Digital Commons Network^™

Maternal Fish Intake In The Year Prior To Conception And Birth Defects, National Birth Defects Prevention Study, 1997-2011, Dorothy Kim Waller, Zeyu Miao, Renata H Benjamin, Richard Finnell, Nithya Lakshmi Mohan Dass, Eirini Nestoridi, Marcia C De Oliveira Otto, Julie Peterson, Tunu Ramadhani, Mark A Canfield

Faculty, Staff and Students Publications

Background: Epidemiologic data on the association between maternal fish intake and birth defects are sparse. Our objective was to assess associations between maternal fish intake and 52 different birth defects, most of which have not been assessed previously.

Methods: Using logistic regression, data was analyzed for 29,242 mothers of infants with birth defects and 10,973 mothers of control infants who participated in the National Birth Defects Prevention Study (NBDPS) and delivered between 1997 and 2011. We focused on associations between mothers who reported high fish intake of 2 or more servings of fish per week for the year prior to …

Dolutegravir Developmental Toxicity Is Mitigated By Magnesium And Folate In Zebrafish Embryos, Robert M Cabrera, Ahmed Mohamed, Ryoko Minowa, Katheryn A Neugebauer, Daniel A Gorelick

Faculty, Staff and Students Publications

Integrase strand transfer inhibitors have transformed human immunodeficiency virus (HIV) therapy, yet the widely prescribed drug dolutegravir (DTG) has been linked to developmental toxicity, and its teratogenic mechanism remains unclear. Here, we used zebrafish to dissect DTG toxicity during early vertebrate development. DTG exposure from 2-4 h post-fertilization (hpf) to 24 hpf produced high mortality and abnormal morphology. Co-treatment with folates partially restored normal morphology, whereas calcium had no effect. Strikingly, supplementation with magnesium (Mg) partially rescued DTG-exposed embryos, implicating Mg availability in protection. In competitive binding assays, Mg increased binding of folate to purified folate receptor (FOLR1) by 30% …

Validation Of The German Version Of The Movement Disorder Society Non-Motor Scale (Mds-Nms), Jonas Bendig, Anika Frank, Adrianna Lipska-Dieck, Kristof Wunderlich, David Geißler-Lösch, Isabel Wurster, Roswitha Kemmner, Kathrin Brockmann, Sheng Luo, Christopher G Goetz, Glenn T Stebbins, Pablo Martinez-Martin, Tiago A Mestre, Alvaro Sanchez-Ferro, Monica M Kurtis, Michelle H S Tosin, Roberta Balestrino, Chi-Ying R Lin, Carmen Gasca-Salas, Heinz Reichmann, Bjoern H Falkenburger

Faculty, Staff and Students Publications

No abstract provided.

Adhesion G Protein-Coupled Receptors, Tobias Langenhan, Garret R Anderson, Demet Araç, Gabriela Aust, Monserrat Avila-Zozaya, Sofie Morsing Bagger, Patrick Barth, Sandra Berndt, Stephen C Blacklow, Beatriz Blanco-Redondo, Antony A Boucard, James P Bridges, Lara-Sophie Brodmerkel, Kathleen M Caron, Yin Kwan Chung, Andrew N Dates, Virginea De Araujo Farias, Daniel Del Toro, Joseph G Duman, Felix B Engel, David M Favara, Caroline J Formstone, Chaoyu Fu, Alain Garcia De Las Bayonas, Anastasia Georgiadi, David E Gloriam, Randy A Hall, Jörg Hamann, Peter W Hildebrand, Cheng-Chih Hsiao, Bill X Huang, Jonathan A Javitch, Hee-Yong Kim, Robert J Kittel, Gunnar Kleinau, Richard Leduc, Ines Liebscher, Hsi-Hsien Lin, Joshua Linnert, Marie-Gabrielle Ludwig, David C Martinelli, Signe Mathiasen, Daniel Matúš, Mariam Melkumyan, Ana L Moreno-Salinas, Jan Mulder, Michael A Nash, Kasturi Pal, Daniel T Pederick, Nicole A Perry-Hauser, Xianhua Piao, Yu-Qi Ping, Dimitris G Placantonakis, Fabian Pohl, Simone Prömel, Mette M Rosenkilde, Laurent Sabbagh, Richard C Sando, Patrick Scheerer, Torsten Schöneberg, Elena Seiradake, Mareike Selcho, Florian Seufert, Abhishek K Singh, Georgios Skiniotis, Katja Spiess, Norbert Sträter, David Strutt, Thomas C Südhof, Jinpeng Sun, Gregory G Tall, Doreen Thor, Douglas G Tilley, Kimberley F Tolias, Mario Vallon, Erwin G Van Meir, Benoit Vanhollebeke, Giselle R Wiggin, Uwe Wolfrum, Jie Yan, Nathan A Zaidman, Yimin Zou, Nicole Scholz

Faculty, Staff and Students Publications

Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly apparent. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in this field and provides a comprehensive …

Assessment Of Correctness, Content Omission, And Risk Of Harm In Large Language Model Responses To Ophthalmology Continuing Medical Education Questions, Jacqueline L Chen, Amanda J Lu, Rohan Verma, Li Wang, Douglas D Koch, Allison J Chen

Faculty, Staff and Students Publications

Purpose: To evaluate the accuracy and prose responses of 2 large language models (LLMs) to ophthalmology continuing medical education questions.

Design: Question prompts and multiple choice (MC) answer options were input into the 2 LLMs, and responses were analyzed for accuracy and assessed for evidence of correctness, completeness, bias, and potential harm using a previously reported standardized rubric.

Subjects: Basic and Clinical Science Course questions and MC answer options from the American Academy of Ophthalmology question bank were used as inputs into the 2 LLMs (ChatGPT-4 and Google Vertex's Gemini Pro 1.5).

Methods: The MC responses were assessed for accuracy …

Antibiotics Aren’T Enough, Andrew R Dinardo, Christoph Lange

Faculty, Staff and Students Publications

No abstract provided.

Risk Factors For The Development Of Food Allergy In Infants And Children: A Systematic Review And Meta-Analysis, Nazmul Islam, Alexandro W L Chu, Falana Sheriff, Farid Foroutan, Gordon H Guyatt, Romina Brignardello-Petersen, Paul Oykhman, Alfonso Iorio, Ariel Izcovich, Katherine M Morrison, Yetiani Roldan Benitez, Rachel J Couban, Dorota Borovsky, Yiming Zhang, Leonardo Ologundudu, Keerthana Pasumarthi, Syed Fahad Farooq, Kyle Tong, Wang-Choi Tang, Haseeb Faisal, Muhammad Faran Khalid, Mohammad Saad Asif, Shannon French, Susan Waserman, R Sharon Chinthrajah, Hugh A Sampson, S Shahzad Mustafa, Jay A Lieberman, Kirsi M Järvinen, Sally Bailey, Philippe Bégin, Scott H Sicherer, Jennifer Gerdts, Melanie Carver, Lynda Mitchell, Kelly Cleary, Matthew J Greenhawt, Julie Wang, Aikaterini Anagnostou, Marcus S Shaker, Anita Chandra-Puri, Patricia C Fulkerson, Robert A Wood, Derek K Chu

Faculty, Staff and Students Publications

Importance: The incidence and risk (predictive) factors for early life food allergy development remain uncertain.

Objective: To estimate the incidence and quantify risk factors for food allergy development.

Data sources: MEDLINE and Embase were systematically searched to January 1, 2025. Data were analyzed from June 1, 2025, to November 25, 2025.

Study selection: Incidence estimates included studies confirming food allergy via food challenge. Risk factor analyses included cohort, case-control, and cross-sectional studies in any language assessing children younger than 6 years using multivariable analyses.

Data extraction and synthesis: Paired reviewers independently extracted data. Random-effects meta-analyses pooled incidence and adjusted odds …

Hiding In Plain Sight: A Call To Prevent Cutaneous Leishmaniasis Transmission In The United States, Juan David Ramírez, Sarah M Gunter, Megan Coffee, Norman Beatty, Dawn M Wetzel

Faculty, Staff and Students Publications

Cutaneous leishmaniasis (CL), once considered a travel-associated tropical disease, is increasingly transmitted within the United States, particularly in southern regions. Despite mounting evidence of local transmission, public health recognition and preventive infrastructure remain limited. This Viewpoint highlights the urgent need to shift the U.S. CL response from questioning endemicity to preventing transmission. We review ecological, clinical, and surveillance data demonstrating the presence of competent vectors, animal reservoirs, and autochthonous human cases. Diagnostic delays, underreporting, and insufficient provider training contribute to missed prevention opportunities. Climate change and peri-urban rodent-human contact data further heighten future risk. A coordinated response is essential, including …

Reducing Transfusions In Neuromuscular Spinal Fusion: A National Surgical Quality Improvement Program-Pediatrics Quality Improvement Project, Holden Archer, Venessa L Pinto, Farrah Russell, Valentina Briceño, Melissa Ard, Lisa Hensch, Jun Teruya, Tanisha G Daugherty, Wallis Molchen, Ryan D Coleman, Darrell Hanson, Frank T Gerow, Nicole I Montgomery

Faculty, Staff and Students Publications

Background: Pediatric spinal fusion can result in substantial blood loss, particularly in patients with scoliosis related to underlying neuromuscular (NM) disease. Transfusion is frequently required but carries risks including transfusion reactions, alloimmunization, volume overload, and infection.

Local problem: The American College of Surgeons National Surgical Quality Improvement Program-Pediatrics (ACS NSQIP-P) is a nationally validated, risk-adjusted national outcomes registry. At our institution, ACS NSQIP-P data identified our institution as a high outlier in transfusion for neuromuscular scoliosis patients.

Methods: A multidisciplinary group convened from January 2024 to June 2024 to design and implement a perioperative pathway with the primary goal of …

Noncanonical Clock Regulators Control Stress Responses In Digestive Diseases, Dishu Zhou, Roberto E López-Valiente, Samer G Mattar, Dongyin Guan

Faculty, Staff and Students Publications

The digestive system is essential for nutrient absorption, processing, and waste elimination. The expression of many genes and physiological processes within this system exhibits a 24-h rhythmicity. However, modern lifestyle factors, such as jet lag, shift work, and irregular eating patterns, significantly disrupt these rhythms, triggering various stress responses and contributing to numerous digestive disorders. Here, we focus on emerging studies on noncanonical clock regulators involved in stress responses, integrate these novel findings into the established model of the core circadian clock, and highlight recent advances in the development of novel therapeutics targeting these 24-h regulators. In addition, we discuss …

High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology Of Lung Cancer Consortium, Yanhong Liu, Yafang Li, Jinyoung Byun, Vikram R Shaw, Claudio Pikielny, Bo Peng, Chao Cheng, Spiridon Tsavachidis, Xiangjun Xiao, Dakai Zhu, Younghun Han, Ivan P Gorlov, Olga Y Gorlova, Michael Cole, Colette R Gaba, Erin L Crawford, Kristen Purrington, Ellen L Goode, Ping Yang, James Mckay, John K Field, Geoffrey Liu, Rayjean J Hung, Jun Xia, Jiyeon Choi, Matthew B Schabath, Jaclyn Lopiccolo, David C Christiani, Joan Bailey-Wilson, Ann G Schwartz, James C Willey, Diptasri Mandal, Susan M Pinney, Christopher I Amos

Faculty, Staff and Students Publications

Introduction: Rare, deleterious germline variants are key contributors to inherited lung cancer (LC) risk. The Genetic Epidemiology of LC Consortium (GELCC) has curated valuable high-risk LC families and is uniquely positioned to uncover rare, high-penetrance variants underlying familial LC (FLC).

Methods: We performed whole-genome and exome sequencing on germline DNA from 120 high-risk LC families (177 FLC cases, 309 unaffected relatives). We prioritized rare (allele frequency < 1% in the genome aggregation database), potentially deleterious variants present in two or more FLC cases. These variants were then validated in 10,085 sporadic LC (SLC) cases and 612,970 controls.

Results: We identified 118 candidate variants, 28 of which were validated in SLC with strong statistical support. We discovered a novel pathogenic axis of three truncating variants in GALNT6, MUC4, and ERBB3 genes, which …

Phenotypic Diversity And Outcomes In Pediatric Nmda Receptor Encephalitis: A 15-Year Retrospective Study From The Largest Children's Hospital In The United States, Alexander J Sandweiss, Timothy Erickson, Yike Jiang, Varun Kannan, Jonathan M Yarimi, Kristen S Fisher, Nikita Shukla, Tim Lotze, Eyal Muscal, Kristy O Murray

Faculty, Staff and Students Publications

Anti‐NMDAR encephalitis (NMDARE) is an autoantibody‐mediated disorder characterized by seizures, movement disorders, neurocognitive deficits, and psychosis, but the complete phenotypic heterogeneity, and outcomes are incompletely understood in children. This single‐center retrospective analysis of NMDARE at the largest pediatric hospital in the United States between 2009 and 2024 screened 115 patients diagnosed with NMDARE. 103 had sufficient clinical data available for analyses. Two‐thirds were Hispanic, disproportionate to the Houston metro area demographics, and Hispanic patients had a higher CSF white cell count and antibody titer. Approximately one‐half of the patients with idiopathic NMDARE presented with a focal cortical phenotype that localized …

Racial, Ethnic, And Neighborhood Disparities In Acute Kidney Injury In Pediatric Acute Leukemia, Wendy C Bravo, Yimei Li, Tamara P Miller, Kelly Getz, Lusha Cao, Edward Krause, Mark Ramos, Judy Lee, Maria Monica Gramatges, Karen R Rabin, Michael Scheurer, Richard Aplenc, Michelle Denburg

Faculty, Staff and Students Publications

Introduction: We sought to identify racial/ethnic and neighborhood disparities in acute kidney injury (AKI) in children with acute lymphoblastic or myeloid leukemia (ALL, AML).

Methods: Electronic health record data were retrospectively collected from patients treated for de novo pediatric ALL or AML in the multicenter Leukemia Electronic Abstraction of Records Network. AKI was defined by modified Kidney Disease Improving Global Outcomes criteria. Neighborhood-level resources were defined by the Child Opportunity Level (COL). Prevalence ratios (PRs) for AKI at diagnosis by race/ethnicity and COL were calculated using modified Poisson regression. Cox regression was used to calculate hazard ratios (HRs) of first …

Interplay Between Genetic Ancestry, Self-Reported Race And Ethnicity, And Clinical Factors In Pediatric Acute Lymphoblastic Leukemia: A Redial Consortium Report, Pragati Kore, Jennifer M Geris, Maria Leon-Camarena, Maria I Castellanos, Olga A Taylor, Veronica Garcia-Morales, Austin L Brown, Pagna Sok, Jeremy M Schraw, Van Huynh, Kathleen F Ludwig, Laura J Klesse, Sandi L Pruitt, Amy E Hughes, Kevin Tien, Kenneth M Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Maria M Gramatges, Elizabeth G Atkinson, Philip J Lupo, Michael E Scheurer, Karen R Rabin

Faculty, Staff and Students Publications

Background: Pediatric acute lymphoblastic leukemia (ALL) is the most common cancer in children, and its incidence and outcomes vary by race and ethnicity.

Methods: The Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium has assembled a cohort of patients < 25 years at diagnosis to examine genetic and neighborhood-level factors influencing ALL. As the cohort is ongoing, for this report, we examined sociodemographic and cytogenetic factors that might be associated with ALL outcome disparities.

Results: Among 2,512 patients diagnosed between 2005 and 2020, we observed distinct patterns of genetic ancestry and residential characteristics across self-reported race and ethnicity. Latino children, who comprised 55.3% of the cohort, had a mean Amerindigenous ancestry proportion of 50.9%, whereas non-Latino White children exhibited a predominantly European ancestry (mean = 78%). Neighborhood-level analysis revealed significant socioeconomic and geographic differences by …

Mislabeling And Inappropriate Analysis Render Interpretations From “The Effect Of The Participatory Heat Education And Awareness Tools (Heat) Intervention On Agricultural Worker Physiological Heat Strain: Results From A Parallel, Comparison, Group Randomized Study” Unreliable, Chelsi M Webster, Yasaman Jamshidi-Naeini, Lilian Golzarri-Arroyo, Colby J Vorland, Zachary J Schlader, Blair D Johnson, David B Allison

Faculty, Staff and Students Publications

No abstract provided.

Inherited Tbx4 Frameshifting Variants Predicted To Escape Nonsense Mediated Decay In Two Families With Variable Phenotypes, Including Lethal Lung Developmental Disorders, Shruti A Pande, Hiuling Chan Joiner, Przemyslaw Szafranski, Tomasz Gambin, Michelle Wright, Qian Wang, Maiah Walters, Jan M Friedman, Jessica Saunders, Nicholas Avdimiretz, Cornelius F Boerkoel, Nahir Cortes-Santiago, Gail Deutsch, Pawel Stankiewicz

Faculty, Staff and Students Publications

Background: Pathogenic variants involving the transcription factor TBX4 gene have been associated with various skeletal and pulmonary abnormalities, including lethal lung developmental disorders (LLDD).

Methods: Whole-genome sequencing (WGS) with AI-powered platform for variant detection and interpretation followed by Sanger sequencing targeted variant segregation analysis were used. Reverse transcription quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) studies were performed to assess gene and protein expression levels, respectively.

Results: We describe two unrelated families with intrafamilial variability in the TBX4 phenotypic expressivity, including LLDDs. WGS analyses revealed two frameshift variants, c.1019del; p.(Arg340GlnfsTer40) in the penultimate exon and c.1167dup; p.(Arg390GlnfsTer30) in the last exon …

Culturally Tailored Materials For Smoking Cessation And Hiv Care Adherence Among Hispanic Adults: Protocol For Content Development And Formative Evaluation, Lorra Garey, Jacqueline J Charles, Ashley L Ruiz, Rodrigo Castillo-Avilés, Virmarie Correa-Fernández, Marshall K Cheney, Thomas P Giordano, Michael J Zvolensky

Faculty, Staff and Students Publications

Background: Hispanic people with HIV who smoke cigarettes experience unique stressors (eg, stigma), which contribute to health disparities. Anxiety sensitivity (AS) may worsen mood management problems, which are a leading barrier to smoking cessation. Interventions targeting AS can improve HIV-specific outcomes and smoking cessation. However, no prior research has culturally tailored an AS reduction program to improve quality of life among Hispanic people with HIV who smoke. The research team previously developed a mobile health (mHealth) intervention addressing AS reduction, smoking cessation, and HIV care management for Black people with HIV who smoke. Building on this work, this study represents …

Expanding The Mutation Spectrum Of Non-Syndromic Retinitis Pigmentosa In Consanguineous Pakistani Families: Unraveling Novel Pathogenic Variants In Rp1, Pde6b, And Prcd Genes For Precision Diagnosis, Tayyaba Shan, Nimra Mukhtar, Sayyed Hammad Ullah, Asad Ullah, Asfandyar Ahmad Khan, Yumei Li, Meng Wang, Raeesa Tehreem, Amtul Aziz, Kiran Afshan, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

No abstract provided.

Feasibility Of Nationwide Remote Chronic Neural Data Collection From Recording-Enabled Deep Brain Stimulation Systems, Kasra A Mansourian, Ajay D Gandhi, Jonathan H Bentley, Kalman A Katlowitz, Danika L Paulo, Nisha Giridharan, Mohammed A Hasen, Tommy B Liu, Zain U Naqvi, Sarah S Soubra, Thomas A Hamre, Rick R Hanish, Eric A Storch, Wayne K Goodman, Sameer A Sheth, Nicole R Provenza

Faculty, Staff and Students Publications

Introduction: Bidirectional deep brain stimulation (DBS) devices can continuously record neural activity while delivering stimulation. Due to memory limitations on the implanted device on which data are stored, frequent data downloads are required to prevent data loss. In this study, we present a novel collaborative data collection method utilizing a nationwide network of device representatives to allow frequent data transfer that reduces data loss without imposing travel burden on patients.

Methods: We collected chronic neural data from nine patients with severe obsessive-compulsive disorder who received ventral capsule/ventral striatum DBS treatment between May 2023 and August 2024. We included patients implanted …

Disordered Differentiation And Cellular Senescence In Pediatric Hodgkin Reed-Sternberg Cells, Jennifer E Agrusa, Elmoataz Abdel Fattah, Howard Lin, Jessica Velazquez, Sandra Andrea Salinas, Harshal A Abhyankar, Brooks P Scull, Ryan Fleischmann, M Tarek Elghetany, Andrea N Marcogliese, Choladda V Curry, Jyotinder N Punia, Nmazuo W Ozuah, Olive S Eckstein, Nader K El-Mallawany, Nitya Gulati, Joseph Lubega, Terzah M Horton, Kala Y Kamdar, Kenneth L Mcclain, Tsz-Kwong Man, Carl E Allen

Faculty, Staff and Students Publications

Hodgkin lymphoma (HL) is characterized by inflammatory lesions with relatively few (typically < 1%) pathogenic Hodgkin Reed-Sternberg (HRS) cells. The scarcity of malignant HRS cells in HL has historically limited characterization of these disease drivers, and pathogenic mechanisms underlying HL are incompletely defined. Using multiparameter flow cytometry to purify HRS cells and immune cell populations from pediatric HL lesions and control tonsils, we sought to define transcriptional programs in pediatric HRS cells. HRS cells are thought to arise from transformed germinal center B cells. Interestingly, transcriptomic analysis of HRS cells compared to control tonsil CD30+ cells revealed disordered differentiation with multilineage gene expression patterns, and primary HRS cells had distinct transcriptomes compared to HL cell lines. Further, transcriptomic analysis revealed increased expression of senescence-related genes and downregulation of proapoptotic/mitosis-related genes. Gene expression findings were validated by immunohistochemistry and single-cell imaging. In vitro treatment of primary HRS cells with B-cell lymphoma 2 inhibitor, venetoclax, augmented the induction of apoptosis in HRS cells and other cells of the HL immune microenvironment. These findings support the further study of targeting apoptosis resistance as a potential approach to eliminate malignant HRS cells and dismantle inflammatory lesion formation in pediatric HL.

Yap Induces A Prorenewal Metabolic State In Cardiomyocytes, Lin Liu, Jeffrey D Steimle, Chang-Ru Tsai, Fansen Meng, Yuka Morikawa, Yi Zhao, Sandra Carmichael, Xiao Li, James F Martin

Faculty, Staff and Students Publications

BACKGROUND: Cardiomyocytes, as highly specialized and differentiated somatic cells, possess a limited capacity for renewal. Neonatal rodents possess the ability to regenerate cardiomyocytes after injury; however, this regenerative capacity declines rapidly with cardiomyocyte maturation, suggesting an inhibitory network between cellular maturation and cardiomyocyte proliferation. Maturing cardiomyocytes undergo a metabolic shift from predominantly glycolysis in the neonatal state to increased fatty acid oxidation in the mature state, which poses a barrier to cardiomyocyte proliferation and cardiac regenerative repair. YAP, a transcriptional cofactor regulated by the Hippo signaling pathway, promotes cardiac regenerative repair. We investigated the role of YAP in mediating metabolic …

Percutaneous Coronary Intervention And Vascular Access Complications: A Contemporary Review, Tanawat Attachaipanich, Muzamil Khawaja, Edwin A Takahashi, Hafeez Ul Hassan Virk, Mahboob Alam, Ian C Gilchrist, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Transradial approach (TRA) is preferred over transfemoral approach (TFA) for percutaneous coronary interventions due to lower bleeding, vascular complications, and mortality, particularly in acute coronary syndrome. Radial access complications included intraprocedural events (spasm, dissection, and perforation) and postprocedural events (radial artery occlusion, hematoma, pseudoaneurysm, arteriovenous fistula, nerve injury, and infection). TFA remains necessary in certain settings but carries higher complication risk. Optimizing patient selection and procedural planning is essential to minimize vascular complications.

Age-Associated Hematopoietic Variants In The Rhesus Macaque, Josephine De La Fuente, Chiraag D Kapadia, R Alan Harris, Muthuswamy Raveendran, Giovanne B Diniz, John H Morrison, Jeffrey Rogers, Margaret A Goodell

Faculty, Staff and Students Publications

No abstract provided.

An Atlas Of Human Siglecs Integrates Expression, Affinity, And Cis/Trans Sialoglycan Recognition Profiles, Shani Leviatan Ben-Arye, Edward N Schmidt, Zeinab Jame-Chenarboo, Claire Guetta-Oz, Fahima Mozaneh, Jaesoo Jung, Kelli A Mccord, Ronit Rosenfeld, Kan Zhong, Hongzhi Cao, Hai Yu, Xi Chen, Lori J West, Matthew S Macauley, Vered Padler-Karavani

Faculty, Staff and Students Publications

All living cells have a sugar-coat that facilitates communication. Sialic acids cap mammalian glycans and are recognized by immune cells through sialic acid-binding immunoglobulin-like lectins (Siglecs) that regulate signaling by their cytoplasmic motifs. Inconsistent reports of Siglecs expression and sialoglycan recognition limit their therapeutic potential. Here we investigate 14 functional human Siglecs for their expression, glycan interactions and affinities. SIGLEC mRNA is broad in blood-derived monocytes and dendritic cells, restricted in natural-killer/B cells and absent in T cells, with similar Siglec-proteins expression in splenocytes. Binding to 114 glycans across 274 glycan microarrays, 220 splenocytes-assays and 132 cell-based arrays, reveal Siglecs …

Burden Of Cardiovascular Disease In Pakistan – Insight From Global Burden Of Disease Study 2019, Ali Bin Abdul Jabbar, Taha Mansoor, Sana Sheikh, Tazeen H Jafar, Sawera Hanif, Christian Razo, Mahboob Alam, Jamal S Rana, Khurram Nasir, Bashir Hanif, Salim S Virani, Abdul Mannan Khan Minhas

Faculty, Staff and Students Publications

Background: Pakistan, currently the fifth-largest country by population globally, has experienced a population increase of over 100% since 1990. It is facing an escalating challenge from cardiovascular diseases (CVD). The Global Burden of Disease (GBD) 2019 study provides an in-depth evaluation of Pakistan's health situation since 1990, offering essential insights into the nation's overall health conditions.

Methods: The data were obtained from the Global Burden of Disease Study 2019, which provides records for global, regional, and national burden of diseases. Specifically, data regarding CVD and its subtypes, morbidity, and mortality in Pakistan and globally from 1990 to 2019 were used …

Prodromal Lewy Body Disorder Features In Rem Sleep Behavior Disorder With Biomarker-Defined Synucleinopathy, Daniel Weintraub, Michele K York, Roseanne Dobkin, Anuprita R Nair, Ryan Kurth, David-Erick Lafontant, Chelsea Caspell-Garcia, Roy N Alcalay, Ethan G Brown, Lana M Chahine, Christopher Coffey, Tatiana Foroud, Douglas Galasko, Karl Kieburtz, Kenneth Marek, Kalpana Merchant, Brit Mollenhauer, Kathleen L Poston, Andrew Siderowf, Cristina Simonet, Tanya Simuni, Caroline M Tanner, Thomas F Tropea, Aleksandar Videnovic, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

Objective: Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal state for Lewy body disorders and exhibits biological heterogeneity that may influence clinical expression and progression. We examined clinical features in individuals with iRBD and biomarker-defined synucleinopathy.

Methods: Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, multi-center observational study. Participants included polysomnogram (PSG)-confirmed iRBD individuals who were cerebrospinal fluid (CSF) α-synuclein seed amplification assay positive with no clinical diagnosis of Parkinson's disease or dementia with Lewy bodies, along with robust healthy controls (HCs). Clinical and biological features of prodromal PD and DLB, including mild cognitive impairment (MCI), subthreshold …

Cardiovascular Disease And Dyslipidemia In Pediatric Type 1 Diabetes, Grace K Kim, Preneet Cheema Brar, Nidhi Bansal

Faculty, Staff and Students Publications

Purpose of review

Despite advances in type 1 diabetes (T1D) management, mortality is still increased, with cardiovascular disease (CVD) as the leading cause. Dyslipidemia is a highly prevalent modifiable CVD risk factor. We reviewed the existing literature on CVD mortality in T1D to highlight CVD risk in pediatric patients with T1D.

Recent findings

Pathophysiology of T1D and premature CVD risk is still not fully understood. Dyslipidemia remains a highly prevalent and undertreated CV risk factor in T1D. Statins have been shown to be safe and effective to improve CVD risk in adults with T1D, and in children with familial hypercholesterolemia, …

Obstructive Sleep Apnea Treatment Modifies The Effectiveness Of Catheter Ablation For Atrial Fibrillation: Post Hoc Analysis Of The Cabana Trial, Matthew W Segar, Kaleb D Lambeth, Brett Doliner, Joshua R Hirsch, Abdi Rasekh, Mehdi Razavi

Faculty, Staff and Students Publications

No abstract provided.

Designing Next-Generation Cardiometabolic Outcome Trials For Obesity Medicines, Elke Platz, Alexander Peikert, Biykem Bozkurt, Bart Van Der Schueren, Javed Butler, Ildiko Lingvay, Darren K Mcguire, Faiez Zannad, Naveed Sattar

Faculty, Staff and Students Publications

The prevalence of obesity has reached pandemic proportions and is having enormous public health effects. Obesity increases the risk of type 2 diabetes, hypertension, chronic kidney disease, and cardiovascular (CV) disease including coronary artery disease, heart failure, atrial fibrillation, and stroke. Although initial randomized clinical trials of weight-loss strategies through diet and exercise or early medical therapies did not lead to improved CV outcomes, more recent trials using glucagon-like peptide-1 (GLP-1) receptor agonists in individuals with obesity have demonstrated CV benefits. At present, there are multiple cardiovascular outcome trials (CVOTs) of novel GLP-1 receptor agonists and investigational products targeting multiple …

Rhesus Macaques With An Opa1 Mutation Demonstrate Features Of Autosomal Dominant Optic Atrophy, Tracy N Jaggers, Ana Ripolles-Garcia, Ala Moshiri, Brett D Story, Jun Wang, Rui Chen, Lucy G Moore, Leandro B C Teixeira, Jaeho Shim, Ana C Raposo, Maria Isabel Casanova, Sophie M Le, Sangwan Park, Laura J Young, Soohyun Kim, Karolina P Roszak, Vanessa Ureno, Paige M Karpinen, Nayeli Echeverria, Monica Ardon, Brian C Leonard, Marguerite Knipe, Eliza Bliss-Moreau, Brad Fortune, J Timothy Stout, Jeffrey Rogers, Nicholas Marsh-Armstrong, Sara M Thomasy

Faculty, Staff and Students Publications

Autosomal dominant optic atrophy (ADOA) is an inherited optic neuropathy primarily caused by mutations in OPA1. We identified and defined a spontaneous nonhuman primate (NHP) model of ADOA using rhesus macaques heterozygous for a missense mutation (OPA1A8S). With ocular examinations, ophthalmic imaging, electroretinography, histopathology, immunohistochemistry, and transmission electron microscopy (TEM), we documented retinal nerve fiber layer (RNFL) thinning, retinal ganglion cell (RGC) loss and dysfunction, OPA1 mislocalization, and reduced axonal mitochondrial density in affected macaques. Our investigation revealed substantial phenotypic variability among affected macaques, shedding light on the pathogenesis of ADOA. The retinas were evaluated using techniques …