Translational Medical Research Commons^™

Use Of Margins Around Small Brain Metastasis Improves Specificity Of Evaluation Methods For Stereotactic Radiosurgery Treatment Plans, Purity Kemunto Bundi

LSU Master's Theses

Purpose: To reduce the high false positive rates (FPRs ≥ 46%) from the evaluation of Gamma Knife stereotactic radiosurgery (SRS) treatment plans for small brain metastases. Specifically, we modified two evaluation indices, Treated Volume Ratio (TVR) and Gradient Index (GI), which exhibited FPRs exceeding 84%. A false positive result incorrectly indicates that an acceptable plan, as determined by a medical physicist and a radiation oncologist, is inacceptable.

Methods: This study utilized training and validation datasets from Gamma Knife treatment plans from The University of Texas MD Anderson Cancer Center (MDACC) and Mary Bird Perkins Cancer Center (MBPCC). Data included doses, …

Ovarian Cancer G Protein-Coupled Receptor-1 Signaling Bias Dictates Anti-Contractile Effect Of Benzodiazepines On Airway Smooth Muscle, Dominic R. Villalba, Arun K. Jannu, Elham Javed, Isha Dandekar, Ruping Wang, Deepak A. Deshpande, Steven S. An, Reynold A. Panettieri, Dale D. Tang, Raymond B. Penn, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

BACKGROUND: We recently reported that the ovarian cancer G protein-coupled receptor-1 (OGR1) can be pharmacologically biased with specific benzodiazepines to couple with distinct heterotrimeric G proteins in human airway smooth muscle (ASM) cells. Lorazepam stimulated both G

METHODS: Models of histamine (His) -stimulated contraction included imaging of ex vivo human precision cut lung slices (hPCLS) and Magnetic Twisting Cytometry (MTC) analysis of human ASM cell stiffness. To explore mechanisms of regulation, we examined effects on myosin light chain (pMLC) phosphorylation and PKA activity in primary human ASM cultures, as well as actin cytoskeleton integrity as defined by changes in the …

Novel Combination Therapies For Estrogen Receptor-Positive Breast Cancer Driven By Rational Molecular Mechanisms, Anneka Lila Johnson

Dartmouth College Ph.D Dissertations

Breast cancer (BC) is the most common non-keratinocyte cancer diagnosed in women in the United States with approximately 300,000 new cases diagnosed each year. Despite a myriad of treatment options, BC remains the second-most deadly cancer. Estrogen receptor-positive (ER+) BC comprises 60-70% of BC diagnoses and is treated with endocrine therapies that limit ER signaling. Despite endocrine therapy options, ~1/3 of patients experience recurrence within 10-20 years of diagnosis. Novel therapeutic strategies are required to limit BC recurrence-related morbidity and mortality.

Radiotherapy is used as an adjuvant treatment for ER+ BC patients prior to the use of endocrine therapy. Radiation …

Solute Transport From Synovial Fluid To Articular Cartilage And Subchondral Bone At Different Stages Of Osteoarthritis In A Live Mouse Model, Mengcun Chen, Yanmei Yang, Mingshu Cui, Bin Wang

Center for Translational Medicine Faculty Papers

OBJECTIVE: This study aims to (1) identify a simplified method to preserve sample integrity and maintain original fluorescence distribution; (2) assess the diffusivity of small and large molecules within articular cartilage (AC), calcified cartilage (CC), and subchondral bone (SB); and (3) investigate the changes in solute transport at various stages of osteoarthritis (OA) in a destabilization of the medial meniscus (DMM) murine model.

METHODS: Fluorescent dyes of small and large molecules were injected into the knee joints of live mice. Joints were harvested and rapidly frozen immediately post-euthanasia. Optimal dye concentrations and dwelling times were determined through exploratory studies. Mice …

Associations Between Health Literacy And Comprehension Of Health Visits In A Community Setting, Amanda Romaya, Adel Andemeskel, Salim Abdul-Razak, Linda Dillon, Victoria Lucia

Posters

Low health literacy is a significant social determinant of health that is associated with poor health outcomes1-3. Bringing attention to health literacy will aid in promoting the health of the population. However little has been done to implement national policies and interventions that address patient health literacy, especially in a community setting4.

We hypothesized that our assessment of the identified patient population’s health literacy will not meet adequate standards and will indeed demonstrate a need for community-focused interventions

A Review Of Sutures And The Prospective Applications Of Nanofiber Technology In Suture Engineering, Hanna Brancaccio, Dominique Hassinger, Vincent Beachley

Rowan-Virtua Research Day

Introduction: Suturing is a method to close surgical or traumatic wounds to promote healing. The ideal suture should have high tensile strength that loses strength at the same rate as the healing tissue gains strength, be easy to handle and form secure knots, induce minimal inflammation, and stretch/recoil according to wound contraction. While there are suture materials available for use in various procedures that fulfill most requirements, no one suture possesses every desirable characteristic, and limitations are still prevalent. Nanofiber geometry has a well-known ability to modulate cell morphology, attachment, gene expression, extracellular matrix production, and macrophage polarization in …

Assessing Disparities In Sep-1 Bundle Compliance At Corewell Health, Zachary Awad, Mark Munir, Paul Bozyk, Ramin Homayouni

Posters

Sepsis, a life-threatening condition resulting from a dysregulated immune response to infection, carries significant mortality. To improve sepsis management, the Centers for Medicare & Medicaid Services (CMS) introduced the SEP-1 bundle, outlining critical interventions within specified timelines. This study aimed to investigate disparities in SEP-1 bundle compliance, examining variations among septic patients based on sociodemographic factors like age, race, and area deprivation index (ADI), as well as clinical factors like chronic health conditions.

Hypoxia Induced Ribosomal Rna Fragmentation Mediated By Rnase L, Vanessa Kristina Pizutelli, Dimitri G Pestov

Rowan-Virtua Research Day

Ischemic injury contributes to a range of global pathologies. Ischemia/Reperfusion Injury (IRI) is a paradoxical phenomenon that involves an initial restriction of blood flow followed by a sudden restoration of perfusion. This type of injury takes place in conditions such as myocardial infarction, acute kidney disease, and ischemic stroke and often leads to cellular death. Additionally, IRI exacerbates post-surgical outcomes and plays a role in graft dysfunction and transplant rejection. Despite efforts to develop therapies targeting known IRI pathways, clinical trials have largely been unsuccessful, underscoring the need for alternative mechanisms and biomarkers associated with IRI-induced apoptosis. Reactive oxygen species …

Allergies Coinciding With Central Sensitization Syndromes (Access), Jacqueline Morey, Alemu Fite, Carl Lauter, Matthew Sims

Posters

Significance of Reported Allergies: Many reported drug allergies are mislabeled side effects or misinterpretations, leading to suboptimal treatment, antibiotic resistance, and worse patient outcomes.¹

Central Sensitization Syndromes (CSS): CSSs are chronic pain conditions linked to altered sensory perception, including pain, fatigue, and neurologic dysfunction.² These patients may be more likely to misattribute medication side effects as allergies.

Previous Findings & Hypothesis: Prior research found high allergy reporting in interstitial cystitis and fibromyalgia—both CSS conditions.⁴ We hypothesized that other CSS diagnoses also correlate with increased allergy reporting, emphasizing the need for better allergy evaluation.

Epic Best Practice Alerts Increases Sep1 Orderset Usage, Mark Munir, Zachary Awad, Paul Bozyk, Ramin Homayouni

Posters

Sepsis is a massive, system-wide inflammatory response to an infection that can lead to multisystem organ failure.1 Sepsis has a very high mortality rate of 20-50% in patients with severe sepsis and is the 10th leading cause of death in the United States.2 One of the most significant ways of reducing mortality from sepsis is timely detection and initiation of treatment in septic patients.3

Electronic medical records such as Epic have implemented sepsis warning algorithms and alerts to facilitate quicker detection of sepsis and thus earlier initiation of treatment. The goal of this study is to determine if an Epic …

Implementation Of An Opioid Free Pediatric Hernia Repair Protocol, Corey Shafer, Antonela Muca, Randy Hilleary, Kristin Lemarbe, Diane Studzinsk, Kaveh Aslani, Nathan Novotny, Pavan Brahmamdam, Begum Akay

Posters

Surgery most often provides children with their first exposure to opioids which may lead to misuse and overuse. Protocolizing pain management perioperatively can reduce opioid exposure in children while still providing adequate pain management.

Surgical Site Infection Bundle For Babies: Preliminary Data, Cullen Woodley, John Nida, Alexis Lonjin, Katelyn Ward, Diane Studzinski, Begum Akay

Posters

Surgical Site Infections (SSIs) are infections that occur in or around the area where a surgery was recently performed. They are estimated to account for 20% of all healthcare associated infection, and lead to an increase in morbidity and mortality. Perioperative care bundles show promise in reducing SSIs in adults but are not often used in neonatal surgery. Infections in babies after surgery are less common than adults but carry significant morbidity in a fragile patient.

Enhancing Reproductive Anatomy Education: A Comprehensive Approach Integrating Near-Peer And Reciprocal Peer Tutoring, Hope Hefferan, Emelie-Jo Scheffler, Erin Mueller, Varna Taranikanti

Posters

• Near-peer tutoring (NPT): Tutors are more advanced than tutees, typically offering support in understanding complex concepts.1

• Reciprocal peer tutoring (RPT): Students with similar levels of training alternate between tutor and tutee roles, facilitating collaborative learning.1

• Peer tutoring fosters professional development and improves long-term retention of complex medical concepts.3,4,5

• Reproductive anatomy is a challenging area for many medical students; Innovative peer tutoring methods may help improve understanding and retention of anatomical structures.

• We hypothesize that integrating NPT and RPT within the laboratory setting in the reproductive organ system course will enhance student motivation, self-efficacy, and long-term …

Examining Health Disparities: An Observational Study On Peripheral Vascular Access Outcomes Among Hospitalized Patients, Charlotte O’Sullivan, Nicholas Mielke, Yuying Xing, Amit Bahl

Posters

Peripheral intravenous catheter (PIVC) placement is the most common invasive procedure performed in healthcare, with an estimated 90% of hospitalized patients requiring PIVC access during their stay. This equates to around two billion PIVCs used annually.1–3 Studies report 36% to 63% of catheters fail due to a variety of complications, including infiltration, occlusion, phlebitis, dislodgment, and infection. 2–6 These failures not only cause immediate patient discomfort and increased clinical workload but also have wider implications such as prolonged hospital stays and delays in critical treatments.2 The factors contributing to PIVC failure are multifaceted, involving clinical presentation, patient anatomy, provider skill …

From Trauma To Treatment: Chronic Neurobehavioral Consequences And Emerging Treatments, Moriah E. Mcguier

Dartmouth College Ph.D Dissertations

Severe trauma exposure related to traumatic brain injury (TBI) or psychiatric disorders like post-traumatic stress disorder (PTSD) leads to neurobehavioral and physiological impairments that reduce the quality of life of individuals and remain difficult to treat with current therapeutic options. Further, these conditions are highly comorbid, notably in PTSD with blast-traumatic brain injury (bTBI) commonly experienced by military members via explosive forces, leading to complex and heterogenous outcomes. To address this, preclinical models have been developed to recapitulate aspects of TBI and PTSD. This thesis utilizes two such models in rats, bTBI and the single prolonged stress (SPS) model for …

Channeling Relaxation Through Multiple Means: Tmem16a Antagonism For Asthma, Arun K. Jannu, Raymond B. Penn

Center for Translational Medicine Faculty Papers

No abstract provided.

The Development Of Magmas Inhibition As A Potential Therapeutic Target In Temozolomide Resistant Glioma, Jennifer Duyen Tran

Electronic Theses, Projects, and Dissertations

Glioblastoma (GBM) is a highly aggressive brain tumor that remains a significant challenge in neuro-oncology today. Approximately 90% of GBM patients experience tumor recurrence within one to two years of diagnosis. Therefore, due to its high resistance to conventional therapies, new treatment strategies are urgently needed. The current standard of care for GBM is the chemotherapeutic Temozolomide (TMZ). TMZ is an oral alkylating agent, it functions by delivering a methyl group to purine bases. The development of resistance to TMZ is partially regulated by the DNA repair enzyme O6- methylguanine-DNA methyltransferase (MGMT). Despite the potential shown by MGMT promoter methylation …

Developing Novel Therapies Targeting The Tumor Microenvironment Of Aggressive Breast Cancer, Lan T H Phi

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) are the most aggressive breast cancer subtypes. The tumor microenvironment (TME) is critical in driving these aggressive breast cancers' clinical phenotype and aggressiveness. Therefore, we explored novel actionable targets and complementary therapies targeting the TME to improve the outcomes of patients with these cancers.

In this thesis, we identified AXL as a potential therapeutic target in IBC due to its role in generating an immunosuppressive TME. Indeed, inhibiting the AXL pathway suppresses IBC tumor growth and reduces M2 macrophage populations in various mouse models. Mechanistically, AXL facilitates the polarization of M2 …

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

Overcoming Resistance To Cdk4/6-Targeted Therapy Using Jak2/Stat3 Inhibitor In Triple-Negative Breast Cancer, Chuling Zhuang

Dissertations and Theses (Open Access)

Breast cancer is the most common type of cancer diagnosed in women, with nearly 30% of cases becoming metastatic accounting for over 90% of breast cancer-related deaths. Among different breast cancer subtypes, triple-negative breast cancer (TNBC) has the worst prognosis and the highest propensity to metastasize. However, TNBC patients have limited treatment options due to their lack of actionable drug targets while therapeutic resistances result in high rates of recurrence and metastasis. Cyclin-dependent kinase 4 and 6 (CDK4/6) are major cell cycle regulators that control G1 to S phase transition and aberrant hyperactivation of the CDK4/6 pathway results in uncontrolled …