Medical Specialties Commons^™

The Overlooked Impact Of Background Diet And Adherence In Nutrition Trials, Javier I Ottaviani, Hagen Schroeter, Dennis M Bier, John W Erdman, Howard D Sesso, Joann E Manson, Gunter G C Kuhnle

Children’s Nutrition Research Center Staff Publications

Randomised controlled trials in nutrition (RCTN) face unique challenges, including the considerable influence of the background diet and the challenge of assuring intervention adherence by participants. The impact of these factors on the outcome of RCTNs has been difficult to quantify, but nutritional biomarkers represent a valuable tool to address these challenges. Using flavanols as a model dietary intervention and a set of recently validated flavanol biomarkers, we here investigated the impact of background diet and adherence on the outcomes of a subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS, NCT 02422745). We found that 20% of participants …

Large B Cell Lymphoma Microenvironment Archetype Profiles, Xubin Li, Kartik Singhal, Qing Deng, Dai Chihara, David Russler-Germain, R Andrew Harkins, Jared Henderson, Kotaro Arita, Atish Kizhakeyil, Ryan Sun, Priya Lakra, Usama Hussein, Jennifer A Foltz, Ashley Wilson, Evelyn Schmidt, Imran Nizamuddin, Tommy Dinh, Akhil Kesaraju, Mark P Hamilton, Carl Allen, Maher K Gandhi, Joshua Tobin, Aixiang Jiang, Laura Hilton, David W Scott, Francisco Vega, Christopher R Flowers, Jason R Westin, Obi L Griffith, Todd A Fehniger, Malachi Griffith, Michael R Green

Faculty, Staff and Student Publications

Large B cell lymphomas (LBCL) are clinically and biologically heterogeneous lymphoid malignancies with complex microenvironments that are central to disease etiology. Here we have employed single-nucleus multiome profiling of 232 tumor and control biopsies to characterize diverse cell types and subsets that are present in LBCL tumors, effectively capturing the lymphoid, myeloid, and non-hematopoietic cell compartments. Cell subsets co-occurred in stereotypical Lymphoma Microenvironment Archetype Profiles (LymphoMAPs) defined by; (i) a sparsity of T cells and high frequencies of cancer-associated fibroblasts and tumor-associated macrophages [FMAC]; (ii) lymph node architectural cell types with naïve and memory T cells [LN]; or (iii) activated …

Mbiochemical Identification And Clinical Description Of Edetomidine Exposure In People Who Use Fentanyl In Philadelphia, Pa, Phil Durney, Jennifer L. Kahoud, Tareva Warrick-Stone, Maeve Montesi, Meg Carter, Sabrina Butt, Alberto Martinez Mencia, Louisa Omoregie, Monali Shah, Mariah Bloomfield, Nicholas Tomasko, Rebecca C. Jaffe, Allison Herens, Warren R. Korn, Karen Alexander, Douglas F. Stickle, Dennis Goodstein, Lara Weinstein, Kory S. London

Department of Emergency Medicine Faculty Papers

Medetomidine, a veterinary α2-adrenergic agonist, has recently emerged as an adulterant in the non-medical opioid supply, yet human exposure has remained poorly characterized. We conducted a pragmatic retrospective cohort analysis utilizing chart review and liquid chromatography-tandem mass spectrometry (LC-MS/MS) toxicology testing on available urine samples from patients presenting to two hospitals in Philadelphia, PA, who fit two clinical phenotypes, intoxication or withdrawal. Samples also underwent glucuronidase pre-treatment to assess impact on the yield of medetomidine and xylazine metabolite detection. Testing identified universal exposure to medetomidine (58/58 samples) via the 3-hydroxy-medetomidine (3-OH-M) metabolite, post glucuronidase treatment and variable xylazine exposure (40/58 …

Savings Associated With Bundled Payments For Outpatient Spine Surgery Among Medicare Beneficiaries, Austin S. Kilaru, Grace Y. Ng, Erkuan Wang, Erin Huang, Aidan P. Crowley, Jingsan Zhu, Joshua M. Liao, Said A. Ibrahim, Torrey Shirk, Deborah S. Cousins, Neil R. Malhotra, Amol S. Navathe

Department of Medicine Faculty Papers

IMPORTANCE: Few value-based payment programs have targeted outpatient surgery, although these procedures comprise most surgeries performed in hospitals. In 2018, the Centers for Medicare and Medicaid Services introduced Bundled Payments for Care Improvement Advanced (BPCI Advanced), the first episode-based payment model to include an outpatient surgical condition-spine surgery. It is not known whether bundled payments reduce spending or improve quality for outpatient surgery, despite plans to expand outpatient episodes in future models.

OBJECTIVE: To determine whether hospital participation in the first year of BPCI Advanced for outpatient and inpatient spine surgery (back and neck except spinal fusion procedures [BNESF]) was …

Hepatitis Patients Undergoing Cardiac Surgery: A Single-Center Retrospective Study, Jin-Long Ju, Yun-Tai Yao, Jun Li, Zhi Cheng, Ling-Ling Fan, Yu-Long Zhong

Faculty, Staff and Student Publications

This study aimed to investigate whether there is difference among various clinical variables, especially blood loss and total drainage volume, among patients with different types of hepatitis undergoing cardiac surgery. A retrospective study was performed on 150 hepatitis patients (127 hepatitis B and 23 hepatitis C) who underwent cardiac surgery at a single cardiovascular center in 2020. Data on their preoperative, intraoperative, and postoperative variables were collected and statistically analyzed to assess the inter-group differences in the following variables: intraoperative blood loss, postoperative drainage volume, proportion of patients treated with blood transfusion, proportion of patients treated with vasoactive drugs, and …

Prognostic Value Of Lipoprotein(A) For Cardiovascular Events After Lower Limb Revascularization In Diabetic Patients With Chronic Limb-Threatening Ischemia, Federico Biscetti, Maria Margherita Rando, Maria Anna Nicolazzi, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

BACKGROUND: Chronic limb-threatening ischemia (CLTI) presents a major clinical challenge in patients with Type 2 Diabetes Mellitus (T2DM), requiring lower extremity revascularization (LER) to mitigate adverse cardiovascular and limb outcomes. Lipoprotein(a) (Lp(a)) has been implicated in cardiovascular risk, but its role in patients with T2DM and CLTI undergoing revascularization remains unclear. Thus, this study aimed to investigate the prognostic value of Lp(a) levels in diabetic CLTI patients for major adverse cardiovascular events (MACE), major adverse limb events (MALE), or both after LER.

METHODS: In this prospective cohort study of 158 individuals with T2DM and CLTI undergoing LER, baseline clinical data …

The Impact Of Genetic Ancestry On Survival Outcomes In Pediatric Rhabdomyosarcoma: A Report From The Children’S Oncology Group, Ekene A Onwuka, Christina L Magyar, Bailey A Martin-Giacalone, Michael E Scheurer, Deborah A Marquez-Do, Mark Zobeck, Elizabeth G Atkinson, Erin R Rudzinski, Michael A Arnold, Donald A Barkauskas, David Hall, Javed Khan, Jack F Shern, Paul Scheet, Brian Crompton, Corinne M Linardic, Douglas S Hawkins, Rajkumar Venkatramani, Lisa Mirabello, Chad D Huff, Melissa A Richard, Philip J Lupo

Faculty, Staff and Student Publications

Emerging evidence suggests genetic ancestry may influence childhood cancer outcomes, but its impact on pediatric rhabdomyosarcoma (RMS) is unknown. We explored genetic ancestry's impact on survival among children with RMS. This multi-center observational cohort study is a secondary analysis of previously collected biobanking, genomic, and clinical data. The study included 920 individuals with newly diagnosed RMS under 40 years of age enrolled from 2005 to 2017 under the COG soft tissue sarcoma biobanking protocol D9902. The primary endpoints were (1) event-free survival (EFS), defined as the time from study enrollment to tumor recurrence/progression, secondary malignancy, or death from any cause; …

Braf V600e-Positive Mononuclear Cells In Blood At Diagnosis Portend Treatment Failure And Neurodegeneration In Pediatric Lch, Howard Lin, Akanksha Batajoo, Erin Peckham-Gregory, Daniel Zinn, Olive S Eckstein, Nader Kim El-Mallawany, Nitya Gulati, Zachary D Prudowsky, Brooks Scull, Jessica Velazquez, Harshal Abhyankar, Stephen J Simko, Daria Vakula, Ryan Fleischmann, Vivekanudeep Karri, M John Hicks, Kevin E Fisher, Choladda V Curry, Angshumoy Roy, Deborah Schiff, Kenneth M Heym, Michael E Scheurer, D Williams Parsons, Miriam Merad, Tsz-Kwong Man, Kenneth L Mcclain, Jennifer Picarsic, Carl E Allen

Faculty, Staff and Students Publications

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder driven by mitogen-activated protein kinase (MAPK) activation in hematopoietic cells. Historically, LCH has been staged according to involvement of "risk organs" (bone marrow, liver, and spleen), based on risk of death. With improvements in supportive care and efficacy of MAPK pathway inhibitors, patients with LCH now rarely die. However, most patients with LCH with multisystem disease are not cured with current front-line chemotherapy, and treatment failure is associated with long-term morbidity, including LCH-associated neurodegeneration (LCH-ND). In this study, we evaluated the impact of extent of LCH at presentation, tumor genotype, and …

Inferring Chromosome Segregation Error Stage And Crossover In Trisomic Disorders With Application To Down Syndrome, Zhenhua Li, Wenjian Yang, Gang Wu, Ti-Cheng Chang, Zhongshan Cheng, Meenakshi Devidas, Mary Shago, Andrew J Carroll, Nyla A Heerema, Julie M Gastier-Foster, Brent L Wood, Lauren Sanclemente, Elizabeth A Raetz, Stephen P Hunger, Mignon L Loh, Eleanor Feingold, Tracie C Rosser, Emily G Allen, Stephanie L Sherman, Karen R Rabin, Philip J Lupo, Jun J Yang

Faculty, Staff and Students Publications

Errors in chromosome segregation during gametogenesis, such as nondisjunction (NDJ) errors, have severe consequences in human reproduction, and a better understanding of their etiology is of fundamental interest in genetics. Mapping NDJ errors to meiotic/mitotic stages typically requires proband-parent comparison, limiting its applicability. Herein, we develop Mis-segregation Error Identification through Hidden Markov Models (MeiHMM), a method for inferring NDJ error stage and crossover events based on only genomic data of trisomic probands. Guided by triallelic genotype/haplotype configurations, MeiHMM discerns the allelic origin at each locus, which informs NDJ error during gamete formation, without identifying the parental origin of the trisomy. …

Flipping The Curriculum For Resident Didactics: In-Training And Certifying Examination Scores In An Internal Medicine Residency, Luke Mccoy, Ronald J. Markert, Elysha Thoms, Olivia Noall, Kathryn Burtson

Internal Medicine Faculty Publications

Purpose The flipped classroom (FC) model is increasingly used in undergraduate medical education, where it has been associated with improved knowledge acquisition. However, its impact on graduate medical education (GME) remains underexplored. We hypothesized that implementing a flipped didactics curriculum in our internal medicine residency program would improve performance on the Internal Medicine In-Training Examination (IM-ITE) and the American Board of Internal Medicine Certifying Examination (IM-CE). Methods In 2017, we transitioned from a traditional lecture-based (LB) curriculum to a flipped model. Noon conferences were replaced with problem-based learning (PBL) sessions three days per week, with additional active learning formats used …

Opposing Roles For Myeloid And Smooth Muscle Cell Sting In Pulmonary Hypertension, Ann T Pham, Shiza Virk, Aline C Oliveira, Matthew D Alves, Chunhua Fu, Yutao Zhang, Jimena Alvarez-Castanon, Brian B Lee, Keira L Lee, Radwan Mashina, Katherine E Ray, Patrick Donabedian, Elnaz Ebrahimi, Harsh Patel, Reeha Patel, Duncan Lewis, Zhiguang Huo, Harry Karmouty-Quintana, Li Chen, Lei Jin, Andrew J Bryant

Faculty, Staff and Student Publications

There is an emerging role for stimulator of interferon genes (STING) signaling in pulmonary hypertension (PH) development. Related to this, prior research has demonstrated the relevance of immune checkpoint protein programmed death ligand 1 (PD-L1) expression by immunoregulatory myeloid cells in PH. However, there remains a need to elucidate the cell-specific role of STING expression, and the STING/PD-L1 signaling axis in PH, before readily available disease-modifying therapies can be applied for patients with the disease. Here, through generation of bone marrow chimeric mice, we show that STING-/- mice receiving WT bone marrow were protected against PH secondary to chronic hypoxia. …

Nivolumab Plus Relatlimab For Patients With Relapsed Or Progressed B-Cell Malignancies In Relativity-022, Ajay K Gopal, Philippe Armand, Sattva S Neelapu, Nancy L Bartlett, Stephen E Spurgeon, John Kuruvilla, Kerry J Savage, John P Leonard, Arnold B Gelb, Nasir Ahmed, Shiqi Dong, Sai Praneeth Bathena, Rasika Suryawanshi, Jenny Qun Wu, Sheen Wang, Douglas E Gladstone

Faculty, Staff and Student Publications

Despite high response rates, anti-programmed death 1 (anti-PD-1) monotherapy eventually fails in most patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) and is ineffective in most other B-cell malignancies. The lymphocyte activation gene 3 (LAG-3) cell-surface receptor represents another immune checkpoint that can be targeted to induce remissions in these diseases; dual inhibition of PD-1 and LAG-3 is approved in advanced melanoma. We performed a multicenter phase 1/2a open-label study of the anti-LAG-3 antibody relatlimab (RELATIVITY-022) administered as monotherapy or in combination with nivolumab in patients with R/R B-cell malignancies. We treated 106 patients and no dose-limiting toxicities were observed during …

Pulsed Field Ablation Of Persistent Atrial Fibrillation With Continuous Electrocardiographic Monitoring Follow-Up: Advantage Af Phase 2., Vivek Y Reddy, Edward P Gerstenfeld, Boris Schmidt, Jason G Andrade, Devi Nair, Andrea Natale, Walid Saliba, Philipp Sommer, Andreas Metzner, Atul Verma, Troy Hounshell, Anish Amin, Philip Gentlesk, Stanislav Weiner, Frank A Cuoco, Jamie Kim, Mohit K Turagam, Gery Tomassoni, Chinmay Patel, Ziad Issa, Michael Shehata, Allison M Anderson, Thomas J Stoltz, Jonathan D Raybuck, Torri Schwartz, Brad S Sutton, Moussa Mansour

Heart and Vascular Articles

BACKGROUND: There are sparse high-quality safety and effectiveness data for pulsed field ablation (PFA) of persistent atrial fibrillation (PerAF), in which lesions beyond pulmonary vein isolation (PVI) are often placed. In addition, no large trials have used insertable cardiac monitors for continuous rhythm monitoring after ablation in patients with PerAF or after PFA in any atrial fibrillation population. In Phase 2 of the ADVANTAGE AF study (A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects With Persistent Atrial Fibrillation), patients with PerAF underwent PFA for PVI and posterior wall ablation (PWA) and, in …

High-Affinity Cd16a Polymorphism Associated With Reduced Risk Ofsevere Covid-19, Anita E Qualls, Tasha Tsao, Irene Lui, Shion A Lim, Yapeng Su, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Christian Bime, Carolyn S Calfee, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Impacc Network, Jason D Goldman, Daniel R Calabrese, James R Heath, James A Wells, Elaine F Reed, Lewis L Lanier, Harry Pickering, Oscar A Aguilar

Faculty, Staff and Students Publications

CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, particularly whether it limits viral spread and disease severity or contributes to the immunopathogenesis of COVID-19. We hypothesized that the high-affinity CD16AV176 polymorphism influences these outcomes. Using an in vitro reporter system, we demonstrated that CD16AV176 is a more potent and sensitive activator than the common CD16AF176 allele. To assess its clinical relevance, we analyzed 1,027 patients hospitalized with COVID-19 from the Immunophenotyping Assessment in a COVID-19 …

Development And Validation Of A Novel Clinical Risk Score To Predict Hypoxaemia In Children With Pneumonia Using The Who Prepare Dataset, Rainer Tan, Arjun Chandna, Tim Colbourn, Shubhada Hooli, Carina King, Norman Lufesi, Eric D Mccollum, Charles Mwansambo, Joseph L Mathew, Clare L Cutland, Shabir A Madhi, Marta Nunes, Sudha Basnet, Tor A Strand, Kerry-Ann F O'Grady, Brad Gessner, Emmanuel Addo-Yobo, Noel Chisaka, Patricia Hibberd, Prakash M Jeena, Juan M Lozano, William B Maleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Marilla Lucero, Syed Mohammad Akram Uz Zaman, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Mathuram Santosham, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean William Pape, Glaucia Paranhos-Baccala, Valentina S Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Romina Libster, Alexey W Clara, Fenella Beynon, Gillian Levine, Chris A Rees, Mark I Neuman, Shamim Qazi, Yasir Bin Nisar, World Health Organization Prepare Study Group

Faculty, Staff and Students Publications

Background: Hypoxaemia predicts mortality at all levels of care, and appropriate management can reduce preventable deaths. However, pulse oximetry and oxygen therapy remain inaccessible in many primary care health facilities. We aimed to develop and validate a simple risk score comprising commonly evaluated clinical features to predict hypoxaemia in 2-59-month-old children with pneumonia.

Methods: Data from seven studies conducted in five countries from the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) dataset were included. Readily available clinical features and demographic variables were used to develop a multivariable logistic regression model to predict hypoxemia (oxygen saturation < 90%) at presentation to care. The adjusted log coefficients were transformed to derive the PREPARE hypoxemia risk score and its diagnostic value was assessed in a held-out, temporal validation dataset. The model and risk score were analysed by evaluating the area under the receiver operating characteristic curve (AUC), sensitivity and specificity.

Results: We included 14 …

Supporting Patients With Advanced Cancer And Their Spouses In Parenting Minor Children: Results Of A Randomized Controlled Trial, Kathrin Milbury, Sujin Ann-Yi, Meagan S Whisenant, Morgan Jones, Yisheng Li, Victoria Necroto, Sania D Yousuf, Mariana Chavez-Macgregor, Larrisa Meyers, Eduardo Bruera

Faculty, Staff and Student Publications

Introduction: Patients with advanced cancer and their spousal caregivers who parent minor children report unmet parenting concerns and increased psychological distress. Seeking to address these important supportive care needs, this RCT examined the feasibility, acceptability, and initial evidence for the efficacy of a novel psychosocial intervention.

Patients and methods: Patients with a metastatic solid malignancy and their spouses completed self-reported validated assessments of psychological symptoms and cancer-related parenting outcomes and were then randomized to the parent support intervention or a usual care (UC) group. Both groups were reassessed 6 and 12 weeks later. Dyads randomized to the counselor-led intervention attended …

Transcriptomic And Histological Characteristics Of Innate Immune Activation In Brain Parenchyma In A Rat Model Of Neonatal Intraventricular Hemorrhage, Miriam Zamorano, Sanjna Udtha, Aidan M Collier, Erica Underwood, Razan El Sayed, Ankit Agarwal, Devin S Hatchell, Chunfeng Tan, Paul J Nietert, Scott D Olson, Brandon A Miller

Faculty, Staff and Student Publications

Background: Intraventricular hemorrhage (IVH) remains a major complication in preterm infants with lifelong sequelae. There is no effective treatment for IVH other than supportive care and surgery for post-hemorrhagic hydrocephalus. We previously reported that the innate neuroimmune response in an animal model of IVH was dependent on developmental stage, only occurring in older animals.

Methods: This study utilized a lysed-blood injection model of IVH in rats. This model specifically captures the effects of blood products released by IVH on brain parenchyma. We performed RNAseq and differential gene expression analysis on CD11b/c-positive cells in the brain (microglia/macrophages) to define gene expression …

Ptpn11 Mutations Define A Rare But Highly Adverse Subset Of Myelodysplastic Syndromes, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Kelly Chien, Koji Sasaki, Wei Ying Jen, Mahesh Swaminathan, Tapan Kadia, Courtney Dinardo, Farhad Ravandi, Guillermo Garcia-Manero, Hagop Kantarjian

Faculty, Staff and Student Publications

No abstract provided.

Genome-Wide Association Study For Lung Cancer In 6531 African Americans Reveals New Susceptibility Loci, Jinyoung Byun, Younghun Han, Jiyeon Choi, Ryan Sun, Vikram R Shaw, Catherine Zhu, Xiangjun Xiao, Christine Lusk, Hoda Badr, Hyun-Sung Lee, Hee-Jin Jang, Yafang Li, Hyeyeun Lim, Erping Long, Yanhong Liu, Linda Kachuri, Kyle M Walsh, John K Wiencke, Demetrius Albanes, Stephen Lam, Adonina Tardon, Marian L Neuhouser, Matt J Barnett, Chu Chen, Stig Bojesen, Hermann Brenner, Maria Teresa Landi, Mattias Johansson, Angela Risch, H-Erich Wichmann, Heike Bickeböller, David C Christiani, Gad Rennert, Susanne Arnold, John K Field, Sanjay Shete, Loic Le Marchand, Geoffrey Liu, Angeline S Andrew, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil Caporaso, Fiona Taylor, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Alpa Patel, Xihong Lin, Krista A Zanetti, Curtis C Harris, Stephen Chanock, James Mckay, Ann G Schwartz, Rayjean J Hung, Christopher I Amos

Faculty, Staff and Student Publications

Despite lung cancer affecting all races and ethnicities, disparities are observed in incidence and mortality rates among different ethnic groups in the United States. Non-Hispanic African Americans had a high incidence rate of lung cancer at 55.8 per 100 000 people, as well as the highest death rate at 37.2 per 100 000 people from 2016 to 2020. While previous genome-wide association studies (GWAS) have identified over 45 susceptibility risk loci that influence lung cancer development, few GWAS have investigated the etiology of lung cancer in African Americans. To address this gap in knowledge, we conducted GWAS of lung cancer …

Genomic Rare Variant Mechanisms For Congenital Cardiac Laterality Defect: A Digenic Model Approach, Archana Rai, Jonathan Klonowski, Bo Yuan, Karen J Coveler, Zain Dardas, Iman Egab, Jiaoyang Xu, Philip J Lupo, A J Agopian, Dennis Kostka, Cecilia W Lo, S Stephen Yi, Bruce D Gelb, Christine E Seidman, Eric Boerwinkle, Jennifer E Posey, Richard A Gibbs, James R Lupski, Shaine A Morris, Zeynep Coban-Akdemir

Faculty, Staff and Students Publications

Laterality defects are defined by perturbations in the usual left-right asymmetry of organs. The genetic etiology that underlies congenital heart disease (CHD) is often unknown (less than 40%), so we used a digenic model approach for the identification of contributing variants in known laterality-defect-associated genes (n = 115) in the exome/genome sequencing (ES/GS) data from individuals with clinically diagnosed laterality defects. The unsolved ES/GS data were analyzed from three CHD cohorts: Baylor College of Medicine-Genomics Research to Elucidate the Genetics of Rare Diseases (BCM-GREGoR; n= 251 proband ES), Gabriella Miller Kids First Pediatric Research Program (Kids First; n = 158 …

Testosterone Deficiency And Treatments: Common Misconceptions And Practical Guidance For Patient Care, Mohit Khera, James M Hotaling, Martin Miner

Faculty, Staff and Students Publications

Introduction: Misconceptions about testosterone therapy are prevalent and there is an unmet need for a review of current literature that can be leveraged by physicians to deliver safe and effective care for men with hypogonadism.

Objectives: This review aims to address common misconceptions about testosterone therapy using current literature and synthesize practical guidance for clinicians with patients who are starting testosterone therapy.

Methods: A literature search of PubMed, Embase, CINAHL was carried out to identify associations between testosterone therapy and prostate cancer, cardiovascular risk, and hepatic toxicity; definitions of hypogonadism; and practical guidance for clinician with patients starting testosterone therapy. …

Assessment Of Functioning Using The Whodas 20 Among People With Myasthenia Gravis-Associated Disability: A Nationwide Follow-Up Study, Jia-Pei Hong, Chih-Hong Lee, Chien Tai Hong, Lung Chan, Chen-Chih Chung, Prangthip Charoenpong, Hou-Chang Chiu, Tsan-Hon Liou

Faculty, Staff and Students Publications

Background: Advancements in treatment have increased the life expectancy of patients with Myasthenia Gravis (MG), yet the understanding of functional changes in these individuals remains limited. In our study, we explored the functional abilities of individuals with MG using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).

Methods: This observational study analyzed data from 286 patients with MG, acquired from the Data Bank of Persons with Disabilities (TDPD) in Taiwan between July 11, 2012, and December 31, 2021. Participants were diagnosed with MG after the acute phase. The functional disability outcome was assessed using the WHODAS 2.0. Due …

Immature Acta2r179c/+ Smooth Muscle Cells Cause Moyamoya-Like Cerebrovascular Lesions In Mice Prevented By Boosting Oxphos, Anita Kaw, Suravi Majumder, Jose E Esparza Pinelo, Ting Wu, Zbigniew Starosolski, Zhen Zhou, Albert J Pedroza, Xueyan Duan, Kaveeta Kaw, Angie D Gonzalez, Ripon Sarkar, Michael P Fischbein, Philip L Lorenzi, Lin Tan, Sara A Martinez, Iqbal Mahmud, Laxman Devkota, L Maximilian Buja, Heinrich Taegtmeyer, Ketan B Ghaghada, Sean P Marrelli, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

ACTA2 pathogenic variants altering arginine 179 cause childhood-onset strokes due to moyamoya disease (MMD)-like occlusions of the distal internal carotid arteries, but the mechanisms of pathogenesis are unknown and no preventive treatments exist. Here we show that Acta2R179C/+ smooth muscle cells (SMCs) fail to fully differentiate and maintain stem cell-like features, including increased migration and glycolytic flux compared to wildtype (WT) SMCs. Increasing mitochondrial respiration with nicotinamide riboside (NR) drives differentiation and decreases migration of Acta2R179C/+ SMCs. Carotid artery injury of Acta2SMC-R179C/+ mice leads to premature death, intraluminal SMC accumulation leading to MMD-like occlusive lesions, neurologic symptoms, …

Serological Analysis Indicating The Exposure Of Two Volunteers To Relapsing Fever Borrelia Sp. In Nayarit, Mexico, Sofía L Luna-Rojas, Edwin Vázquez-Guerrero, Jose A Hernández-Martínez, Jeanet Serafín-López, Fernando Martínez-Hernández, José Alejandro Martinez-Ibarra, Rigoberto Hernández-Castro, Job E López, J Antonio Ibarra

Faculty, Staff and Students Publications

Relapsing fever caused by Borrelia sp. is a neglected disease in Mexico and more studies are needed to update its presence in multiple regions of the country. Here, recombinant proteins glycerophosphodiester phosphodiesterase (GlpQ) and three Borrelia immunogenic protein A (BipA) variants were used for serosurveillance in 142 human serum samples. Results showed that two persons were positive to Borrelia extracts and GlpQ but negative to all three BipA, suggesting they were infected by relapsing fever spirochetes of a yet to be determined species. This shows that testing for GlpQ and Borrelia extracts are a useful tool for potential infections and …

Evaluation Of The Feasibility And Effectiveness Of Trauma-Focused Cognitive Behavioural Therapy For Children And Youth In Ukraine During The War, Elisa Pfeiffer, Maike Garbade, Renee Beer, Anette Birgersson, Natalie Cabrera, Judith A Cohen, Esther Deblinger, Rafaela Gjini, Veronica Kirsch, Zlatina Kostova, Michael Larsson, Anthony Mannarino, Gavin Moffitt, Marja Onsjö, Tale Ostensjo, Anna Vikgren, Hanna Weyler, Vitalii Klymchuk, Cedric Sachser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: The large-scale Russian invasion of Ukraine in early 2022 resulted in a humanitarian crisis with hundreds of thousands of children exposed to traumatic events. To date, trauma-focused evidence-based treatments (EBTs) for children and youth have not been systematically evaluated and implemented in Ukraine. This study aims at evaluating 1) the feasibility of a training program for Ukrainian therapists on Trauma-Focused Cognitive Behavioural Therapy (TF-CBT) and 2) the feasibility and effectiveness of the treatment for children, youth, and their families in and from Ukraine during the ongoing war.

METHODS: The project "TF-CBT Ukraine" was implemented between March 2022 and May …

C-Terminal Frameshift Variants In Gpkow Are Associated With A Multisystemic X-Linked Disorder, Jung-Wan Mok, Laura Mackay, Maria Blazo, Elizabeth Mizerik, Jozef Gecz, Renee Carroll, Mathilde Nizon, Sophie Rondeau, Madeleine Joubert, Silvestre Cuinat, Wallid Deb, Fernanda Valle Sirias, Monika Weisz-Hubshman, Shamika Ketkar, Urszula Polak, Alyssa A Tran, Debra Kearney, Neil A Hanchard, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Brendan H Lee, Shinya Yamamoto, Keren Machol

Duncan NRI Faculty and Staff Publications

Purpose: GPKOW, a gene on the X-chromosome, encodes a nuclear RNA-binding protein important in messenger RNA (mRNA) processing as a spliceosome subunit. This work aims to establish GPKOW as a disease-associated gene.

Methods: We describe 3 males from 2 unrelated families with hemizygous frameshift variants affecting the last exon of GPKOW p.(Arg441SerfsTer30) and p.(Ser444GlufsTer28). The effect of p.(Ser444GlufsTer28) on gene expression was evaluated in patient's fibroblasts. In vivo studies in Drosophila melanogaster targeting the sole GPKOW fly ortholog, CG10324 (Gpkow) were performed.

Results: Clinical presentations included intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities. Heterozygote females presented …

Systemic Exogenous Progestins With Or Without Estrogens Are Associated With Decreased Rates Of Venous Procedures For Varicose Veins, Paarth Jain, Adam M. Ostrovsky, Paul J Dimuzio, Luis H. Eraso, Michael Nooromid, Dawn Salvatore, Babak Abai

Department of Surgery Faculty Papers

OBJECTIVES: Risk factors for varicose veins (VVs) such as female sex, pregnancy, and obesity are high estrogen states, yet the role of systemic progestins with or without estrogens (SPEs) in VV management is not well characterized. This study investigates how SPE use affects rates of venous procedures for patients with VV.

METHODS: The TriNetX database was queried for subjects with International Classification of Diseases, 10th edition, diagnoses of asymptomatic VV, chronic venous insufficiency, and complicated VV (inflammation or ulceration). Patients were divided into a control cohort with no subsequent SPE use, a progestin-only cohort, and a combined estrogen-progestin (CEP) cohort. …

Who Reconstitutes The Chemotherapy? The Educational And Practice Needs Of Oncology Pharmacists In West Africa: A Call For Multidisciplinary Team Approach In Oncology Care., Runcie C.W. Chidebe, Ramatu M. Alabelewe, Krishna Prasad Sapkota, Darlingtina K. Esiaka, Candidus C. Nwakasi, Gloria C. Okwu, Jacinta Emejulu, Adamu A. Umar, Ndifreke Okwuegbunam, Funsho David, Toyosi Adepoju, Agha A. Agha, Ejike S. Ugwu, Simeon C. Aruah, Richard Mshelia, Rob Duncombe, Noel N. Wannang, Peace C. Babalola, R. Donald Harvey, Cindy O'Bryant, Folakemi T. Odedina

Behavioral Science Faculty Publications

PURPOSE: Oncology pharmacists (OPs) play a crucial role in cancer care, treatment, survivorship, and multidisciplinary teams (MDTs). OPs have specialized training in designing, administering, monitoring, and modifying oncology chemotherapy; managing adverse events; and evaluating clinical trials and investigational drugs. Yet, the state of OP has remained largely unknown in the clinical oncology workforce of the West African region. Therefore, this study aimed to understand who reconstitutes chemotherapy and to explain the OP educational and practice needs, challenges, and solutions in Nigeria.

MATERIALS AND METHODS: Using a concurrent embedded mixed method design, 35 OPs completed a questionnaire, and 12 others responded …

Individualized Functional And Structural Language Lateralities In Temporal Lobe Epilepsy And Their Impact On Memory, Ankeeta Ankeeta, Qirui Zhang, Sam Sharifzadeh Javidi, Shilpi Modi, Michael R. Sperling, Joseph I. Tracy

Department of Neurology Faculty Papers

The basis and impact of functional asymmetries in the brain, particularly language lateralization, are not fully understood, and the relationship between functional and structural asymmetries remains largely untested. This study investigated the degree to which asymmetries in hemispheric language laterality are concordant with asymmetries in gray matter (GM) structure and whether the hemispheric organization of memory is influenced by functional language asymmetries. Structural and functional MR data was acquired from 261 individuals, including those with unilateral temporal lobe epilepsy (LTLE = 96, RTLE = 69) and matched with healthy participants (HPs = 96). Functional language laterality indices (LIs) were calculated …

Multiple Subcortical And Subcortico-Cortico Dynamic Network Reconfigurations Characterize Focal-To-Bilateral Tonic-Clonic Seizures, Shilpi Modi, A. Ankeeta, Walter Hinds, Michael R. Sperling, Xiaosong He, Joseph I. Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE) is the most common focal epilepsy, with focal to bilateral tonic-clonic seizures (FBTCS+) a more severe form of the disorder. Evidence has underscored the critical role of the thalamus, mesial temporal region, basal ganglia and cerebellum, along with the cortex, in the propagation, termination, and modulation of seizure activity. We examined time variant patterns of interaction within and between 7 cortical and 4 subcortical systems in 55 healthy controls and 56 patients with TLE (n = 40 with FBTCS+ and 15 without), isolating those patterns most distinctive of FBTCS+ utilizing tools from dynamic network neuroscience on …