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A Phase-Ii Randomized Controlled Pilot Study Of Nicotinamide Riboside Supplementation In Older Adults With Amnestic Mild Cognitive Impairment, Christopher Martens, Kevin Decker, Theodore Deconne, Faria Sanjana, Fiona Horvat, Nicholas Rizzi, Catherine Awad, Elizabeth Habash, Joshua Hobson, Mary Kramer, Michael Armstrong, Nichole Reisdorph, Ryan Pohlig, Alyssa Lanzi, Curtis Johnson, Matthew Cohen, James Ellison

Department of Psychiatry and Human Behavior Faculty Papers

INTRODUCTION: Declining nicotinamide adenine dinucleotide (NAD+) may elevate risk of Alzheimer's disease.

METHODS: We conducted a 12-week double-blind, randomized, placebo-controlled pilot study to evaluate the safety, tolerability, and preliminary efficacy of the NAD+ precursor, nicotinamide riboside (NR), for enhancing cognitive function and cerebral blood flow (CBF) in adults with amnestic mild cognitive impairment (aMCI).

RESULTS: 42 participants completed the study (NR = 22, placebo = 20). Adherence was similar between groups with no serious adverse effects. Blood NAD+ increased twofold in the NR group. There were no improvements in cognitive function (primary outcome), total CBF, or blood pressure (secondary outcomes). …

Relationship Of Early Rapid Weight Loss To Efficacy And Safety Of Tirzepatide And Semaglutide For Obesity: Surmount-5 Post Hoc Analysis, Louis J Aronne, Deborah B Horn, Alexander D Kokkinos, Beverly L Falcon, Hui Wang, Hunter T Hoffmann, Clare J Lee, Julia P Dunn

Faculty, Staff and Student Publications

Background: A knowledge gap remains in how the rate of body weight reduction impacts efficacy and safety of obesity management medications. This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.

Methods: Rapid responders and non-rapid responders were defined as participants that obtained ≥ 15% and < 15% body weight reduction by Week 24, respectively. Baseline characteristics, and proportion of participants achieving body weight reduction thresholds by Week 72 were assessed. End-of-study safety and gastrointestinal adverse events measures were summarized.

Results: Overall, 32.3% were rapid responders (tirzepatide: 44%, semaglutide: 21%). The proportions of participants achieving body weight reduction thresholds by Week 72 were higher for rapid responders versus non-rapid responders. Safety trends for tirzepatide and semaglutide were similar between …

Proteogenomics Of Hypertrophic Cardiomyopathy Reveals Subtype-Specific Therapy, Ke Ma, Jie Yang, Hongchang Guo, Ping Li, Xiaowei Li, Zhujun Dong, Jing Zhang, Congcong Zhang, Pengli Yang, Chongpei Hua, Shuolin Zhu, Guoqing Li, Jianchao Zhang, Ningyu Ding, Jizheng Wang, Xin-Liang Ma, Zhuofeng Lin, Jianzeng Dong, Yang Li, Yulin Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease with diverse prognosis. The underlying mechanisms remain unknown, resulting in limited risk stratification and therapeutic strategies. This study aimed to elucidate molecular subtypes of HCM through integrated proteogenomic analysis and explore subtype-specific therapeutic strategies.

METHODS: We conducted an integrated proteogenomic analysis of 132 patients with HCM using myocardial samples, incorporating whole-exome sequencing, RNA sequencing, and proteomics. Unsupervised clustering was used to identify HCM subtypes, which were validated in heart tissues and human induced pluripotent stem cell-derived cardiomyocytes from 2 independent HCM subsets. Subtype-specific signatures and pathways were explored, and their causal link …

Donor-Derived Cell-Free Dna As A Prognostic Biomarker After Heart Transplantation: The Define-Ht Study, Palak Shah, Paul J. Kim, Kelly H. Schlendorf, David A. Baran, Monica M. Colvin, Adam D. Devore, Howard Eisen, Kambiz Ghafourian, Michael M. Givertz, Eileen Hsich, Jaime L. W. Kennedy, Evan P. Kransdorf, Jose N. Nativi-Nicolau, Jignesh Patel, Eleni Tseliou, Omar Wever-Pinzon, Andrew Doud, Michelle S. Bloom, Sandra A. Carey, Navchetan Kaur, D Giovanni Biagini, Kyle E. Marshall, Michael Olympios, Mandeep R. Mehra, Josef Stehlik

Department of Medicine Faculty Papers

BACKGROUND: Measurement of donor-derived cell-free DNA fraction (dd-cfDNA%) and donor quantity score (DQS) is a noninvasive biomarker of acute rejection in heart transplantation (HT). Its prognostic value beyond histopathology remains uncertain.

OBJECTIVES: This study sought to evaluate associations between donor-derived cell-free DNA (dd-cfDNA) and clinically meaningful outcomes using a composite endpoint of treated rejection, graft dysfunction, retransplantation, or death within 1 year post-HT.

METHODS: The DEFINE-HT (Development of Noninvasive Cell-free DNA to Supplant Invasive Biopsy in Heart Transplantation) was a prospective, observational study following adult HT recipients at 10 U.S. centers for 1-year post-HT; blood was collected for dd-cfDNA testing …

Pearson Syndrome: Expanding The Clinical Spectrum Of A Mitochondrial Cytopathy-A Case Report, Alizah Faisal, Hooria Waqas, Hania Masood, Armeen Butt, Saad Rahman, Muhammad Sheraz Hameed, Syed Rafay Hussain Zaidi, Ali Iqbal, Muhammad Usama Naveed

Department of Medicine Faculty Papers

BACKGROUND: Pearson syndrome (PS) is a rare multisystem mitochondrial disorder characterized by single large-scale mitochondrial DNA deletions (SLSMDs). It typically presents in infancy with refractory sideroblastic anemia, exocrine pancreatic insufficiency, and failure to thrive. Due to its heterogeneous manifestations and resemblance to other hematological conditions, early diagnosis remains a clinical challenge.

CASE PRESENTATION: A south asian male infant presented with persistent pancytopenia, severe anemia unresponsive to intravenous and oral iron and multivitamin supplements, exocrine pancreatic insufficiency, failure to thrive, and metabolic acidosis. Born to consanguineous parents, the child had a significant family history of early infant deaths and hematological abnormalities. …

Mapping Dna Methylation Signatures To Identify Epigenetic Variation Across Subcortical Regions Of The Human Posttraumatic Stress Disorder Brain, Hongyu Li, Yujing Liu, Yiming Shi, Jiawei Wang, Tuan P Nguyen, Yuhan Xie, Wangjie Zheng, Youshu Cheng, Dianne A Cruz, Jennifer L Modliszewski, Rosemarie Terwilliger, Alexa-Nicole Sliby, José Jaime Martínez-Magaña, Janitza L Montalvo-Ortiz, John D Roache, Lynnette A Averill, Stacey Young-Mccaughan, Paulo R Shiroma, Bertrand R Huber, David A Lewis, Jill Glausier, Paul Holtzheimer, Matthew J Friedman, Jing Zhang, Alan L Peterson, Chadi G Abdallah, Amir Valizadeh, Xinyu Zhang, Ke Xu, John H Krystal, Ronald S Duman, Hongyu Zhao, David L Corcoran, Douglas E Williamson, Matthew J Girgenti

Staff and Researcher Publications

Background: Posttraumatic stress disorder (PTSD) is a mental disorder that may occur in the aftermath of severe psychological trauma. Epigenetic changes in the brain may play a critical role in understanding the neurobiology of PTSD by linking environmental traumatic stress exposure to lasting alterations in gene expression that shape neuronal function.

Methods: We examined 1,065,750 DNA methylation (DNAm) sites from 171 donors including neurotypical controls and PTSD and major depressive disorder (MDD) cases across 6 regions implicated in the fear circuitry of the brain. We performed RNA sequencing (RNA-seq) to examine changes in gene expression and linked these changes to …

An Integrated Cardiometabolic Genetic Testing Program In A Predominantly Hispanic Population Within A Community Setting, Bo Yuan, Layla A Abushamat, Stacey Pereira, Surya Narayan Mulukutla, Grace E Tietz, Eric Venner, Sara E Kalla, Breanna Lee, Donna Muzny, Ginger Metcalf, Mullai Murugan, Sarah H Elsea, Senkottuvelan Kadirvel, Lele Li, Joshi Stephen, Shengfeng Xu, Victoria Yi, Monica Sulit, Christie L Kovar, Kimberly Walker, Marie-Claude Gingras, Jianhong Hu, Fei Yan, Taeko Gerber, Viktoriya Korchina, C Michael Fordis, Ruchi Gaba, Mahesh Changlani, Herschl Silberman, Hadley Stevens Smith, Christine M Eng, Jennifer E Posey, Clarisa Medina, Lisa R Treviño, Christie M Ballantyne, Richard A Gibbs, Ashok Balasubramanyam

Center for Medical Ethics and Health Policy Staff Publications

Purpose: This study aimed to apply cardiometabolic genetic testing in a community setting with a predominantly Hispanic population and assess feasibility and perspectives toward genetic testing.

Methods: A genome-sequencing-based genetic panel for cardiometabolic disorders (177 genes related to monogenic conditions, 2 LPA risk alleles, 2 pharmacogenomic loci, and ancestry-adjusted polygenic risk scores for type 2 diabetes and coronary artery disease) was deployed in community cardiology and endocrinology clinics in South Texas. A survey on perceptions toward genetic testing was administered after return of results.

Results: Testing was completed for 776 patients (18-92 years old, 92% Hispanic). 26 patients (3.4%) were …

Patient Perspectives On Psychiatric Polygenic Risk Scores In Reproductive Decision-Making And Polygenic Embryo Screening., Lauren A Ginn, Amanda R Merner, Page M Trotter, Kaitlynn P Craig, Abigail C Martinez, Ana Lucía Battaglino, Dorit Barlevy, Daphne M Ayton, Takahiro Soda, Eric A Storch, Gabriel Lázaro-Muñoz, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Polygenic risk scores (PRS) estimate individuals' genetic risk for developing multifactorial conditions. Recent genome-wide association studies have enabled development of psychiatric PRS, which hold potential to streamline diagnosis and treatment of psychiatric conditions. As individuals with mental illness often identify concern about passing on psychiatric conditions as a key factor in family planning, some may also seek to use psychiatric PRS in reproductive decisions like childbearing or embryo selection for in vitro fertilization. Despite calls for increased regulation, there remains no clinical consensus on the utility of psychiatric PRS in reproductive contexts. Therefore, we conducted semi-structured interviews of adults with …

Clinical Features And Dental Pathologies In Maxillary Sinus Fungal Balls And Odontogenic Sinusitis, Eunice Im, Lane Donaldson, Avraham Adelman, Nithin D Adappa, Yi-Wei Chen, Nikita Chapurin, Jennifer E Douglas, Glen E D'Souza, Jacob Eide, Maria Espinosa, Chia-Hsiang Fu, Meha G Fox, Rohit Garg, Edward C Kuan, Michael A Kohanski, Marta Kwiatkowska, Kevin Li, Derek H Liu, Tran Bao Locke, Chih-Feng Lin, Chadi Makary, Alice Ottavi, Peter Papagiannopoulos, James N Palmer, Charles C L Tong, Bobby A Tajudeen, Sanjena Venkatesh, Kimberly Wei, Frederick Yoo, Alison J Yu, Jun Jin, Alberto M Saibene, John R Craig

Faculty, Staff and Students Publications

Objectives: While maxillary sinus fungal balls (MSFB) can be associated with odontogenic conditions (MSFBO), MSFBO clinical and dental features have not been compared to odontogenic sinusitis (ODS). This multicenter study aimed to compare characteristics of MSFB, MSFBO, and ODS.

Methods: A multicenter international retrospective cohort study was conducted on adults with MSFBs and ODS who underwent sinus surgery. First in MSFBs, it was determined whether different dental conditions were more likely in FB versus non-FB sides. Second, clinical features and dental pathologies were compared between MSFBO and ODS. For analyses, dental conditions were considered individually and as two groups: infectious …

Social Determinants As Pathways In Disparities In Oral Cavity Cancer Stage At Diagnosis: A Registry-Based Analysis From 2010–2020, Guillermo A Tortolero, Erich M Sturgis, Itunu O Sokale, Abiodun Oluyomi, Kristina R Dahlstrom, Aaron P Thrift

Faculty, Staff and Students Publications

Purpose: Racial and ethnic differences in oral cavity cancer (OCC) stage at diagnosis are substantial, but the reasons remain unclear. We assessed insurance status and social neighborhood factors as potential pathways.

Methods: Using the Texas Cancer Registry, we identified adults diagnosed with OCC between 2010 and 2020. We examined the crude and multivariable associations of race and ethnicity, insurance status, and social neighborhood factors with stage at diagnosis. We investigated the mediating effects of insurance status and neighborhood-level social factors on racial and ethnic differences in stage at diagnosis using four-way decomposition with modified Poisson regression and robust standard errors. …

Adlm Guidance Document On Incorporating Gender Diversity In Pathology And Laboratory Medicine, Tiffany A Thomas, Gabrielle N Winston-Mcpherson, Ina Amarillo, Alisha D Berry, Caroline J Davidge-Pitts, Sridevi Devaraj, Zil Goldstein, Brad S Karon, Brooke M Katzman, Mahmoud A Khalifa, Hung S Luu, James H Nichols, Tracy L Stockley, Michelle R Stoffel, Dina N Greene, Matthew D Krasowski

Faculty, Staff and Students Publications

Background: The first international clinical standards of care for the gender-diverse population were formulated in the late 1970s. In the last 15 years, multiple subspecialty societies within the United States have developed clinical care guidelines for those with gender dysphoria, including gender-affirming hormone therapy (GAHT) and surgical treatments. To date, there are no pathology- and laboratory medicine-specific recommendations in the United States for the gender-diverse population.

Content: This document outlines pathology- and laboratory medicine-specific recommendations for providing optimal care to the gender-diverse population, with a predominant focus on the adult population. The scope of this document focuses on the following …

Upholding Our Promise: Negotiating Belonging And Professional Identity Formation In Underrepresented In Medicine Pediatric Residents, Oriaku A Kas-Osoka, Courtney A Gilliam, Lahia Yemane, Candice Taylor Lucas, Rebecca Blankenburg, H Mollie Grow, Laura Kester-Prakash, Jyothi Marbin, Patricia Poitevien, Audrea M Burns

Faculty, Staff and Students Publications

Objective: To explore UIM pediatric residents' perspectives on how belonging impacts PIF and Well-BP.

Methods: We conducted a national qualitative study grounded in a critical interpretivist paradigm using virtual focus groups with UIM pediatric residents between June 2022 and April 2023. Data were analyzed by 4 authors using reflexive thematic analysis until theoretical sufficiency was reached. Member-checking was conducted to ensure the trustworthiness of the themes.

Results: Twenty-four UIM pediatric residents across 20 programs participated. Five themes emerged as follows: 1) Belonging is a dynamic process shaped by daily affirmations and invalidations; 2) Clinical learning environments often erode belonging through …

Reclassifying Pediatric Nafld Using The Steatotic Liver Disease Framework: A Multicenter Retrospective Study From The Nash Crn, Tin Bo Nicholas Lam, Katherine P Yates, Sheila L Noon, Kimberly P Newton, Mark H Fishbein, Jean P Molleston, Stavra A Xanthakos, Ajay K Jain, Miriam B Vos, Niviann M Blondet, Krupa R Mysore, Cynthia A Behling, Laura A Wilson, Jeffrey B Schwimmer

Faculty, Staff and Students Publications

Background and aims: The terminology for hepatic steatosis and NAFLD was revised under the umbrella of steatotic liver disease, with metabolic dysfunction-associated steatotic liver disease (MASLD) as the primary subtype. MASLD is defined by hepatic steatosis plus at least 1 cardiometabolic risk factor. A new category, Met-ALD, describes MASLD with alcohol consumption below the defined thresholds for alcohol-associated liver disease (ALD). While adult studies have demonstrated strong concordance between NAFLD and MASLD, the applicability of this framework in children remains unclear.

Approach and results: We assessed children clinically diagnosed with NAFLD and enrolled in the NASH CRN who had available …

Epinephrine Underuse For Anaphylaxis In Infants And Toddlers: A Practical Review For Pediatricians, Stephanie Leeds, Aikaterini Anagnostou, Michael Pistiner, Jay Lieberman, Nicole B Ramsey, Rachael Griffiths, Julie Wang

Faculty, Staff and Students Publications

A recent consensus report defined anaphylaxis as a serious allergic reaction that may involve the skin/mucosa, respiratory, cardiovascular, and/or gastrointestinal systems that can progress rapidly and may cause death. Epinephrine treatment is recommended in suspected anaphylaxis cases; however, numerous barriers exist to consistent, widespread epinephrine use, including difficulty identifying anaphylaxis signs and symptoms; challenges recognizing when to use epinephrine; low propensity of prescribing and filling prescriptions; low epinephrine carrying rates; knowledge gaps in epinephrine administration techniques; fears of contacting emergency medical services; use of antihistamines, inhaled bronchodilators, and other medications as first-line agents over epinephrine; and limited epinephrine device availability …

Longitudinal And Cross-Sectional Evidence That Daily Resting And Activity Energy Expenditures Are Independent In Humans, Andrew K Yegian, Elizabeth Pachus, Leanne M Redman, Steven B Heymsfield, K Falkenhain, Alexandra R Harris, Shaji K Chacko, William W Wong, Daniel E Lieberman

Faculty, Staff and Students Publications

Total energy expenditure (TEE) is commonly modelled as the sum of resting energy expenditure (REE), activity energy expenditure (AEE), and diet-induced thermogenesis (DIT). This additive model has recently been challenged by the constrained energy balance model, which proposes that reductions in mass-adjusted REE compensate to some extent for increases in AEE, rendering mass-adjusted TEE effectively invariant. We tested these competing models using two complementary approaches. First, we conducted a short-term longitudinal, repeated-measures experiment in 12 adults who completed 10-day periods of high and low physical activity separated by a washout period. TEE was measured with doubly labelled water, AEE with …

Na-Gst-1 Adsorbed On Alhydrogel Co-Administered With Different Toll-Like Receptor Agonists In Hookworm-Naive Adults Using A Controlled Human Infection Model In The Usa: A Phase 2, Double-Blind, Randomised Controlled Trial, Caroline K Dirosato, Elissa M Malkin, Sean M Lee, Guacyara Erwin, Lara Hoeweler, Larissa Scholte, Maria Elena Bottazzi, David I Pritchard, Peter J Hotez, Jeffrey M Bethony, David J Diemert

Faculty, Staff and Students Publications

Background: Necator americanus glutathione S-transferase-1 (Na-GST-1) performs a crucial enzymatic step in hookworm blood feeding and is a leading target for vaccine development. Phase 1 trials in Brazil, Gabon, and the USA of recombinant Na-GST-1 adsorbed on Alhydrogel (Na-GST-1/Al), co-administered with or without AP 10-701 (Toll-like receptor [TLR] 4 agonist) or CpG 10104 (TLR9 agonist), showed the vaccine was well tolerated, safe, and immunogenic. A controlled human hookworm infection (CHHI) model was previously developed to evaluate the effect of candidate hookworm vaccines on infection. We aimed to assess the effect of vaccination with three different Na-GST-1 vaccine formulations on subsequent …

Helminth-Infected Mozambican Children With Malaria Have Increased Anaemia, Cytokines And Helminth-Specific Antibodies, Inocência Cuamba, Rebeca Santano, Berta Grau-Pujol, Marta Vidal, Anélsio Cossa, Chenjerai Jairoce, Rojelio Mejía, José Muñoz, Ruth Aguilar, Bin Zhan, Augusto Nhabomba, Gemma Moncunill, Carlota Dobaño

Faculty, Staff and Students Publications

Owing to their overlapping geographical distribution and the consequent occurrence of coinfections, several studies have evaluated the impact of helminth infections on malaria immune responses and clinical outcomes. However, little has been reported on how malaria coinfection affects anthelmintic responses in children harbouring worm infections. We therefore aimed to assess the impact of malaria coinfection on helminth-related clinical and immune outcomes in children. Here, we measured in plasma the levels of 30 cytokines, total IgE, and helminth-specific IgM, IgA, IgG, IgG1-4, and IgE antibodies to a panel of 11 helminth antigens by Luminex. Samples were obtained from 441 children aged …

An Examination Of Buprenorphine And Norbuprenorphine Concentrations In Inpatients Receiving Medications For Opioid Use Disorder, Michèle Haykal, Benjamin Li, Andres Avellaneda Ojeda, Roberto Sanchez, Nancy Shenoi, Asim Shah, Nidal Moukaddam

Faculty, Staff and Students Publications

Background: Interpretation of urine buprenorphine and norbuprenorphine concentrations is widely used to assess adherence during treatment for opioid use disorder. However, the relationships between dose, timing of sample collection, and metabolite ratios remain unclear, leading to potential misinterpretation in clinical practice.

Methods: Data were collected from patients on a psychiatry unit who were either inducted on or continued buprenorphine therapy and underwent urine testing for buprenorphine and its metabolite, norbuprenorphine. Urine samples were collected 16 to 786 min after the last buprenorphine dose. Norbuprenorphine-to-buprenorphine ratios were calculated. Data analysis using Python included polynomial regression and random forest models.

Results: Daily …

Blinded, Bias-Controlled Multi-Rater Evaluation Of Human-Versus-Ai Brain Metastasis Segmentation Using A Hybrid Foundation-Model Framework, Yiding Han, Enze Zhu, Mhd Hasan Ai Mekdash, Omar Awad, Piyush Pathak, Shixiao Liang, Daniel Allan Hamstra, Xizhe Zhang, Zaid Ali Siddiqui, Baozhou Sun

Faculty, Staff and Students Publications

Background: Accurate segmentation of brain metastases (BM) is essential for diagnosis, stereotactic radiosurgery planning, and longitudinal assessment. However, manual contouring is time-intensive, limiting clinical scalability, and exhibits substantial inter-observer variability. This variability complicates objective assessment of automated segmentation methods and challenges interpretation of model performance.

Purpose: To address these limitations, we developed TUM-SAM, a hybrid foundation-model framework for fully automated BM segmentation, and introduced a bias-controlled, blinded multi-rater evaluation paradigm to determine whether AI-based BM segmentation has reached expert-level performance and whether AI-generated contours are preferred by human experts under unbiased assessment.

Methods: TUM-SAM integrates nnU-Net-based lesion detection with a …

Comprehensive Assessment Of Direct And Passive Smoking Across The Pancreatitis Spectrum, Samuel Han, Dhiraj Yadav, Jun Xu, Melena D Bellin, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Liang Li, Stephen J Pandol, Walter G Park, Guru Trikudanathan, Stephen K Van Den Eeden, Santhi Swaroop Vege, Darwin L Conwell, Christie Y Jeon, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Objectives: Smoking is a key risk factor for pancreatitis, contributing to pathogenesis and disease progression. Data regarding second-hand smoking, or passive smoking (PS) exposure, are lacking. We therefore aimed to assess the impact of PS exposure across the pancreatitis spectrum.

Methods: We analyzed baseline data from the PROCEED study, a multicenter study in the United States including patients with acute (AP), recurrent acute (RAP), and chronic (CP) pancreatitis. Participants detailed their individual smoking history and PS exposure, which was compared between AP, RAP, and CP subgroups. Participant factors and clinical characteristics were compared by level of individual and PS exposure. …

Development Of An Educational Curriculum For The Surgical Implantation Of Dbs Systems, David Bieber, Rany T Abdallah, Alaa Ab-Elsayed, Adam R Burkey, Dario J Englot, Kunal Gupta, Charles N Munyon, Casey H Halpern, Kai J Miller, Joshua M Rosenow, Ahmed M Raslan, Konstantin V Slavin, Jennifer A Sweet, Sameer Sheth, Nestor Tomycz, Ashwin Viswanathan, Chengyuan Wu, Jeffrey S Raskin

Faculty, Staff and Students Publications

Background: Deep-brain stimulation (DBS) systems are implanted for movement disorders, epilepsy, and psychiatric conditions. Neurologic surgery remains the only discipline credentialed to implant DBS devices, although significant practice variation exists, partly due to heterogeneous training. The North American Neuromodulation Society (NANS) education committee offers a granular recommendation for the progression of an early learner through the practitioner level. It is contextualized within the six-core competency rubric for the surgical implantation of DBS devices.

Materials and methods: Guided by the Accreditation Council for Graduate Medical Education (ACGME) core competencies, a subcommittee of the NANS education committee met virtually and in-person over …

A Nationwide Central Diagnosis For Pediatric Cns Tumors In Japan: The Jccg Brain Tumor And Pathology Committees, Yoshiko Nakano, Junko Hirato, Takako Yoshioka, Tetsuya Takimoto, Sumihito Nobusawa, Kaishi Satomi, Ran Tomomasa, Seiji Yamada, Taku Homma, Shoh Sasaki, Ayako Yamazaki, Maki Sakaguchi, Yasuhide Takeuchi, Nei Fukazawa, Kai Yamasaki, Kohei Fukuoka, Yui Shinohara Kimura, Yuki Nagayama, Yohei Inoue, Akira Miyahira, Ema Yoshioka, Asako Katsuma, Hayato Fukusumi, Tomoko Shofuda, Yuko Hibiya, Yuko Matsushita, Mai Honda Kitahara, Yuki Yomoda, Miho Kato, Michael D Taylor, Yasuhito Arai, Tatsuhiro Shibata, Hiroaki Sakamoto, Keita Terashima, Yoshiki Arakawa, Toshihiro Kumabe, Ryo Nishikawa, Junichi Hara, Yonehiro Kanemura, Koichi Ichimura

Faculty, Staff and Students Publications

In 2016, the Japan Children's Cancer Group launched a nationwide research initiative to provide central diagnosis incorporating pathology review and molecular profiling for pediatric central nervous system (CNS) tumors. Over the first eight years, 2224 cases were registered. Non-next-generation sequencing analyzes, such as pyrosequencing and NanoString, were routinely performed, mainly for glioma, medulloblastoma, and ependymoma. Additional analyzes, including methylation profiling and RNA sequencing, were conducted for selected diagnostically challenging cases. The most common diagnoses were low-grade glioma (26%), medulloblastoma (18%), germ cell tumor (16%), high-grade glioma (12%), and ependymoma (11%). Diagnostic or targetable alterations were detected in nearly half of …

Fluocinolone Acetonide Implant As A Baseline Therapy For Diabetic Macular Edema: Results From The Randomized Phase 4 New Day Study, Michael A Singer, Charles C Wykoff, Christopher D Riemann, Victor H Gonzalez, Christina Y Weng, Kamel Alkhatib, Rohit A Amarshi, Scott Moody, Mary Pao

Faculty, Staff and Students Publications

Purpose: The NEW DAY (ClinicalTrials.gov identifier, NCT04469595) study assessed the efficacy and safety of the fluocinolone acetonide (FAc; 0.19 mg) intravitreal implant as baseline therapy in diabetic macular edema (DME).

Design: Prospective, randomized, single-masked, active-controlled, multicenter, 18-month, phase 4 study.

Participants: Adults with type 1 or 2 diabetes and center-involving DME confirmed by central subfield thickness (CST).

Methods: Treatment regimens were FAc implant followed by rescue supplemental injections of aflibercept if needed (2 mg/0.05 ml) for 17 months versus aflibercept loading dose (2 mg every 4 weeks for 5 consecutive doses) followed by rescue supplemental injections of aflibercept if …

Mental Health Stigma In Latin American Youth With Obsessive-Compulsive Disorder, Ryan J Mccarty, Matias Jensen, Elissa Paz Jensen Santa Cruz, Melisa N Sagarnaga, Pamela Claisse Quiroz, Tomás Miño, Paola Giusti-Rodriguez, Mayra C Martinez Mallen, Maria B Moyano, Dayan Berrones, Jacey L Anderberg, Renee M Frederick, Hannah C Moore, Josselyn S Muñoz, Vanessa Zavala Cruz, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Working Group (Gttoc), Ogechi C Onyeka, Andrew D Wiese, James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is an impairing mental health condition that affects individuals across the lifespan. Some literature has evaluated mental health stigma in adults with OCD but limited attention has been given to youth, as well as those of Latino ancestry. The present study reported the extent of stigma experiences among Latin American youth with OCD, as well as examined sociodemographic, clinical and psychological correlates. 235 youth with clinician confirmed diagnoses of OCD from 10 North and South American countries completed questionnaires assessing stigma experiences, symptomatology, and functioning. Sociodemographic and clinical variables were also collected. The average OCD stigma response …

Caregiver Satisfaction With Anxiety Treatment For Autistic Youth: A Mixed Methods Examination, Lesley A Norris, Jonathan C Rabner, Marika Marklin, Margaret E Crane, Kathrin Renschler, Emma Jenkins, Joshua Kemp, Eric A Storch, Jeffrey J Wood, Connor M Kerns, Adam B Lewin, Brent J Small, Philip C Kendall

Faculty, Staff and Students Publications

For Cognitive Behavioral Therapy to best meet the specific needs of autistic youth with co-occurring anxiety and to continue to grow as a sustainable treatment option, it is important to incorporate caregiver perspectives and feedback. Data were drawn from a randomized controlled trial and included 148 caregivers of autistic youth (ages 7-13 years, M = 9.89, SD = 1.79; 23% female; 77.7% White) with co-occurring anxiety disorders randomized to one of two active treatment conditions (Coping Cat, n = 72, or Behavioral Interventions for Anxiety in Children with Autism [BIACA], n = 76). A systematic inductive thematic analysis was used …

Reciprocal Compensation Of Caspase-2 And P53 Regulates The Dna Damage Response In Hct116 Colon Cancer Cells, Karla E Lopez, Leslie Bandera, Luiza E Coutinho, Karen Zúñiga, Sarah Wright, Lisa Bouchier-Hayes

Faculty, Staff and Students Publications

Caspase-2 has positive and negative effects on tumor growth in different cancer models. The mechanisms determining these dual outcomes of caspase-2 activation are unclear underscoring the need to assess caspase-2 function in different cell types. We report that high caspase-2 expression is associated with lower survival in patients with colon cancer and increased tumor size in HCT116 colon cancer xenografts. We investigated the interplay between caspase-2 and p53 in regulating the proliferation of these cells. While neither of these proteins had much of an effect on cell cycle arrest on their own, deficiency in both caspase-2 and p53 led to …

Genetics Of Cerebrotendinous Xanthomatosis, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Cerebrotendinous xanthomatosis (CTX) is rare, autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in CYP27A1, which encodes sterile 27 hydroxylase, a key enzyme in bile acid biosynthesis. Enzyme deficiency results in reduced cholic and chenodeoxycholic acid synthesis with accumulation of cholestanol, bile acid intermediates, and bile alcohols, producing a progressive multisystem disorder characterized by chronic diarrhea, juvenile-onset cataracts, tendons xanthomas, and neurological dysfunction. Although CTX typically begins in childhood, diagnosis is frequently delayed until adulthood, limiting the benefit of effective disease modifying therapy with chenodeoxycholic acid. Since the identification of CYP27A1, more than 200 pathogenic variants have …

Evidence-Based Classification Of Genes Implicated In Skeletal Disorders Using The Clingen Curation Framework, Ryan F Webb, Hannah Mccurry, Amanda Girod, Madeline Hughes, Emma Wilcox, Mayher Patel, Eleanor C Broeren, Kezang C Tshering, Marina Distefano, Lorenzo D Botto, Lindsay C Burrage, Valérie Cormier-Daire, Juan Dong, Nadja Ehmke, Deborah Krakow, Shahida Moosa, Geert Mortier, Sandesh Nagamani, Loren Pena, Pedro A Sanchez-Lara, Andrea Superti-Furga, Sheila Unger, Danita Velasco, Matthew L Warman, Kerry Brown, Deepika D'Cunha Burkardt, Carlos R Ferreira

Faculty, Staff and Students Publications

More than 770 genetic skeletal disorders have been described, most with disease-causing variants reported in 1 of over 550 different genes. The ClinGen Skeletal Disorders Gene Curation Expert Panel was established to determine the strength of the evidence that supports specific gene-disease relationships (GDRs). Such information can assist clinical testing laboratories in choosing genes that should be included on diagnostic panels. Nine genes accounting for the most frequently encountered skeletal dysplasias (COL1A1, COL1A2, COL2A1, FGFR3, SLC26A2, TRPV4, COMP, ALPL, and SOX9) associated in the medical literature with 26 different skeletal disorders were reviewed using a semi-quantitative scoring framework. This framework …

Biphasic Sleep Is A Feature Of Sleep Disturbance In Syngap1-Rd, Aida Doucoure, Het Patel, Mark A Abboud, Alice Sperry, Sarah K Wanigatunga, Deana Crocetti, Heather Volk, Adam P Spira, Stewart H Mostofsky, Vaishnav Krishnan, Constance Smith-Hicks

Faculty, Staff and Students Publications

Study objectives: Sleep problems are common in children with SYNGAP1-Related Disorder (SYNGAP1-RD). The use of devices that objectively estimate sleep are complicated by co-occurring sensory disorders in this population. We examined the feasibility and validity of wrist actigraphy to examine sleep and rest-activity rhythms (RAR).

Methods: Data from five children with SYNGAP1-RD and 42 typically developing children were analyzed. All children were asked to wear the Actiwatch-2 for 14 continuous days and caregivers were asked to complete a sleep diary and the Children Sleep Health Questionnaire (CSHQ). Parametric (alpha, beta, acrophase, amplitude, up/down mesor, mesor), nonparametric (intradaily variability, interdaily stability, …

Asynchronous Transitions From High-Risk Hepatoblastoma To Carcinoma, Xinjian Yu, Stephen Sarabia, Martin Urbicain, Sonal Somvanshi, Roma Patel, Priyanka Rao, Tuan M Tran, Yen-Ping Yeh, Keng-Shih Chang, Yi-Tzu Lo, Jessica Epps, Kathleen A Scorsone, Hua-Sheng Chiu, Emporia Faith Hollingsworth, Cintia R Perez, Mohammad Javad Najaf Panah, Barry Zorman, Jordan Muscal, Milton J Finegold, John A Goss, Rita Alaggio, Angshumoy Roy, Kevin E Fisher, Andras Heczey, Sarah Woodfield, Sanjeev Vasudevan, Kalyani Patel, Ting-Wen Chen, Dolores Lopez-Terrada, Pavel Sumazin

Faculty, Staff and Students Publications

Background & aims: Most pediatric hepatocellular tumors are classified as hepatoblastoma (HB) or hepatocellular carcinoma (HCC), yet a subset exhibits mixed histological and molecular features. These hepatoblastomas with carcinoma features (HBCs) include cases provisionally designated as hepatocellular neoplasm-not otherwise specified (HCN-NOS). Their biology remains poorly understood, with unresolved questions about their cellular composition and outcomes. It is unclear whether HBCs comprise hybrid cells with combined HB and HCC characteristics (HBC cells) or admixtures of distinct HB and HCC cells. We characterized the biology, etiology, cellular composition, and evolutionary dynamics of HBCs.

Methods: We performed multi-omics profiling - including single-nucleus RNA …