Digital Commons Network^™

A Mouse Model Of Lipoatrophy Reveals Relationships Between Beige Fat Appearance And Female Fertility, Elizabeth S Anaya, William Dion, Pradip K Saha, Aaron R Cox, Evelyn De Groot, Avery A Ahmed, Jessica B Felix, Bokai Zhu, Stephanie A Pangas, Sean M Hartig

Faculty, Staff and Students Publications

White adipose tissue (WAT) performs vital metabolic and endocrine functions, but roles in female reproduction remain understudied and poorly understood. Here, we report that female mice experiencing progressive lipoatrophy after knockout of Ubc9 in adipocytes (Ubc9fKO) displayed disrupted estrous cycles, reduced ovarian reserve, and subfertility. During aging, female Ubc9fKO mice lose subcutaneous WAT more quickly than their male counterparts and weigh less than littermate controls. Subcutaneous WAT excised from female Ubc9fKO mice strongly enriched for thermogenesis genes generally associated with metabolic benefits. Female Ubc9fKO mice exhibited hypermetabolism and accumulated thermogenic, Uncoupling Protein 1-expressing beige fat cells in residual subcutaneous WAT …

A Comprehensive Study Of C-Kit-Expressing Amacrine Cells In The Mammalian Retina, Zheng Jiang, Wen Shen

Faculty, Staff and Students Publications

Amacrine cells assemble complex circuits in the inner retina, where they integrate, modulate, and relay spatial and temporal information to retinal ganglion cells. Nevertheless, their organization and functional diversity are still not fully understood. In this study, we identify a distinct group of amacrine cells that express the stem cell factor receptor-c-Kit. Using combined techniques of anti-CD117 (c-Kit) immunolabeling, confocal imaging, and computational algorithms, we characterize the morphological features and spatial distribution of the c-Kit-expressing amacrine cells. Our results show that c-Kit-expressing amacrine cells are GABA-positive neurons with medium to wide dendritic fields that stratify within the specific strata in …

Dinaciclib Improves Treatment Response In Chemoresistant Hepatoblastoma, Brian T Hickner, Andres F Espinoza, Rohit K Srivastava, Roma H Patel, Priyanka Rao, Nicholas A O'Brien, Kalyani R Patel, Andrew A Badachhape, Abhishek Kona, Dolores H López-Terrada, Sarah E Woodfield, Sanjeev A Vasudevan

Faculty, Staff and Students Publications

Chemoresistant hepatoblastoma (HB) is associated with poor outcomes. Cyclin-dependent kinases (CDKs) are potential therapeutic targets because of their critical role in cell growth and chemoresistance. To evaluate the efficacy of CDK inhibition, HB cell lines were treated with dinaciclib and evaluated with cytotoxic, cell-death reversal, and immunoblotting assays. A HB patient-derived xenograft (PDX) model was treated with placebo, vincristine + irinotecan (VI), dinaciclib, or VI + dinaciclib to evaluate tumor growth and response to therapy. We found that dinaciclib had a marked effect on HB cell viability, induced PARP cleavage, and decreased CDK9 protein expression in vitro. Overexpression of CDK9 …

Pitx2 Dosage-Dependent Changes In Pacemaker Cell State Underlie Sinus Node Dysfunction And Atrial Arrhythmias, Lieve E Van Der Maarel, M Ridwane Mungroo, Otto J Mulleners, Mathilde R Rivaud, Arie O Verkerk, Karel Van Duijvenboden, Freek H T Tiel Groenestege, Jeffrey D Steimle, Lianne Fokkert, Corrie De Gier-De Vries, Mischa Klerk, Arie R Boender, James F Martin, Bjarke Jensen, Gerard J J Boink, Harsha D Devalla, Vincent M Christoffels

Faculty, Staff and Students Publications

Physiologically relevant increases in transcription factor dosage and their role in development and disease remain largely unexplored. Genomic deletions upstream of the Paired-like homeodomain transcription factor gene (PITX2), identified in patients with sinus node dysfunction and atrial fibrillation and modeled in mice (delB), rewire the local epigenetic landscape, increasing PITX2 expression. Here, we demonstrate that pacemaker cardiomyocytes in the embryonic delB sinus node ectopically express PITX2 at physiological dosages in a heterogeneous pattern. The prenatal delB sinus node forms discrete subdomains showing PITX2 dosage-dependent mild or severe loss of pacemaker cardiomyocyte identity. Respective subdomain sizes and severity of sinus node …

Functional Vs Anatomical Cortico-Striatal Connectivity In The Macaque Brain, Wei Tang, Megan E Monko, Zoe Liu, Ana M G Manea, Fernando A Ortega, Damyan Hart, Jason Zhou, Jan Zimmermann, Sarah R Heilbronner

Faculty, Staff and Students Publications

The cerebral cortex provides the main input to the striatum, constituting the first step in cortico-basal ganglia loops. Decades of careful anatomical tract-tracing research have established the exquisite topography of each cortical region's projection to the striatum in nonhuman primates. In parallel, neuroimaging research has demonstrated the relationship between cortico-striatal resting-state functional connectivity and specific cognitive, behavioral, psychiatric, and neurological states in humans. However, still unclear is the extent to which functional connectivity recapitulates the specific topographies of cortico-striatal anatomical connectivity. Here, we combined datasets of cortico-striatal anatomical and functional connectivity in macaques to determine the degree of overlap between …

Super-Fast, Super-Early: High-Frequency Oscillations May Be A Prelude To Alzheimer's Dementia In Down Syndrome, Manuel Silva-Pérez, Jeannie Chin

Faculty, Staff and Students Publications

Alzheimer's disease (AD) dementia has near full penetrance in adults with Down syndrome (DS) and is strongly linked to late-onset myoclonic epilepsy in Down syndrome (LOMEDS). However, promising biomarkers of epileptogenicity, such as high-frequency oscillations (HFOs >250 Hz), have not been studied. This study is the first to use wideband polysomnography in DS to investigate if HFOs occurred and preceded AD dementia and LOMEDS. Methods: Wideband (0.1 to 500 Hz, 2048 Hz) polysomnography was performed using the international 10–20 system. HFOs were automatically detected during slow-wave sleep, followed by manual review. Results: Fourteen individuals with DS and five age-matched euploid …

Revealing The Nervous System Requirements Of Alzheimer Disease Risk Genes In Drosophila, Jennifer M Deger, Shabab B Hannan, Mingxue Gu, Colleen E Strohlein, Lindsey D Goodman, Sasidhar Pasupuleti, Zahid Shaik, Liwen Ma, Yarong Li, Jiayang Li, Morgan C Stephens, Michal Tyrlík, Zhandong Liu, Ismael Al-Ramahi, Juan Botas, Chad A Shaw, Oguz Kanca, Hugo J Bellen, Joshua M Shulman

Faculty, Staff and Students Publications

Most Alzheimer disease (AD) susceptibility genes have poorly understood roles in the central nervous system (CNS). To address this gap, we systematically characterized 100 conserved candidate AD risk genes using a cross-species strategy in the fruit fly, Drosophila melanogaster. Genes were prioritized based primarily on human functional genomic evidence. We generated custom loss-of-function alleles for each of the conserved fly orthologs. Most of the genes are expressed in the adult brain, including 24 neuron- and 13 glia-specific expression patterns. Overall, we identify 50 candidate AD risk gene homologs with requirements for CNS structure or function, including 18 whose loss of …

Unconventional Binding Of Calmodulin To Chk2 Kinase Inhibits Catalytic Activity, Christopher R Horne, Tingting Wang, Samuel N Young, Toby A Dite, Hunter G Nyvall, Sushant Suresh, Katherine A Davies, Abner Gonzalez Castro, Vineet Vaibhav, Lucy J Mather, Laura F Dagley, Matthew J Belousoff, Gerard Manning, Anthony R Means, John E Burke, Janni Petersen, John W Scott, James M Murphy

Faculty, Staff and Students Publications

Calmodulin (CaM) serves an essential role in eukaryotic cells as a Ca2+ sensor. Ca2+ binding leads to conformation changes in CaM that enable engagement of a repertoire of enzymes and the regulation of their catalytic activities. Classically, Ca2+-CaM binds to an inhibitory pseudosubstrate sequence C-terminal to the kinase domain in members of the Ca2+-CaM-dependent protein kinase (CAMK) family and relieves inhibition to promote catalytic activity. Here, we report an unexpected mechanism by which CaM can bind CHK2 kinase to inhibit its kinase activity. Using biochemical, biophysical and structural mass spectrometry, we identify a direct interaction of Ca2+-CaM with the CHK2 …

A Distinct Pp2a Subunit Regulates Local Protein Phosphorylation At The Axon Initial Segment, Andrew P Anderson, Sanghyun Kim, Allison J Melton, Xiaoyun Ding, Wei Zhang, Alexander B Saltzman, Anna Malovannaya, Matthew N Rasband, Yudong Gao

Faculty, Staff and Students Publications

Protein phosphorylation plays a crucial role in regulating the cytoskeletal and membrane proteins at the axon initial segment (AIS). However, our knowledge of AIS-specific kinases and phosphatases is very limited. Here, we report the identification of a protein phosphatase 2A (PP2A) B55 regulatory subunit enriched at the AIS in mice: Ppp2r2c. Our results demonstrate that PP2A-B55 subunits exhibit substantial heterogeneity in their subcellular localization and function. Notably, the Ppp2r2c subunit is selectively concentrated at the AIS, and this enrichment is driven by its unique structure. Utilizing a microelectrode array system (MEA), we show that Ppp2r2c modulates neuronal activity during in …

Investigating Dysfunctional Cognition Change As A Putative Mechanism Of Cbt For Youth Anxiety, Ocd And Ptsd: Protocol For An Individual Participant Data Meta-Analysis, Ivana Buric, Anke Klein, Ronald M Rapee, Brooke Levis, Philip C Kendall, Eric A Storch, Lynn Mobach

Faculty, Staff and Students Publications

Introduction: Anxiety disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are common in children and adolescents and can lead to significant impairment. Cognitive behavioural therapy (CBT) with exposure is the first-line treatment, yet approximately half of treated youth do not achieve full remission. Dysfunctional cognitions-negative automatic thoughts, maladaptive beliefs and distorted interpretations-are considered key targets of CBT, but evidence in youth is mixed and underpowered. This study will examine whether change in dysfunctional cognitions mediates treatment outcome in anxiety, OCD and PTSD symptoms and whether this association varies across individual characteristics.

Methods and analysis: An individual participant data meta-analysis …

Restoration Of Sfrp3 Preserves The Neural Stem Cell Pool And Spatial Discrimination Ability In A Mouse Model Of Alzheimer's Disease, Chia-Hsuan Fu, Jin Park, Umberto Tosi, Francisco A Blanco, Manuel Silva-Pérez, Kavitha Muralidharan, Jason C You, Minjung Lee, Gabriel S Stephens, Xiaohong Zhang, Yi Zheng, Helen Scharfman, Kimberley F Tolias, Jeannie Chin

Faculty, Staff and Students Publications

Individuals with Alzheimer's disease (AD) have an increased incidence of seizures, which worsen cognitive decline. Using a transgenic mouse model of AD neuropathology that exhibits spontaneous seizures, we previously found that seizure activity stimulates and accelerates depletion of the hippocampal neural stem cell (NSC) pool, which was associated with deficits in neurogenesis-dependent spatial discrimination. However, the precise molecular mechanisms that drive seizure-induced activation and depletion of NSCs are unclear. Here, using mice of both sexes, we performed RNA-sequencing on the hippocampal dentate gyrus and identified differentially expressed regulators of neurogenesis in the Wnt signaling pathway that regulates many aspects of …

Optimizing Perioperative Antibiotic Prophylaxis: A Prospective Cohort Study On Cefazolin Utilization In Surgical Patients With Penicillin Allergy Labels, Cassius Mensah, Anvinh Nguyen, Jenny Pennycuff, Israa Shwaiki, Belle Parizot, Gary Zhang, Xiaofan Huang, Suman Rajagopalan

Faculty, Staff and Students Publications

Background: Penicillin allergy labels frequently lead to second-line antibiotics for surgical prophylaxis, due to concerns for cross-reactivity. This has led to increased patient morbidity, prolonged hospitalization, and increased healthcare costs. The most common perioperative cephalosporin, cefazolin, has unique R groups, the main antigenic portion of penicillin, which makes it safe to use in type 1 hypersensitivity penicillin allergy. We evaluated the effect of education on the incidence of the following: cefazolin usage in penicillin allergy labelled patients, allergic reactions, and surgical site infections.

Methods: As a prospective study with historical controls, perioperative clinicians were educated on the natural history of …

Targeting Tet3 Suppresses Group 3 Medulloblastoma Stemness And Progression Via Impairing Hypomethylation Of Otx2 Super-Enhancer, Xuan Chen, Ziwei Wang, Yan Song, Yu Su, Yahui Zhao, Jiankang Li, Wei Wang, Jiao Zhang, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Yanan Wang, Fei Liu, Kaiwen Deng, Dongming Han, Zijia Liu, Meiyu Li, Liam D Hendrikse, Alexandra Rasnitsyn, Evan Y Wang, Dongyang Wang, Zhaoyang Feng, Yanong Li, Zitong Zhao, Hongyu Yuan, Youliang Sun, Yifei Jiang, Yanfeng Shi, Tao Yang, Xueling Qi, Yong Hou, Chunde Li, Yong-Qiang Liu, Yu Tian, Shuaicheng Li, Xiaoguang Qiu, Michael D Taylor, Guo Liang Li, Tao Jiang, Hailong Liu

Faculty, Staff and Students Publications

Medulloblastoma (MB), particularly Group_3 (G3-MB), remains the most aggressive subgroup due to strong stemness and therapeutic resistance. Through genome-wide DNA methylation and transcriptomic analysis of human MB samples, we identify enhancer hypomethylation as a key feature sustaining G3-MB stemness and tumor progression. Notably, hypomethylation of the Otx2 super-enhancer (SE) is a prognostic marker and potential therapeutic target for G3-MB patients. We demonstrate that disrupting Otx2 SE activity effectively reduces tumor growth in vivo, highlighting its critical role in G3-MB maintenance. TET3, recruited by OTX2, demethylates the Otx2 SE, promoting chromatin opening and sustaining tumor proliferation and stemness. To translate these …

Factors Associated With Child Protective Services Referrals In Young Children With Isolated Skull Fractures, Karli Breeden-Carino, Joanne N Wood, Cindy W Christian, Tagrid M Ruiz-Maldonado, Daniel M Lindberg, Angela Bachim, Lori Frasier, Terra N Frazier, Nancy S Harper, Sara E Kruczek, Farah Brink, Jennifer E Wolford, Jan Leonard, M Katherine Henry

Faculty, Staff and Students Publications

Objective: Many young children with isolated skull fractures are referred to child protective services (CPS) despite being assessed to have a low likelihood of abuse. We sought to identify factors associated with CPS referrals in this population and to quantify hospital-level variation.

Methods: We performed a multicenter retrospective cross-sectional study of children < 2 years with skull fractures with or without a small underlying intracranial hemorrhage (ICH) and no additional injuries undergoing a child abuse pediatrics (CAP) subspecialty evaluation. We explored associations between demographic factors, clinical characteristics, psychosocial risk factors, and hospital site with CPS referral status. We performed multivariable logistic regression, adjusting for transfer status and all significant covariates from unadjusted analyses. We utilized marginal standardization to calculate the estimated probability of CPS referrals at each site, adjusting for all factors in the final model.

Results: Of 528 children, 303 (57.4%) were referred to CPS, with 86.5% referred prior to CAP consultation. In multivariable logistic regression, presence of psychosocial risk factors (OR 4.00; 95% CI 2.25, 7.11), in-person CAP consult (OR 3.93; 1.61, 9.62), inflicted or no trauma history provided (OR 6.15; 3.30, …

Resilience And Childhood Trauma In Mood Disorders: Psychopathological Implications And Treatment Response, Giovanni Camardese, Antonio Maria D'Onofrio, Francesca Bardi, Alessio Simonetti, Alexia Koukopoulos, Delfina Janiri, Lorenzo Moccia, Marianna Mazza, Mauro Pettorruso, Giovanni Martinotti, Gabriele Sani

Faculty, Staff and Students Publications

Background and aim: Childhood trauma is a key risk factor for mood disorders and is associated with greater clinical severity, while resilience may act as a protective factor. This study investigates how childhood trauma and resilience interact to shape psychopathology and treatment response in patients with major depressive disorder (MDD) and bipolar disorder (BD).

Methods: The study included 669 participants: 569 patients (380 MDD, 189 BD) and 100 healthy controls (HC). Symptom severity was assessed using standardized scales, with follow-up evaluations of depressive symptoms at six months. All participants completed the Childhood Trauma Questionnaire (CTQ) and Connor-Davidson Resilience Scale (CD-RISC). …

Fibroblasts Are The Primary Contributors To A Disrupted Micro-Environment In End-Stage Pediatric Hypertrophic Cardiomyopathy, Hanna J Tadros, Diwakar Turaga, Yi Zhao, Chang-Ru Tsai, Iki A Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Background: Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in the pediatric population, and patients with end-stage HCM require heart transplantation. Here, we have examined the transcriptome in ventricular tissue from this patient group to identify cell states and underlying cellular processes unique to pediatric HCM.

Methods: We performed single-nucleus RNA sequencing (snRNA-seq) on explanted hearts at transplant in 3 pediatric patients with end-stage HCM and compared findings to pediatric control and adult HCM.

Results: We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells compared with controls. Pediatric HCM was enriched in cardiomyocytes …

Real-World Adherence And Effectiveness Of Inclisiran In Lowering Ldl-C: Results From 1 Year Of Follow-Up, Christie M Ballantyne, Timothy E Graham, Lucinda J Van Anglen, Bruce J Iteld, Harvey Serota, Xiaoli Niu, Sean Mcelligott, Kelly E Hanna, Tyler J Varisco

Faculty, Staff and Students Publications

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is a global health concern. Reducing low-density lipoprotein cholesterol (LDL-C) is critical in ASCVD prevention and treatment. Inclisiran, a novel RNA therapeutic agent, offers a promising solution by lowering LDL-C with twice-yearly dosing after an initial and 3-month dose. The study objective was to evaluate adherence to inclisiran and its lipid-lowering effectiveness over a year of treatment.

Methods: This retrospective cohort study involved patients over 18 years old with ASCVD or hyperlipidemia who initiated inclisiran between January 1, 2022, and May 17, 2023, in US outpatient clinics. LDL-C reduction was evaluated in patients with ≥ …

A Deep Generative Model For Deciphering Cellular Dynamics And In Silico Drug Discovery In Complex Diseases, Yumin Zheng, Jonas C Schupp, Taylor Adams, Geremy Clair, Aurelien Justet, Farida Ahangari, Xiting Yan, Paul Hansen, Marianne Carlon, Emanuela Cortesi, Marie Vermant, Robin Vos, Laurens J De Sadeleer, Ivan O Rosas, Ricardo Pineda, John Sembrat, Melanie Königshoff, John E Mcdonough, Bart M Vanaudenaerde, Wim A Wuyts, Naftali Kaminski, Jun Ding

Faculty, Staff and Students Publications

Human diseases are characterized by intricate cellular dynamics. Single-cell transcriptomics provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in silico drug interventions. Here we introduce UNAGI, a deep generative neural network tailored to analyse time-series single-cell transcriptomic data. This tool captures the complex cellular dynamics underlying disease progression, enhancing drug perturbation modelling and screening. When applied to a dataset from patients with idiopathic pulmonary fibrosis, UNAGI learns disease-informed cell embeddings that sharpen our understanding of disease progression, leading to the identification of potential therapeutic drug candidates. Validation using proteomics reveals …

Unmasking Hidden Clues In Cutaneous Viral Infections: Histopathological Insights Into Keratinocytic Features Of Herpes Simplex Virus, Varicella Zoster Virus, And Molluscum Contagiosum, Tania Platero Portillo, Dilshad Dhaliwal, Sepideh Mehravaran, Megan Ketcham, Julie Wu, Nisha Ramani, Abdul Hafeez Diwan

Faculty, Staff and Students Publications

Objective: This case study aimed to explore primarily the keratinocytic changes of cutaneous viral infections caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and molluscum contagiosum (MC). The focus was on identifying features and diagnostic clues in cases without typical findings.

Methods: A retrospective analysis encompassing 14 HSV/VZV cases (January 2000 to October 2023) and 22 MC cases (January 2013 to December 2015) was conducted.

Results: In HSV/VZV cases, 71% (10 of 14) exhibited distinctive histopathological features in the adjacent keratinocytes, including nucleolar enlargement and atypical features. Immunohistochemical studies in 40% of the cases (4 of 10) revealed positive …

Difficult Conversation Case: Death Notification, Charles Lei, Tiffany Moadel, Suzanne Bentley, Amrita Vempati, David Fernandez, Daniela Ortiz, Anita Rohra, Stephanie Stapleton, Hillary Moss

Faculty, Staff and Students Publications

Audience: This case is meant for senior emergency medicine (EM) resident physicians as a preparatory tool for the American Board of Emergency Medicine Certifying Exam. However, it is applicable for EM residents at all levels of training.

Introduction: Difficult conversations are an integral part of the practice of emergency medicine. Competent EM physicians routinely engage in challenging conversations with patients and their families (eg, delivering bad news, disclosing medical errors, providing death notifications).1 Despite their importance, communication skills are often not formally taught in residency training.2 Instead, learners frequently rely on role modeling to develop the skills necessary to navigate …

Rbm8a Deficiency Causes Hematopoietic Defects By Modulating Wnt/Pcp Signaling, Agnese Kocere, Elena Chiavacci, Charlotte Soneson, Seth T Jacobson, Emma N Harrison, Kevin Manuel Méndez-Acevedo, Jacalyn S Macgowan, Harrison H Wells, Max S Hiltabidle, Azhwar Raghunath, Jordan A Shavit, Daniela Panáková, Margot L K Williams, Mark D Robinson, Christian Mosimann, Alexa Burger

Faculty, Staff and Students Publications

Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in RBM8A/Y14, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown. Here, we connect zebrafish rbm8a perturbation to early hematopoietic defects via attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling. In hypomorphic rbm8a zebrafish, we observe a reduction of cd41-positive thrombocytes. rbm8a-mutant zebrafish accumulate mRNAs with retained introns, including non-canonical Wnt/PCP pathway components resulting in convergent extension defects. We found that reduced rbm8a …

Plasma Metabolomic And Proteomic Signatures Of Blood Pressure Management After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Juan Pablo Lewinger, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Carmen Chen, Todd M Jenkins, Stephanie Sisley, Stephen R Daniels, Douglas I Walker, Max T Aung, Erika Garcia, Rob Mcconnell, Sandrah P Eckel, Michele A La Merrill, Tanya L Alderete, Zhuanghua Chen, Frank D Gilliland, Thomas H Inge, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Background: Emerging omics approaches, including metabolomics and proteomics, can be integrated into obesity treatment for better blood pressure management. We tested whether preoperative metabolomic and proteomic profiles predict long-term elevated blood pressure (EBP) changes better than known risk factors in adolescents undergoing bariatric surgery.

Methods: We included 108 participants from the Teen-LABS (Teen-Longitudinal Assessment of Bariatric Surgery). Plasma untargeted metabolomics (via liquid chromatography with high-resolution mass spectrometry) and Olink proteomics were assessed pre surgery. An elastic net model with stability selection was used to identify features predictive of EBP reductions 5 years post surgery. Models including identified metabolites, proteins, and …

Gender Matters: A State-Of-The-Art Review Of Transcatheter Structural Interventions In Older Women Vs Men, Jing Liu, Radmila Lyubarova, Jennifer Riggs, Jina Chung, Puja Kiran Mehta, Simrat Kaur, Abdulla Al Damluji, Vasilis Babaliaros, Leslie Cho

Faculty, Staff and Students Publications

With rising life expectancy, the population of older adults over the age of 65 is rapidly expanding, with women comprising the majority. Structural heart disease is common in this group, and transcatheter interventions have transformed its management. Optimal outcomes require careful consideration of sex-specific differences. This review examines transcatheter structural heart interventions in older adults with a focus on sex-based outcomes, procedural planning, and current knowledge gaps.

Racial And Ethnic Disparities In Pediatric Autoimmune Encephalitis: A Systematic Review, Jennifer H Yang, Kristen S Fisher, Julia Dumcum, Sophie Zacharek, Alexandra B Kornbluh, Kelsey Poisson, Mary C Karalius, Leigh Sepeta

Faculty, Staff and Students Publications

Objectives: Health disparities and social determinants of health are increasingly recognized as important predictors for clinical outcomes in autoimmune disease. However, this is poorly studied in pediatric autoimmune encephalitis (AE).

Methods: We conducted a systematic literature review in accordance with PRISMA guidelines. Searches included Medline (Pubmed), EMBASE, and Web of Science databases from inception years to October 4, 2024. Inclusion criteria were: 1) Patients diagnosed with AE ≤ 18 years old; 2) any report of race and/or ethnicity, 3) report of specific diagnostics and disease outcomes, 4) observational cohort studies, epidemiological studies or case series/ cohort studies of n ≥ …

Corrigendum To “Clinical Characteristics And Longitudinal Associations With Obsessive-Compulsive Disorder In Youth Exposed To Trauma” [J Mood Anxiety Disord 10c (2025) 100117], Caitlin M Pinciotti, Paul J Rathouz, Andrew G Guzick, Jeffrey D Shahidullah, Emily J Bivins, David B Riddle, Ogechi Cynthia Onyeka, Eric A Storch, Wayne K Goodman, Kelli Franco, Justin F Rousseau, D Jeffrey Newport, Karen Dineen Wagner, Charles B Nemeroff

Faculty, Staff and Students Publications

This corrects the article "Clinical characteristics and longitudinal associations with obsessive-compulsive disorder in youth exposed to trauma" in volume 10, 100117.

Vaccine Hesitancy At Nine Community Sites Across The United States, Early In Covid-19 Vaccine Rollout, Aneeka Ratnayake, Julie H Hernandez, Jessica Justman, Jason E Farley, Yael Hirsch-Moverman, Ken Ho, Stockton Mayer, Abiodun Oluyomi, Magdalena E Sobieszczyk, Shobha Swaminathan, Timothy Skalland, Jean De Dieu Tapsoba, Patricia J Kissinger

Faculty, Staff and Students Publications

Background: Vaccine hesitancy has been a significant concern throughout the COVID-19 pandemic. Vaccine hesitancy can be attributed to lack of confidence in vaccines, complacency about the health threat, or lack of convenience of vaccination. To date, few studies have used methods designed to include populations underrepresented in research when identifying factors associated with vaccine hesitancy.

Methods: Between January and July 2021, potential participants were recruited from community venues selected through time-location sampling in 15 defined communities in the United States. Study staff administered a questionnaire on demographics, COVID-19 behaviors and attitudes, and vaccination status or intention to consenting individuals. Vaccine …

Biochemical And Clinical Response To A Sulfur-Restricted Diet In Ethylmalonic Encephalopathy, Steven H Lang, Andres Caceres Salgado, Matthew T Snyder, Brandy Rawls-Castillo, Aaron Williams, Charul Gijavanekar, Sarah H Elsea, Xia Wang, Mary Elizabeth M Tessier, Claudia Soler-Alfonso, Fernando Scaglia

Faculty, Staff and Students Publications

Introduction: Ethylmalonic encephalopathy (EE) is an often-severe inborn error of metabolism caused by biallelic variants in the ETHE1 gene leading to impaired detoxification of hydrogen sulfide (H2S). H2S is produced both exogenously by anerobic intestinal bacteria as well as by the endogenous catabolism of the sulfur-containing amino acids methionine and cysteine. Existing therapies including metronidazole, N-acetylcysteine (NAC), and orthotopic liver transplantation (OLT) have been pursued with the objective of reducing or detoxifying exogenously produced H2S. However, strategies to reduce endogenously produced H2S using a methionine and cysteine restricted diet are an understudied therapeutic avenue.

Methods: We performed an open-label, …

Implications Of Cooccurring Adhd For The Cognitive Behavioural Treatment Of Anxiety In Autistic Children, Elise Ng-Cordell, Eric A Storch, Philip C Kendall, Jeffrey J Wood, Amori Yee Mikami, Connor M Kerns

Faculty, Staff and Students Publications

Background: Childhood mental health conditions commonly cooccur, with potential treatment implications. Autistic children frequently experience anxiety and attention deficit/hyperactivity disorder (ADHD). We investigated the implications of this cooccurrence for Cognitive Behavioural Therapy (CBT), a front-line treatment for anxiety in autistic children. We tested whether (1) ADHD predicts anxiety treatment response, (2) ADHD improves in response to anxiety treatment and (3) ADHD improvement is related to reductions in anxiety.

Method: Autistic children with elevated anxiety (N = 167) enrolled in a multisite, randomised controlled trial comparing standard CBT, autism-adapted CBT and treatment as usual. ADHD symptoms and severity were assessed via …

Functional Head Tremor: Contrasting Features With Other Tremor Etiologies, José Fidel Baizabal-Carvallo, Joseph Jankovic

Faculty, Staff and Students Publications

Background: Functional tremor (FT) is considered the most common phenomenology among patients with functional movement disorders (FMDs). Most patients have limb tremor, but they can also present with tremor involving the head and trunk.

Objectives and methods: We aimed to assess the clinical phenomenology of functional head tremor (FHT) and contrast it with features of HT observed in 125 patients with other tremor etiologies (OTE), including 71 patients with essential tremor (ET).

Results: There were 101 consecutive patients (68.3% females) with FT from which n = 36 (35.6%) had FHT. Yes-yes tremor was the most common directionality (47.2%). Functional trunk …

A Multimodal Non-Invasive Approach For Intracranial Pressure Assessment: A Single-Center Study, Dana Klavansky, Helaina Lehrer, Aris Desai, Gabriela Keeton, Neha Dangayach, Alexandra Reynolds, Spyridoula Tsetsou

Faculty, Staff and Students Publications

Background: Intracranial pressure (ICP) monitoring is an integral part of acute brain injury management. While invasive ICP monitoring is the gold standard, there are several medical conditions that preclude its placement. The aim of the present study is to validate a multimodal approach for increasing ICP detection.

Material and methods: In this retrospective study, patients with acute brain injury who had an external ventricular drain (EVD) placement were included. We measured bilateral optic nerve sheath diameter (ONSD) and assessed for optic nerve disk elevation (ONDE) by using ocular ultrasound, bilateral middle cerebral artery pulsatility index (PI) by using transcranial Doppler, …