Medical Biophysics Commons^™

Methods For The Prediction Of Osteoradionecrosis Resulting From Head And Neck Cancer Radiation Therapy, Brandon Reber

Dissertations and Theses (Open Access)

Head and neck cancer (HNC) is the sixth most diagnosed cancer worldwide with over 600,000 patients diagnosed every year. One of the primary methods to treat HNC is through radiation therapy (RT). While RT is effective at treating HNC, late toxicities resulting from treatment can occur months to years post-treatment and can cause debilitating quality of life changes for HNC survivors. One of these late toxicities is osteoradionecrosis (ORN), which is the death of bone due to radiation. For HNC, the mandible is commonly affected and can cause challenges chewing, swallowing, and physical appearance changes. Several factors indicate the pressing …

Inter-Individual Variations In Circadian Misalignment-Induced Nafld Pathophysiology In Mice, Nobuya Koike, Yasuhiro Umemura, Hitoshi Inokawa, Isao Tokuda, Yoshiki Tsuchiya, Yuh Sasawaki, Atsushi Umemura, Naoko Masuzawa, Kazuya Yabumoto, Takashi Seya, Akira Sugimoto, Seung-Hee Yoo, Zheng Chen, Kazuhiro Yagita

Faculty, Staff and Student Publications

Pathological consequences of circadian misalignment, such as shift work, show considerable individual differences, but the lack of mechanistic understanding hinders precision prevention to prevent and mitigate disease symptoms. Here, we employed an integrative approach involving physiological, transcriptional, and histological phenotypes to examine inter-individual differences in pre-symptomatic pathological progression, preceding irreversible disease onset, in wild-type mice exposed to chronic jet-lag (CJL). We observed that CJL markedly increased the prevalence of hepatic steatosis with pronounced inter-individual differences. Stratification of individual mice based on CJL-induced hepatic transcriptomic signature, validated by histopathological analysis, pinpoints dysregulation of lipid metabolism. Moreover, the period and power of …

Editorial; Biophysics Approaches To Investigate Multi-Organ Alcohol-Induced Damage, Janos Paloczi, Youngchan Kim

School of Graduate Studies Faculty Publications

No abstract provided.

The Development Of Artificial Intelligence-Based To Ols For Expert Peer Review Of Radiotherapy Treatment Plans, Mary Gronberg

Dissertations and Theses (Open Access)

Creating a patient-specific radiation treatment plan is a time-consuming and operator-dependent manual process. The treatment planner adjusts the planning parameters in a trial-and-error fashion in an effort to balance the competing clinical objectives of tumor coverage and normal tissue sparing. Often, a plan is selected because it meets basic organ at risk dose thresholds for severe toxicity; however, it is evident that a plan with a decreased risk of normal tissue complication probability could be achieved. This discrepancy between “acceptable” and “best possible” plan is magnified if either the physician or treatment planner lacks focal expertise in the disease site. …

Machine Learning For Ecg Diagnosis And Risk Stratification Of Occlusion Myocardial Infarction, Salah S Al-Zaiti, Christian Martin-Gill, Jessica K Zègre-Hemsey, Zeineb Bouzid, Ziad Faramand, Mohammad O Alrawashdeh, Richard E Gregg, Stephanie Helman, Nathan T Riek, Karina Kraevsky-Phillips, Gilles Clermont, Murat Akcakaya, Susan M Sereika, Peter Van Dam, Stephen W Smith, Yochai Birnbaum, Samir Saba, Ervin Sejdic, Clifton W Callaway

Faculty, Staff and Students Publications

Patients with occlusion myocardial infarction (OMI) and no ST-elevation on presenting electrocardiogram (ECG) are increasing in numbers. These patients have a poor prognosis and would benefit from immediate reperfusion therapy, but, currently, there are no accurate tools to identify them during initial triage. Here we report, to our knowledge, the first observational cohort study to develop machine learning models for the ECG diagnosis of OMI. Using 7,313 consecutive patients from multiple clinical sites, we derived and externally validated an intelligent model that outperformed practicing clinicians and other widely used commercial interpretation systems, substantially boosting both precision and sensitivity. Our derived …

The Role Of Native Cysteine Residues In The Oligomerization Of Kcnq1 Channels, Alison Bates, Rebecca B Stowe, Elizabeth M Travis, Lauryn E Cook, Carole Dabney-Smith, Gary A Lorigan

Faculty, Staff and Student Publications

KCNQ1, the major component of the slow-delayed rectifier potassium channel, is responsible for repolarization of cardiac action potential. Mutations in this channel can lead to a variety of diseases, most notably long QT syndrome. It is currently unknown how many of these mutations change channel function and structure on a molecular level. Since tetramerization is key to proper function and structure of the channel, it is likely that mutations modify the stability of KCNQ1 oligomers. Presently, the C-terminal domain of KCNQ1 has been noted as the driving force for oligomer formation. However, truncated versions of this protein lacking the C-terminal …

Sexual Dimorphism Of Glomerular Capillary Morphology In Rats, Zackarias Coker

Undergraduate Honors Theses

Chronic kidney disease (CKD) progresses faster in males than females; however, the underlying mechanisms remain poorly understood. Sex differences in glomerular capillary morphology has been hypothesized to contribute, in part, to the increased susceptibility to hypertension-induced renal injury and CKD progression in males, but this has not been investigated. The goal of the present study was to assess glomerular capillary morphology in male vs. female rats with intact kidneys and after uninephrectomy (UNX). We hypothesized that glomerular capillary radii (R_CAP) and length (L_CAP) would be greater in male rats.

Male (n=4) and female (n=4) with intact …

Automating The Radiation Therapy Treatment Planning Process For Pediatric Patients With Medulloblastoma, Soleil Hernandez

Dissertations and Theses (Open Access)

Over the past 50 years, pediatric cancer 5-year survival rates increased from 20% to 80% in high-income countries, however, these trends have not been mirrored in low-and-middle-income countries (LMICs). This is due in part to delayed diagnosis, higher rates of advanced disease at presentation and a growing lack of access to high quality medical personnel and technology necessary to deliver complex treatments.

The long-term goal of this study was to alleviate demanding workflows and increase global access to high-quality pediatric radiation therapy by harnessing the power of artificial intelligence to automate the radiation therapy treatment planning process for pediatric patients …

Mechanosensitive Membrane Proteins: Usual And Unusual Suspects In Mediating Mechanotransduction, Miriam B Goodman, Elizabeth S Haswell, Valeria Vásquez

Faculty, Staff and Student Publications

This Viewpoint, which accompanies a Special Issue focusing on membrane mechanosensors, discusses unifying and unique features of both established and emerging mechanosensitive (MS) membrane proteins, their distribution across protein families and phyla, and current and future challenges in the study of these important proteins and their partners. MS membrane proteins are essential for tissue development, cellular motion, osmotic homeostasis, and sensing external and self-generated mechanical cues like those responsible for touch and proprioception. Though researchers' attention and this Viewpoint focus on a few famous ion channels that are considered the usual suspects as MS mechanosensors, we also discuss some of …

Estimation Of Free Water-Corrected Microscopic Fractional Anisotropy., Nico J J Arezza, Tales Santini, Mohammad Omer, Corey A Baron

Medical Biophysics Publications

Water diffusion anisotropy MRI is sensitive to microstructural changes in the brain that are hallmarks of various neurological conditions. However, conventional metrics like fractional anisotropy are confounded by neuron fiber orientation dispersion, and the relatively low resolution of diffusion-weighted MRI gives rise to significant free water partial volume effects in many brain regions that are adjacent to cerebrospinal fluid. Microscopic fractional anisotropy is a recent metric that can report water diffusion anisotropy independent of neuron fiber orientation dispersion but is still susceptible to free water contamination. In this paper, we present a free water elimination (FWE) technique to estimate microscopic …

Longitudinal Oxygen Imaging In 3d (Bio)Printed Models, Ryan Curtis O'Connell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Electron paramagnetic resonance (EPR), and its molecular imaging modality, is a powerful tool to noninvasively map various biological and chemical markers within objects of interest. Reliable data acquisition is a major impeding factor for longitudinal hands-off measurements. Measurements are especially challenging in biomedical applications, as live objects are not static. Frequent changes occur that require constant fine recalibration of the EPR detection system, called the resonator. To enable longitudinal imaging, a technology permitting automatic digital control of resonator coupling, tuning, and EPR data acquisition was developed. Automation was achieved through the utilization of a microcontroller and digital peripheral components such …

Contribution Of Metabolic Cell Swelling On Microcirculatory Perfusion In Septic Shock, Charles E. Payne

Theses and Dissertations

Sepsis, a systemic immunological response that leads to organ-dysfunction, the development of septic shock, and death has mortality rate of 15-25%. A subset of sepsis, septic shock, has an in-hospital mortality rate of 30-50%. Sepsis and its treatment are the most expensive healthcare problem in the United States with the US Agency for Healthcare Research and Quality estimating annual costs over $20 billion. Hypoxia experienced in septic shock induces metabolic cell and tissue swelling leading to further microcirculatory dysfunction and poor tissue perfusion. Reversing metabolic cell swelling corrects these perfusion defects. Two models were used in rats to induce septic …

Characterization And Investigation Of Cold Atmospheric Plasma And Its Effects On Cancer Cell Biology, Thomas M. Ritrosky

Theses and Dissertations

Modern cancer treatment uses radiation therapy in over 50% of patient cases. It is an e↵ective way of treating tumors because the mechanisms of cell killing are well known through the damage that ionizing radiation does to DNA. The amount of radiation can be tracked through measuring the dose of the clinical photon or electron beam used. However, there are limitations in the usage of radiation therapy, for example, a tumor can create hypoxic areas that become radioresistant leading to complete ine↵ectiveness of further radiation treatment. This project looks into the application of cold atmospheric plasma as an adjuvant therapy …

A Learning Health System For Radiation Oncology, Rishabh Kapoor

Theses and Dissertations

The proposed research aims to address the challenges faced by clinical data science researchers in radiation oncology accessing, integrating, and analyzing heterogeneous data from various sources. The research presents a scalable intelligent infrastructure, called the Health Information Gateway and Exchange (HINGE), which captures and structures data from multiple sources into a knowledge base with semantically interlinked entities. This infrastructure enables researchers to mine novel associations and gather relevant knowledge for personalized clinical outcomes.

The dissertation discusses the design framework and implementation of HINGE, which abstracts structured data from treatment planning systems, treatment management systems, and electronic health records. It utilizes …

An Exploration Of The Link Between Vertebral Endplate Fracture, Velocity, And Health Of The Intervertebral Disc., John Mcmorran

Theses and Dissertations (Comprehensive)

The capacity for fractures to manifest in the growth cartilage of the adolescent human spine is well documented, but much of the knowledge available regarding such fractures remains retrospective and is largely composed of small case series made up of relatively few participants. In-vitro tissue testing has demonstrated that pressurization of the intervertebral disc’s nucleus pulposus significantly contributes to the generation of growth plate fractures. However, a comprehensive biomechanical investigation of the mechanical consequences for the intervertebral disc when exposed to ring apophyseal (growth plate) fractures at different velocities remains to be demonstrated.

The first two experiments of the present …

Structural Insights Into Cardiolipin Replacement By Phosphatidylglycerol In A Cardiolipin-Lacking Yeast Respiratory Supercomplex, Elena G Govorunova, Oleg A Sineshchekov, Leonid S Brown, Ana-Nicoleta Bondar, John L Spudich

Faculty, Staff and Student Publications

Potassium-selective channelrhodopsins (KCRs) are light-gated K+ channels recently found in the stramenopile protist Hyphochytrium catenoides. When expressed in neurons, KCRs enable high-precision optical inhibition of spiking (optogenetic silencing). KCRs are capable of discriminating K+ from Na+ without the conventional K+ selectivity filter found in classical K+ channels. The genome of H. catenoides also encodes a third paralog that is more permeable for Na+ than for K+. To identify structural motifs responsible for the unusual K+ selectivity of KCRs, we systematically analyzed a series of chimeras and mutants of this protein. We found that mutations of three critical residues in the …

Risking The Wrist, Tyler Mosier, Evan White

Physician Assistant Capstones, 2020-current

Abstract:

Background: Carpal tunnel syndrome (CTS) is now one of the most common workplace injuries, with nearly 50% of patients eventually requiring CTS release surgery as a permanent solution. With a concern of a younger incidence of CTS developing in a technology dependent society, some patients may fear even a minimal loss of function. To our knowledge there has been no study comparing forearm grip strength before symptoms develop to grip strength after the procedure has been performed.

Objectives: The aim of this study was to determine if there was a significant change in strength of the flexor digitorum superficialis …

Use Of Cardiomems Hf Sensor In Management Of Nyha Class Iii Heart Failure, Trevor Andrunik, Anne Eady

Physician Assistant Capstones, 2020-current

Objective: Assess the ability of continuous pulmonary artery pressure monitoring via implantable CardioMEMs HF device to reduce hospitalization in New York Heart Association (NYHA) Class III heart failure patients over the age of 18. Design: Systematic literature review. Methods: Searches were conducted via PubMed and ClinicalTrials.gov using the single search term “CardioMEMs.” Inclusion criteria narrowed results to studies performed in the last 10 years, randomized control trials, cohort studies, and utilizing heart failure related hospitalization as the primary endpoint. Results: The current data unanimously asserts that the CardioMEMs HF device is effective at reducing heart failure related hospitalizations, with secondary …

Quantifying The Magnitude Of To Tal Dose Deviation Caused By Various Sources Of Error Among Iroc Phantom Irradiation Results, Sharbacha S. Edward

Dissertations and Theses (Open Access)

The Imaging and Radiation Oncology Core (IROC) phantoms are used as an end-to-end test of an institution’s radiotherapy processes, and for clinical trial credentialing. Phantoms are treated like patients, and evaluation of the doses received by the thermoluminescent dosimeters (TLDs) inside the phantom, reflects the accuracy with which an institution can image, plan and irradiate a phantom or patient. Recent phantom results show that among the hundreds of various IROC phantoms irradiated annually, 8-17% of institutions fail this test. The purpose of this work was to investigate the various types of errors that may occur during the treatment process and …

Mesoscale Structure-Function Relationships In Mitochondrial Transcriptional Condensates, Marina Feric, Azadeh Sarfallah, Furqan Dar, Dmitry Temiakov, Rohit V. Pappu, Tom Misteli

Department of Biochemistry and Molecular Biology Faculty Papers

In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized in vitro reaction conditions to probe the structure-function relationships of biomolecular condensates. We find that the core components of the mt-transcription machinery form multiphasic, viscoelastic condensates in vitro. Strikingly, the rates of condensate-mediated transcription are substantially lower than in solution. The condensate-mediated decrease in transcriptional rates is associated with the formation of vesicle-like structures that are driven by the production and accumulation of RNA during transcription. The generation of RNA alters …