Digital Commons Network^™

Nf1 Mutation Disrupts Activity-Dependent Oligodendroglial Plasticity And Motor Learning In Mice, Yuan Pan, Jared D Hysinger, Belgin Yalçın, James J Lennon, Youkyeong Gloria Byun, Preethi Raghavan, Nicole F Schindler, Corina Anastasaki, Jit Chatterjee, Lijun Ni, Haojun Xu, Karen Malacon, Samin M Jahan, Alexis E Ivec, Benjamin E Aghoghovwia, Christopher W Mount, Surya Nagaraja, Suzanne Scheaffer, Laura D Attardi, David H Gutmann, Michelle Monje

Faculty, Staff and Student Publications

Neurogenetic disorders, such as neurofibromatosis type 1 (NF1), can cause cognitive and motor impairments, traditionally attributed to intrinsic neuronal defects such as disruption of synaptic function. Activity-regulated oligodendroglial plasticity also contributes to cognitive and motor functions by tuning neural circuit dynamics. However, the relevance of oligodendroglial plasticity to neurological dysfunction in NF1 is unclear. Here we explore the contribution of oligodendrocyte progenitor cells (OPCs) to pathological features of the NF1 syndrome in mice. Both male and female littermates (4-24 weeks of age) were used equally in this study. We demonstrate that mice with global or OPC-specific Nf1 heterozygosity exhibit defects …

High-Dose Intravenous Vitamin C Combined With Docetaxel In Men With Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase Ii Trial, Channing Paller, Marianna Zahurak, Adel Mandl, Nicole Metri, Aliya Lalji, Elisabeth Heath, William Kelly, Christopher Hoimes, Pedro Barata, Jason Taksey, Dominique Garrison, Kartick Patra, Ginger Milne, Nicole Anders, Julie Nauroth, Jennifer Durham, Catherine Marshall, Mark Markowski, Mario Eisenberger, Emmanuel Antonarakis, Michael Carducci, Samuel Denmeade, Mark Levine

Department of Medicine Faculty Papers

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate …

Structure Of Adenylyl Cyclase 5 In Complex With Gβγ Offers Insights Into Adcy5-Related Dyskinesia, Yu-Chen Yen, Yong Li, Chun-Liang Chen, Thomas Klose, Val J Watts, Carmen W Dessauer, John J G Tesmer

Faculty, Staff and Student Publications

The nine different membrane-anchored adenylyl cyclase isoforms (AC1-9) in mammals are stimulated by the heterotrimeric G protein, Gαs, but their response to Gβγ regulation is isoform specific. In the present study, we report cryo-electron microscope structures of ligand-free AC5 in complex with Gβγ and a dimeric form of AC5 that could be involved in its regulation. Gβγ binds to a coiled-coil domain that links the AC transmembrane region to its catalytic core as well as to a region (C1b) that is known to be a hub for isoform-specific regulation. We confirmed the Gβγ interaction with both purified proteins and cell-based …

Increased Risk Of Cutaneous T-Cell Lymphoma Development After Dupilumab Use For Atopic Dermatitis, Jenna Mandel, Jaanvi Mehta, Ramsay Hafer, Mahaa Ayub, Faria Nusrat, Henry Yang, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

There have been several reports of dupilumab use and the development of CTCL; however, the risk of CTCL development has not been adequately evaluated at the population level. The objective of this study is to determine whether dupilumab administration for AD is associated with an increased risk of developing CTCL and to identify at-risk populations within this group. This retrospective cohort study used TriNetX, a deidentified medical record database including over 107 million patients, to identify eligible patients. Treatment and control groups were evaluated for the development of CTCL. Patients of any age with a documented diagnosis of AD were …

High Prevalence Of Artifacts In Optical Coherence Tomography With Adequate Signal Strength, Wei-Chun Lin, Aaron Coyner, Charles Amankwa, Abigail Lucero, Gadi Wollstein, Joel Schuman, Hiroshi Ishikawa

Wills Eye Hospital Papers

PURPOSE: This study aims to investigate the prevalence of artifacts in optical coherence tomography (OCT) images with acceptable signal strength and evaluate the performance of supervised deep learning models in improving OCT image quality assessment.

METHODS: We conducted a retrospective study on 4555 OCT images from 546 patients, with each image having an acceptable signal strength (≥6). A comprehensive analysis of prevalent OCT artifacts was performed, and five pretrained convolutional neural network models were trained and tested to infer images based on quality.

RESULTS: Our results showed a high prevalence of artifacts in OCT images with acceptable signal strength. Approximately …

"The Hotel Of 10,000 Stars": The Impact Of Social-Structural Determinants Of Health Among Im/Migrant Shrimpers In The Gulf Of Mexico, Shannon Guillot-Wright, Lacy Davis, Linh Truong, Heide Castañeda, Anabel Rodriguez

Faculty, Staff and Student Publications

Objectives. To identify appropriate interventions to prevent injury, we conducted a qualitative study among commercial shrimp fishermen in the Gulf of Mexico.

Methods. Using qualitative and participatory research methods, including interviews, photovoice, and workplace observations in southeast Texas and the Rio Grande Valley in Texas, we examined the social‒structural dimensions that contribute to physical and psychological injury.

Results. We found that multiple layers of vulnerability and danger exist among shrimpers with interacting themes: (1) recognizing risk, (2) precarious employment, and (3) psychological distress.

Conclusions. Our results add to the growing body of knowledge that emphasizes the negative health impacts of …

Molecular Pathways And Cellular Subsets Associated With Adverse Clinical Outcomes In Overlapping Immune-Related Myocarditis And Myositis, Bilal A Siddiqui, Nicolas L Palaskas, Sreyashi Basu, Yibo Dai, Zhong He, Shalini S Yadav, James P Allison, Rahul A Sheth, Sudhakar Tummala, Maximilian Buja, Meenakshi B Bhattacharjee, Cezar Iliescu, Anishia Rawther-Karedath, Anita Deswal, Linghua Wang, Padmanee Sharma, Sumit K Subudhi

Faculty, Staff and Student Publications

Immune checkpoint therapies (ICT) can induce life-threatening immune-related adverse events, including myocarditis and myositis, which are rare but often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood. To address this need, we performed single-cell RNA sequencing of heart and skeletal muscle biopsies obtained from living patients with cancers treated with ICTs and admitted to the hospital with myocarditis and/or myositis (overlapping myocarditis plus myositis, n = 10; myocarditis-only, n = 1) or ICT-exposed patients ruled out for toxicity utilized as controls (n = 9). All biopsies were obtained within 96 hours of clinical presentation. Analyses …

Can Anorectal Stenosis Be Managed With Dilations Alone? A Pcplc Review., Zoe M. Saenz, Kelly Austin, Jeffrey R. Avansino, Andrea Badillo, Casey M. Calkins, Megan M. Durham, Megan K. Fuller, Ankur Rana, Ron W. Reeder, Rebecca M. Rentea, Michael D. Rollins, K Elizabeth Speck, Richard J. Wood, Jamie C. Harris, Jamie Anderson, Maheen Hassan, Payam Saadai, Pediatric Colorectal And Pelvic Learning Consortium (Pcplc)

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Congenital anorectal stenosis is managed by dilations or operative repair. Recent studies now propose use of dilations as the primary treatment modality to potentially defer or eliminate the need for surgical repair. We aim to characterize the management and outcomes of these patients via a multi-institutional review using the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) registry.

METHODS: A retrospective database review was performed using the PCPLC registry. The patients were evaluated for demographics, co-morbidities, diagnostic work-up, surgical intervention, current bowel management, and complications.

RESULTS: 64 patients with anal or rectal stenosis were identified (57 anal, 7 rectal) from …

Hue And Orientation Pinwheels In Macaque Area V4, Arun Parajuli, Daniel J Felleman

Faculty, Staff and Student Publications

Area V4 is an intermediate-level area of the macaque visual cortical hierarchy that serves key functions in visual processing by integrating inputs from lower areas such as V1 and V2 and providing feedforward inputs to many higher cortical areas. Previous V4 imaging studies have focused on differential responses to color, orientation, disparity, and motion stimuli, but many details of the spatial organization of significant hue and orientation tuning have not been fully described. We used support vector machine (SVM) decoding of intrinsic cortical single-condition responses to generate high-resolution maps of hue and orientation tuning and to describe the organization of …

4d Dynamic Spatial Brain Networks At Rest Linked To Cognition Show Atypical Variability And Coupling In Schizophrenia, Krishna Pusuluri, Zening Fu, Robyn Miller, Godfrey Pearlson, Peter Kochunov, Theo G M Van Erp, Armin Iraji, Vince D Calhoun

Faculty, Staff and Student Publications

Despite increasing interest in the dynamics of functional brain networks, most studies focus on the changing relationships over time between spatially static networks or regions. Here we propose an approach to study dynamic spatial brain networks in human resting state functional magnetic resonance imaging (rsfMRI) data and evaluate the temporal changes in the volumes of these 4D networks. Our results show significant volumetric coupling (i.e., synchronized shrinkage and growth) between networks during the scan, that we refer to as dynamic spatial network connectivity (dSNC). We find that several features of such dynamic spatial brain networks are associated with cognition, with …

Myeloablation Followed By Hematopoietic Stem Cell Transplantation And Long-Term Normalization Of Systemic Sclerosis Molecular Signatures, Nancy Wareing, Xuan Wang, Lynette Keyes-Elstein, Ellen A Goldmuntz, Marka A Lyons, Peter Mcsweeney, Daniel E Furst, Richard A Nash, Leslie J Crofford, Beverly Welch, Ashley Pinckney, Maureen D Mayes, Keith M Sullivan, Shervin Assassi

Faculty, Staff and Student Publications

Objective: In the randomized Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial, myeloablation, followed by hematopoietic stem cell transplantation (HSCT), led to the normalization of systemic sclerosis (SSc) peripheral blood cell (PBC) gene expression signature at the 26-month visit. Herein, we examined long-term molecular changes ensuing 54 months after randomization for individuals receiving an HSCT or 12 months of intravenous cyclophosphamide (CYC).

Methods: Global PBC transcript studies were performed in study participants at pretreatment baseline and at 38 months and 54 months after randomization, as well as in healthy controls using Illumina HT-12 arrays.

Results: Thirty (HSCT = 19 and CYC = …

A 3d Dual-Echo Spiral Sequence For Simultaneous Dynamic Susceptibility Contrast And Dynamic Contrast-Enhanced Mri With Single Bolus Injection, Zhiqiang Li, Dinghui Wang, Melvyn B Ooi, Poonam Choudhary, Sudarshan Ragunathan, John P Karis, James G Pipe, C Chad Quarles, Ashley M Stokes

Faculty, Staff and Student Publications

Purpose: Perfusion MRI reveals important tumor physiological and pathophysiologic information, making it a critical component in managing brain tumor patients. This study aimed to develop a dual-echo 3D spiral technique with a single-bolus scheme to simultaneously acquire both dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) data and overcome the limitations of current EPI-based techniques.

Methods: A 3D spiral-based technique with dual-echo acquisition was implemented and optimized on a 3T MRI scanner with a spiral staircase trajectory and through-plane SENSE acceleration for improved speed and image quality, in-plane variable-density undersampling combined with a sliding-window acquisition and reconstruction approach for increased …

Deletion Of Mipep In Adipocytes Protects Against Obesity And Insulin Resistance By Boosting Muscle Metabolism, Alexis Diaz-Vegas, Kristen C Cooke, Harry B Cutler, Belinda Yau, Stewart W C Masson, Dylan Harney, Oliver K Fuller, Meg Potter, Søren Madsen, Niamh R Craw, Yiju Zhang, Cesar L Moreno, Melkam A Kebede, G Gregory Neely, Jacqueline Stöckli, James G Burchfield, David E James

Faculty, Staff and Students Publications

Mitochondria facilitate thousands of biochemical reactions, covering a broad spectrum of anabolic and catabolic processes. Here we demonstrate that the adipocyte mitochondrial proteome is markedly altered across multiple models of insulin resistance and reveal a consistent decrease in the level of the mitochondrial processing peptidase miPEP.

OBJECTIVE: To determine the role of miPEP in insulin resistance.

METHODS: To experimentally test this observation, we generated adipocyte-specific miPEP knockout mice to interrogate its role in the aetiology of insulin resistance.

RESULTS: We observed a strong phenotype characterised by enhanced insulin sensitivity and reduced adiposity, despite normal food intake and physical activity. Strikingly, …

De Novo Variants In The Rnu4-2 Snrna Cause A Frequent Neurodevelopmental Syndrome, Yuyang Chen, Ruebena Dawes, Hyung Chul Kim, Alicia Ljungdahl, Sarah L Stenton, Susan Walker, Jenny Lord, Gabrielle Lemire, Alexandra C Martin-Geary, Vijay S Ganesh, Jialan Ma, Jamie M Ellingford, Erwan Delage, Elston N D'Souza, Shan Dong, David R Adams, Kirsten Allan, Madhura Bakshi, Erin E Baldwin, Seth I Berger, Jonathan A Bernstein, Ishita Bhatnagar, Ed Blair, Natasha J Brown, Lindsay C Burrage, Kimberly Chapman, David J Coman, Alison G Compton, Chloe A Cunningham, Precilla D'Souza, Petr Danecek, Emmanuèle C Délot, Kerith-Rae Dias, Ellen R Elias, Frances Elmslie, Care-Anne Evans, Lisa Ewans, Kimberly Ezell, Jamie L Fraser, Lyndon Gallacher, Casie A Genetti, Anne Goriely, Christina L Grant, Tobias Haack, Jenny E Higgs, Anjali G Hinch, Matthew E Hurles, Alma Kuechler, Katherine L Lachlan, Seema R Lalani, François Lecoquierre, Elsa Leitão, Anna Le Fevre, Richard J Leventer, Jan E Liebelt, Sarah Lindsay, Paul J Lockhart, Alan S Ma, Ellen F Macnamara, Sahar Mansour, Taylor M Maurer, Hector R Mendez, Kay Metcalfe, Stephen B Montgomery, Mariya Moosajee, Marie-Cécile Nassogne, Serena Neumann, Michael O'Donoghue, Melanie O'Leary, Elizabeth E Palmer, Nikhil Pattani, John Phillips, Georgia Pitsava, Ryan Pysar, Heidi L Rehm, Chloe M Reuter, Nicole Revencu, Angelika Riess, Rocio Rius, Lance Rodan, Tony Roscioli, Jill A Rosenfeld, Rani Sachdev, Charles J Shaw-Smith, Cas Simons, Sanjay M Sisodiya, Penny Snell, Laura St Clair, Zornitza Stark, Helen S Stewart, Tiong Yang Tan, Natalie B Tan, Suzanna E L Temple, David R Thorburn, Cynthia J Tifft, Eloise Uebergang, Grace E Vannoy, Pradeep Vasudevan, Eric Vilain, David H Viskochil, Laura Wedd, Matthew T Wheeler, Susan M White, Monica Wojcik, Lynne A Wolfe, Zoe Wolfenson, Caroline F Wright, Changrui Xiao, David Zocche, John L Rubenstein, Eirene Markenscoff-Papadimitriou, Sebastian M Fica, Diana Baralle, Christel Depienne, Daniel G Macarthur, Joanna M M Howson, Stephan J Sanders, Anne O'Donnell-Luria, Nicola Whiffin

Faculty, Staff and Students Publications

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of …

The Role Of The Cerebellum In Learning To Predict Reward: Evidence From Cerebellar Ataxia, Jonathan Nicholas, Christian Amlang, Chi-Ying R Lin, Leila Montaser-Kouhsari, Natasha Desai, Ming-Kai Pan, Sheng-Han Kuo, Daphna Shohamy

Faculty, Staff and Students Publications

Recent findings in animals have challenged the traditional view of the cerebellum solely as the site of motor control, suggesting that the cerebellum may also be important for learning to predict reward from trial-and-error feedback. Yet, evidence for the role of the cerebellum in reward learning in humans is lacking. Moreover, open questions remain about which specific aspects of reward learning the cerebellum may contribute to. Here we address this gap through an investigation of multiple forms of reward learning in individuals with cerebellum dysfunction, represented by cerebellar ataxia cases. Nineteen participants with cerebellar ataxia and 57 age- and sex-matched …

Frontiers In Congenital Disorders Of Glycosylation Consortium, A Cross-Sectional Study Report At Year 5 Of 280 Individuals In The Natural History Cohort, Christina Lam, Fernando Scaglia, Gerard T Berry, Austin Larson, Kyriakie Sarafoglou, Hans C Andersson, Evgenia Sklirou, Queenie K G Tan, Rodrigo T Starosta, Mustafa Sadek, Lynne Wolfe, Seishu Horikoshi, May Ali, Rita Barone, Teresa Campbell, Irene J Chang, Kiaira Coles, Edward Cook, Erik A Eklund, Nicole M Engelhardt, Mary Freeman, Jennifer Friedman, Debbie Y T Fu, Grace Botzo, Brandy Rawls, Christien Hernandez, Christin Johnsen, Kierstin Keller, Sara Kramer, Bryce Kuschel, Angela Leshinski, Ivan Martinez-Duncker, Gina L Mazza, Saadet Mercimek-Andrews, Bradley S Miller, Karthik Muthusamy, Juanita Neira, Marc C Patterson, Natalie Pogorelc, Lex N Powers, Elizabeth Ramey, Michaela Reinhart, Audrey Squire, Jenny Thies, Jerry Vockley, Hayden Vreugdenhil, Peter Witters, Mehdi Youbi, Aziza Zeighami, Roni Zemet, Andrew C Edmondson, Eva Morava

Faculty, Staff and Students Publications

Objective: Our report describes clinical, genetic, and biochemical features of participants with a molecularly confirmed congenital disorder of glycosylation (CDG) enrolled in the Frontiers in Congenital Disorders of Glycosylation (FCDGC) Natural History cohort at year 5 of the study.

Methods: We enrolled individuals with a known or suspected CDG into the FCDGC Natural History Study, a multicenter prospective and retrospective natural history study of all genetic causes of CDG. We conducted a cross-sectional analysis of baseline study visit data from participants with confirmed CDG who were consented into the FCDGC Natural History Study (5U54NS115198) from October 2019 to November 2023. …

Fathers In The United States Are Getting Older, Larry I Lipshultz, Blair T Stocks

Faculty, Staff and Students Publications

No abstract provided.

Amoxicillin And Penicillin G Dosing In Pediatric Community-Acquired Pneumococcal Pneumonia In The Era Of Conjugate Pneumococcal Vaccines, Dustin Huynh, Norint Tung, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Allison Nguyen, Tyler H Do, Amartya Setty, Jennifer Le

Faculty, Staff and Students Publications

Background: Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data.

Methods: Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12 h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages …

Asynchronous Online Training Increased Knowledge, Confidence, And Intent To Screen And Treat Substance Use Disorders Among Primary Care Clinicians Practicing In Texas, Roger Zoorob, Sung In Kim-Vences, Jacqueline M Hirth, Kylie Schaper, Larissa Grigoryan, Sandra Gonzalez, Alicia Kowalchuk

Faculty, Staff and Students Publications

Introduction: Despite increasing prevalence of substance use disorders (SUD), few patients are diagnosed and treated in primary care settings. This study evaluated changes in knowledge, confidence, and intention to implement screening and brief intervention (SBI) and SUD treatment after clinicians participated in an asynchronous online education course.

Methods: A self-selected sample of primary care clinicians in Texas participated in online SBI and SUD education March 2021-July 2023. Baseline and post-training surveys evaluated changes in knowledge, confidence, and intent to implement SBI and SUD treatment. Changes were compared using paired t-tests. Multivariable linear regression examined factors potentially associated with confidence and …

An Atypical Form Of 60s Ribosomal Subunit In Diamond-Blackfan Anemia Linked To Rpl17 Variants., Florence Fellmann, Carol J. Saunders, Marie-Françoise O'Donohue, David W. Reid, Kelsey A. Mcfadden, Nathalie Montel-Lehry, Cong Yu, Mingyan Fang, Jianguo Zhang, Beryl Royer-Bertrand, Pietro Farinelli, Narjesse Karboul, Jason R. Willer, Lorraine Fievet, Zahurul Alam Bhuiyan, Alissa Lw Kleinhenz, Julie Jadeau, Joy M. Fulbright, Carlo Rivolta, Raffaele Renella, Nicholas Katsanis, Jacques S. Beckmann, Christopher V. Nicchitta, Lydie Da Costa, Erica E. Davis, Pierre-Emmanuel Gleizes

Manuscripts, Articles, Book Chapters and Other Papers

Diamond-Blackfan anemia syndrome (DBA) is a ribosomopathy associated with loss-of-function variants in more than 20 ribosomal protein (RP) genes. Here, we report the genetic, functional, and biochemical dissection of 2 multigenerational pedigrees with variants in RPL17, a large ribosomal subunit protein-encoding gene. Affected individuals had clinical features and erythroid proliferation defects consistent with DBA. Further, RPL17/uL22 depletion resulted in anemia and micrognathia in zebrafish larvae, and in vivo complementation studies indicated that RPL17 variants were pathogenic. Lymphoblastoid cell lines (LCLs) derived from patients displayed a ribosomal RNA maturation defect reflecting haploinsufficiency of RPL17. The proteins encoded by RPL17 variants were …

Lisocabtagene Maraleucel In Follicular Lymphoma: The Phase 2 Transcend Fl Study, Franck Morschhauser, Brad Kahl, Et Al.

2020-Current year OA Pubs

An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor outcomes. Chimeric antigen receptor (CAR) T cell therapy is an option in R/R FL after two or more lines of prior systemic therapy, but there is no consensus on its optimal timing in the disease course of FL, and there are no data in second-line (2L) treatment of patients with high-risk features. …

Promoting Resilience In Stress Management For Adolescents With Type 1 Diabetes: A Randomized Clinical Trial, Joyce P Yi-Frazier, Marisa E Hilliard, Maeve B O'Donnell, Chuan Zhou, Britney M Ellisor, Samantha Garcia Perez, Brenda Duran, Yuliana Rojas, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Miranda C Bradford, Samantha Scott, Sridevi Devaraj, Abby R Rosenberg

Faculty, Staff and Students Publications

IMPORTANCE: Type 1 diabetes (T1D) requires demanding self-management health behaviors, and adolescents with T1D are at risk for poor psychosocial and medical outcomes. Developing resilience skills may help adolescents with T1D and elevated distress navigate common stressors and achieve positive outcomes.

OBJECTIVE: To test the efficacy of the Promoting Resilience in Stress Management (PRISM) intervention on levels of hemoglobin A1c (HbA1c), diabetes distress, self-management behaviors, resilience, and quality of life among adolescents.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, parallel, 1:1 randomized clinical trial that followed up 172 participants for 12 months was conducted from January 1, 2020, to November …

Parkinson’S Disease Variant Detection And Disclosure: Pd Generation, A North American Study, Lola Cook, Jennifer Verbrugge, Tae-Hwi Schwantes-An, Jeanine Schulze, Tatiana Foroud, Anne Hall, Karen S Marder, Ignacio F Mata, Niccolò E Mencacci, Martha A Nance, Michael A Schwarzschild, Tanya Simuni, Susan Bressman, Anne-Marie Wills, Hubert H Fernandez, Irene Litvan, Kelly E Lyons, Holly A Shill, Carlos Singer, Thomas F Tropea, Nora Vanegas Arroyave, Janfreisy Carbonell, Rossy Cruz Vicioso, Linn Katus, Joseph F Quinn, Priscila D Hodges, Yan Meng, Samuel P Strom, Cornelis Blauwendraat, Katja Lohmann, Cynthia Casaceli, Shilpa C Rao, Kamalini Ghosh Galvelis, Anna Naito, James C Beck, Roy N Alcalay

Faculty, Staff and Students Publications

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's …

Sensory Symptoms Across The Lifespan In People With Cerebral Palsy, Ariel M Lyons-Warren, Danielle Guez-Barber, Sruthi P Thomas, Evelyne K Tantry, Aditya Mahat, Bhooma Aravamuthan

Faculty, Staff and Students Publications

Background: To estimate the prevalence of sensory symptoms in people with cerebral palsy (CP) across the lifespan.

Methods: In this cross-sectional study, the self-reported Sensory Processing Scale Inventory (SPS-I) was administered via Research Electronic Data Capture (REDCap) between February 1, 2022, and August 15, 2022, to people with CP or their caregivers enrolled in the online MyCP Community Registry. We determined the association between SPS-I scores and age (Pearson correlation) and functional status as assessed using five validated functional classification systems for CP (analysis of variance [ANOVA]). We hypothesized that sensory symptoms would differ between younger and older individuals with …

A Content Analysis Of Self-Report Child Anxiety Measures, Minjee Kook, Jane W Clinger, Eric Lee, Sophie C Schneider, Eric A Storch, Andrew G Guzick

Faculty, Staff and Students Publications

A clear understanding of the item content of psychological assessments is critical but often overlooked. This study describes the content overlap of seven commonly used and psychometrically validated measures of anxiety among children and adolescents. Symptom codes were created for all items across measures and items were sorted by these codes, which all fell into specific symptom categories. We conducted two analyses of all items: a "bottom-up" content categorization approach, which used symptom categories that were developed during this study, and a "top-down" DSM-5 categorization which mapped items onto symptoms of anxiety disorders in the DSM-5. Findings reveal a weak …

Molecular And Physiological Changes In The Spacex Inspiration4 Civilian Crew, Christopher W Jones, Eliah G Overbey, Jerome Lacombe, Adrian J Ecker, Cem Meydan, Krista Ryon, Braden Tierney, Namita Damle, Matthew Mackay, Evan E Afshin, Jonathan Foox, Jiwoon Park, Theodore M Nelson, Mir Suhail Mohamad, Syed Gufran Ahmad Byhaqui, Burhan Aslam, Ummer Akbar Tali, Liaqun Nisa, Priya V Menon, Chintan O Patel, Sharib A Khan, Doug J Ebert, Aaron Everson, Michael C Schubert, Nabila N Ali, Mallika S Sarma, Jangkeun Kim, Nadia Houerbi, Kirill Grigorev, J Sebastian Garcia Medina, Alexander J Summers, Jian Gu, John A Altin, Ali Fattahi, Mohammad I Hirzallah, Jimmy H Wu, Alexander C Stahn, Afshin Beheshti, Remi Klotz, Veronica Ortiz, Min Yu, Laura Patras, Irina Matei, David Lyden, Ari Melnick, Neil Banerjee, Sean Mullane, Ashley S Kleinman, Michael Loesche, Anil S Menon, Dorit B Donoviel, Emmanuel Urquieta, Jaime Mateus, Ashot E Sargsyan, Mark Shelhamer, Frederic Zenhausern, Eric M Bershad, Mathias Basner, Christopher E Mason

Faculty, Staff and Students Publications

Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged 29), new in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables and immune profiling), ocular alignment measurements and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular …

Fetal Malrotation With Midgut Volvulus: Prenatal Diagnosis And Planning, Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Flavia Massey, Valentina Turchetti, Tracy Lau, Edward Cook, Javeria Raza Alvi, Hasnaa M Elbendary, Jerry L Jewell, Antonella Riva, Alessandro Orsini, Aglaia Vignoli, Zara Federico, Jessica Rosenblum, An-Sofie Schoonjans, Matthias De Wachter, Ignacio Delgado Alvarez, Ana Felipe-Rucián, Nourelhoda A Haridy, Shahzad Haider, Mashaya Zaman, Selina Banu, Najwa Anwaar, Fatima Rahman, Shazia Maqbool, Rashmi Yadav, Vincenzo Salpietro, Reza Maroofian, Rajan Patel, Rupa Radhakrishnan, Sanjay P Prabhu, Klaske Lichtenbelt, Helen Stewart, Yoshiko Murakami, Ulrike Löbel, Felice D'Arco, Emma Wakeling, Wendy Jones, Eleanor Hay, Sanjay Bhate, Thomas S Jacques, David M Mirsky, Matthew T Whitehead, Maha S Zaki, Tipu Sultan, Pasquale Striano, Anna C Jansen, Maarten Lequin, Linda S De Vries, Mariasavina Severino, Andrew C Edmondson, Lara Menzies, Philippe M Campeau, Henry Houlden, Amy Mctague, Stephanie Efthymiou, Kshitij Mankad

Faculty, Staff and Students Publications

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals; the largest single cohort to date. Core clinical features were developmental delay or …

Plasma Proteomic Signature Predicts Myeloid Neoplasm Risk, Duc Tran, J Scott Beeler, Jie Liu, Brian Wiley, Irenaeus C C Chan, Zilan Xin, Michael H Kramer, Armel L Batchi-Bouyou, Xiaoyu Zong, Matthew J Walter, Giulia E M Petrone, Sarantis Chlamydas, Francesca Ferraro, Stephen T Oh, Daniel C Link, Ben Busby, Yin Cao, Kelly L Bolton

2020-Current year OA Pubs

PURPOSE: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet, our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our understanding of the mechanisms promoting MN development.

EXPERIMENTAL DESIGN: We jointly characterized CH and plasma proteomic profiles of 46,237 individuals in the UK Biobank at baseline study entry. During 500,036 person-years of follow-up, 115 individuals developed MN. Cox proportional hazard …

The Isr Downstream Target Atf4 Represses Long-Term Memory In A Cell Type-Specific Manner, Niaz Mahmood, Jung-Hyun Choi, Pei You Wu, Sean W Dooling, Trent A Watkins, Ziying Huang, Jesse Lipman, Hanjie Zhao, Anqi Yang, Jake Silversmith, Yanis Inglebert, Constantinos Koumenis, Vijendra Sharma, Jean-Claude Lacaille, Wayne S Sossin, Arkady Khoutorsky, R Anne Mckinney, Mauro Costa-Mattioli, Nahum Sonenberg

Faculty, Staff and Students Publications

The integrated stress response (ISR), a pivotal protein homeostasis network, plays a critical role in the formation of long-term memory (LTM). The precise mechanism by which the ISR controls LTM is not well understood. Here, we report insights into how the ISR modulates the mnemonic process by using targeted deletion of the activating transcription factor 4 (ATF4), a key downstream effector of the ISR, in various neuronal and non-neuronal cell types. We found that the removal of ATF4 from forebrain excitatory neurons (but not from inhibitory neurons, cholinergic neurons, or astrocytes) enhances LTM formation. Furthermore, the deletion of ATF4 in …

Cerebellar Nuclei Cells Produce Distinct Pathogenic Spike Signatures In Mouse Models Of Ataxia, Dystonia, And Tremor, Meike E Van Der Heijden, Amanda M Brown, Dominic J Kizek, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

The cerebellum contributes to a diverse array of motor conditions, including ataxia, dystonia, and tremor. The neural substrates that encode this diversity are unclear. Here, we tested whether the neural spike activity of cerebellar output neurons is distinct between movement disorders with different impairments, generalizable across movement disorders with similar impairments, and capable of causing distinct movement impairments. Using in vivo awake recordings as input data, we trained a supervised classifier model to differentiate the spike parameters between mouse models for ataxia, dystonia, and tremor. The classifier model correctly assigned mouse phenotypes based on single-neuron signatures. Spike signatures were shared …