Translational Medical Research Commons^™

A Phase I Study Of Docetaxel Plus Synthetic Lycopene In Metastatic Prostate Cancer Patients, Michael B Lilly, Chunli Wu, Yu Ke, Wen-Pin Chen, Adam C Soloff, Kent Armeson, Noriko N Yokoyama, Xiaotian Li, Liankun Song, Ying Yuan, Christine E Mclaren, Xiaolin Zi

Faculty, Staff and Student Publications

Purpose: Our preclinical studies showed that lycopene enhanced the anti-prostate cancer efficacy of docetaxel in animal models. A phase I trial (NCT0149519) was conducted to identify an optimum dose of synthetic lycopene in combination with docetaxel (and androgen blockade [androgen deprivation therapy, ADT]), and to evaluate its effect on the safety and pharmacokinetics of docetaxel in men with metastatic prostate cancer.

Methods: Subjects were treated with 21-day cycles of 75 mg/m2 docetaxel (and ADT), plus lycopene at 30, 90 or 150 mg/day. A Bayesian model averaging continual reassessment method was used to guide dose escalation. Pharmacokinetics of docetaxel …

Lack Of Alternatives To Colonoscopy Limits Care Of Patients Unable To Complete Bowel Preparation, Tala Al-Saghir

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Benech N, Vinet O, Gaudin JL, et al.: The ONECC Study Group. Colon capsule endoscopy in clinical practice: lessons from a national 5-year observational prospective cohort. Endosc Int Open. 2021;9(10):E1542-E1548. https://doi.org/10.1055/a-1526-09231

for a patient with incomplete bowel preparation and colonoscopy.

Multiple Daily Injection Insulin Regimen Is An Effective, And More Economical, Alternative To Continuous Insulin Infusion For Type 1 Diabetics, Julia Yee

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Heller S, White D, Lee E, et al. A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial. Health Technol Assess. 2017 Apr;21(20):1-278. https://doi.org/10.3310/hta21200

for a patient with type 1 diabetes.

Nur77 Mitigates Endothelial Dysfunction Through Activation Of Both Nitric Oxide Production And Anti-Oxidant Pathways, Lin Lu, Soohwa Jang, Jiaqi Zhu, Qing Qin, Lijun Sun, Jianxin Sun

Center for Translational Medicine Faculty Papers

BACKGROUND: Nur77 belongs to the member of orphan nuclear receptor 4A family that plays critical roles in maintaining vascular homeostasis. This study aims to determine whether Nur77 plays a role in attenuating vascular dysfunction, and if so, to determine the molecular mechanisms involved.

METHODS: Both Nur77 knockout (Nur77 KO) and Nur77 endothelial specific transgenic mice (Nur77-Tg) were employed to examine the functional significance of Nur77 in vascular endothelium in vivo. Endothelium-dependent vasodilatation to acetylcholine (Ach) and reactive oxygen species (ROS) production was determined under inflammatory and high glucose conditions. Expression of genes was determined by real-time PCR and western blot …

No Difference In Pullout Strength Between A Bio-Inductive Implant And A Semitendinosus Tendon Graft In A Biomechanical Study Of Medial Patellofemoral Ligament Repair Augmentation, Austin Wetzler, Sean Mcmillan, Erik Brewer, Aakash Patel, Samuel Handy, Merrick Wetzler

Rowan-Virtua School of Translational Biomedical Engineering & Sciences Departmental Research

Purpose: To compare the pullout strength of a bio-inductive implant (BI) used to augment a medial patellofemoral ligament (MPFL) repair with the pullout strength of semitendinosus graft in a biomechanical cadaveric model. Methods: Six matched pairs of cadavers (12 knees) were used in the biomechanical testing comparing semitendinosus tendon (Semi-T) versus a BI. The Semi-T was harvested from 1 of the matched pairs. A standard double-bundle technique using 2 sockets in the upper two-thirds of the patella 15 mm apart was performed. After docking of the graft into the patella, the patella was dissected free of soft tissues and potted …

Enabling The Clinical Application Of Artificial Intelligence In Genomics: A Perspective Of The Amia Genomics And Translational Bioinformatics Workgroup, Nephi A Walton, Radha Nagarajan, Chen Wang, Murat Sincan, Robert R Freimuth, David B Everman, Derek C Walton, Scott P Mcgrath, Dominick J Lemas, Panayiotis V Benos, Alexander V Alekseyenko, Qianqian Song, Ece Gamsiz Uzun, Casey Overby Taylor, Alper Uzun, Thomas Nate Person, Nadav Rappoport, Zhongming Zhao, Marc S Williams

Faculty, Staff and Student Publications

OBJECTIVE: Given the importance AI in genomics and its potential impact on human health, the American Medical Informatics Association-Genomics and Translational Biomedical Informatics (GenTBI) Workgroup developed this assessment of factors that can further enable the clinical application of AI in this space.

PROCESS: A list of relevant factors was developed through GenTBI workgroup discussions in multiple in-person and online meetings, along with review of pertinent publications. This list was then summarized and reviewed to achieve consensus among the group members.

CONCLUSIONS: Substantial informatics research and development are needed to fully realize the clinical potential of such technologies. The development of …

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba

Posters-at-the-Capitol

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro …

Craftivism As Inquiry: Holding Life’S Threads, Chloe Watfern, Gaynor Macdonald, Michele Elliot, Lynne Stone, Imelda Gilmore, Manuel Tecson, Najla Turk, Penny Bingham, Jane Mears, Ann Dadich, Barbara Doran, Katherine Boydell, Sarah Wallace

The Qualitative Report

In this article, we share insights regarding an arts-based research project where carers of people with dementia conveyed their experiences in cloth. Carers face high rates of mental ill health and burnout, while forming a largely undervalued and unrecognised workforce. Through this project, carers’ knowledge was valued and amplified using an innovative methodology – craftivism. During a series of five workshops in 2021, a small group of carers, researchers and artists gathered online to develop an exhibition of craftivist textile works. They evoked the complexity of their makers’ journeys supporting loved ones at the end of life, finding joy and …

Research Annual Report Fy2024, Children's Mercy Kansas City

Research Annual Reports

Annual report of the research at Children's Mercy Kansas City in Kansas City MO, a pediatric medical center.

Challenges In Post Graduate General Surgery Training In Tanzania: A Trainee’S Perspective, Shabbir Adamjee

Master of Surgery

v>

General Surgery residency training is a complex vigorous program which includes long working hours and complex surgical cases, in order to develop and attain the knowledge and the skills the trainee needs by the end of the program. Worldwide, general surgery programs have high attrition rates and residents have identified challenges which may be work related, related to social wellbeing and/or the residency program structure. Tanzania has public and private institutions providing general surgery residency training and although most have a quality assessment program the data is not readily available. Each institution has its personalized curriculum with its unique …

Prosthetic Attention In Upper Limb Loss: User Experiences, Clinical Perceptions, And Developing Candidate Items, Tanu Bhargava

Theses and Dissertations

The human hand is a powerful tool essential for performing a range of tasks from simple to complex, and it plays a crucial role in social interactions and environmental engagement. Upper limb (UL) loss disrupts these functions and significantly impacts daily life. Prosthetic devices can partially restore these abilities and improve quality of life, but they lack the intuitive control and sensory feedback of natural hands. Consequently, operating a UL prosthesis requires substantial attentional demands, a factor that potentially contributes to high rates of device dissatisfaction and disuse. For UL prosthesis users, managing attentional resources is critical to efficiently controlling …

The Splice Index As A Prognostic Biomarker Of Strength And Function In Myotonic Dystrophy Type 1, Marina Provenzano

Theses and Dissertations

Myotonic dystrophy type 1 (DM1) is a slowly progressive, multisystem disorder caused by a CTG repeat expansion in the DMPK 3’UTR that leads to global dysregulation of alternative splicing. The resulting decline in physical function is slow, and no reliable biomarkers exist for predicting disease progression; however, an RNA mis-splicing biomarker associated with weakness may have utility in predicting functional outcomes. Here we validate the Splice Index (SI) as a potential biomarker of DM1-associated strength and function. Muscle biopsies of the tibialis anterior were collected from DM1-affected individuals at baseline (n = 46) and 3-months (n = 34), along with …

Key To Success: A Comprehensive Examination Of Support Personnel In School-Based Speech-Language Telepractice, Hannah Douglass

Theses and Dissertations--Rehabilitation Sciences

In the school setting, the telepractice team primarily consists of the clinician and a support person known as a telefacilitator. Though telepractice is an accepted method for delivering school-based speech-language therapy, many barriers to the integration of telepractice as routine care persist. A major barrier is clinicians' acceptance of telehealth. However, there has been limited investigation of factors that influence clinician acceptance. Another barrier is related to support personnel. Telefacilitators have been shown to be an integral part of the telepractice program. Yet there are significant gaps in knowledge regarding the roles and responsibilities, staffing and management, and barriers/facilitators to …

Glutamate Optimization As A Treatment For Depression: A Clinical Guideline, Luisa Angeles Collins Villares

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Based on the use of drugs to treat hypertension and tuberculosis for depression, the monoamine hypothesis led to the development of antidepressants in 1952. Serotonin was recognized as a deficiency associated with depression in 1967. As a fine-tuning orchestration of neurotransmitters and neuromodulators, the glutamate system became known using Spravato in 2019 and Auvelity in 2022. In this pilot study, mental health experts rated the importance of 24 science-based recommendations to optimize glutamatergic therapy in depression for a proposed guideline on a Likert scale from zero to four. The results were analyzed using a non-parametric predictive modeling method called Chi-Square …

Modulating The Mtor Pathway Using Inducible Retrogradely Transported Aavs As A Novel Approach To Improve Motor Recovery In Spinal Cord Injury, Christopher Bosse-Joseph

Theses and Dissertations--Medical Sciences

Spinal cord injury poses multiple regeneration barriers, including neuronal-intrinsic and extrinsic factors. Overcoming these barriers has stood as a longstanding challenge in neuroscience. A well-studied mechanism to promote spinal cord regeneration and locomotor recovery is activating the PI3K/mTOR pathway by knocking out phosphatase and tensin homolog protein (PTEN). PTEN knockout (PTEN-KO) studies have traditionally used adeno-associated virus (AAV) viral vectors to improve functional recovery. The use of traditional AAV serotypes to induce PTEN-KO has shown promise to improve functional recovery in rodent models; however, these approaches show significant limitations for translational utility. Firstly, the use of traditional AAV serotypes to …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …

The Enact Network Is Acting On Housing Instability And The Unhoused Using The Open Health Natural Language Processing Toolkit, Daniel R Harris, Sunyang Fu, Andrew Wen, Alexandria Corbeau, Darren Henderson, Jordan Hilsman, David Oniani, Yanshan Wang

Faculty, Staff and Student Publications

Housing is an environmental social determinant of health that is linked to mortality and clinical outcomes. We developed a lexicon of housing-related concepts and rule-based natural language processing methods for identifying these housing-related concepts within clinical text. We piloted our methods on several test cohorts: a synthetic cohort generated by ChatGPT for initial infrastructure testing, a cohort with substance use disorders (SUD), and a cohort diagnosed with problems related to housing and economic circumstances (HEC). Our methods successfully identified housing concepts in our ChatGPT notes (recall = 1.0, precision = 1.0), our SUD population (recall = 0.9798, precision = 0.9898), …

Analysis Of The Immune Response After Readministration Of A Novel Aav6 Gene Therapy Containing Tlr9 Inhibitory Sequences, Sarah Elysse Allen

MUSC Theses and Dissertations

Therapeutic options for the treatment of Surfactant Protein-B (SP-B) deficiency, an autosomal recessive disorder that leads to fatal respiratory distress, are extremely limited with the exception of double lung transplantation. One method for treating this monogenic lung disease is with adeno-associated virus (AAV) gene therapy treatment that delivers the hSFTPB transgene into the lungs. The transient nature of AAV transgene expression led to a need for sustained gene expression, which could possibly be achieved through redosing. The main obstacle with redosing is the innate immune response and subsequent inflammatory response pathways that are activated after recognition of unmethylated CpG motifs …

Novel Engineering Approaches For Orthopedic Injury Treatment And Infection Diagnosis, Cynthia Co

Bioengineering Dissertations - Archive

Bioengineering has made significant contributions to the treatment of orthopedic injury through interdisciplinary approaches. Central to these advancements are many orthopedic implants, including anchors and joint replacements, which have been designed to restore mobility. Despite their functional efficacy, these products have limited lifespan and are associated with many complications, such as implant-associated infection. The success of implant design and function, both in the short and long term, is paramount for enhancing patient outcomes and overall well-being. Therefore, my thesis work is dedicated to addressing these critical challenges, aiming to maximize their treatment effect while minimizing the implant-associated complications.

Long-term patient …

Examining Occupation-Based Outcome Measure Use In A Neurologic Outpatient Occupational Therapy Setting: A Knowledge Translation Initiative, Elizabeth Yost, Suzanne Trojanowski, Taylor Jarnigin, Kevin De Bear, Amy Yorke

Translational Science in Occupation

Abstract

Importance: Occupation-based outcome measures (OBOMs) are an evidence-based recommendation for occupational therapy evaluations. Knowledge translation (KT) is a process used to help integrate evidence into clinical practice. The authors identified a KT opportunity to examine occupational therapy practitioners’ (OTPs) use of outcome measures in an outpatient practice setting and assess a Know-Do Gap as the first step in the Action phase of a KT initiative.

Objective: Describe the frequency and types of outcome measures documented in occupational therapy (OT) evaluations, with a focus on OBOMs.

Design: Cross-sectional descriptive study.

Setting: Three outpatient clinic sites (under one parent company) in …

Evaluation Of Silk Fibroin And Hylauronic Acid As Otic Drug Delivery System Additives; Investigation Of Silk Fibroins Responses To Enviromental Stimulii, Kolton Charles Sandau

Graduate Student Theses, Dissertations, & Professional Papers

The Serban lab has previously developed and reported on a single application drug delivery system for the treatment of otitis externa. Otitis externa also known as outer ear infections is a very common ailment that impacts large portions of both human and domestic animal populations. Typical treatment for otitis externa typically requires an extended dosing regimen over several days that is inconvenient and can lead to poor clinical outcomes due to poor patient compliance. Our delivery system employs a thixotropic gel to deliver a steady dose of medication over the duration of the infection.

Here we evaluated the reproducibility and …

Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar

Honors Undergraduate Theses

Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …

Effects Of Huoxue Qufeng Decoction Combined With Tongguan Liquefying Acupoint Penetration Therapy On Swallowing Function And Quality Of Life In Patients With Ischemic Stroke, Xuzhong Liang, Li Ma, Lixia Zhang, Dongnian Yang, Lanrui Zeng

Faculty, Staff and Student Publications

Objective: To analyze the effects of Huoxue Qufeng Decoction combined with Tongguan Liquefying Acupoint Penetration therapy on swallowing function and quality of life in patients with ischemic stroke.

Methods: A total of 145 patients with post-stroke dysphagia admitted to Dingxi People's Hospital from January 2019 to May 2022 were selected with 65 patients in the control group and 80 patients in the observation group. The control group received Huoxue Qufeng Decoction alone, while the observation group received additional Tongguan Liquefying Acupoint Penetration therapy. Clinical efficacy, NIH Stroke Scale (NIHSS) score, Water Swallow Test, Swallowing Function Assessment (SSA) score, MD Anderson …

Characterizing Treatment Non-Responders And Responders In Completed Alzheimer's Disease Clinical Trials, Dulin Wang, Yaobin Ling, Kristofer Harris, Paul E Schulz, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Characterizing differential responses to Alzheimer's disease (AD) drugs will provide better insights into personalized treatment strategies. Our study aims to identify heterogeneous treatment effects and pre-treatment features that moderate the treatment effect of Galantamine, Bapineuzumab, and Semagacestat from completed trial data. The causal forest method can capture heterogeneity in treatment responses. We applied causal forest modeling to estimate the treatment effect and identify efficacy moderators in each trial. We found several patient's pretreatment conditions that determined treatment efficacy. For example, in Galantamine trials, whole brain volume (1092.54 vs. 1060.67 ml, P < .001) and right hippocampal volume (2.43e-3 vs. 2.79e-3, P < .001) are significantly different between responsive and non-responsive subgroups. Overall, our implementation of causal forests in AD clinical trials reveals the heterogeneous treatment effects and different moderators for AD drug responses, highlighting promising personalized treatment based on patient-specific characteristics in AD research and drug development.

Diet-Stimulated Marrow Adiposity Fails To Worsen Early, Age-Related Bone Loss, Cody Mcgrath, Sarah E Little-Letsinger, Gabriel M Pagnotti, Buer Sen, Zhihui Xie, Gunes Uzer, Guniz B Uzer, Xiaopeng Zong, Martin A Styner, Janet Rubin, Maya Styner

Faculty, Staff and Student Publications

Introduction: Longitudinal effect of diet-induced obesity on bone is uncertain. Prior work showed both no effect and a decrement in bone density or quality when obesity begins prior to skeletal maturity. We aimed to quantify long-term effects of obesity on bone and bone marrow adipose tissue (BMAT) in adulthood.

Methods: Skeletally mature, female C57BL/6 mice (n = 70) aged 12 weeks were randomly allocated to low-fat diet (LFD; 10% kcal fat; n = 30) or high-fat diet (HFD; 60% kcal fat; n = 30), with analyses at 12, 15, 18, and 24 weeks (n = 10/group). Tibial microarchitecture was analyzed …

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 …