: A Case Report, Naveed U Saqib

Faculty, Staff and Student Publications

Carotid endarterectomy (CEA) remains the gold standard for carotid revascularization, though transcarotid artery revascularization (TCAR) has emerged as a less invasive alternative. We present a 67-year-old man with prior bilateral TCAR who developed severe right internal carotid artery restenosis 14 months after the procedure. Imaging confirmed >80% stenosis due to progressive plaque burden compressing the stent. The patient underwent successful CEA with en bloc stent explant using a standard technique. Recovery was uneventful. This case demonstrates the technical feasibility and safety of surgical stent explant after TCAR and reinforces CEA as a reliable salvage strategy when stent failure or disease …

Complex Iliac Artery And Iliocaval Venous Reconstruction Using Temporary, Redundant Graft To Facilitate Resection Of Recurrent Metastatic Sex Stromal Tumor, Justin E Bird

Faculty, Staff and Student Publications

We report a complex case of recurrent, metastatic sex cord stromal tumor involving the pelvic vasculature and spinal nerves. Posterior and anterior approaches were required with redo iliac artery reconstruction using a temporary, redundant aortoiliac to right external iliac artery graft and iliocaval venous reconstruction. After completion of tumor resection from nerve structures, reconstruction of the right iliac veins was completed and the redundant aortoiliac arterial graft was shortened. The redundant graft minimized ischemia time, enabling meticulous dissection and tumor removal. This case underscores the importance of multidisciplinary collaboration in managing rare, aggressive malignancies with complex vascular and neural involvement.