Medical Specialties Commons^™

The Mitochondria As An Emerging Target Of Self- Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly, Evelyn Winter, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

Acute lymphocytic leukemia (ALL) is the most common leukemia in children, with the T-cell subtype (T- ALL) accounting for 15% of those cases. Despite advancements in the treatment of T-ALL, patients still face a dismal prognosis following their first relapse. Relapse can be attributed to the inability of chemotherapy agents to eradicate leukemia stem cells (LSC), which possess self-renewal capabilities and are responsible for the long-term maintenance of the disease. Mitochondria have been recognized as a therapeutic vulnerability for cancer stem cells, including LSCs. Mitocans have shown promise in T-ALL both in vitro and in vivo, with some currently in …

Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn- Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger

Markey Cancer Center Faculty Publications

MYCN-amplification is a genetic hallmark of ~40% of high-risk neuroblastomas (NBs). Altered glycosylation is a common feature of adult cancer progression, but little is known about how genetic signatures such as MYCN-amplification alter glycosylation profiles. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased core fucosylated glycan abundance within neuroblast-rich regions of human MYCN-amplified NB tumors. GDP-mannose 4,6-dehydratase (GMDS) is responsible for the first-committed and rate-limiting step of de novo GDP-fucose synthesis. High GMDS expression was found to be associated with poor patient survival, advanced stage disease, and MYCN-amplification in human NB tumors. Chromatin immunoprecipitation and promoter reporter assays …

A Comparison Of Commonly Utilized Diagnostic Biopsy Techniques For Pediatric Patients With Cancer: A Systematic Review By The Apsa Cancer Committee., Martha Teke, Barrie S. Rich, Ashley Walther, Dana Schwartz, Lucas A. Mcduffie, Gisela Butera, Jonathan P. Roach, David H. Rothstein, Dave R. Lal, Kimberly Riehle, Andres Espinoza, Nicholas Cost, Elisabeth Tracy, David Rodeberg, Timothy Lautz, Jennifer H. Aldrink, Erin G. Brown

Surgery Faculty Publications

BACKGROUND: Historically, surgical biopsy (SB) for diagnosis of pediatric solid tumors was considered necessary to provide adequate tissue for histologic and molecular analysis. Less invasive biopsy techniques such as image-guided core needle biopsy (CNB), have shown comparable accuracy with decreased morbidity in some adult studies. However, data regarding the safety and efficacy of CNB in pediatric tumors is limited. This study's aim was to assess the overall rate of successful diagnosis and safety of CNB compared to SB in children with malignancies.

METHODS: A PRISMA compliant systematic review was performed in MEDLINE via PubMed, Embase and CINAHL Plus database searches …

Establishing A Student-Run Mobile Clinic In Appalachian Kentucky: A Community-Based Pilot Program To Address Health Inequities, Bradley A. Firchow, John C. Cornelius

Journal of Appalachian Health

The establishment of a student-run mobile clinic in Morehead, Kentucky, led by students from the University of Kentucky College of Medicine’s (UKCOM) Rural Physician Leadership Program (RPLP), aims to address health inequities in rural Appalachian communities. This pilot program is designed to serve vulnerable populations, including the unhoused, by delivering free, accessible healthcare services directly to underserved populations. This program serves as a model for expanding access to healthcare in rural regions while promoting a collaborative, community-based approach to addressing social determinants of health.

Current Attitudes And Barriers Among Appalachian Patients Towards Orthopaedic Surgery, Dylan Smith Md, Justin B. West Ms, Wade Smith Md, Micah Macaskill Md, Jonathan Lash, Matthew W. Bullock Do, Mpt

Journal of Appalachian Health

Introduction: This study explores the challenges faced by residents of rural West Virginia in accessing orthopaedic care due to geographic and socioeconomic barriers.

Purpose: This study seeks to survey rural West Virginia residents about their attitudes and experiences regarding access to orthopaedic care in southern West Virginia.

Methods: A total of 132 electronic surveys were collected from rural West Virginia residents during an appointment with their primary care provider located at an affiliated outreach clinic. The survey was designed to investigate various factors influencing their access to orthopaedic care.

Results: Delays in seeking orthpaedic care are common in rural West …

Plasma S100Β Is A Predictor For Pathology And Cognitive Decline In Alzheimer’S Disease, Geetika Nehra, Bryan J. Maloney, Rebecca Smith, Wijitra Chumboatong, Erin L. Abner, Peter T. Nelson, Björn Bauer, Anika M. S. Hartz

UK CARES Faculty Publications

Background Blood–brain barrier dysfunction is one characteristic of Alzheimer’s disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment.

Methods We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who …

Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …

Metformin In Overcoming Enzalutamide Resistance In Castration-Resistant Prostate Cancer, Kendall Simpson, Derek B. Allison, Daheng He, Jinpeng Liu, Chi Wang, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Androgen deprivation is the standard treatment for patients with prostate cancer. However, the disease eventually progresses as castration-resistant prostate cancer (CRPC). Enzalutamide, an androgen receptor inhibitor, is a typical drug for treating CRPC and with continuous reliance on the drug, can lead to enzalutamide resistance. This highlights the necessity for developing novel therapeutic targets to combat the gain of resistance. Metformin has been recently investigated for its potential antitumorigenic effects in many cancer types. In this study, we used enzalutamide and metformin in combination to explore the possible rescued efficacy of enzalutamide in the treatment of enzalutamide-resistant CRPC. We first …

Portable Multi-Parametric Microscopy For Noninvasive Metabolic And Vascular Imaging Of Orthotopic Tongue Cancer Models In Vivo, Pranto Soumik Saha, Jing Yan, Caigang Zhu

Markey Cancer Center Faculty Publications

Significance: Precise imaging of tumor metabolism with its vascular microenvironment becomes emerging critical for cancer research because increasing evidence shows that the key attribute that allows a tumor to survive therapies is metabolic and vascular reprogramming. However, there are surprisingly few imaging techniques available to provide a systems-level view of tumor metabolism and vasculature in vivo on small animals for cancer discoveries.

Aim: We aim to develop a new multi-parametric microscope that can faithfully recapitulate in vivo metabolic and vascular changes with a wide field of view and microscope-level resolution to advance cancer-related investigations. To maximize the ease and accessibility …

Dihydropyrimidine Enzyme Activity And Its Effect On Chemotherapy Toxicity: Importance Of Genetic Testing, Alexia Shamaei Zadeh, Danielle Roberts, Abby Williams, Deepali Pandey, John L. Villano

Markey Cancer Center Faculty Publications

Purpose

Patients with partial or complete DPD deficiency have decreased capacity to degrade fluorouracil and are at risk of developing toxicity, which can be even life-threatening.

Case

A 43-year-old man with moderately differentiated rectal adenocarcinoma on capecitabine presented to the emergency department with complaints of nausea, vomiting, diarrhea, weakness, and lower abdominal pain for several days. Laboratory findings include grade 4 neutropenia (ANC 10) and thrombocytopenia (platelets 36,000). Capecitabine is used as a component of first-line adjuvant therapy by approximately 2 million patients worldwide each year. Capecitabine is metabolized to fluorouracil via the enzyme dihydropyrimidine dehydrogenase (DPD). With worsening pancytopenia …

A Knowledge-Based Planning Model To Identify Fraction-Reduction Opportunities In Brain Stereotactic Radiotherapy, Shane Mccarthy, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Objective: To develop and validate a HyperArc-based RapidPlan (HARP) model for three-fraction brain stereotactic radiotherapy (SRT) plans to then use to replan previously treated five-fraction SRT plans. Demonstrating the possibility of reducing the number of fractions while achieving acceptable organs-at-risk (OAR) doses with improved target biological effective dose (BED) to brain lesions. Methods: Thirty-nine high-quality clinical three-fraction HyperArc brain SRT plans (24–27 Gy) were used to train the HARP model, with a separate 10 plans used to validate its effectiveness. Fifty-eight five-fraction HyperArc brain SRT plans (30–40 Gy) attempted to be retrospectively replanned for three fractions scheme using the HARP …

An Investigation Into The Feasibility And Efficacy Of Stereotactic Radiosurgery For 1–3 Cm Single Brain Lesions On The Ring-Mounted Halcyon Linac, Kristin J. Hazelwood, Shane Mccarthy, Josh Misa, David Castelvetere, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose: An evaluation of the accuracy, safety, and efficiency of the Halcyon ring delivery system (RDS) for stereotactic radiosurgery (SRS) treatment to relatively small (1–3 cm) brain lesions.

Methods: After completing the extensive in-house quality assurance checks including Winston–Lutz test and independent dose verification via MD Anderson IROC SRS head phantom irradiation on Halcyon, fifteen brain SRS patients previously treated with a single dose of 20 Gy on TrueBeam (6MV-FFF) with HyperArc geometry were retrospectively replanned on Halcyon (6MV-FFF). Plan quality metrics including conformity index (CI), gradient index (GI), gradient distance (GD), PTV coverage, gross tumor volume (GTV) dose, heterogeneity …

A Predictive Quality Assurance Model For Patient-Specific Gamma Passing Rate Of Hyperarc-Based Stereotactic Radiotherapy And Radiosurgery Of Brain Metastases, Shane Mccarthy, Brent Harrison, Damodar Pokhrel

Radiation Medicine Faculty Publications

Objective: Measurement-based patient specific quality assurance (PSQA) is an increasingly debated topic among medical physicists. Developments like online adaptive radiotherapy and same-day stereotactic treatments limit the time to do measurement-based PSQA. Herein, we develop a predictive machine learning model to supplement PSQA by predicting the gamma passing rate (GPR) per stereotactic arc. This streamlines PSQA, providing planners the insight to replan potentially sub-optimal plans, to mitigate machine time inefficiencies.

Methods: 122 patients that had previously received HyperArc stereotactic radiosurgery/radiotherapy on a TrueBeam LINAC (Millenium 120 MLCs, 6MV-FFF) were used to generate a long short-term memory (LSTM) recurrent neural network to …

Automated Hippocampal Sparing Whole Brain Radiotherapy With Simultaneous Integrated Boost For Multiple Brain Metastases: Halcyon, Hyperarc On Truebeam, And Coplanar Truebeam, Shane Mccarthy, Ryan Clark, Anthony Magliari, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose: To demonstrate the ease and feasibility that hippocampal sparing whole brain (WB) simultaneous integrated boost (HSWB-SIB) plans can be generated using knowledge-based planning and Eclipse Scripting Application Programming Interface (ESAPI) for three different modalities, HyperArc on TrueBeam (TB-HA), a coplanar beam arrangement on TrueBeam (TB-Co), and the ring-mounted Halcyon LINAC (Hal).

Methods: Twelve patients with 2–14 brain metastases were retrospectively replanned for HSWB-SIB using a published HSWB RapidPlan model with modifications for the automated addition of SIB to metastases. Prescribed dose was 30 Gy to the WB planning target volume (PTV) and 50 Gy to the metastases in 10 …

Feasibility Of Treatment Planning With Hyperarc Stereotactic Radiosurgery Methods For Ocular Tumors, Chase Cochran, Shane Mccarthy, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose/objectives

Currently, ocular disease is primarily managed with COMS plaque brachytherapy. Various stereotactic radiosurgery (SRS) platforms have also been employed, yet widespread access remains a challenge. Herein, we demonstrate the feasibility of using the HyperArc SRS system to provide an additional platform for the treatment of ocular malignancies.

Materials/methods

Twenty previously treated COMS patients with ocular melanoma were selected for a retrospective HyperArc SRS planning study. The average gross tumor volume (GTV) derived from MRI was 1.19 ± 0.60 cc. Planning target volumes (PTV) were generated from a 2 mm expansion of the GTVs. HyperArc plans were created for a …

Establishing A Variant Allele Frequency Cutoff For Manual Curation Of Medical Exome Sequencing Data, Kate Sears, Caylin Hickey, Ryan Vincent, Jennifer Stocks-Candelaria, Jason Tate, Cody Bumgardner, Shulin Zhang, Justin B. Miller

Pathology and Laboratory Medicine Faculty Publications

Medical exome sequencing pipelines consist of various preprocessing steps to prioritize credible causal variants before a pathologist or variant curation scientist manually interprets potential findings that are then reported to patients. The variant allele frequency (VAF), reported as the fraction of sequencing reads supporting a variant call, can be used to screen for technical artifacts, yet a specific filtering threshold has yet to be established. A total of 13,122 manually curated variants, sequenced from 289 patients using the Agilent SureSelect Focused Exome enrichment kit at the University of Kentucky Clinical Genomics laboratory from October 2019 to May 2023, were evaluated. …

Converting “Nonlesional” Imaging Occult Epilepsy Into A Focal Lesional Entity Using Advanced Imaging Techniques: Illustrative Case, Muhammad Usman Khalid, Flavius D. Raslau, Valentinos Zachariou, David Powell, Zachary Winder, Ryan Cloyd, Sarah Helen Thomas, John Kuipers, Rachel Ward Mitchell, Riham H. El Khouli, Timothy J. Ainger, Sally Mathias, Farhan A. Mirza

Neurosurgery Faculty Publications

BACKGROUND To achieve the best possible outcome in surgical refractory epilepsy, the seizure onset zone must be accurately identified prior to treatment.

OBSERVATIONS A 38-year-old man presented with tonic-clonic and focal seizures 2–3 times per month, refractory to antiseizure medications. Scalp EEG, MRI, PET, ictal SPECT, magnetoencephalography, and stereo-EEG (SEEG) did not provide conclusive seizure onset zone localization. Subsequently, the patient was included in the authors’ ongoing postictal arterial spin labeling (ASL) study and additional postprocessing was performed with a morphometric analysis program (MAP) and texture analysis. Using these results, the authors reexamined the original structural MR images, with attention …

Efficacy Of Deferoxamine Mesylate In Serum And Serum-Free Media: Adult Ventral Root Schwann Cell Survival Following Hydrogen Peroxide-Induced Cell Death, Yee Hang Ethan Ma, Abhinay R. Putta, Cyrus H. H. Chan, Stephen R. Vidman, Paula V. Monje, Giles W. Plant

Neurosurgery Faculty Publications

Schwann cell (SC) transplantation shows promise in treating spinal cord injury as a pro-regenerative agent to allow host endogenous neurons to bridge over the lesion. However, SC transplants face significant oxidative stress facilitated by ROS in the lesion, leading to poor survival. deferoxamine mesylate (DFO) is a neuroprotective agent shown to reduce H₂O₂-induced cell death in serum-containing conditions. Here we show that DFO is not necessary to induce neuroprotection under serum-free conditions by cell survival quantification and phenotypic analysis via immunohistochemistry, Hif1α and collagen IV quantification via whole cell corrected total cell fluorescence, and cell death …

Folliculin (Flcn) In Thyroid Tumors: Incidence, Significance, And Role As A Driver Gene And Secondary Alteration, Faisal Hassan, Camryn Slone, Robert J. Mcdonald, Julie C. Dueber, Adeel M. Ashraf, Melina Windon, Oliver J. Fackelmayer, Cortney Y. Lee, Therese J. Bocklage, Derek B. Allison

Pathology and Laboratory Medicine Faculty Publications

Thyroid carcinomas are driven by diverse molecular alterations, but the tumor suppressor gene folliculin (FLCN), best known for its role in Birt–Hogg–Dubé (BHD) syndrome, has received limited attention in thyroid tumors. Here, we describe two thyroid tumors with pathogenic FLCN alterations—one germline and one somatic—and analyze the broader prevalence and significance of FLCN in thyroid carcinomas using multiple large sequencing datasets, including ORIEN-AVATAR. Patient 1, with a germline FLCN mutation and a history of BHD syndrome, presented with a well-circumscribed oncocytic adenoma. Molecular testing confirmed biallelic FLCN inactivation, but no additional mutations or aggressive features were observed, and the patient …

Characterizing And Targeting The Non-Catalytic Functions Of Phosphatase Of Regenerating Liver 3 (Prl-3) In Oncogenesis And Cancer Progression, Jeffery T. Jolly

Theses and Dissertations--Molecular and Cellular Biochemistry

Phosphatase of Regenerating Liver 3 (PRL-3) is frequently upregulated in various cancers and is associated with poor patient prognosis. Although traditionally studied for its phosphatase activity, PRL-3 also interacts with the CNNM family of magnesium transporters through its catalytic site, and these two functions are mutually exclusive at any given time. Most previous studies relied on a commonly used PRL-3 mutation that disrupts both phosphatase activity and CNNM binding, making it challenging to determine which function drives its oncogenic effects. To address this gap in the field, I utilized a panel of PRL-3 mutants that selectively disrupt either phosphatase activity …

Complete High Thoracic Spinal Cord Injury Causes Bowel Dysfunction In Mice, Olivia Wireman, Ellie L. Sams, Lynnet E. Richey, Gabrielle V. Hammers, Andrew N. Stewart, William M. Bailey, Samir P. Patel, John C. Gensel

Spinal Cord and Brain Injury Research Center Faculty Publications

Bowel dysfunction, is a prevalent and life-impacting comorbidity of spinal cord injury (SCI) with no long-term treatment available. SCI-induced colon changes including motility and fibrosis are understudied as are strategies to address SCI bowel dysfunction. This need remains partly due to the lack of a mouse model that recapitulates the human condition. We hypothesized that a high thoracic spinal transection in mice would trigger bowel dysfunction with coincident colon pathology similar to humans and rats after SCI. We observed bowel dysfunction as increased fecal pellet numbers within the colon, smaller pellet size, and decreased motility. Fecal pellets numbers in the …

Early Changes In Inflammation-Related Proteins In The Cerebrospinal Fluid And Plasma Of Patients With Aneurysmal Subarachnoid Hemorrhage, David J. Braun, Kevin W. Hatton, Justin F. Fraser, Robert M. Flight, Hunter N. B. Moseley, Caleb S. Bailey, Josh M. Morganti, Bingqing Zhang, Ishara S. Ariyapala, Tae K. Kim, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is a relatively uncommon but high mortality form of stroke that can result in long-lasting disability. A better understanding of key neuroinflammatory changes during the early phase (< 72 h) may provide potential avenues of treatment.

Methods

In an attempt to understand these early changes, we recruited 7 aSAH patients for profiling of longitudinal plasma and cerebrospinal fluid (CSF) proteins at up to 72 h post injury. We additionally compared this to control plasma obtained previously from healthy elderly volunteers. Using the Alamar Biosciences NULISAseq platform, we obtained a comprehensive picture of early peripheral and central inflammatory changes after injury.

Results

This study …

Nicorandil Treatment Improves Survival And Spatial Learning In Aged Granulin Knockout Mice, Dana M. Niedowicz, Wang-Xia Wang, Paresh Prajapati, Yu Zhong, Shuling X. Fister, Colin B. Rogers, Pradoldej Sompol, David K. Powell, Indumati Patel, Christopher M. Norris, Kathryn E. Saatman, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Mutations in the human granulin (GRN) gene are associated with multiple diseases, including dementia disorders such as frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). We studied a Grn knockout (Grn-KO) mouse model in order to evaluate a potential therapeutic strategy for these diseases using nicorandil, a commercially available agonist for the ABCC9/Abcc9-encoded regulatory subunit of the “K⁺ATP” channel that is well-tolerated in humans. Aged (13 months) Grn-KO and wild-type (WT) mice were treated as controls or with nicorandil (15 mg/kg/day) in drinking water for 7 months, then tested for neurobehavioral …

Gait Variability As A Marker Of White Matter Integrity In Individuals With Down Syndrome, Elizabeth M. Leach, David K. Powell, Amanda C. Glueck, Elizabeth Head, Moaz W. Ibrahim, Amelia J. Anderson-Mooney, Kathryn L. Van Pelt, Jordan P. Harp, Frederick A. Schmitt, Ahmed A. Bahrani

Sanders-Brown Center on Aging Faculty Publications

Introduction: Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS.

Methods: The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years).

Results: DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores …

Disrupted Calcium Dynamics In Reactive Astrocytes Occur With End Feet–Arteriole Decoupling In An Amyloid Mouse Model Of Alzheimer’S Disease, Blaine Weiss, John C. Gant, Ruei-Lung Lin, Jenna L. Gollihue, Colin B. Rogers, Susan D. Kraner, Edmund B. Rucker, Yuriko Katsumata, Yang Jiang, Peter T. Nelson, Donna M. Wilcock, Pradoldej Sompol, Olivier Thibault, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

While cerebrovascular dysfunction and reactive astrocytosis are extensively characterized hallmarks of Alzheimer's disease (AD) and related dementias, the dynamic relationship between reactive astrocytes and cerebral vessels remains poorly understood. Here, we used jGCaMP8f and two-photon microscopy to investigate calcium signaling in multiple astrocyte subcompartments, concurrent with changes in cerebral arteriole activity, in fully awake 7- to 8-month-old male and female 5xFAD mice, a model for AD-like pathology, and wild-type (WT) littermates. In the absence of movement, spontaneous calcium transients in barrel cortex occurred more frequently in astrocyte somata, processes, and perivascular regions of 5xFAD mice. However, evoked arteriole dilations (in …

Demonstration Of An Enhanced Dosing Pattern For Debulking Large And Bulky Unresectable Tumors Via Differential Hole-Size Spatially Fractionated Radiotherapy, Joshua Misa, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose/objective

We propose a novel lattice deployment for spatially fractionated radiotherapy (SFRT) treatments. In this approach, a larger diameter high-dose sphere is centrally placed in the bulky tumor mass and surrounded by smaller diameter high-dose spheres.

Materials/methods

Thirty SFRT patients (10 head and neck [HN], 10 abdominal/pelvis, and 10 chest/lung cases) treated with an MLC-based crossfire method were retrospectively analyzed. Eleven differential hole-size lattice patterns were benchmarked against the clinically delivered SFRT plans (1 cm diameter cylinders, 2 cm spacing) and the standard uniform lattice pattern (1.5 cm diameter spheres, 3 cm spacing). These patterns varied in core diameter (C: …

In Vitro Α/Β Ratio Variations In Cervical Cancer, With Consequent Effects On Equivalent Dose In 2 Gy Fraction In High-Dose-Rate Brachytherapy, Cameron Thayer-Freeman, Brien Washington, Denise Fabian, Dennis C. Cheek, William St. Clair, Mark E. Bernard, Wei Luo

Radiation Medicine Faculty Publications

Purpose: To determine the distributions of published α/β values measured in vitro and the resulting uncertainties in the equivalent dose in 2 Gy fractions (EQD ₂ ) when applied to high-dose-rate brachytherapy (HDR-BT) for cervical cancer.

Methods and Materials: An analysis of 98 published α/β values from 31 papers was conducted, spanning 23 cervical cancer cell lines. Values were further divided into squamous cell carcinoma and adenocarcinoma histologies. Probability distributions were fit to histograms using the bootstrapped Kolmogorov-Smirnov goodness-of-fit test. Both average and most probable α/β values for cervical cancer were determined. The probability distributions were then applied to three …

Innovative Biomechanical And Engineering-Based Assessments Of Hip Mechanics In Individuals With Hip-Related Pain, Holly M. Stanze

Theses and Dissertations--Kinesiology and Health Promotion

Individuals with hip-related pain exhibit altered movement patterns, and worse fear of movement (kinesiophobia), compared to asymptomatic controls. Exacerbation of hip pain during movement and the role of hip symptom duration may help further our understanding of specific movement patterns that are associated with hip-related pain. A better understanding of the potential connections between hip-related symptom duration, kinesiophobia, hip pain during movement, and lower limb mechanics in those with hip-related pain may allow for more efficient referrals to clinicians and lead to more effective rehabilitation. In addition, the impact of hip-related pain on intra-articular hip loading patterns is not well …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Immune Dynamics And B Cell Contributions To Neuroplasticity And Recovery After Stroke, Thomas A. Ujas

Theses and Dissertations--Neuroscience

This dissertation explores the dynamic interplay between the immune system and the brain across stroke and aging using clinical, post-mortem, and pre-clinical models. The immune system plays critical roles in shaping brain function, responding to injury, and mediating recovery. These studies aim to enhance our understanding of neuroimmune dynamics across spatial and temporal dimensions.

In the first part, we conducted longitudinal sampling of aneurysmal subarachnoid hemorrhage (aSAH) patients to track immune cell and cytokine changes at days 3, 5, 7, 10, and 14 post-stroke, with a focus on delayed cerebral ischemia (DCI), a common complication. We observed distinct temporal patterns, …