Digital Commons Network^™

Evaluating The Human Abuse Potential Of Concurrent Use Of Electronic Cigarettes And Low Nicotine Cigarettes Among Adults Who Smoke, Jason D Robinson, Yong Cui, George Kypriotakis, Jeffrey M Engelmann, Maher Karam-Hage, Jennifer A Minnix, Charles E Green, Sanjay Shete, Dorothy K Hatsukami, Eric C Donny, Sharon E Murphy, Stephen S Hecht, Thomas Eissenberg, David W Wetter, Paul M Cinciripini

Faculty, Staff and Student Publications

The U.S. Food and Drug Administration has stated its intention to reduce the nicotine content of combustible cigarettes to render them less addictive. This study evaluated the impact of providing adults who smoke with both very low nicotine content cigarettes (VLNCCs) and electronic cigarettes (ECs) of varying nicotine content on measures of human abuse potential. Participants (

Project Gender Nutriscope: Methods Of A Mixed Methods, Community-Engaged Study Design To Explore The Nutritional Needs Of Transgender And Gender-Diverse Youth And Young Adults., Heather E Schier, Krithika Chetty, Shivakriti Induri, Liam Gallagher, Miriam Knopp, Julie Kennel, Whitney Linsenmeyer, Avery M Anderson, Matthew Adkins, Irene E Hatsu, Janna D Stephens, Carolyn Gunther

Ambulatory and Primary Care Articles

OBJECTIVE: Despite growing evidence of distinct nutrition-related experiences and disparities, transgender and gender-diverse (TGD) youth and young adults are an underrepresented population in nutrition research. This paper describes the methods and study design from Project Gender NutriScope, a study that will explore the nutritional needs of TGD youth and young adults.

DESIGN: Parallel convergent cross-sectional mixed methods; community-engaged.

SETTING: A purposive sample will be recruited in a Midwest city through clinics, youth organizations, and a large state university.

PARTICIPANTS: Transgender and gender-diverse youth and young adults aged 13-24 years.

INTERVENTION: Findings from this formative study will be used to inform …

De Novo Variants In Rybp Are Associated With A Severe Neurodevelopmental Disorder And Congenital Anomalies, Monika Weisz-Hubshman, Lindsay C Burrage, Sharayu V Jangam, Jill A Rosenfeld, Sandra Von Hardenberg, Anke Bergmann, Manuela Friederike Richter, Malgorzata Rydzanicz, Rafal Ploski, Agnieszka Stembalska, Wendy K Chung, Rebecca R Hernan, Foong Y Lim, Theresa Brunet, Steffen Syrbe, Boris Keren, Solveig Heide, David R Murdock, Hongzheng Dai, Fan Xia, Shamika Ketkar, Brian Dawson, Vinodh Narayanan, Hillary K Graves, Undiagnosed Diseases Network, Michael F Wangler, Carlos Bacino, Brendan Lee

Duncan NRI Faculty and Staff Publications

Purpose: Polycomb group proteins are key epigenetic transcriptional regulators. Multiple neurodevelopmental disorders are associated with pathogenic variants of the genes encoding Polycomb group proteins. RYBP is a core component of the noncanonical Polycomb Repressor Complex 1; however, its role in disease is unclear.

Methods: Functional consequences of RYBP variants were assessed using in vitro cellular and in vivo Drosophila melanogaster studies.

Results: We described 7 individuals with heterozygous de novo variants of RYBP and their clinical findings, including severe developmental delay, dysmorphisms, and multiple congenital anomalies. We showed that all single-nucleotide variants in RYBP localize to the N-terminal domain of …

Gastroesophageal Reflux And Gastrointestinal Symptoms After Metabolic And Bariatric Surgery In Adolescents: An 8-Year Follow-Up Analysis, John B Rode, Suhail A Zeineddin, Jane C Khoury, Todd M Jenkins, Stephanie R Sisley, Anita P Courcoulas, Justin R Ryder, Marc P Michalsky, Thomas H Inge

Children’s Nutrition Research Center Staff Publications

Importance: Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed metabolic and bariatric surgery (MBS) procedures in adolescents and adults. Despite their safety and effectiveness, there is concern over postoperative gastrointestinal symptoms (GIS), especially gastroesophageal reflux symptoms (GERS), in those undergoing VSG.

Objective: To evaluate the long-term prevalence of GIS in adolescents who underwent RYGB or VSG.

Design, setting, and participants: This is a prospective, multicenter, observational cohort study at five academic referral centers in the United States. Patients were enrolled from February 28, 2007, through December 30, 2011. The analysis included 228 adolescents: 161 …

Personality Factors Associated With Manner Of Death: A Psychological Autopsy Study, Christopher I Gurguis, Scott D Lane, Edison Leung, Joy M Schmitz, Consuelo Walss-Bass, Thomas D Meyer

Staff and Researcher Publications

Psychological autopsies are a well-established tool for understanding contributing factors in suicide completion. These tools have been used less often to understand personality characteristics of people with other manners of death (e.g. overdose). This study examined personality characteristics related to the manner of death in 83 autopsy cases using the UTHealth Psychological Autopsy Interview Schedule (UTH-PAIS), a psychological autopsy which assesses the presence of mental illness or substance use disorder but also includes items to capture transdiagnostic personality factors. Exploratory factor analysis of the items assessing personality factors was used to examine patterns in personality, and these factors were confirmed …

Alpha-Synuclein Phosphomimetic Y39e And S129d Knock-In Mice Show Cytosolic Alpha-Synuclein Localization Without Developing Neurodegeneration Or Motor Deficits, Youngdoo Kim, Bhupesh Vaidya, Joseph Mcinnes, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor symptoms. Its pathological hallmarks include the accumulation of misfolded alpha-synuclein (α-Syn) in Lewy bodies and Lewy neurites. Phosphorylation of α-Syn is a prominent feature of these inclusions, but its role in disease pathogenesis remains unclear. To identify the role of α-Syn phosphorylation in synucleinopathy, we generated two Snca knock-in (KI) mouse models carrying phosphomimetic mutations at SncaY39 or SncaS129 (Snca^Y39E or Snca^S129D) which manipulated epitopes phosphorylated in the PD brain. Both Snca^Y39E and Snca^S129D KI mice displayed increased α-Syn phosphorylation, enhanced …

Eight Weeks Of High-Intensity Interval Training Alters The Tongue Microbiome And Impacts Nitrate And Nitrite Levels In Previously Sedentary Men, Annabel Simpson, Andrea M. Pilotto, Lorenza Brocca, Raffaele Mazzolari, Bob T. Rosier, Miguel Carda-Dieguez, Patricia Casas-Agustench, Raul Bescos, Simone Porcelli, Alex Mira, Chris Easton, Fiona L. Henriquez, Mia Burleigh

School of Health Professions

Nitric oxide (∗NO) is a key signalling molecule, produced enzymatically via ∗NO synthases (NOS) or following the stepwise reduction of nitrate to nitrite via oral bacteria. Exercise training upregulates NOS expression and improves systemic health, but its effect on oral health, and more particularly the oral microbiome, has not been investigated. We used an exercise training study design to investigate changes in the tongue dorsum microbiome, and in nitrate and nitrite levels in the saliva, plasma and muscle, before, during and after an exercise training period. Eleven untrained males (age 25 ± 5 years, mass 64.0 ± 11.2 kg, stature …

Single-Cell Transcriptomic Analysis Of Kaposi Sarcoma, Daniel A. Rauch, Paula Valiño Ramos, Mariam Khanfar, John Harding, Ancy Joseph, Anam Fahad, Paul Simonson, Isabel Risch, Obi Griffith, Malachi Griffith, Lee Ratner

2020-Current year OA Pubs

Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of "spindle cells", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined twenty-five skin and blood samples from sixteen subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a CD34-negative proliferative fraction of endothelial cells, and the second representing CD34-positive cells expressing endothelial genes found in a variety of cell types including high endothelial venules, fenestrated capillaries, and endothelial tip …

Methylomic Signature Of Current Cannabis Use In Two First-Episode Psychosis Cohorts, Emma L Dempster, Emma C Johnson, Et Al.

2020-Current year OA Pubs

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples …

Acute Trem2 Inhibition Depletes Mafb-High Microglia And Hinders Remyelination, Jinchao Hou, Roberta Magliozzi, Yun Chen, Junjie Wu, John Wulf Ii, Gregory Strout, Xiangming Fang, Marco Colonna

2020-Current year OA Pubs

We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting the

Navigating The Complexities Of End-Stage Kidney Disease (Eskd) From Risk Factors To Outcome: Insights From The Uk Biobank Cohort, Debasish Kar, Richard Byng, Aziz Sheikh, Mintu Nath, Bedowra Zabeen, Shubharthi Kar, Shakila Banu, Habibur Rahman, Navid Khan, Durjoy Acharjee, Shafiqul Islam, Victoria Allgar, Jose Ordonez-Mena, Aya El-Wazir, Soon Song, Ashish Verma, Umesh Kadam, Simon De Lusignan

Peninsula Medical School

BACKGROUND: The global prevalence of end-stage kidney disease (ESKD) is increasing despite optimal management of traditional risk factors such as hyperglycaemia, hypertension, and dyslipidaemia. This study examines the influence of cardiorenal risk factors, socioeconomic status, and ethnic and cardiovascular comorbidities on ESKD outcomes in the general population.

METHODS: This cross-sectional study analysed data from 502,408 UK Biobank study participants recruited between 2006 and 2010. Multivariable logistic regression models were fitted to assess risk factors for ESKD, with results presented as adjusted odds ratio (aOR) and 95% confidence intervals (95% CI).

RESULTS: A total of 1191 (0.2%) of the study participants …

Multi-Omic Analysis Of Biological Aging Biomarkers In Long-Term Calorie Restriction And Endurance Exercise Practitioners: A Cross-Sectional Study, Giovanni Fiorito, Valeria Tosti, Silvia Polidoro, Beatrice Bertozzi, Nicola Veronese, Edda Cava, Francesco Spelta, Laura Piccio, Dayna S Early, Daniel Raftery, Paolo Vineis, Luigi Fontana

2020-Current year OA Pubs

Calorie restriction (CR) and physical exercise (EX) are well-established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long-term follow-up. This study compared BioAge biomarkers in 41 middle-aged and older adult long-term CR practitioners, 41 age- and sex-matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood-biomarkers. Additionally, a subset of …

Guideline-Directed Medical Therapy And Outcomes In The Ischemia Trial, David J Maron, Jonathan D Newman, Rebecca Anthopolos, Ying Lu, Susanna Stevens, William E Boden, Kreton Mavromatis, Jason Linefsky, Rajesh G Nair, Olga Bockeria, Gilbert Gosselin, Gian P Perna, Elena Demchenko, David Foo, Michael D Shapiro, Mary Ann Champagne, Christie Ballantyne, Peter Mccullough, Jose Luis Lopez-Sendon, Frank Rockhold, Frank Harrell, Yves Rosenberg, Gregg W Stone, Sripal Bangalore, Harmony R Reynolds, John A Spertus, Judith S Hochman

Faculty, Staff and Students Publications

Background: Guideline-directed medical therapy (GDMT) with multiple risk factor goals is recommended for patients with chronic coronary disease (CCD), yet achieving all GDMT goals is uncommon. The relative importance of these goals and timing of their attainment on cardiovascular events is uncertain.

Objectives: This study aims to describe the relationship between achieving specific GDMT goals, when they are achieved, and clinical outcomes.

Methods: This was an observational study of participants with CCD in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. The primary outcome was cardiovascular (CV) death or myocardial infarction (MI). GDMT goals …

First-In-Human Phase I Study Of A Cd16a Bispecific Innate Cell Engager, Afm24, Targeting Egfr-Expressing Solid Tumors, Anthony El-Khoueiry, Todd A Fehniger, Mark Foster, Melissa M Berrien-Elliott, Et Al.

2020-Current year OA Pubs

PURPOSE: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on NK cells/macrophages and EGFR on tumor cells, redirecting antitumor activity toward tumors. The safety and tolerability of AFM24 were evaluated in this phase I/IIa dose-escalation/dose-expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

PATIENTS AND METHODS: The main objective in phase I was to determine the MTD and/or recommended phase II dose. The primary endpoint was the incidence of dose-limiting toxicities during the observation period. Secondary endpoints included the incidence …

Genomic Analysis Of 11,555 Probands Identifies 60 Dominant Congenital Heart Disease Genes, Michael C Sierant, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes in 11,555 CHD probands. The results identified 60 genes with a significant burden of heterozygous damaging variants. Variants in these genes accounted for CHD in 10.1% of probands with similar contributions from de novo and transmitted variants in parent-offspring trios that showed incomplete penetrance. DNMs in these genes accounted for 58% of the signal from DNMs. Thirty-three genes were linked to a single CHD subtype while 12 genes were associated with 2 to …

Hypertension Diagnosis And Management In Bamako, Mali, Issiaka Camara, Mohamed Traore, Mamoudou Maiga, Dike Ojji, Jane Holl, Souleymane Coulibaly, Mark D Huffman

2020-Current year OA Pubs

PROBLEM: The capacity and site readiness for delivering hypertension management services in Mali were unknown, hindering the effective implementation of the World Health Organization (WHO) HEARTS technical package for cardiovascular disease management.

APPROACH: We selected one tertiary and two secondary hospitals to be assessed. From December 2021 to January 2022, hospital cardiologists collected data on indicators of capacity and site readiness using an adapted version of the WHO service availability and readiness assessment questionnaire. The study team verified the collected data through site inspection and review of administrative documents.

LOCAL SETTING: Mali, a low-income country with a population of 22 …

Systemic Inflammation Is Associated With Worse Outcomes From Sars-Cov-2 Infection But Not Neutralizing Antibody, Christopher W Farnsworth, Brittany Roemmich, John Prostko, Gerard Davis, Gillian Murtagh, Laurel Jackson, Christopher Jacobson, Nicolette Jeanblanc, Timothy Griffiths, Edwin Frias, David J Daghfal

2020-Current year OA Pubs

Systemic inflammation is associated with COVID-19 mortality rates, but the impact of inflammation on neutralizing antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and on outcomes is poorly understood. This study aimed to determine the association between neutralizing antibody responses, inflammation, and clinical outcomes in hospitalized patients with COVID-19. Two hundred and eight patients presenting to the ED with symptomatic SARS-CoV-2 were included. Neutralization was assessed using the architect angiotensin-converting enzyme-2 (ACE2) binding inhibition assay, and inflammation was assessed using C reactive protein (CRP) and interleukin 6 (IL-6). Medical records were examined for 30-day mortality and 10-day intubation. Correlation …

Current Burden Of Steatotic Liver Disease And Fibrosis Among Adults In The United States, 2017-2023, Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed

Faculty, Staff and Students Publications

Background/aims: Multi-society experts proposed the adoption of new terminology, metabolic dysfunctionassociated steatotic liver disease (MASLD) and steatotic liver disease (SLD). We studied the current prevalence of SLD and its subcategories in the US.

Methods: Using the recent National Health and Nutrition Examination Survey from 2017 to 2023, we analyzed data from 12,199 participants (≥18 years) who completed transient elastography. SLD and its subcategories, including MASLD, metabolic and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), were categorized according to consensus nomenclature.

Results: The age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% confidence interval [CI] 33.4-36.7). Within this …

Career Choices For Graduates Of Combined Medicine-Pediatrics Residency Programs: A Multi-Year Survey, Anoop Agrawal, Michael Aronica, Michael Kisielewski, Benjamin Doolittle

Faculty, Staff and Students Publications

Background: Combined medicine-pediatrics training was formally established in 1967 by the American Board of Pediatrics and the American Board of Internal Medicine. More than 8000 physicians have completed dual training. Their career choices are not well-described.

Objective: To describe career choices among graduates of combined medicine-pediatrics training programs.

Methods: Nationally representative research surveys conducted each winter from 2017 to 2023 of combined medicine-pediatrics (Med-Peds) residency program directors (PDs), whose programs were (1) of continued accreditation status with the Accreditation Council for Graduate Medical Education (N = 77 to 80) and (2) members of the Medicine Pediatrics Program Directors Association. One …

Foamy Monocytes And Atherogenesis In Mice With Combined Hyperlipidemia And Effects Of Antisense Knockdown Of Apociii, Xueying Peng, Zeqin Lian, Veronica O'Brien, Jing Xiao, Benjamin A Litchfield, Xiao-Yuan Dai Perrard, Lu Xu, Jing Ni, Aparna Mukherjee, Timothy Simmons, Henry Dong, Adam E Mullick, Rosanne Crooke, Henry J Pownall, Scott I Simon, Christie M Ballantyne, Huaizhu Wu

Faculty, Staff and Students Publications

Hypertriglyceridemia (HTG), particularly in combined hyperlipidemia, increases risk for atherosclerotic cardiovascular disease, but the underlying mechanisms remain incompletely understood. We sought to determine contributions of circulating monocytes to atherosclerosis associated with HTG in combined hyperlipidemia, created by transgenic expression of human apoCIII in Ldlr−/− mice (Ldlr−/−ApoCIIItg) fed Western high-fat diet (WD). Tissue culture with THP-1 and primary human monocytes was used to examine effects of triglyceride (TG)-rich lipoproteins on monocytes. Ldlr−/−ApoCIIItg mice were also treated with apoCIII antisense oligonucleotide (ASO) and examined for foamy monocytes and atherosclerosis. Compared to Ldlr−/− mice, Ldlr−/−ApoCIIItg mice fed …

Telehealth Is Effective In The Evaluation Of Individuals With Undiagnosed Rare Disorders: An Undiagnosed Diseases Network Study, Queenie K-G Tan, Allyn Mcconkie-Rosell, Rachel Mahoney, Rebecca C Spillmann, Kelly Schoch, Sirisak Chanprasert, Maria T Acosta, Camilo Toro, Jill A Rosenfeld, James P Orengo, Daryl A Scott, Jorge L Granadillo, Kathleen Sisco, Daniel J Wegner, Mustafa Tekin, Stephanie Bivona, Léshon Peart, Lance Rodan, Devon Bonner, Matthew T Wheeler, Jonathan A Bernstein, Maura Ruzhnikov, Undiagnosed Diseases Network, David R Adams, Fuki M Hisama, Vandana Shashi

Faculty, Staff and Students Publications

Patients with undiagnosed and/or rare disorders frequently manifest dysmorphic and neurological features. There is a lack of information on the effectiveness of telehealth in the evaluation of these disorders. We thus compared an unassisted virtual physical examination (PE) with an in-person PE in undiagnosed individuals and also assessed participant telehealth satisfaction. Twenty-six individuals enrolled in the Undiagnosed Diseases Network study underwent an in-home synchronous virtual PE, and a subsequent in-person PE, by the same clinician. The participants completed surveys on telehealth usability and provider empathy. On PE, general appearance and craniofacial features showed near perfect agreement (κ = 0.81-1.00) between …

Clinical And Genetic Delineation Of Autosomal Recessive And Dominant Actl6b-Related Developmental Brain Disorders, Elisa Cali, Tania Quirin, Clarissa Rocca, Stephanie Efthymiou, Antonella Riva, Dana Marafi, Maha S Zaki, Mohnish Suri, Roberto Dominguez, Hasnaa M Elbendary, Shahryar Alavi, Mohamed S Abdel-Hamid, Heba Morsy, Frederic Tran Mau-Them, Mathilde Nizon, Pavel Tesner, Lukáš Ryba, Faisal Zafar, Nuzhat Rana, Nebal W Saadi, Zahra Firoozfar, Pinar Gencpinar, Bulent Unay, Canan Ustun, Ange-Line Bruel, Christine Coubes, Jennifer Stefanich, Ozlem Sezer, Emanuele Agolini, Antonio Novelli, Gessica Vasco, Donatella Lettori, Mathieu Milh, Laurent Villard, Shimriet Zeidler, Henry Opperman, Vincent Strehlow, Mahmoud Y Issa, Hebatallah El Khassab, Prem Chand, Shahnaz Ibrahim, Ali Rashidi-Nezhad, Mohammad Miryounesi, Pegah Larki, Jennifer Morrison, Ingrid Cristian, Isabelle Thiffault, Nicole L Bertsch, Grace J Noh, John Pappas, Ellen Moran, Nikolaos M Marinakis, Joanne Traeger-Synodinos, Susan Hosseini, Mohammad Reza Abbaszadegan, Roseline Caumes, Lisenka E L M Vissers, Maedeh Neshatdoust, Mostafa Montazer Zohour, Elmostafa El Fahime, Christina Canavati, Lara Kamal, Moien Kanaan, Omar Askander, Victoria Voinova, Olga Levchenko, Shahzhad Haider, Sara S Halbach, Rayana Elias Maia, Salehi Mansoor, Vivek Jain, Sanjukta Tawde, Viveka Santhosh R Challa, Vykuntaraju K Gowda, Varunvenkat M Srinivasan, Lucas Alves Victor, Benito Pinero-Banos, Jennifer Hague, Heba Ahmed Elawady, Adelia Maria De Miranda Henriques-Souza, Huma Arshad Cheema, Muhammad Nadeem Anjum, Sara Idkaidak, Firas Alqarajeh, Osama Atawneh, Hagar Mor-Shaked, Tamar Harel, Giovanni Zifarelli, Peter Bauer, Fernando Kok, Joao Paulo Kitajima, Fabiola Monteiro, Juliana Josahkian, Gaetan Lesca, Nicolas Chatron, Dorothe Ville, David Murphy, Jeffrey L Neul, Sureni V Mullegama, Amber Begtrup, Isabella Herman, Tadahiro Mitani, Jennifer E Posey, Chee Geap Tay, Iram Javed, Lucinda Carr, Farah Kanani, Fiona Beecroft, Lee Hane, Elsayed Abdelkreem, Milan Macek, Luciana Bispo, Marwa Abd Elmaksoud, Farzad Hashemi-Gorji, Davut Pehlivan, David J Amor, Rami Abou Jamra, Wendy K Chung, Eshan Ghayoor Karimiani, Philippe M Campeau, Fowzan S Alkuraya, Alistair T Pagnamenta, Joseph G Gleeson, James R Lupski, Pasquale Striano, Andres Moreno-De-Luca, Denis L J Lafontaine, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis.

Results: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absent speech, autistic features, dystonia, …

Foraging Animals Use Dynamic Bayesian Updating To Model Meta-Uncertainty In Environment Representations, James Webb, Paul Steffan, Benjamin Y Hayden, Daeyeol Lee, Caleb Kemere, Matthew Mcginley

Faculty, Staff and Students Publications

Foraging theory predicts animal behavior in many contexts. In patch-based foraging behaviors, the marginal value theorem (MVT) gives the optimal strategy for deterministic environments whose parameters are fully known to the forager. In natural settings, environmental parameters exhibit variability and are only partially known to the animal based on its experience, creating uncertainty. Models of uncertainty in foraging are well established. However, natural environments also exhibit unpredicted changes in their statistics. As a result, animals must ascertain whether the currently observed quality of the environment is consistent with their internal models, or whether something has changed, creating meta-uncertainty. Behavioral strategies …

Predictors And Outcomes Of First Pass Efficacy In Posterior Circulation Strokes: Insights From Star Collaboration, Muhammad U Hafeez, Muhammed A Essibayi, Daniel Raper, Omar Tanweer, Mithun Sattur, Sami Al-Kasab, Joshua Burks, Robert Townsend, Diana Alsbrook, Travis Dumont, Min S Park, Nitin Goyal, Adam S Arthur, Ilko Maier, Justin Mascitelli, Robert Starke, Stacey Wolfe, Kyle Fargen, Alejandro Spiotta, Peter T Kan

Faculty, Staff and Students Publications

Background: First-pass efficacy (FPE) has been established as an important predictor of favorable functional outcomes after endovascular thrombectomy (ET) in anterior circulation strokes. In this retrospective cohort study, we investigate predictors and clinical outcomes of FPE in posterior circulation strokes (pcAIS).

Methods: The Stroke Thrombectomy and Aneurysm Registry database was used to identify pcAIS patients who achieved FPE. Their baseline characteristics and outcomes were compared with the non-FPE group. The primary outcome was a 90-day modified Rankin Scale (mRS) of 0-3. Univariate (UVA) and multivariate (MVA) analyses were done to evaluate predictors of FPE. Safety outcomes included distal emboli, vessel …

Atrial Cardiomyocyte-Restricted Cleavage Of Gasdermin D Promotes Atrial Arrhythmogenesis, Yue Yuan, Pascal Martsch, Xiaohui Chen, Enrique Martinez, Luge Li, Jia Song, Theresa Poppenborg, Florian Bruns, Jong Hwan Kim, Markus Kamler, James F Martin, Issam Abu-Taha, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

Background and aims: Enhanced inflammatory signalling causally contributes to atrial fibrillation (AF) development. Gasdermin D (GSDMD) is an important downstream effector of several inflammasome pathways. However, the role of GSDMD, particularly the cleaved N-terminal (NT)-GSDMD, in non-immune cells remains elusive. This study aimed to elucidate the function of NT-GSDMD in atrial cardiomyocytes (ACMs) and determine its contribution to atrial arrhythmogenesis.

Methods: Human atrial appendages were used to assess the protein levels and localization. A modified adeno-associated virus 9 was employed to establish ACM-restricted overexpression of NT-GSDMD in mice.

Results: The cleavage of GSDMD was enhanced in ACMs of AF patients. …

Postnatal Zika And Dengue Infection And Their Effects On Neurodevelopment Among Children Living In Rural Guatemala, Edwin J Asturias, Amy K Connery, Daniel Olson, Molly M Lamb, Alejandra Paniagua-Avila, Evan J Anderson, Chris Focht, Alison M Colbert, Muktha Natrajan, Jesse J Waggoner, Erin Scherer, D Mirella Calvimontes, Guillermo A Bolaños, Desirée Bauer, Paola Arroyave, Sara Hernández, Maria A Martinez, Aida V Ralda, Neudy Rojop, Edgar E Barrios, Andrea Chacon, Walla Dempsey, Kay M Tomashek, Wendy A Keitel, Hana M El Sahly, Flor M Muñoz

Faculty, Staff and Students Publications

Background: Prenatal Zika virus (ZIKV) infection leads to microcephaly and adverse neurodevelopment. The effects of postnatal ZIKV infection on the developing brain are unknown. We assessed the neurodevelopmental outcomes of children exposed postnatally during the ZIKV epidemic.

Methods: A prospective study enrolled infants 0-3 months of age and their mothers, and children 1.5-3.5 years of age in rural Guatemala from 2017 and were followed for 12 months until 2019. Neurodevelopment was evaluated using the Mullen Scales of Early Learning (MSEL). ZIKV and dengue virus (DENV) infections were identified by polymerase chain reaction (PCR) using active surveillance. Serological analyses, stratified by …

Hospital-Onset Bacteremia In The Neonatal Intensive Care Unit: Strategies For Risk Adjustment, Erica C Prochaska, Shaoming Xiao, Elizabeth Colantuoni, Nora Elhaissouni, Reese H Clark, Julia Johnson, Sagori Mukhopadhyay, Ibukunoluwa C Kalu, Danielle M Zerr, Patrick J Reich, Jessica Roberts, Dustin D Flannery, Aaron M Milstone, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

OBJECTIVE: To quantify the impact of patient- and unit-level risk adjustment on infant hospital-onset bacteremia (HOB) standardized infection ratio (SIR) ranking.

DESIGN: A retrospective, multicenter cohort study.

SETTING AND PARTICIPANTS: Infants admitted to 284 neonatal intensive care units (NICUs) in the United States between 2016 and 2021.

METHODS: Expected HOB rates and SIRs were calculated using four adjustment strategies: birthweight (model 1), birthweight and postnatal age (model 2), birthweight and NICU complexity (model 3), and birthweight, postnatal age, and NICU complexity (model 4). Sites were ranked according to the unadjusted HOB rate, and these rankings were compared to rankings based …

Combined Systemic Immunotherapy And Intrathecal Dexamethasone In Febrile Infection Related Epilepsy Syndrome, Kristen S Fisher, Alexander Ankar, Jon Cokley, Eyal Muscal, James J Riviello, Yi-Chen Lai

Faculty, Staff and Students Publications

Febrile infection related epilepsy syndrome (FIRES) is a rare presentation of refractory status epilepticus with immune dysregulation as a potential pathologic mechanism. Despite promising results from second-line immunomodulators, approximately 30% remain refractory to treatment. We describe two children with FIRES who were unable to wean from anesthetic infusions with immunomodulatory treatment and subsequently received concurrent intrathecal dexamethasone and anakinra/tocilizumab as escalation of therapy. Following the initiation of this combined regimen, anesthetic infusions were decreased while maintaining seizure freedom. These cases demonstrate proof of principle that a multi-modal approach may be beneficial and should be considered in the treatment of FIRES.

Preferences For Survivorship Education And Delivery Among Latino And Non-Latino Childhood Cancer Survivors And Caregivers, Omar Shakeel, Shiley Aguilar, Alicia Howell, Ashley Ikwuezunma, Olga Taylor, M Fatih Okcu, Ranjan Bista, Jill Hartley, Rodrigo Eraña, Juan Carlos Bernini, Lisa Kahalley, Michael Scheurer, Maria Monica Gramatges

Faculty, Staff and Students Publications

Purpose: To assess survivor and parent perceptions of the long-term survivor visit and preferences regarding accessing health information, survivorship education, and support networks in rural and metropolitan regions of Texas.

Methods: Leveraging the multi-institutional Survivorship and Access to Care for Latinos to Understand Disparities (SALUD) cohort, we administered a 26-item bilingual survey to adult survivors of childhood cancer and parents of younger survivors. Characteristics and responses were compared between survivors vs. parents and Latinos vs. non-Latinos using a t test or Fisher exact test. Odds ratios for the outcomes of interest were calculated with 95% confidence intervals.

Results: We received …

Inhibitory Specificity From A Connectomic Census Of Mouse Visual Cortex, Casey M Schneider-Mizell, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Leila Elabbady, Clare Gamlin, Daniel Kapner, Sam Kinn, Gayathri Mahalingam, Sharmishtaa Seshamani, Shelby Suckow, Marc Takeno, Russel Torres, Wenjing Yin, Sven Dorkenwald, J Alexander Bae, Manuel A Castro, Akhilesh Halageri, Zhen Jia, Chris Jordan, Nico Kemnitz, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, William Silversmith, Nicholas L Turner, William Wong, Jingpeng Wu, Jacob Reimer, Andreas S Tolias, H Sebastian Seung, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa

Faculty, Staff and Students Publications

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties1. Synaptic connectivity shapes how each cell type participates in the cortical circuit, but mapping connectivity rules at the resolution of distinct cell types remains difficult. Here we used millimetre-scale volumetric electron microscopy2 to investigate the connectivity of all inhibitory neurons across a densely segmented neuronal population of 1,352 cells spanning all layers of mouse visual cortex, producing a wiring diagram of inhibition with more than 70,000 synapses. Inspired by classical neuroanatomy, we classified inhibitory neurons based on targeting of …