Medicine and Health Sciences Commons^™

Global Dna Methylation Differences Involving Germline Structural Variation Impact Gene Expression In Pediatric Brain Tumors, Fengju Chen, Yiqun Zhang, Wei Li, Fritz J Sedlazeck, Lanlan Shen, Chad J Creighton

Children’s Nutrition Research Center Staff Publications

The extent of genetic variation and its influence on gene expression across multiple tissue and cellular contexts is still being characterized, with germline Structural Variants (SVs) being historically understudied. DNA methylation also represents a component of normal germline variation across individuals. Here, we combine germline SVs (by short-read sequencing) with tumor DNA methylation across 1292 pediatric brain tumor patients. For thousands of methylation probes for CpG Islands (CGIs) or enhancers, rare and common SV breakpoints upstream or downstream associate with differential methylation in tumors spanning various histologic types, a significant subset involving genes with SV-associated differential expression. Cancer predisposition genes …

Investigating The Role Of Lysophosphatidic Acid Receptor 3 In Ocular Surface Ion Transport And Fluid Secretion, Ethan Lindgren

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Dry eye disease (DED) is a multifactorial disease that drives tear film instability and hyperosmolarity, directly damaging the ocular surface epithelium. Lysophosphatidic acid receptor (LPAR) is a G-protein coupled receptor (GPCR) responsible for Ca²⁺ and cAMP mobilization via PLC and adenylyl cyclase activation, respectively. LPAR signaling is involved in cell proliferation and wound healing in human corneal epithelial cells (HCECs) as well as in neuropathic pain. This study aims to investigate expression and functional roles of LPAR3 in ocular surface. Ocular surface potential difference (OSPD) and tear fluid volume measurements were performed in mice with topically applied LPAR modulators. …

Ion-Dna Interactions As A Key Determinant Of Uracil Dna Glycosylase Activity., Sharon N Greenwood, Alexis N Dispensa, Matthew Wang, Justin R Bauer, Timothy D Vaden, Zhiwei Liu, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Because of their ubiquitous presence, ions interact with numerous macromolecules in the cell and affect critical biological processes. Here, we discuss how cations including Mg²⁺ alter the enzymatic activity of a DNA glycosylase by tuning its affinity for DNA. The response of uracil DNA glycosylase (UNG2) to Mg²⁺ ions in solution is biphasic and paradoxical, where low concentrations of the ion stimulate the enzyme, but high concentrations inhibit the enzyme. We analyzed this phenomenon by modeling experimental data with a statistical framework that we empirically derived to understand molecular systems that display biphasic behaviors. Parameters from our statistical …

Informatics Hygiene To Support Reuse Of Routinely Collected Health Care Data For Evidence-Based Practice, Elmer V Bernstam, Alejandro Araya, Matthew Decaro, Todd R Johnson

Faculty, Staff and Student Publications

No abstract provided.

Histone Methyltransferase Ash1l Primes Metastases And Metabolic Reprogramming Of Macrophages In The Bone Niche, Chenling Meng, Kevin Lin, Wei Shi, Hongqi Teng, Xinhai Wan, Anna Debruine, Yin Wang, Xin Liang, Javier Leo, Feiyu Chen, Qianlin Gu, Jie Zhang, Vivien Van, Kiersten L Maldonado, Boyi Gan, Li Ma, Yue Lu, Di Zhao

Faculty, Staff and Student Publications

Bone metastasis is a major cause of cancer death; however, the epigenetic determinants driving this process remain elusive. Here, we report that histone methyltransferase ASH1L is genetically amplified and is required for bone metastasis in men with prostate cancer. ASH1L rewires histone methylations and cooperates with HIF-1α to induce pro-metastatic transcriptome in invading cancer cells, resulting in monocyte differentiation into lipid-associated macrophage (LA-TAM) and enhancing their pro-tumoral phenotype in the metastatic bone niche. We identified IGF-2 as a direct target of ASH1L/HIF-1α and mediates LA-TAMs' differentiation and phenotypic changes by reprogramming oxidative phosphorylation. Pharmacologic inhibition of the ASH1L-HIF-1α-macrophages axis elicits …

Multimodal Spatial Proteomic Profiling In Acute Myeloid Leukemia, Christopher P Ly, Ivo Veletic, Christopher D Pacheco, Enes Dasdemir, Fatima Z Jelloul, Sammy Ferri-Borgogno, Akshay V Basi, Javier A Gomez, Jessica L Root, Patrick K Reville, Sonali Jindal, Sreyashi Basu, Padmanee Sharma, Andres E Quesada, Carlos Bueso-Ramos, Taghi Manshouri, Branko Cuglievan, Miriam Garcia, Jared K Burks, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) resides in an immune-rich microenvironment, yet, immune-based therapies have faltered in eliciting durable responses. Bridging this paradox requires a comprehensive understanding of leukemic interactions within the bone marrow microenvironment. We optimized a high-throughput tissue-microarray-based pipeline for high-plex spatial immunofluorescence and mass cytometry imaging on a single slide, capturing immune, tumor, and structural components. Using unbiased clustering on the spatial K function, we unveiled the presence of tertiary lymphoid-like aggregates in bone marrow, which we validated using spatial transcriptomics and an independent proteomics approach. We then found validated TLS signatures predictive of outcomes in AML using an …

Myocardin Effector Proteins Affect Tgf-Beta-Induced Myofibroblast Differentiation In Ipf Cells, Allison Gonzalez

Biotechnology Theses

Idiopathic pulmonary fibrosis (IPF) is an incurable interstitial lung disease defined by the progressive, irreversible scarring of the tissues between the lung’s alveoli. To date, only two drugs have received approval for treatment. However, these medications are not considered cures since they do not stop the progression of the disease. A deeper understanding of the mechanisms underlying IPF could aid in discovering a cure. We recently found that myocardin (MyoCD) regulates SMAD2/3 transcription factors in the TGF-β signaling pathway and governs the genes involved in pleural fibrosis. However, it is unclear whether MyoCD plays a critical role in IPF by …

A Fundamentally New Direction In Embolization Using Reactive Chemistry In A Swine Model, Erik Cressman, Danielle Stolley, Shubhneet Warar, Natalie W Fowlkes, David Fuentes

Faculty, Staff and Student Publications

Liver cancer carries a poor prognosis and incidence continues to increase. The main therapy for unresectable disease > 3 cm in diameter is Transarterial Chemoembolization. Unfortunately, overall survival for these patients has improved little in the past two decades. To address this, we propose a new approach using a chemical reaction in situ. We report here our results in a pilot study using a swine model. Domestic swine (n = 3) were treated in the liver with dichloroacetic anhydride in ethiodized oil. CT imaging was followed 24 h after the procedure by necropsy, histopathology, and mass spectrometry imaging. Animals tolerated the …

Misused And Misunderstood: Examining The Inappropriate Use Of Stimulant Medications, Connor Dains, Madilyn Paphanchith, Makayla Eversole, Chaehyeon Jin, Minhwan Yang, Joshua Honaker, Samantha Mccord, Kayla Petkus

Pharmacy and Wellness Review

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children, characterized by inattention, hyperactivity, and impulsivity. The American Academy of Pediatrics (AAP) endorses stimulant medications as the first-line treatment option. When combined with behavioral therapy, this pharmacologic class can improve focus, executive functioning, and the overall quality of life. While stimulant prescriptions can have a positive effect when used as directed, there is concern for the potential of provider overprescription and patient misuse related to these medications. Consequently, the Food and Drug Administration (FDA) revised the boxed warning and prescribing information for stimulant medications. Healthcare providers must educate …

Neoadjuvant With Low-Dose Radiotherapy, Tislelizumab, Albumin-Bound Paclitaxel, And Cisplatin For Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma: Phase Ii Single-Arm Trial, Zhigang Liu, Dong Wang, Guanjun Li, Muhua Yi, Zhaoyuan Zhang, Guihua Zhong, Liangfu Xu, Rong Jiang, Yannan Zheng, Linxuan Huang, Yingpeng Peng, Lizhong Liang, Jianpeng Li, Ye Liu, Jun Lai, Xianjuan Lv, Yongqiang Xu, Qiaodan Liu, Zhiqiang Wang, Zhutian Liu, Qinan Yang, Li Nie, Jiao Lei, Xiaotao Huang, Zhijie Liu, Wen Jiang

Faculty, Staff and Student Publications

Although pathological complete response (pCR) and major pathological response (MPR) rates of neoadjuvant immunotherapy combined with chemotherapy in head and neck squamous cell carcinoma (HNSCC) trials remain suboptimal, emerging evidence highlights the synergistic potential of combining low-dose radiotherapy with immunotherapy to promote the efficacy of immunotherapy. This phase II, open-label, single-arm, multicenter trial (NCT05343325) enrolled 28 patients with untreated stage III-IVB HNSCC (NeoRTPC02). Patients received neoadjuvant low-dose radiotherapy, the programmed death-1 (PD-1) inhibitor tislelizumab, albumin-bound paclitaxel, and cisplatin for two cycles, followed by radical resection ~4 weeks after treatment completion. The primary endpoint, pCR rate, was achieved in 14 of …

Endophenotype-Informed Association Analyses For Liver Fat Accumulation And Metabolic Dysfunction In The Fels Longitudinal Study, Ariana L. Garza, John Blangero, Miryoung Lee, Cici X. Bauer, Stefan A. Czerwinski, Audrey Choh

School of Medicine Publications

The identification of causal genomic regions for liver fat accumulation in the context of metabolic dysfunction remains a challenging goal. This study aimed to identify potential endophenotypes for liver fat content and employ them in bivariate linkage searches for pleiotropic genetic regions where targeted association analysis is more likely to reveal significant variants. Multiple metabolic risk and adiposity distribution traits were assessed using the endophenotype ranking value. The top-ranked endophenotypes were then used in a bivariate linkage analysis, paired with liver fat content. Quantitative trait loci (QTLs) identified as significant or suggestive were targeted for measured genotype association analyses. The …

Diagnostic And Clinical Utility Of Oncoscan Microarray And Ngs-Based Sequencing In Pediatric Solid Tumors: Children’S Mercy Hospital’S Experience, Aravindh Nagarajan, Lisa Lansdon, Midhat Farooqi, Lei Zhang, Elena Repnikova

Research Days

This papers attempts to evaluate the diagnostic and clinical utility of microarray-based OS+ in detecting clinically relevant genetic alterations in FFPE solid tumor samples and to compare the yield of somatic mutation detection by WGS/WES in pediatric solid tumors at Children’s Mercy Hospital - Kansas City.

Variability In Methotrexate Metabolites In A Cohort Of Jia Patients, Nuria Lara Castillo, Mara Becker, Marc Sudman, Susan Thompson, Laura Ramsey

Research Days

Background: Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug for the treatment of Juvenile Idiopathic Arthritis (JIA). While most patients receiving MTX have a favorable outcome, approximately 30% do not respond, and several experience toxic events, suggesting interindividual difference. Furthermore, evaluation of MTX response takes several months, with the risk of missing the early “window of opportunity” for treatment. Predicting MTX response prior to administration would greatly benefit these patients and their treating physicians by saving valuable time during the early stages of the disease onset. MTX is a folate antagonist and, similar to folate, it undergoes polyglutamation inside the …

Viral Detection In Anterior Nasal Swabs Versus Nasopharyngeal Swabs In Children, Nicole Neeley, Abby Kietzman, Rangaraj Selvarangan, Dithi Banerjee, Jennifer Goldman, Jennifer Schuster

Research Days

Background: Respiratory viruses are a significant cause of pediatric illness and healthcare utilization. Diagnostic testing for respiratory viruses is generally performed using nasopharyngeal (NP) specimens obtained by trained staff, limiting testing to medical settings. Evaluating additional sampling methods in children that are easier to collect and can be performed outside of medical settings, such as anterior nasal swab (NS) specimens may expand access to diagnostic testing and aid public health surveillance.

Methods: Eligible children hospitalized at Children’s Mercy Hospital who had a standard of care NP specimen collected for respiratory viral testing were enrolled. Research NS specimens were obtained through …

06.16.2025 Ored Connect, Liz Williamson

ORED Newsletter

Email address Matters with SPAN and ARC Forms

Participant Support Costs training for PIs available in Blackboard

Monoclonal Antibodies Targeting Candida Disrupt Biofilms And Inhibit Growth Across Global Clinical Isolates, Jonothan Rosario-Colon, Karen Eberle, Hong Xin

School of Graduate Studies Faculty Publications

Candida species are a major cause of severe fungal infections, particularly in immunocompromised individuals and hospitalized patients. Among these, Candida auris stands out as an emerging “superbug”, responsible for life-threatening bloodstream infections with mortality rates up to 60%. This multidrug-resistant, hospital-acquired pathogen has been declared a serious global health threat, complicating effective treatment and increasing mortality risks. Our research has identified universal monoclonal antibodies (mAbs) targeting Candida albicans cell wall epitopes, which are highly homologous to those in other pathogenic Candida species, including C. auris. Passive transfer of mAbs—C3.1 (anti-β-1,2-mannotriose) and 9F2 (anti-phosphoglycerate kinase 1)—significantly extended survival and improved fungal …

Assessing One-Year Health Impacts From Wildfires In Rural Communities: Roles For Extension In Promoting Wildfire Preparedness And Recovery, Marc T. Braverman, Sandi Cleveland Phibbs, Emily Jane Davis, Amanda Rau, Elijah Penner

Journal of Extension

Wildfires can produce health impacts that persist for years in affected communities. This article describes an Extension-led study of health impacts in rural Oregon communities one year after a destructive wildfire. Data collection included key informant interviews (n=36), an online survey (n=80), and three focus group interviews with survivors (n=23). Mental health, exposure to contaminants, physical stress, food insecurity, and other issues were frequently identified health concerns. Survivors’ difficulties in dealing with housing displacement significantly exacerbated health challenges. We describe potential roles for Extension in addressing wildfire risk and mitigating health impacts, including a description of the Oregon Fire Program.

Reaching Tomorrow’S Extension Customer: A Food And Health Needs Assessment, Morgan Szczepaniak, Sarah L. Francis, Ruth Litchfield, Ulrike Genschel, Shannon Coleman, Anirudh Naig

Journal of Extension

The food and health needs and preferences of Iowans (n=452) were examined. The leading food and health information sources were online platforms, social media, and print media. Program topics with high participation likelihood were cooking, food preservation, food safety, and gardening. Short, low-cost, online programs were preferred. Extension use was more likely among those who identified as persons of color, Hispanic/Latino, or were food insecure (p < 0.030). Those with less education and chronic disease were less likely to be interested in Extension programming (p < 0.040). These results provide valuable information regarding future directions for Extension programming.

Are We Ready For Ai-Augmented Generalists?, Jiajie Zhang

Faculty, Staff and Student Publications

Artificial Intelligence (AI) is reshaping medical practice and education by unifying the knowledge of medical specialties and subspecialties into a single, intelligent system. This system functions not only as an integrated knowledge base but also as an active cognitive collaborator. By bridging knowledge gaps beyond the capacity of any individual clinician, AI could enable physicians to function as AI-augmented generalists who can perform certain tasks that require specialist training. These generalists may help mitigate care fragmentation, but realizing their potential will require significant changes in medical education.

High Kynu Expression Is Associated With Poor Prognosis, Keap1/Stk11 Mutations, And Immunosuppressive Metabolism In Patient-Derived But Not Murine Lung Adenocarcinomas, Ling Cai, Thomas J Rogers, Reza Mousavi Jafarabad, Hieu Vu, Chendong Yang, Nicole Novaresi, Ana Galán-Cobo, Luc Girard, Edwin J Ostrin, Johannes F Fahrmann, Jiyeon Kim, John V Heymach, Kathryn A O'Donnell, Guanghua Xiao, Yang Xie, Ralph J Deberardinis, John D Minna

Faculty, Staff and Student Publications

Background/Objectives: We aimed to discover genes with bimodal expression linked to patient outcomes, to reveal underlying oncogenotypes and identify new therapeutic insights in lung adenocarcinoma (LUAD).

Methods: We performed meta-analysis to screen LUAD datasets for prognostic genes with bimodal expression patterns. Kynureninase (KYNU), a key enzyme in tryptophan catabolism, emerged as a top candidate. We then examined its relationship with LUAD mutations, metabolic alterations, immune microenvironment states, and expression patterns in human and mouse models using bulk and single-cell transcriptomics, metabolomics, and preclinical model datasets. Pan-cancer prognostic associations were also assessed.

Results: Model-based clustering of KYNU expression outperformed median-based dichotomization …

A Description Of Mental Health Policies In Ohio Secondary Schools, Laura L. Harris, Molly Rowe

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE To compare secondary school mental health policies implemented for the student body with those implemented for student athletes.

Athletic Trainers Confidence In Evaluating And Treating Emergent Conditions, Andrea Cripps, Jenny Toonstra, Sara Stiltner

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE The profession of Athletic Training (AT) has undergone a substantial educational overhaul in the last decade, adding more advanced knowledge and skills than ever before. With more than 50% of the profession having obtained their certification more than 10 years prior,¹ it is essential that we understand the varying levels of confidence in evaluating and managing these new skills, so that appropriate continuing education opportunities can be developed to bridge any gaps that may be identified. The purpose of this study to examine self-reported confidence in evaluating and managing acute care skills.

Sternocleidomastoid Syndrome In A Collegiate Basketball Athlete: A Case Study, Sara Stiltner, Rob Whitehurst, Eric Avers

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

BACKGROUND
20-year-old male basketball athlete with recurring upper and lower extremity instability injuries presented fall 2021 with shoulder and ankle instability. A past medical history of thermal capsulorrhaphy from high school with surgical intervention May 2021 (college first year). October 2021 athlete began experiencing rotator cuff strains in both shoulders. November 2021, December 2021, January 2022 athlete experiences recurrent right ankle sprains. Each ankle sprain resulted in two weeks of lost participation, followed by one week of active participation. The third ankle sprain associated with increased swelling and pain over medial ankle. Upon referral and MRI a deltoid ligament sprain …

Causes Of Athletic Trainer Attrition: A Critically Appraised Topic, Mckenna E. Tuttle, Klevione D. Brown, Elizabeth A. Starns

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Athletic Training (AT) attrition has been a persistent issue within the profession for years^1,2. By identifying the factors contributing to the attrition rates among Athletic Trainers, targeted interventions can be developed to mitigate turnover and decrease attrition within the profession.

Kinematic Analysis Of Lower Extremity Movement Patterns During Functional Tests In Collegiate Track And Field Runners To Predict Injury Incidence, Maddie Hoyt, Brooke Parker, Bailey Weise, Andrew Busch

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE
Lower extremity overuse injuries are becoming increasingly more prevalent in endurance-based running sports^1,2,3,4,5,6. These injuries negatively impact an athlete’s sports performance and increase the risk of additional injuries^3,4. The purpose of this study was to first examine kinematic and kinetic variables within distance runners and compare those with previous lower extremity injuries to those without reported injuries; and second to understand if such variables predicted future injuries sustained throughout a track season.

Injury Epidemiology In Collegiate Marching Band, Morgan Davis, Jinghzen Yang, Matthew Brancaleone

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE
Marching bands have become more popular and physically demanding, with performers taking up to 16,174 steps on game days, which may increase their risk of musculoskeletal injuries. However, research on these performers remains limited. The purpose of this study was to describe the incidence of reported injury and pain and soreness experienced by marching artists within a collegiate marching band.

Atypical Anterior Tibial Stress Fracture Leading To Acute Fracture And Intermedullary Rodding, Emily Mulkey Swisher, Chad Cochran, Raymond Duffett

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE
This case highlights an unusual stress fracture progressing to an acute tibial fracture requiring intermedullary rodding.

The Athletic Trainer's Responsibility In Disability Exercise Adherence, Elizabeth Starns, Stephanie M. Kubiak, Rebecca J. Wehler

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE
This study examined exercise adherence to aerobic and strength training exercise guidelines in individuals with disabilities, highlighting the implications for athletic training (AT). Because disabilities impact over 25% of the U.S. population¹, an understanding of the varied exercise adherence patterns can inform inclusive AT best practices and assist in promoting exercise and sport participation.

Emergency Action Planning In Collegiate Athletics: An Evaluation Of The Current Adoption Of Best Practice Recommendations, Kyler Conn, Ken Blood, Genna Fusco

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE
The primary objective of this study was to assess the current adoption of the National Athletic Trainers’ Association’s (NATA) best practice recommendations regarding emergency planning, outlined in the NATA Position Statement: Emergency Planning in Athletics, at the collegiate level.

Effect Of Hearing Status On Modified Balance Error Scoring System Performance, Matthew Brancaleone, Claire Akard, Jaclyn Caccese

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE
Concussion assessments typically include evaluations of self-reported symptoms, neurocognitive function, and postural control. Specifically, postural control is often assessed using the modified Balance Error Scoring System (mBESS). Although normative mBESS data exist, they may not be appropriate for all athletes, such as those who are deaf or hard-of-hearing (D/HoH). Given the relationship between the cochlea and the vestibular system, athletes who are D/HoH may exhibit differences in postural control due to potential vestibular dysfunction. Therefore, the objective of this study was to compare mBESS performance between athletes who are D/HoH and athletes who are hearing.