Digital Commons Network^™

Spotlight On Nociceptin/Orphanin Fq Receptor In The Treatment Of Pain, Amal El Daibani, Tao Che

Open Access Publications

No abstract provided.

Diagnostic Challenges In Ovarian Hyperthecosis: Clinical Presentation With Subdiagnostic Testosterone Levels, Sanket Shah, Callie Torres, Naser Gharaibeh

Open Access Publications

Symptoms of hyperandrogenism and virilization in postmenopausal women warrant workup for ovarian hyperthecosis. In this case series, we discuss two patients who presented with symptoms of hyperandrogenism and metabolic abnormalities including insulin resistance stemming from ovarian hyperthecosis. Imaging revealed normal ovaries in both patients. However, both patients had total serum testosterone levels below the lower diagnostic limit for ovarian hyperthecosis. Due to high clinical suspicion of ovarian hyperthecosis, both patients underwent bilateral oophorectomy without venous sampling for ovarian androgens. The diagnosis of ovarian hyperthecosis was confirmed on histological examination. Both women had improvement in their hyperandrogenic symptoms, testosterone levels, and …

Reevaluation Of The Role Of Lip-1 As An Erk/Mpk-1 Dual Specificity Phosphatase In The C. Elegans Germline, Debabrata Das, Jacob Seemann, David Greenstein, Tim Schedl, Swathi Arur

Open Access Publications

The fidelity of a signaling pathway depends on its tight regulation in space and time. Extracellular signal-regulated kinase (ERK) controls wide-ranging cellular processes to promote organismal development and tissue homeostasis. ERK activation depends on a reversible dual phosphorylation on the TEY motif in its active site by ERK kinase (MEK) and dephosphorylation by DUSPs (dual specificity phosphatases). LIP-1, a DUSP6/7 homolog, was proposed to function as an ERK (MPK-1) DUSP in the

Resting State Functional Connectivity Provides Mechanistic Predictions Of Future Changes In Sedentary Behavior, Timothy P Morris, Aaron Kucyi, Sheeba Arnold Anteraper, Maiya Rachel Geddes, Alfonso Nieto-Castañon, Agnieszka Burzynska, Neha P Gothe, Jason Fanning, Elizabeth A Salerno, Susan Whitfield-Gabrieli, Charles H Hillman, Edward Mcauley, Arthur F Kramer

Open Access Publications

Sedentary behaviors are increasing at the cost of millions of dollars spent in health care and productivity losses due to physical inactivity-related deaths worldwide. Understanding the mechanistic predictors of sedentary behaviors will improve future intervention development and precision medicine approaches. It has been posited that humans have an innate attraction towards effort minimization and that inhibitory control is required to overcome this prepotent disposition. Consequently, we hypothesized that individual differences in the functional connectivity of brain regions implicated in inhibitory control and physical effort decision making at the beginning of an exercise intervention in older adults would predict the change …

Comparative Genomics Of Borderline Oxacillin-Resistant Staphylococcus Aureus Detected During A Pseudo-Outbreak Of Methicillin-Resistant S. Aureus In A Neonatal Intensive Care Unit, Sanjam S Sawhney, Eric M Ransom, Meghan A Wallace, Patrick J Reich, Gautam Dantas, Carey-Ann D Burnham

Open Access Publications

Active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) is a component of our neonatal intensive care unit (NICU) infection prevention efforts. Recent atypical trends prompted review of 42 suspected MRSA isolates. Species identification was confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and methicillin resistance was reevaluated by PBP2a lateral flow assay, cefoxitin/oxacillin susceptibility testing,

Post-Hpv-Vaccination Mast Cell Activation Syndrome: Possible Vaccine-Triggered Escalation Of Undiagnosed Pre-Existing Mast Cell Disease?, Lawrence B Afrin, Tania T Dempsey, Leonard B Weinstock

Open Access Publications

For nearly a decade, case reports and series have emerged regarding dysautonomias-particularly postural orthostatic tachycardia syndrome (POTS)-presenting soon after vaccination against human papilloma virus (HPV). We too have observed a number of such cases (all following vaccination with the Gardasil product), and have found several to have detectable mast cell activation syndrome (MCAS) as well as histories suggesting that MCAS was likely present long before vaccination. We detail 11 such cases here, posing a hypothesis that HPV vaccination (at least with the Gardasil product) may have triggered or exacerbated MCAS in teenagers previously not recognized to have it. Only recently …

From Karyotypes To Precision Genomics In 9p Deletion And Duplication Syndromes, Eleanor I Sams, Jeffrey K Ng, Victoria Tate, Ying-Chen Claire Hou, Yang Cao, Lucinda Antonacci-Fulton, Khadija Belhassan, Julie Neidich, Robi D Mitra, F Sessions Cole, Patricia Dickson, Jeffrey Milbrandt, Tychele N Turner

Open Access Publications

While 9p deletion and duplication syndromes have been studied for several years, small sample sizes and minimal high-resolution data have limited a comprehensive delineation of genotypic and phenotypic characteristics. In this study, we examined genetic data from 719 individuals in the worldwide 9p Network Cohort: a cohort seven to nine times larger than any previous study of 9p. Most breakpoints occur in bands 9p22 and 9p24, accounting for 35% and 38% of all breakpoints, respectively. Bands 9p11 and 9p12 have the fewest breakpoints, with each accounting for 0.6% of all breakpoints. The most common phenotype in 9p deletion and duplication …

Antibiotic Therapy And Risk Of Early-Onset Colorectal Cancer: A National Case-Control Study, Long H Nguyen, Yin Cao, Nurgul Batyrbekova, Bjorn Roelstraete, Wenjie Ma, Hamed Khalili, Mingyang Song, Andrew T Chan, Jonas F Ludvigsson

Open Access Publications

INTRODUCTION: Antibiotic use has emerged as a risk factor for colorectal neoplasia and is hypothesized as a contributor to the rising incidence of colorectal cancer under age 50 years or early-onset colorectal cancer (EOCRC). However, the impact of antibiotic use and risk of EOCRC is unknown.

METHODS: We conducted a population-based case-control study of CRC among individuals aged ≥18 years in the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort (2006-2016). The primary outcome was EOCRC. A secondary outcome was CRC at any age. Incident CRC was pathologically confirmed, and for each, up to 5 population-based controls were matched …

Dansr: A Tool For The Detection Of Annotated And Novel Small Rnas, Jin Zhang, Abdallah M Eteleeb, Emily B Rozycki, Matthew J Inkman, Amy Ly, Russell E Scharf, Kay Jayachandran, Bradley A Krasnick, Thomas Mazur, Nicole M White, Ryan C Fields, Christopher A Maher

Open Access Publications

Existing small noncoding RNA analysis tools are optimized for processing short sequencing reads (17-35 nucleotides) to monitor microRNA expression. However, these strategies under-represent many biologically relevant classes of small noncoding RNAs in the 36-200 nucleotides length range (tRNAs, snoRNAs, etc.). To address this, we developed DANSR, a tool for the detection of annotated and novel small RNAs using sequencing reads with variable lengths (ranging from 17-200 nt). While DANSR is broadly applicable to any small RNA dataset, we applied it to a cohort of matched normal, primary, and distant metastatic colorectal cancer specimens to demonstrate its ability to quantify annotated …

Metabolic Sensing In Agrp Neurons Integrates Homeostatic State With Dopamine Signalling In The Striatum, Alex Reichenbach, Alexxai V. Kravitz, Et Al

Open Access Publications

Agouti-related peptide (AgRP) neurons increase motivation for food, however, whether metabolic sensing of homeostatic state in AgRP neurons potentiates motivation by interacting with dopamine reward systems is unexplored. As a model of impaired metabolic-sensing, we used the AgRP-specific deletion of carnitine acetyltransferase (

Myocardial Afterload Is A Key Biomechanical Regulator Of Atrioventricular Myocyte Differentiation In Zebrafish, Neha Ahuja, Paige Ostwald, Alex Gendernalik, Elena Guzzolino, Letizia Pitto, David Bark, Deborah M Garrity

Open Access Publications

Heart valve development is governed by both genetic and biomechanical inputs. Prior work has demonstrated that oscillating shear stress associated with blood flow is required for normal atrioventricular (AV) valve development. Cardiac afterload is defined as the pressure the ventricle must overcome in order to pump blood throughout the circulatory system. In human patients, conditions of high afterload can cause valve pathology. Whether high afterload adversely affects embryonic valve development remains poorly understood. Here we describe a zebrafish model exhibiting increased myocardial afterload, caused by vasopressin, a vasoconstrictive drug. We show that the application of vasopressin reliably produces an increase …

Serpinb3 (Scca1) Inhibits Cathepsin L And Lysoptosis, Protecting Cervical Cancer Cells From Chemoradiation, Songyan Wang, Cliff J Luke, Stephen C Pak, Victoria Shi, Liyun Chen, Jonathan Moore, Arlise P Andress, Kay Jayachandran, Jin Zhang, Yi Huang, Marina Platik, Anthony A Apicelli, Julie K Schwarz, Perry W Grigsby, Gary A Silverman, Stephanie Markovina

Open Access Publications

The endogenous lysosomal cysteine protease inhibitor SERPINB3 (squamous cell carcinoma antigen 1, SCCA1) is elevated in patients with cervical cancer and other malignancies. High serum SERPINB3 is prognostic for recurrence and death following chemoradiation therapy. Cervical cancer cells genetically lacking SERPINB3 are more sensitive to ionizing radiation (IR), suggesting this protease inhibitor plays a role in therapeutic response. Here we demonstrate that SERPINB3-deficient cells have enhanced sensitivity to IR-induced cell death. Knock out of SERPINB3 sensitizes cells to a greater extent than cisplatin, the current standard of care. IR in SERPINB3 deficient cervical carcinoma cells induces predominantly necrotic cell death, …

Lysoptosis Is An Evolutionarily Conserved Cell Death Pathway Moderated By Intracellular Serpins, Cliff J Luke, Stephanie Markovina, Misty Good, Ira E Wight, Brian J Thomas, John M Linneman, Wyatt E Lanik, Olga Koroleva, Maggie R Coffman, Mark T Miedel, Qingqing Gong, Arlise Andress, Marlene Campos Guerrero, Songyan Wang, Liyun Chen, Wandy L Beatty, Kelsey N Hausmann, Frances V White, James A J Fitzpatrick, Anthony Orvedahl, Stephen C Pak, Gary A Silverman

Open Access Publications

Lysosomal membrane permeabilization (LMP) and cathepsin release typifies lysosome-dependent cell death (LDCD). However, LMP occurs in most regulated cell death programs suggesting LDCD is not an independent cell death pathway, but is conscripted to facilitate the final cellular demise by other cell death routines. Previously, we demonstrated that Caenorhabditis elegans (C. elegans) null for a cysteine protease inhibitor, srp-6, undergo a specific LDCD pathway characterized by LMP and cathepsin-dependent cytoplasmic proteolysis. We designated this cell death routine, lysoptosis, to distinguish it from other pathways employing LMP. In this study, mouse and human epithelial cells lacking srp-6 homologues, mSerpinb3a and SERPINB3, …

Targeting The Fusion Process Of Sars-Cov-2 Infection By Small Molecule Inhibitors, Seung Bum Park, Parker Irvin, Zongyi Hu, Mohsin Khan, Xin Hu, Qiru Zeng, Catherine Chen, Miao Xu, Madeleine Leek, Ruochen Zang, James Brett Case, Wei Zheng, Siyuan Ding, T. Jake Liang

Open Access Publications

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a serious threat to global public health, underscoring the urgency of developing effective therapies. Therapeutics and, more specifically, direct-acting antiviral development are still very much in their infancy. Here, we report that two hepatitis C virus (HCV) fusion inhibitors identified in our previous study, dichlorcyclizine and fluoxazolevir, broadly block human coronavirus entry into various cell types. Both compounds were effective against various human-pathogenic CoVs in multiple assays based on vesicular stomatitis virus (VSV) pseudotyped with the spike protein and spike-mediated syncytium formation. The antiviral effects …

Astrocytic 4r Tau Expression Drives Astrocyte Reactivity And Dysfunction, Lubov A. Ezerskiy, Kathleen M. Schoch, Chihiro Sato, Mariana Beltcheva, Kanta Horie, Frank Rigo, Ryan Martynowicz, Celeste M. Karch, Randall J. Bateman, Timothy M. Miller

Open Access Publications

The protein tau and its isoforms are associated with several neurodegenerative diseases, many of which are characterized by greater deposition of the 4-repeat (4R) tau isoform; however, the role of 4R tau in disease pathogenesis remains unclear. We created antisense oligonucleotides (ASOs) that alter the ratio of 3R to 4R tau to investigate the role of specific tau isoforms in disease. Preferential expression of 4R tau in human tau-expressing (hTau-expressing) mice was previously shown to increase seizure severity and phosphorylated tau deposition without neuronal or synaptic loss. In this study, we observed strong colocalization of 4R tau within reactive astrocytes …

Fasn-Dependent De Novo Lipogenesis Is Required For Brain Development, Daniel Gonzalez-Bohorquez, Isabel M Gallego López, Baptiste N Jaeger, Sibylle Pfammatter, Megan Bowers, Clay F Semenkovich, Sebastian Jessberger

Open Access Publications

Fate and behavior of neural progenitor cells are tightly regulated during mammalian brain development. Metabolic pathways, such as glycolysis and oxidative phosphorylation, that are required for supplying energy and providing molecular building blocks to generate cells govern progenitor function. However, the role of de novo lipogenesis, which is the conversion of glucose into fatty acids through the multienzyme protein fatty acid synthase (FASN), for brain development remains unknown. Using Emx1Cre-mediated, tissue-specific deletion of

Microbial Enzymes Induce Colitis By Reactivating Triclosan In The Mouse Gastrointestinal Tract, Jianan Zhang, Morgan E. Walker, Katherine Z. Sanidad, Hongna Zhang, Michael B. Major, Dennis Goldfarb, Et Al

Open Access Publications

No abstract provided.

Total Energy Expenditure Is Repeatable In Adults But Not Associated With Short-Term Changes In Body Composition, Rebecca Rimbach, Susan B. Racette, John R. Speakman, Herman Pontzer, Et Al

Open Access Publications

No abstract provided.

Transcriptomes Of Peripheral Blood Mononuclear Cells From Juvenile Dermatomyositis Patients Show Elevated Inflammation Even When Clinically Inactive, Elisha D O Roberson, Rosana A Mesa, Gabrielle A Morgan, Li Cao, Wilfredo Marin, Lauren M Pachman

Open Access Publications

In juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, weakness is accompanied by a characteristic rash that often becomes chronic and is associated with vascular damage. We hoped to understand the molecular underpinnings of JDM, particularly when untreated, which would facilitate the identification of novel mechanisms and clinical targets that might disrupt disease progression. We studied the RNA-Seq data from untreated JDM peripheral blood mononuclear cells (PBMCs; n = 11), PBMCs from a subset of the same patients when clinically inactive (n = 8/11), and separate samples of untreated JDM skin and muscle (n = 4 each). All JDM …

Ablation Of Vla4 In Multiple Myeloma Cells Redirects Tumor Spread And Prolongs Survival, Deep Hathi, Chantiya Chanswangphuwana, Nicholas Cho, Francesca Fontana, Dolonchampa Maji, Julie Ritchey, Julie O'Neal, Anchal Ghai, Kathleen Duncan, Walter J Akers, Mark Fiala, Ravi Vij, John F Dipersio, Michael Rettig, Monica Shokeen

Open Access Publications

Multiple myeloma (MM) is a cancer of bone marrow (BM) plasma cells, which is increasingly treatable but still incurable. In 90% of MM patients, severe osteolysis results from pathological interactions between MM cells and the bone microenvironment. Delineating specific molecules and pathways for their role in cancer supportive interactions in the BM is vital for developing new therapies. Very Late Antigen 4 (VLA4, integrin α

Transcriptional Profile And Chromatin Accessibility In Zebrafish Melanocytes And Melanoma Tumors, Eva Kramer, Paula Godoy, Charles Kaufman

Open Access Publications

Transcriptional and epigenetic characterization of melanocytes and melanoma cells isolated from their in vivo context promises to unveil key differences between these developmentally related normal and cancer cell populations. We therefore engineered an enhanced Danio rerio (zebrafish) melanoma model with fluorescently labeled melanocytes to allow for isolation of normal (wild type) and premalignant (BRAFV600E-mutant) populations for comparison to fully transformed BRAFV600E-mutant, p53 loss-of-function melanoma cells. Using fluorescence-activated cell sorting to isolate these populations, we performed high-quality RNA- and ATAC-seq on sorted zebrafish melanocytes vs. melanoma cells, which we provide as a resource here. Melanocytes had consistent transcriptional and accessibility profiles, …

Polyunsaturated Fatty Acids Inhibit A Pentameric Ligand-Gated Ion Channel Through One Of Two Binding Sites, Noah M. Dietzen, Mark J. Arcario, Lawrence J. Chen, John T. Petroff, K. Trent Moreland, Kathiresan Krishnan, Grace Brannigan, Douglas F. Covey, Wayland W.I. Cheng

Open Access Publications

Polyunsaturated fatty acids (PUFAs) inhibit pentameric ligand-gated ion channels (pLGICs) but the mechanism of inhibition is not well understood. The PUFA, docosahexaenoic acid (DHA), inhibits agonist responses of the pLGIC, ELIC, more effectively than palmitic acid, similar to the effects observed in the GABA

Sars-Cov-2 Spreads Through Cell-To-Cell Transmission, Cong Zeng, John P Evans, Tiffany King, Yi-Min Zheng, Eugene M Oltz, Sean P J Whelan, Linda J Saif, Mark E Peeples, Shan-Lu Liu

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein, we provide evidence that SARS-CoV-2 spreads through cell-cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cell-to-cell transmission than is SARS-CoV spike, which reflects, in part, their differential cell-cell fusion activity. Interestingly, treatment of cocultured cells with endosomal entry inhibitors impairs cell-to-cell transmission, implicating endosomal membrane fusion as an underlying mechanism. Compared with cell-free infection, cell-to-cell transmission of SARS-CoV-2 is refractory to inhibition by neutralizing antibody or convalescent sera of COVID-19 patients. While angiotensin-converting …

Procedural Risk In Congenital Cardiac Catheterization (Predic3t), Brian P Quinn, David Balzer, Et Al

Open Access Publications

Background Advancements in the field, including novel procedures and multiple interventions, require an updated approach to accurately assess patient risk. This study aims to modernize patient hemodynamic and procedural risk classification through the creation of risk assessment tools to be used in congenital cardiac catheterization. Methods and Results Data were collected for all cases performed at sites participating in the C3PO (Congenital Cardiac Catheterization Project on Outcomes) multicenter registry. Between January 2014 and December 2017, 23 119 cases were recorded in 13 participating institutions, of which 88% of patients were <18 years of age and 25% <1 year of age; a high-severity adverse event occurred in 1193 (5.2%). Case types were defined by procedure(s) performed and grouped on the basis of association with the outcome, high-severity adverse event. Thirty-four unique case types were determined and stratified into 6 risk categories. Six hemodynamic indicator variables were empirically assessed, and a novel hemodynamic vulnerability score was determined by the frequency of high-severity adverse events. In a multivariable model, case-type risk category (odds ratios for category: 0=0.46, 1=1.00, 2=1.40, 3=2.68, 4=3.64, and 5=5.25; all

The Yersinia High-Pathogenicity Island Encodes A Siderophore-Dependent Copper Response System In Uropathogenic Escherichia Coli, George L Katumba, Hung Tran, Jeffrey P Henderson

Open Access Publications

Siderophores are iron chelators used by microbes to bind and acquire iron, which, once in the cell, inhibits siderophore production through feedback repression mediated by the ferric uptake repressor (Fur). Yersiniabactin (Ybt), a siderophore associated with enhanced pathogenic potential among

Comparison Of Etdrs 7-Field To 4-Widefield Digital Imaging In The Evaluation Of Diabetic Retinopathy Severity, Barbara A Blodi, Amitha Domalpally, Ashley H Tjaden, Nancy Barrett, Emily Y Chew, William C Knowler, Christine G Lee, Xavier Pi-Sunyer, Amisha Wallia, Neil H White, Marinella Temprosa

Open Access Publications

Purpose: To compare Early Treatment Diabetic Retinopathy Study (ETDRS) severity levels between two digital fundus imaging protocols for research studies of diabetic retinopathy: the gold standard 7-field (7F) imaging and the more recent 4-widefield (4W) imaging.

Methods: Two hundred twenty-two participants enrolled in the Diabetes Prevention Program Outcomes Study underwent concurrent 7F and 4W imaging. The ETDRS levels from 220 paired gradable images were determined by masked graders. Each image was graded by two independent graders with adjudication by a senior grader, if necessary. Percent agreement between graders and between imaging protocols was evaluated with kappa statistics and weighted kappa …

Simulated Cost-Effectiveness And Long-Term Clinical Outcomes Of Addiction Care And Antibiotic Therapy Strategies For Patients With Injection Drug Use-Associated Infective Endocarditis, Joëlla W. Adams, Alexandra Savinkina, James C. Hudspeth, Mam Jarra Gai, Raagini Jawa, Laura R. Marks, Benjamin P. Linas, Alison Hill, Jason Flood, Simeon Kimmel, Joshua A. Barocas

Open Access Publications

Importance: Emerging evidence supports the use of outpatient parenteral antimicrobial therapy (OPAT) and, in many cases, partial oral antibiotic therapy for the treatment of injection drug use-associated infective endocarditis (IDU-IE); however, long-term outcomes and cost-effectiveness remain unknown.

Objective: To compare the added value of inpatient addiction care services and the cost-effectiveness and clinical outcomes of alternative antibiotic treatment strategies for patients with IDU-IE.

Design, Setting, and Participants: This decision analytical modeling study used a validated microsimulation model to compare antibiotic treatment strategies for patients with IDU-IE. Model inputs were derived from clinical trials and observational cohort studies. The model included …

Visually Guided Respiratory Motion Management For Ethos Adaptive Radiotherapy, Taeho Kim, Zhen Ji, Benjamin Lewis, Eric Laugeman, Alex Price, Yao Hao, Geoffrey Hugo, Nels Knutson, Bin Cai, Hyun Kim, Lauren Henke

Open Access Publications

PURPOSE: Ethos adaptive radiotherapy (ART) is emerging with AI-enhanced adaptive planning and high-quality cone-beam computed tomography (CBCT). Although a respiratory motion management solution is critical for reducing motion artifacts on abdominothoracic CBCT and improving tumor motion control during beam delivery, our institutional Ethos system has not incorporated a commercial solution. Here we developed an institutional visually guided respiratory motion management system to coach patients in regular breathing or breath hold during intrafractional CBCT scans and beam delivery with Ethos ART.

METHODS: The institutional visual-guidance respiratory motion management system has three components: (1) a respiratory motion detection system, (2) an in-room …

Identification Of Gut Bacteria Such As Lactobacillus Johnsonii That Disseminate To Systemic Tissues Of Wild Type And Myd88-/- Mice, Sreeram Udayan, Panagiota Stamou, Fiona Crispie, Ana Hickey, Alexandria N Floyd, Chyi-Song Hsieh, Paul D Cotter, Orla O'Sullivan, Silvia Melgar, Paul W O'Toole, Rodney D Newberry, Valerio Rossini, Ken Nally

Open Access Publications

In healthy hosts the gut microbiota is restricted to gut tissues by several barriers some of which require MyD88-dependent innate immune sensor pathways. Nevertheless, some gut taxa have been reported to disseminate to systemic tissues. However, the extent to which this normally occurs during homeostasis in healthy organisms is still unknown. In this study, we recovered viable gut bacteria from systemic tissues of healthy wild type (WT) and MyD88

Serologic And Cytokine Signatures In Children With Multisystem Inflammatory Syndrome And Coronavirus Disease 2019, Stacey A. Lapp, Carol M. Kao, David A. Hunstad, Et Al

Open Access Publications

Background: The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.

Methods: We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and …