Medicine and Health Sciences Commons^™

Employing A Machine Learning Approach In Precision Oncology To Predict Pik3ca Functional Status And Identify Phenocopying Variants Of Deleterious Pik3ca Mutations, Javier Castillo

CMC Senior Theses

The following proposal describes a modular machine learning approach that detects malfunctioning genes and pathways in cancer using the transcriptome of cancer patients. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders. Applied to the PI3K/AKT/mTOR pathway, this method can be used to predict PIK3CA functional status and identify phenocopying variants of deleterious PIK3CA mutations. The classifier will do this by integrating RNA-seq, copy number, and mutation data from tumors to determine the functional status of PIK3CA using a set of learned gene-specific weights. The classifier will then be …

Analysis Of Biologically Effective Dose For Retroactive Yttrium-90 Trans-Arterial Radioembolization Treatment Optimization, Mj Lindsey

CMC Senior Theses

Trans-arterial radioembolization (TARE) is a protracted modality of radiation therapy where radionuclides labeled with Yttrium-90 (⁹⁰Y) are inserted inside a patient's hepatic artery to treat hepatocellular carcinoma (HCC). While TARE has been shown to be a clinically effective and safe treatment, there is little understanding of the radiobiological relationship between absorbed dose and tissue response, and thus there is no dosimetric standard for treatment planning. The Biologically Effective Dose (BED) formalism, derived from the Linear-Quadratic model of radiobiology, is used to weigh the absorbed dose by the time pattern of delivery. BED is a virtual dose that can …

Investigating The Physiological Use Of An Organ-On-A-Chip Device Through The Design And Fabrication Of A Micro-Electrical Blood-Brain Barrier (Μe-Bbb) System, Amrita Srinivasan, Kiana Aran, Jonalyn Herce, Noor Chaudhry, Allexa Ortiz

CMC Senior Theses

Aging is considered the main risk factor for various neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Aging is associated with an increase in neuroinflammation, which is a significant contributor to cognitive impairment observed in these age-related neurodegenerative diseases. However, studying brain behavior remains a challenge due to the complex nature of isolating brain tissue from an organism. Modeling the brain allows for further study of these neurodegenerative diseases. Organ-on-a- chip (OoC), a system containing engineered or natural tissues grown within microfluidic chips, has emerged as a promising tool for mimicking human physiology in a controlled microenvironment. A …

Investigation Into The Potential For Acquired Cross Tolerances Of Amphetamines, Benjamin Weldon

CMC Senior Theses

In the United States, the treatment of ADHD through use of psychostimulants in adolescents is a growing reality that many people know today and many more will know in the coming years. Although the effectiveness of psychostimulants is a known asset, the benefits of these medications may not be a permanent solution, suggesting not only the presence of a tolerance build up, but as many stimulants are prescribed in a joint effort to combat ADHD, a possible cross tolerance between two prescribed medications. There are minimal studies published that have addressed the topic of cross stimulation tolerance buildup between prescription …

The Development Of A Brain Penetrating Erythropoietin For The Treatment Of Alzheimer’S Disease, Joshua Yang

KGI Theses and Dissertations

The development of a neurotherapeutic for the treatment of Alzheimer’s Disease (AD) is challenging due to limited endpoint efficacy. Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for AD but has limited blood-brain barrier (BBB) permeability. A chimeric fusion protein of EPO bound to the transferrin receptor monoclonal antibody (cTfRMAb) can act as a molecular trojan horse for brain drug delivery, shuttling EPO into the brain via the transvascular route. However, cTfRMAbs have Fc-effector function adverse effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly (cTfRMAb-N292G-EPO) reduces this Fc effector function. Hence, developing this …

Detection Of Sickle Cell Disease-Associated Single Nucleotide Polymorphism Using A Graphene Field Effect Transistor, Kandace Fung

CMC Senior Theses

Sickle Cell Disease (SCD) is a hereditary monogenic disorder that affects millions of people worldwide and is associated with symptoms such as stroke, lethargy, chronic anemia, and increased mortality. SCD can be quickly detected and diagnosed using a simple blood test as an infant, but as of now, there is currently limited treatment to cure an individual of sickle cell disease. Recently, there have been several promising developments in CRISPR-Cas-associated gene-editing therapeutics; however, there have been limitations in gene-editing efficiency monitoring, which if improved, could be beneficial to advancing CRISPR-based therapy, especially in SCD. The CRISPR-Chip, a three-terminal graphene-based field …

Integrating Alexander Technique Into Treatment Of Adolescent Idiopathic Scoliosis To Improve Patient Quality Of Life, Ana Nishioka

Scripps Senior Theses

The following thesis posits training in the Alexander Technique as a possible solution to address the comorbidities of poor body image and reduced feelings of efficacy in patients treated for adolescent idiopathic scoliosis (AIS). Both literature and personal accounts of AIS highlight that current conservative methods of treating AIS offered by the Western medical sphere, including observation, bracing, and physical therapy, do not adequately address, and may actually exacerbate, negative mental health symptoms. Patients are often represented as their external orthopedic diagnosis and receive limited emotional guidance in exploring their internal feelings about their body and its capabilities. Alexander Technique …

A Dna Computer For Glioblastoma Multiforme Diagnosis And Drug Delivery, Sumaiya F. Hashmi

CMC Senior Theses

Glioblastoma multiforme (GBM) is a debilitating malignant brain tumor with expected patient survival of less than a year and limited responsiveness to most treatments, often requiring biopsy for diagnosis and invasive surgery for treatment. We propose a DNA computer system, consisting of input, computation, and output components, for diagnosis and treatment. The input component will detect the presence of three GBM biomarkers: vascular endothelial growth factor (VEGF), caveolin-1α (CAV), and B2 receptors. The computation component will include indicator segments for each of these genes, and ensure that output is only released if all the biomarkers are present. The output component …

A Machine Learning Approach To Diagnosis Of Parkinson’S Disease, Sumaiya F. Hashmi

CMC Senior Theses

I will investigate applications of machine learning algorithms to medical data, adaptations of differences in data collection, and the use of ensemble techniques.

Focusing on the binary classification problem of Parkinson’s Disease (PD) diagnosis, I will apply machine learning algorithms to a primary dataset consisting of voice recordings from healthy and PD subjects. Specifically, I will use Artificial Neural Networks, Support Vector Machines, and an Ensemble Learning algorithm to reproduce results from [MS12] and [GM09].

Next, I will adapt a secondary regression dataset of PD recordings and combine it with the primary binary classification dataset, testing various techniques to consolidate …

Electromyographic Analysis Of Trunk Muscle Activation During A Throwing Pattern Following Rotator Cuff Mobilization, Aubrey L. Doede

CMC Senior Theses

Correct muscular activation of the body segments during an overhand throw is achieved when movement originates in the larger and more proximal legs and trunk and moves sequentially to the smaller, distal segments of the shoulder and arm. This sequence permits angular velocity to transfer progressively through the throw as part of an open kinetic chain. The athlete can summate angular velocity and segmental forces only if he is able to create a separation between the body segments during the movement pattern, and this separation is thus essential to effective segmental sequencing for activation of the trunk muscles to occur …

Mathematical Aids Epidemic Model: Preferential Anti-Retroviral Therapy Distribution In Resource Constrained Countries, Nadia Abuelezam

HMC Senior Theses

HIV/AIDS is one of the largest health problems the world is currently facing. Even with anti-retroviral therapies (ART), many resource-constrained countries are unable to meet the treatment needs of their infected populations. ART-distribution methods need to be created that prevent the largest number of future HIV infections. We have developed a compartment model that tracks the spread of HIV in multiple two-sex populations over time in the presence of limited treatment. The model has been fit to represent the HIV epidemic in rural and urban areas in Uganda. With the model we examine the spread of HIV among urban and …