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Mouse Alport Podocytes Are Susceptible To Aav9 Transduction In Vivo, Meei-Hua Lin, Kohei Omachi, Joshua F Begin, Jennifer L Richardson, Jeffrey H Miner

2020-Current year OA Pubs

INTRODUCTION: Alport syndrome features a defective glomerular basement membrane (GBM) due to variants in COL4A3, COL4A4, and COL4A5. The most severe forms, which lack the GBM's collagen α3α4α5(IV) network, progress from hematuria in early childhood to proteinuria, chronic kidney disease, and kidney failure by the age of ∼30. As a monogenic disease without specific treatments, and with podocytes being the only glomerular cells that synthesize collagen α3α4α5(IV), the ability to efficiently deliver genes to Alport podocytes could open up new possibilities for treatment.

METHODS: As a proof-of-concept study, we investigated whether podocytes in X-linked Alport mice were susceptible to transduction …

Biological Aging Acceleration In Major Depressive Disorder: A Multi-Omics Analysis, Breno Satler Diniz, Shangshu Zhao, Gabin Drouard, Eero Vuoksimaa, Miina Ollikainen, Eric J Lenze, Ming Xu, Richard H Fortinsky, George A Kuchel, Jaakko Kaprio, Chia-Ling Kuo

2020-Current year OA Pubs

Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ-specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ-specific levels-including the brain-in both cohorts, with stronger associations than those observed with systemic epigenetic aging. Systemic and brain-specific proteomic aging acceleration were linked to higher risks of incident MDD and a greater risk of Alzheimer's disease, …

Alzheimer's Disease Stage 1 And 2: Biology, Diagnostics, And Treatment, Suzanne E. Schindler, Sarah M. Hartz, Et Al.

2020-Current year OA Pubs

No abstract provided.

Psychometric Properties Of A Novel Affective Bias Task And Its Application In Clinical And Nonclinical Populations, Prathik Kalva, Kourtney Kanja, Brian A Metzger, Xiaoxu Fan, Brian Cui, Bailey Pascuzzi, John Magnotti, Madaline Mocchi, Raissa Mathura, Kelly R Bijanki

Faculty, Staff and Students Publications

To mitigate limitations in self-reported mood assessments, we introduce a novel affective bias task (ABT). The task quantifies instantaneous emotional state by leveraging the phenomenon of affective bias, in which people interpret external emotional stimuli in a manner consistent with their current emotional state. This study establishes task stability in measuring and tracking depressive symptoms in clinical and non-clinical populations. Initial assessment in a large non-clinical sample established normative ratings. Depressive symptoms were tracked relative to task performance in a non-clinical sample, as well as in a clinical cohort undergoing surgical evaluation for severe epilepsy. In both cohorts, a stronger …

Cgrp Expression And Signaling Sensitization In A Mouse Model Of Chronic Oxaliplatin-Induced Peripheral Neuropathy, Junwei Du, Leland C Sudlow, Margaret H Johnson, Kanishk Satish, Abraham Villagomez, Hongzhen Hu, Mikhail Y Berezin

2020-Current year OA Pubs

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting side effect of oxaliplatin treatment, yet its molecular mechanisms remain incompletely understood. Calcitonin gene-related peptide alpha (CGRPα, encoded by

Exploring The Prevalence Of Eating Disorders, Low Sex Drive, And Exercise Compulsion Among Professional And Non-Professional Elite Male Rugby Union Players, Gary Sweeney, Siobhain Mcardle, Danielle Logue, Nessan Costello, Kieran Collins

Research Outputs: 2025-Present

Rugby union exhibits large variations in the idealised player physical profiles across positions. The pursuit of physique ideals with limited professional support can influence eating disorder symptomology, exercise compulsion, and low sexual drive. The primary aims were to (1) explore the prevalence of elite male rugby union players who are at risk for eating disorders, low sex drive, and exercise compulsion, and (2) explore the relationship between risk and players’ professional status, weight, age, and playing position. A secondary aim was to explore the nutritional service support and dietary monitoring practices experienced by the players. Participants were recruited from four …

Myopia And Eye Disease: From Correlation To Causation, James Loughman, Mark A. Bullimore, Daniel Ian Flitcroft

Research Outputs: 2025-Present

Myopia is increasingly recognised as a risk factor strongly linked to visual impairment and sight-threatening ocular disease rather than a simple refractive state. The assumption of causality to these secondary effects underpins myopia control and its long-term public health value. This review considers epidemiologic, longitudinal, mechanistic, interventional, natural-experiment, and genetic evidence to evaluate causality based on Bradford Hill's nine criteria: strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy. The graded dose-response relationship between myopia and visual impairment has been demonstrated across multiple populations. Similar patterns are shown for a range of myopia-related ocular diseases. Risks for myopic …

Alignment Of The Planetary Health Diet With Pregnancy Dietary Guidelines: Insights From Two Cohorts, Aoife Davis, Sophie Callanan, Gillian A. Corbett, Eileen C. O’Brien, Alexander Douglass, Fionnuala M. Mcauliffe

Research Outputs: 2025-Present

The Planetary Health Diet (PHD) is a mostly plant-based diet that aims to optimise human health whilst minimising the environmental impact of food production. Limited data exists on whether the PHD fulfils key nutritional requirements during pregnancy. This research aimed to examine the PHD in early pregnancy and how it aligns with daily nutrient intake and European Food Safety Authority (EFSA) dietary guidelines. Pregnant women (n=678) from two Irish cohorts (ROLO and MicrobeMom) were analysed. Dietary intakes in early pregnancy were determined using a 3-day food diary and used to calculate PHD Index (PHDI) scores. Women were dichotomised by the …

Physique Development And Management Shape Experiences Of Low Energy Availability Risk In Elite Professional Male Rugby Union Players, Gary Sweeney, Siobhain Mcardle, Nessan Costello, Kieran Collins

Research Outputs: 2025-Present

This study aimed to explore elite male rugby union players’ perceptions and lived experiences of physique development and management in relation to low energy availability risk. Semi-structured interviews (29 ± 8 min) were conducted with 18 players (senior: n = 9; academy: n = 9; mean age: 23 ± 3) across four professional rugby union clubs in Ireland. Through reflexive thematic analysis, the following themes were constructed. Players had limited awareness of low energy availability, yet described experiences consistent with symptoms, including fatigue, low mood and reduced libido. A pervasive physique culture, characterised by body composition ‘ideals’ and weight or …

From Platelets To Particles: Optimizing Extracellular Vesicle Isolation In A National Blood Centre, Y. Chintala, A. Waters, F. Mcgrath, A. Lorusso, C. Wynne, S. Meaney

Research Outputs: 2025-Present

Background and Objectives: Platelet-derived extracellular vesicles (PEVs) are submicron, membrane-bound particles released upon platelet activation, with a recognized role in haemostasis, inflammation and immunoregulation. PEVs remain insufficiently characterized in blood products. This study compared four isolation methods to evaluate their impact on PEV yield, purity and characteristics, aiming to identify a practical approach for transfusion service workflows. Materials and Methods: PEVs were isolated from expired single-donor aphaeresis platelet concentrates (n = 12) using methods based on different isolation principles: ultracentrifugation (UC), size exclusion chromatography (SEC), mixed size/charge separation (hybrid) and an affinity-based spin column method (affinity). Size, number and biochemical …

Developing Forensic Entomology Practice In Ireland: Case Applications And Operational Considerations, Claudio Tersaruolo, Yiyang Sun, Sally Anne Collis, Jesus Frias, Linda Mulligan, Orla Howe

Research Outputs: 2025-Present

Forensic entomology is valuable in legal investigations for estimating the minimum post-mortem interval (minPMI) by insect species and their lifecycles on decomposing remains. While forensic entomology is well established in central-northern Europe and the UK, it has been rarely practiced in Ireland due to a lack of demand and practical expertise. Office of the State Pathologist (OSP) provides the national forensic pathology service; however specialised forensic entomology services are outsourced and instructed on a case-by-case basis. A collaboration was established between the OSP, Technological University Dublin (TU Dublin) and University of Strathclyde over the past two years. This collaboration enabled …

Understanding The Epigenetic Landscape Of Barrett's Esophagus And Esophageal Cancer: A Review Of Current Findings, Caveats And Future Directions, Louise Lawless, Trevor Doherty, Carla Surlis, Niamh Gilmartin, Therese M. Murphy

Research Outputs: 2025-Present

Esophageal cancer (OC) is currently the eighth most common form of cancer worldwide with a 5-year survival rate of 10%–20%, with the primary risk factor of esophageal adenocarcinoma (OAC) being the development of Barrett's Esophagus (BO). Despite its clinical significance, the molecular pathogenesis underlying both BO and OC is not well understood. In recent years, epigenetic dysregulation, particularly aberrant DNA methylation, has emerged as a critical area of investigation, given its potential utility in the identification of diagnostic, prognostic, and therapeutic biomarkers. This review examines the evolving epigenetic landscape of esophageal cancer, including a focus on its origins in BO …

Application Of Machine Learning To Blood-Based Biomarkers Of Alzheimer's Disease In Down Syndrome, Patrick H Luckett, Melissa Petersen, Sid O'Bryant, Mark Mapstone, Brad T Christian, Benjamin Handen, Elizabeth Head, Beau M Ances, Alzheimer's Biomarker Consortium‐Down Syndrome

2020-Current year OA Pubs

INTRODUCTION: Blood-based biomarkers can improve Alzheimer's disease (AD) characterization in Down syndrome (DS). This study applied hierarchical clustering and machine learning-based feature selection to identify biomarkers associated with disease progression.

METHODS: Cross-sectional blood-based biomarkers were analyzed from 211 DS participants (

RESULTS: The strongest predictors overall were neurofilament light chain (NfL), tau/amyloid beta (Aβ)40, Aβ42/Aβ40, alpha-2-macroglobulin (A2M), and interleukin (IL)-10. Within the CS group, NfL, tau/Aβ40, A2M, and IL-10 were strong predictors. In MCI, Aβ42/Aβ40, NfL, A2M, and IL-10 were strong predictors. In DS-AD, Aβ42/Aβ40, NfL, and tau/Aβ40 were the top predictors. Cluster membership varied based on disease stage.

DISCUSSION: …

Development Of Colonic Polyposis In A Woman With Chronic Myeloid Leukemia Treated With Dasatinib, Guido Pelaez, Behram Suha Yildiz, Mert Candan, Mohammad Ismail, Francesca Vacca, Marianna B Ruzinova, Samuel Ballentine, Kathleen Byrnes, Armin Ghobadi

2020-Current year OA Pubs

INTRODUCTION: Chronic myeloid leukemia (CML) is a hematopoietic malignancy driven by constitutive tyrosine kinase activity. Dasatinib, a second-generation (2G) tyrosine kinase inhibitor (TKI), is a preferred treatment due to its superior, durable, and rapid response rates. While dasatinib has known gastrointestinal (GI) side effects, colonic polyposis is a rare complication, not well described in the literature.

CASE PRESENTATION: Upon routine colonoscopy, a 66-year-old woman with chronic-phase CML was incidentally discovered to have asymptomatic colonic polyposis after 11 months of dasatinib therapy. Histopathology revealed reactive inflammatory changes without evidence of dysplasia or neoplasia. The polyposis resolved completely after cessation of dasatinib. …

Novel Insights Into Early Alzheimer's Disease: Quantitative Gradient Recalled Echo Mri Reveals Preatrophic Neuronal And Myelin Injury Concurrent With Emerging Amyloid Pathology, Satya V V N Kothapalli, Tammie L S Benzinger, Randall J Bateman, Melody Li, Cihat Eldeniz, John C Morris, Dmitriy A Yablonskiy

2020-Current year OA Pubs

BACKGROUND: Brain amyloid accumulation is considered an early sign of Alzheimer's disease (AD) pathology, appearing decades before manifestation of clinical symptoms. However, very little is known about neurodegeneration during this early AD stage. Herein we use quantitative gradient recalled echo (qGRE) magnetic resonance imaging (MRI) to reveal preatrophic microstructural neuronal and myelin damage concurrent with amyloid pathology.

METHODS: qGRE MRI and positron emission tomography (PET) amyloid [

RESULTS: qGRE detected significantly lower gray matter neuronal density and white matter myelination in the group of participants with amyloid level below the conventional amyloid-positive threshold (mean cortical standardized uptake value ratio of …

The Association Between Major Depressive Disorder, Plasma Biomarkers Of Alzheimer's Disease, And Mild Behavioral Impairment Among Older Adults, Yiqi Zhu, Jean-Francois Trani, Ramkrishna K Singh, Semere Bekena, Jonathan Williams, Eric J Lenze, Ganesh M Babulal

2020-Current year OA Pubs

INTRODUCTION: Plasma biomarkers and mild behavioral impairment (MBI) are associated with dementia risk, but their relationships with major depressive disorder (MDD) are understudied. This study aimed to examine associations between plasma biomarkers of Alzheimer's disease (AD) and MBI among older adults with and without MDD.

METHODS: Older adults aged ≥65 were recruited from longitudinal studies of depression and AD (

RESULTS: Older adults with MDD were more likely to endorse MBI. After adjustment, Aβ42/Aβ40 and p-tau217/np-tau217 positivity were associated with MBI among those with MDD but not among those without.

DISCUSSION: Neuropsychatric symptoms (NPS) and biomarkers are AD risk factors. …

The Impact Of Congenital Heart Disease On The Timing Of Alzheimer's Disease In Down Syndrome, Julianne G Clina, Beau Ances, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS.

METHODS: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (

RESULTS: People with CHD scored lower for visuospatial ability (

DISCUSSION: Presence of CHD may influence AD progression in DS.

HIGHLIGHTS: In adults with Down syndrome (DS), those with congenital heart disease (CHD) had higher amyloid beta and reached the …

Criterion And Convergent Validity Of Plasma Biomarkers In Early-Onset Alzheimer's Disease: Initial Findings From Leads, Dustin B Hammers, Kyle Womack, Erik Musiek, Et Al.

2020-Current year OA Pubs

No abstract provided.

Eligibility For Anti-Amyloid Treatment In A Multiethnic Community-Based Study, Lydia Trudel, Joseph Therriault, Arthur C Macedo, Karin L Meeker, Meredith N Braskie, Arthur W Toga, Serge Gauthier, Paolo Vitali, Suzanne E Schindler, Sid E O'Bryant, Pedro Rosa-Neto

2020-Current year OA Pubs

INTRODUCTION: The approval of anti-amyloid monoclonal antibodies (mAbs), including lecanemab and donanemab, represents a significant advance in disease-modifying therapies (DMTs) for early Alzheimer's disease (AD). While appropriate use recommendations (AURs) have been established to guide clinical decision-making, the proportion of individuals with cognitive impairment in real-world, multiethnic populations meeting eligibility criteria remains unknown, as do potential differences in treatment-related risks across ethnic groups.

METHODS: We included 513 cognitively impaired individuals from the Health and Aging Brain Study-Health Disparities study, a multiethnic community-based cohort. Eligibility for lecanemab and donanemab was determined using published AUR criteria. Counts of amyloid-related imaging abnormalities were …

Rationale And Trial Design Of Ribolaris: A Phase Ii Trial Of Neoadjuvant And Adjuvant Ribociclib Plus Endocrine Therapy For Clinically High-Risk Hr+/Her2-Negative Breast Cancer, Paul Cottu, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite advances in endocrine therapy, patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC) remain at risk of recurrence (ROR). Chemotherapy is often used in high-risk cases, but not all patients benefit.

OBJECTIVES: To evaluate whether chemotherapy can be safely omitted in patients with stage II, grade 2/3 HR+/HER2- eBC who convert to low genomic risk (ROR-low) following neoadjuvant ribociclib plus letrozole.

METHODS: RIBOLARIS (NCT05296746) is an open-label, multicenter phase II trial in patients with stage II, grade 2 or 3, HR+/HER2- eBC defined as high risk based on a Ki-67 index ⩾20% …

Establishing Demographic-Based Normative Values For Neurofilament Light Chain And Glial Fibrillary Acidic Protein In Serum And Plasma Samples, Tyler L Borko, Salim Chahin, Et Al.

2020-Current year OA Pubs

BACKGROUND: Interpretation of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels in blood requires reference ranges from healthy cohorts, accounting for demographic features.

OBJECTIVE: To compare serum and plasma NfL and GFAP in healthy individuals, accounting for age, sex, and body mass index (BMI).

METHODS: Adolescents through older adults were recruited at Colorado community events and a senior clinic. A neurologist reviewed self-reported medical histories. Paired serum and EDTA plasma samples were assayed using the Quanterix SR-X Simoa Neuro 4-Plex. Log-linear models estimated percent change per year of age, per BMI unit, and sex ratios. GFAP used …

Concordance Of Fluorescence In Situ Hybridization, Whole-Exome Sequencing, And Chromosomal Microarray For Evaluating High-Risk Molecular Features In Meningiomas, Brenndan Crumley, Emilie Russler-Germain, Sonika Dahiya

2020-Current year OA Pubs

BACKGROUND: Meningiomas are the most common primary intracranial tumors, classified into three WHO grades based on histologic and/or molecular criteria. cIMPACT-NOW Update 8 underscores the increasing importance of molecular testing in grading and risk stratification, noting that morphologically WHO grade 1 tumors with concurrent 1p and 22q losses demonstrate clinical behavior comparable to WHO grade 2 meningiomas. This study aimed to assess the concordance of fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and whole-exome sequencing (WES) in defining the molecular risk profile of meningiomas.

METHODS: A total of 113 meningiomas were analyzed by WHO grade to assess the …

2024 Annual Operations And Maintenance Report - 2024 Bres Annual Summary Report For Work Completed In Quadrant 4, Butte-Silver Bow Department Of Reclamation And Environmental Services

Silver Bow Creek/Butte Area Superfund Site

No abstract provided.