Comprehensive Investigation Of Proteoglycan Gene Expression In Breast Cancer: Discovery Of A Unique Proteoglycan Gene Signature Linked To The Malignant Phenotype, Simone Buraschi, Gabriel Pascal, Federico Liberatore, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Solid tumors present a formidable challenge in oncology, necessitating innovative approaches to improve therapeutic outcomes. Proteoglycans, multifaceted molecules within the tumor microenvironment, have garnered attention due to their diverse roles in cancer progression. Their unique ability to interact with specific membrane receptors, growth factors, and cytokines provides a promising avenue for the development of recombinant proteoglycan-based therapies that could enhance the precision and efficacy of cancer treatment. In this study, we performed a comprehensive analysis of the proteoglycan gene landscape in human breast carcinomas. Leveraging the available wealth of genomic and clinical data regarding gene expression in breast carcinoma and …

The Passing Of A Giant In Proteoglycan Research: Robert J. Linhardt (1953–2025), Renato V. Iozzo, Fuming Zhang, Paul L. Deangelis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Exploring The Role Of Irf4 In The Sensitivity Of Mantle Cell Lymphoma Cells To Bruton's Tyrosine Kinase Inhibitors, Artjoms Portnojs

Peninsula Medical School Theses

Introduction and aim: Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell lymphoma. Therapy using Bruton’s tyrosine kinase (BTK) inhibitors has improved clinical outcomes but primary and secondary resistance to BTK inhibitor (BTKi) therapy affects more than half of MCL patients. Resistance most often arises through gene mutations in cells protected from BTKi effects within the local tissue microenvironment. This thesis develops previous work by the group identifying IRF4 as a central mediator of resistance to BTK inhibitors in MCL; the thesis aims to understand how resistance develops and to identify mechanisms to prevent or overcome BTKi resistance in …

Improving The Efficiency Of Modelling Complex Physical Activity Data Using Longitudinal Compositional Data Analysis, Jade Chynoweth

Peninsula Medical School Theses

Physical activity (PA) data are often objectively collected using an accelerometer worn by the participant, with data collected over a pre-specified period. PA has historically been summarised as a single numerical measure, often the number of minutes spent in moderate-to-vigorous PA, disregarding PA performed at lower intensities. The number of minutes spent in PA during the collection period is also associated with wear time of the accelerometer. Therefore, modelling all PA intensities as proportions of the total is more appropriate.Standard statistical methods cannot model more than one intensity of PA within a single model, as the intensities are likely to …

The Discovery Of P62-Dependent Processing Bodies, Elizabeth Barrow

Peninsula Medical School Theses

The cellular degradation process autophagy can be a selective process during which, cellular components, such as excess proteins, can be marked for degradation by the post translational modification ubiquitination. Proteins that act as selective autophagy receptors can recognise the ubiquitinated substrates and target them to the selective autophagy pathway, facilitating their degradation and thereby mediating cellular homeostasis. The selective autophagy receptor Sequestome 1 (p62) undergoes liquid-liquid phase separation (LLPS) to form p62 bodies to mediate the autophagic degradation of ubiquitinated proteins. At the time of this research, it was unknown whether p62 could exist in a differential droplet form to …

Links Between Adhesion Signalling And Cell Cycle Regulation In Bladder Cancer Cells, Michael Jones

Peninsula Medical School Theses

Bladder cancer is the most common malignancy of the urinary tract. However, bladder cancer is a highly heterogenous disease and our understanding of the mechanisms that drive disease progression remain ill-defined. Additionally, a limited range of therapeutics and the dismal prognosis of patients with advanced disease highlights a need for better understanding of the mechanisms that drive bladder cancer progression, in order to identify new avenues for therapy. The extracellular matrix (ECM) represents a key component of the tumour microenvironment whose biochemical and mechanical characteristics contribute to all the hallmarks of cancer. However, the role of the ECM in bladder …

Acute, Low-Grade Inflammation Elevates White Matter Sensitivity To Ischaemia, Alex Mellor

Peninsula Medical School Theses

Ischaemic brain injuries, including ischaemic stroke, are highly prevalent neurological diseases. Acute, low-grade inflammation, often resulting from peripheral infection, has emerged as a risk factor. White matter axons, and their supporting glia, are susceptible to both ischaemic and neuroinflammatory injury. The mechanisms behind ischaemic injury in white matter are well established. However, the white matter response to acute, low-grade inflammation, and how this can interact with co-morbidities such as cerebral ischaemia, are yet to be examined. This thesis evaluated the response of white matter to acute, low-grade inflammation and the downstream effects this had on its sensitivity to ischaemia. Here, …

Exploring The Immune Landscape Of The Tumour Microenvironment In Meningiomas And The Role Of Immune Infiltration In Meningioma Models, Ting Zhang

Peninsula Medical School Theses

Background: Meningiomas are the most common primary intracranial tumours, ranging from benign to highly aggressive forms. While surgery is effective for low-grade meningiomas, certain grade 1 tumours, as well as grade 2, 3, and recurrent cases are more aggressive and require new therapeutic approaches. Immunotherapy shows promise, however, the role of tumour microenvironment (TME), particularly tumour-associated macrophages (TAMs), in meningiomas remains poorly understood, especially concerning genomic alterations. Aims: To investigate the immune landscape of meningiomas classified by grades, genotypes and methylation classes (MCs), and to elucidate the role of the TAMs in meningioma progression utilising a patient-derived 3D co-culture model.Methods: …

Targeting Aldehyde Dehydrogenases In Nf2-Null Meningioma And Schwannoma, Libby Williams

Peninsula Medical School Theses

Meningioma and schwannoma are tumours of the brain and nervous system that are frequently driven by loss or mutation of the gene NF2, which encodes the tumour suppressor protein Merlin. Dysregulated Hippo pathway signalling, caused by NF2 loss, drives overexpression of aldehyde dehydrogenase 1A1 (ALDH1A1) in NF2-null schwannoma. High expression of ALDH1A1, and the related isoform ALDH1A3 have been identified as markers of cancer stem cell activity and have been correlated with poor prognosis and chemoresistance in several cancers. This project aims to clarify the role ofaldehyde dehydrogenase (ALDH) enzymes in meningioma tumours and evaluate their potential as future therapeutic …

Targeting Mertk On Tumour Cells And Macrophages: A Potential Intervention For Sporadic And Nf2-Related Meningioma And Schwannoma Tumours, Kevin Herrera Keane

Peninsula Medical School Theses

Although schwannomas and meningiomas are generally benign and slow-growing, the mass effect of either tumour within the nervous system causes life-altering symptoms. Individuals with NF2-related schwannomatosis may develop schwannomas and meningiomas, increasing tumour burden. The primary treatment for large or symptomatic schwannomas and meningiomas is surgical resection, which may not be suitable in cases involving tumours located near sensitive neuroanatomy or clinically vulnerable individuals. Not all schwannomas and meningiomas respond to alternative targeted treatments such as stereotactic radiosurgery or the vascular endothelial growth factor inhibitor bevacizumab. The main objective of this thesis was to investigate targeting of the receptor tyrosine …

Autolyzed Brewer's Yeast Enhances Growth And Intestinal Health In Early Life Stages Of Nile Tilapia (Oreochromis Niloticus L.), Sheu Odu-Onikosi, Taofik Momoh, Ben Eynon, Nicola Pontefract, Victor Kuri, Holger Kühlwein, Daniel Merrifield

School of Biological and Marine Sciences

The early life stages of fish are critical for determining the overall productivity and sustainability of aquaculture operations. This study investigated the effects of dietary autolyzed brewer's yeast (ABY) on the growth performance and intestinal health of Nile tilapia fry (Oreochromis niloticus). A 35-day feeding trial with 480 Nile tilapia fry across 12 experimental tanks tested the effects of diets supplemented with 1, 2, and 4 g/kg of ABY, with a control diet for comparison. The results indicated that the diet which had 1 g/kg ABY supplementation (ABY1) significantly enhanced the weight gain and specific growth rate (SGR) while reducing …

Expression Of Dementia Biomarkers In Appalachian And Non-Appalachian Elvo Patients During Thrombectomy, Neha Anil, Christopher J. Mclouth, Hunter S. Hazelwood, Elise Dahlke, Jacqueline A. Frank, Nathan Millson, Mais Al-Kawaz, Jordan P. Harp, Will Cranford, Shivani Pahwa, David Dornbos, Justin F. Fraser, Keith R. Pennypacker

Biostatistics Faculty Publications

Background/Context: Vascular Cognitive Impairment and Dementia (VCID) affects 25-30% of stroke patients and includes cognitive impairments caused by vascular injury, such as post-stroke dementia. Rehabilitation has the potential to improve the quality of life for patients at risk of developing dementia. However, there is currently no reliable method to identify those at risk of dementia after a stroke. Several biomarkers, including ADRD (Alzheimer’s disease and related dementias) biomarkers (Ab, tau, NfL, and GFAP) and angiogenic factors (VEGF, Flt-1, Tie-2, PIGF, and FGF) have been associated with the development of dementia. Populations in Appalachia experience a higher incidence of stroke and …

Effects Of Dietary L-Tryptophan On Growth Performance, Feed Utilization, And Protein Metabolism In Nile Tilapia (Oreochromis Niloticus), Israt Mishu, Lindee Mason, Ahmed Mustafa

Mansoura Veterinary Medical Journal

This research examines the impact of dietary L-tryptophan supplementation on growth performance, feed efficiency, and protein metabolism in Nile tilapia (Oreochromis niloticus) under stress and non-stress settings. This experiment evaluated essential growth metrics, encompassing weight gain, length gain, specific growth rate, feed conversion ratio, and protein energy retention. Nile tilapia were categorized into four experimental groups: a control group on a commercial diet, a control group supplemented with L-tryptophan (0.33%/kg feed), a stress-induced group receiving cortisol (0.02%/kg feed), and a stress-induced group receiving both cortisol (0.02%/kg feed) and L-tryptophan supplementation (0.33%/kg feed). The findings indicated that Ltryptophan supplementation significantly enhanced …

Securing The Internet Of Wetland Things (Iowt) Using Machine And Deep Learning Methods: A Survey, Guma Ali, Wamusi Robert, Maad M. Mijwil, Malik Sallam, Jenan Ayad

Mesopotamian Journal of Computer Science

Wetlands are essential ecosystems that provide ecological, hydrological, and economic benefits. However, human activities and climate change are degrading their health and jeopardizing their long-term sustainability. To address these challenges, the Internet of Wetland Things (IoWT) has emerged as an innovative framework integrating advanced sensing, data collection, and communication technologies to monitor and manage wetland ecosystems. Despite its potential, the IoWT faces substantial security and privacy risks, compromising its effectiveness and hindering adoption. This survey explores integrating machine learning (ML) and deep learning (DL) techniques as solutions to address the security threats, vulnerabilities, and challenges inherent in IoWT ecosystems. The …

Towards Achieving The Un Sustainable Development Goals: The Role Of Ai In Municipality Services, Thabit Sultan Mohammed, Karim Mohammed Aljebory, Ahmed Thabit Sultan

Mesopotamian Journal of Computer Science

In 2015, the United Nations adopted the Sustainable Development Goals (SDGs) to end poverty, protect the planet, and ensure global peace and prosperity by 2030. However, progress has been hindered by challenges like the COVID-19 pandemic, climate change, funding shortages, political instability, and data limitations. Municipal services, crucial to achieving the SDGs, provide essential functions like waste management, healthcare, and public safety. Artificial Intelligence (AI) offers innovative solutions to enhance these services, improving urban sustainability and fostering public-private collaboration. This research examines AI's role in municipal services, analyzing its applications, benefits, challenges, and future potential through case studies and expert …

Retinal Vessel Image Segmentation Based On Guided Filter And Neural Networks, Ibrahem Al-Jadir, Jawad S. Hameed, Husam Yahya, Dalia N. Al-Oboudi

Mesopotamian Journal of Artificial Intelligence in Healthcare

Accurate segmentation of retinal blood vessels is essential for the early diagnosis and monitoring of various ophthalmic and systemic diseases. This work shows how to use a modified U-Net architecture to improve how retinal blood vessels are segmented. The method uses rolling guidance filters with two different sets of parameters to make the edges of the vessels sharper and make it easier to tell them apart. Separate U-Net models process each filtered image independently, and then the outputs are combined to make the final segmentation result. Both networks are trained at the same time using a shared loss function. Tests …

Kafka In The Plague Years: Reinterpreting Absurdity In The 2020s, Chris Lownie

Electronic Theses & Dissertations (2024 - present)

No word better encapsulates the confusion and inequality proliferating in the post-2020 global world than “absurd.” Absurdity consumes the way we interact with one another, going about life-as-usual in pocket worlds in which the individual is alienated from both oneself and others. Life is defined by a series of problems that regularly go ignored by both institution and general populace alike, but not by the human body: the effects of sustained illness and reinfection by recurrent viruses in a world that no longer acknowledges their severity nor their pervasiveness nor steps we may take towards personal safety. Daily life has …

Explaining Mass Shooting Motivations: A Case Survey Analysis Of Us Mass Shootings (2006-2024), Isaiah H. Harris

Electronic Theses & Dissertations (2024 - present)

Research on the motivations behind mass shootings remains inconclusive as these events often lack a singular or explicit cause. The motivations of mass shooters are complex, shaped by the interplay of psychological, social, and ideological factors. While some attacks are clearly driven by extremist beliefs, others appear to stem from less defined forces such as depravity or sadistic intent. Existing typologies, such as Langman’s (2009) analysis of school shooters, offer valuable insight but are limited in scope. This study expands upon previous research by examining U.S. mass shootings from 2006 to 2024 to determine whether such events are more frequently …

A Social Exchange Perspective On Attentiveness As A Resource In Newcomer Relationship Development And Assimilation, Huy Q. Le

Electronic Theses & Dissertations (2024 - present)

My dissertation investigates the role of social relationships in newcomer socialization within organizations, emphasizing the importance of extra-role conversations in building affective trust and facilitating integration. I hypothesize that while attention to work-related tasks is crucial, engaging in extra-role conversations with supervisors and co-workers fosters affective trust, a key factor in socialization. I integrate social exchange theory, proposing that attention acts as a socioemotional resource exchanged in social interactions, leading to stronger affective trust and ultimately socialization outcomes. These informal interactions help newcomers adopt organizational values and integrate into social groups. I test my hypotheses using longitudinal archival data collected …

A Study Of Glyphosate, Pesticide Mixtures, And Metabolic Health Outcomes: Integrating Epidemiologic, Mechanistic, And Ecological Evidence On Environmental Drivers Of Metabolic Health, Sarah Otaru

Electronic Theses & Dissertations (2024 - present)

Glyphosate, the most extensively used herbicide worldwide, has become a ubiquitous environmental contaminant. Although initially considered safe due to its specific biochemical target in plants, emerging evidence suggests that chronic, low-level human exposure may disrupt metabolic processes. Simultaneously, the global rise in metabolic disorders such as metabolic syndrome (MetS), obesity, and type 2 diabetes, has created a pressing need to identify novel, potentially modifiable environmental contributors. This dissertation investigates the relationship between glyphosate and metabolic health through a triangulated framework that integrates individual-level epidemiological analysis, systematic synthesis of mechanistic evidence, and ecological evaluation of pesticide mixtures.

The first study employed …

Technological Development Of In-Cell Nmr: Microfluidic, Metabolomic, And Fluxomic Approaches, Nicholas Sciolino

Electronic Theses & Dissertations (2024 - present)

In the fields of structural biology, metabolomics, and fluxomics, there is a driving, technique-based concern when it comes to high-resolution spectrometry and its marriage to biological and physiological relevance. Sample preparation often involves cellular perturbation, lysate separation schemes, combinations with non-biological reagents, and timeline slack. Conceptually, the farther we get from the cell, the greater the potential disparity between what exists in vivo and our in vitro manipulations. This is particularly true when seeking to collect data on transfected targets of interest, and on sensitive metabolic equilibria that occur on the order of minutes. The question remains: if we are …

Assessing Antiretroviral Therapy Prescribing Practices In New York State For Pregnant People Living With Hiv, Beverly Amofah

Electronic Theses & Dissertations (2024 - present)

ABSTRACT

Objective: The Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission advises patient counseling to facilitate informed decision-making when evaluating changes in antiretroviral therapy (ART) during pregnancy and for patients to stay on suppressive regimens regardless of drug class. The purpose of this study was to investigate racial and ethnic disparities in the prescription of ‘preferred’ HIV drug regimens for pregnant people living with diagnosed HIV in New York State (NYS). This research also assessed whether prescribing practices for pregnant people on ART were consistent with Department of Health and Human Services (DHHS) guidelines.

Methods: A …

The Theoretical And Practical Limits Of Kolmogorov-Zurbenko Periodograms With Dynamic Smoothing In The Spectral Analysis Of Time Series Data, Barry M. Loneck

Electronic Theses & Dissertations (2024 - present)

The purpose of this Dissertation was to establish the theoretical and practical limits of Kolmogorov-Zurbenko periodograms with dynamic smoothing in contrast to standard periodograms with static smoothing, along with a practical application of Kolmogorov-Zurbenko time series analysis methods. It was determined that Kolmogorov-Zurbenko periodograms with dynamic smoothing were superior to standard periodograms with static smoothing in estimating signal frequencies with respect to sensitivity, accuracy, and resolution, and that they are robust in the face of missing data. However, their precision in estimating signal strength exceeds that of standard periodograms with static smoothing in only the most extreme circumstances and, thus, …

How Does Social Capital Influence The Preferences For Aging In The Community? Based On The Study Toward Older Adults In Yuexiu District, Guangzhou City, Biyun Xiang

Electronic Theses & Dissertations (2024 - present)

This study examines how social capital influences older adults’ preferences for aging in the community, focusing on Yuexiu District, Guangzhou. Using a mixed-methods approach, the study explores family, structural, and cognitive dimensions of social capital.

Quantitative data were collected through 439 surveys, with 400 valid responses from adults aged 60 and above. Regression analysis identified key predictors of aging-in-community preferences, including family financial support, care commitment, activities with grandchildren, community trust, mutual help, and service satisfaction.

Qualitative data from 10 interviews with community service workers revealed six themes: (1) access to services like fitness and health screenings; (2) levels of …

Essays On Place-Based Policy And Regional Economic Development, Tingting Peng

Electronic Theses & Dissertations (2024 - present)

The first chapter examines the economic impacts of large theme park openings in China from 2000 to 2020 using a newly compiled dataset on county-level theme parks and entrepreneurship. Leveraging the staggered openings of theme parks across various counties, we document three main findings. First, theme park openings lead to a 14% increase in entrepreneurial activities, especially in tourism-related service sectors. This result is robust to the instrumental variable approach, the heterogeneous treatment effect, alternative specification and measurement, and propensity score matching. Second, theme park openings generate spillover effects on neighboring counties within a 50-75 kilometer radius. Third, we identify …

Grandparenthood And Psychological Well-Being Of Middle-Aged And Older Adults: Multigenerational Family Relationships In China, Dandan Zhao

Electronic Theses & Dissertations (2024 - present)

This dissertation examines whether and how experiences of grandparenthood—including becoming a grandparent, providing grandchild care, living with grandchildren, and exchanging intergenerational support—affect the well-being of middle-aged and older adults in China. Drawing on data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018), a nationally representative survey of Chinese adults aged 45 and older, the study employs Ordinary Least Squares (OLS) regression and random effects models to investigate the associations between multigenerational family relationships and depressive symptoms among this population.

There is limited evidence that the transition to grandparenthood itself has a significant impact on psychological well-being. However, patterns …

Nat10 Stabilizes Immune Response Factors Aiding With Cellular Immune Response To Zika Virus Infection, Shawn Gianola

Electronic Theses & Dissertations (2024 - present)

Zika virus (ZIKV) remains a significant public health concern due to major gaps in our understanding of its infection mechanisms and immune evasion strategies. Despite its link to severe complications such as microcephaly and Guillain-Barré Syndrome (GBS), no vaccine or targeted antiviral therapies exist. Compounding this concern is the expanding habitat of ZIKV-carrying mosquito vectors, driven by climate change, which increases the risk of future outbreaks in previously unaffected regions.

One promising area of investigation involves post-transcriptional modifications (PTMs) chemical alterations to RNA that influence its stability, translation, and function. Although over 170 PTMs have been identified, their roles remain …

Exploring Characteristics Of Indiana's Local Park And Recreation Leaders, Amy L. Gregg, James A. Jones, Halyn Ferris

Midwest Social Sciences Journal

This was an exploratory study about the characteristics of Indiana’s local leaders in parks and recreation. Results of a statewide survey showed different roles of employees and volunteers in local agencies. In managing the supply side of recreation, they reported vast differences in scale of levels of populations served and natural resources managed, such as acres and trails. The Northern, Central and Southern regions were compared for types of local government, communities of different sizes, and nonprofit collaboration. Local leaders represented municipal, township and county providers collaborating with other local community organizations. Results showed that size of community served affected …

The Impossibility Of Religious Equality, Zalman Rothschild

Articles

The Supreme Court has recently adopted a new rule of religious equality: Laws unconstitutionally discriminate against religion when they deny religious exemptions but provide secular exemptions that undermine the law’s interests to the same degree as would a religious exemption. All the Justices and a cadre of scholars have agreed in principle with this approach to religious equality. This Essay argues that this new rule of religious equality is inherently unworkable, in part because it turns on treating that which is religious the same as its secular “comparators.” But religion is not comparable to anything neither in terms of its …

Towards A Framework To Integrate Smart Urban Agriculture Into City Planning In Egypt, Heba Adel Ahmed Hussein

Mansoura Engineering Journal

This study discusses challenges facing the expansion of urban agriculture in Egypt, investigates overcoming these challenges using smart solutions, and proposes a framework to integrate smart urban agriculture (SUA) into Egyptian cities’ plans. The proposed framework provides an insight into the aspects that should be considered before, during, and after transformation to SUA. This study could serve as a basis for the integration of smart agriculture into urban planning theories and practices, and as an inspiration for urban planners, designers, landscape architects, policymakers, and decision-makers to create strategies for promoting digital transformation in Egyptian cities.