Digital Commons Network^™

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 …

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 …

Mif-Cd74 Signaling Drives Immune Modulation In Medulloblastoma, Benjamin Draper, Zhen You, Dean Thompson, Xu Guo, Alaide Morcavallo, Diego Chillon Pino, Carlos Lorenzo Gido Nery, Sumana Shrestha, Chantelle E Bowers, Courtney Himsworth, Alberto Delaidelli, Bethany Remeniuk, Sonia Morlando, Brandon Wade, Freya Gordon, Yara Sanchez-Corrales, Bei Hopkins, Natalie Monteiro, Darren Locke, Miao Liu, Jacob Torrejon Diaz, Kevin Greenslade, Barbara Martins Da Costa, Karen Barker, Colin Kwok, Olumide Ogunbiyi, Anya Fletcher, Stacey Richardson, Carlos Custodia, Rafael Roque, Thomas Jackson, Regan Barfoot, Sergi Castellano, Rebecca M Hill, Olivier Saulnier, Thomas S Jacques, Michael D Taylor, Claudia C Faria, Olivier Ayrault, Poul H Sorensen, John Anderson, Louis Chesler, L Frank Huang, Steven C Clifford, Laura K Donovan

Faculty, Staff and Students Publications

Background: Relapsed medulloblastoma remains a significant therapeutic challenge as it is near universally fatal. The tumor microenvironment of medulloblastoma plays a critical role in tumor progression, influencing tumor growth, immune evasion, and therapeutic resistance. We hypothesized that defining tumor-immune interactions in diagnostic and relapsed medulloblastoma may uncover mechanisms of immune evasion and identify novel therapeutic targets.

Methods: We analyzed paired primary and recurrent RNA-sequencing data from 140 medulloblastoma patients to profile immune cell composition and validate spatial relationships within the TME. To identify key tumor-immune interactions, we developed a novel algorithm to detect receptor-ligand pairs using single-cell RNA-sequencing data. These …

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 …

Single-Nuclei Transcriptomic Profiling Of Human Myocardium In Long-Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase Deficiency, Hanna J Tadros, Diwakar Turaga, Yi Zhao, Chang-Ru Tsai, Lalita Wadhwa, Debra L Kearney, Iki Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

No abstract provided.

Protecting Minors From Medical Malpractice Act: Implications For Otolaryngology-Head & Neck Surgery, Shiven Sharma, Margo K Mckenna, Julina Ongkasuwan, Michael J Brenner

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 …

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 …

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 …

Vo: The Vaccine Ontology, Jie Zheng, Asiyah Yu Lin, Anthony Huffman, Anna Maria Masci, Rebecca Racz, Guanming Wu, Kallan Roan, Edison Ong, Sirarat Sarntivijai, Joy Hu, Eliyas Asfaw, Hayleigh Kahn, Xingxian Li, Xumeng Zhang, Joshua Monickaraj, Nilufer Kosar, Jianfu Li, Warren Manuel, Rashmie Abeysinghe, Hasin Rehana, Benu Bansal, Yuanyi Pan, Jinjing Guo, Virginia He, Justin Song, Andrey I Seleznev, Katelyn Hur, Anna He, Alexander Davydov, Qi Yang, Anna Ostropolets, Randi Vita, Bjoern Peters, Alan Ruttenberg, Alexander D Diehl, Charles Tapley Hoyt, Paola Roncaglia, Rachael P Huntley, Richard H Scheuermann, Melanie Courtot, Thomas Todd, Samantha Sayers, Fang Chen, Xinna Li, Feng-Yu Yeh, Zuoshuang Xiang, Arzucan Ozgur, Patricia L Whetzel, Mark A Musen, Christopher J Mungall, Wolfgang W Leitner, Licong Cui, Lesley A Colby, Harry L T Mobley, Brian D Athey, Gilbert S Omenn, Lindsay G Cowell, Cui Tao, Junguk Hur, Barry Smith, Yongqun He

Faculty, Staff and Student Publications

Vaccines are widely used in both research and clinical settings. To facilitate FAIR data practices, we urgently need to standardize vaccine representation, integrate information across diverse vaccine types, and support computer-assisted reasoning. Accordingly, we have since 2007 developed the community-based Vaccine Ontology (VO), which aligns with the Basic Formal Ontology and adheres to OBO Foundry principles. VO ontologically models vaccines, vaccine components, vaccine immune responses, vaccine investigation studies and other vaccine-related topics. VO represents more than 10,000 vaccines targeting 289 infectious pathogens and cancers in humans and over 30 nonhuman animal species. VO provides mappings to external resources such as …

Admixture-Informed Polygenic Risk Reporting Using The Eprs Framework, Yu-Jyun Huang, Nuzulul Kurniansyah, Matthew O Goodman, Brian W Spitzer, Jiongming Wang, Adrienne Stilp, Cecelia Laurie, Paul S De Vries, Han Chen, Yuan-I Min, Mario Sims, Gina M Peloso, Xiuqing Guo, Joshua C Bis, Jennifer A Brody, Laura M Raffield, Jennifer A Smith, Wei Zhao, Jerome I Rotter, Stephen S Rich, Susan Redline, Myriam Fornage, Robert Kaplan, Nora Franceschini, Daniel Levy, Alanna C Morrison, Eric Boerwinkle, Nicholas L Smith, Charles Kooperberg, Bruce M Psaty, Sebastian Zöllner, Tamar Sofer

Faculty, Staff and Student Publications

Polygenic risk score values vary with genetic ancestry due to differences in population-specific allele frequencies and linkage disequilibrium patterns. We present a framework to calibrate polygenic risk scores based on ancestral makeup. We propose the "expected polygenic risk score" or ePRS, defined as the expected value of a polygenic risk score based on one's global or local admixture patterns. We further define the "residual polygenic risk score" or rPRS as measuring the deviation of the polygenic risk score from the ePRS. The ePRS reflects the baseline ancestry-driven component of genetic risk, whereas the rPRS isolates an ancestry-agnostic measure of genetic …

Hyperdynamic Microtubule-Based Structural Changes In Monocyte-Derived-Neuronal-Like Cells From Patients With Schizophrenia, Alfredo Bellon, Alonso Cortez-Resendiz, Lauren N Forrest, Omar Elmarasi, Janani Iyer, Anjali Iyer, Chachrit Khunsriraksakul, Dajiang Liu, L Elliot Hong, Therese M Jay, Marie-Odile Krebs, Anne Hosmalin

Faculty, Staff and Student Publications

A consistent postmortem finding in schizophrenia (SCZ) is reduction in dendrites' size. However, neurons with larger dendritic trees have also been encountered. In vitro experiments with neurons and neuronal-like cells coming directly from patients with SCZ showed similar results, evidencing at times more extensions and at others less arborizations. The process of extending and retracting neuronal outgrowths depends on microtubules polymerization and depolymerization. The possibility that microtubule polymerization/depolymerization is related to defects in the neuronal structure comes from several microtubular anomalies reported in SCZ such as its abnormal distribution in the cytoplasm, irregular shape of microtubules and even absence of …

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 …

Inhibition Of Epac1 Prevents Neuronal Death Mediated By Diesel Exhaust Particles In Ferroptotic Cell Death Conditions, Hong Yan, Leshan Zhang, Ana L Manzano-Covarrubias, Phoeja S Gadjdjoe, Anja Land, Christina H J T M Van Der Veen, Teresa Mitchell-Garcia, Heba A Fayyaz, Marco Venema, Christoffer Åberg, Marieke Van Der Hart, Frank Lezoualc'h, Xiaodong Cheng, Amalia M Dolga, Martina Schmidt

The Brown Foundation: Institute of Molecular Medicine

Air pollution is a growing hazard to global health. Epidemiological studies have reported a potential role of air pollutant exposure in the development or aggravation of neurodegenerative diseases. However, the underlying mechanisms are ill-defined. Ferroptosis is an iron- and reactive oxygen species (ROS)-dependent form of cell death that drives neuronal loss in neurodegenerative diseases. Our previous studies reported the involvement of adenosine 3',5'-cyclic monophosphate (cAMP) and EPAC (exchange protein directly activated by cAMP) in ferroptotic cell death. Here, we investigated the effects of diesel exhaust particles (DEP) in mouse hippocampal (HT22) neuronal cells. Our data showed that toxicity induced by …

The Right Time For A Synapse To Change: Windows And Mechanisms Of Multiday Training Trials, Rong-Yu Liu, Yili Zhang, Roberta Calvo, Paul Smolen, John H Byrne

Faculty, Staff and Student Publications

Although learning over multiple days is more effective than a single day of training, the underlying cellular mechanisms of repeated training trials remain poorly understood. With a combination of empirical and computational approaches, we determined a critical time window for a second stimulus block of a multiday training protocol to augment long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse and long-term enhancement of neuronal excitability (LTEE), two cellular correlates of learning and memory. A second stimulus block delivered 24 h after the first block significantly enhanced LTF and LTEE, but was without effect at 18 or 32 h. This …

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.

Cross-Sectional Associations Of Metabolically Healthy Obesity, Lifestyle Factors, And Steatotic Liver Disease In Adults From The Fels Longitudinal Study, Ariana L Garza, Audrey C Choh, John Blangero, Cici X Bauer, Stefan A Czerwinski, Miryoung Lee

Faculty, Staff and Student Publications

Objective: To examine the associations of metabolic health and obesity phenotypes with liver fat accumulation and hepatic steatosis in adults.

Methods: We analyzed 676 non-Hispanic white adults (18-95 years; 55.8% female) from the Fels Longitudinal Study using a cross-sectional design. Participants were classified into metabolically healthy normal weight (MHNW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obesity (MUO) phenotypes. Metabolically unhealthy status was defined as the presence of ≥1 metabolic dysfunction, consistent with prior epidemiological definitions; secondary analyses using ≥2 were also performed. Obesity was defined using DXA-derived body fat percentage. Liver fat (%) was …

Risk Of Alzheimer Dementia After High-Dose Vs Standard-Dose Influenza Vaccination, Avram Samuel Bukhbinder, Yaobin Ling, Lauren Jhin, Elizabeth He, Kristofer Harris, Mya Rodriguez, Jenna Thomas, Gabriela Cruz, Kamal Phelps, Yejin Kim, Luyao Chen, Xiaoqian Jiang, Paul E Schulz

Faculty, Staff and Student Publications

Background and objectives: Previous studies, including large cohort analyses comparing vaccinated and unvaccinated adults, suggest that routine immunizations such as inactivated influenza vaccines (IIVs) may reduce Alzheimer dementia (AD) risk. Whether AD risk differs after high-dose IIV (H-IIV) vs standard-dose IIV (S-IIV) remains unexamined. We hypothesized that AD risk would be lower among adults ≥65 years after H-IIV compared with S-IIV.

Methods: This retrospective cohort study analyzed data spanning 2014-2019 from IQVIA PharMetrics Plus for Academics, a US health care claims database. Eligible participants were ≥65 years with ≥2 years of continuous medical and pharmaceutical coverage and no previous diagnostic …

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 …

Engineering Function In Lung Biology: Integrating Imaging, Regenerative Constructs, And Functional Biodesign, Rene A Girard, Jamie Tran, Yuqing Cai, Mary C Farach-Carson, Hadi T Nia, Allison M Greaney, Laura E Niklason, Killian Hurley, Elvin Blanco, Sinem Koc-Günel, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The lung is a uniquely demanding target for regeneration because function depends on the coordinated integration of cellular diversity, three-dimensional architecture, cyclic mechanical forces, vascular perfusion, immune surveillance, and extracellular matrix remodeling. While single-cell and spatial profiling, lineage tracing, and iPSC-derived models have transformed our understanding of lung cell states and developmental potential, these descriptive approaches have also highlighted a central bottleneck: the field still lacks broadly adopted platforms to test whether engineered tissues and regenerative interventions restore function under physiologic load. In this review, we focus on emerging technologies that enable functional biodesign in lung biology by coupling engineered …

Modeling Early Human Heart Development Using An Ipsc-Based 3d Bioprinted Model Of Embryonic Heart Tube, Linqi Jin, Christian Park, Sunder Neelakantan, Shweta Karnik, Arnab Dey, Sarah Fineman, Roshni Nandwani, Carmen J Gil, Boeun Hwang, Melissa A Cadena, Vani Sridhar, Jing Wang, Yuxiao Wu, Connor J Evans, Lan Li, Sarah Rezapourdamanab, Mehdi Salar Amoli, Martin L Tomov, Ryan K Roeder, Reza Avazmohammadi, Lakshmi Prasad Dasi, Hanjoong Jo, Eric Weeks, Holly D Bauser-Heaton, Sean M Wu, Vahid Serpooshan

Faculty, Staff and Student Publications

Human heart development depends on tightly coordinated genetic programs and biomechanical cues, yet the underlying cell-microenvironment interactions remain poorly understood because the developing heart is difficult to study in utero and accurate experimental models are lacking. Recent advances in stem cell biology and three-dimensional (3D) bioprinting now allow the construction of human tissue analogues with defined structure and function. Here we show a perfusable 3D bioprinted model of the human embryonic heart tube composed of layered myocardium, cardiac jelly, and endocardium. Human induced pluripotent stem cell-derived cardiomyocytes and endothelial cells are cultured under controlled flow conditions, producing constructs with high …

Functional Requirement For Dicer Helicase Arginine Methylation In 26 G Sirna Biogenesis And Oocyte Meiotic Program, Nick Newkirk, Shin-Yu Chen, Tokiko Furuta, Kenneth A Trimmer, Leilei Shi, Sabrina Stratton, Hongyuan Li, Xiaodong Cheng, Mark T Bedford, Swathi Arur

The Brown Foundation: Institute of Molecular Medicine

Spatiotemporal regulation of Dicer is essential for small RNA biogenesis and fertility, yet how its helicase domain is controlled remains unclear. Using Caenorhabditis elegans, we identify a regulatory role for the arginine-rich GRARR motif within helicase domain motif VI of DCR-1. Mutating conserved arginines in this sequence disrupts maternal 26 G endo-siRNA production, impairs oocyte meiosis I and II, and reduces fertility. Biochemically, an asymmetrically dimethylated DCR-1 GRA[R495*]R peptide enhances interaction with ERI-5, a tandem-Tudor protein in the ERIC complex, while loss of DCR-1(R495) diminishes this interaction in vivo. Genetically, eri-5 deletion phenocopies the dcr-1 R495K mutant, supporting a functional …

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.

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 …

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 …

Diagnostic Potential For Igm Antibody Detection By The Dpp Syphilis Tnt Assay In Neonates At Risk For Congenital Syphilis, Irene A Stafford, Lierni Ugartemendia Ugalde, Laura M Goetzl, Analuisa Mosqueda, Sabrina Dacosta, Dhammika Gunasekera, Mark Rivieccio, Javan Esfandiari, Konstantin P Lyashchenko

Faculty, Staff and Student Publications

Neonatal IgM antibodies reflect an in utero immune response to Treponema pallidum and may offer added diagnostic value. This study evaluated the test performance of treponemal IgM levels measured by the research-use-only (RUO) Dual Path Platform (DPP) Syphilis TnT point-of-care (POC) assay for congenital syphilis (CS) risk stratification. Conducted from May 2023 to May 2025, this study tested neonatal serum samples from infants born to mothers with syphilis using the DPP Syphilis TnT RUO POC assay, which reports treponemal and nontreponemal IgM levels as relative light units (RLU). Neonates were classified as confirmed proven or highly probable CS, possible …

Genome-Wide Association Study Of Copy Number Variations In Parkinson’S Disease, Zied Landoulsi, Ashwin Ashok Kumar Sreelatha, Nicole Kuznetsov, Claudia Schulte, Dheeraj Reddy Bobbili, Ludovica Montanucci, Costin Leu, Lisa-Marie Niestroj, Emadeldin Hassanin, Cloé Domenighetti, Pierre-Emmanuel Sugier, Milena Radivojkov-Blagojevic, Peter Lichtner, Berta Portugal, Connor Edsall, Jens Krüger, Dena G Hernandez, Cornelis Blauwendraat, George D Mellick, Alexander Zimprich, Walter Pirker, Manuela Tan, Ekaterina Rogaeva, Anthony Lang, Sulev Koks, Pille Taba, Suzanne Lesage, Alexis Brice, Jean-Christophe Corvol, Marie-Christine Chartier-Harlin, Eugenie Mutez, Kathrin Brockmann, Angela B Deutschländer, Georges M Hadjigeorgiou, Efthimos Dardiotis, Leonidas Stefanis, Athina Maria Simitsi, Enza Maria Valente, Simona Petrucci, Letizia Straniero, Anna Zecchinelli, Gianni Pezzoli, Laura Brighina, Carlo Ferrarese, Grazia Annesi, Andrea Quattrone, Monica Gagliardi, Lena F Burbulla, Hirotaka Matsuo, Akiyoshi Nakayama, Nobutaka Hattori, Kenya Nishioka, Sun Ju Chung, Yun Joong Kim, Lukas Pavelka, Pierre Kolber, Bart Pc Van De Warrenburg, Bastiaan R Bloem, Andrew B Singleton, Dan Vitale, Mathias Toft, Lasse Pihlstrom, Leonor Correia Guedes, Joaquim J Ferreira, Soraya Bardien, Jonathan Carr, Eduardo Tolosa, Mario Ezquerra, Pau Pastor, Karin Wirdefeldt, Nancy L Pedersen, Caroline Ran, Andrea C Belin, Andreas Puschmann, Carl E Clarke, Karen E Morrison, Dimitri Krainc, Matt J Farrer, Dennis Lal, Alexis Elbaz, Thomas Gasser, Rejko Krüger, Manu Sharma, Patrick May

Faculty, Staff and Student Publications

We investigated the role of copy number variations (CNVs) in Parkinson's disease (PD) using genotyping data from 10,815 patients (2731 early-onset PD, EOPD) and 8901 controls from the COURAGE-PD consortium. CNVs were analyzed using a sliding window genome-wide association and burden approach. No genome-wide significant CNVs were detected in the overall cohort, but a robust deletion spanning exons 2-6 of PRKN was identified in EOPD cases, validated by MLPA, and replicated in the GP2 dataset (23,089 cases, 18,824 controls). CNV burden was significantly enriched in PD-related genes, primarily driven by PRKN, with the strongest effect observed in EOPD. PRKN CNV …

Lotilaner Ophthalmic Solution 0.25% In The Treatment Of Demodex Blepharitis: A Case Report, Paul Karpecki, Brandon Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Cecelia Koetting, Richard Lindstrom, Selina Mcgee, Kelly K Nichols, Laura M Periman, Stephen Pflugfelder, Christopher Starr, Nandini Venkateswaran, Elizabeth Yeu

Faculty, Staff and Students Publications

Demodex blepharitis is a chronic inflammatory ocular condition caused by Demodex mite infestation of the eyelid that can negatively impact quality of life. Currently, lotilaner ophthalmic solution 0.25% is the only FDA-approved treatment for Demodex blepharitis. The Demodex Expert Panel on Treatment and Eyelid Health has established consensus that lotilaner ophthalmic solution 0.25% should be considered the preferred first-line treatment for Demodex blepharitis. We report a patient who presented with collarettes, the pathognomonic sign of Demodex blepharitis, meibomian gland dysfunction, and poor visual acuity. The patient also had a history of neovascular age-related macular degeneration. Consistent with the Demodex Expert …