Translational Medical Research Commons^™

Increased Glucose Availability Sensitizes Pancreatic Cancer To Chemotherapy, Ali Vaziri-Gohar, Jonathan J. Hue, Ata Abbas, Hallie J. Graor, Omid Hajihassani, Mehrdad Zarei, George Titomihelakis, John Feczko, Moeez Rathore, Sylwia Chelstowska, Alexander W. Loftus, Rui Wang, Mahsa Zarei, Maryam Goudarzi, Renliang Zhang, Belinda Willard, Li Zhang, Adam Kresak, Joseph E. Willis, Gi-Ming Wang, Curtis Tatsuoka, Joseph M. Salvino, Ilya Bederman, Henri Brunengraber, Costas A. Lyssiotis, Jonathan R. Brody, Jordan M. Winter

Student Papers, Posters & Projects

Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies …

Implementation Barriers Of Multidisciplinary Care In Chronic Kidney Disease Through A Cfir Framework: A Narrative Review, Max J. Goodman, Amalia Jereczek

Cooper Rowan Medical Journal

Introduction: 37 million Americans suffer from chronic kidney disease, which affects multiple organ systems and requires multidisciplinary care. Multidisciplinary care is an inherently broad and complex topic, and while it is being implemented across healthcare in the United States and abroad, multidisciplinary care outcomes are poor in this patient population. It is possible that there exists gaps in the literature regarding implementation and replication of multidisciplinary care interventions such that healthcare practices are unable to fully take advantage of multidisciplinary care publications for chronic kidney disease. This narrative review utilizes the five domains of the Consolidated Framework for Implementation Research …

Comparison Of The Biological Basis For Non-Hiv Transmission To Hiv-Exposed Seronegative Individuals, Disease Non-Progression In Hiv Long-Term Non-Progressors And Elite Controllers, Joseph Hokello, Priya Tyagi, Shelly Dimri, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

HIV-exposed seronegative individuals (HESIs) are a small fraction of persons who are multiply exposed to human immunodeficiency virus (HIV), but do not exhibit serological or clinical evidence of HIV infection. In other words, they are groups of people maintaining an uninfected status for a long time, even after being exposed to HIV several times. The long-term non-progressors (LTNPs), on the other hand, are a group of HIV-infected individuals (approx. 5%) who remain clinically and immunologically stable for an extended number of years without combination antiretroviral therapy (cART). Meanwhile, elite controllers are comprise a much lower number (0.5%) of HIV-infected persons …

Apoe4, Age, And Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia, Jayakrishnan Nair, Joseph F. Welch, Alexandria B. Marciante, Tingting Hou, Qing Lu, Emily J. Fox, Gordon S. Mitchell

Department of Physical Therapy Faculty Papers

Rational

Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses.

Objectives

Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH).

Methods

In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures …

Crosstalk Between Diacylglycerol Kinase And Protein Kinase A In The Regulation Of Airway Smooth Muscle Cell Proliferation, Miguel Angel Hernandez-Lara, Santosh Kumar Yadav, Stanley Conaway, Sushrut D. Shah, Raymond B. Penn, Phd, Deepak A. Deshpande, Phd

Center for Translational Medicine Faculty Papers

Background: Diacylglycerol kinase (DGK) regulates intracellular signaling and functions by converting diacylglycerol (DAG) into phosphatidic acid. We previously demonstrated that DGK inhibition attenuates airway smooth muscle (ASM) cell proliferation, however, the mechanisms mediating this effect are not well established. Given the capacity of protein kinase A (PKA) to effect inhibition of ASM cells growth in response to mitogens, we employed multiple molecular and pharmacological approaches to examine the putative role of PKA in the inhibition of mitogen-induced ASM cell proliferation by the small molecular DGK inhibitor I (DGK I).

Methods: We assayed cell proliferation using CyQUANT™ NF assay, protein expression …

A Review Of Isomirs In Colorectal Cancer, Molly A. Lausten, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

As advancements in sequencing technology rapidly continue to develop, a new classification of microRNAs has occurred with the discovery of isomiRs, which are relatively common microRNAs with sequence variations compared to their established template microRNAs. This review article seeks to compile all known information about isomiRs in colorectal cancer (CRC), which has not, to our knowledge, been gathered previously to any great extent. A brief overview is given of the history of microRNAs, their implications in colon cancer, the canonical pathway of biogenesis and isomiR classification. This is followed by a comprehensive review of the literature that is available on …

Building Up Cal Poly Global Brigades Student Group: Reflections On Designing And Implementing One Undergraduate-Led Community Info Session, Caroline Nicole Smith, Jafra D. Thomas

Kinesiology and Public Health

Intro: Global Brigades, an international non-profit organization, trains college students and other pre-professionals in community-based health promotion by mobilizing community service trips around the world, which are taught and led by local community groups. Cal Poly’s Global Brigades student group was founded in 2018, and thus far, they have carried out three annual, medically-focused brigades to Honduras (two in-person, one virtual).

Purpose: The aim of this report is to present the findings of one experiential senior project to promote Cal Poly’s Global Brigades student group^[1] (conducted January to March 2023).

Methods: The student designed material for …

Summary Of: Why Did Some Rural Mainers Accept Novel Covid-19 Vaccines When Rolled Out In 2021, While Others Did Not?, Michael Kohut Phd, Liz Scharnetzki, Joseph Pajka, Elizabeth Jacobs, Kathleen Fairfield

Northern New England Clinical & Translational Research

Many people, especially in rural areas of the United States, choose not to receive novel COVID-19 vaccinations despite public health recommendations.

Understanding how people describe decisions to get vaccinated or not may help to address hesitancy.

Study @ "Decisions about adopting novel COVID-19 vaccines among White adults in" by Michael Kohut PhD, Liz Scharnetzki et al.

Test-Retest Reliability Of Virtual Reality Devices In Quantifying For Relative Afferent Pupillary Defect, Prithul Sarker, Nasif Zaman, Joshua Ong, Phani Paladugu, Molly Aldred, Ethan Waisberg, Andrew G. Lee, Alireza Tavakkoli

Student Papers, Posters & Projects

Background: The swinging flashlight test (SFT) is one of the most prominent clinical tests for detecting the relative afferent pupillary defect (RAPD). A positive RAPD localizes the lesion to the affected afferent pupil pathway and is a critical part of any ophthalmic exam. Testing for an RAPD, however, can be challenging (especially when small), and there is significant intrarater and interrater variability.

Methods: Prior studies have shown that the pupillometer can improve the detection and measurement of RAPD. In our previous research, we have demonstrated an automatic SFT by utilizing virtual reality (VR), named VR-SFT. We applied our methods to …

Metabolic Profiling Reveals Differential Alterations In Serum And Brain Metabolites During The Progression Of Huntington’S Disease In An R6/2 Transgenic Mouse Model, Nadia Ashrafi, Sumeyya Akyol, Sangeetha Vishweswaraiah, Ali Yilmaz, Leva Kerševičiūtė, Juozas Gordevicius, Stewart Graham

Conference Presentation Abstracts

No abstract provided.

Particle Arc Single-Isocenter Stereotactic Radiosurgery Of Multiple Brain Metastases, L Volz, S Mein, T Tessonnier, Peilin Liu, A Mairani, M Durante, Xuanfeng Ding, C Graeff, T Li

Conference Presentation Abstracts

Purpose: To develop spot-scanning proton (SPArc) and heavy ion (SHArc) arc therapy for single-isocenter stereotatic radiosurgery (SISRS) of multiple brain metastases (MBMs). First results achieved with dedicated planning infrastructure are compared to state-of-the -art volumetric modulated photon arc therapy (HA-VMAT). Methods: A multi-institutional collaboration was established to develop bespoke SPArc and SHArc SISRS infrastructure with available research and commercial treatment planning systems. Devised planning and delivery methods considered dedicated energy, spot, and multi-arc selection strategies. SPArc and SHArc (carbon and helium ions) plans were generated for MBM patients exhibiting 3-12 intracranial lesions with GTV volumes between 0.03ccm and 19.8ccm, at …

Integrative Analysis Of Metabolome And Methylome Identifies The Correlation Of Aminoacyl-Trna Biosynthesis Metabolitesand Sepsecs Gene Methylation In Huntington’S Disease Brain Tissue, Sangeetha Vishweswaraiah, Ali Yilmaz, Nadia Ashrafi, Nazia Saiyed, Abdulla Khalid, Purvesh R. Koladiya, Xiaobei Pan, Shirin Macias, Uppala Radhakrishna, Stewart F. Graham

Conference Presentation Abstracts

No abstract provided.

Urinary Cytokines As Potential Biomarkers Of Mild Cognitive Impairment And Alzheimer’S Disease: A Pilot Study, Nazia Saiyed, Ali Yilmaz, Sangeetha Vishweswaraiah, Abhishek Maiti, Ilyas Ustun, Sarah Bartolone, Travonia Brown-Hughes, Roland Thorpe Jr, Tammy Osentoski, Stacey Ruff, Amita Pai, Michael E. Maddens, Khaled Imam, Stewart Graham

Conference Presentation Abstracts

No abstract provided.

Human Serum Metabolites Signature The Prodromal Biomarkers Of Parkinson’S Disease: Lrkk2 Longitudinal Stu, Ali Yilmaz, Nadia Ashrafi, Sumeyya Akyol, Ieva Kerševičiūtė, Milda Milčiūtė, Juozas Gordevicius, Stewart Graham

Conference Presentation Abstracts

BACKGROUND: The complex and heterogeneous nature of Parkinson’s disease (PD) and variability in their progression hampers its early diagnosis and treatment. Consequently, there is much interest in developing models that can predict PD progression and help to deepen our understanding of PD pathology. Metabolomics might shed light on the PD imprint seeking a broader view of the biochemical remodeling induced by this disease in an early and pre-symptomatic stage, unveiling potential biomarkers and developing new novel therapeutic targets

METHODS: In this novel study utilizing ¹H NMR and DI-LC-MS/MS we conducted metabolomics investigation on the serum samples from a clinically well …

A Comprehensive Investigation Of Linear Energy Transfer Optimization Effectiveness In Intensity-Modulated Proton Therapy Via Alternating Direction Method Of Multipliers (Impt Let-Admm), Q Fan, G Liu, Lewei Zhao, Xiaoqiang Li, Xuanfeng Ding, S Dai

Conference Presentation Abstracts

Linear energy transfer (LET)-guided optimization in intensity-modulated proton therapy (IMPT) via alternating direction method of multipliers (ADMM) has the potential to improve its biological effectiveness (IMPTLET- ADMM), in which the LET distribution in target can be escalated, while the LET distribution in the organs at risk can be mitigated. This study aims to quantitatively investigate the effectiveness of LET optimization in IMPT via ADMM with different solvers in its iteration loop. Methods: The clinical dose-volume-histogram (DVH) constraint noted dose sub-problem and clinical LET -volume-histogram (LVH) constraint noted LET sub-problem are combined to generate a composite objective function, which is available …

Does Proton Arc Therapy Has Potential Clinical Benefits For Hepatocellular Carcinoma?, Peilin Liu, R Dalfsen, M Soukup, Shupeng Chen, Lewei Zhao, Z Wang, X S. Gao, Thomas Quinn, Craig Stevens, Rohan Deraniyagala, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To investigate the potential clinical benefits and dose-averaged Linear Energy Transfer (LETd) sparing, utilizing proton arc plan for Hepatocellular carcinoma (HCC) patients in comparison with Intensity Modulated Proton Therapy (IMPT). Methods: Ten HCC patients have been retrospectively selected. Two planning groups were created: Proton Arc plans using Monaco ver. 6 and the clinical IMPT plan. Both planning groups used the same robustness parameters. The prescription dose is 67.5 Gy (RBE) in 15 fractions/ 66 GyE in 10 fractions of the Clinical Target Volume (CTV) following clinical IMPT plan. Robustness evaluations were performed to ensure target dose coverage. Normal Tissue …

An Analytic Model Of The External Beam Dose Rate Effect On Immune Cells In Blood Dosimetry, Lewei Zhao, Peilin Liu, G Liu, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: Radiation therapy is a double-edged sword with regard to its immunomodulatory effect. It is critical to find how it is affected by dose rate. Thus, we developed an analytic model for calculating the number of immune cells receiving radiation. Methods: Suppose the blood is received radiation by constant dose rate. The blood is one-way flow without circulation in the radiation delivery at a constant velocity. Two kinds of lung treatment regimens were considered standard delivery 2Gy per fx total 30fx and hypo-fractionation SBRT 12 Gy per fx total 5 fx. Two different dose rates were simulated for standard treatment: …

Investigate The Delivery Efficiency Improvement For Sparc Compared To Impt, Peilin Liu, B A. De Jong, S Chang, Lewei Zhao, G Liu, Craig Stevens, Rohan Deraniyagala, E W. Korevaar, J A. Langendijk, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To assess the efficiency improvement of SPArc compared to IMPT in proton clinical operation.Methods: A random clinical operation day at a proton therapy center with a two room system. Aa total of 10 Head & Neck cancer cases treated on Jan 6th, 2021were selected and SPArc plans were generated for all the cases with similar target coverage and dose constraints of organ at risk (OARs). 3% range uncertainties and 3mm setup uncertainties were applied for robust optimization. The log files of clinical IMPT were exported to calculate true treatment delivery time. The machine-specific delivery sequence model was utilized to …

The Effects Of Dual Iqos And Cigarette Smoke Exposure On Airway Epithelial Cells: Implications For Lung Health And Respiratory Disease Pathogenesis, Pritam Saha, Siddhi Jain, Ipsita Mukherjee, Samir R. Panda, Amir A. Zeki, V.G.M. Naidu, Pawan Sharma

Center for Translational Medicine Faculty Papers

Background Cigarette smoking remains a primary cause of chronic lung diseases. After a steady decline, smoking rates have recently increased especially with the introduction of newer electronic nicotine delivery devices, and it is also emerging that dual- or poly-product usage is on the rise. Additionally, with the introduction of IQOS (a heated tobacco product) globally, its impact on human health needs to be investigated. In this study we tested if dual exposure (cigarette smoke (CS)+IQOS) is detrimental to lung epithelial cells when compared with CS or IQOS exposure alone.

Methods Human airway epithelial cells (BEAS-2B) were exposed to either CS, …

Comparing Performance Of Spectral Image Analysis Approaches For Detection Of Cellular Signals In Time-Lapse Hyperspectral Imaging Fluorescence Excitation-Scanning Microscopy, Marina Parker, Naga S. Annamdevula, Donald Pleshinger, Zara Ijaz, Josephine Jalkh, Raymond Penn, Deepak Deshpande, Thomas C. Rich, Silas J. Leavesley

Center for Translational Medicine Faculty Papers

Hyperspectral imaging (HSI) technology has been applied in a range of fields for target detection and mixture analysis. While HSI was originally developed for remote sensing applications, modern uses include agriculture, historical document authentication, and medicine. HSI has also shown great utility in fluorescence microscopy. However, traditional fluorescence microscopy HSI systems have suffered from limited signal strength due to the need to filter or disperse the emitted light across many spectral bands. We have previously demonstrated that sampling the fluorescence excitation spectrum may provide an alternative approach with improved signal strength. Here, we report on the use of excitation-scanning HSI …

Gp38 As A Vaccine Target For Crimean-Congo Hemorrhagic Fever Virus, Gabrielle Scher, Dennis A. Bente, Megan C. Mears, Maria N.B. Cajimat, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne virus that causes severe hemorrhagic disease in humans. There is a great need for effective vaccines and therapeutics against CCHFV for humans, as none are currently internationally approved. Recently, a monoclonal antibody against the GP38 glycoprotein protected mice against lethal CCHFV challenge. To show that GP38 is required and sufficient for protection against CCHFV, we used three inactivated rhabdoviral-based CCHFV-M vaccines, with or without GP38 in the presence or absence of the other CCHFV glycoproteins. All three vaccines elicited strong antibody responses against the respective CCHFV glycoproteins. However, only vaccines containing GP38 …

Protocol Of A Multicentre Randomised Controlled Trial Assessing Transperineal Prostate Biopsy To Reduce Infectiouscomplications, Jim Hu, Alec Zhu, Andrew Vickers, Mohamad Ezzeddine Allaf, Behfar Ehdaie, Anthony Schaeffer, Christian Pavlovich, Ashley E. Ross, David A. Green, Gerald Wang, Serge Ginzburg, Jeffrey S. Montgomery, Arvin George, John N. Graham, Benjamin T. Ristau, Andres Correa, Jonathan E. Shoag, Keith J. Kowalczyk, Tenny R. Zhang, E.M. Schaeffer

Einstein Health Papers

Introduction Approximately one million prostate biopsies are performed annually in the USA, and most are performed using a transrectal approach under local anaesthesia. The risk of postbiopsy infection is increasing due to increasing antibiotic resistance of rectal flora. Single-centre studies suggest that a clean, percutaneous transperineal approach to prostate biopsy may have a lower risk of infection. To date, there is no high-level evidence comparing transperineal versus transrectal prostate biopsy. We hypothesise that transperineal versus transrectal prostate biopsy under local anaesthesia has a significantly lower risk of infection, similar pain/discomfort levels and comparable detection of non-low-grade prostate cancer.

Methods and …

Noninvasively Monitoring Of Cerebral Blood Flow In Piglet Models Of Graded Hemorrhage And Hypoxic Ischemic Brain Injury Using Diffuse Correlation Spectroscopy And Near-Infrared Spectroscopy, Randolph Sinahon, Danielle Shoshany, Shadi Malaeb, Mert Deniz Polat, Meltem Izzetoglu, Kurtulus Izzetoglu

St. Chris Research Day

No abstract provided.

Functional Evaluation Of A Novel Rpl30 Mutation And Its Role In Diamond Blackfan Anemia (Dba), Alexandra Prosser, Alexandria Cockrell, Danny Miller, Chris Seidel, Tamara Potapova, John M. Perry, Midhat Farooqi, Erin M. Guest, Jennifer Gerton

Research Days

Background: Bone marrow failure is life-threatening and requires prompt, intensive treatment, which is dependent upon identification of genetic drivers. Although there has been investigation into associated genetic mutations, especially in Diamond Blackfan anemia (DBA), the relationship between genotype and phenotype remains unclear.DBA has been identified as a ribosomopathy, also known as a disease associated with defects in ribosome biogenesis. We identified a novel heterozygous variant (c.167+769C >T) in the noncoding region of RPL30 in a patient with clinical diagnosis of DBA. Clinical RNA sequencing (RNA-seq) suggests the variant generates a novel splice acceptor site resulting in truncated RPL30 transcripts. Elucidation …

Spanish Club For Healthcare Professionals, Sophie Stallings

Honors Theses

Spanish Club for Healthcare Professionals was registered as an approved student organization in January of 2023, and the first meeting was January 30. The objective of this club is to educate students entering different healthcare fields on how to communicate with Spanish speaking patients. During my time serving as the founder and president of this organization, I strived to provide a resource that would help lower the language barrier that is present in today’s society with regards to a lack of Spanish- speaking healthcare professionals. The goal is not for students to be fully fluent in Spanish but simply learn …

Oxidative Damage Together With Post-Occlusive Re-Oxygenation Kinetics, In Calf Muscle, Implicate Microvessels In The Myopathy Of Peripheral Artery Disease, Molly Schieber

Theses & Dissertations

Background:Peripheral Artery Disease (PAD) is characterized by calf muscle fibrosis and myofiber oxidative damage (OxD). Our laboratory has demonstrated architectural changes of calf-muscle microvessels (

Methods:Gastrocnemius biopsies were collected from controls, patients with Stage II PAD, and Stage IV patients with limb-threatening ischemia. Carbonyl adducts (CA; oxidative damage), and Heme Oxygenase-1 (HO-1; anti-OxD in microvessels) were quantified in microvessels (

Results: Post-occlusive re-oxygenation of calf muscle was slowed in Stage II patients versus controls. Kinetic parameters correlated poorly with Ankle-Brachial Index. Microvessel CA was increased in pre- and post-exercise Stage II patients and in Stage IV patients versus …

Awareness & Prevention Of Health Hazards For Americans Embarking In Space Tourism, Krzysztof Zembrzuski

Rowan-Virtua Research Day

Since the beginning of spaceflight, keeping humans healthy has been a serious concern. Prior to 2021, astronauts had to undergo an elite selection process to embark in space travel. Now that commercial spaceflight is a reality, the criteria to experience space has been significantly loosened, raising health concerns to a larger and unhealthier pool of travelers. Most commercial spaceflight clients are anticipated to be middle-aged adults, which implies many will suffer from high blood pressure and heart disease, both of which are frequent ailments in this age group. Because of the massive compression the body undergoes during takeoff and return, …

Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques.

Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients.

Methods: We selected Western blotting technique to study …

Application Of Informatics Tools To Facilitate The Practice Of Precision Medicine With Genomic Testing And Clinical Data, Michael Sayer

Pharmaceutical Sciences (PhD) Dissertations

The practice of precision medicine considers a variety of sources of information to optimize patient care. Factors such as patient demographics, clinical history, and lab test values have well understood effects on treatment outcomes and influence decision making. However, effective inclusion of biomolecular data such as protein expression and DNA sequencing data within the practice of precision medicine needs continued study. Informatics tools offer solutions to allow these complex data sources to be effectively embraced. Utilization of informatics tools to visualize data pertaining to the gene selection practices of pharmacogenomic (PGx) tests effectively communicated large amounts of information into concise …

Immobilization And Its Effects On Functional Recovery After Spinal Cord Injury., William H. Gregory

College of Arts & Sciences Senior Theses

Recovery, or rather the failure to recover, is a perplexing issue of spinal cord injury that is currently being investigated. This issue becomes more puzzling when investigating models in which spinal cord injury (SCI) is studied. There appears to be greater functional recovery experienced by animals within these models after injury as compared to patients in the clinical setting. While many things could contribute to this disparity, one difference that stands out when comparing the basic research model and clinical experience of SCI is the inactivity and limb disuse after the injury. This same level of immobility is rarely accounted …