Disease Modeling Commons^™

Identifying Novel Molecular Targets To Induce Ferroptosis In Drug-Tolerant Cancer Cells Through Computational Modeling, Haris J. Rana

Biological Sciences Undergraduate Honors Theses

Ferroptosis is an iron-dependent, reactive oxygen species (ROS)-driven form of regulated cell death in which the cell membrane is degraded by lipid peroxidation. It is regulated by multiple enzymes, such as glutathione peroxidase 4 (GPX4), which prevents membrane degradation by reducing lipid peroxides and protecting cells from oxidative damage. When inhibitors like RSL3 target GPX4, lipid peroxides build up, and toxic ROS compromises membrane integrity. Traditional anticancer treatments, such as most chemotherapies, aim to eliminate tumor cells by damaging DNA and triggering apoptosis. However, resistance to apoptosis is a “hallmark of cancer,” often resulting in treatment failure. As a distinct …

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 …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Transport Barriers Influence The Activation Of Anti-Tumor Immunity: A Systems Biology Analysis, Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Lance L. Munn

Faculty Journal Articles

Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and …

In Vitro And In Vivo Diabetic Models For Assessment Of Tissue Engineered Vascular Grafts, Juan Carlos Carrillo Garcia

All Dissertations

Diabetes has become one of the leading causes of lower-limb loss worldwide. Every 30 seconds, a person loses a limb due to diabetic-related vascular complications. About one-third of patients needing lower-limb bypass surgery have debilitated autologous vessels unsuitable for use, and no other good long-term options are available. These detrimental effects on the vasculature are caused mainly by the hyperglycemic and hyperlipidemic conditions derived from diabetes. Under these conditions, an increase in advanced glycation end products (AGEs) and reactive oxygen species leads to irreversible crosslinks of extracellular matrix proteins, accelerating vascular pathology through vascular stiffening, endothelial dysfunction, inflammation, atherosclerosis, fibrosis, …

Development Of A Computational Model To Investigate Pathways And The Effects Of Treatment In Fanconi Anemia, Sabrina Kellett

Biological Sciences Undergraduate Honors Theses

Fanconi Anemia (FA) is a rare type of anemia that is not easily studied and can have very detrimental effects. This disease compromises the bone marrow, resulting in decreased hemopoiesis. Symptoms of FA also include abnormalities in the brain and spinal cord, incorrect formation of the kidneys, abnormal formation of the heart and lungs, and a dramatically increased risk of developing cancer. FA can be caused by various mutations in any of the 22 genes that encode for proteins involved in what is called the FA DNA repair pathway. In healthy individuals, this pathway specifically repairs interstrand cross-links (ICLs) recognized …

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 …

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 …

A Unified Health Information System Framework For Connecting Data, People, Devices, And Systems, Wu He, Justin Zuopeng Zhang, Huanmei Wu, Wenzhuo Li, Sachin Shetty

Information Technology & Decision Sciences Faculty Publications

The COVID-19 pandemic has heightened the necessity for pervasive data and system interoperability to manage healthcare information and knowledge. There is an urgent need to better understand the role of interoperability in improving the societal responses to the pandemic. This paper explores data and system interoperability, a very specific area that could contribute to fighting COVID-19. Specifically, the authors propose a unified health information system framework to connect data, systems, and devices to increase interoperability and manage healthcare information and knowledge. A blockchain-based solution is also provided as a recommendation for improving the data and system interoperability in healthcare.

Novel Approaches For Enhancing Cell Survival And Function In Vivo, Ou Wang

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

FDA has approved several cell-based therapeutics and hundreds of cell therapy clinical trials are ongoing. Cells will be a significant type of medicine after small molecule and protein drugs. However, several obstacles need to be addressed to achieve the widespread use of cellular therapeutics. The first challenge is the low efficacy of cell transplantation due to low retention, survival, integration, and function of cells in vivo. The second challenge is producing a massive number of cells for clinical treatment with cost-effectively and reproducibly technologies.

In this thesis, we proposed and investigated two approaches to address these challenges. To begin …

Personalized Digital Phenotype Score, Healthcare Management And Intervention Strategies Using Knowledge Enabled Digital Health Framework For Pediatric Asthma, Utkarshani Jaimini, Amit Sheth

Publications

Asthma is a personalized, and multi-trigger respiratory condition which requires continuous monitoring and management of symptoms and medication adherence. We developed kHealth: Knowledge-enabled Digital Healthcare Framework to monitor and manage the asthma symptoms, medication adherence, lung function, daily activity, sleep quality, indoor, and outdoor environmental triggers of pediatric asthma patients. The kHealth framework collects up to 1852 data points per patient per day. It is practically impossible for the clinicians, parents, and the patient to analyze this vast amount of multimodal data collected from the kHealth framework. In this chapter, we describe the personalized scores, clinically relevant asthma categorization using …

A Model For Inhalation Of Infectious Aerosol Contaminants In An Aircraft Passenger Cabin, Bert A. Silich

International Journal of Aviation, Aeronautics, and Aerospace

Aerosol contamination of an aircraft cabin by infectious passengers is a concern of passengers, aircrew and the aviation industry. This may be especially important during a pandemic, such as COVID-19, where the full extent of aerosol transmission is not well understood. A statistical method to determine the number of infectious passengers on board along with a mathematical model estimating the contaminant concentration of aerosols in the cabin and the number of inhaled infectious particles by passengers is presented. An example is used to demonstrated how the results can be estimated during normal operations and emergency conditions with malfunctions of the …

Bibliometric Review On Applications Of Disease Detection Using Digital Image Processing Techniques, Jayant Jagtap, Rahil Sharma, Aryan Sinha, Nikhil Panda, Amulya Reddy

Library Philosophy and Practice (e-journal)

Advances around the field of deep learning and cognitive computing have allowed mankind to look and solve the problems of the world in a completely new way. Deep learning has been making huge advancements in the field of healthcare, which most importantly focuses upon disease detection and disease prediction. Techniques such as these have been conceptualized the idea of early detection and economical ways of treating the predicted disease in particular. Still, it has been observed that there seems to be no change in the way diagnosis of a particular disease takes place even in the 21^st generation of …

Feasibility Of Continuous Fever Monitoring Using Wearable Devices, Benjamin L. Smarr, Kirstin Aschbacher, Sarah M. Fisher, Anoushka Chowdhary, Stephan Dilchert, Karena Puldon, Adam Rao, Frederick M. Hecht, Ashley E. Mason

Publications and Research

Elevated core temperature constitutes an important biomarker for COVID-19 infection; however, no standards currently exist to monitor fever using wearable peripheral temperature sensors. Evidence that sensors could be used to develop fever monitoring capabilities would enable large-scale health-monitoring research and provide high-temporal resolution data on fever responses across heterogeneous populations. We launched the TemPredict study in March of 2020 to capture continuous physiological data, including peripheral temperature, from a commercially available wearable device during the novel coronavirus pandemic. We coupled these data with symptom reports and COVID-19 diagnosis data. Here we report findings from the first 50 subjects who reported …

Characterization Of Bone Pathology In Sickle Cell Disease And Therapeutic Strategies, Mykel D. Green

Dissertations and Theses

Sickle cell disease (SCD) is a genetic hemoglobinopathy that has grown into a global health concern. While the advances in medical treatment and management of SCD during childhood have drastically improved the overall survival of children, the transition from pediatric to adult services is significantly inadequate in comparison. Life expectancies of patients with SCD in first world countries such as the United States are shortened to averages of 42 and 48 years for men and women, respectively. Despite the increasing number of people living with SCD, remarkably, few detailed studies have described the clinical course and complications of the disease …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Seeing Eye To Eye: A Machine Learning Approach To Automated Saccade Analysis, Maigh Attre

Honors Scholar Theses

Abnormal ocular motility is a common manifestation of many underlying pathologies particularly those that are neurological. Dynamics of saccades, when the eye rapidly changes its point of fixation, have been characterized for many neurological disorders including concussions, traumatic brain injuries (TBI), and Parkinson’s disease. However, widespread saccade analysis for diagnostic and research purposes requires the recognition of certain eye movement parameters. Key information such as velocity and duration must be determined from data based on a wide set of patients’ characteristics that may range in eye shapes and iris, hair and skin pigmentation [36]. Previous work on saccade analysis has …

Modeling In The Physiology Classroom, Sowmya Anjur

Faculty Publications & Research

Physiology and Disease is a Biology elective at IMSA that has been developed to be mostly student-centered. Some examples of student projects include modeling heart structure to reflect function and creating LED arduino monitors to measure heart rate. Students also measure their lung capacity and blood pressure to demonstrate correlation of these values with heart rate, and trace the correlation back to neuronal controls. Projects such as these integrate other disciplines such as engineering and conform to NGSS Science and Engineering standards and NGSS Cross cutting Concepts standards. Students take responsibility for their own learning and articulate better on tests.

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline Alexandria De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation …

Investigating Smoke Exposure And Chronic Obstructive Pulmonary Disease (Copd) With A Calibrated Agent Based Model (Abm) Of In Vitro Fibroblast Wound Healing., J Alex Ratti, Angela Reynolds, Rebecca L. Heise

Biology and Medicine Through Mathematics Conference

No abstract provided.

Modeling Pharmaceutical Inhibition Of Glucose-Stimulated Renin-Angiotensin System In Kidneys, Ashlee N. Ford Versypt, Minu R. Pilvankar, Hui Ling Yong

Biology and Medicine Through Mathematics Conference

No abstract provided.

Investigating Smoke Exposure And Chronic Obstructive Pulmonary Disease (Copd) With A Calibrated Agent Based Model (Abm) Of In Vitro Fibroblast Wound Healing., James A. Ratti

Theses and Dissertations

COPD is characterized by tissue inflammation and impaired remodeling that suggests fibroblast maintenance of structural homeostasis is dysregulated. Thus, we performed in vitro wound healing experiments on normal and diseased human lung fibroblasts and developed an ABM of fibroblasts closing a scratched monolayer using NetLogo to evaluate differences due to COPD or cigarette smoke condensate exposure. This ABM consists of a rule-set governing the healing response, accounting for cell migration, proliferation, death, activation and senescence rates; along with the effects of heterogeneous activation, phenotypic changes, serum deprivation and exposure to cigarette smoke condensate or bFGF. Simulations were performed to calibrate …

Pattern Discovery In Brain Imaging Genetics Via Scca Modeling With A Generic Non-Convex Penalty, Lei Du, Kefei Liu, Xiaohui Yao, Jingwen Yan, Shannon L. Risacher, Junwei Han, Lei Guo, Andrew J. Saykin, Li Shen, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, Charles D. Smith, Gregory Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Neurology Faculty Publications

Brain imaging genetics intends to uncover associations between genetic markers and neuroimaging quantitative traits. Sparse canonical correlation analysis (SCCA) can discover bi-multivariate associations and select relevant features, and is becoming popular in imaging genetic studies. The L1-norm function is not only convex, but also singular at the origin, which is a necessary condition for sparsity. Thus most SCCA methods impose ℓ₁-norm onto the individual feature or the structure level of features to pursuit corresponding sparsity. However, the ℓ₁-norm penalty over-penalizes large coefficients and may incurs estimation bias. A number of non-convex penalties are proposed to reduce …

A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner

Biomedical Engineering ETDs

Multiscale, hybrid computer modeling has emerged as a valuable tool in the fields of computational systems biology and mathematical oncology. In this work, we present an overview of the motivations for, and development and implementation of, three hybrid multiscale models of the mammary gland system and early stage ductal carcinoma in situ (DCIS) in the gland. Pubertal mammary gland development was described first using a two-dimensional, lattice-based hybrid agent-based model description of the mammary terminal end bud (TEB), and then with a three-dimensional lattice-free TEB model. Both models implement a discrete, agent-based description of the cell scale, and a continuum, …

Using Mathematical Modeling To Unmask The Concealed Nature Of Long Qt-3 Syndrome, Steven Poelzing, Amara Greer-Short, Seth H. Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Ischemia Impairs Vasodilation In Skeletal Muscle Resistance Artery, Kyle Remington Struthers

Master's Theses

Functional vasodilation in arterioles is impaired with chronic ischemia. We sought to examine the impact of chronic ischemia and age on skeletal muscle resistance artery function. To examine the impact of chronic ischemia, the femoral artery was resected from young (2-3mo) and adult (6-7mo) mice and the profunda femoris artery diameter was measured at rest and following gracilis muscle contraction 14 days later using intravital microscopy. Functional vasodilation was significantly impaired in ischemic mice (14.4±4.6% vs. 137.8±14.3%, p<0.0001 n=8) and non-ischemic adult mice (103.0±9.4% vs. 137.8±14.3%, p=0.05 n=10). In order to analyze the cellular mechanisms of the impairment, a protocol was developed to apply pharmacological agents to the experimental preparation while maintaining tissue homeostasis. Endothelial and smooth muscle dependent vasodilation were impaired with ischemia, 39.6 ± 13.6% vs. 80.5 ± 11.4% and 43.0 ± 11.7% vs. 85.1 ± 10.5%, respectively. From this data, it can be supported that smooth muscle dysfunction is the reason for the observed impairment in arterial vasodilation.