Digital Commons Network^™

Population-Scale Sequencing Resolves Determinants Of Persistent Ebv Dna, Sherry S Nyeo, Erin M Cumming, Oliver S Burren, Meghana S Pagadala, Jacob C Gutierrez, Thahmina A Ali, Laura C Kida, Yifan Chen, Hoyin Chu, Fengyuan Hu, Xueqing Zoe Zou, Benjamin Hollis, Margarete A Fabre, Stewart Macarthur, Quanli Wang, Leif S Ludwig, Kushal K Dey, Slavé Petrovski, Ryan S Dhindsa, Caleb A Lareau

Duncan NRI Faculty and Staff Publications

Epstein–Barr virus (EBV) is an endemic herpesvirus implicated in autoimmunity, cancer and neurological disorders. Although primary infection is often subclinical, persistent EBV infection can drive immune dysregulation and long-term complications. Despite the ubiquity of infection, the determinants of EBV persistence following primary exposure remain poorly understood, although human genetic variation partially contributes to this phenotypic spectrum1–3. Here we demonstrate that existing whole genome sequencing (WGS) data of human populations can be used to quantify persistent EBV DNA. Using WGS and health record data from the UK Biobank (n = 490,560) and All of Us ( …

Maternal Myo-Inositol Intake And Congenital Heart Defects In Offspring: A Population-Based Case-Control Study, Ruiqi Cen, L Joseph Su, Jun Ying, Mohammed S Orloff, Elijah H Bolin, Xiangyang Lou, Lynn M Almli, Lorenzo D Botto, Marilyn L Browne, Richard H Finnell, Mary M Jenkins, Eirini Nestoridi, Andrew F Olshan, Paul A Romitti, Gary M Shaw, Wendy N Nembhard

Faculty, Staff and Students Publications

Objective: To investigate associations between maternal periconceptional (three months prior through the third pregnancy month) myo-inositol intake and the odds of selected congenital heart defects in offspring.

Design: A population-based case-control study using the National Birth Defects Prevention Study (NBDPS) database.

Setting: United States.

Population or sample: Women with singleton live births without major birth defects (controls) and women with singleton live births, stillbirths, or terminations with selected nonsyndromic congenital heart defects (CHD; cases).

Methods: Descriptive analyses, logistic regression models, ascertainment of myo-inositol intake from supplements and food using a shortened food frequency questionnaire and survey.

Main outcome measures: Odds …

Purpuric Pityriasis Rosea In A 7-Year-Old Girl: A Rare Variant With Generalized Involvement, Ying-Ying Qian, Ya-Fen Wu, Ting Zhang, Ji-Bing Li, Si-Yuan Song, Wei Li

Faculty, Staff and Students Publications

A 7-year-old girl presented with a 10-day history of generalized purpura and petechiae. The eruption began with a solitary violaceous macule on the trunk and progressed within 1 week to multiple oval and round dark-red to violaceous purpuric macules, ecchymoses, and petechiae affecting the face, trunk, and extremities. Lesions were distributed parallel to skin cleavage lines with a characteristic “Christmas-tree” pattern on the back (Fig 1). No oropharyngeal lesions were noted on examination, and the patient denied sore throat or oral discomfort. She reported no pruritus, pain, fever, or systemic symptoms.

Prospective Evaluation Of The European Society Of Cardiology 0/1h-Algorithm’S Safety And Efficacy For Triage Of Patients With Suspected Myocardial Infarction (Presc1se-Mi): Rationale And Design Of A Prospective International Multicenter Stepped-Wedge Cluster Randomized Controlled Trial, Jasper Boeddinghaus, Paolo Bima, Luca Crisanti, Dagmar I Keller, Ksenija Slankamenac, Michael Christ, Philipp Schuetz, Andrea Wiencierz, Ivo Strebel, Julia Reinhardt, Iryna Vyshnevska, Tzu-Ying Tsao, Felix Mahfoud, Maria Pia Ruggieri, Stephan Steuer, Òscar Miró, Veli-Pekka Harjola, Fulvio Morello, Peiman Nazerian, Dominik Roth, José Luis Zamorano, Deborah Erica Gannon, Jason Pott, Mohammed Oa Abubakr, Hyun Suk Yang, Joe Young, Richina Bicette, Andreea Cuculici, Héctor Bueno, Juan Sanchis, Christian Mueller

Faculty, Staff and Students Publications

Background: International practice guidelines recommend the more rapid European Society of Cardiology (ESC) 0/1h-algorithm for the triage of patients with suspected myocardial infarction (MI) as the preferred option and consider the ESC 0/3h-algorithm as an alternative. However, many centers worldwide have not yet adopted the ESC 0/1h-algorithm in clinical practice due to uncertainty which approach best balances safety and efficacy.

Methods: PRESC1SE-MI (PRospective Evaluation of the European Society of Cardiology 0/1h-algorithm`s Safety and Efficacy for Triage of Patients with Suspected Myocardial Infarction) is an international, investigator-initiated multicenter, stepped-wedge, cluster randomized controlled trial. At least 52,156 consecutive adult patients with nontraumatic …

Training In Medications For Opioid Use Disorder And Buprenorphine Prescribing In The Post X-Waiver Era: Insights From A Nationwide, Multispecialty Survey, Sung In H Kim-Vences, Justin Nguyen, Jacqueline M Hirth, Kyle P Suen, Colleen A Keough, Roger Zoorob, Alicia A Kowalchuk

Faculty, Staff and Students Publications

Objective: The January 2023 repeal of the X-waiver aimed to reduce regulatory barriers to buprenorphine prescribing and enhance patient access to medications for opioid use disorder (MOUD). Its impact on prescribing by non-addiction-trained physicians, the integration of MOUD training into residency programs, and the role of mandated training on clinical practice remain unclear.

Methods: A 2024 online survey assessed physicians' awareness of the X-waiver repeal, exposure to MOUD training, and changes in buprenorphine prescribing. Multivariable logistic regression evaluated the independent effect of MOUD training and whether mandatory versus voluntary formats influenced prescribing behavior.

Results: Among 959 physicians (42.7 % residents), …

Baseline Characteristics In The Synchronize™-2 Randomized Phase 3 Trial Of Survodutide, A Glucagon Receptor/Glp-1 Receptor Dual Agonist, For Obesity In People With Type 2 Diabetes, Sean Wharton, Carel W Le Roux, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide is an investigational glucagon receptor/glucagon-like peptide-1 receptor dual agonist that has shown promise for treating obesity and its complications in Phase 2 trials. Two double-blind, randomized, global Phase 3 trials are designed to assess the efficacy and safety of survodutide for treatment of obesity-SYNCHRONIZE™-1 in people with obesity without type 2 diabetes (T2D) and SYNCHRONIZE™-2 in people with obesity and T2D. This paper describes the baseline characteristics of participants in SYNCHRONIZE-2 (ClinicalTrials.gov identifier NCT06066528).

Materials and methods: Participants aged ≥18 years with a body mass index (BMI) ≥27 kg/m2 and T2D were randomized 1:1:1 to weekly subcutaneous …

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 …

Factors Associated With Rare Pediatric Cancer Trial Enrollment: A Report From The Children's Oncology Group Rare Tumors Committee, Brian R Englum, Jin Piao, Lindsay Younis, Reto M Baertschiger, Kenneth S Chen, Emily Christison-Lagay, Hetal Dholaria, Robyn Gartrell, M John Hicks, Junne Kamihara, Sarah G Mitchell, Manuela Orjuela-Grimm, Farzana Pashankar, Samara L Potter, Jennifer H Aldrink, Jeremy Rosenblum, Michael R Sargen, Kris Ann P Schultz, Brittani K N Seynnaeve, Mary Wedekind, Theodore W Laetsch

Faculty, Staff and Students Publications

Background: Over 90% of US children with cancer are treated at Children's Oncology Group (COG) centers, which seek to maximize enrollment in therapeutic and biobanking studies. Rare cancers have demonstrated lower than expected COG enrollment. We evaluated trends in COG rare cancer enrollment compared to US incidence from Surveillance, Epidemiology, and End Results (SEER) registries, examining the impact of COG therapeutic trials and Project:EveryChild, a cancer biobank/registry.

Procedure: COG and SEER data from 2002 to 2020 were queried for US patients younger than 18 years old with adrenocortical carcinoma (ACC), nasopharyngeal carcinoma (NPC), retinoblastoma (RB), thyroid carcinoma, and melanoma. We …

Internet-Delivered Cognitive-Behavioral Intervention For Pain In Pediatric Acute Recurrent And Chronic Pancreatitis: A Multicenter Randomized Controlled Trial, Tonya M Palermo, Rui Li, Chuan Zhou, Homer Aalfs, Gretchen Cress, Mark Lowe, Maisam Abu-El-Haija, Ankur Chugh, Elissa M Downs, Douglas S Fishman, Alvin Jay Freeman, Matthew J Giefer, Tanja Y Gonska, Sohail Z Husain, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Robert Adam Noel, Emily R Perito, Fuchenchu Wang, Ying Yuan, Yuhua Zheng, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Objectives: Abdominal pain is common and associated with high disease burden and health care costs in pediatric acute recurrent (ARP) and chronic pancreatitis (CP). Despite the effectiveness of psychological interventions in other abdominal pain populations, studies have not evaluated these interventions for pediatric pancreatitis pain. We evaluated the feasibility, acceptability, and preliminary efficacy of internet-delivered cognitive-behavioral therapy (CBT) for reducing pancreatitis-related abdominal pain and improving pain interference, anxiety, depression, activity limitations, and health-related quality of life.

Methods: We enrolled 90 adolescents (ages 10-19, 63% female) with ARP or CP and their parents into this randomized placebo-controlled multicenter trial from 15 …

Dolichocolon Is Common In Pediatric Gastroenterology Patients With Constipation And Associated Complaints, David Simon, Donovan Berens, Raul Zambrana Valenzuela, Arvind Mohan, Partha Chakraborty, Timot Kellermayer, Eric H Chiou, Craig L Jensen, Ricardo A Arbizu, Marla B K Sammer, Richard Kellermayer

Faculty, Staff and Students Publications

Objectives: Dolichocolon (DC), classified under International Classification of Diseases, Tenth Revision (ICD-10) code Q43.8 ("Other specified congenital malformations of intestine"), refers to an elongated or redundant large intestine. Recent studies in adults indicate a role for dolichocolon in constipation and disorders of gut-brain interaction. Contrast enema (CE) imaging is commonly used to identify DC, typically defined as a sigmoid colon extending above, or a transverse colon descending below, the iliac crest line. Despite its potential relevance, the prevalence and clinical significance of DC in pediatric gastroenterology remain poorly understood.

Methods: This retrospective study assessed the prevalence of DC in pediatric …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach, Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary A Churchill, David B Allison

Children’s Nutrition Research Center Staff Publications

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

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 …

Rare Heterozygous Missense Variants In Vsx2 Are Associated With Retinal Detachment, Daniel C Brock, Justin S Dhindsa, Yifan Chen, Vida Ravanmehr, Jonathan Mitchell, Fengyuan Hu, Xiaoyin Li, Likhita Nandigam, Quanli Wang, Kevin Wu, Jessica C Butts, Hardeep S Dhindsa, Benjamin J Frankfort, Nicholas M Tran, Slavé Petrovski, Ryan S Dhindsa

Duncan NRI Faculty and Staff Publications

Retinal detachment (RD) is a sight-threatening emergency requiring urgent intervention to prevent permanent vision loss. While both environmental and genetic risk factors contribute to RD, its complete genetic architecture remains unknown. Here, we performed the largest whole genome sequencing-based case-control study in RD to date, including data from 7,276 RD cases and 236,741 controls in the UK Biobank. Through variant- and gene-level association analyses, we identified VSX2 as a genetic determinant of RD risk while confirming established associations including FAT3, RDH5, and COL2A1. Gene-level collapsing analysis revealed that rare heterozygous missense variants in VSX2 confer a 2.8-fold …

Computational Single-Neuron Mechanisms Of Visual Object Coding In The Human Temporal Lobe, Runnan Cao, Jie Zhang, Jie Zheng, Yue Wang, Peter Brunner, Jon T Willie, Shuo Wang

2020-Current year OA Pubs

Understanding how the human brain encodes visual objects involves deciphering the neural computations and circuits in the temporal lobe. Here, we recorded intracranial EEG from the human ventral temporal cortex (VTC) and medial temporal lobe (MTL), as well as single-neuron activity in the MTL, to investigate the computational mechanisms of neural object coding. The VTC exhibited axis-based feature coding, and a neural feature space could be constructed using VTC neural axes, within which visual objects clustered according to high-level categorical relationships. Importantly, MTL neurons encoded receptive fields within this VTC neural feature space, exhibiting selective responses to objects that shared …

Prediabetes Associates With Musculoskeletal Alterations Independent Of Total Body Adiposity, Alan Fappi, Clifton J Holmes, Chao Cao, Vasavi Shabrish, Aman P Aher, Karen Shen, Paul K Commean, Dwight A Towler, Dominic N Reeds, Gretchen A Meyer, Bettina Mittendorfer

2020-Current year OA Pubs

BACKGROUND: Excess adiposity is a major risk factor for insulin resistance, prediabetes, and Type 2 diabetes and increases the risk for sarcopenia and osteosarcopenia later in life. It has been proposed that altered metabolic function and musculoskeletal status in people with obesity are directly linked, presumably because they share common pathophysiological mechanisms. However, the effect of metabolic dysfunction, independent of adiposity, on musculoskeletal status is unknown.

METHODS: We performed a comprehensive assessment of musculoskeletal status in people with overweight/obesity and prediabetes (n = 12; 72% women; age: 67 ± 6 years; weight: 81 ± 11 kg; mean ± SD) and …

Clinical Evaluation Of Nasal Swab Specimens In Vtm/Utm And Respdirect Estm Using The Panther Fusion Sars-Cov-2/Flu A/B/Rsv Assay., Salika M. Shakir, Robert K. Mccall, Rangaraj Selvarangan, Dithi Banerjee, Yitz Goldstein, Christine Lansang, Rachel Bogh, Carmelle V. Remillard, Respdirect Clinical Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Respiratory viral infections by SARS-CoV-2, influenza A and B viruses, and RSV overlap in disease signs and symptomology, but differ in treatment modality. Nasal swab specimens have been shown to be an effective alternative specimen type for SARS-CoV-2 detection.

OBJECTIVES: This study evaluated the performance of the Panther Fusion® SARS-CoV-2/Flu A/B/RSV assay in anterior nasal swab specimens (self- or healthcare professional [HCP]-) collected in either viral/universal (VTM/UTM) transport media or the Hologic® RespDirect® collection kit (RespDirect swab in enhanced specimen transport media [eSTM]).

STUDY DESIGN: A multicenter study was conducted from October 2022 to March 2024. A total of …

Progressive Neuroinflammation And Deficits In Motor Function In A Mouse Model With An Epg5 Pathogenic Variant Of Vici Syndrome., Bradley Thornton, Alexandra G. Hardinger, Laramie Pence, Priyanka Prem Kumar, Nikolas Connolly, Scott J. Weir, Jay L. Vivian

Manuscripts, Articles, Book Chapters and Other Papers

Vici syndrome (VS) is a rare pediatric genetic disorder characterized by profound developmental delay, seizures, immune deficits, cardiomyopathy and progressive motor dysfunction. This devastating condition is caused by pathogenic variants in the EPG5 gene, which encodes a regulator of autophagy, leading to the accumulation of toxic intracellular material and widespread cellular dysfunction. Less-severe EPG5 pathogenic variants have recently been linked to rare familial forms of Parkinson's disease, suggesting deficits in EPG5 function drive a range of neurodegenerative disorders. Currently, there are no effective treatments for any disorders associated with pathogenic variants of EPG5. The underlying cellular mechanisms driving the progressive …

Intraoperative Care And Complications Of Symptomatic Adolescent And Young Adult Patients Undergoing Laparoscopy To Diagnose And/Or To Treat Endometrioses: A Multi-Institutional Review., Jacquelyn R. Evans, Katherine Bergus, Lindsey Asti, Lesley L. Breech, Ruiqi Cen, Yuan Yuan Gong, S Paige Hertweck, Holly R. Hoefgen, Anne H. Horne, Ashli A. Lawson, Seema Menon, Kathleen E. O'Brien, Shashwati Pradhan, Brenna Rachwal, Yolanda R. Smith, Priya Suvarna, Sarah Van Son, Geri Hewitt

Manuscripts, Articles, Book Chapters and Other Papers

STUDY OBJECTIVE: This multi-institutional, retrospective study explores the risks of laparoscopy for diagnosis and treatment of endometriosis to facilitate shared medical decision-making in patients age < 22 years old with chronic pain considering surgery.

METHODS: A retrospective review of patients less than 22 years old who had surgically proven endometriosis at eight pediatric hospitals was completed. Patient demographics, operative interventions, concurrent procedures, and complications were evaluated.

RESULTS: There were 284 patients with pathologically confirmed endometriosis with a median age of 16.86 years (15.51, 18.06). During the index procedure, diagnostic biopsy alone was performed (35.92%), followed by ablation (29.93%), excision (20.07%), excision and ablation (12.68%), and cryoablation (1.41%). Most common …

Flare Guns And Trauma: Patterns, Severity, And Clinical Implications From Case And National Surveillance Data, Ramsay Hafer, Andrew Huff, Lara Phillips

Department of Emergency Medicine Faculty Papers

Flare guns are pyrotechnic devices capable of causing serious injury due to high-temperature combustion and projectile discharge. Though intended for signaling in maritime or wilderness settings, improper use can result in trauma patterns distinct from those seen with typical burns or fireworks. Despite their severity, flare gun injuries remain underreported and poorly characterized. We conducted a scoping review of PubMed, Scopus, and Ovid to identify 12 case reports involving 13 patients, and reviewed US National Electronic Injury Surveillance System records from 2015 to 2024, identifying 18 flare gun-specific injuries for a combined total of 31 injuries. Demographic, injury mechanism, body …

Leveraging The Pedsnet Clinical Research Network And Electronic Health Record Data To Enhance Efficiency Of Trial Enrollment For A Rare Pediatric Rheumatic Disease, Pamela F Weiss, Levon Utidjian, Mitchell Maltenfort, Hanieh Razzaghi, Timothy G Brandon, Cassandra Muir, Cora Sears, Edward J Oberle, Jennifer Cooper, Kevin Baszis, Mary B Toth, Esi M Morgan, Christopher B Forrest

2020-Current year OA Pubs

BACKGROUND: We evaluated the PEDSnet clinical research network for study enrollment of juvenile spondyloarthritis, a rare rheumatic disease that includes enthesitis-related arthritis (ERA) and psoriatic arthritis (PsA). METHODS: An electronic health record (EHR)-based typology was developed by an interdisciplinary team to query EHR data for a spectrum of pediatric rheumatic diseases (2009–2023) from 8 PEDSnet centers. The prevalence, characteristics and drug exposures for juvenile spondyloarthritis was explored to gauge feasibility of leveraging the network for study enrollment. Next, the typology was adapted to identify subjects for a clinical trial; the efficiency of EHR typology query was compared to standard screening …

Sequential Platinum And Parp Inhibition Enhances Pd1 Immunotherapy Efficacy In Murine Brca2 Mutated Pancreatic Cancer, John C Mcvey, Max M Wattenberg, Heather Coho, Kayjana Infante, Kelly Markowitz, Devora Delman, Cynthia Clendenin, Emma E Furth, Rashmi Tondon, Ben Z Stanger, Robert H Vonderheide, Kim A Reiss, Gregory L Beatty

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) is a challenging malignancy to treat, but emerging evidence suggests that specific subtypes may respond more favorably to certain therapies. BRCA-mutated PDAC represents a distinct subtype that is particularly sensitive to DNA-damaging therapies. The current standard of care for advanced BRCA-mutated PDAC involves induction platinum-based chemotherapy followed by maintenance therapy with a poly (ADP-ribose) polymerase inhibitor (PARPi). However, the randomized phase III POLO trial, upon which this standard is based, did not demonstrate an improved overall survival in patients who received olaparib compared to those who received placebo, highlighting the need for new therapeutic approaches. Additionally, …

Partial Versus Full Revision In Cementless Single-Stage Exchange For Hip Periprosthetic Joint Infection: A Multicenter Comparative Study With 10-Year Survivorship Analysis, Wenbo Mu, Atthakorn Jarusriwanna, Boyong Xu, Scot A. Brown, Xiaogang Zhang, Alexander Dawes, Javad Parvizi Md, Li Cao

Rothman Institute Papers

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most challenging complications following total hip arthroplasty (THA). Traditional management typically involves full revision to ensure comprehensive infection eradication. However, for patients with well-fixed implants, partial revision in a single-stage cementless approach may provide a viable alternative, potentially preserving bone stock and reducing operative time. The relative efficacy of this approach compared with full revision remains to be fully explored. This multicenter study aims to determine whether partial revision in cementless single-stage exchange surgery offers comparable infection control outcomes to full revision for select patients with well-fixed implants.

METHODS: We conducted …

Olutasidenib In Recurrent/Relapsed Locally Advanced Or Metastatic Idh1-Mutated Chondrosarcoma: Phase 1b/2 Trial, Robin L Jones, Roman Groisberg, Jean-Yves Blay, Howard Colman, Macarena De La Fuente, Patricia Roxburgh, Mwe Mwe Chao, Hua Tian, Florence Duffaud, Rastislav Bahleda, Brian A Van Tine

2020-Current year OA Pubs

Chondrosarcomas are rare cartilaginous neoplasms with limited treatment options. Isocitrate dehydrogenase 1/2 (mIDH1/2) mutations occur in 65% of chondrosarcomas. Here we report safety and efficacy of olutasidenib, an mIDH1 inhibitor, evaluated in patients with locally advanced or metastatic mIDH1 chondrosarcoma (Clinicaltrials.gov identifier: NCT03684811). The primary endpoint was objective response rate by tumor evaluation; secondary endpoints included adverse events, progression-free and overall survival. Patients received olutasidenib 150 mg twice daily. Twenty-three patients were enrolled; 16 were diagnosed with conventional chondrosarcoma (cCS). Median age was 57 (range, 30-71) years. In 21 response-evaluable patients, 11 (52%) had stable disease, 8 (38%) had progressive …

Establishing T1 And Ecv Mapping Based Nomogram Differentiate Acute Ischemic And Nonischemic Myocardial Injury: A Proof-Of-Concept Study, Yanping Su, Kan Liu, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To develop and validate a nomogram based on T1 and extracellular volume fraction (ECV) mapping derived from cardiovascular magnetic resonance (CMR) for differentiating ischemic from nonischemic cardiomyopathies during the acute phase.

METHODS: This retrospective study included patients who underwent CMR at the Fifth Affiliated Hospital of Wenzhou Medical University (internal dataset) and the Fifth Affiliated Hospital of Sun Yat-sen University (external dataset). Patients were assigned to a training set (n = 73), a test set (n = 30), an internal validation set (n = 28), and an external validation set (n = 16). Six multivariable logistic regression models were …

Downregulation Of Slc40a1 Leads To Iron Accumulation In Fibrotic Lung Fibroblasts, Quanjin Dang, Chaoqun Huang, Yurong Liang, Akshaya Surendran, Dharanya Muthiah, Kishore Vaddadi, Sankha Hewawasam, Tingting W Mills, Lin Liu

Faculty, Staff and Student Publications

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbestos-induced lung fibrosis mice. Iron was partially co-localized with the …

Mast Cells Promote Pathology And Susceptibility In Tuberculosis, Ananya Gupta, Vibha Taneja, Javier Rangel-Moreno, Nilofer Naqvi, Abhimanyu, Yun Tao, Mushtaq Ahmed, Kuldeep Singh Chauhan, Daniela Trejo-Ponce De Leon, Gustavo Ramírez-Martínez, Luis Jiménez-Alvarez, Cesar Luna-Rivero, Joaquin Zuniga, Deepak Kaushal, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the bacterium

Designing Inclusive Newborn Sequencing Research: Insights From Parents In Underrepresented Communities, Maya C Del Rosario, Sheyenne A Walmsley, Barbara W Harrison, Crystal T Stephens, Bethany Zettler, Greysha Rivera-Cruz, Priyal Agrawal, Amy Brower, Stephanie Chigbu, Kurt D Christensen, Casie A Genetti, Richetta Givens, Nina B Gold, Inez V Reeves, Isabella Schichter, Habib Shariat, Sandra Simon, Hadley Stevens Smith, Melissa Uveges, Robert C Green, Ingrid A Holm, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Background: It is essential that studies of genomic sequencing (GS) in newborns and children include individuals from under-represented racial and ethnic groups (URG) to ensure future applications are equitably implemented. We conducted interviews with parents from URG to better understand their perspectives on GS research, develop strategies to reduce barriers to enrollment, and facilitate research participation.

Methods: Semi-structured interviews with 50 parents from URG.

Results: Nearly all parents said they would be interested in participating in an infant GS study. Parents were interested in participating in GS research for reasons including clinical utility, personal utility, and/or family health benefits. Deterrents …

Biomarkers Of Response To Neoadjuvant Palbociclib Plus Anastrozole In Endocrine-Resistant Estrogen Receptor-Positive/Her2-Negative Breast Cancer: A Phase 2 Trial, Tim Kong, Alex Mabry, Maureen Highkin, Jeremy Hoog, Zhanfang Guo, Adrian Gonzales-Gonzales, Shana Thomas, Yingduo Song, Feng Gao, Mateusz Opyrchal, Lindsay Peterson, Foluso Ademuyiwa, Julie Margenthaler, Rebecca Aft, Katherine Glover-Collins, Leslie Nehring, Yu Tao, Souzan Sanati, Ian S Hagemann, Fouad Boulos, Li Ding, Stephen T Oh, Ron Bose, Jason D Weber, Jingqin Luo, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

CDK4/6 inhibitors (CDK4/6i) improve outcomes for estrogen receptor (ER) positive/HER2-negative breast cancers (BCs), yet intrinsic and acquired resistance exist. Here, we evaluated anastrozole in combination with palbociclib (ANA/PAL) in the NeoPalAna Endocrine-Resistant cohort (NCT01723774). Thirty-four patients with clinical stage II/III ER + /HER2- BCs resistant to standard neoadjuvant endocrine therapy (on-treatment Ki67 > 10%) received neoadjuvant ANA/PAL, with serial biopsies analyzed. The primary endpoint, complete cell cycle arrest (CCCA; Ki67

Stat-Independent Functions Of Janus Kinases 1 And 2 Are Obligatory For The Postnatal Development Of Mammary Epithelial Ducts, Rayane Dennaoui, Madison N. Wicker, Carson Moen, Michaela Schlederer, Kerry Vistisen, Aleata A. Triplett, Thomas Rülicke, Hallgeir Rui, Lukas Kenner, Emilio Casanova, Kay-Uwe Wagner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Janus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation …

Expression Spectrum Of Te-Driven Transcripts In Human Adult Tissues, Benpeng Miao, Xinlong Luo, Amina Ademovic, Yushan Yang, Tao P Wu, Bo A Zhang

Faculty, Staff and Students Publications

Background

Transposable elements (TEs) are vital components of eukaryotic genomes and have played a critical role in genome evolution. Although most TEs are silenced in the mammalian genome, increasing evidence suggests that certain TEs are actively involved in gene regulation during early developmental stages. However, the extent to which human TEs drive gene transcription in adult tissues remains largely unexplored.

Results

In this study, we systematically analyze 17,329 human transcriptomes to investigate how TEs influence gene transcription across 47 adult tissues. Our findings reveal that TE-driven transcripts are broadly expressed in human tissues, contributing to both housekeeping functions and tissue-specific …