Digital Commons Network^™

Sufex-Enabled Stereospecific Deoxygenative Diversification Of Alcohols, Amaechi Odoh

All Dissertations

Alcohols represent an important class of functional group in organic synthesis and medicinal chemistry, given that they are structurally diverse and prevalent in many natural products, biomolecules and renewable feedstocks. As such, they are highly attractive precursors for building-block synthesis, late-stage functionalization, and numerous synthetic transformations. However, existing strategies for the deoxygenative diversification of alcohols operate under constrained conditions, often leading to competing pathways (such as elimination), poor stereospecificity, low efficiencies, and limited substrate compatibility. To address these challenges, we have developed a conceptually novel use of sulfonyl fluorides as bifunctional reagents for the one-step deoxygenative diversification of complex alcohol …

Neural Operator And Physics-Informed Deep Learning Approaches For Inverse Design Of Composites And Manufacturing Processes, Minglei Lu

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In this dissertation, artificial intelligence (AI) models are designed and used to accelerate inverse design of composites and manufacturing processes. The critical bottlenecks in machine learning (ML) including data availability, data quality, model generalization and adaptation, interpretability, physical consistency, and the ’black box’ nature of models for the inverse design are addressed. And the proposed AI models are tested under different engineering scenarios. Firstly, a fast deep neural operator (DNO) structure was developed to significantly reduce training time. This model was tested in the context of additive manufacturing, a transformative industrial technology that allows for the creation of materials with …

An Exploration Of The Role Of The Disorienting Dilemma In Professional Learning For Academic Library Instructors, Anne Grant

All Dissertations

This study uses an explanatory sequential mixed method design to understand more about the learning experiences of academic library instructors from 2- and 4-year institutions during a professional development session centered on using Universal Design for Learning. Transformative Learning Theory served as the lens to examine data, and the concept of a disorienting dilemma that serves as a trigger for deep learning in adults. The experiences of the participants are explained using data from a pre- and post-survey as well as semi-structured interviews with participants to learn more about factors that may predict whether or not participants experience a disorienting …

Integrating Social And Ecological Insights In The Management Plan For An Emerging Conservation Landscape: Kanha-Pench Corridor, Hrishita Negi

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Since its inception in 1973, Project Tiger, which laid the groundwork for India's tiger conservation program, has grown from 9 to 53 intensively monitored and managed tiger reserves. With an increase in tigers' permanent occupancy outside of designated tiger reserves, one of the many challenges confronting India's tiger conservation has been managing its success, with a particular emphasis on this spillover population that ranges extensively in human-dominated, multi-use forest landscapes. This research illustrates the application of a participatory modeling approach to integrate human dimensions with ecological knowledge about tigers in a previously identified forest corridor in Central India. Key dimensions …

Optimization Of Polymeric Micelles As A Delivery System For Crispr/Cas9 Ribonucleoprotein, Lucian Williams

All Dissertations

Clustered regularly interspaced short palindromic repeats (CRISPR) is an adaptive immune system in bacteria that has been harnessed to perform precise genetic modifications in mammalian cells. Among CRISPR-associated (Cas) proteins, Cas9 has emerged as a transformative tool in gene editing due to its simplicity, high specificity, and versatility compared to the other Cas proteins and gene-editing technologies. Despite its potential to cure genetic disorders, the clinical application of Cas9 has been hindered by challenges such as immunogenicity, off-target effects, and low delivery efficiency. To address these issues, this dissertation explores using polymeric nanoparticle systems to encapsulate and protect Cas9 and …

Composites From The Reaction Of Elemental Sulfur With Post-Consumer Plastic/Packaging Materials And Food Waste, Katelyn Derr

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Plastic waste is a growing epidemic. While advancements have been made in the chemical recycling of plastics, most waste plastics are deposited in the environment or landfills where they leech into their surroundings, creating a threat to ecological health. The reaction of these waste materials with elemental sulfur, an underutilized byproduct of the fossil fuel refining industry, to create high-sulfur content materials is a promising route to address the chemical recycling of plastics and proposes alternative building materials to environmentally unfriendly mineral-based materials. Single-use plastics such as food and beverage packaging account for a significant amount of plastic waste. The …

Advancing Visual Geometric Perception: Camera-Based Depth, Reconstruction, And Active Vision, Ziyue Feng

All Dissertations

The advancement of autonomous driving technology and intelligent robotic applications has emerged as a focal point in the realm of autonomy. One of the driving forces behind this trend is the profound understanding of the environment, and at the core of this endeavor lies the three-dimensional geometric perception. This dissertation embarks on a comprehensive exploration of this domain, emphasizing the advances of depth prediction, 3D scene reconstruction, and active vision to enhance geometric perception and scene understanding capabilities in autonomous driving, embodied AI, and robotics. In the domain of depth prediction, this research addresses the challenges of accurately inferring three-dimensional …

Polymersomes As Chemotherapeutic Agents Towards Non-Invasive Treatment Of Glioblastoma, Molli Garifo

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Glioblastoma (GBM) accounts for over 66% of all malignant central nervous system and brain tumors with a 5-year survival rate below 5%, which has remained relatively unchanged over the last four decades. To bypass the most challenging barrier to treatment, the blood-brain barrier (BBB), one intracranial implant is clinically available for GBM treatment. However, this treatment produces severe adverse effects with no significant improvements in patient outcomes. Developing an improved delivery system with a more effective chemotherapy drug will provide more controlled and specific treatment through local delivery. In this dissertation, I evaluate a hyaluronic acid-b-polylactic acid (HA-PLA) polymersome system …

Cross-Interactions Of Amyloid Proteins: Implications For Aggregation Dynamics And Disease Pathology, Zhiyuan Song

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Amyloid aggregation is a pervasive form of protein misfolding implicated in the pathology of several prominent human diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and type 2 diabetes (T2D). These diseases are marked by the accumulation of amyloid fibrils and toxic oligomers, which are highly dynamic and heterogeneous, posing challenges for understanding their roles in disease progression. Despite significant advances in the diagnosis and management of these conditions, no definitive cure is available. We investigate amyloid aggregation and cross-seeding, with a focus on amyloid-beta (Aβ), tau, alpha-synuclein (αS), and human islet amyloid polypeptide (IAPP) through discrete molecular dynamics (DMD) …

An Efficient Computational Frameworks For Design And Analysis Of Metamaterials, Raj Pradip Khawale

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Advancement in additive manufacturing helps in building artificial lattice structures with unique properties that are not available in naturally occurring materials or in continuum structures. Specifically, beam-based lattices are well known for producing lightweight structures with very high strength, auxetic behavior, and energy absorption capabilities. In recent years, numerous research studies have been conducted on generating algorithms and frameworks to obtain unusual properties based on the variation in the cell geometry and material properties. However, the exploration of the full design space is hampered in practice primarily due to restrictions on cell tiling variation. Additionally, the lattices are very intricate, …

Genetic Testing And Anorexia Nervosa: Knowledge, Attitudes And Awareness, Sarah Ramsay

All Dissertations

This dissertation consists of three parts, each building on the results of the former, evaluating the treatment and research of anorexia nervosa (AN) from a healthcare genetics perspective. These three parts are bookended by an introduction and a conclusion summarizing key findings and providing suggestions for future work. First, in order to assess how Severe and Enduring Anorexia Nervosa (SE-AN) is defined in the literature, and inclusion of those with SE-AN in genetics research, a comprehensive literature review was performed. The review found a lack of consistent identification and inclusion of the SE-AN subtype in AN genetic study participants. Second, …

Agricultural Water Use In South Carolina - A Series Of Investigations To Support Long-Term Planning, Charles Pellett

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Agricultural water use in South Carolina has been the subject of some public debate. While there are several sources of information available, the accuracy of the relevant data has been called into doubt. Self-reported estimates may be biased; survey sampling and extrapolation methods yield wide ranges of uncertainty; and reporting compliance or response rate can change over time.

Agricultural water users self-report that their estimates of water use volumes are less accurate than the other major sectors of water use. Center pivot irrigation is the largest and fastest growing kind of agricultural water use in SC. Since the year 2000, …

Radiation-Induced Macrovessel/Microvessel Disease, Jun-Ichi Abe, Bryan G Allen, Andreas M Beyer, David Lewandowski, Kranti A Mapuskar, Michelle R Tamplin

Faculty, Staff and Student Publications

Radiation therapy (RT) is a cornerstone in cancer treatment (used in 50% of cases), yet challenges persist because damage to normal tissue through direct impact of radiation or bystander effects is inevitable. Injury of macrovessels by RT manifests as obstructive disease, which is akin to atherosclerotic disease. Historically observed in coronary arteries of patients treated for breast cancer and lymphoma, it also affects patients receiving contemporary therapy for lung and chest cancers. Moreover, radiation at various sites can lead to peripheral vascular disease. An aspect of radiation-induced injury that has received little attention is microvascular injury, which typically results from …

Keratinocyte Carcinomas In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Christina Boull, Yan Chen, Cindy Im, Alan Geller, Yadav Sapkota, Rebecca Howell, Miriam Conces, Louis S Constine, Leslie Robison, Yutaka Yasui, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: Childhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established.

Objective: Identify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS.

Methods: KC were identified among Childhood Cancer Survivor Study participants, a cohort of 5-year cancer survivors diagnosed < 21 years of age between 1970 and 1999 in North America. Cumulative incidence was estimated and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics.

Results: Among 25,658 participants, 1446 developed 5363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy). Mean lesion count was 3.7 with 26.1% experiencing ≥4. Radiotherapy imparted …

Artificial Intelligence Uncertainty Quantification In Radiotherapy Applications – A Scoping Review, Kareem A Wahid, Zaphanlene Y Kaffey, David P Farris, Laia Humbert-Vidan, Amy C Moreno, Jintao Ren, Tucker J Netherton, Stine Korreman, Guha Balakrishnan, Clifton D Fuller, David Fuentes, Michael J Dohopolski

Faculty, Staff and Student Publications

Background/purpose: The use of artificial intelligence (AI) in radiotherapy (RT) is expanding rapidly. However, there exists a notable lack of clinician trust in AI models, underscoring the need for effective uncertainty quantification (UQ) methods. The purpose of this study was to scope existing literature related to UQ in RT, identify areas of improvement, and determine future directions.

Methods: We followed the PRISMA-ScR scoping review reporting guidelines. We utilized the population (human cancer patients), concept (utilization of AI UQ), context (radiotherapy applications) framework to structure our search and screening process. We conducted a systematic search spanning seven databases, supplemented by manual …

Body Composition In Recurrent Prostate Cancer And The Role Of Steroidogenic Genotype, Neha Venkatesh, Rebecca S Tidwell, Yao Yu, Ana Aparicio, Amado J Zurita, Bilal A Siddiqui, Justin R Gregg, Paul G Corn, Efstratios Koutroumpakis, Jennifer L Mcquade, Daniel E Frigo, Patrick G Pilie, Chad Huff, Christopher J Logothetis, Andrew W Hahn

Faculty, Staff and Student Publications

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biological and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential changes in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: i) CT imaging of L3 prior to and after treatment; and ii) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. …

Assessment Of Racial Bias Within The Risk Analysis Index Of Frailty, Michael A Jacobs, Leslie R M Hausmann, Robert M Handzel, Susanne Schmidt, Carly A Jacobs

Faculty, Staff and Student Publications

Objective: Our objective was to assess potential racial bias within the Risk Analysis Index (RAI).

Background: Patient risk measures are rarely tested for racial bias. Measures of frailty, like the RAI, need to be evaluated for poor predictive performance among Black patients.

Methods: Retrospective cohort study using April 2010-March 2019 Veterans Affairs Surgical Quality Improvement Program and 2010-2019 National Surgical Quality Improvement Program data. The performance of the RAI and several potential variants were compared between Black and White cases using various metrics to predict mortality (180-day for Veterans Affairs Surgical Quality Improvement Program, 30-day for National Surgical Quality Improvement …

Association Between Chronotype And Chronic Neuropathic Pain Sensitivity: A Pilot Prospective, Observational, Single-Center, Cross-Sectional Study, Michael Kim, Yuri C Martins, Kishan Patel, Chiu-Hsieh Hsu, Mohab Ibrahim, Amol M Patwardhan

Faculty, Staff and Student Publications

Background: Chronotype defines an organism's biological preference for timing of activity and sleep. Being a morning chronotype (i.e., tending to wake up early and go to bed earlier at night) is associated with protection against chronic musculoskeletal pain and headaches, but the relationship between chronotype and neuropathic pain sensitivity remains unclear.

Objectives: The aim of this pilot study was to explore the relationship among chronotype, neuropathic pain sensitivity, and pain interference in patients with chronic neuropathic pain disorders.

Study design: This was a prospective, observational, single-center, cross-sectional study.

Setting: Patients were recruited from pain management clinics.

Methods: The Morningness-Eveningness Questionnaire …

Artificial Intelligence And Machine Learning In Cancer Pain: A Systematic Review, Vivian Salama, Brandon Godinich, Yimin Geng, Laia Humbert-Vidan, Laura Maule, Mohamed A Naser, Abdallah S R Mohamed, Clifton D Fuller, Amy C Moreno

Faculty, Staff and Student Publications

Background/objectives: Pain is a challenging multifaceted symptom reported by most cancer patients. This systematic review aims to explore applications of artificial intelligence/machine learning (AI/ML) in predicting pain-related outcomes and pain management in cancer.

Methods: A comprehensive search of Ovid MEDLINE, EMBASE and Web of Science databases was conducted using terms: "Cancer," "Pain," "Pain Management," "Analgesics," "Artificial Intelligence," "Machine Learning," and "Neural Networks" published up to September 7, 2023. AI/ML models, their validation and performance were summarized. Quality assessment was conducted using PROBAST risk-of-bias andadherence to TRIPOD guidelines.

Results: Forty four studies from 2006 to 2023 were included. Nineteen studies used …

3d Gamma Analysis Between Treatment Plans For Nominally Beam-Matched Medical Linear Accelerators Using Pymedphys, Fada Guan, William Donahue, Simon Biggs, Matthew Jennings, Emily Draeger, Yuenan Wang, David J Carlson, Zhe Chen, Dae Yup Han

Faculty, Staff and Student Publications

Beam-matched linear accelerators (linacs) enable flexible patient scheduling and efficient treatment delivery in the event of unexpected machine downtime. The purpose of this study was to test the feasibility of 3D gamma index as an additional metric beyond standard measurement-based comparisons for more efficient evaluation of treatment plans between linacs with nominally matched beam models to ensure safe patient transfer. Seventeen 3D conformal radiotherapy (3DCRT) plans and thirty-six volumetric-modulated radiation therapy (VMAT) plans for different disease sites were selected from the original linac. An in-house script was used to automatically create new plans for the target linac and calculate dose …

Prediction Of Pathological Complete Response To Chemotherapy For Breast Cancer Using Deep Neural Network With Uncertainty Quantification, Bowen Jing, Kai Wang, Erich Schmitz, Shanshan Tang, Yunxiang Li, Jing Wang

Faculty, Staff and Student Publications

Background: The I-SPY 2 trial is a national-wide, multi-institutional clinical trial designed to evaluate multiple new therapeutic drugs for high-risk breast cancer. Previous studies suggest that pathological complete response (pCR) is a viable indicator of long-term outcomes of neoadjuvant chemotherapy for high-risk breast cancer. While pCR can be assessed during surgery after the chemotherapy, early prediction of pCR before the completion of the chemotherapy may facilitate personalized treatment management to achieve an improved outcome. Notably, the acquisition of dynamic contrast-enhanced magnetic resonance (DCEMR) images at multiple time points during the I-SPY 2 trial opens up the possibility of achieving early …

Mimicking Large Spot-Scanning Radiation Fields For Proton Flash Preclinical Studies With A Robotic Motion Platform, Fada Guan, Dadi Jiang, Xiaochun Wang, Ming Yang, Kiminori Iga, Lawrence Bronk, Liang Wang, Youming Guo, Narayan Sahoo, David R Grosshans, Albert C Koong, Xiaorong R Zhu, Radhe Mohan

Faculty, Staff and Student Publications

Previously, a synchrotron-based horizontal proton beamline (87.2 MeV) was successfully commissioned to deliver radiation doses in FLASH and conventional dose rate modes to small fields and volumes. In this study, we developed a strategy to increase the effective radiation field size using a custom robotic motion platform to automatically shift the positions of biological samples. The beam was first broadened with a thin tungsten scatterer and shaped by customized brass collimators for irradiating cell/organoid cultures in 96-well plates (a 7-mm-diameter circle) or for irradiating mice (1-cm

Off-Protocol Radiation Therapy In Phase 3 Metastatic Solid Tumor Trials, Alexander D Sherry, Timothy A Lin, Zachary R Mccaw, Esther J Beck, Ramez Kouzy, Adina H Passy, Gabrielle S Kupferman, Clifton David Fuller, Charles R Thomas, Eugene J Koay, Chad Tang, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: Increasing data suggest that radiation therapy, particularly ablative radiation therapy, alters the natural history of metastatic disease. For patients with metastatic disease enrolled in prospective trials testing systemic therapy, the use of off-protocol radiation therapy to improve clinical symptoms or extend the duration of study systemic therapy may influence study endpoints. We sought to evaluate how often off-protocol radiation therapy was permitted among systemic therapy phase 3 trials, how often off-protocol radiation therapy is used, and whether off-protocol radiation therapy correlated with study outcomes.

Methods and materials: Two-arm, superiority-design, phase 3 randomized trials testing systemic therapy were screened from …

Sleep Disturbances Based On Patient Reported Outcomes In Patients With Breast Cancer, Saadia A Faiz, Ashley S Knox, Bryan Fellman, Bibi Aneesah Jaumally, G Nancy Pacheco, Reeba Mathew, Jennifer K Litton, Diwakar D Balachandran, Lara Bashoura

Faculty, Staff and Student Publications

Purpose: Sleep disturbances are common in patients with breast cancer, but comprehensive evaluations with patient-reported outcomes (PRO) and sleep evaluation with polysomnography (PSG) are lacking. This study describes sleep disruption using PROs and PSG to identify underlying sleep disorders.

Methods: A retrospective review of patients with breast cancer undergoing formal sleep evaluation from 4/1/2009 to 7/31/2014 was performed. Clinical characteristics, PROs using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), and PSG data were reviewed.

Results: 404 patients were identified with 43% early, 30% locally advanced and 17% metastatic disease. PSQI revealed poor sleep in 75%, and ESS …

Promotion And Tenure For Medical Physicists Should Be Based On Article Specific Measures And Not On Journal Impact Factor, Samantha Hedrick, Jinzhong Yang, Yi Rong

Faculty, Staff and Student Publications

No abstract provided.

Pathobiology Of Myocardial And Cardiomyocyte Injury In Ischemic Heart Disease: Perspective From Seventy Years Of Cell Injury Research, L Maximilian Buja

Faculty, Staff and Student Publications

This review presents a perspective on the pathobiology of acute myocardial infarction, a major manifestation of ischemic heart disease, and related mechanisms of ischemic and toxic cardiomyocyte injury, based on advances and insights that have accrued over the last seventy years, including my sixty years of involvement in the field as a physician-scientist-pathologist. This analysis is based on integration of my research within the broader context of research in the field. A particular focus has been on direct measurements in cardiomyocytes of electrolyte content by electron probe X-ray microanalysis (EPXMA) and Ca2+ fluxes by fura-2 microspectrofluorometry. These studies established that …

Defining Breast Cryoablation Treatment Success: A Guide For The Curative And Palliative Treatment Of Breast Cancer, Monica L Huang, Deanna L Lane, Lauren Q Chang Sen, Rosalind P Candelaria, Henry M Kuerer, Kelly K Hunt, Catherine Akay, Bora Lim, Simona Shaitelman, Rosa F Hwang, Hui Chen, Rajani Katta, Lumarie Santiago

Faculty, Staff and Student Publications

Rationale and objectives: Recent ICE3 trial of breast cryoablation for breast cancer demonstrated 98% success rate, similar to breast-conserving surgery. However, ICE3 and other published studies did not differentiate curative from palliative treatment nor define patient-specific treatment objectives. We sought to define treatment success of curative and palliative breast cryoablation for breast cancer in meeting procedure objectives and patient-specific treatment objectives.

Materials and methods: We conducted a retrospective analysis of breast cancer patients who underwent breast cryoablation during 2021-2024. Breast radiologists performed outpatient cryoablation using local anesthesia and argon gas cryoprobes under ultrasound or MRI guidance. Patient demographics, referral indications, …

A Shared Mechanism For Tnp-Atp Recognition By Members Of The P2x Receptor Family, Jin Wang, Motoyuki Hattori, Chang-Zhu Li, Ye Yu, Chang-Run Guo

Faculty, Staff and Student Publications

P2X receptors (P2X1-7) are non-selective cation channels involved in many physiological activities such as synaptic transmission, immunological modulation, and cardiovascular function. These receptors share a conserved mechanism to sense extracellular ATP. TNP-ATP is an ATP derivative acting as a nonselective competitive P2X antagonist. Understanding how it occupies the orthosteric site in the absence of agonism may help reveal the key allostery during P2X gating. However, TNP-ATP/P2X complexes (TNP-ATP/human P2X3 (hP2X3) and TNP-ATP/chicken P2X7 (ckP2X7)) with distinct conformations and different mechanisms of action have been proposed. Whether these represent species and subtype variations or experimental differences remains unclear. Here, we show …

Development Of Novel Ionization Chambers For Reference Dosimetry In Electron Flash Radiotherapy, Kevin Liu, Shannon Holmes, Ahtesham Ullah Khan, Brian Hooten, Larry Dewerd, Sam Beddar

Faculty, Staff and Student Publications

Background: Reference dosimetry in ultra-high dose rate (UHDR) beamlines is significantly hindered by limitations in conventional ionization chamber design. In particular, conventional chambers suffer from severe charge collection efficiency (CCE) degradation in high dose per pulse (DPP) beams.

Purpose: The aim of this study was to optimize the design and performance of parallel plate ion chambers for use in UHDR dosimetry applications, and evaluate their potential as reference class chambers for calibration purposes. Three chamber designs were produced to determine the influence of the ion chamber response on electrode separation, field strength, and collection volume on the ion chamber response …

Psychophysical And Functional Outcomes In Chemotherapy-Induced Peripheral Neuropathy After Spinal Cord Stimulation: A Narrative Review And Case Series, Peter D Vu, Kathleen Erin Mcdonough, Patrick M Dougherty, Ryan S D'Souza, Saba Javed

Faculty, Staff and Student Publications

Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a complication that may occur after treatment with various anticancer drugs. In refractory CIPN cases, spinal cord stimulation (SCS) has garnered increased attention. The use of gait analysis and psychophysical quantitative sensory testing (QST) as an objective measurement of CIPN-related damage has burgeoned; however, these changes have not been reported for patients with CIPN after SCS implantation using either burst or tonic stimulation.

Materials and methods: This manuscript encompasses two parts: 1) a presentation of pain improvement in a series of patients who underwent tonic vs burst SCS for CIPN measured by gait and …