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Impaired Arginine, Citrulline And Glutamine Metabolism In Type 2 Diabetes: Insights From A Stable Isotope Study, Mustafa Tosur, Raven A Wierzchowska-Mcnew, Nicolaas E P Deutz, Mariëlle P K J Engelen

Children’s Nutrition Research Center Staff Publications

Context: Arginine (Arg) is an important amino acid in T2D as a potent insulin secretagogue and precursor for nitric oxide (NO). Citrulline (Cit), the substrate for de novo Arg synthesis, is mostly produced from glutamine (Gln).

Objective: We aimed to investigate their metabolism in T2D using novel stable isotope tracer approach.

Methods: We studied 42 individuals (21 with T2D, 21 controls). After overnight fasting, blood samples were collected following pulse administration of stable amino acid tracers. Plasma concentrations and isotopic enrichments were measured by LC-MS/MS, and compartmental analyses were performed to calculate their whole-body production (WBP) rates and kinetics.

Results: …

Early Prediction And Diagnosis Of Peripheral Neuropathy In Type 2 Diabetes Using Biochemical Parameters, Eman Naim Taher, Narjis Hadi Al – Saadi

Al-Ameed Journal for Medical Research and Health Sciences

Background: Type II diabetes mellitus is commonly related to diabetic peripheral neuropathy (DPNP), which manifests as a gradual progression of damage to the peripheral nerves after excluding other causes. As initial alterations may lie hidden, focus has moved to easy crude markers. Neuron-specific Enolase (NSE) was chosen since it increases early after axonal injury, Whereas, Nerve Growth Factor (NGF) reflects neurotrophic activity. Material and Methods: A case control study was done on 45 cases of DPNP after diagnosing through a nerve conduction study (NCS), 48 diabetics without neuropathy DWNP and 45 healthy individuals. Ages ranged from 35 to 60. …

Genome And Transcriptome-Wide Analyses Identify Multiple Candidate Genes And A Significant Polygenic Contribution In Bicuspid Aortic Valve, Sébastien Thériault, Jacob A Holdcraft, Dinara Sharipova, Adèle Faucherre, Radoslaw M Debiec, Gina M Peloso, Baravan Al-Kassou, Sary Aranki, Elena Ashikhmina Swan, Andrea Ballotta, Michele Bellino, Hanna M Björck, Anne Sophie Boureau, Peter S Braund, François Corriveau, François Dagenais, Lasse Folkersen, Amalia Forte, Michael D Francke, Alessandro Frigiola, Svetlana Gorbatov, Dongchuan Guo, Karam M Habchi, Mahyar Heydarpour, Eric M Isselbacher, Chris Jopling, Fabien Laporte, Solena Le Scouarnec, Zhonglin Li, Peter Lichtner, Carlo Maj, Hasanga D Manikpurage, Christopher P Nelson, Thy B Nguyen, Russell A Norris, Chin Siang Ong, Philippe Pibarot, Tanmoy Roychowdhury, Berardo Sarubbi, Floriane Simonet, Thoralf Sundt, Ida Surakka, Idit Tessler, Cristen J Willer, Susanne Wittmann, Bo Yang, Igor Berezovets, Stefanie A Doppler, Martina Dreßen, Katharina Knoll, Thomas Puehler, Heribert Schunkert, Jean-François Avierinos, Malenka M Bissell, Aidan P Bolger, Yohan Bossé, Eduardo Bossone, María Brion, Rodolfo Citro, Carlo De Vincentiis, G Michael Deeb, Alessandro Della Corte, Christian Dina, Ronen Durst, Stephan Ensminger, Per Eriksson, Arturo Evangelista, Anders Franco-Cereceda, Dan Gilon, Betti Giusti, Simon L Hetherington, Gordon S Huggins, Markus Krane, Thierry Le Tourneau, Giuseppe Limongelli, Patrick Mathieu, David Messika-Zeitoun, Hector I Michelena, Dianna Milewicz, Jochen D Muehlschlegel, David R Murdock, Georg Nickenig, Stefano Nistri, Markus M Nöthen, Francesca Pluchinotta, Siddharth K Prakash, Nilesh J Samani, Jean-Jacques Schott, Tom R Webb, Stéphane Zaffran, Salim Abdelilah-Seyfried, Kim Eagle, Johannes Schumacher, Teresa Trenkwalder, Simon Body

Faculty, Staff and Student Publications

Background: Bicuspid aortic valve (BAV) is a frequent congenital heart defect with a high heritability. Despite this, only a limited number of genes have been associated with the disease, and the molecular mechanisms remain unexplained in most cases. This study aimed to further understand the genetic architecture of BAV.

Methods: A genome-wide association study meta-analysis including 9631 cases among 65 677 participants was performed. Genes were prioritized using transcriptomic analyses based on RNA sequencing in relevant tissues, including human fetal and adult aortic valves. The impact of the knockdown or knockout of 4 candidate genes on cardiac development was verified …

Defining Clinically Relevant Responses In Erectile Function: An Smsna Position Statement, Landon Trost, Faysal Yafi, Alan Shindel, Mohit Khera, Raymond C Rosen, Petar Bajic, Helen Bernie, Martin Gross, Johanna Hannan, Sevann Helo, Lawrence Jenkins Ii, Carol Podlasek, Daniel Watter, Matthew Ziegelmann, Tobias Köhler

Faculty, Staff and Students Publications

Background: To date, no scoring system has adequately defined clinical efficacy of erectile dysfunction (ED) therapies when evaluating differences between cohorts or in meta-analytic studies.

Aim: To outline the minimal criteria required for any therapy to be considered clinically effective in the treatment of ED.

Methods: An analytic review was performed of standardized ED questionnaires, with a particular emphasis placed on the International Index of Erectile Function, Erectile Function Domain (IIEF-EFD), and the minimally clinically important difference (MCID) concept. The data were used to create a societal position statement and recommendations on best practices within clinical trials to determine treatment …

Identification Of A Cytokine Biomarker For Prognostic Modeling Of Breast Cancer-Related Lymphedema, Alison J Wu, Neil Lin, Jie Su, Cherie Lin, Madison-Shira Hossack, Wei Shi, Farnoosh Abbas-Aghababazadeh, Wei Xu, Benjamin Haibe-Kains, Simona F Shaitelman, Melissa B Aldrich, Fei-Fei Liu, Jennifer Y Y Kwan

Faculty, Staff and Student Publications

Lymphedema is a chronic complication of breast cancer treatment, and early intervention is crucial to reduce morbidity. This study evaluated the role of blood-based cytokine biomarkers in the prognostication of breast cancer-related lymphedema (BCRL) to improve risk prediction. A secondary analysis of inflammatory biomarkers for BCRL was performed using a previously published cohort of 147 breast cancer patients who had undergone serum cytokine profiling during their treatment at the Princess Margaret Cancer Centre from 2010-2014. Prognostic cytokine variables for lymphedema were selected by regression analysis and independence from known clinical risk factors. Regression-based modeling was employed to integrate prognostic variables …

Evidence-Based Team Intervention To Reduce Diagnostic Errors In Anaemia And Ckd Diagnoses In Primary Care: Protocol For A Stepped-Wedge Cluster Rct, Zhanna Novikov, Nikhilesh Mehra, Xiao Li, Rebecca Wells, Madelene Ottosen, Kevin Hwang, Elenir B C Avritscher, Charles Green, Kyung Hyun Lee, Xochitl Oguin, Mariesa Janecka, Mary Espinoza, Bolanle Adebowale, Alejandro Araya, Amer Wahed, Eric Thomas

Faculty, Staff and Student Publications

Introduction: Diagnostic errors in primary care are common, particularly in the interpretation and follow-up of abnormal haemoglobin (Hgb) and estimated glomerular filtration rate (eGFR) results. These errors frequently result in missed or delayed diagnoses of serious conditions such as anaemia and chronic kidney disease. This protocol describes a stepped-wedge cluster randomised controlled trial designed to evaluate a novel, evidence-based, team-based intervention aimed at improving diagnostic safety and efficiency.

Methods and analysis: The study will be conducted across 12 University of Texas Physicians (UTPs) primary care clinics in Houston, Texas, USA. Adult patients (≥18 years) with newly identified abnormal Hgb or …

The Next Layer: Augmenting Foundation Models With Structure-Preserving And Attention-Guided Learning For Local Patches To Global Context Awareness In Computational Pathology, Muhammad Waqas, Rukhmini Bandyopadhyay, Eman Showkatian, Amgad Muneer, Anas Zafar, Frank R Alvarez, Maricel Corredor Marin, Wentao Li, David Jaffray, Cara Haymaker, John V Heymach, Natalie Vokes, Luisa M Solis Soto, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Foundation models have emerged as powerful feature extractors in computational pathology. However, they typically omit mechanisms for leveraging the global spatial structure of tissues and the local contextual relationships among diagnostically relevant regions-key elements for understanding the tumor microenvironment. Multiple instance learning (MIL) remains an essential next step following the foundation model, designing a framework to aggregate patch-level features into slide-level predictions. We present EAGLE-Net, a structure-preserving, attention-guided MIL architecture designed to augment prediction and interpretability. EAGLE-Net integrates multi-scale absolute spatial encoding to capture global tissue architecture, a top-K neighborhood-aware loss to focus attention on local microenvironments, and background suppression …

Patient-Specific Computational Flow Simulation Reveals Adverse Hemodynamic Factors Associated With Occlusion Of Directional Branches After Fenestrated-Branched Endovascular Aneurysm Repair, Kenneth Tran, Jesse Chait, Emmanuel Tenorio, Weiguang Yang, Alison Marsden, Bernardo Mendes, Jason T Lee, Gustavo S Oderich

Faculty, Staff and Students Publications

Background: Fenestrated and branched endovascular aneurysm repair can be complicated by branch vessel occlusion in the absence of structural stenosis. We hypothesized that computational flow simulation could identify adverse hemodynamic features associated with postfenestrated and branched endovascular aneurysm repair branch occlusion.

Methods: Patients undergoing 4-vessel fenestrated and branched endovascular aneurysm repair for Extent II to IV thoracoabdominal aortic aneurysms were retrospectively reviewed. Branches that occluded without identifiable kinking or stenosis on computed tomography were included, along with an equal cohort of anatomy-matched patent controls. Patient-specific pulsatile rigid-wall simulations were performed using SimVascular with individualized geometries and boundary conditions. Abnormal time-averaged …

Systematic Evaluation Of Batch Effects In The Cancer Genome Atlas Program Underscores The Need For Batch-Controlled Analysis, Zhongxuan Chen, Stepan Nersisyan, Isidore Rigoutsos, Eric Londin

Alpha Omega Alpha Research Symposium Posters

Purpose: To systematically assess the impact of batch effects on differential expression of isomiR, mRNA, and non-coding RNA (sncRNA) across 13 The Cancer Genome Atlas (TCGA) cancer types and develop a standardized, batch-controlled analysis protocol for TCGA datasets.

Methods: Data analysis and visualization were performed using Python v3.12. Plots were generated using matplotlib and seaborn. isomiR, mRNA, and sncRNA sequences across 13 TCGA cancer types were used. Principal Component Analysis (PCA) was performed using scikit-learn for dimensionality reduction. Differential expression was conducted using DESeq2 under the following protocols: 1) primary tumor samples vs matched normal samples processed in the same …

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

Lysine Demethylase 4a (Kdm4a) Maintains Basal Body Architecture And Protects Against Ciliary Destabilization, Manga Motrapu, Lindsey Hudson, Pratim Chowdhury, Xiaoli Wang, Yuya Nakatani, Sofia Vargas-Hernandez, Sung Y Jung, Menuka Karki, Cheryl Walker, Anna-Karin Gustavsson, Ruhee Dere

Faculty, Staff and Students Publications

Primary cilia are sensory organelles essential for signaling and defects in formation, maintenance or structure underlie diverse ciliopathies. Here, we identify lysine demethylase 4A (KDM4A) as a previously unrecognized mediator of ciliogenesis. Using genetic depletion and pharmacologic inhibition, we show that KDM4A is required for cilia assembly and maintenance. Super-resolution imaging reveals KDM4A localization at the basal body, where it distinctively wraps around the centrioles. We uncover a direct interaction between KDM4A and Rootletin (CROCC), a structural protein mediating centriole cohesion, and demonstrate that KDM4A loss increases inter-centriolar distances, implicating basal body architecture in ciliary failure. Together, these findings define …

Mapping The Causal Chain From Genetic Risk Variants To Lipid Dysmetabolism In Parkinson’S Disease, Ruth B De-Paula, Jonggeol Kim, Herve Rhinn, Hiba Saade, Fatima Chavez, Téah Segura, Maria Valeria Lozano, Michelle Etoundi, Karla Silos, Naomi Kass, Viktoriya Korchina, Harshavardhan Doddapaneni, Eric Venner, Joseph C Masdeu, Valory Pavlik, Melissa M Yu, Chi-Ying R Lin, Joseph Jankovic, Aron S Buchman, Donna Muzny, Richard A Gibbs, Sarah H Elsea, Asa Abeliovich, Peter Lansbury, Nora Vanegas-Arroyave, Chad A Shaw, Joshua M Shulman

Faculty, Staff and Students Publications

The molecular pathways linking genetic variants to Parkinson's disease (PD) onset and progression remain incompletely defined; however, risk alleles in multiple genes, including GBA1, strongly implicate lipid metabolism. To systematically identify causal biomarker signatures, we analyzed comprehensive metabolome profiles from blood plasma in 149 PD patients and 150 controls, along with complementary genetic, RNA-sequencing, and metabolic data from other available clinical and pathologic cohorts. Using colocalization and summary-data-based Mendelian randomization, we tested whether expression and metabolic quantitative trait loci mediate the association between implicated genetic variants and PD risk. We further integrated differential metabolomics and proteomics from blood and brain …

Rare Event: Neonatal Anaphylaxis Following Hepatitis B Vaccination – A Case Series From A Tertiary Care Center In India, Aarthi Ma, Revanth R

Advances in Clinical Medical Research and Healthcare Delivery

We report two cases of anaphylaxis following Hepatitis B vaccination in one-day-old neonates at a tertiary care hospital in India. Both cases presented with similar patterns of cutaneous reactions and respiratory symptoms shortly after intramuscular administration of the Hepatitis B vaccine. To our knowledge, this is among the few documented case series of neonatal anaphylaxis post–Hepatitis B vaccination, underscoring its rarity yet clinical importance. The cases highlight the critical importance of vigilant post-vaccination monitoring and prompt recognition of vaccine-associated adverse events in neonates. This report reviews current literature on anaphylaxis following vaccination and discusses optimal management strategies.

Hallucinations And Diabetes – Could It Be The Hip? An Interesting Case Of Cobalt Poisoning, Mahrukh Tariq, Zauraiz Anjum

Advances in Clinical Medical Research and Healthcare Delivery

Cobalt (Co) poisoning has been described historically in beer-drinkers when cobalt was used as an additive. In present times, this type of poisoning is usually caused by occupational exposure or metal prosthesis breakdown. We present a case of Co poisoning from metal prosthesis breakdown with exceptionally high levels, and thus, some unique symptoms. Interestingly our patient not only had symptoms commonly associated with Co poisoning, e.g., paresthesia, sensory-neural hearing loss, acute kidney failure, but also developed new onset diabetes, which is not commonly associated with this type of pathology. Moreover, when we had this patient under our care, we had …

Bilateral Congenital Radioulnar Synostosis - Case Report, Derek A. Diangelis, Matthew J. Hudson

Advances in Clinical Medical Research and Healthcare Delivery

A 2-year-old male presented to an orthopedic outpatient office due to a supination defect in both of his upper limbs. X-rays of the affected limbs revealed fusion of the proximal radioulnar joints indicating congenital radioulnar synostosis (CRUS). CRUS is abnormal development of the upper limbs occurring during weeks 3—7 of embryological development. Causes of CRUS include genetic syndromes and spontaneous mutations. Treatment options include nonoperative and surgical treatments, however, treatment is controversial due to a lack of clinical evidence. Proposed screening methods could help improve detection rates and improve clinical management. This report aims to increase awareness of CRUS and …

The Long-Term Effectiveness Of The Anti-Obesity Medication Phentermine (Leap) Trial: Rationale, Design, And Baseline Characteristics, Caroline Blackwell Young, Emily Rives, Kimberly A Gudzune, Byron C Jaeger, Courtney G Simmons, Brian N White, Stephanie A Hooker, Deborah B Horn, Deborah R Young, Jennifer Vesely, Amanda Velazquez, Catherine Price, Shelly D Cook, Katy Martin-Fernandez, Galina Inzhakova, Nicholas M Pajewski, Jamy D Ard, Kristina H Lewis

Faculty, Staff and Student Publications

Background: Current clinical practice guidelines support the long-term use of pharmacotherapy for obesity treatment. Historically, phentermine has been one of the most prescribed obesity medications (OMs), however, its long-term efficacy and safety have never been evaluated in a randomized trial as its market approval predates such requirements. Here we describe the design, rationale, and baseline characteristics for a 24-month, double-blind, randomized controlled trial evaluating the efficacy, cardiovascular risk, and safety of phentermine in adults with overweight or obesity.

Methods: This multicenter trial will compare outcomes among participants randomized to phentermine 24 mg daily versus placebo for 24 months. All participants …

Associations Between County-Level Vape-Free Air Law Coverage And E-Cigarette Use Behaviors Among U.S. Adolescents In Monitoring The Future, James H. Buszkiewicz, Yanmei Xie, Catherine A. Vander Woude, Steven Cook, Bukola Usidame, Megan E. Patrick, Michael R. Elliott, James F. Thrasher, Nancy L. Fleischer

Department of Health and Kinesiology Faculty Publications

Purpose

We examined whether workplace and hospitality vape-free air law (VAL) population coverage was associated with adolescent e-cigarette use and related disparities in the United States.

Methods

We analyzed associations between county-level workplace and hospitality VAL coverage (100% vs. < 100%) and current e-cigarette use (2014–2022) and first e-cigarette initiation (2015–2022) among US 8th, 10th, and 12th graders using nationally representative, cross-sectional Monitoring the Future data. We implemented weighted, grade-stratified, modified Poisson regression models, adjusted for individual-, county-, and state-level confounding factors, examining disparities by sex, race and ethnicity, parental education, and college educational expectations through two-way interactions.

Results

Workplace and hospitality VAL coverage was not associated with adolescent e-cigarette use or initiation overall. However, we did find that VAL coverage was associated with lower current e-cigarette use in some sociodemographic subgroups. Full (100%) hospitality VAL coverage was linked to lower e-cigarette use among male 8th and 12th graders, 12th graders with parents without a bachelor's degree, Hispanic 8th …

Engineering Enac Constructs To Examine Pip2 And Ubiquitin Competition On Enac Regulation And Stability, Lacie Johnson

Chemistry & Biochemistry Undergraduate Honors Theses

The epithelial sodium channel (ENaC) plays a critical role in sodium homeostasis, fluid balance, and blood pressure regulation. ENaC activity is tightly controlled by post-translational mechanisms, including ubiquitination-mediated degradation and phosphatidylinositol 4,5-bisphosphate (PIP2) dependent channel activation. PIP2 is a phospholipid necessary to facilitate the maximal channel opening. Previous studies suggest that intracellular PIP2 binding sites are located in proximity to ubiquitination sites on ENaC subunits, raising the possibility of PIP2 binding to influence channel stability and function. This thesis aimed to engineer and validate molecular tools capable of examining the interplay between PIP2 binding and ubiquitination in ENaC regulation. A …

Fireproof: Intricacies Of Microglial Biology, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …

The American College Of Radiology Diagnostic Fluoroscopy Dose Index Registry Pilot: Dosimetric Performance And Benchmarking Challenges, Steve D Mann, Donald L Miller, Grant Fong, Allen R Goode, Emily L Marshall, Thomas Nishino, Pavlina Boxx, Liqiang Ren, Celalettin Topbas, Alan H Schoenfeld, Vivek Singh, Jie Zhang

Faculty, Staff and Student Publications

Background: The ACR Diagnostic Fluoroscopy Dose Index Registry (DIR-Fluoro) is expanding to include diagnostic fluoroscopy. Variations in dose reference points and overhead radiography events may introduce unique challenges for benchmarking.

Purpose: To survey the technological status and dosimetric performance of fluoroscopes participating in the DIR-Fluoro pilot project, focusing on longitudinal stability and variability of fluoroscopic dose reporting accuracy across multiple institutions and vendors.

Methods: Sixty-six fluoroscopic systems from nine institutions (24 facilities) were surveyed for facility type, fluoroscope type, image receptor type, age, dose reporting capabilities, and other key features. Of these, 56 were evaluable. Semi-annual measurements assessed reference air …

Convolutional Neural Networks For Automatic Tuber Segmentation And Quantification Of Tuber Burden In Tuberous Sclerosis Complex, Iván Sánchez Fernández, Matheus D Soldatelli, Gillian N Miller, Catharina F Gout, Ellen C Broekhuizen, Iris C J Den Hertog, Daan A Pijs, Errol Apostolopoulos, Prabhjot Kaur, Abdelhakim Ouaalam, Martina E Bebin, Hope Northrup, Darcy A Krueger, Joyce Y Wu, Alexander L Cohen, Mustafa Sahin, Davood Karimi, Simon K Warfield, Jurriaan M Peters

Faculty, Staff and Student Publications

Objective: This study was undertaken to develop a fully automated algorithm for tuber segmentation and quantification of tuber volume that performs similarly to the gold standard human neuroradiologist.

Methods: We used brain magnetic resonance imaging (MRI) from patients with tuberous sclerosis complex (TSC) to train and validate a convolutional neural network (CNN), which was evaluated on segmentation with the Dice-Sørensen similarity coefficient (DSSC) and on tuber burden quantification with Spearman correlation coefficient against a neuroradiologist's gold standard in the test set.

Results: We collected 263 MRIs from 196 patients (57% males) with median (25th percentile-75th percentile) age of 4.3 (3.0-10.1) …

Presenilin L166p Mutation, A Model Of Familial Alzheimer's Disease, Leads To Early Onset Bone Loss, Vidyani Suryadevara, Connor J Krehbial, Anuradha K Valiya, Melinda Vang, Julian Balanta-Melo, Pierre P Eleniste, Sumana Posritong, Jung Min Hong, Katie Chester, Gabriel M Pagnotti, Teresita Bellido, Monte S Willis, Angela Bruzzaniti

Faculty, Staff and Student Publications

Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with …

Retrospective Analysis Of Cutaneous Immune-Related Adverse Events Following Checkpoint Inhibitor Therapy In Melanoma Patients Reveals Increased Risk Associated With The Hla-B*51:01 Allele, Mckenzie Dileo, Samantha Oglesby, Cheuk Hong Leung, Kristen E Pauken, Sahira Farooq, Lauren E Haydu, Shelby L Kubicki, Rebeca Martinez, Macartney Welborn, Sana Zahiruddin, Jun Zou, Kai Cao, Anisha B Patel

Faculty, Staff and Student Publications

Background: While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.

Methods: A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as …

A Guide To Transcriptomic Deconvolution In Cancer, Yaoyi Dai, Shuai Guo, Yidan Pan, Carla Castignani, Matthew D Montierth, Peter Van Loo, Wenyi Wang

Faculty, Staff and Student Publications

Cancer tissues are heterogeneous mixtures of tumour, stromal and immune cells, where each component comprises multiple distinct cell types and/or states. Mapping this heterogeneity and understanding the unique contributions of each cell type to the tumour transcriptome is crucial for advancing cancer biology, yet high-throughput expression profiles from tumour tissues only represent combined signals from all cellular sources. Computational deconvolution of these mixed signals has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns. Here, we provide a comprehensive guide to transcriptomic deconvolution, specifically tailored for cancer researchers, presenting a systematic framework for selecting and …

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

Background

Objective

Methods

Melody: Mediation Analysis In Logistic Regression For High-Dimensional Mediators And A Binary Outcome, Sunyi Chi, Xingyu Li, Peng Wei, Xuelin Huang

Faculty, Staff and Student Publications

Mediation analysis is a pivotal tool for elucidating the indirect effect of an environmental factor or treatment on disease through potentially high‐dimensional omics data, such as gene expression profiles. However, traditional mediation analysis methods tailored for binary outcomes often rely on the rare disease assumption in logistic regression and provide inadequate measures of total mediation effect when multiple mediators have effects in different directions. In this paper, we develop a MEdiation analysis framework in LOgistic regression for high‐Dimensional mediators and a binarY outcome (MELODY). It leverages a second‐moment‐based measure analogous to the ��2 for linear models to quantify the total …

The Concept Of Environmental Injustice In Allergy And Asthma, Ekta Perera, Christopher Codispoti, Mahboobeh Mahdavinia

Faculty, Staff and Student Publications

Purpose of review: This review examines how environmental injustice contributes to disparities in allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. It focuses on the role of social, geographic, and economic inequities in shaping disease prevalence, severity, and access to care among underrepresented racial and ethnic communities.

Recent findings: Recent studies emphasize the persistent exposure of low-income and racially marginalized populations to environmental hazards such as air pollution, substandard housing, and climate-related changes, factors that are linked to increased prevalence and severity of allergic diseases. While environmental policies have led to overall improvements in air quality, disparities in exposure …

Urinary Biomarkers Of Acute Kidney Injury In Neonates < 25 Weeks’ Gestation: A Pilot Study, Jazmin D Humphreys, Aman Jain, Amir M Khan, Tina O Findley, Mar Romero-Lopez, Sepideh Saroukhani, Rita D Swinford, Matthew A Rysavy

Faculty, Staff and Student Publications

Background: Acute kidney injury (AKI) occurs in 30% of premature neonates and is associated with adverse outcomes that may be mitigated with early detection. Diagnosis of AKI relies on serum creatinine (SCr) which has several limitations, including lack of sensitivity and specificity. There are limited data on the utility of alternative urine biomarkers to predict AKI in neonates born at < 25 weeks' gestation.

Methods: Urine was collected from neonates born at < 25 weeks' gestation during the first postnatal week. Two urine AKI biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and epidermal growth factor (EGF) were measured. Study participants were prospectively followed to determine development of AKI, defined by the neonatal modified Kidney Disease-Improving Global Outcomes (KDIGO) criteria, during the first postnatal week. The association of NGAL and EGF with AKI was analyzed using mixed-effect linear regression models adjusting for gestational age at birth.

Results: A total of 26 neonates were enrolled in this study. After adjusting for gestational age at birth, the mean difference in log-transformed biomarkers at three time points for urine NGAL and …

Preliminary In Vivo Evaluation Of Coracoclavicular Ligament Mechanics During Shoulder Elevation After Acromioclavicular Joint Reconstruction, Jason Konrath, Sydney Wheaton, Alonso Figueroa, James Gregory, Payam Zandiyeh

Faculty, Staff and Student Publications

Background: Persistent instability and altered scapular mechanics after acromioclavicular joint (ACJ) reconstruction may stem from inadequate replication of native coracoclavicular (CC) ligament function. However, in vivo data on postoperative CC ligament behavior during dynamic shoulder motion remain lacking.

Purpose: To assess in vivo functional distance and timing characteristics of the conoid and trapezoid ligaments during active shoulder elevation after ACJ reconstruction, using dynamic stereo x-ray (DSX) imaging and patient-specific 3-dimensional (3D) models.

Study design: Cross-sectional study; Level of evidence, 3.

Methods: Twelve participants (10 men and 2 women, mean age 39 ± 10 years, mean body mass 92 ± 17 …