Disease Modeling Commons^™

Mglu5 Inhibition In The Basolateral Amygdala Prevents Estrous Cycle-Dependent Changes In Cue-Induced Cocaine Seeking, Claire M. Corbett, Emily N. D. Miller, Jessica A. Loweth

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced craving and relapse vulnerability compared to males. In a rodent model of cocaine craving and relapse vulnerability, cue-induced cocaine seeking behavior following weeks of withdrawal from extended-access cocaine self-administration is higher in females in the estrus stage of the reproductive (estrous) cycle (Estrus Females) compared to both Males and females in all other stages (Non-Estrus Females). However, the neuronal substrates and cellular mechanisms underlying these …

Vitamin C Contributes To Epigenetic Regulation Of Genes Related To Diabetic Retinopathy In Retinal Endothelial Cells, Elizabeth L. Turner, Jonathon Reynolds, Walker Kay, Marianne Becnel, Matthew Conway, Alexander Kim, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

Potential Alzheimer's Disease Plasma Biomarkers, Taylor Estepp

Theses and Dissertations--Epidemiology and Biostatistics

In this series of studies, we examined the potential of a variety of blood-based plasma biomarkers for the identification of Alzheimer's disease (AD) progression and cognitive decline. With the end goal of studying these biomarkers via mixture modeling, we began with a literature review of the methodology. An examination of the biomarkers with demographics and other health factors found evidence of minimal risk of confounding along the causal pathway from biomarkers to cognitive performance. Further study examined the usefulness of linear combinations of biomarkers, achieved via partial least squares (PLS) analysis, as predictors of various cognitive assessment scores and clinical …

Sex Dimorphisms Of Aldosterone And High Salt Induced Aortic Aneurysms In Mice, Xufang Mu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aortic aneurysms, a permanent enlargement in the aorta, is a devastating disease with a high mortality rate after rupture. Aortic aneurysms exhibit strong sex dimorphisms: men are at higher risk than women while women experience worse outcomes if diagnosed. Currently, the only intervention is by open surgery or endovascular repair, and no drugs are approved for blunting the disease progression. This highlights the needs for mechanistic studies for sex-specific therapeutic targets.

Our lab established the mouse model in which mineralocorticoid receptor (MR) agonist aldosterone induces aortic aneurysms in the presence of high salt in male mice age-dependently, mimicking the aging …

Marineepi: A Gui-Based Matlab Toolbox To Simulate Marine Pathogen Transmission, Gorka Bidegain, Tal Ben-Horin, Eric N. Powell, John M. Klinck, Eileen E. Hofmann

CCPO Publications

The Graphical User Interface (GUI) MarineEpi is presented as a Matlab toolbox for easily (i) constructing disease transmission models for different marine host-pathogen systems, (ii) running simulations by specifying initial conditions and model parameters, and (iii) interpreting the resulting time series of the host and pathogen population dynamics. MarineEpi users can generate models for systems in which pathogen transmission occurs through contact with infected individuals (SI), contact with dead infected individuals (SID), contact with environmental pathogens released by infected individuals (SIP), and contact with environmental pathogens released by dead infected individuals (SIPD). MarineEpi is a freely available GUI that provides …

Heart Disease Prediction Using Stacking Model With Balancing Techniques And Dimensionality Reduction, Ayesha Noor, Nadeem Javaid, Nabil Alrajeh, Babar Mansoor, Ali Khaqan, Safdar Hussain Bouk

School of Cybersecurity Faculty Publications

Heart disease is a serious worldwide health issue with wide-reaching effects. Since heart disease is one of the leading causes of mortality worldwide, early detection is crucial. Emerging technologies like Machine Learning (ML) are currently being actively used by the biomedical, healthcare, and health prediction industries. PaRSEL, a new stacking model is proposed in this research, that combines four classifiers, Passive Aggressive Classifier (PAC), Ridge Classifier (RC), Stochastic Gradient Descent Classifier (SGDC), and eXtreme Gradient Boosting (XGBoost), at the base layer, and LogitBoost is deployed for the final predictions at the meta layer. The imbalanced and irrelevant features in the …

Burkholderia Collagen-Like Protein 8, Bucl8, Is An Outer-Membrane Component Of A Novel Efflux Pump And Immunogenic Vaccine Candidate, Megan Elizabeth Grund

Graduate Theses, Dissertations, and Problem Reports (ETD)

Burkholderia spp. are Gram‐negative intrinsically resistant bacteria that are responsible for environmental and nosocomial infections of clinical and biodefense concern. Our laboratory previously identified in silico Burkholderia collagen-like protein 8 (Bucl8) in the BSL-3 pathogens Burkholderia pseudomallei and Burkholderia mallei (Figure 1). The protein sequence of Bucl8 contains tandem outer-membrane efflux protein domains (OEP) typical of efflux systems and a unique collagen-like domain (CL) consisting of a repeating sequence of Glycine-Alanine-Serine (GAS). Because efflux pumps are often a mechanism of pathogenicity and antibiotic resistance, we investigated Bucl8 further. Here, we determined that the locus of bucl8 contains genes …

Cost-Benefit Analysis Of Increased Water Treatment Plant Service Goals On Reducing Water Quality Risk, Briton Polen, Kendra Sanner

Williams Honors College, Honors Research Projects

To treat water to make it safe to drink, disinfection processes are used in water treatment plants. These disinfection processes produce disinfection byproducts (DBPs) through the reaction of organic matter and the disinfectant, such as chlorine. DBPs have been shown to pose a cancer risk to consumers. In this report, the focus is on two types of DBPs, trihalomethanes (THMs) and haloacetic acids (HAAs). The cancer risks associated with DBPs are analyzed through ingestion and inhalation pathways. Ingestion and inhalation consist of common water uses like drinking, cooking, or bathing. In addition to this, DBPs have been shown to increase …

A Machine Learning Approach For Early Diagnosis Of Transthyretin Amyloid Cardiomyopathy Among Heart Failure Patients, Tanjim Ahmed

Graduate Theses, Dissertations, and Problem Reports (ETD)

Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a rare, progressive, and fatal disease. Prevalence of ATTR-CM ranges from 4 to 17 per 100000 cases where the mean survival time is less than 4 years. It has a history of being underdiagnosed and misdiagnosed. The diagnosis delay has a weighted mean of 6.1 years for wild-type ATTR-CM. Low awareness, the necessity of invasive procedures, and lack of treatment are the key reasons for delayed diagnosis. But, with the introduction of non-invasive tests like nuclear scintigraphy with ^99mTC-PYP and the disease modifying drug Tafamidis, the diagnosis delay signifies a missed opportunity to increase …

Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cells rely on heat shock proteins (HSP) to facilitate and regulate the folding of the substrate proteins into their native state, and degradation if misfolding cannot be prevented. HSP90, a member of the HSP family, is a potential target for treatment of cancer and neurodegenerative diseases. Unfortunately, several clinical trials for cancer treatment have been discontinued due to cell toxicity accompanying HSP90 inhibition. HSP90 has four distinct but structurally similar paralogs. HSP90 inhibitors target all the paralogs despite increasing proof of functional differences among the paralogs. Understanding the in vivo function of HSP90 and the role played by each paralog …

Establishment Of An In Vivo Streptozotocin-Induced Type 1 Diabetes Model Recapitulating Early Brain And Retinal Fibrosis, Kia Bourdot, Lucy Dawson, Igor Kuzin, Arturo Bravo Nuevo, Zeus Antonello

Cooper Rowan Medical Journal

INTRODUCTION: Diabetes has risen to one of the top American public health concerns. The hyperglycemic state of chronic diabetes leads to microvascular and macrovascular changes that predispose patients to delayed wound healing and organ fibrosis. The validation of models to specifically detect early, quantifiable fibrotic changes seen in the diabetic state is of fundamental importance for understanding the diabetic pathophysiology and exploring earlier management options. Here, we investigated if we could detect early signs of internal fibrosis in a streptozotocin (STZ) diabetic mouse model by quantifying α-SMA expression in various organs using flow cytometry.

METHODS: We used a low-dose STZ-induced …

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations and Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) is a rapidly progressing, rare and highly lethal form of breast cancer. IBC is a clinical diagnosis, requiring >1/3 involvement on the affected breast and/or skin by erythema, and disease onset of < 6 months. The clinical symptoms of IBC vary in severity and presentation, these include redness, warmth, skin thickening and bruised or pink/purple discoloration appearance and skin changes such as peau d’orange. These skin symptoms are not attributed to inflammation, rather IBC is characterized by florid lymphovascular tumor emboli clogging dermal lymphatics. This leads to “classic” symptoms of breast swelling and skin edema or discoloration. To date, unique genomic drivers which differentiate IBC from non-IBC invasive breast cancers have not been identified highlighting a role for the microenvironment. Several epidemiological studies have unveiled subtype-specific risk factors associated with IBC that are known to alter the microenvironment. Obesity is an established risk factor for all subtypes of IBC. Never-breastfeeding increases risk for developing the most aggressive, triple-negative IBC. Further, never breastfeeding is associated with later clinical stage and worse outcomes. We worked to model these overlapping risk factors to understand microenvironment changes that may lead to the lymphatic change’s indicative of IBC.

First, we investigated the association of a “classic” triad of clinical IBC signs with overall survival among patients to demonstrate the most overt clinical findings of lymphatic involvement were impacting prognosis. We evaluated a triad of IBC signs, including swollen involved breast, nipple change, and diffuse skin change, using breast medical photographs from patients enrolled on a prospective IBC registry. We reported that the …

Species Data And Vector Modeling: Evaluating Datasets For Improved Models Of Ixodes Ricinus Tick Distribution In Europe Under A Changing Climate, Steven Jones

Electronic Theses and Dissertations

To increase capacity for monitoring and surveillance of tick-borne diseases, publicly available tick distribution and climate change datasets are required to create accurate predictive distribution models. It is difficult, however, to assess model accuracy and utility when using incomplete datasets.  The more recent development of comprehensive tick databases for Europe and availability of climate change scenarios from multiple IPCC Assessment Reports allows for improved modeling efforts. Multiple tick datasets were combined and three climate change projections were compared by predicting current and future distributions of Ixodes ricinus ticks in Europe using the MaxEnt species distribution model. Overall, much of Europe …

Physics-Informed Neural Networks For Informed Vaccine Distribution In Heterogeneously Mixed Populations, Alvan Arulandu, Padmanabhan Seshaiyer

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Humanizing Mathematical Biology Research And Education, Carrie Diaz Eaton, Ognyan Simeonov

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Effect Of Vaccine Misinformation On Disease Spread, Anthony Delegge, Yina Wang

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Stochastic Models Of Zoonotic Avian Influenza With Multiple Hosts, Environmental Transmission, And Migration In The Natural Reservoir, Kaia Smith

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Modeling The Effects Of Media Awareness On Sars-Cov-2 Transmission In Georgia, Eric Numfor

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

An Agent-Based Model Of Environmental Transmission Of Clostridioides Difficile In Healthcare Settings, Max Lewis, Laila Mahrat, Cara Sulyok, Brittany Stephenson

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.