Medical Specialties Commons^™

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 …

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.

Spontaneous Pneumothorax In A Male High School Wrestler, Laura Breese, Sara Stiltner

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

OBJECTIVE/BACKGROUND
A pneumothorax is the presence of air in the pleural space, it is a life threatening condition and can be classified as spontaneous, acquired, or by pathophysiology. (1)(2) This specific case presents the incident of a spontaneous pneumothorax in an adolescent population.

Engineering A Novel Treg Population To Control Autoimmune Diabetes, Sofia Colon Guzman, Elly Puckett, Mary A. Markiewicz, Ryan T. Fischer

Research Days

We created a model to test the immunosuppressive capacity of Helios+FOXP3+ eTregs compared to nTregs against islet-specific autoreactive T cells. We also showed that nTregs decrease the response of these cytotoxic T cells when co-cultured with BetaLox5 cells.

The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna

Faculty, Staff and Student Publications

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, …

G-Quadruplex Stabilizer Cx-5461 Effectively Combines With Radiotherapy To Target Α-Thalassemia/Mental Retardation X-Linked-Deficient Malignant Glioma, Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse

Faculty, Staff and Student Publications

Background: Inactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models.

Methods: Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the …

Long-Term Efficacy Of Pembrolizumab And The Clinical Utility Of Ctdna In Locally Advanced Dmmr/Msi-H Solid Tumors, Michael Lapelusa, Wei Qiao, Bryan Iorgulescu, Francis San Lucas, Keyur Patel, Deepak Bhamidipati, Jane Varkey Thomas, Nancy You, Wai Chin Foo, Dipen Maru, Selvi Thirumurthi, Van Morris, Scott Kopetz, Michael Overman, Kaysia Ludford

Faculty, Staff and Student Publications

Neoadjuvant immunotherapy can induce pathologic complete response (pCR) in patients with localized deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors. The long-term outcomes of these patients are unknown, as is the clinical utility of measuring circulating tumor DNA (ctDNA). Follow-up was evaluated in patients enrolled in a phase II trial (NCT04082572) that evaluated the efficacy and safety of pembrolizumab in patients with localized dMMR/MSI-H tumors. The primary outcomes of this trial have previously been reported. 3-year EFS and OS rates were 80% (95% CI: 66% - 93%) and 94% (95% CI: 86% - 100%). Patients without detectable ctDNA after pembrolizumab had …

Ubiquitin-Conjugating Enzyme Ube2n Modulates Proteostasis In Immunoproteasome-Positive Acute Myeloid Leukemia, Chiharu Ishikawa, Laura Barreyro, Avery M Sampson, Kathleen M Hueneman, Kwangmin Choi, Sophia Y Philbrook, Issac Choi, Lyndsey C Bolanos, Mark Wunderlich, Andrew G Volk, Stephanie S Watowich, Kenneth D Greis, Daniel T Starczynowski

Faculty, Staff and Student Publications

Altered protein homeostasis through proteasomal degradation of ubiquitinated proteins is a hallmark of many cancers. Ubiquitination, coordinated by E1, E2, and E3 enzymes, involves up to 40 E2-conjugating enzymes in humans to specify substrates and ubiquitin linkages. In a screen for E2 dependencies in acute myeloid leukemia (AML), ubiquitin conjugating enzyme E2 N (UBE2N) emerged as the top candidate. To investigate UBE2N's role in AML, we characterized an enzymatically defective mouse model of UBE2N, revealing UBE2N's requirement in AML without an impact on normal hematopoiesis. Unlike other E2s, which mediate lysine-48 (K48) polyubiquitination and degradation of proteins, UBE2N primarily synthesizes …

Early Hematopoietic Differentiation Of An Inducible Pluripotent Stem Cell Model Of Infant Lymphoblastic Leukemia, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Priyanka Kumar, Jay L. Vivian, John M. Perry

Research Days

This abstract describes our work regarding the differentiation of human inducible pluripotent stem cells into hematopoietic stem and progenitor cells as the groundwork for the development of a genomics driven inducible pluripotent stem cell model of KMT2A rearranged infant acute lymphoblastic leukemia.

Immunotherapy With Nebulized Pattern Recognition Receptor Agonists Restores Severe Immune Paralysis And Improves Outcomes In Mice With Influenza-Associated Pulmonary Aspergillosis, Jezreel Pantaleón García, Sebastian Wurster, Nathaniel D Albert, Uddalak Bharadwaj, Keerthi Bhoda, Vikram K Kulkarni, Mbaya Ntita, Paris Rodríguez Carstens, Madeleine Burch-Eapen, Daniela Covarrubias López, Jania Foncerrada Lizaola, Katherine E Larsen, Lauren M Matula, Seyed J Moghaddam, Yongxing Wang, Dimitrios P Kontoyiannis, Scott E Evans

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a potentially deadly superinfection in patients with influenza pneumonia, especially those with severe disease, underlying immunosuppression, corticosteroid therapy, or requiring intensive care support. Given the high mortality of IAPA, adjunct immunomodulatory strategies remain a critical unmet need. Previously, the desensitization of pattern recognition pathways has been described as a hallmark of IAPA pathogenesis and a predictor of mortality in IAPA patients. Therefore, we studied the impact of nebulized Toll-like receptor 2/6/9 agonists Pam2 CSK4 (Pam2) and CpG oligodeoxynucleotides (ODNs) on infection outcomes and pulmonary immunopathology in a corticosteroid-immunosuppressed murine IAPA model. Mice with IAPA receiving …

Clinical And Fundamental Research Progressions On Tumor-Infiltrating Lymphocytes Therapy In Cancer, Jiandong Hu, Mengli Jin, Weihong Feng, Barbara Nassif-Rausseo, Alexandre Reuben, Chunhua Ma, Gregory Lizee, Fenge Li

Faculty, Staff and Student Publications

Malignant tumors represent a significant threat to human health. Among the various therapeutic strategies available, cancer immunotherapy-encompassing adoptive cell transfer (ACT) and immune checkpoint blockade therapy-has emerged as a particularly promising approach following surgical resection, radiotherapy, chemotherapy, and molecular targeted therapies. This form of treatment elicits substantial antigen-specific immune responses, enhances or restores anti-tumor immunity, thereby facilitating the control and destruction of tumor cells, and yielding durable responses across a range of cancers, which can lead to the eradication of tumor lesions and the prevention of recurrence. Tumor-infiltrating lymphocytes (TILs), a subset of ACT, are characterized by their heterogeneity and …

Molecular Characterization And Predictors Of Relapse In Patients With Ph + All After Frontline Ponatinib And Blinatumomab, Nicholas J Short, Hagop Kantarjian, Ken Furudate, Nitin Jain, Farhad Ravandi, Omer Karrar, Sanam Loghavi, Lewis Nasr, Fadi G Haddad, Jayastu Senapati, Rebecca Garris, Koichi Takahashi, Elias Jabbour

Faculty, Staff and Student Publications

Background: Several studies have suggested that chemotherapy-free regimens consisting of blinatumomab and a BCR::ABL1 tyrosine kinase inhibitor are highly effective in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, the clinical and molecular characteristics that predict for relapse with these chemotherapy-free regimens are largely unknown.

Methods: We conducted a prospective phase II clinical trial of the combination of blinatumomab and ponatinib in 76 patients with newly diagnosed Ph + ALL. Patients received 12-15 doses of intrathecal chemotherapy as central nervous systemic (CNS) prophylaxis. The patterns of relapse and the clinical and molecular predictors of relapse were analyzed.

Results: With …

Theta Oscillons In Behaving Rats, M S Zobaer, Nastaran Lotfi, Carli M Domenico, Clarissa Hoffman, Luca Perotti, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Recently discovered constituents of the brain waves—the oscillons—provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional θ-waves. The resemblances between θ-oscillons and the conventional θ-waves are manifested primarily at the ballpark level—mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms’ structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled …

Ogg1s326c Variant Frequent In Human Populations Facilitates Inflammatory Responses Due To Its Extended Interaction With Dna Substrate, Jinling Han, Meichen Zhang, Jiakun Ge, Zhihua Ji, Jianyi Zhao, Yinchao Hu, Chunshuang Li, Yaoyao Xue, Xining Li, Haiwang Zhao, Zixu Cui, Miaomiao Tian, Xu Zheng, Dapeng Wang, Jing Wang, Min Wei, Zsolt Radak, Yusaku Nakabeppu, Istvan Boldogh, Xueqing Ba

Faculty, Staff and Student Publications

8-oxoguanine (8-oxoGua) is one of the most frequent forms of oxidative DNA base lesions, repaired by 8-oxoguanine DNA glycosylase 1 (OGG1) via base excision repair (BER) pathway to maintain genome fidelity. The human allelic variant hOGG1^S326C, prevalent in Caucasians and Asians, has been regarded as a susceptibility factor for various diseases, yet its pathogenic mechanism remains elusive. In this study, we demonstrate that Ogg1^S326C/S326C mice exhibit increased and sustained airway inflammation compared with wild-type (WT) Ogg1^S326/S326 mice. Mechanistically, in response to inflammatory stimulation, OGG1S326C undergoes reactive oxygen species-induced dimerization, which impairs its base excision function, but …

A Pharmacokinetic And Safety Study Of Oral Arsenic Trioxide In Patients With Acute Promyelocytic Leukemia, Farhad Ravandi, Sravanti Rangaraju, Hagop Kantarjian, Guillermo Garcia-Manero, Musa Yilmaz, Kristen Baker, Terence Hall, Joy Grabenstein, Pourab Roy, Beth A Zamboni, William C Zamboni, Erica Warlick, Michael Kelly, David A Roth, Gabriel Ghiaur

Faculty, Staff and Student Publications

SY-2101 is a novel oral formulation of arsenic trioxide (ATO). Although IV ATO in combination with all trans retinoic acid is highly efficacious in treating acute promyelocytic leukemia (APL), there remains a significant unmet need due to the treatment burden associated with receiving daily ATO infusions for nearly a year and the risk of complications associated with indwelling central catheters. The pharmacokinetics (PK), safety, and tolerability of SY-2101 and ATO IV after single- and multiple-dose administration and the impact of food on PK for SY-2101 were evaluated in this phase 1 study in 15 participants with APL. SY-2101 in the …

Phase I Study Of Pomalidomide In Relapsed Or Refractory Waldenström Macroglobulinaemia, Karan L Chohan, Donna M Weber, Lei Feng, L Michael Wang, Sattva S Neelapu, Jasper Olsem, Ralph J Johnson, Claudia Morales De Partovi, Robert Z Orlowski, Sheeba K Thomas

Faculty, Staff and Student Publications

No abstract provided.

Relationship Between Maternal Plasma Retinol And Provitamin A Carotenoids With Fetal And Infant Kidney Development, Anum Akbar

Theses & Dissertations

Vitamin A plays a critical role in fetal organ development. Studies suggest that maternal vitamin A deficiency affects fetal nephron numbers, potentially leading to smaller kidney sizes and an increased risk of chronic kidney disease later in life. However, human studies exploring maternal vitamin A's impact on fetal kidney development lack longitudinal data and within-cohort comparisons. Furthermore, the influence of provitamin A carotenoids (α-carotene, β-carotene, β-cryptoxanthin) on kidney size remains unexplored. This dissertation addresses these gaps by analyzing relationships between maternal and cord plasma retinol and provitamin A carotenoid concentrations with fetal and infant kidney sizes. Our prospective cohort …

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

Neurodegenerative Disease Mechanisms: Mitochondrial Impairment, Tau Aggregation, And Neuroinflammation As Central Drivers Of Disease Progression, Luis D. Estrella

Theses & Dissertations

The study of the intricate molecular mechanisms behind the pathology of neurodegenerative diseases has become a primary research area in the past decades. The major branches of these studies involve both disease progression and disease pathogenesis, in which neuroscientists have studied, and continue to study, the role that mitochondrial dysfunction, aberrant protein aggregation (like Tau), and immune cell reactions have on these. However, more recent studies have shined light to the fact that these three pathological features are not independent from one another and that their synchronous contributions may be the ultimate driver of neurodegeneration. This dissertation encompasses four different …

Cholestasis And Fluid Flow Are Biomechanic Regulators Of Cholangiocarcinoma Progression, Andrew Oleksijew

Theses & Dissertations

Cholestasis, altered or absent bile flow, is associated with poor survival in patients with cholangiocarcinoma, an aggressive cancer of the biliary epithelium. Changes in bile flow often result in stricture or obstruction. Experimental cholestasis promoted tumor growth and progression. However, studies are needed that directly assess the mechanical interaction between bile flow, or bile shear stress, and cholangiocarcinoma signaling. We hypothesized that cholestasis and absent bile shear stress activated cancer signaling and increased aggressive cellular behaviors such as proliferation and migration. Fluid shear stress approximating bile flow was applied by orbital culture plate method and compared to identical static culture …