Disease Modeling Commons^™

Mathematical Modelling Of Disease Outbreak, Favour Christian, Matthew Molloy

SURE Journal: Science Undergraduate Research Experience Journal

Establishing a model framework for more research necessitates a thorough understanding of the causes, distribution, prevalence, and evolution of infectious illnesses. The main mathematical concept used in this modelling simulation is ordinary differential equations (ODEs). The purpose of this study was to investigate the significance of the many criteria linked to a zombie virus spread. The zombie framework provides an accessible and relatively simple representation of the nature of infectious disease spread, allowing for tractable assumptions and the development of more complex situations.

The models are designed around a zombie outbreak in which the zombie virus is spread through a …

Early Ctdna Kinetics As A Dynamic Biomarker Of Cancer Treatment Response, Aaron Li, Emil Lou, Kevin Leder, Jasmine Foo

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Repurposing Bt-11 To Treat Alzheimer’S Disease: Exploring The Glutathione-S-Transferase Lancl2 As A Target, Emily Birnbaum

Dissertations, Theses, and Capstone Projects

Approximately 99.6% of potential Alzheimer’s drugs fail, thus developing successful drugs is a high priority. The failure at developing successful drugs relates to the complex nature of the disease itself. Many components act together to trigger a cascade that ultimately results in neurodegeneration and cognitive dysfunction associated with the disease. In building a multiplex model of Alzheimer’s it is important to understand its specific biological mechanisms. One of these key pathological mechanisms is neuroinflammation. Understanding the pathways involved in neuroinflammation in Alzheimer’s is an urgent need, as it poses a promising avenue for future effective therapeutics. Specifically, as many investigational …

Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov

Theses & Dissertations

Colitis-associated cancer (CAC) is the most devastating complication of longstanding inflammatory bowel disease (IBD). Understanding the mechanisms underlying the switch from damage-repair to dysplasia in IBD is critical for identifying novel therapies to facilitate mucosal healing while mitigating CAC risk. Microtubule-associated serine-threonine kinase-like (MASTL), though crucial in cell growth and repair, is upregulated in sporadic colorectal cancer and CAC. This study sought to delineate the role of MASTL in colitis and CAC development.

First, we examined whether MASTL is associated with colitis and recovery. Review of publicly available data found significant elevation of MASTL and interleukin (IL)-22 in biopsies from …

Modeling The Effect Of Human Behavior On Disease Transmission, Katie Yan

Rose-Hulman Undergraduate Mathematics Journal

Many infectious disease models build upon the classic Susceptible-Infected-Recovered (SIR) model, a compartmental system that is used to simulate disease transmission in a population. The SIR model focuses on the transmission of disease but rarely includes behavioral or informational components that explore how disease perception influences transmission. In this paper, we propose a six-compartment behavioral SIR model that further segments the classic SIR system based on knowledge of information about the disease, and we explore how sharing information affects disease transmission. We designate two states as aware and unaware based on whether the relevant information is known by the population. …

Perturbations In Risk/Reward Decision Making And Frontal Cortical Catecholamine Regulation Induced By Mild Traumatic Brain Injury, Christopher P Knapp, Eleni Papadopoulos, Jessica A Loweth, Ramesh Raghupathi, Stan B Floresco, Barry D Waterhouse, Rachel L Navarra

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC. Rats were exposed to sham, single (smTBI), or three closed-head controlled cortical impact (CH-CCI) injuries and …

Deciphering The Contribution Of Microglia To Neurodegeneration In Friedreich's Ataxia, Sydney N. Gillette

Master's Theses

Friedreich's ataxia (FRDA) is the most prevalent inherited ataxia, affecting one in every 50,000 individuals in the United States. This hereditary condition is caused by an abnormal GAA trinucleotide repeat expansion within the first intron of the frataxin gene resulting in decreased levels of the frataxin protein (FXN). Insufficient cellular frataxin levels results in iron accumulation, increased reactive oxygen species production and mitochondrial dysfunction. Tissues most heavily impacted are those most dependent on oxidative phosphorylation as an energy source and include the nervous system and muscle tissue. This is evident in the clinical phenotype which includes muscle weakness, ataxia, neurodegeneration …

Blunt Cerebrovascular Injury (Bcvi): Universal Cta Neck Screening At Level 2 Trauma Center, Tamine Gogel

Doctor of Nursing Practice Projects

Blunt Cerebrovascular Injury (BCVI) refers to injuries to the vessels supplying blood to the brain, primarily carotid and vertebral arteries, and can result from trauma, resulting in stroke by vessel dissection, thrombus formation, embolization, and hemorrhage. Timely identification is crucial for effective intervention and improved outcomes. This doctoral project proposes the implementation of universal screening using Computed Tomography Angiography (CTA) of the neck during initial workup for blunt force trauma at a Level II ACS-verified trauma center. The primary objective is to mitigate potential delays in diagnosing and treating BCVI, thereby reducing the likelihood of complications. Patients ≥ 15 years …

Modeling Fast Information And Slow(Er) Disease Spreading: A Geometric Analysis, Iulia Martina Bulai, Mattia Sensi, Sara Sottile

Biology and Medicine Through Mathematics Conference

No abstract provided.

Assessing The Impact And Cost-Effectiveness Of Covid-19 Testing In Adult Social Care Homes In England, Siyu Chen

Biology and Medicine Through Mathematics Conference

No abstract provided.

Dual-Domain Clustering Of Spatiotemporal Infectious Disease Data, Samuel R. Thornton, Erin C.S. Acquesta, Patrick D. Finley, Mansoor A. Haider

Biology and Medicine Through Mathematics Conference

No abstract provided.

Information Feedback Delays Within Epidemic Models And Their Effect On Model Dynamics., Maria K. Bouka, Christopher Strickland Dr

Biology and Medicine Through Mathematics Conference

No abstract provided.

Statistical Approaches For The Early Detection Of Colorectal Cancer Using Longitudinal Biomarkers, Emily Berry

Statistical Science Theses and Dissertations

Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States [45]. CRC is believed to advance from adenomatous polyps creating a unique opportunity for both early detection and cancer prevention [4, 23]. Like other diseases, CRC screening reduces mortality by detecting cancer at earlier, more treatable stages; however, it can also reduce incidence through the removal of precancerous lesions [4]. As a result, screening is recommended for average-risk adults ≥ 45 years of age and includes a variety of tests [4, 12]. Despite alternate screening options, colonoscopy capacity is often cited as a barrier to …

Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das

Theses & Dissertations

Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …

Unraveling The Role Of Gjb3 In Lung Adenocarcinoma, Swathi M. Priyanka

Theses & Dissertations

Lung cancer stands as a leading cause of cancer-related mortality worldwide, with small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) comprising its primary categories. NSCLC, representing nearly 85% of cases, exhibits a 5-year survival rate of less than 21%. Among NSCLC subtypes, lung adenocarcinoma (LUAD) prevails as the most common, followed by squamous cell carcinoma and large cell carcinoma. Gap junctions are crucial for intercellular communication and cellular homeostasis maintenance, demonstrate altered expression patterns in various diseases, including cancer. Gap junction beta 3 (GJB3 or Connexin31) exhibits significant expression in both preclinical and clinical LUAD samples, prompting investigation into …

Interactions Between Repetitive Mild Traumatic Brain Injury And Methylphenidate Administration On Catecholamine Transporter Protein Levels Within The Rodent Prefrontal Cortex, Anna Abrimian, Eleni Papadopoulos, Christopher P. Knapp, J. Loweth, Barry Waterhouse, Rachel Navarra

Rowan-Virtua Research Day

It is theorized that low concentrations of dopamine (DA) and norepinephrine (NE) within in the prefrontal cortex (PFC) following traumatic brain injury (TBI) leads to increased risky behavior. Our lab has shown that repeated mild TBI (rmTBI) sex-differentially increases risky behavior in a rodent model. Methylphenidate (MPH) is a psychostimulant drug used to treat symptoms of Attention-Deficit Hyperactivity Disorder (ADHD), also driven by a hypo-catecholaminergic PFC. MPH elevates catecholamine levels by blocking DA and NE transporters, DAT and NET. While the potential of psychostimulants to treat post-TBI symptoms have been explored, the effects of sub-chronic MPH on transporter levels following …

Identifying Chewing Alterations In A Parkinsonian Model, Nicholas Zanghi, Taylor Good, Shivam Patel, Francois Gould

Rowan-Virtua Research Day

Patients suffering from Parkinson’s Disease will typically experience a range of motor and nonmotor symptoms. Characteristic signs of Parkinson’s include pill-rolling tremor, stooped posture, and shuffling gate. Patients with this disease can also develop oropharyngeal dysfunction, which can disable patients from meeting their physiologic needs. Understanding this disability and the changes in mastication kinematics can lead to potential future treatment. Our study induced Parkinson’s in rats with rotenone injections. Their jaw kinematics were identified through fluoroscopy of radio-opaque beads implanted into different areas of their jaws. The Parkinson’s induction altered mastication significantly with an increase in anterior/posterior range of motion …

Fos Expression In Lateral Hypothalamus/Perifornical Area Is Correlated With Psychosocial Stress-Induced Cocaine-Seeking Behavior In A Sex-Specific Manner, Milena Sudarikov, Nicole M. Hinds, Ireneusz D. Wojtas, Desta M. Pulley, Daniel F. Manvich

Rowan-Virtua Research Day

Cocaine Use Disorder persists as a significant public health concern in the United States. Recent epidemiological data indicate that rates of cocaine-involved overdose deaths are rising, and treatment of Cocaine Use Disorder is challenging due to a lack of FDA-approved medications to help patients achieve abstinence and avoid relapse. Stress can precipitate cocaine craving and trigger relapse episodes, however the underlying neural circuitry by which stressors drive cocaine seeking is not completely understood. Our laboratory has recently identified the potential involvement of the rostrolateral aspect of the periaqueductal gray (rlPAG) in psychosocial stress-induced cocaine-seeking behavior using a rodent model of …

A Preliminary Report On The Role Of Lipoxin A4 In Reinstating The Blood-Brain Barrier Integrity In A Rodent Model Of Acute Inflammation With Impaired Cerebrovasculature, Minjal Patel, Shruti Varshney, Ananya Nethikunta, George G. Godsey, Mary C. Kosciuk, Ana Rodriguez, Bernd Spur, Kingsley Yin, Randel L. Swanson, Venkat Venkataraman, Robert G. Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: The blood-brain barrier (BBB) is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI). Lipoxins (LXs) are a class of arachidonate-derived eicosanoids, which are a class of specialized pro-resolving lipid mediators (SPMs). SPMs are known to inhibit immune response through inhibition of cellular infiltration, downregulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Hence, LXs are recognized as “breaking signals” in the inflammatory process. One form of LXs, Lipoxin A4 (LXA4) …

Efficacy Of Psilocybin In The Treatment Of Substance And Alcohol Use Disorders, Hanna Brancaccio

Rowan-Virtua Research Day

Introduction: Substance use disorder (SUD) and alcohol use disorder (AUD) are major public health crises, affecting millions of Americans. Current treatment options include behavioral therapies and medications. In this review, we explored psilocybin’s efficacy in treating SUD and AUD.

Methods: Key terms were used to search databases to identify articles that addressed psilocybin in the treatment of SUD. Included in the review were indexed, peer-reviewed, primary sources that were published within the last 10 years. Excluded studies were non-peer reviewed, not relevant to the thesis, and did not have an English translation.

Results: The psychodynamic antidepressant effects of psilocybin mark …

The Effects Of Circadian Misalignment On Astrocyte Morphology In The Nucleus Tractus Solitarius, Kush C. Patel, Mina Shenouda, Diana Martinez

Rowan-Virtua Research Day

Circadian misalignment, as experienced by shift workers, was found to increase the number of astrocytes in the nucleus tractus solitarius (nTS) - a brain region crucial for autonomic control of blood pressure. Sprague Dawley rats subjected to a 6-hour light-dark phase delay every 2 days to simulate shift work exhibited a significant increase in astrocyte cell bodies compared to control rats, both at 9am and 9pm timepoints. The increase in astrocytes may lead to greater glutamate uptake, reducing extracellular glutamate levels in the nTS. Decreased glutamatergic neurotransmission in this region has been linked to the development of hypertension. These findings …

Effect Of Dosage On Severity Of Dysphagia In A Toxicological Rat Model Of Parkinson's Disease, Shivam Patel, Taylor Good, Nicholas Zanghi, Francois Gould

Rowan-Virtua Research Day

Parkinson’s Disease (PD) is a prevalent and devastating neurodegenerative disorder that causes progressively worsening motor symptoms affecting locomotor and oropharyngeal function. There is limited research in animal models on swallowing dysfunction in PD. To examine how neurodegeneration in PD produces progressive impairment in the oropharyngeal and locomotor processes, rotenone, a type II mitochondrial inhibitor, was injected into Lewis rat models to reproduce a parkinsonian phenotype. We hypothesized that the animal models injected with the rotenone will exhibit both oropharyngeal dysfunction and locomotor deficiency with an increased deficit that correlates with prolonged treatment. We utilized 18 rats receiving either 2.75 mg/kg …

Pediatric Neurotropic Infection Alters Synaptic Development In The Developing Brain, Anuoluwapo Grace Fadare, Yashika S. Kamte, Manish N. Chandwani, Lauren A. O'Donnell

Rowan-Virtua Research Day

Many neurotropic viruses cause more significant pathology in younger hosts as their brains are still developing. This experiment asked how central nervous system (CNS) viral-infections affect the development of synapses in the pediatric brain during infection and post-infection. Synaptogenesis is at its peak in pediatric mice (10 days old) and we hypothesized that a neurotropic infection could disrupt synaptic proteins. We used a transgenic mouse model where measles virus (MV) infects only mature neurons, leading us to question whether synapses were impacted. We examined synaptic markers in the cerebellum and hippocampus in MV-infected and uninfected mice 9 days and 90 …

Intra-Accumbens Microinfusion Of The Dopamine D3 Receptor Partial Agonist (±)Vk4-40 Does Not Affect Basal Locomotion In Mice, Yeonwoo Sim, Nicole M. Hinds, Amy Hauck Newman, Daniel F. Manvich

Rowan-Virtua Research Day

The opioid epidemic remains a pressing public health crisis, prompting the search for alternative pharmacotherapies for Opioid Use Disorder (OUD). This study explores the potential of the dopamine D3 receptor (D3R) partial agonist, (±)VK4-40, as a novel treatment option. We investigated the impact of intra-nucleus accumbens (NAc) microinfusion of VK4-40 on basal locomotion in mice. Results indicate that VK4-40 did not significantly alter basal locomotion, suggesting that its therapeutic effects may not be mediated through disruptions in generalized motor function. Future research will focus on elucidating the neuropharmacological mechanisms underlying VK4-40's therapeutic actions and exploring its effects on psychostimulant-induced hyperlocomotion. …

Exploring The Neuroprotective Effects Of Cannabinoids On Oxygen Glucose Deprived Neurons In An In-Vitro Model Of Stroke, Bhavya Chatragadda, Emily Potts, Hang Ma, Navindra Seeram, Claudia Fallini

Senior Honors Projects

Stroke is a leading cause of long-term disability and decreased mobility worldwide. During stroke, neuronal damage results from both the initial oxygen-glucose deprivation and the increase in excitotoxicity and oxidative stress after restoration of blood flow, a phase called Ischemia-Reperfusion Injury (IRI). Reducing the impact of these processes could result in better outcomes for post-stroke patients by preventing excessive neuronal death. Many natural compounds derived from the Cannabis Sativa plant have been tested for neuroprotective effects due to their potential antioxidant properties. We hypothesized that neurons treated with cannabinoids immediately after experiencing an acute ischemic event will have an overall …

Code For Care: Hypertension Prediction In Women Aged 18-39 Years, Kruti Sheth

Electronic Theses, Projects, and Dissertations

The longstanding prevalence of hypertension, often undiagnosed, poses significant risks of severe chronic and cardiovascular complications if left untreated. This study investigated the causes and underlying risks of hypertension in females aged between 18-39 years. The research questions were: (Q1.) What factors affect the occurrence of hypertension in females aged 18-39 years? (Q2.) What machine learning algorithms are suited for effectively predicting hypertension? (Q3.) How can SHAP values be leveraged to analyze the factors from model outputs? The findings are: (Q1.) Performing Feature selection using binary classification Logistic regression algorithm reveals an array of 30 most influential factors at an …

Modeling An Infection Outbreak With Quarantine: The Sibkr Model, Mikenna Dew, Amanda Langosch, Theadora Baker-Wallerstein

Rose-Hulman Undergraduate Mathematics Journal

Influenza is a respiratory infection that places a substantial burden in the world population each year. In this project, we study and interpret a data set from a flu outbreak in a British boarding school in 1978 with mathematical modeling. First, we propose a generalization of the SIR model based on the quarantine measure in place and establish the long-time behavior of the model. By analyzing the model mathematically, we determine the analytic formulas of the basic reproduction number, the long-time limit of solutions, and the maximum number of infection population. Moreover, we estimate the parameters of the model based …

Nanoparticles For Applications In Specific Diagnostics And Precision Medicine, Naxhije Berisha

Dissertations, Theses, and Capstone Projects

Heterogeneity is common in the expression of cancer and treatment response. Precision medicine enables healthcare providers to tailor medical care to an individual's distinct genetic and environmental makeup. This customization has the potential to result in more efficient treatments while minimizing side effects. We believe that by studying the interface of nanotechnology and cancer medicine we can elucidate innovative solutions that address the challenges of disease heterogeneity. This includes advancements in drug delivery, formulations development, and diagnostic sensing. We highlight three studies that use nanotechnology for applications in precision medicine. In Chapter 2, we highlight design optimization of drug formulations …

A Tale Of Two Viruses: Why Smallpox Was Eradicated And Polio Persists, Katherine G. Mcgough, Erin N. Bodine

Spora: A Journal of Biomathematics

The smallpox and poliomyelitis (polio) viruses were, at a time, one of the largest threats to global public health killing millions until global eradication campaigns were put into effect. Vaccination led to the eradication of smallpox and the elimination of polio for most of the world. However, polio continues to persist at endemic levels in Pakistan and Afghanistan. We developed ODE models of smallpox and polio to explore differences in transmission dynamics and determine if the underlying biology has made poliomyelitis more difficult to eradicate. Our model analysis shows there are multiple factors which should allow polio to have a …

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …