Medical Specialties Commons^™

Glycolic Acid (Ga) Peel Versus Dermapen In Management Of Acne Scars Among Egyptian Patients: A Comparative Study, Rania Emam Elbanna

Journal of Medicine in Scientific Research

Aim of the work: To assess and contrast dermapen, glycolic acid (GA) peel, and a combination of the two therapys' safety and effectiveness in treating acne scars. Cases and methods: Thirty cases with acne scars participated in this trial. Ten cases each were divided into three cohorts at random; cohort I had dermapen therapy, whereas cohort II received glycolic peel therapy. Both procedures were administered to Cohort III. Six sessions were given to each case at intervals of two weeks. The quartile grading scale, the degree of case satisfaction, and the qualitative global scar grading system before and after therapy …

Maternal Immunization With Vp8* Mrna Vaccine Yields Superior Passive Transfer Of Rotavirus-Neutralizing Antibodies To Foals, Karin E R Borba, Rebecca M Legere, Nathan M Canaday, Jill W Skrobarczyk, Zachary W T Arnold, Elena Cotton-Betteridge, Cristina Poveda, Michael F Criscitiello, Angela I Bordin, Luc R Berghman, Jeroen B K Pollet, Noah D Cohen

Faculty, Staff and Students Publications

Background: Despite the availability of a killed whole-virus (KV) vaccine, diarrhea caused by equine rotavirus group A (ERVA) remains a significant health concern for foals in the United States. The vaccine is administered to pregnant mares, with foals protected by passive transfer of colostral antibodies. However, KV-induced immunity is only partially protective and maternal antibody levels in foals are often low and wane rapidly. To address these limitations, we developed a mRNA-based ERVA vaccine encoding the highly conserved VP8* protein to evaluate whether it can provide improved immune protection.

Methods: Pregnant mares (n = 12 per group) were …

Prognostic Value Of Baseline Qfr In Single-Vessel Intermediate Coronary Stenosis, Yanfeng Lu, Abdulrahman Alqazzaz, Jasmine Bao, Gary S. Mintz, Jiahao Feng, Yong Zhang, Shanshan Gao, Qiang Song, Feifei Ning, Xin Huang, Ning Guo

Student Papers, Posters & Projects

BACKGROUND AND OBJECTIVES: The prognostic value of baseline Quantitative Flow Ratio (QFR) in real-world patients remains unclear. This study aimed to evaluate the prognostic value of baseline QFR and its three-tier model-low, grey-zone, and high QFR-in patients with single-vessel intermediate stenosis.

METHODS: This retrospective study included 478 patients with QFR between 0.70 and 0.90 who underwent coronary angiography between May and June 2023. Patients were stratified into Low (0.70-0.74), Grey-Zone (0.75-0.85), and High (0.86-0.90) QFR groups. The primary endpoint was major adverse cardiac events (MACE); the key secondary endpoint was target vessel failure (TVF). Kaplan-Meier and Cox proportional hazards models …

Clinical And Dosimetric Dataset Of Time-To-Event Normal Tissue Complication Probability For Osteoradionecrosis, Natalie A West, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, G Elisabeta Marai, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Renjie He, Mohamed A Naser, Katherine A Hutcheson, Abdallah S R Mohamed, Lisanne V Van Dijk, Amy C Moreno, Stephen Y Lai, Clifton D Fuller, Laia Humbert-Vidan

Faculty, Staff and Student Publications

Osteoradionecrosis of the jaw (ORNJ) is a radiation-induced late toxicity that can dramatically decrease patients' quality of life. Recent increases in survival rates of head and neck cancers associated with human papillomavirus (HPV) infection have resulted in a higher frequency of radiation-induced toxicities, particularly ORNJ. Recent work with Normal Tissue Complication Probability (NTCP) models and a Weibull Accelerated Failure Time (WAFT) model have further developed our understanding of ORNJ clinical/dosimetric risk factors and longitudinal features, respectively. In this data descriptor, 1129 head and neck cancer (HNC) patients received curative intent radiotherapy (RT) at MD Anderson Cancer Center and were followed …

An Integrated Single-Cell And Spatial Transcriptomic Atlas Of Thyroid Cancer Progression Identifies Prognostic Fibroblast Subpopulations, Matthew A Loberg, George J Xu, Sheau-Chiann Chen, Hua-Chang Chen, Claudia C Wahoski, Kailey P Caroland, Megan L Tigue, Heather A Hartmann, Jean-Nicolas Gallant, Courtney J Phifer, Andres A Ocampo, Dayle K Wang, Reilly G Fankhauser, Kirti A Karunakaran, Chia-Chin Wu, Maxime Tarabichi, Sophia M Shaddy, James L Netterville, Sarah L Rohde, Carmen C Solórzano, Lindsay A Bischoff, Naira Baregamian, Barbara A Murphy, Jennifer H Choe, Jennifer R Wang, Eric C Huang, Quanhu Sheng, Luciane T Kagohara, Elizabeth M Jaffee, Ryan H Belcher, Ken S Lau, Fei Ye, Ethan Lee, Vivian L Weiss

Faculty, Staff and Student Publications

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts …

Primary Cortical Neurons Precipitate And Extrude Large Mitochondria-Associated Calcium-Phosphate Sheets With A Bone-Precursor-Like Ultrastructure, Erik D Anderson, Christopher A Cronkite, Philip R Baldwin, Carlota P Abella, Joseph G Duman, Ashleigh N Simmonds, M Neal Waxham, Kimberley F Tolias, Steven J Ludtke

Faculty, Staff and Students Publications

Calcium-phosphate (CaP) is a ubiquitous inorganic compound that plays an important structural role in healthy bone and teeth formation, but its pathologic buildup can occur in dyshomeostatic calcium disorders like Alzheimer's disease and Leigh syndrome. The nexus of pathologic extracellular CaP in the nervous system is not well understood, but prior evidence suggests mitochondria could be a source. We have observed mitochondria-sized sheet-like CaP aggregates within functional wild type cortical neuron cultures at 1 and 20 days in vitro. Neurons were extracted from embryonic day 18 (E18) rat embryos following standard protocols to study neuronal structure and function. We have …

Multi-Institutional Normal Tissue Complication Probability (Ntcp) Prediction Model For Mandibular Osteoradionecrosis: Results From The Predmorn Study, Laia Humbert-Vidan, Christian R Hansen, Steven Petit, Carles Muñoz-Montplet, Katrina Hueniken, Abdallah S R Mohamed, Deborah P Saunders, Vinod Patel, Gerda M Verduijn, Wilma D Heemsbergen, Arjen Van Der Schaaf, Max Witjes, Suzanne P M De Vette, Mohammad Moharrami, Abdul A Khan, Jordi Marruecos Querol, Irene Oliveras Cancio, Mike Oliver, Peter Reich, Stacey A Santi, Andrew G Pearce, Stephen Y Lai, Andrew P King, Ali Hosni, Andrew J Hope, Erin E Watson, Johannes A Langendijk, Jørgen Johansen, Amy C Moreno, Clifton D Fuller, Lisanne V Van Dijk, Teresa Guerrero Urbano

Faculty, Staff and Student Publications

Purpose: Mandibular osteoradionecrosis (ORN) is a severe late complication affecting patients with head and neck cancer (HNC) treated with radiation therapy (RT) that significantly impacts patients' quality of life and can require costly interventions. Although radiation dose is a key factor, other clinical and demographic risk factors also influence ORN development. Previous predictive models have primarily been single-institutional, limiting their generalizability. In this first analysis from the PREDMORN Consortium, we have aimed to reproduce existing statistical association and modeling analyses on the largest and most diverse mandibular ORN cohort worldwide to allow comparison with previous studies.

Methods and materials: This …

Disparities In Cardiovascular Disease Burden Among Black And Hispanic Survivors Of Adolescent And Young Adult (Aya) Cancer, Tori Tonn, Maanvi Thawani, Margaret Mazer, Greg Aune, Debra Eshelman-Kent, Karen Albritton, Efstratios Koutroumpakis, Michael E Roth, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: Despite significant improvements in long-term survival outcomes for adolescents and young adults (AYAs) with cancer, common treatment regimens often pose substantial risks to the cardiovascular health of this survivor population. Differences in cardiovascular events by race/ethnicity and genetic ancestry within this at risk population remain unclear.

Methods: In this study, we investigated adverse cardiovascular outcomes in a diverse population of AYA cancer survivors (n = 346) treated at MD Anderson Cancer Center for Hodgkin lymphoma and sarcoma. Analysis was conducted by self-identified race/ethnicity and by genetic ancestry.

Results: Black and Hispanic survivors demonstrated the greatest burden of poor …

The Vascular Density/Angiogenesis Marker Cd31/Pecam1 Does Not Correlate With Overall Survival In Neuroendocrine Tumors, Nicholas J. Skill, Kenneth Avanzino, Yvette Bren-Mattison, J. Philip Boudreaux, Ramcharan Thiagarajan, Mary Maluccio

School of Medicine Faculty Publications

Abstract: Neuroendocrine neoplasms (NENs) are rare cancers. CD31/PECAM1 is an adhesion molecule that modulates endothelial cell-to-cell contact. Increased CD31 expression is a marker for tumor growth, and cancer aggressiveness. The purpose of this study was to better understand the prognostic value of CD31 expression in primary and metastatic NEN tumors in terms of correlations with overall survival and pathological metrics, tumor grade, and tumor primary/metastatic location. As NENs are highly vascular tumors, the hypothesis is that CD31 staining is an important prognostic biomarker and target. This is based on prior correlations between CD31 staining and 3-year recurrence-free survival in pancreas …

Machine Learning-Based Multimodal Biomarkers Enable Accurate Diagnosis And Early Detection Of Pancreatic Ductal Adenocarcinoma, Tsung-Hung Yao, Warapen Treekitkarnmongkol, Nagireddy Putluri, Deivendran Sankaran, Tristian Nguyen, Seetharaman Balasenthil, Mark W Hurd, Meng Chen, Randall E Brand, Paul D Lampe, Abu Hena M Kamal, Vasanta Putluri, Tony Y Hu, Anirban Maitra, Eugene J Koay, Ann M Killary, Subrata Sen, Suprateek Kundu

Faculty, Staff and Students Publications

While there has been some progress on discovering clinically validated biomarkers for early detection in pancreatic ductal adenocarcinoma (PDAC), several challenges remain. Most approaches rely on single-modality biomarkers with limited sensitivity and/or specificity. Using data from a multicenter study with an age-matched cohort (n = 203 with healthy controls n = 46, pancreatitis controls n = 36, and diagnosed cases n = 121), we developed a machine learning approach integrating 2,096 microRNAs, 125 metabolites, and CA19-9. Our method performs unsupervised selection of an optimal subset of biomarkers with maximal discriminatory power for diagnosis and early detection. In training data, the …

Thermodynamic Stability Modulates Chaperone-Mediated Disaggregation Of Α-Synuclein Fibrils, Celia Fricke, Antonin Kunka, Rasmus K Norrild, Shuangyan Wang, Thi Lieu Dang, Jonas Folke, Mohammad Shahnawaz, Claudio Soto, Susana Aznar, Anne S Wentink, Bernd Bukau, Alexander K Buell

Faculty, Staff and Student Publications

Aggregation of the intrinsically disordered protein alpha-synuclein into amyloid fibrils and their subsequent intracellular accumulation are hallmark features of several neurodegenerative disorders, including Parkinson's disease, for which no curative treatments currently exist. In this study, we investigate the relationship between fibril morphology, thermodynamic stability, and susceptibility to disaggregation by the human chaperone system comprising HSP70, DNAJB1, and Apg2. By varying assembly conditions and incubation times, we generated alpha-synuclein fibrils with diverse morphological and biochemical properties, including a broad range of thermodynamic stabilities, which we quantified using a chemical depolymerization assay. The chaperone system effectively disaggregated three of the four fibril …

Characterization Of Inflammatory Pseudotumors In A Large Animal Model Of Liver Cancer, Erik N K Cressman, Samantha Hicks, Natalie W Fowlkes, Danielle L Stolley, Maria Sophia Stenkamp

Faculty, Staff and Student Publications

Background: The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease. Transgenic approaches hold promise in addressing this complex problem. One such model, the Oncopig, has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation. However, the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.

Methods: Herein, we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and replaced …

Defective Dna Damage Response Is A Targetable Therapeutic Vulnerability In Esr1 Mutant Breast Cancer, Sarah K Herzog, Jessica H Stevens, Guowei Gu, Sandra L Grimm, Kloma Cardoza, Autumn G M Hawkins, Hangqing Lin, Daniela Ramos, Amanda R Beyer, David G Edwards, Derek Dustin, Harry J Yang, Nicole Liang, Ashfia F Khan, Tasneem Bawa-Khalfe, Daniel J Mcgrail, Shiaw-Yih Lin, Cristian Coarfa, Suzanne A W Fuqua

Faculty, Staff and Student Publications

ESR1 mutations are the leading cause of endocrine therapy resistance and progression in ER-positive metastatic breast cancer. ESR1 mutations are detected in ~50% of metastatic breast cancer patients, and identification of effective targeted therapeutics are critically needed. Here, we identified enrichment of dysregulated replication stress and DNA damage responses in multiple ESR1 mutant models. Targeting the replication stress response utilizing checkpoint inhibition in combination with PARP inhibition synergistically suppressed growth, induced cell cycle arrest, and attenuated DNA replication. PARP inhibition blocked metastatic dissemination in vivo and reduced both PARP1 and ER-regulated protein expression. PARP trapping by olaparib treatment with or …

Loss Of Kdm6a-Mediated Genomic Instability And Metabolic Reprogramming Regulates Response To Therapeutic Perturbations In Bladder Cancer, Pratishtha Singh, Ranit D'Rozario, Bidisha Chakraborty, Swadhin Meher, Deblina Raychaudhuri, Aminah J Tannir, Yang Li, Anurag Majumdar, Jessalyn Hawkins, Yun Xiong, Philip Lorenzi, Padmanee Sharma, Kadir Akdemir, Patrick Pilie, Abhinav K Jain, Byron Hing Lung Lee, Sangeeta Goswami

Faculty, Staff and Student Publications

Mutations in epigenetic regulators are common in bladder cancer, yet their impact on therapeutic responses remains unclear. Here, we identify that loss-of-function mutations in KDM6A, a histone demethylase altered in about 26% of advanced bladder cancers, are associated with poor survival after cisplatin chemotherapy, whereas they correlate with improved outcomes with anti-PD-1 therapy. Using CRISPR-Cas9-engineered murine and human bladder cancer models, we show that KDM6A deficiency increases formation of extrachromosomal circular DNA carrying chemoresistance loci, promoting cisplatin resistance. In parallel, KDM6A loss impairs DNA repair and rewires tumor metabolism, reducing glycolysis and lactate output. This metabolic shift diminishes histone lactylation …

3d Reconstruction Of Spatial Transcriptomics With Spatial Pattern Enhanced Graph Convolutional Neural Network, Chen Tang, Yuansheng Zhou, Xue Xiao, Lei Dong, Lei Yu, Qiwei Li, Guanghua Xiao, Lin Xu

Faculty, Staff and Student Publications

Spatially resolved transcriptomics (SRT) is a promising new technology that enables simultaneous analysis of gene expression and spatial information for biomedical research. However, the existing statistical and deep learning algorithms used for analyzing SRT data rely solely on two-dimensional (2D) spatial coordinates, which limits their ability to accurately identify spatial domains, spatially variable genes (SVGs), cell-to-cell communications, and developmental trajectories in a three-dimensional (3D) spatial manner. To address these limitations, we introduced Spa3D, which utilized the anti-leakage Fourier transform and graph convolutional neural network model to reconstruct 3D-based spatial structures from multiple 2D SRT slices. We demonstrate that Spa3D is …

Spatially Resolved Integrative Analysis Of Transcriptomic And Metabolomic Changes In Tissue Injury Studies, Eleanor C Williams, Lovisa Franzén, Martina Olsson Lindvall, Gregory Hamm, Steven Oag, Muntasir Mamun Majumder, James Denholm, Azam Hamidinekoo, Javier Escudero Morlanes, Marco Vicari, Joakim Lundeberg, Laura Setyo, Trevor M Godfrey, Livia S Eberlin, Aleksandr Zakirov, Jorrit J Hornberg, Marianna Stamou, Patrik L Ståhl, Anna Ollerstam, Jennifer Y Tan, Irina Mohorianu

Faculty, Staff and Students Publications

Recent developments in spatially resolved -omics have enabled the joint study of gene expression, metabolite levels and tissue morphology, offering greater insights into biological pathways. Integrating these modalities from matched tissue sections to probe spatially-coordinated processes, however, remains challenging. Here we introduce MAGPIE, a framework for co-registering spatially resolved transcriptomics, metabolomics, and tissue morphology from the same or consecutive sections. We show MAGPIE's generalisability and scalability on spatial multi-omics data from multiple tissues, combining Visium with MALDI and DESI mass spectrometry imaging. MAGPIE was also applied to new multi-modal datasets generated with a specialised sampling strategy to characterise the metabolic …

Association Between Ultraprocessed Food Consumption And Cardiovascular Disease Risk: Mesa (Multiethnic Study Of Atherosclerosis), Amier Haidar, Rishi Rikhi, Karol E Watson, Alexis C Wood, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ultraprocessed foods (UPFs) have been linked to adverse cardiometabolic outcomes and increased atherosclerotic cardiovascular disease (CVD) (ASCVD) risk. However, prior research has largely focused on homogenous populations, lacking racial and ethnic diversity.

Objectives: The objectives are to examine the longitudinal relationship between UPF consumption and ASCVD risk and to investigate whether these associations differ by race/ethnicity, sex, or socioeconomic status.

Methods: The MESA (Multiethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 U.S. adults aged 45 to 84 years, without clinically apparent CVD. UPF consumption was classified according to the Nova classification system. Multivariable cox proportional hazards …

N-Palmitoyl Glutamine Is A Candidate Mediator Of Cardiorespiratory Fitness, Jeremy M Robbins, Mark Benson, Anthony R P Verkerke, Gaurav Tiwari, Shuliang Deng, Prashant Rao, Usman A Tahir, Julian Avila-Pacheco, Xu Shi, Yuntian Guan, Foje-Geh Tendoh, Jacob L Barber, Patricia E Miller, Andrew S Perry, Michael E Hall, Alexis C Wood, Kent D Taylor, Wendy S Post, Stephen S Rich, Matthew Nayor, James G Wilson, Gregory D Lewis, Ravi V Shah, Jerome I Rotter, Scott A Summers, Laura M Raffield, Shingo Kajimura, Claude Bouchard, Clary B Clish, Mark A Sarzynski, Robert E Gerszten

Children’s Nutrition Research Center Staff Publications

Background: Cardiorespiratory fitness is an integrative measure of cardiometabolic health and predictor of survival, yet little is known about its molecular underpinnings. Small molecule metabolites and lipids are increasingly recognized as exercise-stimulated signaling molecules and candidate molecular transducers of cardiorespiratory fitness.

Methods: We performed nontargeted liquid chromatography mass spectrometry-based plasma metabolomics in 654 participants (mean age, 35 years; 55% women) from the HERITAGE Family Study (Health, Risk Factors, Exercise Training, and Genetics) who had cardiorespiratory fitness (maximal oxygen uptake [VO2max]) measured by cardiopulmonary exercise testing and underwent 20 weeks of supervised endurance training. Metabolite-VO2max relationships were assessed using linear regression …

Inhibition Of Gpx4 Induces The Death Of P53-Mutant Triple-Negative Breast Cancer Cells, William M Tahaney, Amanda Lanier, Jing Qian, Cassandra L Moyer, Nghi Nguyen, Yanxia Ma, Jamal Hill, Reid T Powell, Clifford C Stephan, Peter J A Davies, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high rates of tumor protein 53 (TP53) mutation and with limited targeted therapies. Despite being clinically advantageous, direct targeting of mutant TP53 has been challenging. Therefore, we hypothesized that p53-mutant TNBC cells rely upon other potentially targetable survival pathways.

Methods: In vitro and in silico screens were used to identify drugs that induced preferential death in TP53-mutant cells. The effect of the ferroptosis inducer ML-162 was tested both in vitro and in vivo and the mechanism of cell death following ML-162 treatment or GPX4 knockout was …

Peripheral Nerve Injury Reduces Macrophage Efferocytosis To Facilitate Neuropathic Pain, Vipul K Pandey, Tusar K Acharya, Kendal F Willcox, Sandeep Dembla, Ajeena Ramanujan, Anamaria R Grieco, Younus A Zuberi, Rajasekaran Mahalingam, Andrew J Shepherd, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

For reasons not fully understood, proresolving immune processes sometimes fail to engage after peripheral nerve injury (PNI), leading to enhanced neuropathic pain and inflammation. Here, we implicate reduced efferocytosis due to proteolytic cleavage of surface MER tyrosine kinase (MERTK) from macrophages at the site of PNI. After PNI, the proportion of macrophages expressing MERTK progressively decreased, while soluble (cleaved) MER increased. Using male and female knock-in mice encoding cleavage-resistant Mertk, we demonstrated that cleavage of MERTK from macrophages at the PNI site led to exaggerated pain-related behaviors. PNI-induced hyperactivity of TRPV1+ sensory neurons and damage to myelin and myelinated …

Correction: Sadagopan Et Al Reduced Computed Tomography Scan Speed Improves Alignment Errors For Patients Undergoing Thoracic Stereotactic Body Radiation Therapy, Ramaswamy Sadagopan, Rachael M Martin-Paulpeter, Christopher R Peeler, Xiaochun Wang, Paige Nitsch, Julianne M Pollard-Larkin

Faculty, Staff and Student Publications

In the original publication [...].

Modality-Agnostic, Patient-Specific Digital Twins Modeling Temporally Varying Digestive Motion, Jorge Tapias Gomez, Nishant Nadkarni, Lando S Bosma, Jue Jiang, Ergys D Subashi, William P Segars, James M Balter, Mert R Sabuncu, Neelam Tyagi, Harini Veeraraghavan

Faculty, Staff and Student Publications

No abstract provided.

Predicting Sepsis In Heart Failure Patients Supported By Left Ventricular Assist Devices: The Role Of Ve-Cadherin And Adam10, Shiyi Li, Iván Murrieta-Álvarez, Ismael Garcia, Katherine V Nordick, Rishav Bhattacharya, Shreyo Ghosh, Ronald A Shaju, Adel M Hassan, Carl P Walther, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Vascular endothelial cadherin (VE-Cadherin) is a major endothelial adhesion molecule and can be cleaved explicitly by metalloproteinase domain-containing protein 10 (ADAM10). Vascular hyperpermeability may contribute to a greater susceptibility to sepsis in left ventricular assist device (LVAD) support patients. We aim to evaluate the efficacy of VE-Cadherin and ADAM10 for predicting sepsis in LVAD patients. We prospectively recruited 50 patients with advanced heart failure receiving LVAD therapy. Baseline and weekly postoperative blood samples (weeks 1-4) were collected, and plasma VE-cadherin and ADAM10 levels were measured. Sepsis occurred in 9 of 50 patients (18.0%). Across all sampling points, plasma VE-cadherin and …

Neuronal Subtype Governs Amyloid Structure, Cellular Response, And Cognitive Outcome In Genetically Targeted App Mouse Models, Gabriella A Perez, Zoe Lai, George A Edwards Iii, Jacob M Dundee, Shannon N Leahy, Chuangye Qi, Yanyan Qi, Ye-Jin Park, Tzu-Chiao Lu, M Danish Uddin, Rong Zhao, Hui Zheng, Hongjie Li, Joanna L Jankowsky

Faculty, Staff and Students Publications

Pathological heterogeneity is increasingly appreciated in Alzheimer’s disease, yet we do not know how distinct aggregate conformations arise or influence cognitive outcomes. In an amyloid mouse model, we found that different brain regions formed structurally distinct Aβ deposits, prompting us to test whether neuronal subtypes shape aggregate conformation. To address this, we created transgenic mice expressing the same APP construct in either glutamatergic or GABAergic neurons. APP expression in GABAergic neurons resulted in diffuse plaques with high Aβ42/Aβ40 ratios and minimal gliosis, while glutamatergic expression produced neuritic plaques with activated glia. Despite similar Aβ levels, only mice with neuritic plaques …

Pathogenesis Of Polyglutamine Diseases: Piecing Together A Complex Molecular Puzzle, Esmeralda Villavicencio Gonzalez, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

Polyglutamine (polyQ) diseases, caused by a CAG repeat expansion encoding a glutamine tract in nine distinct proteins, present a complex molecular puzzle in which each piece contributes to neurodegeneration. While each of the causative proteins has a distinct function, the downstream consequences of polyQ toxicity are often similar, including protein accumulation, transcriptional dysregulation, somatic CAG repeat instability, disrupted energy homeostasis, compromised synaptic function, and selective neuronal death. This review summarizes emerging insights into how proteins with an expanded polyQ tract disrupt distinct cellular functions, and we examine a multitude of discoveries that are inspiring and reshaping novel therapeutic strategies.

A Systematic Literature Review Of Cvid Reveals Pervasive Detrimental Noninfectious Manifestations, G Michelle Ducasa, Rebecca A Marsh, Ali Mojebi, Hsi-En Ho, Charlotte Cunningham-Rundles, Lisa Forbes Satter, Elena W Y Hsieh, Sinisa Savic, Marta Dafne Cabañero-Navalón, Hector Balastegui-Martin, Joud Hajjar, Gulbu Uzel, Kevin S Thorneloe, Jocelyn R Farmer

Faculty, Staff and Students Publications

Noninfectious manifestations of common variable immunodeficiency (CVID) are not formally summarized. We performed a systematic literature review to generate a comprehensive reference for the field. Splenomegaly was the most reported manifestation across 53 publications, occurring in a median of 35.2% of patients. Frequently reported digestive system manifestations included diarrhea (median 27.8%; 21 publications), hepato(spleno)megaly (median, 21.0%; 19 publications), portal hypertension (median 21.0%; 3 publications), nodular lymphoid hyperplasia (median, 17.0%; 9 publications), and enteropathy (median, 16.0%; 34 publications). Other notable manifestations included interstitial lung disease (median, 8.7%; 32 publications) and autoimmune cytopenias (median 18.0%; 21 publications). Steroids and rituximab were the …

Neurodevelopmental Outcomes Following Hematopoietic Cell Transplantation For Patients With Severe Combined Immunodeficiency (Scid): A Pidtc Study, Virdette L Brumm, Sharon A Kidd, Brent R Logan, Farheen Chunara, Jennifer Heimall, Linda M Griffith, Donald B Kohn, Lauren Sanchez, Jeffrey J Bednarski, Caridad Martinez, Mark Vander Lugt, Neena Kapoor, Nicola Wright, Barbara Spitzer, Joseph H Oved, Sharat Chandra, Deepak Chellapandian, Christen L Ebens, Aleks Petrovic, Ahmad Rayes, Hilary L Haines, Hannah Lust, Hannah-Lise Tirado Schofield, Lauren Christopher, Lynnette L Harris, Lisa Forbes Satter, Lauri Burroughs, Christopher C Dvorak, Elie Haddad, Jennifer W Leiding, Rebecca A Marsh, Luigi D Notarangelo, Sung Yun Pai, Michael A Pulsipher, Jennifer M Puck, Morton J Cowan, Ami J Shah

Faculty, Staff and Students Publications

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for severe combined immunodeficiency (SCID). Since the initiation of newborn screening (NBS), survival rates have improved significantly, but the impact of HCT upon neurodevelopment for patients with SCID requires more investigation. We performed a cross-sectional study of subjects with SCID in North America to assess the impact of NBS, transplant conditioning regimen, and genotype on neurodevelopmental outcomes after HCT. 69 subjects with SCID from 17 PIDTC centers (excluding those with ADA deficiency), ages 6-16 years, received comprehensive standardized neurodevelopmental testing of cognitive, behavioral, and emotional function. Compared with the normative population, …

Vacmap: An Accurate Long-Read Aligner For Unraveling Complex Genomic Rearrangements, Hongyu Ding, Fritz J Sedlazeck, Christos Proukakis, Caoimhe Morley, Marco Toffoli, Anthony Hv Schapira, Zhirui Liao, Lianrong Pu, Shanfeng Zhu

Faculty, Staff and Students Publications

Sequence alignment is essential for genomic research and clinical diagnostics, yet detecting complex rearrangements such as inversions, duplications, and gene conversions remains challenging due to allele complexity and limitations of current methods. We introduce VACmap, a non-linear mapping approach to enhance the detection and representation of all genetic variations. VACmap improves duplication detection from 20% to 90% in the Challenging Medically-Relevant Genes (CMRG) benchmark and improves characterization of complex inversions in repetitive regions and gene conversion events. It improves resolving clinically significant loci, including the LPA gene (with repetitive KIV-2 units linked to coronary heart disease), GBA1 and STRC genes …

Conclusions Are Not Supported By The Published Statistical Analysis Comment On López-Toledo Et Al Flaxseed Improves Glucose And Lipid Metabolism In Mexican Subjects With Type 2 Diabetes: A Parallel Randomized Clinical Trial, Robert W Spitz, Deependra K Thapa, Thirupathi Reddy Mokalla, Wasiuddin Najam, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

López-Toledo et al [...].

Performance Of A Rapid, Highly Multiplexed Nucleic Acid Detection Assay For Identification Of Viral And Bacterial Pathogens From Upper Respiratory Tract Specimens, Coreen L Johnson, James J Dunn

Faculty, Staff and Students Publications

Background: Accurate and timely identification of upper respiratory tract pathogens can improve patient management by decreasing unnecessary additional testing, reducing the cost of care, and informing antimicrobial stewardship. We evaluated the FDA-cleared Diasorin LIAISON PLEX® Respiratory Flex (RSP Flex), a highly multiplexed, rapid nucleic acid detection assay that can identify 14 viral and 5 bacterial respiratory pathogens.

Methods: In total, 215 residual patient upper respiratory tract specimens were tested using the RSP Flex assay and results compared to standard-of-care (SOC) molecular testing.

Results: Positive percentage agreement (PPA) was 100% for the following targets: adenovirus, human coronavirus, Bordetella pertussis, Bordetella parapertussis, …