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The Influence Of Scientific, Genetic, And Health Literacy On Carrier Screening Decision-Making, Brenna D. Albracht May 2025

The Influence Of Scientific, Genetic, And Health Literacy On Carrier Screening Decision-Making, Brenna D. Albracht

Dissertations and Theses (Open Access)

For those wishing to assess their reproductive risks and make informed decisions in their reproductive planning, carrier screening for autosomal recessive and X-linked conditions, as well as cell-free DNA (cfDNA) screening for aneuploidy, are recommended during pregnancy. Despite similarities in purpose, sample requirements, insurance coverage, and safety, a lower percentage of individuals elect carrier screening than cfDNA screening, suggesting there may be a disconnect in what patients perceive as valuable information for their pregnancy. Previous studies have attempted to explain the factors associated with carrier screening uptake or decline; however, no models have yet accounted for a patient’s literacy level …


Achieving The Practice-Based Competencies: Are More Than 50 Cases Needed?, Farren Lopez May 2025

Achieving The Practice-Based Competencies: Are More Than 50 Cases Needed?, Farren Lopez

Dissertations and Theses (Open Access)

Genetic counseling graduate programs are required to provide didactic coursework and fieldwork experiences to foster development of the practice-based competencies (PBCs) in trainees. Currently, every graduating trainee must log a minimum of 50 participatory encounters to demonstrate readiness for entry-level practice of the PBCs. Previous studies have noted that many trainees exceed the 50-case standard, raising the question of whether this minimum satisfies the training needs of every student. To assess the perceived number of encounters needed for graduates to independently perform the PBCs, a survey was administered to 2023 and 2024 graduates of North American genetic counseling training programs. …


Uncovering A Fundamental Mechanism Underlying Female Oocyte Quality And Rasopathies Using C. Elegans As A Model System, Han Bit Baek May 2025

Uncovering A Fundamental Mechanism Underlying Female Oocyte Quality And Rasopathies Using C. Elegans As A Model System, Han Bit Baek

Dissertations and Theses (Open Access)

Signaling pathways are molecular networks that allow cells to communicate between and within themselves. They are crucial for the coordination of diverse cellular processes and are the molecular mechanism in which cells sense and respond to their environment. RAS (Rat Sarcoma) is a small GTPase that transmits extracellular growth factor signals through a downstream kinase cascade and ERK (Extracellular-signal regulated kinase) is the terminal kinase, and it controls cellular processes such as proliferation, differentiation, and survival by phosphorylating its downstream effectors. This post translational modification regulates the effector by modulating its activity, levels, and/or interaction with other molecules. Given the …


Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield May 2025

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …


Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave May 2025

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …


Denial Of Inpatient Genetic Testing: A Study On Outpatient Yield And Outcomes, Cindy Y. Canales May 2025

Denial Of Inpatient Genetic Testing: A Study On Outpatient Yield And Outcomes, Cindy Y. Canales

Dissertations and Theses (Open Access)

This study investigates the difference in diagnostic yield between patients approved for inpatient genetic testing compared to those denied inpatient testing and the effect of an earlier diagnosis on outcomes and medical/clinical care. In the literature, research has explored the impact of a diagnostic delay for patients with genetics conditions, assessed the utility of genetic testing in the inpatient setting, and described the impact to care of an earlier diagnosis. However, gaps remain on research exploring the diagnostic yields of inpatient versus outpatient settings and the potential impact to care an inpatient genetic testing request denial may pose. This is …


Evaluating Bone Fracture Healing In A Rabbit Model Using Doppler Imaging Modes, Shear Wave Elastography, X-Ray, And Dual-Energy X-Ray Absorptiometry, Priscilla Machado, Rachel Blackman, Ji-Bin Liu, Collleen Dempsey, Flemming Forsberg, Traci Fox May 2025

Evaluating Bone Fracture Healing In A Rabbit Model Using Doppler Imaging Modes, Shear Wave Elastography, X-Ray, And Dual-Energy X-Ray Absorptiometry, Priscilla Machado, Rachel Blackman, Ji-Bin Liu, Collleen Dempsey, Flemming Forsberg, Traci Fox

Department of Radiology Faculty Papers

OBJECTIVE: This study investigated methods of evaluating the bone fracture healing process using superb microvascular imaging (SMI; two modes color SMI [cSMI] and monochromeSMI [mSMI]), and shear wave elastography (SWE), relative to X-ray, dual-energy X-ray absorptiometry (DXA), and platelet endothelial cell adhesion molecule 1 (PECAM-1) also know as cluster of differentiation 31 (CD-31) staining in a rabbit model.

METHODS: This IACUC-approved study involved eight rabbits that underwent a bilateral fibula osteotomy and were followed for 7 or 21 days (Groups 1 and 2 with 4 rabbits in each). Ultrasound examinations using cSMI, mSMI, and SWE were performed on Days 0, …


Pregnancy Care Integrating Translational Science, Everywhere (Precise): A Prospective Cohort Study Of African Pregnant And Non-Pregnant Women To Investigate Placental Disorders – Cohort Profile, Rachel Craik, Joseph Akuze, Marie-Laure Volvert, Hannah Blencowe, Moses Mukhanya, Angela Koech, Grace Mwashigadi, Marleen Temmerman, Marvin Ochieng, Emily Mwadime May 2025

Pregnancy Care Integrating Translational Science, Everywhere (Precise): A Prospective Cohort Study Of African Pregnant And Non-Pregnant Women To Investigate Placental Disorders – Cohort Profile, Rachel Craik, Joseph Akuze, Marie-Laure Volvert, Hannah Blencowe, Moses Mukhanya, Angela Koech, Grace Mwashigadi, Marleen Temmerman, Marvin Ochieng, Emily Mwadime

Centre of Excellence in Women and Child Health

Purpose: The Pregnancies' Care Integrating translational Science, Everywhere Network was established to investigate specific placental disorders (pregnancy hypertension, preterm birth, fetal growth restriction and stillbirth) in sub-Saharan Africa. We created a repository of clinical and social data with associated biological samples from pregnant and non-pregnant women. Alongside this, local infrastructure and expertise in the field of maternal and child health research were enhanced.

Participants: Pregnant women were recruited in participating health facilities in The Gambia, Kenya and Mozambique at their first antenatal visit or at the time a placental disorder was diagnosed (Kenya and The Gambia only). Follow-up study …


Bridging Theory And Practice: Aquatic Occupational Therapy For Functional Rehabilitation In Parkinson’S Disease, Chelsea L. Tate May 2025

Bridging Theory And Practice: Aquatic Occupational Therapy For Functional Rehabilitation In Parkinson’S Disease, Chelsea L. Tate

Occupational Therapy Doctoral Capstones

The purpose of the Doctoral Capstone Experience and Project is to develop a theoretical framework and supporting program to guide the application of aquatic interventions specific to Parkinson’s disease treatment, while highlighting the therapeutic benefits that can be integrated into occupational therapy practice. The framework and program focus on improving overall physicality, cognitive, and functional performance for individuals with Parkinson’s disease.


Insights Into The Role Of The Glymphatic System In The Pathogenesis Of Post-Hemorrhagic Hydrocephalus, Ahmed T Massoud, Dillon A Noltensmeyer, Jenifer Juranek, Charles S Cox, Fred Christian Velasquez, Banghe Zhu, Eva M Sevick-Muraca, Manish N Shah May 2025

Insights Into The Role Of The Glymphatic System In The Pathogenesis Of Post-Hemorrhagic Hydrocephalus, Ahmed T Massoud, Dillon A Noltensmeyer, Jenifer Juranek, Charles S Cox, Fred Christian Velasquez, Banghe Zhu, Eva M Sevick-Muraca, Manish N Shah

The Brown Foundation: Institute of Molecular Medicine

Recently, it has been well-established that the glymphatic or glial-lymphatic system plays a vital role in the pathophysiology of various neurological compromise, especially hydrocephalus (HCP). Till now, the complete pathway is not yet fully understood, and little evidence is available from the literature that links hydrocephalus to disorders of the glymphatic system. Most published molecular studies and animal research have shown that, in models with hydrocephalus, the drainage of cerebrospinal fluid (CSF) via the glymphatic system is disrupted. This is strongly observed in normal pressure and post-hemorrhagic hydrocephalus cases. A thorough search of the literature to date yields scarce evidence …


A Psychometric Evaluation Of The Intentionality Bias Task, David Willard May 2025

A Psychometric Evaluation Of The Intentionality Bias Task, David Willard

Graduate Theses and Dissertations (2019 - present)

Intentionality Bias Task (IBT) provides quick and easy assessment of the tendency to overattribute intentionality to the behaviors of others. The IBT has been used repeatedly in research that has attempted to connect intentionality bias to a wide range of disorders and socio-emotional abilities, including schizophrenia spectrum disorder, autism spectrum disorder, and cognitive empathy. To date, however, there has been no systematic examination of the IBT’s psychometric properties. The present study attempts to fill this gap by testing whether the IBT possesses a reliable factor structure. Specifically, the 34 items of the IBT were written to reflect two types of …


Survival In Patients With Rheumatoid Arthritis And Recently Diagnosed Early-Stage Colorectal, Lung, Or Prostate Cancer Receiving Tumour Necrosis Factor Inhibitors: A Retrospective Cohort Study, Juan I Ruiz, Xiudong Lei, Sharon H Giordano, Hui Zhao, Suja S Rajan, Heather Lin, Maria E Suarez-Almazor May 2025

Survival In Patients With Rheumatoid Arthritis And Recently Diagnosed Early-Stage Colorectal, Lung, Or Prostate Cancer Receiving Tumour Necrosis Factor Inhibitors: A Retrospective Cohort Study, Juan I Ruiz, Xiudong Lei, Sharon H Giordano, Hui Zhao, Suja S Rajan, Heather Lin, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Background: Tumor necrosis factor (TNF) inhibitors could impair tumoural immunity in patients with rheumatoid arthritis and cancer. We aimed to investigate the association between survival and TNF inhibitor treatment during the first 3 years after a diagnosis of colorectal, lung, or prostate cancer in patients with rheumatoid arthritis.

Methods: In this cohort study, we conducted a secondary data analysis of the Surveillance, Epidemiology, and End Results Medicare-linked dataset. We included patients aged 66 years and older with rheumatoid arthritis diagnosed with colorectal, lung, or prostate cancer between Jan 1, 2008, and Dec 31, 2019, using ICD-O-3 site and histology codes. …


A Sex Comparison On The Effects Of Caveolin Scaffolding Domain On Fibrosis Formation After Chronic Sympathetic Stimulation, Crimsyn Price May 2025

A Sex Comparison On The Effects Of Caveolin Scaffolding Domain On Fibrosis Formation After Chronic Sympathetic Stimulation, Crimsyn Price

Undergraduate Honors Theses

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. There are various trends that influence the rates of cardiovascular disease in each country. Factors that create these trends involve diet, exercise, genetics, socioeconomic status, and geographical location. Additionally, CVD is typically higher in middle-income and lower-income classes. Hospital routes, rates of poverty, insurance policies, and lifestyle culture are all factors that can impact the time of treatment which in turn affect the rate of CVD. However, we explored in this study the shift in CVD women experience after menopause. Women were excluded from clinical trials until 1986, and the …


Finding Strength In The Struggle: The Impact Of Resilience On Life Satisfaction Among Veterans With Mental Illness, Marissa Gonzalez May 2025

Finding Strength In The Struggle: The Impact Of Resilience On Life Satisfaction Among Veterans With Mental Illness, Marissa Gonzalez

Open Access Theses & Dissertations

Background: Veterans living with mental illness often face challenges that impact their overall life satisfaction and adjustment to civilian life. While resilience is widely considered a protective factor, limited research has examined its role in conjunction with personality traits, psychosocial factors, and demographic characteristics. Purpose: This cross-sectional study examined the associations between resilience and life satisfaction among U.S. veterans with mental illnesses, while accounting for personality dimensions, demographic variables, and psychosocial factors. Methods: Secondary data from 156 veterans diagnosed with mental illness were analyzed. Hierarchical linear regression was used to assess the relationship between resilience and life satisfaction, controlling for …


The Relationships Between Behavioral And Sociocultural Constructs And Electronic Nicotine Delivery Systems (Ends) And Cannabis Patterns In Hispanic Young Adult University Students, Kevin Sandoval Medina May 2025

The Relationships Between Behavioral And Sociocultural Constructs And Electronic Nicotine Delivery Systems (Ends) And Cannabis Patterns In Hispanic Young Adult University Students, Kevin Sandoval Medina

Open Access Theses & Dissertations

The proliferation of both electronic nicotine delivery systems (ENDS) and cannabis has contributed to a concerning trend of dual usage, posing a greater public health risk, particularly pronounced among at-risk populations of increased substance use, such as Hispanic young adult college students. This study utilized the socioecological framework and social cognitive theory to observe behavioral and sociocultural constructs associated with dual use and identify potential risk and protective factors. Four hundred and twenty-one Hispanic young adult university students completed a cross-sectional survey assessing sociodemographics, depression, anxiety, stress, familism, acculturation, self-efficacy, and past month dual use and dual use recency of …


Racial And Ethnic Differences In Knowledge Of Gender-Affirming Care Among Community And Student Participants In The Bloom Transgender Health Education Program In The Paso Del Norte Region, 2022-2024, Tandra Ghosh May 2025

Racial And Ethnic Differences In Knowledge Of Gender-Affirming Care Among Community And Student Participants In The Bloom Transgender Health Education Program In The Paso Del Norte Region, 2022-2024, Tandra Ghosh

Open Access Theses & Dissertations

SUMMARY OF BACKGROUND AND SIGNIFICANCE: There is a noticeable lack of training and knowledge regarding gender-affirming care (GAC) among providers and within the general community. OBJECTIVE: Assess racial and ethnic disparities in knowledge of GAC among participants in BLOOM, a quasi-experimental transgender health education program in the Paso Del Norte region. HYPOTHESES: Among community and student participants at pre-survey, assess racial and ethnic differences in sociodemographic characteristics, preparedness, attitudes, and basic knowledge regarding LGBT clients/patients and GAC. METHODS: Secondary data among community (pre: 53; post: 14) and student (pre: 29; post: 17) BLOOM participants in 2022-2024 were used. Descriptive statistics …


Stereotypic Behaviors And Physiological Indicators Of Stress Occur In Horses With Restricted Durations Of Turnout, Elizabeth E. Rodgers May 2025

Stereotypic Behaviors And Physiological Indicators Of Stress Occur In Horses With Restricted Durations Of Turnout, Elizabeth E. Rodgers

Department of Animal Science: Dissertations, Theses, and Student Research

The confinement of horses to stalls with limited or no turnout time restricts their natural roaming behaviors, which potentially increases stress and behavioral stereotypies. This study investigated the impact of turnout duration on behavioral and physiological stress indicators in healthy horses. Adult horses (n = 11) were enrolled in a 3 treatment (0-, 15-, and 60-minute turnout/day) Latin square design, including 3 12 d experimental periods over 6 weeks. Horses were acclimated to turnout (24.38 x 64.01m indoor arena) and stalls (2.74 x 4.87m - 3.66 x 3.66m) stalls prior to data collection on day 1. Experienced handlers managed …


Digestibility, Palatability, And Nutrient Composition Of Three Species Of Whole Prey In Three Species Of Snakes, Morgan R. Kienzle May 2025

Digestibility, Palatability, And Nutrient Composition Of Three Species Of Whole Prey In Three Species Of Snakes, Morgan R. Kienzle

Department of Animal Science: Dissertations, Theses, and Student Research

Snakes in human care often lack diversity in the diet. Rodents account for the majority of meals, while wild snakes are consuming a varied diet composed of multiple different whole prey species. By feeding only one species of prey, the chance of nutrient deficiencies and other health concerns increases. To promote variety in the managed diet, two commercially available whole prey species (mice (Mus musculus) and chicks (Gallus spp.)) and one novel species (Seba’s short-tailed bats (Carollia perspicillata)), were analyzed for their dry matter (DM), organic matter (OM), crude protein (CP), crude fat …


Methane Mitigation And Its Effects On Energy Utilization In Lactating Dairy Cattle, Shan C. Sherwood May 2025

Methane Mitigation And Its Effects On Energy Utilization In Lactating Dairy Cattle, Shan C. Sherwood

Department of Animal Science: Dissertations, Theses, and Student Research

Improved methane (CH4) mitigation strategies are needed to achieve the greenhouse gas emission goals of the dairy industry. The first experiment was conducted to evaluate the effects of feeding black cumin (Nigella sativa) seed oil and acetate (BCA) on CH4 production and whole-animal energy utilization. Twelve dry Jersey cows were used in a 2-period crossover design study with 28d periods. The BCA treatment was compared to a control diet with corn oil. Both BCA and corn oil were added to the base diet as a top dress. Results from this study did not show any …


Evolution And Strengths Of School Lunch Programs In The United States And Japan, Sarah Ritterling May 2025

Evolution And Strengths Of School Lunch Programs In The United States And Japan, Sarah Ritterling

Honors Program: Senior Projects (Public)

School lunches around the world perform a vital role in children’s nutritional needs and overall health. These nutritional programs provide a chance for children to learn how to create a balanced meal and about the production and serving of food. However, many countries, including the United States and Japan, have taken different approaches to meet these goals, influenced by the needs of children and communities over time. The United States provides support, funding, and nutritional standards through the National School Lunch Program. Japan promotes the Basic Act of Shokuiku (food and nutrition education) within society and outlines goals for schools …


The Digital Glow: Effects Of Blue Light On Children And The Development Of A Children's Book To Raise Awareness On Eye Health, Mallory Easland May 2025

The Digital Glow: Effects Of Blue Light On Children And The Development Of A Children's Book To Raise Awareness On Eye Health, Mallory Easland

Honors Program: Senior Projects (Public)

As digital screen use continues to rise among children, concerns about the effects of blue light on eye health, sleep patterns, and overall well-being have grown. Research suggests that prolonged exposure to blue light can contribute to digital eye strain, disrupt circadian rhythms, and impact cognitive development. This thesis explores scientific literature on the biological effects of blue light, specifically on children, examining both the risks associated with excessive exposure and strategies for mitigating its impact.

In addition to conducting a comprehensive literature review, this project applies research findings to the creation of an educational children’s book aimed at promoting …


Gut Feeling: A Holistic Digital Tool For Managing Irritable Bowel Syndrome And Food Sensitivities, Hailey M. Olberding May 2025

Gut Feeling: A Holistic Digital Tool For Managing Irritable Bowel Syndrome And Food Sensitivities, Hailey M. Olberding

Honors Program: Senior Projects (Public)

Irritable Bowel Syndrome (IBS) and food intolerances are increasingly prevalent chronic gastrointestinal (GI) conditions that significantly impair quality of life. While the low-Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet has demonstrated success in symptom management, current digital tools fail to offer integrated, user-friendly platforms that holistically track contributing health factors. Gut Feeling is a mobile app (Appendix 1) and complementary website (Appendix 2) developed to fill this gap. By incorporating symptom logging, food intake tracking and complementary database, stress and sleep monitoring, and trend analysis, this platform empowers users to better understand their bodies and manage GI symptoms proactively. …


Entre La Reforma Y La Realidad: Salud Y Derechos Humanos En Costa Rica, Cuba Y Uruguay, Alyssa M. Nielsen May 2025

Entre La Reforma Y La Realidad: Salud Y Derechos Humanos En Costa Rica, Cuba Y Uruguay, Alyssa M. Nielsen

Honors Program: Senior Projects (Public)

Latinoamérica tiene varios sistemas para el cuidado de la salud y el acceso es uno de la lista de los derechos humanos. Esta región es la más desigual del mundo y se han logrado grandes avances, pero no se han distribuido equitativamente. Los sistemas de Cuba, Costa Rica y Uruguay son bien desarrollados, pero funcionan diferente. Costa Rica y Uruguay tienen opciones públicas y privadas y tienen maneras como la Mutualista en Uruguay y la Caja en Costa Rica para cubrir las visitas y servicios necesarios. Cuba es el sistema más controversial y tiene gran influencia de Castro, de donde …


Digital Twins, Synthetic Patient Data, And In-Silico Trials: Can They Empower Paediatric Clinical Trials?, Mohan Pammi, Prakesh S Shah, Liu K Yang, Joseph Hagan, Nima Aghaeepour, Josef Neu May 2025

Digital Twins, Synthetic Patient Data, And In-Silico Trials: Can They Empower Paediatric Clinical Trials?, Mohan Pammi, Prakesh S Shah, Liu K Yang, Joseph Hagan, Nima Aghaeepour, Josef Neu

Faculty, Staff and Students Publications

Randomised controlled trials are the gold standard to assess the effectiveness and safety of clinical interventions; however, many paediatric trials are discontinued early due to challenges in patient enrolment. Hence, most paediatric clinical trials suffer from lack of adequate power. Additionally, trials are expensive and might expose patients to unproven therapies. Alternatives to overcome these issues using virtual patient data—namely, digital twins, synthetic patient data, and in-silico trials—are now possible due to rapid advances in digital health-care tools and interventions. However, such digital innovations have been rarely used in paediatric trials. In this Viewpoint, we propose using virtual patient data …


Metastatic Medulloblastoma Remodels The Local Leptomeningeal Microenvironment To Promote Further Metastatic Colonization And Growth, Namal Abeysundara, Alexandra Rasnitsyn, Vernon Fong, Alexander Bahcheli, Randy Van Ommeren, Kyle Juraschka, Maria Vladoiu, Winnie Ong, Bryn Livingston, Pasqualino De Antonellis, Michelle Ly, Borja López Holgado, Olga Sirbu, Shahrzad Bahrampour, Hyun-Kee Min, Jerry Fan, Carolina Nor, Abhirami Visvanathan, Jiao Zhang, Hao Wang, Lei Qin, Ning Huang, Jonelle Pallotta, Tajana Douglas, Esta Mak, Haipeng Su, Karen Ng, Kevin Yang Zhang, Craig Daniels, Calixto-Hope G Lucas, Charles G Eberhart, Hailong Liu, Tao Jiang, Faiyaz Notta, Vijay Ramaswamy, Jüri Reimand, Marco Gallo, Jeremy N Rich, Xiaochong Wu, Xi Huang, Michael D Taylor May 2025

Metastatic Medulloblastoma Remodels The Local Leptomeningeal Microenvironment To Promote Further Metastatic Colonization And Growth, Namal Abeysundara, Alexandra Rasnitsyn, Vernon Fong, Alexander Bahcheli, Randy Van Ommeren, Kyle Juraschka, Maria Vladoiu, Winnie Ong, Bryn Livingston, Pasqualino De Antonellis, Michelle Ly, Borja López Holgado, Olga Sirbu, Shahrzad Bahrampour, Hyun-Kee Min, Jerry Fan, Carolina Nor, Abhirami Visvanathan, Jiao Zhang, Hao Wang, Lei Qin, Ning Huang, Jonelle Pallotta, Tajana Douglas, Esta Mak, Haipeng Su, Karen Ng, Kevin Yang Zhang, Craig Daniels, Calixto-Hope G Lucas, Charles G Eberhart, Hailong Liu, Tao Jiang, Faiyaz Notta, Vijay Ramaswamy, Jüri Reimand, Marco Gallo, Jeremy N Rich, Xiaochong Wu, Xi Huang, Michael D Taylor

Faculty, Staff and Students Publications

Leptomeningeal metastases are the major source of morbidity and mortality for patients with medulloblastoma. The biology of the leptomeningeal metastases and the local tumour microenvironment are poorly characterized. Here we show that metastasis-associated meningeal fibroblasts (MB-MAFs) are transcriptionally distinct and signal extensively to tumour cells and the tumour microenvironment. Metastatic cells secrete platelet-derived growth factor (PDGF) ligands into the local microenvironment to chemotactically recruit meningeal fibroblasts. Meningeal fibroblasts are reprogrammed to become MB-MAFs, expressing distinct transcriptomes and secretomes, including bone morphogenetic proteins. Active bone morphogenetic protein signalling and co-implantation of tumour cells with MB-MAFs enhances the colonization of the leptomeninges …


Glands Of Moll: History, Current Knowledge And Their Role In Ocular Surface Homeostasis And Disease, Michael Stopfer, Ingrid Zahn, Katharina Jüngert, Gerhard Aumüller, Frans L Moll, Martin Schicht, Helen P Makarenkova, Cintia S De Paiva, Friedrich P Paulsen May 2025

Glands Of Moll: History, Current Knowledge And Their Role In Ocular Surface Homeostasis And Disease, Michael Stopfer, Ingrid Zahn, Katharina Jüngert, Gerhard Aumüller, Frans L Moll, Martin Schicht, Helen P Makarenkova, Cintia S De Paiva, Friedrich P Paulsen

Faculty, Staff and Students Publications

Over the last 20 years, research into the Meibomian glands of the eyelids has increased exponentially and is now widely recognized as a field of research. It is all the more astonishing that knowledge about another type of gland in the eyelids, the Moll glands or ciliary glands, has almost stagnated and there has been little to almost no progress, even though this type of gland as a whole takes up a relatively large volume in the upper and lower eyelids. There is not much information about the namesake Moll or the function of the glands although these are listed …


Multi-Epitope Immunocapture Of Huntingtin Reveals Striatum-Selective Molecular Signatures, Joshua L Justice, Todd M Greco, Josiah E Hutton, Tavis J Reed, Megan L Mair, Juan Botas, Ileana M Cristea May 2025

Multi-Epitope Immunocapture Of Huntingtin Reveals Striatum-Selective Molecular Signatures, Joshua L Justice, Todd M Greco, Josiah E Hutton, Tavis J Reed, Megan L Mair, Juan Botas, Ileana M Cristea

Faculty, Staff and Students Publications

Huntington's disease (HD) is a debilitating neurodegenerative disorder affecting an individual's cognitive and motor abilities. HD is caused by a mutation in the huntingtin gene producing a toxic polyglutamine-expanded protein (mHTT) and leading to degeneration in the striatum and cortex. Yet, the molecular signatures that underlie tissue-specific vulnerabilities remain unclear. Here, we investigate this aspect by leveraging multi-epitope protein interaction assays, subcellular fractionation, thermal proteome profiling, and genetic modifier assays. The use of human cell, mouse, and fly models afforded capture of distinct subcellular pools of epitope-enriched and tissue-dependent interactions linked to dysregulated cellular pathways and disease relevance. We established …


Bi-Allelic Uggt1 Variants Cause A Congenital Disorder Of Glycosylation, Zain Dardas, Laura Harrold, Daniel G Calame, Claire G Salter, Takashi Kikuma, Kevin P Guay, Bobby G Ng, Kanae Sano, Ahmad K Saad, Haowei Du, Riccardo Sangermano, Sohil G Patankar, Shalini N Jhangiani, Semra Gürsoy, Mohamed S Abdel-Hamid, Mahmoud K H Ahmed, Reza Maroofian, Rauan Kaiyrzhanov, Kamran Salayev, Wendy D Jones, Ana Pérez Caballero, Lucy Mcgavin, Michael Spiller, Miranda Durkie, Nick Wood, Lauren O'Grady, Paula Goldenberg, Ann M Neumeyer, Amber Begtrup, Sherif F Abdel-Ghafar, Maha S Zaki, Hilde Van Esch, Jennifer E Posey, Olivia K Wenger, Ethan M Scott, Kinga M Bujakowska, Richard A Gibbs, Davut Pehlivan, Dana Marafi, Joseph S Leslie, Nishanka Ubeyratna, Jacob Day, Martina Owens, Jessica Settle, Soher Balkhy, Abdullah Tamim, Lama Alabdi, Fowzan S Alkuraya, Yoichi Takeda, Hudson H Freeze, Daniel N Hebert, James R Lupski, Andrew H Crosby, Emma L Baple May 2025

Bi-Allelic Uggt1 Variants Cause A Congenital Disorder Of Glycosylation, Zain Dardas, Laura Harrold, Daniel G Calame, Claire G Salter, Takashi Kikuma, Kevin P Guay, Bobby G Ng, Kanae Sano, Ahmad K Saad, Haowei Du, Riccardo Sangermano, Sohil G Patankar, Shalini N Jhangiani, Semra Gürsoy, Mohamed S Abdel-Hamid, Mahmoud K H Ahmed, Reza Maroofian, Rauan Kaiyrzhanov, Kamran Salayev, Wendy D Jones, Ana Pérez Caballero, Lucy Mcgavin, Michael Spiller, Miranda Durkie, Nick Wood, Lauren O'Grady, Paula Goldenberg, Ann M Neumeyer, Amber Begtrup, Sherif F Abdel-Ghafar, Maha S Zaki, Hilde Van Esch, Jennifer E Posey, Olivia K Wenger, Ethan M Scott, Kinga M Bujakowska, Richard A Gibbs, Davut Pehlivan, Dana Marafi, Joseph S Leslie, Nishanka Ubeyratna, Jacob Day, Martina Owens, Jessica Settle, Soher Balkhy, Abdullah Tamim, Lama Alabdi, Fowzan S Alkuraya, Yoichi Takeda, Hudson H Freeze, Daniel N Hebert, James R Lupski, Andrew H Crosby, Emma L Baple

Faculty, Staff and Students Publications

Congenital disorders of glycosylation (CDGs) comprise a large heterogeneous group of metabolic conditions caused by defects in glycoprotein and glycolipid glycan assembly and remodeling, a fundamental molecular process with wide-ranging biological roles. Herein, we describe bi-allelic UGGT1 variants in fifteen individuals from ten unrelated families of various ethnic backgrounds as a cause of a distinctive CDG of variable severity. The cardinal clinical features of UGGT1-CDG involve developmental delay, intellectual disability, seizures, characteristic facial features, and microcephaly in the majority (9/11 affected individuals for whom measurements were available). The more severely affected individuals display congenital heart malformations, variable skeletal abnormalities including …


Characterization Of Human Senescent Cell Biomarkers For Clinical Trials, Joshua N Farr, David G Monroe, Elizabeth J Atkinson, Mitchell N Froemming, Ming Ruan, Nathan K Lebrasseur, Sundeep Khosla May 2025

Characterization Of Human Senescent Cell Biomarkers For Clinical Trials, Joshua N Farr, David G Monroe, Elizabeth J Atkinson, Mitchell N Froemming, Ming Ruan, Nathan K Lebrasseur, Sundeep Khosla

Faculty, Staff and Students Publications

There is an increasing need for biomarkers of senescent cell burden to facilitate the selection of participants for clinical trials. p16 Ink4a is encoded by the CDKN2A locus, which produces five variant transcripts in humans, two of which encode homologous p16 proteins: p16Inka4a, encoded by p16_variant 1, and p16ɣ, encoded by p16_variant 5. While distinct quantitative polymerase chain reaction primers can be designed for p16_variant 5, primers for p16_variant 1 also measure p16_variant 5 (p16_variant 1 + 5). In a recent clinical trial evaluating the effects of the senolytic combination, dasatinib + quercetin (D + Q), on …


Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass May 2025

Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass

Faculty, Staff and Students Publications

Objectives: Circulating Epstein-Barr virus antibodies (EBV-Ab) are used as a biomarker of chronic stress in high-income settings, but their relevance in environments with a high burden of infectious disease, nutritional constraints, and limited resources is less clear. We investigated EBV-Ab as a biomarker of adversity in a setting where local ecology and economy may affect immune development differently than in wealthy countries.

Methods: We measured EBV-Ab in finger-prick dried blood spots collected from Indigenous Shuar (n = 433) and non-Indigenous Colonos (n = 84) ranging from < 1 to 87 years old in Amazonian Ecuador. For a subset of adults (≥ 15 years, n = 210), we collected socioeconomic information (income, education, and occupation) and assessed household-level market integration. We determined the most important predictors of EBV-Ab for adults and children using multi-model averaging of linear regression models.

Results: Male children (< 15 years) had lower EBV-Ab than female children (model averaged β [SE]: -0.238 [0.066]). For adults, Shuar had higher EBV-Ab than Colonos (model averaged β [SE]: 0.235 [0.113]), and high systolic blood pressure was an important predictor of elevated EBV-Ab (model averaged β [SE]: 0.088 [0.047]). Individuals who reported unpaid domestic work as their primary occupation had higher EBV-Ab than agricultural workers (model averaged β [SE]: 0.302 [0.113]). Individuals living in houses with more market-sourced infrastructure had lower EBV-Ab (model averaged β [SE]: -0.088 [0.068]).

Conclusions: Circulating EBV-Ab may capture context-specific aspects of socioecological adversity …