Digital Commons Network^™

The Setd2 L1609p Mutation Found In Leukemia Disrupts Methyltransferase Activity And Reduces Histone H3k36 Trimethylation, Christina Michail, Jérémy Berthelet, Ariel E Mechaly, Linh-Chi Bui, Haopeng Yang, Duo Cai, Amira Al Mahi, Aowei Xie, Valeria Bisio, Valentina Sirri, Jean-Marie Dupret, Fabien Guidez, Ximing Xu, Nicolas Joly, Leslie Regad, Mireille Viguier, Frédérique Deshayes, Nicolas Dulphy, Michael R Green, Ahmed Haouz, Fernando Rodrigues Lima

Faculty, Staff and Student Publications

SETD2 is the primary methyltransferase responsible for generating H3K36me3, an epigenetic mark that is essential for transcriptional regulation and chromatin integrity. SETD2 mutations are frequently observed in various cancers and tend to cluster within its catalytic SET domain. Despite the clinical relevance of SETD2 missense mutations in cancer, their biochemical and structural consequences remain insufficiently characterized. Here, we present the enzymatic and structural characterization of the SETD2 L1609P mutant enzyme identified in leukemia. The L1609 residue is located in the SET domain within a conserved hydrophobic pocket that is involved in substrate H3K36 recognition. Interestingly, site-directed mutagenesis of residues within …

Bi-Allelic Variants In Neuronal Adhesion Molecule Astrotactin 1 Gene Astn1 Cause Diverse Neurodevelopmental Disorders, Jesse M Levine, Daniel G Calame, Riccardo Sangermano, Haowei Du, Ahmed Saad, Jasmin Lisfeld, Tatjana Bierhals, Jonas Denecke, Eyyup Uctepe, Merve Yoldas Celik, Ahmet Yesilyurt, Hilal Yildiz Er, Elif Yilmaz Gulec, Aziza Mushiba, Naif Almontashiri, Pawel Gawlinski, Wojciech Wiszniewski, Ender Karaca, Lama Alabdi, Davut Pehlivan, Dana Marafi, Maha S Zaki, Fowzan S Alkuraya, Joseph G Gleeson, Shalini N Jhangiani, Richard A Gibbs, Jennifer E Posey, Kinga M Bujakowska, James R Lupski

Faculty, Staff and Students Publications

ASTN1 encodes astrotactin 1, a neuronal-glial ligand in the developing brain that promotes neuronal migration along radial glia in brain structures with laminar organization, such as the cerebral cortex, hippocampus, and cerebellum. In mouse models, disruption of Astn1 results in neuronal migration deficits, a mild reduction in cerebellar volume, and balance and coordination deficits. In humans, bi-allelic ASTN1 variants have been identified in nine individuals with neurodevelopmental disorders (NDDs) with or without brain malformations. ASTN1 additionally interacts with astrotactin 2 (ASTN2) to implement neuronal migration; ASTN2 deletions associate with NDDs with reduced penetrance. Here, we describe eighteen individuals with NDDs …

A Case Of Dislocation And Successful Reduction Of A Right Anterior Shoulder Inside A Space Suit: Considerations For Future Protocols, Samuel Beger, Curtis Lowery, Nicolas Heft, Amran Asadi, Brandon Trapp, Jaime Mateus, Alejandro Garbino

Faculty, Staff and Student Publications

Shoulder dislocations are prevalent on Earth and pose unique challenges in spaceflight and spaceflight training, particularly during extravehicular activities (EVAs). This case report describes a 50-year-old male who experienced an anterior shoulder dislocation while performing an emergency egress exercise in a SpaceX EVA suit. The report describes the medical thought process, the operational constraints, and the reduction techniques employed to achieve a successful shoulder reduction without fully removing or damaging the suit. NASA estimates a high likelihood of shoulder injuries during long-duration lunar missions, emphasizing the importance of suit designs and rescue protocols. Quick and effective medical intervention is crucial, …

Infectious Causes Of Acute Febrile Illness In Belize, 2020-2022, Adrianna Maliga, Shannon E Ronca, Russell Manzanero, Roberto Melendez, Sarah M Gunter, Allison Lino, Joy Mackey, Andres Espinosa-Bode, Beatriz Lopez, Rafael Chacon-Fuentes, Freedom M Green, Oluwadara Okeremi, Sarah Strobel, Daniel P Rehm, Flor M Muñoz, Loren Cadena, Melissa Diaz-Musa, Francis Morey, Emily Zielinski-Gutierrez, Gerhaldine Morazan, Kristy O Murray

Faculty, Staff and Students Publications

Acute febrile illness (AFI) surveillance networks can play a key role in identifying emerging pathogens and promoting global health security, especially for vulnerable populations in low- and middle-income countries. In January 2020, the Belize AFI Surveillance network was formed, and 5,643 participants were enrolled over the first 3-year period across 11 participating public hospitals. Using real-time polymerase chain reaction testing for vector-borne pathogen detection and BioFire® diagnostic testing for respiratory and gastrointestinal pathogens, the causes of illness were examined in relation to 54 pathogens in these participants. In response to the coronavirus disease 2019 pandemic, surveillance was expanded to detect …

Tumor Radiosensitization With Gold Nanoparticles: Evolving Strategies To Improve Tumoral Gold Uptake And Catalyze Future Clinical Translation, Prapannajeet Biswal, Geraldine V Vijay, Gabrielle Krouse, Phuoc Minh Quan Mai, Bhoomika Muruvekere Lakshmisha, Sanaz Keshavarz Shahbaz, Mahdieh Yousefi Taba, Aria Sabbagh, Lydia Wt Cheung, Yuri Mackeyev, Khadijeh Koushki, Sunil Krishnan

Faculty, Staff and Student Publications

Radiation therapy is integral to the treatment regimens of over 50% of cancer patients. However, it is not biologically targeted to just the tumor, leading to adverse effects in peritumoral normal tissue. Selective uptake of gold nanoparticles (AuNPs) by tumors realizes tumor-specific radiosensitization via increased secondary electron release from high atomic number gold atoms. Here, we review AuNP-mediated radiosensitization and outline strategies to optimize tumor-targeted AuNP delivery. Modifying the physicochemical characteristics of AuNPs, including size, shape, charge, and surface chemistry, can increase their ability to evade the reticuloendothelial system (RES) and penetrate the dense tumor stromal architecture, thereby promoting tumor …

Repurposing Of The Macrolide Antibiotic Clarithromycin For The Prevention Of Lung Cancer, Shanshan Deng, Tabish Hussain, Thais F Bartelli, Manu M Sebastian, Melody Zarghooni, Walter V Velasco, Brandon Somerville, Linda Phan, Michelle I Savage, Yurong Song, John L Clifford, Humam Kadara, Florencia Mcallister, Powel H Brown, Seyed Javad Moghaddam, C Marcelo Aldaz

Faculty, Staff and Student Publications

Drug repurposing is the process of reusing existing pharmaceuticals for novel clinical purposes, which offers advantages such as streamlined clinical trial access and reduced drug development costs. Clarithromycin (CAM), a member of the macrolide antibiotics family, is a promising candidate for repurposing in cancer therapy due to its known preclinical and clinical immunomodulatory and anticancer properties. In the current study, we investigated whether CAM could be repurposed as a preventive treatment for KRAS-mutant lung cancer, a subtype of lung adenocarcinoma that is strongly associated with heavy smoking. CCSPCre; LSL-KrasG12D mice at an early stage of tumor development were treated with …

Exploring Sex Differences In Stroke Outcomes: A Comprehensive Analysis From The Span 1 Trial, Anjali Chauhan, Eunyoung Angela Lee, Rakesh B Patel, Mariia Kumskova, Enrique C Leira, Anil Chauhan, Yanrong Shi, Suyi Cao, Raymond C Koehler, Krishnan M Dhandapani, Mohammad Badruzzaman Khan, Pradip K Kamat, Ali Arbab, David C Hess, Alison L Herman, Ligia Boisserand, Lauren H Sansing, Andreia Morais, Xuyan Jin, Sanem Aykan, Takahiko Imai, Cenk Ayata, Karisma A Nagarkatti, Jessica Lamb, Márcio A Diniz, Patrick D Lyden, Jaroslaw Aronowski, Louise D Mccullough

Faculty, Staff and Student Publications

Background: Stroke is a sexually dimorphic disease, with different risk factors, incidence, outcomes, and treatment responses in men and women. While sex differences have been documented in preclinical studies, these findings often come from single-site studies with small sample sizes and require validation across diverse research settings.

Methods: We used data from the SPAN (Stroke Preclinical Assessment Network), a randomized, placebo-controlled, blinded, multilaboratory trial, to determine if sex differences in neurological outcomes are present in preclinical stroke models. We analyzed data from 665 stroke animals treated with saline, including young mice, diet-induced obese mice, aging mice, young rats, and spontaneously …

Patient-Specific Computational Flow Simulation Reveals Adverse Hemodynamic Factors Associated With Occlusion Of Directional Branches After Fenestrated-Branched Endovascular Aneurysm Repair, Kenneth Tran, Jesse Chait, Emmanuel Tenorio, Weiguang Yang, Alison Marsden, Bernardo Mendes, Jason T Lee, Gustavo S Oderich

Faculty, Staff and Students Publications

Background: Fenestrated and branched endovascular aneurysm repair can be complicated by branch vessel occlusion in the absence of structural stenosis. We hypothesized that computational flow simulation could identify adverse hemodynamic features associated with postfenestrated and branched endovascular aneurysm repair branch occlusion.

Methods: Patients undergoing 4-vessel fenestrated and branched endovascular aneurysm repair for Extent II to IV thoracoabdominal aortic aneurysms were retrospectively reviewed. Branches that occluded without identifiable kinking or stenosis on computed tomography were included, along with an equal cohort of anatomy-matched patent controls. Patient-specific pulsatile rigid-wall simulations were performed using SimVascular with individualized geometries and boundary conditions. Abnormal time-averaged …

Characterizing The Effects Of Antimuscarinics On Rhoa Signaling, Zuhra Tukhtamisheva, Elizabeth L. Mcduffie, Jordan Lee, Steven S. An, Reynold A. Panettieri Jr., Charles Scott

Alpha Omega Alpha Research Symposium Posters

Purpose: Airway hyperresponsiveness in asthma is driven by acetylcholine-mediated activation of the muscarinic acetylcholine 3 receptor (M3R), promoting bronchoconstriction, mucus hypersecretion, and airway remodeling. Despite directly targeting this pathway, antimuscarinics remain adjunctive rather than first-line therapy, suggesting a disconnect between biological rationale and clinical efficacy. Recent work from the Scott Lab at Thomas Jefferson University demonstrates that M3R in human airway smooth muscle (HASM) cells drives muscle shortening through G_12/13–driven RhoA signaling rather than through G_q/11-dependent calcium flux. We therefore investigated whether clinically prescribed antimuscarinics effectively inhibit G_12/13-dependent RhoA signaling in HASM cells.

Methods: …

Intouch Week Of February 2, 2026, New York Medical College

InTouch

• Campus Illumination and Panel Discussion Honors Holocaust Remembrance Day
• Where Experience Becomes Evidence: Advancing Transplant Education at NYMC
• D.P.T. Student Experience
• Love at NYMC

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

Osimertinib Activates A Tgf-Β2-Dependent Secretory Program That Drives Lung Adenocarcinoma Progression, Madhurima Ghosh, Chao Wu, Abhishek Kumar, Monique Nilsson, John V Heymach, Weina Zhao, Jiang Yu, Xin Liu, Na Ding, Shike Wang, Guan-Yu Xiao, Angelo Chen, Kate Grimley, William K Russell, Chad J Creighton, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

EGFR-mutant lung adenocarcinomas (LUADs) that are vulnerable to the EGFR antagonist osimertinib (Osi) eventually relapse, owing in part to the emergence of drug-tolerant persister (DTP) cells that arise through epigenetic mechanisms. Intratumoral DTP cells can herald a worse clinical outcome, but the way in which DTP cells influence LUAD progression remains unclear. Osi-resistant (OR) cells exhibit typical DTP cell features, including a propensity to undergo senescence and epithelial-mesenchymal transition (EMT), which can activate heightened secretory states. Therefore, we postulated that OR cells influence LUAD progression through paracrine mechanisms. To test this hypothesis, we utilized congenic pairs of EGFR-mutant LUAD cell …

Clinical Features Of Infantile Epileptic Spasms Syndrome: A Systematic Review, Xiao Meng, Danielle S Takacs, Yashaswini Kelagere, Zihan Zhang, Sanjanaa Seshadri, Jiyeon Cha, Ming Li, Lei-Shih Chen

Faculty, Staff and Students Publications

Introduction

Infantile Epileptic Spasms Syndrome (IESS) is a severe epilepsy in children between one month and two years of age. Urgent referral of possible IESS cases from pediatricians and family physicians who care for children to neurologists for diagnosis and treatment has been shown to significantly improve patient health outcomes. Yet, a comprehensive list of IESS clinical features is lacking. We conducted a systematic review of studies to report IESS clinical features.

Methods

Articles from the MEDLINE Complete and Embase databases were searched from the earliest years of databases availability (1979) to July 31, 2024. We followed the Preferred Reporting …

Rare Event: Neonatal Anaphylaxis Following Hepatitis B Vaccination – A Case Series From A Tertiary Care Center In India, Aarthi Ma, Revanth R

Advances in Clinical Medical Research and Healthcare Delivery

We report two cases of anaphylaxis following Hepatitis B vaccination in one-day-old neonates at a tertiary care hospital in India. Both cases presented with similar patterns of cutaneous reactions and respiratory symptoms shortly after intramuscular administration of the Hepatitis B vaccine. To our knowledge, this is among the few documented case series of neonatal anaphylaxis post–Hepatitis B vaccination, underscoring its rarity yet clinical importance. The cases highlight the critical importance of vigilant post-vaccination monitoring and prompt recognition of vaccine-associated adverse events in neonates. This report reviews current literature on anaphylaxis following vaccination and discusses optimal management strategies.

Hallucinations And Diabetes – Could It Be The Hip? An Interesting Case Of Cobalt Poisoning, Mahrukh Tariq, Zauraiz Anjum

Advances in Clinical Medical Research and Healthcare Delivery

Cobalt (Co) poisoning has been described historically in beer-drinkers when cobalt was used as an additive. In present times, this type of poisoning is usually caused by occupational exposure or metal prosthesis breakdown. We present a case of Co poisoning from metal prosthesis breakdown with exceptionally high levels, and thus, some unique symptoms. Interestingly our patient not only had symptoms commonly associated with Co poisoning, e.g., paresthesia, sensory-neural hearing loss, acute kidney failure, but also developed new onset diabetes, which is not commonly associated with this type of pathology. Moreover, when we had this patient under our care, we had …

Rare Presentation Of Omental Tuberculosis With Drug-Induced Jaundice In A Teenage Female: A Case Report, Archana Venkatesan, Krishna Ravi

Advances in Clinical Medical Research and Healthcare Delivery

Omental tuberculosis (TB) is a rare form of abdominal TB, often presenting with nonspecific symptoms that mimic malignancies. We report a case of a 16-year-old female from India who presented with abdominal distension, vomiting, weight loss, and amenorrhea. Imaging revealed an abdominal mass, and a diagnosis of omental TB was confirmed via histopathology. This case highlights the diagnostic challenge posed by such atypical presentations, especially in TB-endemic regions. The patient also developed rifampicin-induced jaundice, which resolved upon drug cessation and supportive care. Anti-TB therapy was cautiously reintroduced at a modified dose. This report underscores the need for high clinical suspicion, …

Bilateral Congenital Radioulnar Synostosis - Case Report, Derek A. Diangelis, Matthew J. Hudson

Advances in Clinical Medical Research and Healthcare Delivery

A 2-year-old male presented to an orthopedic outpatient office due to a supination defect in both of his upper limbs. X-rays of the affected limbs revealed fusion of the proximal radioulnar joints indicating congenital radioulnar synostosis (CRUS). CRUS is abnormal development of the upper limbs occurring during weeks 3—7 of embryological development. Causes of CRUS include genetic syndromes and spontaneous mutations. Treatment options include nonoperative and surgical treatments, however, treatment is controversial due to a lack of clinical evidence. Proposed screening methods could help improve detection rates and improve clinical management. This report aims to increase awareness of CRUS and …

A Case Of Fatal Herpes Zoster Ophthalmicus And Encephalitis In An Immunocompetent Host With A Review Of Literature, Kellyn E. Wilkes, Rutwik Pradeep Sharma, Laurie Proia

Advances in Clinical Medical Research and Healthcare Delivery

Herpes zoster is a common disease that can have several complications. Here, we present a case of herpes zoster ophthalmicus with coexisting encephalitis that unfortunately resulted in patient mortality. A 70-year-old male with a past medical history of Parkinson’s disease and schizophrenia presented to the emergency department after being found altered at home. Physical exam was notable for left-sided crusted facial rash, left conjunctival injection, and purulent drainage coming from the right eye. Given the location and appearance of his rash, he was diagnosed with herpes zoster ophthalmicus. There was suspicion for encephalitis given his altered mental status but unfortunately, …

Mycobacterium Shimoidei: A Case Report Of A Rare Nontuberculous Mycobacterial Infection In An American Patient With A Favorable Outcome, Madison Baker, Farah Majdoub, Asad Nasir

Advances in Clinical Medical Research and Healthcare Delivery

Non-tuberculous mycobacteria (NTM) are common environmental pathogens, but they are an uncommon cause of illness. One such mycobacteria, Mycobacterium shimoidei, was discovered in 1968 and found to cause a respiratory illness in 1975. Since then, fewer than 100 cases have been reported worldwide. Symptoms can include cough, fever, weight loss, and hemoptysis This report describes an American patient with no travel history who was found to have significant pulmonary disease caused by this rare non-tuberculous mycobacteria.

Insomnia In Stimulant Use Disorders: Prevalence And Associations With Negative Affect, Isabella G Bourtin, Constanza De Dios, Jessica Vincent, Joy M Schmitz, Scott D Lane, Heather E Webber

Faculty, Staff and Student Publications

Research suggests that sleep disturbances are common among people who use psychostimulants, including cocaine use and methamphetamine use. These sleep disturbances hinder recovery, heighten relapse risk, and worsen physical and mental health outcomes. This study aimed to estimate the prevalence and severity of insomnia among individuals who use cocaine and methamphetamine and to explore potential psychological factors that are associated with more severe insomnia. The sample included participants who completed in-person screening assessments for ongoing studies at an outpatient research clinic. As a part of this screening, participants completed the Insomnia Severity Index (ISI) and validated assessments of psychological domains …

Plasma Biomarker Progression Across The Alzheimer's Disease Amyloid Beta And Tau Positron Emission Tomography Trajectories, Rodrigo Cánovas, Christopher J. Fowler, Azadeh Feizpour, Vincent Dóre, Pierrick Bourgeat, Ziad S. Saad, Gallen Triana-Baltzer, Hartmuth C. Kolb, Manu Vandijck, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Jurgen Fripp, Simon Laws, Anthony W. Bannon, Kaj Blennow, Henrik Zetterberg, Stephanie Rainey-Smith, Sulantha Mathotaarachchi, Christopher C. Rowe, Colin L. Masters, James D. Doecke

Research outputs 2022 to 2026

Introduction: With increased uptake in disease-modifying treatments for amyloid beta (Aβ) removal, it is important to measure performance of highly sensitive plasma biomarkers to detect the presence of Aβ and tau in cognitively impaired populations. Methods: In this study, we investigated a large set of plasma biomarkers for their capability to predict Aβ and tau positron emission tomography (PET) and their association with increasing Aβ and tau burden. RESULTS: From the biomarkers assessed, tau phosphorylated at threonine 217 (pTau217) showed the largest increases across the full range of Aβ and tau levels. Furthermore, pTau217/Aβ42 had the smallest proportion of participants …

Regulation Of Autophagy-Mediated Pathways By Diet, Physical Activity, And Sleep In Alzheimer's Disease, Ajish Ariyath, Zoe Mputhia, Christopher Dougherty, Bushra Kaleelur Rahuman, W. M.A.D.Binosha Fernando, Belinda Brown, Samantha L. Gardener, Stephanie R. Rainey-Smith, Ralph Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Alzheimer's disease (AD) is a progressive, age-related, neurodegenerative disorder marked by cognitive decline, memory loss, and accumulation of amyloid beta (Aβ) plaques and tau tangles. A key feature of AD is impaired protein homeostasis, often driven by autophagy dysfunction. Autophagy, a cellular degradation and recycling process, plays a vital role in maintaining neuronal health and is increasingly recognized as a therapeutic target in AD. Lifestyle factors such as diet, physical activity, and sleep can positively influence autophagy and support cognitive function. Intermittent fasting (IF) and calorie restriction (CR) activate autophagy and promote longevity; physical activity enhances cerebral blood flow and …

Harmonizing Neuropsychological Test Data Across Prospective Studies, Rosita Shishegar, James D. Doecke, Yen Ying Lim, Pierrick Bourgeat, Vincent Dore, Bhargav Tallapragada, Simon M. Laws, Tenielle Porter, Samantha Burnham, Azadeh Feizpour, Ashley Gillman, Michael Weiner, Jason Hassenstab, Christopher C. Rowe, Victor L. Villemagne, Colin L. Masters, Jurgen Fripp, Hamid Sohrabi, Paul Maruff

Research outputs 2022 to 2026

Introduction: Alzheimer's disease (AD) research relies on large datasets and advanced statistical models. However, individual population studies often lack sufficient sample size for conclusive results. Harmonizing cognitive test data across studies can address this gap, despite differences in testing protocols. This study harmonizes cognitive data from three major AD cohorts to support robust clinical–pathological modelling. Methods: Information from the Alzheimer's Disease Neuroimaging Initiative (N = 1446); Australian Imaging, Biomarkers and Lifestyle (N = 1764); and Open Access Series of Imaging Studies-3 (N = 440) were integrated, including cognitive scores, demographics, genetics, and clinical and neuroimaging data. Neuropsychological tests relevant to …

The Long-Term Effectiveness Of The Anti-Obesity Medication Phentermine (Leap) Trial: Rationale, Design, And Baseline Characteristics, Caroline Blackwell Young, Emily Rives, Kimberly A Gudzune, Byron C Jaeger, Courtney G Simmons, Brian N White, Stephanie A Hooker, Deborah B Horn, Deborah R Young, Jennifer Vesely, Amanda Velazquez, Catherine Price, Shelly D Cook, Katy Martin-Fernandez, Galina Inzhakova, Nicholas M Pajewski, Jamy D Ard, Kristina H Lewis

Faculty, Staff and Student Publications

Background: Current clinical practice guidelines support the long-term use of pharmacotherapy for obesity treatment. Historically, phentermine has been one of the most prescribed obesity medications (OMs), however, its long-term efficacy and safety have never been evaluated in a randomized trial as its market approval predates such requirements. Here we describe the design, rationale, and baseline characteristics for a 24-month, double-blind, randomized controlled trial evaluating the efficacy, cardiovascular risk, and safety of phentermine in adults with overweight or obesity.

Methods: This multicenter trial will compare outcomes among participants randomized to phentermine 24 mg daily versus placebo for 24 months. All participants …

Cleavage And Polyadenylation Specificity Factor Subunit 5 Regulates Pulmonary Artery Smooth Muscle Expansion And Hypoxic Response, Scott D Collum, Lisha Zhu, Tingting W Mills, Rene Girard, Jamie Tran, Tinne C J Mertens, Cory Wilson, Nancy Wareing, Erik E Suarez, Howard J Huang, Rahat Hussain, Bindu Akkanti, Wenjin J Zheng, Hari K Yalamanchili, Bela Patel, Eric J Wagner, Sandeep Agarwal, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Pulmonary hypertension (PH) is a fatal condition that affects individuals with systemic sclerosis (SSc), a multiorgan fibrotic disease with limited treatment options. A central feature of PH is vascular remodeling, defined by the narrowing of the arteriole lumen due to cell proliferation and extracellular matrix deposition. Herein, we identify a central mechanism that can regulate multiple transcripts important for vascular remodeling. The highlight of our study is the demonstration that reduced pulmonary artery smooth muscle (PASMC) Nudt21, which codes for the RNA binding protein Cleavage and Polyadenylation Specificity Factor Subunit 5 (CPSF5) The, known to regulate alternative polyadenylation, results …

Pair-Feeding Study Designs Can Create Biases And Inflate Type I Error Rates: A Simulation Study, Wasiuddin Najam, Daniel E Kpormegbey, Deependra K Thapa, Bret Rust, Lilian Golzarri-Arroyo, Lance H Baumgard, Louis Wai-Tong Fan, Joseph G Ibrahim, Edith J Mayorga, David B Allison

Children’s Nutrition Research Center Staff Publications

Objective: Pair-feeding is a study design element where one group's food intake is provided to another group to assess whether a treatment effect is independent of food intake. Investigators often assume equivalent food intake across experimental conditions and exclude it from the statistical analysis. However, the impact of this practice on type I error (T1Er) rates has not been quantified.

Methods: We conducted a Monte Carlo simulation in which animals were assigned baseline weights and food intakes, then randomized to non-pair-fed or pair-fed groups. Daily food intake for both groups was initially drawn from the baseline food intake distribution. For …

Enteral And Intravenous Supplementation Of Arginine And Citrulline Fail To Prevent Necrotizing Enterocolitis In Preterm Neonatal Pigs, Caitlin Vonderohe, Julia Garcia Mancebo, Valeria Melendez Hebib, Barbara Stoll, Inka Didelija, Sarah Elefson, Mahmoud Mohammad, Brooklynn Earls, Greg Guthrie, Doug Burrin

Children’s Nutrition Research Center Staff Publications

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants with a morality rate that approaches 50%. Arginine has been widely studied in the field of clinical nutrition as a supplement for patients experiencing critical illness because it can be metabolized into nitric oxide, an important agent for supporting immunity and microcirculation. Citrulline has received less attention but can be metabolized into arginine and has a much longer plasma half-life than arginine. We used the highly translational preterm pig model to determine the effect of intravenous and enteral supplementation of arginine and citrulline on NEC incidence in …

Differential Longitudinal Effects Of Glucose-Lowering Medications On Glucagon And C-Peptide Responses In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness Study (Grade), Steven E Kahn, Mark Tripputi, John M Lachin, Ashok Balasubramanyam, Mary Ann Banerji, Joshua Barzilay, Robert M Cohen, W Timothy Garvey, Michaela R Gramzinski, Neda Rasouli, Mary Rhee, Jesse C Seegmiller, Vatsala Singh, William I Sivitz, Michael W Steffes, Kristina Utzschneider, Ralph A Defronzo

Faculty, Staff and Students Publications

Objective: To determine the longitudinal effects on α-cell function of four classes of glucose-lowering agents added to metformin in adults with type 2 diabetes.

Research design and methods: In a multicenter, randomized study, 5,047 participants ≥30 years of age with type 2 diabetes taking 1,000-2,000 mg metformin daily, HbA1c 6.8%-8.5%, were randomized to receive insulin glargine U100, glimepiride, liraglutide, or sitagliptin. In a subset of 724 participants, baseline and longitudinal measures of α-cell function were assessed as the fasting glucagon concentration and change in glucagon from fasting to 30 min following oral glucose (glucagon index [GGI]). Whether these measures and …

Unusual Endoscopic Remission In An Anti-Tumor Necrosis Factor Refractory Case Of Severe Ulcerative Colitis During Upadacitinib Therapy, Carine A Halaby, Charlotte F Kim, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Multi-Institutional Modified Delphi For Genomics In Expert Consensus Survey Of Genomic Testing For Anterior Skull Base Malignancies, Anirudh Saraswathula, Shreya Sriram, Corinna Levine, Nyall R London, Shirley Y Su, Mathew Geltzeiler, Sanjeet V Rangarajan, Ian Witterick, Brian Thorp, Kathleen Kelly Gallagher, Kenneth Byrd, Ricardo Carrau, Waleed Abuzeid, Eric Wang, Carl Snyderman, Erin L Mckean

Faculty, Staff and Students Publications

Objectives: The use of genomic testing for patients with anterior skull base malignancies has grown dramatically. There are no clear guidelines on indications for testing. As the literature on the subject is still in early stages, there is a need for expert consensus. We conducted a modified Delphi expert consensus process with high-volume North American cranial base surgical programs.

Design setting participants: A modified Delphi consensus approach was used, following the method laid out by the American Academy of Otolaryngology-Head and Neck Surgery, and included 13 high-volume care centers. An otolaryngologist was appointed at each location to serve as the …