Translational Medical Research Commons^™

A Predictive Coding Account Of Spatial Working Memory Following Prophylactic Levetiracetam Administration Prior To Traumatic Brain Injury, Omeima Mutwali

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) symptom prevention and remediation is an important area of research that would benefit vulnerable groups, including active-duty and veteran soldiers. These patients can sustain penetrative forces in fields of combat or in training, which result in focal lesions that trigger inflammatory and degenerative processes in the brain. Both primary and secondary injuries are associated with changes to cognition, behavior and affective state. This disease poses increased risk of epileptogenesis, as well. Given these outcomes, prior research has evaluated levetiracetam (LEV) as a prophylactic treatment for seizures, cognitive deficits and negative emotionality. LEV acts as a presynaptic …

Rhythms Of Hippocampal Function And Memory After Moderate Prenatal Alcohol Exposure, Lilliana May Sanchez

Psychology ETDs

Fetal Alcohol Spectrum Disorders involve morphologic and neurobiological abnormalities in offspring subjected to prenatal alcohol exposure. Although not as well studied as high exposure, moderate prenatal alcohol exposure represents the most common and undetected form in humans. While learning and memory deficits have been well characterized at the behavioral level in humans with Fetal Alcohol Spectrum Disorders and in animal models of moderate prenatal alcohol exposure, few studies have determined the circuit or systems level mechanisms of the behavioral deficits. A complete understanding of the neural bases of memory deficits after moderate prenatal alcohol exposure is needed to ultimately identify …

Multiple Interest Holder Perspectives Of The True Grit Sci Residential Program: A Mixed Methods Program Evaluation, Keara Mcnair

Seton Hall University Dissertations and Theses (ETDs)

Young adults with spinal cord injury (SCI) face significant challenges during the transition to adulthood, including barriers to independence, community participation, and psychosocial adjustment (Ingimarsdóttir et al., 2023; Zebracki et al., 2010). Current rehabilitation models in the United States prioritize short-term physical recovery and offer limited support for the developmental and contextual needs that shape long-term outcomes after SCI, particularly during transitions from inpatient rehabilitation to the community (Anderson et al., 2024; Bryden & Gran, 2024). Community-based programs may help address these gaps, though few have been rigorously evaluated using implementation science frameworks that attend to health equity, contextual influences, …

The Effects Of Acute Exercise And Observation On Procedural Learning: Considerations Of Biological Sex, Madeline R. Gossett

Honors Theses

As memories are formed or learning progresses, neurons within the brain establish a strong connection in what is referred to as a “neural engram.” This neural engram can be strengthened or weakened by certain physiological factors. Dopamine, for example, is released during physical exercise or when positive reinforcement is incorporated (Greenwood, 2019). This is a neurotransmitter that leads to a stronger connection between neurons, which in turn leads to a stronger memory formed in the brain. These physiological relationships that contribute to cognition are still being discovered, so research in this area is ongoing (Guskjolen and Cembrowski, 2023).

Memory is …

The Impact Of Increased Beef Intake On Cardiometabolic Health In Postmenopausal Women: A 16-Week Randomized Controlled Trial, Leen Samman

Biological Sciences Undergraduate Honors Theses

By 2030, it is projected that the number of post-menopausal women globally will reach 1.2 billion. Moreover, because of increases in life expectancy, women will spend a greater proportion of their later years at elevated risk of chronic disease associated with the hormonal changes of the menopausal transition. Dietary interventions, specifically high-protein diets have shown potential mitigating effects; however, most interventions have focused on total protein intake or protein supplements, not whole foods like lean beef. This randomized controlled trial aimed to assess the effects of daily lean beef consumption as part of a higher protein diet on cardiometabolic markers …

Nurse Driven Intervention To Address Cesarean Section Rates, Cavetta Tulloch-Lewis

Doctor of Nursing Practice (DNP) Translational and Clinical Research Projects

Abstract

Cesarean sections (C-sections) account for approximately one-third of births in the United States and remain the most common inpatient surgical procedure. Primary cesarean sections are a major contributor to rising rates, often leading to repeat cesareans in subsequent pregnancies. While medically necessary C-sections are lifesaving, their overuse in low-risk pregnancies is associated with increased maternal morbidity. Labor dystocia is one of the leading indications for primary cesarean delivery and may be mitigated through evidence-based, nurse-driven interventions such as maternal positioning and peanut ball utilization. Registered nurses are uniquely positioned to influence labor progression and promote vaginal birth through continuous …

Facebook Interaction As A Potential Marker Of Cognitive Decline: Pilot Study, Esraa M. Qansuwa

Theses and Dissertations

One of the critical challenges in brain disorder research is the early identification of individuals with mild cognitive impairment (MCI) who may later develop Alzheimer’s disease (AD) or other dementias. MCI in older adults is frequently associated with diminished social engagement and observable behavioral changes. With the rapid expansion of social media platforms and advances in Machine Learning (ML), digital traces from online activity present a novel and scalable avenue for mental health screening. In particular, predictive ML approaches have demonstrated strong potential in building reliable classifiers for early detection of neurocognitive decline. This study introduces an innovative framework that …

Volumetric Wear Analysis Of Polyethylene Orthopedic Liners Using Point Clouds, Gabriel Landi

Dartmouth College Master’s Theses

In vivo wear of ultra-high molecular weight polyethylene (UHMWPE) orthopedic bearings represents a major problem in shoulder and knee arthroplasty, with significant amounts of devices failing due to the complication itself, and even more due to associated reasons for retrieval, including aseptic loosening. However, quantification of UHMWPE wear has largely been limited to linear and in vitro volumetric analyses, obscuring the understanding of the amount of clinically relevant material loss. This study proposes new methods to measure articular, rim, and backside surfaces of retrieved shoulder and knee UHMWPE liners, centered around the coordinate measuring machine (CMM)-based collection of high density …

The Functional Significance Of Plk1 Phosphorylation Of Nrf2 In Prostate Cancer Progression, Maria Nur

Theses and Dissertations--Toxicology and Cancer Biology

Prostate cancer progression and therapeutic resistance are closely linked to alterations in redox homeostasis and cell cycle regulation. Nuclear factor erythroid 2–related factor 2 (NRF2) is a master regulator of antioxidant responses, yet the mechanisms integrating cell cycle signaling with NRF2 activity in prostate cancer remain poorly defined. In this study, we identify polo‑like kinase 1 (PLK1) as a novel regulator of NRF2 through direct phosphorylation at serine 253 (S253). Using bioinformatic prediction, mass spectrometry, in vitro kinase assays, and cell‑based analyses, we demonstrate that PLK1 phosphorylates NRF2 at S253 in a cell cycle–dependent manner, with maximal phosphorylation during mitosis. …

Biomechanical Effects Of Exercise-Based Interventions In Chronic Nonspecific Low Back Pain: A Systematic Review And Meta-Analysis, Lara De Vecchi Machado

Theses and Dissertations--Kinesiology and Health Promotion

Chronic nonspecific low back pain (CNLBP) is the leading cause of years lived with disability worldwide and represents a complex, multifactorial, and heterogeneous condition. It is characterized by substantial interindividual variability in muscle activation patterns, lumbo-pelvic coordination, and movement strategies. Although exercise is widely recommended as a first-line intervention and its clinical benefits are well established, the biomechanical mechanisms underlying functional improvement remain fragmented in the literature and are rarely synthesized quantitatively.

This dissertation conducted a systematic review with meta-analysis to investigate the biomechanical effects of exercise-based interventions in individuals with CNLBP. A total of 39 studies were included and …

The Immune Hangover: Understanding The Influence Of Alcohol Use, Abstinence, And Post-Abstinence Drinking On Monocyte Plasticity, Madison B. Blanton

Theses and Dissertations--Pharmacy

Alcohol consumption is widespread in the United States, with 80% of individuals aged 12 and older reporting alcohol use and 1-in-4 engaging in risky drinking behaviors. Alcohol misuse heightens susceptibility to infections and delays wound healing, indicating a disrupted immune system. Previous studies show alcohol rewires immune cells, especially monocytes and macrophages, which play critical roles in tissue homeostasis and host defense.

Using a rhesus macaque model of ethanol self-administration, we demonstrate that after 6-months of drinking, monocytes exhibit decreased cytokine production and significant transcriptomic changes, indicating a hypo-inflammatory state. In contrast, 12-months of chronic alcohol use induces hyperinflammatory responses, …

Synthesis And Characterization Of Glass-Ceramic Nanoparticles And Nanobubbles For Integration Into Bone Regenerative Biomaterials, Sun Latt

Honors Undergraduate Theses

Osteoporosis affects over 200 million individuals worldwide and is characterized by an imbalance between osteoclastic bone resorption and osteoblastic bone formation, leading to fragility fractures that significantly diminish quality of life. Current clinical bone cements, such as poly(methyl methacrylate), are limited by poor osseointegration, toxic monomers, and an inability to address the underlying pathophysiology of osteoporosis. This work presents the synthesis, characterization, and systematic in vitro evaluation of a sol-gel-derived, magnesium-incorporated glass-ceramic (GC) nanoparticle within the CaO-MgO-SiO₂ system for incorporation into a novel hydrogel bone cement and bioresorbable magnesium implants. XRD confirmed a biphasic amorphous-crystalline diopside composition, and TEM …

A Chicken Model For Non-Invasive Diagnosis Of Infant Developmental Dysplasia Of The Hip (Ddh) Using Acoustic Transmission Measurements, Aliza Shah

Honors Undergraduate Theses

Developmental dysplasia of the hip (DDH) is a condition characterized by abnormal development and stability of the hip joint. In a healthy infant, the femoral head (ball) fits securely within the acetabulum (socket of the pelvis), allowing for proper joint function. In DDH, the relationship is disrupted, ranging from mild acetabular dysplasia to partial (subluxation) or complete dislocation of the femoral head. This condition represents a range of structural abnormalities that develop during early growth. The integrity of the hip joint is essential for physical mobility, and disruption of this structure can lead to significant functional impairment. DDH may result …

Use Of Transcranial Magnetic Stimulation As An Assessment Of Corticospinal Excitability In Individuals With Persistent Postural Perceptual Dizziness, Elizabeth Cornforth

Theses and Dissertations

Persistent postural-perceptual dizziness (PPPD) is a common, disabling, chronic vestibular disorder whereby individuals experience symptoms of non-vertiginous dizziness, unsteadiness, and sway or rocking that are present most hours of the day, most days of the week. Individuals with PPPD have been noted to have an increased burden of dizziness and reduced quality of life compared to other dizziness diagnoses. The cause of PPPD is not well understood which can lead to years of diagnostic testing, failed therapies, and poor symptom management. It is important to understand PPPD pathophysiology so that optimal treatment interventions can be developed for this disorder to …

Translational Research On Color Vision: From Mechanisms To Performance Enhancement In Diverse Settings, Jewearly Lundby

Theses & Dissertations

This dissertation investigated the mechanisms and applications for optimizing color vision performance across diverse contexts. In a world where color cues augment critical decisions to optimize performance and safety in transportation (e.g., aviation, railway), military, law enforcement, medical diagnostics, and myriad occupational tasks, deficiencies in color perception pose significant challenges. By uniting four interrelated studies, this work explored intrinsic retinal processes, assistive technologies for deficiencies, and novel pathways that challenge conventional understandings of vision. The research bridged fundamental vision science with applications in occupational settings, low vision rehabilitation, and clinical diagnostics, ultimately aiming to optimize color performance.

The first study …

Sik2 Inhibitor Grn-300 Enhances Sensitivity To Paclitaxel Treatment In Triple-Negative Breast Cancer, Marc A. Pina

Dissertations and Theses (Open Access)

Breast cancer is one of the most frequently diagnosed cancers worldwide, with approximately 15% classified as Triple-Negative Breast Cancer (TNBC). TNBC lacks expression of estrogen (ER) and progesterone (PR), and does not overexpress HER-2, leaving patients without effective targeted therapies. As a result, treatment primarily relies on chemotherapy, most commonly paclitaxel, a taxane that stabilize microtubules, disrupts chromosome separation and induces apoptosis. However, TNBCs are an aggressive cancer subtype, and patients often will develop resistance after a few rounds of chemotherapy. This study addresses a critical unmet need for more effective TNBC therapies by targeting Salt-Inducible Kinase 2 (SIK2), which …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

Acceptability Of Corticosteroid Use In The Treatment Of Infant Bronchiolitis: Utilizing The Theoretical Framework Of Acceptability To Design Research Instruments, Caroline R. Smetanka

Capstone Experience: Master of Public Health

Bronchiolitis is the leading cause of hospitalization among infants under six months, yet treatment remains largely supportive due to clinical guidelines that discourage pharmacologic intervention. Recent research suggests that bronchiolitis is not a uniform condition, and a subgroup of infants (those classified within “Profile A”) may benefit from targeted corticosteroid therapy. However, these treatments remain outside current clinical guidelines, and their successful adoption depends on stakeholder acceptability. This Capstone project developed and refined four data collection instruments- two questionnaires and two interview guides- designed to assess how healthcare providers and caregivers perceive the acceptability of corticosteroid treatment for Profile A …

Colostrum Extracellular Vesicle Are Neuroprotective In The Mptp Intoxicated Mouse Model Of Parkinson's Disease, Samia Akter

Theses & Dissertations

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. Dopaminergic neuronal loss in the substantia nigra and the formation of Lewy bodies are the disease pathological hallmarks. We demonstrate that bovine colostrum extracellular vesicles (EVs) induce anti-inflammatory and neuroprotective activities during MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intoxication. Treatment these mice with colostrum EVs reduced the extent of activated microglia and neurodegenerative activities. RNA sequencing and transcriptomic analysis revealed a significant decrease in pro- inflammatory responses, as well as reduced recruitment and activation of immunocytes in affected brain tissues. Decreased expression of pro-inflammatory cytokines and chemokines, as well as suppressed canonical inflammasomes, was …

Therapeutic Potential Of Sglt2 Inhibitors In A Repeated Love Dose Cisplatin Model., Dianet C. Sanchez

Electronic Theses and Dissertations

Cisplatin is a potent chemotherapeutic, thirty percent of patients develop Acute Kidney Injury (AKI). These patients are ten times more likely to develop chronic kidney disease (CKD). Sodium-glucose-cotransporter-2-inhibitors (SGLT2i), FDA approved for diabetes, has shown protection in multiple mouse models of AKI-CKD. We hypothesize SGLT2i can protect the kidney in a model of repeated low dose cisplatin with/without cancer. B6:129 mice with/without lung adenocarcinoma (Lung-adeno) were treated daily with SGLT2i dapagliflozin (10mg/kg)/vehicle control. After seven days, weekly cisplatin (7mg/kg)/vehicle control was initiated for 3-4 weeks. Following final cisplatin dose, kidney function, injury, fibrosis, inflammation was assessed. SGLT2i treatment attenuated alterations …

Impact Of S-Phase Kinase Protien 2 Blockades On Hematopoetic Stem Cell Metabolism, Nicole Elmaraghy

Electronic Theses, Projects, and Dissertations

Hematopoietic stem and progenitor cells (HSPCs) quiescence is vital for the success of bone marrow transplantation, as it preserves long term self- renewal and prevents premature exhaustion (Takubo et al., 2013; Wilson et al., 2008). However, bone marrow transplant (BMT) failure remains a clinical challenge, often due to lack of long-term engraftment and insufficient stress reliance. Both of these characteristics are tightly linked to disrupted stem cell quiescence and metabolic imbalance (Anso et al., 2017; Vannini et al., 2016). One key player is S-phase kinase protein (SKP2), an E3 ubiquitin ligase that targets cell cycle inhibitors, like p27, for proteosome …

Advancing Novel Contrast Agents For Applications In Fluorescence-Guided Neurosurgery Using Fluorescence Cryotomography, Augustino Vittorio Scorzo

Dartmouth College Ph.D Dissertations

Fluorescence guided surgery (FGS) is an emerging surgical technique that aims to help surgeons identify tissue types to assist in surgical decision making - ideally providing “cut-by-color” guidance. A primary application for this approach is the identification of tumor tissue to achieve more accurate and complete tumor removal while simultaneously minimizing damage to surrounding normal tissue. The cornerstone of tumor visualization for FGS is the administration of fluorescent contrast agents, or in some cases metabolic precursors, designed to accumulate specifically in tumor tissue, and a wide range of agents that use different targeting mechanisms are currently under investigation. Although these …

Mechanistic Insights Into The Flash Effect: The Role Of Oxygen And Radiation Chemistry In Ultra-High Dose Rate Radiation Therapy, Jacob Pierce Sunnerberg

Dartmouth College Ph.D Dissertations

The development of new cancer therapies focuses on widening the therapeutic ratio between tumor control and normal tissue toxicity. Over the last decade, ultra-high dose rate (UHDR) radiation therapy, commonly known as FLASH radiotherapy (FLASH-RT), has shown promising potential to reduce normal tissue toxicity while maintaining tumor control. However, the underlying mechanisms of the FLASH effect remain poorly understood. This thesis explores the radiation-chemical basis of FLASH-RT, focusing on the role of oxygen and reactive oxygen species in modulating biological outcomes.

A comprehensive set of in vitro studies demonstrated that UHDR delivery significantly alters radiation chemistry compared to conventional dose …

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, …

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 …

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 …

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 …

Elucidating The Multi-Omics Of Early-Onset Colorectal Cancer, Jumanah Alshenaifi

Dissertations and Theses (Open Access)

The incidence and mortality rates of sporadic early-onset colorectal cancer have increased in recent decades, but there is no clear etiological basis for this trend. EOCRC is commonly defined as colon and rectal cancers diagnosed before the age of 50 years. The rising incidence of EOCRC has made it the second most common cancer and the third leading cause of cancer death in this age group. The rising incidence of EOCRC is also documented internationally in more than 20 countries across different continents. Clinically, EOCRC has a distinct, more aggressive clinical profile than LOCRC. While approximately 15% of EOCRC cases …