Translational Medical Research Commons^™

Feasibility Of Using Podcasts For Knowledge Dissemination To Reduce Health Disparities For Women Targeting Preventative Initiatives And Lifestyle Medicine Interventions, Kristin Stovern

Doctor of Nursing Practice Scholarly Project

The purpose of this feasibility project was to look at podcasts to shed light on the issues that affect the well-being of women with gender-based disparities in healthcare. Women face persistent obstacles when it comes to the quality of healthcare they receive. One of the barriers that has been ever-present is with failure of the medical system to rigorously study the effects of diseases and drugs on women or to fund studies on women’s health conditions. Implicit biases and lack of access to care inhibit the quality of healthcare. Collectively, these issues result in unnecessary sickness, disability, and decreased quality …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Pkcε Activator Protects Hippocampal Microvascular Disruption And Memory Defect In 3×Tg-Alzheimer's Disease Mice With Cerebral Microinfarcts, Huaixing Wang, Zongxiu Zhang, Jarin Hongpaisan

Center for Translational Medicine Faculty Papers

BACKGROUND: Current evidence suggests that microvessel disease is involved in Alzheimer's disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs.

METHODS: To induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 …

Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala

Center for Translational Medicine Faculty Papers

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA …

Translational Research Targeting Biliary Tract Cancer, Yan Zhu

Dissertations and Theses (Open Access)

Biliary tract cancer (BTC) is malignant tumor that originates from the biliary tract, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC). In this translational research program targeting BTC, we focus on three aspects: the development of a combination treatment against CCA, the exploration of the immune background of GBC, and the establishment of a CCA mouse model mimicking mutation profiles of CCA patients.

Patients with cholangiocarcinoma have poor clinical outcomes due to late diagnoses, poor prognoses, and limited treatment strategies. To identify novel drug combinations for this disease, we have conducted a genome wide CRISPR screen anchored on the bromodomain and …

Reactive Oxygen Species Behaving Badly: Oxidized Phosphatidylcholines Corrupt Ca2+ Signaling In Airway Smooth Muscle, Deepak A. Deshpande, Raymond B. Penn

Center for Translational Medicine Faculty Papers

No abstract provided.

A Novel Ngs Assay To Detect Any Kmt2a Fusion Transcript At Low Levels, Ghayas Issa

Dissertations and Theses (Open Access)

Measurable residual disease (MRD) detection is associated with cancer relapse. Leukemias with rearrangement of the lysine methyltransferase 2 A gene (KMT2Ar) have an adverse prognosis with more than 80 possible fusion partner genes (FPG) identified. With the advent of effective targeted therapies for KMT2Ar leukemia such as menin inhibitors, there is an unmet need for sensitive assays to detect these various fusions. Standard next-generation sequencing (NGS) methods cannot accurately detect genetic alterations at low frequencies because of inherent technical errors and the need for high sequencing depth. Blocker Displacement Amplification (BDA) technology enables selective detection of such rare …

Single Cell Proteogenomics Analysis Of Aml Samples Treated With Decitabine And Venetoclax Reveals Divergent Treatment Escape Mechanisms, Yi June Kim

Dissertations and Theses (Open Access)

Venetoclax is a small molecule inhibitor targeting BCL-2. Since its approval, the combination therapy of hypomethylating agents and Venetoclax (HMA+Ven) has become a standard of care for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. Nonetheless, clinical challenges persist as patients either do not respond or eventually relapse, and the underlying mechanisms of these outcomes are not yet fully understood. Prior studies have identified genetic factors (TP53 and RTK/RAS pathway mutations) and phenotypic factors (monocytic differentiation) to be associated with resistance. In this light, we hypothesized that integrative assessment of genetic and phenotypic factors could further elucidate the unknown …

“Be Sustainable”: Eosc-Life Recommendations For Implementation Of Fair Principles In Life Science Data Handling, Romain David, Arina Rybina, Jean-Marie Burel, Jean-Karim Heriche, Pauline Audergon, Jan-Willem Boiten, Frederik Coppens, Sara Crockett, Katrina Exter, Sven Fahrner, Maddalena Fratelli, Carole Goble, Philipp Gormanns, Tobias Grantner, Björn Grüning, Kim Tamara Gurwitz, John M Hancock, Henriette Harmse, Petr Holub, Nick Juty, Geoffrey Karnbach, Emma Karoune, Antje Keppler, Jessica Klemeier, Carla Lancelotti, Jean-Luc Legras, Allyson L Lister, Dario Livio Longo, Rebecca Ludwig, Bénédicte Madon, Marzia Massimi, Vera Matser, Rafaele Matteoni, Michaela Th Mayrhofer, Christian Ohmann, Maria Panagiotopoulou, Helen Parkinson, Isabelle Perseil, Claudia Pfander, Roland Pieruschka, Michael Raess, Andreas Rauber, Audrey S Richard, Paolo Romano, Antonio Rosato, Alex Sánchez-Pla, Susanna-Assunta Sansone, Ugis Sarkans, Beatriz Serrano-Solano, Jing Tang, Ziaurrehman Tanoli, Jonathan Tedds, Harald Wagener, Martin Weise, Hans V Westerhoff, Rudolf Wittner, Jonathan Ewbank, Niklas Blomberg, Philip Gribbon

Faculty, Staff and Student Publications

The main goals and challenges for the life science communities in the Open Science framework are to increase reuse and sustainability of data resources, software tools, and workflows, especially in large-scale data-driven research and computational analyses. Here, we present key findings, procedures, effective measures and recommendations for generating and establishing sustainable life science resources based on the collaborative, cross-disciplinary work done within the EOSC-Life (European Open Science Cloud for Life Sciences) consortium. Bringing together 13 European life science research infrastructures, it has laid the foundation for an open, digital space to support biological and medical research. Using lessons learned from …

Breast Cancer In Pms2 Related Lynch Syndrome: Evidence Of A Possible Association?, Ujjwal Karki, Tara Rangarajan, Dana Zakalik

Conference Presentation Abstracts

Background: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome caused by pathogenic variants (PVs) in mismatch repair genes, MLH1, MSH2, MSH6, and PMS2. LS is associated with increased risk of colorectal, and endometrial cancers but breast cancer risk is uncertain, with some studies suggesting MSH6 and PMS2 PVs may have a higher risk for breast cancer. Our study outlines the incidence and clinical characteristics of breast cancer in PMS2-related LS identified at a large academic center. Methods: Patients with PMS2 PVs identified between July 2009 and May 2023 were selected from a database at the Nancy and James Grosfeld …

Characteristics Of Breast Cancer In Carriers Of Pathogenic Variant In Atm In A Large Academic Health Center, Ujjwal Karki, Tara Rangarajan, Dana Zakalik

Conference Presentation Abstracts

Background: Pathogenic variants (PVs) in ATM are associated with an increased risk of breast, pancreas, and other cancers. The clinical and pathological characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing between December 2012 and May 2023 and were identified to harbor ATM PVs were included in the study. We analyzed demographics, germline findings, histopathology, genomic recurrence score, and management of ATM PV carriers with breast cancer. Results: A total of 222 individuals were identified to have PVs in ATM, of whom 184 (83%) were female. The majority were Caucasian (n = …

Standardized Total Fitness Scores And Phase Angle In Cancer Survivors, Paulette Yamada, Trevor Short

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 4: Issue 1, Article 20, 2023. Cancer treatment can lead to decrement in all components of fitness. Exercise can attenuate these effects and build fitness. Exercise program design for this population continues to evolve with high-intensity interval training at the forefront. Phase angle (PhA) is an indirect measure of cellular health and function and is associated with fitness, health, and reduced disease severity. Continued exploration spurs an emerging question: What type of training should be used to maximize improvements in PhA? We provide a visualization of a cancer rehabilitation fitness profile and present …

Promoting Mammography Screenings In African American Women: Media, Church, And Health Providers, Lasonya Little, Debra C. Wallace, K.Jay Poole

Journal of Health Disparities Research and Practice

Due to the underutilization of screening mammography, African American women (AAW) are more likely to experience negative health outcomes after receiving a late-stage breast cancer diagnosis than White Women (WW). The purpose of this article is to examine the roles of the media, health community and the African American church and pastor and their potential impact in AAW screening decisions. Fifteen AAW, ages 45 and older, were invited to participate in a semi-structured interview. Most women agreed the African American pastor and church as well as the health community, and media are an integral part of their lives. Therefore, specific …

An American Medical Economics Phenomenon, Richard Guthmann Md, Mph

Clinical Research in Practice: The Journal of Team Hippocrates

The author reflects on his own experience with medical economics-driven phenomena in healthcare.

Increase In Hnrnpa1 Expression Suffices To Kill Motor Neurons In Transgenic Rats, Xionghao Liu, Tingting Zhang, Qinxue Wu, Cao Huang, Xu-Gang Xia, Hongxia Zhou, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. …

Immune Responses Induced At One Hour Post Cataract Surgery Wounding Of The Chick Lens, Jodirae Dedreu, Morgan Basta, Janice Walker, Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While the lens is an avascular tissue with an immune-privileged status, studies have now revealed that there are immune responses specifically linked to the lens. The response to lens injury, such as following cataract surgery, has been shown to involve the activation of the resident immune cell population of the lens and the induction of immunomodulatory factors by the wounded epithelium. However, there has been limited investigation into the immediate response of the lens to wounding, particularly those induced factors that are intrinsic to the lens and its associated resident immune cells. Using an established chick embryo ex vivo cataract …

Understanding How Patient Engagement Is Enacted Through Telehealth: A Grounded Theory Study, Patricia Deyo

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: The COVID-19 pandemic forced a sudden shift in how healthcare was provided leading to a rapid implementation of telehealth in March 2020. While telehealth had been used in some populations and areas, it was not widely implemented throughout the U.S. Healthcare organizations were challenged to implement telehealth overnight for people to continue to seek medical care. Regulations related to reimbursement and medical licensing were loosened during the COVID-19 pandemic which removed some of the long-standing barriers to telehealth. As telehealth continued in practice, providers and practices were challenged to find new and creative ways to engage patients through telehealth. …

Social Determinants May Limit The Success Of Pcsk9 Inhibitors, An Effective Treatment For Hyperlipidemia In Statin-Intolerant Patients, Abigail C. Kuplicki

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Moriarty PM, Thompson PD, Cannon CP, et al. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J. Clin. Lipidol. 2015;9(6):758-769. https://doi.org/10.1016/j.jacl.2015.08.006

for a statin-intolerant patient with hyperlipidemia.

Renal Disease Rehabilitation And Delaying Dialysis, Spencer Brown, Natalie Sterner

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Greenwood SA, Koufaki P, Mercer TH, et al. Effect of exercise training on estimated GFR, vascular health, and cardiorespiratory fitness in patients with CKD: a pilot randomized controlled trial. Am J Kidney Dis. 2015;65(3):425-434. https://doi.org/10.1053/j.ajkd.2014.07.015

for a patient with non-dialysis CKD interested in slowing the progression toward necessary dialysis.

Slow Surgical Correction Affects More Than Just The Bowels, Emilia M. Clementi

Clinical Research in Practice: The Journal of Team Hippocrates

Reflection on how delayed colostomy reversal affects a patient's mental and physical well-being.

Whole Genome-Based Dna Methylation Profiling In Covid-19 Patients Reveals Alterations In Pathways Linked To Neurological Dysfunctions, Syed Zameer, Juozas Gordevicius, Eman Anis, Qiong Sha, Martha L. Escobar Galvis, Michael Henderson, Andrew Pospisilik, Patrik Brundin, Stewart Graham

Conference Presentation Abstracts

The sever acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a highly transmissible viruswhich causes a life-threatening illness called coronavirus (COVID-19). It has cost millions ofdeath worldwide. This novel RNA betacorona virus is manifested by varying clinical symptomsranging from asymptomatic to mild to severe systemic illness with deadly outcomes. Muchevidence revealed the differences in the severity of COVID-19 infection varied widely accordingto host factors and comorbidities. It is critical to understand the interplay of genetic and epigeneticfactors and host response to this fatal virus. A substantial number of epigenome-wide associationstudies acknowledged that SARS-CoV-2 manipulate the host epigenome via DNA methylation …

Uptitrating Mycophenolate Mofetil Therapy In A Patient With Lupus Cerebritis Doesn’T Increase Risk Of Infection Compared To Cyclophosphamide, Gautham Pavar

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising

Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20(5):1103-1112. https://doi.org/10.1681/ASN.2008101028

for a patient with neuropsychiatric lupus.

Stigma And Patient-Controlled Analgesia: Trust Is The Essential Ingredient Of Successful Patient Education In The Patient-Doctor Relationship, Trey D. Vanaken

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Van Beers EJ, Van Tuijn CFJ, Nieuwkerk PT, et al. Patient-controlled analgesia versus continuous infusion of morphine during vaso-occlusive crisis in sickle cell disease, a randomized controlled trial. Am J Hematol. 2007;82(11):955-960. https://doi.org/10.1002/ajh.20944.

for a patient with recurrent vaso-occlusive crisis secondary to Sickle Cell Disease.

Early Closure Of Colostomy From Abdominal Trauma May Be Beneficial In Otherwise Healthy Patients, Nicole Xu

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising

Khalid MS, Moeen S, Khan AW, Arshad R, Khan AF. Same admission colostomy closure: a prospective, randomised study in selected patient groups. Surgeon. 2005;3(1):11-14. https://doi.org/10.1016/s1479-666x(05)80004-6

for a patient with loop transverse colostomy due to trauma

Evaluating The Use Of Cheaper, Less Effective Medications In Patients With Cost-Based Medication Nonadherence, Muneer F. Hasso

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Sangaralingham LR, Sangaralingham SJ, Shah ND, Yao X, Dunlay SM. Adoption of Sacubitril/Valsartan for the Management of Patients With Heart Failure. Circ Heart Fail. 2018;11(2):e004302. https://doi.org/10.1161/circheartfailure.117.004302

for a patient with low medication adherence rates due to the high out-of-pocket costs of newer medications.

Motivational Interviewing May Resolve Vaccine Hesitancy, Scott L. Baughan

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Gagneur A, Lemaître T, Gosselin V, et al. A postpartum vaccination promotion intervention using motivational interviewing techniques improves short-term vaccine coverage: PromoVac study. BMC public health. 2018;18(1):811. https://doi.org/10.1186/s12889-018-5724-y

for a juvenile patient with a caregiver who is skeptical about the safety of routine vaccinations.

Buprenorphine/Suboxone Is Safe In Pregnancy: Substance Use And Stigma In The Healthcare Professions, Blake S. Sanford

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Mullins N, Galvin SL, Ramage M, et al. Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study. J Addict Med. 2020;14(3):185-192. https://doi.org/10.1097/ADM.0000000000000562

for a woman with opioid use disorder during pregnancy.

Flexner Report 3.0—Structurally Competent Healthcare, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

The editor advocates to formalize the addition of “Medical Social Sciences” as a basic science in our Schools of Medicine and “Clinical Decision Science” as the corollary clinical practice discipline: a “Flexner Report 3.0."

Editorial: Debates In Cardiovascular Pharmacology And Drug Discovery: 2022, Keman Xu, Fatma Saaoud, Ying Shao, Yifan Lu, Xiaohua Jiang, Sheng Wu, Jianxin Sun, Filipe Fernades Conti, Laisel Martinez, Roberto Vazquez-Padron, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

No abstract provided.

Reap-2: An Interactive Quantitative Tool For Robust And Efficient Dose-Response Curve Estimation, Xinying Fang, Xinyi Liu, Vernon M Chinchilli, Michael Wang, Hong-Gang Wang, Nikolay V Dokholyan, Chan Shen, J Jack Lee, Shouhao Zhou

Faculty, Staff and Student Publications

REAP-2 is an interactive dose-response curve estimation tool for Robust and Efficient Assessment of drug Potency. It provides user-friendly dose-response curve estimation for in vitro studies and conducts statistical testing for model comparisons with a redesigned user interface. We also make a major update of the underlying estimation method with penalized beta regression, which demonstrates great reliability and accuracy in dose estimation and uncertainty quantification. In this note, we describe the method and implementation of REAP-2 with a highlight on potency estimation and drug comparison.