Translational Medical Research Commons^™

Identifying Sleep-Related Factors Associated With Cognitive Function In A Hispanics/Latinos Cohort: A Dual Random Forest Approach, Li Xiaojin, Cui Licong, Wang Fei, Paul E Schulz, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Disordered sleep is associated with poor cognitive function and cognitive decline. However, little is known regarding the association of sleep-related factors with cognitive function in underrepresented cohorts such as the Hispanic/Latino population. Leveraging the National Sleep Research Resource, one of the most comprehensive collections of sleep studies, we identified a Hispanic/Latino cohort of 1,031 lower cognitive function cases and 2,062 normal controls. We developed a novel dual random forest (DRF) approach to discriminate cases against controls for estimating the potential impact of sleep-related variables related to the decline of cognitive function. Several important sleep-related factors were identified which may be …

The Use Of Mechanotherapy To Promote The Recovery From Disuse Atrophy In Aging Rat Skeletal Muscle, Zachary Hettinger

Theses and Dissertations--Rehabilitation Sciences

The combination of age and disuse-related skeletal muscle atrophy predisposes older adults to reduced mobility, loss of independence, and poor quality of life. Poor health outcomes resulting from periods of disuse in older adults are exacerbated by an inability to fully recover, ultimately accelerating geriatric populations towards further functional decline. Aged-related changes to skeletal muscle viscoelastic properties, specifically of muscle extracellular matrix (ECM) stiffness, may not only impact how muscle responds during recovery, but also to interventions intended to augment recovery. Remodeling of muscle ECM in the aged may therefore benefit muscle mass recovery, yet therapies focused on ECM remodeling …

A Comparison Of Exhaustive And Non-Lattice-Based Methods For Auditing Hierarchical Relations In Gene Ontology, Rashmie Abeysinghe, Fengbo Zheng, Licong Cui

Faculty, Staff and Student Publications

Uncovering and fixing errors in biomedical terminologies is essential so that they provide accurate knowledge to downstream applications that rely on them. Non-lattice-based methods have been applied to identify various kinds of inconsistencies in different biomedical terminologies. In previous work, we have introduced two inference-based approaches that were applied in an exhaustive manner to audit hierarchical relations in the Gene Ontology: (1) Lexical-based inference framework, and (2) Subsumption-based sub-term inference framework. However, it is unclear how effective these exhaustive approaches perform compared with their corresponding non-lattice-based approaches. Therefore, in this paper, we implement the non-lattice versions of these two exhaustive …

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4⁺ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4⁺ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski

Theses and Dissertations--Clinical and Translational Science

The development of patient-derived tumor organoids (TOs) from epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine.

Here, we utilize TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high grade serous epithelial ovarian cancer tumor organoids from tissue obtained during debulking surgery (2 neoadjuvant carboplatin exposed, 4 chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1 and 0.1µM). Cell viability curves and resultant EC50 values were determined …

Statins In Patients With Covid-19: A Retrospective Cohort Study In Iranian Covid-19 Patients., Payam Peymani, Tania Dehesh, Farnaz Aligolighasemabadi, Mohammadamin Sadeghdoust, Katarzyna Kotfis, Mazaher Ahmadi, Parvaneh Mehrbod, Pooya Iranpour, Sanaz Dastghaib, Ahmad Nasimian, Amir Ravandi, Biniam Kidane, Naseer Ahmed, Pawan Sharma, Shahla Shojaei, Kamran Bagheri Lankarani, Andrzej Madej, Nima Rezaei, Tayyebeh Madrakian, Marek J Los, Hagar Ibrahim Labouta, Pooneh Mokarram, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Background: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is globally spreading at an alarming rate. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and various known beneficial pleiotropic effects. Our previous …

Covid-10, Healthcare Interior Design + Provider Experience - How Does Your Space Work For You?, Ruth E.P. Deibler

Graduate Research Posters

The lack of research on healthcare staff experience and interior design of the spaces they work in is evident. A focus on staff perspective is needed, particularly staff who navigated the COVID-19 pandemic. This research seeks to capture those stories to develop further research in order to improve staff experience. The initial phase of this mixed-methods approach is a survey. Hypothetically, by placing providers at the center of qualitative research related to healthcare interior design, we can better understand existing healthcare spaces. Ideally, we can develop additional evidence-based, human-centered solutions to transform interior environments in healthcare.

The 20-year Women’s Health …

The Precaution Adoption Process Model In Describing Emergency Action Plan Adoption, Samantha E. Scarneo-Miller, Douglas J. Casa, Shuang Yin, Timothy E. Moore, Yuki Murata, Johna Kay Register-Mihalik, Lindsay J. Distefano

Internet Journal of Allied Health Sciences and Practice

Purpose: The purpose of this study was to identify the ability of the Precaution Adoption Process Model (PAPM) to classify athletic trainers (ATs) and athletic directors (ADs) readiness to act with regards to adopting an emergency action plan (EAP), and describe factors influencing PAPM stages. Method: We used a cross-sectional questionnaire design to evaluate readiness to act for developing an EAP among ATs and ADs working in United States high schools. The PAPM is a participant-driven model to identify someone’s readiness to act or change and has seven stages: Unaware, Unengaged, Undecided, Decided not to Act, Decided to Act, Acting …

Enlightening Ways To Relax Airway Smooth Muscle: Opsins., Vera P. Krymskaya, Raymond B. Penn

Center for Translational Medicine Faculty Papers

No abstract provided.

Role Of P53 Deficient Clonogenic Endothelial Cells In The Pathogenesis Of Pulmonary Hypertension, Aneel Roy Bhagwani

Theses and Dissertations

Pulmonary Artery Hypertension (PAH) is a progressive disorder of the small vessels of the pulmonary vasculature. It is characterized by occlusive vascular remodeling leading to right heart failure and ultimately death. PAH pathogenesis involves a multifactorial etiology leading to formation of occlusive lesions in small (preacinary) pulmonary arteries. These lesions contain hyper-proliferative, apoptosis resistant endothelial cells (ECs), smooth muscle cells and fibroblasts. ECs play a major role in the development of PAH. These ECs in vascular lesions are primitive and express progenitor cell markers, including CD117 (c-kit).

We have isolated clonally expanded, c-kit+ ECs from the lungs of Green Fluorescent …

A Novel Immunostimulatory Platform For Amplifying The Abscopal Response Rates Of Radiation Therapy, Patrick A. Paez

Theses and Dissertations

Radiation therapy (RT) is one of the primary treatment modalities for head and neck squamous cell carcinoma (HNSCC). At the time of diagnosis two-thirds of HNSCC patients have local-advanced disease and 50-60% of these patients will experience a local-regional or metastatic relapse within three years. Improving the immunogenic response of RT may help address this clinical problem. However, current RT regimens have failed to reliably generate robust antitumor immunity as evidenced by the rarity of clinical abscopal responses. Recently we engineered a chimeric fusion molecule called Flagrp170, a novel immunostimulatory agent highly capable of promoting antigen presentation and T-cell activation. …

Another Step In Diagnostics Consultation Model© Actualization: Examining The Impact Of Consultation Workflow Processes On Providers' Clinical Decision Making, Elizabeth K. Leibach

Theses and Dissertations

Background
Communication errors in health services delivery significantly compromise quality in clinical decision making (CDM). Diagnostic information generated by clinical laboratories (CL) accounts for as much as 93% of objective data in the clinical record and therefore is foundational in CDM. This work describes the Diagnostics Consultation Model© (DCM©), a CL communications portal, which supports CDM within interprofessional teams, providers, and institutions. Specific aims were to develop and validate a workflow prediction index (the complexity index, CI) to assign resolution of consultation requests based on an algorithm comprised of characteristics available at the point of consultation initiation. The CI functions …

Contralateral Effects Of Unilateral Strength And Skill Training: Modified Delphi Consensus To Establish Key Aspects Of Cross-Education, A. Manca, T. Hortobágyi, T. J. Carroll, R. M. Enoka, J. P. Farthing, S. C. Gandevia, D. J. Kidgell, Janet L. Taylor, F. Deriu

Research outputs 2014 to 2021

© 2020, The Author(s). Background: Cross-education refers to increased motor output (i.e., force generation, skill) of the opposite, untrained limb following a period of unilateral exercise training. Despite extensive research, several aspects of the transfer phenomenon remain controversial. Methods: A modified two-round Delphi online survey was conducted among international experts to reach consensus on terminology, methodology, mechanisms of action, and translational potential of cross-education, and to provide a framework for future research. Results: Through purposive sampling of the literature, we identified 56 noted experts in the field, of whom 32 completed the survey, and reached consensus (75% threshold) on 17 …

Intermittent Theta Burst Stimulation: Application To Spinal Cord Injury Rehabilitation And Computational Modeling, Neil Mittal

Theses and Dissertations

Loss of motor function from spinal cord injuries (SCI) results in loss of independence. Rehabilitation efforts are targeted to enhance the ability to perform activities of daily living (ADLs), but outcomes from physical therapy alone are often insufficient. Neuromodulation techniques that induce neuroplasticity may push the limits on recovery. Neuromodulation by intermittent theta burst transcranial magnetic stimulation (iTBS) induces neuroplasticity by increasing corticomotor excitability, though this has most frequently been studied with motor targets and on individuals not in need of rehabilitation. Increased corticomotor excitability is associated with motor learning. The response to iTBS, however, is highly variable and unpredictable, …

Peer-Taught Virtual Research Workshops For Surgical Residents: Protocol For A Novel And Sustainable Solution To Improving Surgical Research In Pakistan, Russell S. Martins, Ronika Devi Ukrani, Mohummad Hassan Raza Raja, Maria Khan, Haissan Iftikhar, Syeda Sadia Fatima, Saulat Fatimi

Medical College Documents

Objective: To generate a protocol describing the methodology for a study assessing the effectiveness of a comprehensive series of peer-taught online research workshops for surgical residents across Pakistan in terms of improving research-related knowledge and skills, and long-term research involvement and output.
Methods: The quasi-experimental study will consist of a series of six online research workshops conducted over Zoom for surgical residents across Pakistan. An online sign-up form will be circulated on social media to current surgical residents throughout Pakistan. Curricular content covered in the workshops will be developed in collaboration with experienced research faculty at the Departments of Surgery …

Student-Led Surgical Research Network: Enhancing Medical Student Research Opportunities, Ronika Devi Ukrani, Muhammad Musaab Munir, Areesh Bhatti, Shahryar Noordin

Medical College Documents

The current paper was planned to describe a student-led surgical research network established by the Research Division of the Surgery Interest Group at the Aga Khan University, Karachi. The project involved the creation of a collaborative network to provide opportunities to medical students to work with faculty on research projects. Over 25 students were directly connected with faculty and research mentors to work on research projects in the surgical specialty of their choice. The initiative of establishing a student-led surgical research network was successfully implemented and provided medical students with novel research opportunities by helping bridge the gap between the …

Comparison Of Circulating Tumour Dna And Extracellular Vesicle Dna By Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers Of Disease In A Breast Cancer Patient, Olivia Ruhen, Bob Mirzai, Michael E. Clark, Bella Nguyen, Carlos Salomon, Wendy Erber, Katie Meehan

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. There is increasing recognition of circulating tumour DNA (ctDNA) as a non-invasive alternative to tumour tissue for the molecular characterisation and monitoring of disease. Recent evidence suggests that cancer-associated changes can also be detected in the DNA contained within extracellular vesicles (EVs). As yet, there has been limited investigation into the relationship between EV DNA and ctDNA, and no studies have examined the EV DNA of breast cancer patients. The aim of this study was to use low-pass whole-genome sequencing to identify copy number variants (CNVs) in serial samples of both …

Electrophysiological Properties Of The Mitochondrial Permeability Transition Pores: Channel Diversity And Disease Implication., M. A. Neginskaya, E. V. Pavlov, S.-S. Sheu

Center for Translational Medicine Faculty Papers

The mitochondrial permeability transition pore (mPTP) is a channel that, when open, is responsible for a dramatic increase in the permeability of the mitochondrial inner membrane, a process known as the mitochondrial permeability transition (mPT). mPTP activation during Ca2+ dyshomeostasis and oxidative stress disrupts normal mitochondrial function and induces cell death. mPTP opening has been implicated as a critical event in many diseases, including hypoxic injuries, neurodegeneration, and diabetes. Discoveries of recent years indicate that mPTP demonstrates very complicated behavior and regulation, and depending on specific induction or stress conditions, it can function as a high-conductance pore, a small channel, …

The Er Stress/Upr Axis In Chronic Obstructive Pulmonary Disease And Idiopathic Pulmonary Fibrosis., Mahmoud Aghaei, Sanaz Dastghaib, Sajjad Aftabi, Mohamad-Reza Aghanoori, Javad Alizadeh, Pooneh Mokarram, Parvaneh Mehrbod, Milad Ashrafizadeh, Ali Zarrabi, Kielan Darcy Mcalinden, Mathew Suji Eapen, Sukhwinder Singh Sohal, Pawan Sharma, Amir A Zeki, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Cellular protein homeostasis in the lungs is constantly disrupted by recurrent exposure to various external and internal stressors, which may cause considerable protein secretion pressure on the endoplasmic reticulum (ER), resulting in the survival and differentiation of these cell types to meet the increased functional demands. Cells are able to induce a highly conserved adaptive mechanism, known as the unfolded protein response (UPR), to manage such stresses. UPR dysregulation and ER stress are involved in numerous human illnesses, such as metabolic syndrome, fibrotic diseases, and neurodegeneration, and cancer. Therefore, effective and specific compounds targeting the UPR pathway are being considered …

Modelling Cross-Disciplinary Integration In Fda Multidisciplinary And Interdisciplinary Reviews For New Drug Products: A Phenomenological Descriptive Comparative Case Study, Kevin Bugin

Doctor of Philosophy in Translational Health Sciences Dissertations

Cross-disciplinary integration is a key feature of interdisciplinary research and the collaborative form is often one of the desired outcomes of Team Science endeavors. In 2019 the FDA began rolling out a new interdisciplinary approach to their cross-disciplinary assessment of marketing applications, with the key feature being integrated, collaborative review documents (Woodcock et al., 2020). FDA’s assessment of new drug products to allow them to enter the marketplace is a critical translational activity to protect the US public’s health that requires team-based integration and transparency (Woodcock, 2018). And, while increased cross-disciplinary integration through enhanced collaboration and communication is sought through …