Digital Commons Network^™

Outcomes Of Minimally Invasive Isolated Tricuspid Valve Repair And Replacement Through Right Mini-Thoracotomy, Ahmed Alnajar, Subhasis Chatterjee, Jacqueline K Olive, Mahmut S Kaymakci, Lauren Gray, Zachary Gray, Joao R Breda, Joseph Lamelas

Faculty, Staff and Students Publications

OBJECTIVE: Isolated tricuspid valve surgery is uncommon and associated with high perioperative morbidity and mortality. We aimed to study the overall outcomes of patients who underwent minimally invasive right thoracotomy tricuspid valve surgery (Mini-TVS), consisting of either tricuspid valve repair (TVre) or replacement (TVR).

METHODS: We performed a retrospective analysis of all Mini-TVS procedures (2017-2022), through which we identified isolated tricuspid valve surgeries. We examined in-hospital outcomes, survival analysis over a 4-year period, and competing risk analysis for reoperative surgery.

RESULTS: Among a total of 51 patients, the average age was 60 ± 16 years, and 67% (n = 34) …

Maternal Vaccine Effectiveness Against Influenza-Associated Hospitalizations And Emergency Department Visits In Infants, Leila C Sahni, Samantha M Olson, Natasha B Halasa, Laura S Stewart, Marian G Michaels, John V Williams, Janet A Englund, Eileen J Klein, Mary A Staat, Elizabeth P Schlaudecker, Rangaraj Selvarangan, Jennifer E Schuster, Geoffrey A Weinberg, Peter G Szilagyi, Julie A Boom, Manish M Patel, Flor M Muñoz, New Vaccine Surveillance Network Collaborators

Faculty, Staff and Students Publications

IMPORTANCE: Influenza virus infection during pregnancy is associated with severe maternal disease and may be associated with adverse birth outcomes. Inactivated influenza vaccine during pregnancy is safe and effective and can protect young infants, but recent evidence, particularly after the 2009 novel influenza A (H1N1) pandemic, is limited.

OBJECTIVE: To evaluate the effectiveness of influenza vaccination during pregnancy against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits in infants younger than 6 months.

DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, test-negative case-control study using data from the New Vaccine Surveillance Network from the 2016 to 2017 through 2019 to …

Long-Term Non-Progression And Risk Factors For Disease Progression Among Children Living With Hiv In Botswana And Uganda: A Retrospective Cohort Study, Samuel Kyobe, Grace Kisitu, Savannah Mwesigwa, John Farirai, Eric Katagirya, Gaone Retshabile, Lesedi Williams, Angela Mirembe, Lesego Ketumile, Misaki Wayengera, John Mukisa, Gaseene Sebetso, Thabo Diphoko, Marion Amujal, Edgar Kigozi, Fred Katabazi, Ronald Oceng, Busisiwe Mlotshwa, Koketso Morapedi, Betty Nsangi, Edward Wampande, Masego Tsimako, Chester Brown, Ishmael Kasvosve, Moses Joloba, Gabriel Anabwani, Sununguko Mpoloka, Graeme Mardon, Adeodata Kekitiinwa, Neil A Hanchard, Jacqueline Kyosiimire-Lugemwa, Mogomotsi Matshaba, Dithan Kiragga

Faculty, Staff and Students Publications

OBJECTIVES: We utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda.

METHODS: Electronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era.

RESULTS: Between the two countries, 14,246 antiretroviral therapy-naïve …

The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier

Faculty, Staff and Students Publications

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory …

Endothelial Cells Adopt A Pro-Reparative Immune Responsive Signature During Cardiac Injury, Hali Long, Jeffrey D Steimle, Francisco Jose Grisanti Canozo, Jong Hwan Kim, Xiao Li, Yuka Morikawa, Minjun Park, Diwakar Turaga, Iki Adachi, Joshua D Wythe, Md Abul Hassan Samee, James F Martin

Faculty, Staff and Students Publications

Modulation of the heart’s immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors …

Anticoagulation With Osocimab In Patients With Kidney Failure Undergoing Hemodialysis: A Randomized Phase 2 Trial, Jeffrey I Weitz, László B Tankó, Jürgen Floege, Keith A A Fox, Deepak L Bhatt, Ravi Thadhani, James Hung, Ákos F Pap, Dagmar Kubitza, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation, is emerging as an attractive target for new anticoagulants that may be safer than existing agents. Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such patients. We conducted a phase 2b, double-blind, placebo-controlled trial, in which 704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized to receive lower- or higher-dose osocimab or placebo. In total, 686 participants (436 male, 250 female) received treatment for ≤18 months (planned minimal treatment period of …

Mapping Gray And White Matter Volume Abnormalities In Early-Onset Psychosis: An Enigma Multicenter Voxel-Based Morphometry Study, Shuqing Si, Anbreen Bi, Zhaoying Yu, Cheryl See, Sinead Kelly, Sonia Ambrogi, Celso Arango, Inmaculada Baeza, Nerisa Banaj, Michael Berk, Josefina Castro-Fornieles, Benedicto Crespo-Facorro, Jacob J Crouse, Covadonga M Díaz-Caneja, Anne-Kathrin Fett, Adriana Fortea, Sophia Frangou, Benjamin I Goldstein, Ian B Hickie, Joost Janssen, Kody G Kennedy, Lydia Krabbendam, Marinos Kyriakopoulos, Bradley J Macintosh, Pedro Morgado, Stener Nerland, Saül Pascual-Diaz, Maria Picó-Pérez, Fabrizio Piras, Bjørn Rishovd Rund, Elena De La Serna, Gianfranco Spalletta, Gisela Sugranyes, Chao Suo, Diana Tordesillas-Gutiérrez, Daniela Vecchio, Joaquim Radua, Philip Mcguire, Sophia I Thomopoulos, Neda Jahanshad, Paul M Thompson, Claudia Barth, Ingrid Agartz, Anthony James, Matthew J Kempton

Faculty, Staff and Students Publications

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.

METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the …

The Future Of International Classification Of Diseases Coding In Steatotic Liver Disease: An Expert Panel Delphi Consensus Statement, Hannes Hagström, Leon A Adams, Alina M Allen, Christopher D Byrne, Yoosoo Chang, Ajay Duseja, Henning Grønbæk, Mona H Ismail, Peter Jepsen, Fasiha Kanwal, Jennifer Kramer, Rohit Loomba, Henry E Mark, Philip N Newsome, Mary E Rinella, Ian A Rowe, Seungho Ryu, Arun Sanyal, Jörn M Schattenberg, Marina Serper, Nick Sheron, Tracey G Simon, C Wendy Spearman, Elliot B Tapper, Marcela Villota-Rivas, Sarah H Wild, Vincent Wai-Sun Wong, Yusuf Yilmaz, Shira Zelber-Sagi, Fredrik Åberg, Jeffrey V Lazarus

Faculty, Staff and Students Publications

BACKGROUND: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy.

METHODS: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries.

RESULTS: Consensus ranged from 88.8% to 96.9% (mean = 92.3%).

CONCLUSIONS: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic …

Host Gastric Corpus Microenvironment Facilitates Ascaris Suum Larval Hatching And Infection In A Murine Model, Yifan Wu, Grace Adeniyi-Ipadeola, Mahliyah Adkins-Threats, Matthew Seasock, Charlie Suarez-Reyes, Ricardo Fujiwara, Maria Elena Bottazzi, Lizhen Song, Jason C Mills, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric …

Unanswered Questions Following Reports Of Secondary Malignancies After Car-T Cell Therapy, Bruce L Levine, Marcelo C Pasquini, John E Connolly, David L Porter, Michael P Gustafson, Jaap J Boelens, Edwin M Horwitz, Stephan A Grupp, Marcela V Maus, Frederick L Locke, Fabio Ciceri, Annalisa Ruggeri, John Snowden, Helen E Heslop, Crystal L Mackall, Carl H June, Anna M Sureda, Miguel-Angel Perales

Faculty, Staff and Students Publications

Reports of T cell malignancies after CAR-T cell therapy should be investigated, but existing data from follow-up studies suggest a low risk compared with other cancer treatments.

Antiretroviral Therapy In Pregnancy: A 2023 Review Of The Literature, Alison N Goulding, Kasey Meeks, Lena Shay, Sarah Casey, Colton Applegarth, Jennifer Mckinney

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Selection of antiretroviral therapy during pregnancy must consider maternal physiology and resulting pharmacokinetic changes in pregnancy, resistance and efficacy profiles, tolerability and frequency of adverse effects, teratogenicity, and maternal, neonatal, and pregnancy outcomes. The objective of this review is to summarize the underlying data that informs the current clinical perinatal guidelines in the USA.

RECENT FINDINGS: Data now supports the use of dolutegravir at all stages of pregnancy with no significant increase in neural tube defects. Safety and pharmacokinetic data on newer antiretroviral medications in pregnancy continue to lag behind the general population. While there are multiple …

Correction To: Ssr White Paper: Guidelines For Utilization And Performance Of Direct Mr Arthrography, Eric Y Chang, Jenny T Bencardino, Cristy N French, Jan Fritz, Chris J Hanrahan, Zaid Jibri, Ara Kassarjian, Kambiz Motamedi, Michael D Ringler, Colin D Strickland, Christin A Tiegs-Heiden, Richard E A Walker

Faculty, Staff and Students Publications

No abstract provided.

Pediatric Cancer Incidence Among Individuals With Overgrowth Syndromes And Overgrowth Features: A Population-Based Assessment In Seven Million Children, Gillean K Connolly, Rachel D Harris, Charles Shumate, Surya P Rednam, Mark A Canfield, Sharon E Plon, Joanne Nguyen, Jeremy M Schraw, Philip J Lupo

Faculty, Staff and Students Publications

Background: Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study.

Methods: This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models …

Regulation Of Androgen Receptor Stability By The Β1pix/Stub1 Complex, Ahmed Chahdi, Carolina Jorgez, Abhishek Seth

Faculty, Staff and Students Publications

The Androgen Receptor (AR) is essential in the development and differentiation of testes and male genitalia. AR expression is tightly regulated at the translational and posttranslational levels. AR posttranscriptional regulation is a major determinant of AR availability since AR is a direct target of E3 ubiquitin ligase STUB1. Our work indicated that the Rac/Cdc42 guanosine triphosphatase guanine nucleotide exchange factor, β1Pix, enhanced AR levels after AR stimulation in HEK293 and HeLa cells. AR stimulation decreased AR ubiquitination which is accompanied by increased β1Pix binding to AR. Ectopic expression of β1Pix decreased AR ubiquitination in Tm4 and HEK293 cells. We demonstrated …

A Practical Guide To Evaluating And Using Big Data In Digestive Disease Research, Madeline Alizadeh, Natalia Sampaio Moura, Alyssa Schledwitz, Seema A Patil, Hashem El-Serag, Jacques Ravel, Jean-Pierre Raufman

Faculty, Staff and Students Publications

No abstract provided.

Timely Delivery Of Port For Head And Neck Squamous Cell Carcinoma In A County Hospital, Ana Maria Rosas Herrera, Angela D Haskins, Alexander N Hanania, Pavan M Jhaveri, Christina H Chapman, Quillan Huang, David J Hernandez

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study was to compare the rate of post-operative radiation therapy (PORT) initiation within 6 weeks for head and neck squamous cell carcinoma patients treated at a safety net, academic institutio between 2019 and 2021 versus those treated in 2022 after implementation of a new clinical pathway.

METHODS: A retrospective case-control study was performed at a single tertiary care, safety-net, academic institution. Patient demographics, tumor characteristics, dates of surgery, and other treatment dates were collected from the electronic medical record. The time from surgery to PORT was calculated. Patients who started radiation treatment within 42 days …

Rates, Patterns, And Predictors Of Specialty Palliative Care Consultation Among Patients With Acute-On-Chronic Liver Failure, Arpan Patel, Anne Walling, Fasiha Kanwal, Marina Serper, Ruben Hernaez, Vinay Sundaram, David Kaplan, Tamar Taddei, Nadim Mahmud

Faculty, Staff and Students Publications

BACKGROUND & AIMS: There is growing acceptance that principles of palliative care should be integrated into the management of serious illnesses affecting the liver, such as acute-on-chronic liver failure (ACLF). However, rates, patterns, and predictors of specialty palliative care consultation among patients with ACLF have not been well-described.

METHODS: We performed a retrospective cohort study of patients hospitalized with ACLF between 1/1/2008 and 12/31/2018 using the VOCAL cohort. Patients were followed until 6/2021. We used mixed-effects regression analyses to identify significant patient and facility factors associated with palliative care consultation. We examined timing of consultation, the influence of ACLF characteristics, …

Abortion Patients’ Decision Making About Where To Obtain Out-Of-State Care Following Texas’ 2021 Abortion Ban, Kari White, Whitney Arey, Brooke Whitfield, Asha Dane'el, Laura Dixon, Joseph E Potter, Tony Ogburn, Anitra D Beasley

Faculty, Staff and Students Publications

OBJECTIVE: To assess pregnant Texans' decisions about where to obtain out-of-state abortion care following the September 2021 implementation of Senate Bill 8 (SB8), which prohibited abortions after detectable embryonic cardiac activity.

DATA SOURCE: In-depth telephone interviews with Texas residents ≥15 years of age who obtained out-of-state abortion care after SB8's implementation.

STUDY DESIGN: This qualitative study explored participants' experiences identifying and contacting abortion facilities and their concerns and considerations about traveling out of state. We used inductive and deductive codes in our thematic analysis describing people's decisions about where to obtain care and how they evaluated available options.

DATA COLLECTION: …

The Role Of Family Accommodation In Child Posttraumatic Stress Symptoms And Functional Impairment In The Context Of Cognitive Behavioral Therapy, Ogechi Cynthia Onyeka, Samuel D Spencer, Alison Salloum, Katie Jiannetto, Eric A Storch

Faculty, Staff and Students Publications

BACKGROUND: Caregiver behaviors such as family accommodation (FA) are negatively reinforced by reduced distress in the short term, but ultimately maintain symptoms. It is important to explore the role of FA on symptoms and impairment. The current study examined the relationship among FA, posttraumatic stress symptoms (PTSS), and functional impairment in a sample of children and their caregivers who completed trauma treatment.

METHOD: Participants included 183 children and their caregivers (M age = 7.89; 55.19 % female; 73.22 % non-Hispanic; 51.37 % White). Data consisted of parent-reported measures collected at baseline, post-treatment, and 12-month follow-up from a randomized control trial …

Distribution Of P2y And P2x Purinergic Receptor Expression Within The Intestine, Kristen A Engevik, Francesca J Scribano, J Thomas Gebert, Jacob L Perry, Sue E Crawford, Joseph M Hyser

Faculty, Staff and Students Publications

Nucleotides are potent extracellular signaling molecules during homeostasis, infection, and injury due to their ability to activate purinergic receptors. The nucleotide ATP activates P2X receptors (P2RXs), whereas the nucleotides ADP, ATP, UTP, and UDP-glucose selectively activate different P2Y receptors (P2RYs). Several studies have established crucial roles for P2 receptors during intestinal inflammatory and infectious diseases, yet the most extensive characterization of purinergic signaling has focused on immune cells and the central and enteric nervous systems. As epithelial cells serve as the first barrier against irritants and infection, we hypothesized that the gut epithelium may express multiple purinergic receptors that respond …

Strategies For Secondary Use Of Real-World Clinical And Administrative Data For Outcome Ascertainment In Pragmatic Clinical Trials, Cynthia Hau, Patricia A Woods, Amanda S Guski, Srihari I Raju, Liang Zhu, Patrick R Alba, William C Cushman, Peter A Glassman, Areef Ishani, Addison A Taylor, Ryan E Ferguson, Sarah M Leatherman

Faculty, Staff and Students Publications

Background: Pragmatic trials are gaining popularity as a cost-effective way to examine treatment effectiveness and generate timely comparative evidence. Incorporating supplementary real-world data is recommended for robust outcome monitoring. However, detailed operational guidelines are needed to inform effective use and integration of heterogeneous databases.

Objective: Lessons learned from the Veterans Affairs (VA) Diuretic Comparison Project (DCP) are reviewed, providing adaptable recommendations to capture clinical outcomes from real-world data.

Methods: Non-cancer deaths and major cardiovascular (CV) outcomes were determined using VA, Medicare, and National Death Index (NDI) data. Multiple ascertainment strategies were applied, including claims-based algorithms, natural language processing, and systematic …

Outcomes After Bioprosthetic Versus Mechanical Mitral Valve Replacement For Infective Endocarditis In The United States, Katie J Hogan, Christopher B Sylvester, Matthew J Wall, Todd K Rosengart, Joseph S Coselli, Marc R Moon, Subhasis Chatterjee, Ravi K Ghanta

Faculty, Staff and Students Publications

Objective

In patients who underwent mitral valve replacement for infectious endocarditis, we evaluated the association of prosthesis choice with readmission rates and causes (the primary outcomes), as well as with in-hospital mortality, cost, and length of stay (the secondary outcomes).

Methods

Patients with infectious endocarditis who underwent isolated mitral valve replacement from January 2016 to December 2018 were identified in the United States Nationwide Readmissions Database and stratified by valve type. Propensity score matching was used to compare adjusted outcomes.

Results

A weighted total of 4206 patients with infectious endocarditis underwent bioprosthetic mitral valve replacement (n = 3132) and mechanical …

Role Of Camk2d In Neurodevelopment And Associated Conditions, Pomme M F Rigter, Charlotte De Konink, Matthew J Dunn, Martina Proietti Onori, Jennifer B Humberson, Matthew Thomas, Caitlin Barnes, Carlos E Prada, K Nicole Weaver, Thomas D Ryan, Oana Caluseriu, Jennifer Conway, Emily Calamaro, Chin-To Fong, Wim Wuyts, Marije Meuwissen, Eva Hordijk, Carsten N Jonkers, Lucas Anderson, Berfin Yuseinova, Sarah Polonia, Diane Beysen, Zornitza Stark, Elena Savva, Cathryn Poulton, Fiona Mckenzie, Elizabeth Bhoj, Caleb P Bupp, Stéphane Bézieau, Sandra Mercier, Amy Blevins, Ingrid M Wentzensen, Fan Xia, Jill A Rosenfeld, Tzung-Chien Hsieh, Peter M Krawitz, Miriam Elbracht, Danielle C M Veenma, Howard Schulman, Margaret M Stratton, Sébastien Küry, Geeske M Van Woerden

Faculty, Staff and Students Publications

The calcium/calmodulin-dependent protein kinase type 2 (CAMK2) family consists of four different isozymes, encoded by four different genes-CAMK2A, CAMK2B, CAMK2G, and CAMK2D-of which the first three have been associated recently with neurodevelopmental disorders. CAMK2D is one of the major CAMK2 proteins expressed in the heart and has been associated with cardiac anomalies. Although this CAMK2 isoform is also known to be one of the major CAMK2 subtypes expressed during early brain development, it has never been linked with neurodevelopmental disorders until now. Here we show that CAMK2D plays an important role in neurodevelopment not only in mice but also in …

Examining The Association Between Posttraumatic Stress Disorder And Disruptions In Cortical Networks Identified Using Data-Driven Methods, Jin Yang, Ashley A Huggins, Delin Sun, C Lexi Baird, Courtney C Haswell, Jessie L Frijling, Miranda Olff, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawijn, Dick J Veltman, Benjamin Suarez-Jimenez, Xi Zhu, Yuval Neria, Anna R Hudson, Sven C Mueller, Justin T Baker, Lauren A M Lebois, Milissa L Kaufman, Rongfeng Qi, Guang Ming Lu, Pavel Říha, Ivan Rektor, Emily L Dennis, Christopher R K Ching, Sophia I Thomopoulos, Lauren E Salminen, Neda Jahanshad, Paul M Thompson, Dan J Stein, Sheri M Koopowitz, Jonathan C Ipser, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Li Wang, Ye Zhu, Gen Li, Anika Sierk, Antje Manthey, Henrik Walter, Judith K Daniels, Christian Schmahl, Julia I Herzog, Israel Liberzon, Anthony King, Mike Angstadt, Nicholas D Davenport, Scott R Sponheim, Seth G Disner, Thomas Straube, David Hofmann, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Jennifer U Blackford, Bunmi O Olatunji, Evan M Gordon, Geoffrey May, Steven M Nelson, Chadi G Abdallah, Ifat Levy, Ilan Harpaz-Rotem, John H Krystal, Rajendra A Morey, Aristeidis Sotiras

Faculty, Staff and Students Publications

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD …

Generation Of Five Induced Pluripotent Stem Cell Lines From Patients With Mecp2 Duplication Syndrome, Danielle Mendonca, Gerarda Cappuccio, Jennifer Sheppard, Magdalena Delacruz, Jesse Bengtsson, Claudia M B Carvalho, Aleksandar Bajic, Hyekyung Park, Jean J Kim, Paymaan Jafar-Nejad, Christine Coquery, Davut Pehlivan, Bernhard Suter, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

MECP2 Duplication Syndrome (MDS) is a rare, severe neurodevelopmental disorder arising from duplications in the Xq28 region containing the MECP2 gene that predominantly affects males. We generated five human induced pluripotent stem cell (iPSC) lines from the fibroblasts of individuals carrying between 0.355 and 11.2 Mb size duplications in the chromosomal locus containing MECP2. All lines underwent extensive testing to confirm MECP2 duplication and iPSC-related features such as morphology, pluripotency markers, and trilineage differentiation potential. These lines are a valuable resource for molecular and functional studies of MDS as well as screening for a variety of therapeutic approaches.

Using Mobile Technology For Family-Based Prevention In Families With Low Incomes: Lessons From A Randomized Controlled Trial Of A Childhood Obesity Prevention Program, Thomas G Power, Susan S Baker, Karen V Barale, M Catalina Aragón, Jane D Lanigan, Louise Parker, Karina Silva Garcia, Garry Auld, Nilda Micheli, Sheryl O Hughes

Faculty, Staff and Students Publications

Researchers are increasingly using web-based technologies to deliver family-based, prevention programming. Few studies have examined the success of such approaches for families with low incomes. The purpose of this study was to describe the level of in-class and online engagement in a childhood obesity prevention program for parents with low incomes, to examine the demographic correlates of parent engagement, and to examine dosage effects on parental feeding outcomes as a function of online exposure. All participants attended in-class nutrition education classes (Eating Smart · Being Active) as part of the Expanded Food and Nutrition Education Program (EFNEP) in Colorado and …

Leptin Reduction As A Required Component For Weight Loss, Shangang Zhao, Na Li, Wei Xiong, Guannan Li, Sijia He, Zhuzhen Zhang, Qingzhang Zhu, Nisi Jiang, Christian Ikejiofor, Yi Zhu, May-Yun Wang, Xianlin Han, Ningyang Zhang, Carolina Solis-Herrera, Christine Kusminski, Zhiqiang An, Joel K Elmquist, Philipp E Scherer

Faculty, Staff and Students Publications

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or …

Biallelic Creld1 Variants Cause A Multisystem Syndrome, Including Neurodevelopmental Phenotypes, Cardiac Dysrhythmias, And Frequent Infections, Lauren Jeffries, Emily K Mis, Kirsty Mcwalter, Sandra Donkervoort, Nina N Brodsky, Jean-Marie Carpier, Weizhen Ji, Cristian Ionita, Bhaskar Roy, Jon S Morrow, Armine Darbinyan, Krishna Iyer, Ritu B Aul, Siddharth Banka, Katherine R Chao, Laura Cobbold, Stacey Cohen, Helena M Custodio, Margaret Drummond-Borg, Frances Elmslie, Erika Finanger, Bryan E Hainline, Ingo Helbig, Stacy Hewson, Ying Hu, Adam Jackson, Dragana Josifova, Monica Konstantino, Meganne E Leach, Bryan Mak, David Mccormick, Elisabeth Mcgee, Stanley Nelson, Joanne Nguyen, Kimberly Nugent, Lucy Ortega, Howard P Goodkin, Elizabeth Roeder, Sani Roy, Katie Sapp, Dimah Saade, Sanjay M Sisodiya, Karen Stals, Shelley Towner, William Wilson, Deciphering Developmental Disorders, Genomics England Research Consortium, Undiagnosed Disease Network, Mustafa K Khokha, Carsten G Bönnemann, Carrie L Lucas, Saquib A Lakhani

Faculty, Staff and Students Publications

PURPOSE: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants.

METHODS: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells.

RESULTS: Biallelic variants in CRELD1 were found in 18 participants from 14 families. Affected individuals displayed an array of phenotypes involving developmental delay, early-onset epilepsy, and hypotonia, with about half demonstrating cardiac arrhythmias and some experiencing recurrent infections. Most harbored a frameshift in trans with a missense …

Cardiac Magnetic Resonance Imaging In Detection Of Progressive Graft Dysfunction In Pediatric Heart Transplantation, Kae Watanabe, Nicoleta C Arva, Joshua D Robinson, Cynthia Rigsby, Michael Markl, Melanie Sojka, Paul Tannous, Jennifer Arzu, Nazia Husain

Faculty, Staff and Students Publications

BACKGROUND: Chronic graft failure (CGF) in pediatric heart transplant (PHT) is multifactorial and may present with findings of fibrosis and microvessel disease (MVD) on endomyocardial biopsy (EMB). There is no optimal CGF surveillance method. We evaluated associations between cardiac magnetic resonance imaging (CMR) and historical/EMB correlates of CGF to assess CMR's utility as a surveillance method.

METHODS: Retrospective analysis of PHT undergoing comprehensive CMR between September 2015 and January 2022 was performed. EMB within 6 months was graded for fibrosis (scale 0-5) and MVD (number of capillaries with stenotic wall thickening per field of view). Correlation analysis and logistic regression …

Evolving Concepts In Helicobacter Pylori Management, Steven F Moss, Shailja C Shah, Mimi C Tan, Hashem B El-Serag

Faculty, Staff and Students Publications

Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain …