Pediatrics Commons^™

Bortezomib And Vorinostat In Combination With Mitoxantrone, Dexamethasone, And Pegasparaginase During Induction And Reinduction For Infants With Acute Lymphoblastic Leukaemia: A Multicentre Single-Arm Phase 1/2 Study, Tanja A. Gruber, Sima Jeha, Rebecca J. Deyell, Victor Lewis, Bill H. Chang, Eric J. Lowe, Jamie Frediani, Catherine Vezina, Bruno Michon, Michael Richards, Erin H. Breese, Thai-Hoa Tran, Norman Lacayo, Christine Bolen, Sunil Desai, Jennifer L. Pauley, Minxuan Huang, Emily Ashcraft, Cheng Cheng, Kirk R. Schultz, Linda Stork, Krysta Schlis, Van T. Huynh, Nathan Gossai, Yoav H. Messinger, Henrique Bittencourt, Terzah M. Horton, Uma Athale, Duncan Stearns, Deborah Schiff, Paul S. Gaynon

Department of Pediatrics Faculty Publications

Background: Acute lymphoblastic leukaemia in infants remains a therapeutic challenge. In preclinical studies we previously identified bortezomib and vorinostat as active agents against KMT2A rearranged (KMT2Ar) leukaemia. The aim of this study was to determine the tolerability of incorporating bortezomib and vorinostat into an acute lymphoblastic leukaemia-chemotherapy backbone for newly diagnosed infants with acute lymphoblastic leukaemia both with and without KMT2Ar.

Methods: In this single-arm phase 1/2 study conducted at 18 hospitals in the USA and Canada, we enrolled patients aged 1 year or younger at the time of diagnosis with newly diagnosed acute lymphoblastic leukaemia or undifferentiated leukaemia (with …

Family Mental Health – A Case Report, Vikrant Arora, Medha Kosireddy, Mathumitha Ananth, Kishor M. Manohar Rao

Digital Journal of Clinical Medicine

Psychiatric illness in India is estimated to be 15% as per National Mental Health Survey 2015-16.  Mental health challenges within families, especially depression, anxiety disorders that are not common and when unaddressed exert cascading effects on all members, disrupting emotional cohesion, relational functioning, and socioeconomic stability. There are few case reports on entire family presenting to psychiatry department.

With informed consent a city-based middle-class family of non-consanguineous origin, where the 40-year-old female, presented with intractable limb pains and health anxiety, she had multiple consultation in last few months and her 48-year-old husband also had with episodic pains, irritability and her …

Pulmonary Hemosiderosis In A Young Child Presenting With Recurrent Respiratory Illness And Refractory Anemia: A Case Report, Praveen Das, Ratnapriya Chowdhry, Neha Bhongale, Poonam Wade

Digital Journal of Clinical Medicine

Pulmonary hemosiderosis (PH) is a rare cause of diffuse alveolar hemorrhage in children and often presents with nonspecific respiratory symptoms and refractory iron‑deficiency anemia. We report a 2.5‑year‑old girl with recurrent lower respiratory tract infections, severe transfusion‑dependent anemia, failure to thrive, and persistent bilateral pulmonary infiltrates since infancy. Bronchoalveolar lavage demonstrated hemosiderin‑laden macrophages, confirming pulmonary hemosiderosis. Further evaluation revealed C‑ANCA positivity and PR3‑ANCA negativity, raising suspicion for an ANCA‑associated vasculitis; however, there was no renal, ear‑nose‑throat, or other systemic involvement, and a lung biopsy could not be performed. The child was managed with systemic corticosteroids with clinical improvement. This case …

Senolytic-Resistant Senescent Cells Have A Distinct Sasp Profile And Functional Impact: The Path To Developing Senosensitizers, Utkarsh Tripathi, Masayoshi Suda, Vagisha Kulshreshtha, Bryan T Piatkowski, Allyson K Palmer, Nino Giorgadze, Christina Inman, Nathan Gasek, Ming Xu, Kurt O Johnson, Tamar Pirtskhalava, Selim Chaib, Larissa P G Langhi Prata, Yi Zhu, Renuka Kandhaya-Pillai, Stefan G Tullius, Saranya P Wyles, Rambabu Majji, Hari Krishna Yalamanchili, David B Allison, Tamar Tchkonia, James L Kirkland

Faculty, Staff and Students Publications

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant". Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro-inflammatory. In cell cultures, the 30%-70% of human senescent preadipocytes or human umbilical …

Developing And Evaluating A Young Adult Peer Mentor Training Program, Beth H Garland, Demonica L Jones, Cassandra J Enzler, Jean L Raphael, Albert C Hergenroeder, Rachel S Wolfe, Sarah C Graham, Constance M Wiemann

Faculty, Staff and Students Publications

Improving self-management skills for adolescents and emerging adults (AEA) with chronic health conditions is critical for successful transition to adult-based care. Peer-mentoring has been effective in improving the self-management skills of AEA. However, the components of training a successful young adult peer mentors (YAPM), especially interpersonal aspects of the role, such as communication skills and navigating mentee ambivalence are not well understood. This descriptive study created and pilot-tested a training curriculum for YAPM as part of a larger study to build self-management skills in the context of healthcare transition from pediatric to adult care. Five YAPM completed the training curriculum. …

Integrating A Project-Based Learning Methodology Into A Department-Wide Quality Improvement Curriculum: A Nine-Year Experience In Pediatric Subspecialty Training, Venessa Lynn Pinto, Danny Castro, Constance M Wiemann, Liza Bonin, Cagri Yildirim-Toruner, Nicholas A Ettinger, Sharada Hiranya Gowda, Joyee Vachani, Mehmet Fatih Okcu

Faculty, Staff and Students Publications

Background: Quality improvement (QI) training of subspecialty fellows is an essential component of graduate medical education, yet often delivered in silos within departments through a variety of instructional methodologies.

Objective: We applied project-based learning (PjBL) as a guiding methodology for a QI curriculum for pediatric subspecialty fellows and describe our curriculum development, instructional design, and its implementation.

Methods: We integrated the Institute for Healthcare Improvement (IHI) Model for Improvement with the 6 key features of PjBL: a driving question, defined learning goals, active participation in educational tasks, collaboration among learners, scaffolding with learning technology, and production of tangible artifacts. The …

When Targeted Gene Testing Falls Short: Case Report Of A Novel Slc4a3 F347s Genetic Variant Associated With Short Qt Syndrome, Chelsea A Boyd, Tyler J Novy, Taylor A Beecroft-Dawson, Connor A Bell, Emily M Bland, Christina Y Miyake

Faculty, Staff and Students Publications

No abstract provided.

The Lived Experience Of Pediatric Pain Management: Insights From Families And Providers, Samrithaa Balakrishnan, Annesha Dey, Aarti Bavare, Paul Checchia, Katherine Shwetz, Natasha Afonso

Faculty, Staff and Students Publications

Pain represents a subjective experience that manifests with emotional and physical discomfort. In pediatric care, pain management is especially complex due to communicative limitations, which creates a unique point of entry for parents to contribute to their child's treatment process. In this study, we explored whether families' perceptions of their child's pain and preferences for treatment were aligned with healthcare providers' pain management decisions. Using narrative-informed techniques in interviews with families and healthcare providers in pediatric care settings, we analyzed areas of concordance and discordance in pain assessment and treatment priorities. Our findings show that trust is built over time …

Point-Of-Care Ultrasound Foundations In Physics And Image Acquisition: An Innovative Hands-On Active Learning Workshop, Cherie Tator, Saul Flores, Alan Riley, Kiyetta Alade

Faculty, Staff and Students Publications

Introduction: We developed an innovative, active learning workshop to introduce foundations of point-of-care ultrasound (POCUS) physics and instrumentation. The workshop design aimed to reduce cognitive load and encourage learner-centered engagement through hands-on exploration that reinforces key principles and connects theory to practice.

Methods: First-year medical students participated in small-group, student-driven exercises to explore POCUS machine controls, transducers, and image acquisition skills. Each group was supported by a faculty member to guide activities and ensure accuracy. Students scanned pickles, hard-boiled eggs, and olives with pits; these items were selected for their low cost, sonographic characteristics, and recognizability. Later in the semester, …

Pd-L1-Centric Whole Blood-Based Immune Signature Profiles Of Tuberculosis Patients During Therapy, Johanna Eggeling, Martina Sester, Christoph Lange, Jan Heyckendorf, Barbara Kalsdorf, Anna M Mandalakas, Andrew R Dinardo, David Lewinsohn, Dagmar Schaub, Tina Schmidt, Eva Tolosa, Maja Reimann, Patricia M Sánchez Carballo

Faculty, Staff and Students Publications

This prospective study investigated whole blood-based immune cell biomarkers for pulmonary tuberculosis (TB) immunoprofiling. Blood samples from 34 healthy controls and 51 tuberculosis patients were analyzed at three timepoints: Prior to therapy (T0), after 14 days of therapy (T1), and at the end of treatment (Te). Using multiparameter flow cytometry, 386 immune cell populations were analyzed. Predictive models were developed using two machine learning algorithms. A TB5LF change score, which was based on five cell populations, effectively distinguished tuberculosis patients from controls (AUC = 0.89) and tuberculosis patients before and at the end of treatment (AUC = 0.92). Similarly, the …

A Review Of Current Research And Barriers To Access: Exploring Disparities In Pediatric Epilepsy Surgery, Nikita Das, Ali A Mohamed, Akshat Katyayan, Meena Vessell

Faculty, Staff and Students Publications

Background: Drug-resistant epilepsy (DRE) impacts at least 30% of pediatric epilepsy patients, adversely affecting neurodevelopment and quality of life, as well as risk of sudden unexplained death in epilepsy (SUDEP). While surgical intervention has proven to be an effective treatment for DRE, disparities in access to surgical care persist. Compared to adults, pediatric patients face unique challenges, including delayed recognition of surgical candidacy, limited access to specialized epilepsy centers, complex care coordination, and socioeconomic barriers.

Summary: This review explores the current state of pediatric epilepsy surgery, highlighting its effectiveness in achieving seizure freedom, improving neurocognitive outcomes, and reducing long-term healthcare …

Sodium Supplementation Algorithm To Promote Growth In Infants Who Are Preterm: Randomized Clinical Trial, Brianna M Liberio, Gregory M Sokol, Hannah Rakow, Kelly Mosesso, Valerie Hole, William W Wong, Shaji K Chacko, Jeffrey L Segar

Faculty, Staff and Students Publications

Objective: Evaluate the effectiveness of an algorithm using urine sodium (Na) concentration to guide dietary Na supplementation compared with standard care to promote growth in infants who are preterm.

Methods: A randomized trial was conducted in 4 neonatal units in Indianapolis, Indiana, involving infants between 250/7 to 296/7 weeks gestation with birthweight > 500 g. Study arms consisted of standard care or use of algorithm beginning at 14 to 17 days postnatal age. The primary outcomes were somatic growth (weight, length, and head circumference) measured by change in Z-score between aged 2 weeks and 36 weeks postmenstrual age (PMA). Secondary outcomes …

Layers To Leaves: A Suite Of Modular 3d Printed Hydroponics Components For Research And Education, Ethan A Shaw, Suraj K Chandramouli, Michael P Dzakovich

Faculty, Staff and Students Publications

Hydroponics is a widely utilized technique to precisely control the plant growing environment and maximize productivity. In some cases, hydroponics systems can be expensive and require specialized expertise to build and maintain. Here, we present a suite of 3D-printed devices that can be constructed into a single or double tower hydroponics system of variable height and composition. This system is easily scalable to fit the needs of a user and can be implemented in a variety of research and educational contexts. Components in this suite can be made from inexpensive plastic filament using household-grade 3D printers. The vertical design of …

Tracheobronchial Mucoepidermoid Carcinoma In Four Pediatric Patients, Kalen Hendra, Muhammad Ijlal Khan, Mitali Thanawala, Manuel Silva-Carmona, Eric D Zee

Faculty, Staff and Students Publications

Pediatric tracheobronchial mucoepidermoid carcinoma (MEC), also called pulmonary MEC, is a rare malignant primary lung neoplasm that is typically found in the large airways. Patients may present with symptoms such as cough, pneumonia, fever, hemoptysis, dyspnea, wheezing, chest pain, weight loss, and fatigue. These nonspecific symptoms (or lack of symptoms in some cases) often result in a delayed diagnosis. Chest CT typically demonstrates findings consistent with bronchial obstruction and diagnosis is made via histopathology. Surgical resection is the mainstay of treatment and children often have favorable outcomes. Here we present four cases of tracheobronchial MEC in children treated at three …

Use Of New Tobacco And Nicotine Products As A Harm Reduction Strategy: A Critical Review Of The Evidence, Carlos Andrés Jimenez-Ruiz, José Ignacio De Granda-Orive, Carlos Rábade Castedo, Harold J Farber, Angélica Ocampo, Susana Luhning, Beatriz Raboso-Moreno, Lola Del Puerto-Garcia, Daniel Buljubasich, Manuel Conrado Pacheco-Gallego, José Antonio Castillo-Vizueta, Rosa Mirambeaux-Villalona, Marcos García-Rueda, Juan Antonio Riesco-Miranda, Ángela Ramos-Pinedo, Jaime Signes-Costa, Ledys Blanquicett-Barrios, Eva De Higes-Martinez, Catalina Casillas-Suarez, Concepción Rodríguez-García, Cristina Villar-Laguna, Gloria Francisco-Corral, Esther Pastor-Esplá, Paz Vaquero-Lozano, Francisco Carrion-Valero, Lourdes Cañón-Barroso, Raúl Sandoval-Contreras, Inmaculada Gorordo-Unzueta, Ruth Pitti-Pérez, María Ángeles Muñoz-Vidal, Susana Calvo-Pascual, Eva Cabrera-Cesar, Germán Díaz-Santos, Maribel Cristóbal-Fernández

Faculty, Staff and Students Publications

The sale, distribution, and indiscriminate use of new tobacco and nicotine products have multiplied. The most relevant products are: electronic cigarettes (ECs), heated tobacco (HT), and nicotine pouches (NPs). From the tobacco industry and its related health sectors, and even from some health institutions with no clear influence from this industry, the use of all these devices is being promoted as an excellent harm reduction strategy for those conventional tobacco smokers who do not want to or cannot quit smoking. This paper reviewed the lack of scientific evidence of this strategy.

Injuries In Children Undergoing Subspecialty Abuse Evaluations Because Of Intimate Partner Violence, M Katherine Henry, Gunjan Tiyyagura, Joanne N Wood, Jan Leonard, Kristine A Campbell, Daniel M Lindberg, Angela N Bachim, Farah W Brink, Lori D Frasier, Nancy S Harper, Claire Hickey, Natalie Laub, John D Melville, Hannah Sahud, Philip V Scribano

Faculty, Staff and Students Publications

Background and objectives: Intimate partner violence (IPV) and child physical abuse often co-occur, but the frequency and risk factors for abusive injuries in IPV-exposed children remain unknown. Our objectives were to (1) determine frequency of skeletal surveys (SSs) and neuroimaging use because of IPV and their diagnostic value in children aged less than 24 months evaluated by a child abuse pediatrics specialist (CAP) and (2) identify factors associated with performance of and findings on SS and neuroimaging.

Methods: We conducted a retrospective study of children aged less than 24 months undergoing CAP consultations because of IPV exposure from February 2021 …

Use Of A Medication Management Algorithm In Depressed Youth Living With Hiv: Secondary Analysis Of A Multisite Randomized Controlled Trial, Graham J Emslie, Beth D Kennard, Kristin Baltrusaitis, Sophia M Jones, Jessica M Jones, Jaime G Deville, Kathleen Pitts, David E Shapiro, Allison Eliscu, Larry K Brown

Faculty, Staff and Students Publications

Objectives: Depression is a prevalent co-occurring condition in youth living with HIV. This report is a secondary analysis of a multisite cluster randomized trial evaluating the efficacy of a health and wellness cognitive behavioral therapy (CBT) combined with a medication management algorithm utilizing measure-based care (COMB-R) compared with enhanced standard of care (ESC). We describe and compare antidepressant prescribing strategies (i.e., antidepressant treatment, type of antidepressant) for youth living with HIV at COMB-R sites to those at ESC sites over the 24-week intervention. We also describe self-reported adherence to antidepressants.

Methods: Participants (12-24 years) were youth living with HIV diagnosed …

Host- And Pathogen-Related Determinants Of Pulmonary Versus Extrapulmonary Tuberculosis, Begna Tulu, Thomas Theo Brehm, Reinout Van Crevel, Tobias Dallenga, Andrew R Dinardo, Keertan Dheda, Johanna Eggeling, Wendemagegn Enbiale, Matthias I Gröschel, Jialun Hao, Vinod Kumar, Arjan Van Laarhoven, Rolanda Londt, Gareth Prosser, Philippa Randall, Norbert Reiling, Jan Rybniker, Ulrich E Schaible, Erwin Schurr, Isabelle Suarez, Sebastian J Theobald, Robert J Wilkinson, Christoph Lange

Faculty, Staff and Students Publications

Tuberculosis (TB) primarily manifests as pulmonary TB (PTB), but extrapulmonary TB (EPTB) remains a major clinical challenge. Distinct diagnostic and therapeutic difficulties arise from differences in immune responses, pathogen behaviour and host susceptibility. However, the factors driving disease localisation are still incompletely understood. We conducted a comprehensive narrative review of studies examining differences between PTB and EPTB in terms of epidemiology, mycobacterial factors, genetic and epigenetic determinants, host immune responses, transcriptomic profiles, cytokine and chemokine patterns, and immunophenotypes. EPTB is more common among females, children, older adults and immunocompromised individuals with deficient granuloma formation. This review is intended to provide …

A Year In Review On Tuberculosis And Non-Tuberculous Mycobacteria Disease: A 2026 Update For Clinicians And Scientists, Simone Tunesi, Graham Bothamley, Gunar Günther, Yousra Kherabi, Liga Kuksa, Berit Lange, Christoph Lange, Natalie Lorent, Francesca Saluzzo, Martina Sester, Xenia Emilie Sinding Iversen, Marc Tebruegge, Conor Tweed, Anca Vasiliu, Lorenzo Guglielmetti, Tuberculosis Network European Trials Group (Tbnet)

Faculty, Staff and Students Publications

Background: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide, while infections from non-tuberculous mycobacteria (NTM) represent a growing public health threat. In its 20th year of activity, the Tuberculosis Network European Trials group (TBnet; www.tbnet.eu) is one of the leading research networks in Europe. In this review, we summarize the main advances in TB and NTM that occurred in 2025.

Methods: We conducted a non-systematic review of articles published in 2025, with a strong emphasis on research with current or potential impact on clinical practice. We also selected the most impactful papers regarding the management of adult …

Updates In The Management Of Peanut Allergy, S Shahzad Mustafa, Aikaterini Anagnostou, Matthew Greenhawt

Faculty, Staff and Students Publications

Peanut allergy is a significant rising public health problem affecting both children and adults. Early peanut introduction has been adopted in multiple westernized nations as a preventative strategic measure to reduce the risk of developing peanut allergy, although implementation faces barriers. Multiple therapies to treat peanut allergy have been developed, including oral immunotherapy and omalizumab as approved treatments to provide protection against reactions from accidental exposure and reduce the risk of anaphylaxis, offering options beyond strict avoidance. Strategies in the developmental pipeline include epicutaneous immunotherapy and sublingual immunotherapy. The future is bright for individuals with peanut allergy, as these breakthroughs …

Improving Compliance With Safe Sleep Guidelines For Vulnerable Patients In A Community Safety Net Hospital Neonatal Intensive Care Unit, Andrew Beverstock, Samantha Carlton, Hillary Lee, Thomas Lu, Kelsi Morgan, Ashlee Smith-Patel, Kelli Phillips, Joseph Hagan, Pablo Lohmann, Caraciolo Fernandes, Lisa Owens, Daniela Dinu

Faculty, Staff and Students Publications

Objectives: Congenital diaphragmatic hernia (CDH) often coexists with fetal growth restriction (FGR). The observed-to-expected (O/E) total fetal lung volume (TFLV) is used to assess CDH severity, predict outcomes, and direct fetal interventions. Expected TFLV measurements traditionally rely only on gestation age (GA). This simulation assesses how incorporating weight-adjusted GA norms affects O/E TFLV calculations in patients with isolated CDH and FGR.

Methods: A simulated dataset (n=1,005) utilized published mean fetal weight and TFLV references. Computer-generated variables included observed weights (3rd-10th %ile), O/E TFLV (10-65 %), and percent liver herniation (0-42 %). GA estimates were corrected by weight and used to …

Improving Compliance With Safe Sleep Guidelines For Vulnerable Patients In A Community Safety Net Hospital Neonatal Intensive Care Unit, Andrew Beverstock, Samantha Carlton, Hillary Lee, Thomas Lu, Kelsi Morgan, Ashlee Smith-Patel, Kelli Phillips, Joseph Hagan, Pablo Lohmann, Caraciolo Fernandes, Lisa Owens, Daniela Dinu

Faculty, Staff and Students Publications

Introduction: Modeling safe sleep in the neonatal intensive care unit (NICU) increases the likelihood that parents will follow these practices after discharge. Many NICU infants are put to sleep unsafely, and unsafe sleep practices are the leading cause of nonnatural death among children locally. We created safe sleep standards for infants older than 32 weeks based on national guidelines: infants should be placed supine in a flat, empty crib and should never be swaddled loosely. We aimed to increase the weekly percentage compliance with safe sleep recommendations from a baseline of 58% (0.58 compliant) to 85% (0.85 compliant) by March …

Nutrition Support Adequacy In Children With Biliary Atresia After Liver Transplant, Nicole Knebusch, Manpreet Virk, Moreshwar S Desai, Marwa Mansour, Stacey Beer, Brittany Pearo, Kelby Fuller, Krupa Mysore, John Goss, Thomas Fogarty, Fernando Stein, Jorge A Coss-Bu

Faculty, Staff and Students Publications

No abstract provided.

Non-Invasive Diagnosis Of Pulmonary Tuberculosis Using Face Mask Sampling: A Prospective Study In Adults, Dariusz Woelk, Lennard Meiwes, Nelly Ciobanu, Valeriu Crudu, Anna-Marya Comanac, Stela Kulcitkaia, Anca Vasiliu, Anna Maria Mandalakas, Christoph Lange, Thomas Theo Brehm, Dumitru Chesov

Faculty, Staff and Students Publications

Objectives: Sputum-based diagnostic methods for pulmonary tuberculosis (TB), including culture and nucleic acid amplification tests, provide high sensitivity and specificity. However, these methods rely on the patients' ability to produce sputum. In cases where sputum cannot be obtained, invasive procedures like bronchoscopy may become necessary. Our objective was to evaluate the diagnostic accuracy of face mask sampling (FMS) as a non-invasive alternative.

Methods: Adults with microbiologically confirmed pulmonary TB who had received fewer than three days of anti-TB therapy were recruited in Chişinău, Moldova. FMS was conducted and samples were analyzed on-site using Xpert MTB/RIF Ultra. Diagnostic performance was compared …

Managing The Uncertainty Of "Precision" While Navigating Goals Of Care: A Framework For Collaborative Interpretation Of Complex Genomic Testing Results In Critically-Ill Neonates, Donnamaria E. Cortezzo, Katharine Press Callahan, Bimal P. Chaudhari, Elliott M. Weiss, Monica Hsiung Wojcik, Krishna Acharya, Amy B. Schlegel, Kevin M. Sullivan, Jessica T. Fry

Department of Pediatrics Faculty Papers

Each year, many neonates are born with genetic diagnoses that carry a range of prognoses. As the types and availability of genetic testing have expanded, neonatal intensive care units (NICUs) have served as "launching points" for their clinical application. Broad genetic testing has both improved diagnostic precision and expanded uncertainty. Genetic information may be explicitly uncertain, as in the case of a variant of unknown significance (VUS). But it is also frequently uncertain whether/how the information relates to a patient's phenotype or what it may mean for a child's future. Even without ambiguity in the diagnosis or prognosis, the significance …

Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan

School of Graduate Studies Faculty Publications

Neuroblastoma (NB), a pediatric cancer of sympatho-adrenal (SA) lineage, is marked by disrupted differentiation and cellular heterogeneity. INSM1, a zinc-finger transcription factor, is highly expressed in NB and developing SA tissues, where it regulates neuroendocrine differentiation, especially in chromaffin cells. We investigated INSM1's role in maintaining an undifferentiated, progenitor-like state in NB and its regulation via metabolic and epigenetic mechanisms. Transcriptomic profiling, promoter assays, and metabolic flux analysis revealed that INSM1 expression correlates with methionine cycle activity, particularly the S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio. Disruption of SAM/SAH balance altered INSM1 promoter activity and histone methylation, implicating epigenetic control in NB cell …

Daily Intake Of A Lycopene-Rich Juice Is Associated With Reductions In Inflammatory Markers But Not Increases In Skin Carotenoids In A Pilot Study Among Participants With Obesity, Stephanie B Jilcott Pitts, Qiang Wu, Melissa N Laska, Elizabeth Gates, Megumi H Seese, Katelyn E Senkus, Santiago Carrero Longlax, Alexandra Portillo-Varela, Andrew R Dinardo, Nancy E Moran

Faculty, Staff and Students Publications

Background

Obesity is associated with systemic inflammation, increasing chronic disease risk. Carotenoids possess anti-inflammatory properties, yet the short-term impact of carotenoid-rich juice intake on inflammation in individuals with obesity remains unclear. Therefore, the purpose of this paper was to examine: (1) participant adherence to a 3-week lycopene-rich juice intervention; (2) variance and effect sizes of responses to the dietary intervention; (3) changes in skin and plasma carotenoids, and inflammatory markers among adults with obesity.

Methods

Twenty-five participants with body mass index (BMI) > 30 kg/m2 were recruited and completed the study. Participants drank 4 ounces (118.3 mL) of study-provided tomato juice, …

Life-Threatening Bradycardia In Anti-Nmda-Receptor Encephalitis And A Novel Use For Permanent Pacing, Sarah Tucker, Abhijit Das, Andres Jimenez, Areeba Basit, Yike Jiang, Emily A Smitherman, Heather Van Mater, Taylor Howard, Alexander J Sandweiss, Kristen S Fisher

Faculty, Staff and Students Publications

Background: Pediatric anti-NMDA receptor encephalitis (pNMDARE) is an autoantibody-mediated disorder that can cause severe autonomic dysfunction, including symptomatic bradycardia and asystole. Dysautonomia can last for years, making it very challenging to manage.

Objective: To describe outcomes of 5 pNMDARE patients with life-threatening bradycardic and/or asystolic events who were managed with permanent or semi-permanent pacemaker implantation.

Methods: We performed a retrospective chart review of 5 patients from multiple institutions. We included patients with a diagnosis of pNMDARE (confirmed by positive cerebrospinal fluid and/or serum anti-NMDAR antibodies) who had a permanent or semi-permanent pacemaker placed due to symptomatic bradycardia, sinus pauses, and/or …

Clinical Practice Variation Among Pediatric Rheumatologists Treating Kawasaki Disease: Results Of A North American Survey, Daniel Ibanez, Bianca Lang, Julia Shalen, Ali Yalcindag, Linda Wagner-Weiner, Kenneth N Schikler, Shoghik Akoghlanian, Hulya Bukulmez, Kristen Hayward, Laura Berbert, Sivia Lapidus, Andrea A Ramirez, Cagri Yildirim-Toruner

Faculty, Staff and Students Publications

Background: The best treatment for children with KD who fail to respond to the first dose of IVIG (refractory KD) is currently unknown. The purpose of this study was to determine treatment practices of pediatric rheumatologists in North America who manage IVIG-refractory KD.

Methods: A 34-item web-based survey was sent to 102 randomly selected members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). The anonymous survey addressed the use of primary intensification as well as the treatment of IVIG-refractory KD.

Results: The response rate was 82%; 56% (all pediatric rheumatologists) completed the survey. Primary intensification was …

Mrna Vaccines Encoding Variant Forms Of Sm-Tsp-2 Confer Protective Immunity Against Schistosoma Mansoni, Athos Silva De Oliveira, Sevan Alwan, Philip T Loverde, Ramiz Shaheed, Pranav Mandyam, Rakesh Adhikari, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

This study explored the development and evaluation of mRNA vaccine candidates targeting Schistosoma mansoni tetraspanin-2 (Sm-TSP-2). We designed constructs encoding either full-length Sm-TSP-2, or its large extracellular loop (EC2) domain in secretory, membrane-anchored, or cytosolic forms. In a murine model, the secreted and membrane-anchored versions of Sm-TSP-2-EC2 induced the highest antigen-specific antibody titers. These two construct designs, along with full-length Sm-TSP-2 mRNA, also significantly reduced adult worm and egg burden compared to controls. The membrane-anchored Sm-TSP-2-EC2 mRNA was the most effective, lowering worm and egg burdens by 66.7% and 66.9%, respectively. Protective responses induced by the mRNA vaccines were comparable …