Digital Commons Network^™

Making An Impact On Kidney Disease In People With Type 2 Diabetes: The Importance Of Screening For Albuminuria, Janet B Mcgill, Hermann Haller, Prabir Roy-Chaudhury, Andrea Cherrington, Takashi Wada, Christoph Wanner, Linong Ji, Peter Rossing

Open Access Publications

Albuminuria is useful for early screening and diagnosis of kidney impairment, especially in people with pre-diabetes or type 2 diabetes (T2D), which is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), associated with increased mortality, poor cardiovascular outcomes, and high economic burden. Identifying patients with CKD who are most likely to progress to ESKD permits timely implementation of appropriate interventions. The early stages of CKD are asymptomatic, which means identification of CKD relies on routine assessment of kidney damage and function. Both albuminuria and estimated glomerular filtration rate are measures of kidney function. This review …

A Randomized, Double-Blind Trial Of Triheptanoin For Drug-Resistant Epilepsy In Glucose Transporter 1 Deficiency Syndrome, Pasquale Striano, Stéphane Auvin, Abigail Collins, Rita Horvath, Ingrid E Scheffer, Michal Tzadok, Ian Miller, Mary Kay Koenig, Adrian Lacy, Ronald Davis, Angela Garcia-Cazorla, Russell P Saneto, Melanie Brandabur, Susan Blair, Tony Koutsoukos, Darryl De Vivo

Faculty, Staff and Student Publications

Objective: This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS).

Methods: UX007G-CL201 was a randomized, double-blind, placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo. Dosing was titrated to 35% of total daily calories over 2 weeks. After an 8-week placebo-controlled period, all patients received open-label triheptanoin through Week 52.

Results: The study included 36 patients (15 children, 13 adolescents, eight adults). A median 12.6% reduction in overall seizure …

Contributions Of Semantic And Phonological Working Memory To Narrative Language Independent Of Single Word Production: Evidence From Acute Stroke, Rachel Zahn, Tatiana T Schnur, Randi C Martin

Faculty, Staff and Student Publications

Neuropsychological case studies have provided evidence that individuals with semantic, but not phonological, working memory (WM) deficits have difficulty producing phrases containing several content words. These findings supported the claim of a phrasal scope of planning at the grammatical formulation stage of production, where semantic WM supports the maintenance of lexical-semantic representations as they are inserted into slots in phrasal constituents. Recent narrative production results for individuals at the acute stage of stroke supported the role for semantic WM in phrasal elaboration while suggesting a role for phonological WM at a subsequent phonological encoding stage in supporting fluent, rapid speech. …

Self-Selection Vs Randomized Assignment Of Treatment For Appendicitis, Giana H Davidson, Sarah E Monsell, Heather Evans, Emily C Voldal, Erin Fannon, Sarah O Lawrence, Anusha Krishnadasan, David A Talan, Bonnie Bizzell, Patrick J Heagerty, Bryan A Comstock, Danielle C Lavallee, Cassandra Villegas, Robert Winchell, Callie M Thompson, Wesley H Self, Lillian S Kao, Shah-Jahan Dodwad, Amber K Sabbatini, David Droullard, David Machado-Aranda, Melinda Maggard Gibbons, Amy H Kaji, Daniel A Deugarte, Lisa Ferrigno, Matthew Salzberg, Katherine A Mandell, Nicole Siparsky, Thea P Price, Anooradha Raman, Joshua Corsa, Jon Wisler, Patricia Ayoung-Chee, Jesse Victory, Alan Jones, Matthew Kutcher, Karen Mcgrane, Julie Holihan, Mike K Liang, Joseph Cuschieri, Jeffrey Johnson, Katherine Fischkoff, F Thurston Drake, Sabrina E Sanchez, Stephen R Odom, Larry G Kessler, David R Flum

Faculty, Staff and Student Publications

Importance: For adults with appendicitis, several randomized clinical trials have demonstrated that antibiotics are an effective alternative to appendectomy. However, it remains unknown how the characteristics of patients in such trials compare with those of patients who select their treatment and whether outcomes differ.

Objective: To compare participants in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial (RCT) with a parallel cohort study of participants who declined randomization and self-selected treatment.

Design, setting, and participants: The CODA trial was conducted in 25 US medical centers. Participants were enrolled between May 3, 2016, and February 5, …

The Relationship Between The Field-Shifting Phenomenon And Representational Coherence Of Place Cells In Ca1 And Ca3 In A Cue-Altered Environment, Jeremy Miciak, Yusra Ahmed, Phil Capin, David J Francis

Faculty, Staff and Student Publications

Few studies have systematically investigated the reading skill profiles of English Learners (ELs) in late elementary school, a critical developmental period for language and literacy and the most common grades for initial identification with specific learning disabilities (O’Connor et al., 2013). We investigated the reading skill profiles of 331 ELs in 3rd and 4th grades, including ELs with and without risk for dyslexia due to significant deficits in word and pseudo-word reading accuracy and fluency. We utilized latent profile analysis and factor mixture modeling to investigate: (1) the nature and distribution of reading skill profiles; (2) whether these …

Algorithmic Approach To The Diagnosis Of Organizing Pneumonia: A Correlation Of Clinical, Radiologic, And Pathologic Features, Sujith V Cherian, Dhara Patel, Stephen Machnicki, David Naidich, Diane Stover, William D Travis, Kevin K Brown, Jason J Naidich, Akhilesh Mahajan, Michael Esposito, Bushra Mina, Viera Lakticova, Stuart L Cohen, Nestor L Muller, Jenna Schulner, Rakesh Shah, Suhail Raoof

Faculty, Staff and Student Publications

Organizing pneumonia (OP), characterized histopathologically by patchy filling of alveoli and bronchioles by loose plugs of connective tissue, may be seen in a variety of conditions. These include but are not limited to after an infection, drug reactions, radiation therapy, and collagen vascular diseases. When a specific cause is responsible for this entity, it is referred to as "secondary OP." When an extensive search fails to reveal a cause, it is referred to as "cryptogenic OP" (previously called "bronchiolitis obliterans with OP"), which is a clinical, radiologic, and pathologic entity classified as an interstitial lung disease. The clinical presentation of …

A Spef1-Interacting Microtubule Quartet Protein In Trypanosoma Brucei Promotes Flagellar Inheritance By Regulating Basal Body Segregation, Kieu T M Pham, Qing Zhou, Kyu Joon Lee, Ziyin Li

Faculty, Staff and Student Publications

The human parasite Trypanosoma brucei contains a motile flagellum that determines the plane of cell division, controls cell morphology, and mediates cell-cell communication. During the cell cycle, inheritance of the newly formed flagellum requires its correct positioning toward the posterior of the cell, which depends on the faithful segregation of multiple flagellum-associated cytoskeletal structures including the basal body, the flagellar pocket collar, the flagellum attachment zone, and the hook complex. A specialized group of four microtubules termed the microtubule quartet (MtQ) originates from the basal body and runs through the flagellar pocket collar and the hook complex to extend, along …

Estimated Size Of The Clinical Medical Imaging Physics Workforce In The United States, Sean D Rose, David W Jordan, Nicholas B Bevins, Jaydev K Dave, David E Hintenlang, Brad K Lofton, Pankaj Patel

Faculty, Staff and Student Publications

There is no current authoritative accounting of the number of clinical imaging physicists practicing in the United States. Information about the workforce is needed to inform future efforts to secure training pathways and opportunities. In this study, the AAPM Diagnostic Demand and Supply Projection Working Group collected lists of medical physicists from several state registration and licensure programs and the Conference of Radiation Control Program Directors (CRCPD) registry. By cross-referencing individuals among these lists, we were able to estimate the current imaging physics workforce in the United States by extrapolating based on population. The imaging physics workforce in the United …

Estimated Size Of The Clinical Medical Imaging Physics Workforce In The United States, Sean D. Rose, David W. Jordan, Nicholas B. Bevins, Jaydev K. Dave, David E. Hintenlang, Brad K. Lofton, Pankaj Patel

Diagnostic Radiology Articles

There is no current authoritative accounting of the number of clinical imaging physicists practicing in the United States. Information about the workforce is needed to inform future efforts to secure training pathways and opportunities. In this study, the AAPM Diagnostic Demand and Supply Projection Working Group collected lists of medical physicists from several state registration and licensure programs and the Conference of Radiation Control Program Directors (CRCPD) registry. By cross-referencing individuals among these lists, we were able to estimate the current imaging physics workforce in the United States by extrapolating based on population. The imaging physics workforce in the United …

Analysis Of Neonatal Neurobehavior And Developmental Outcomes Among Preterm Infants., Elisabeth C. Mcgowan, Julie A. Hofheimer, T Michael O'Shea, Howard Kilbride, Brian S. Carter, Jennifer Check, Jennifer Helderman, Charles R. Neal, Steve Pastyrnak, Lynne M. Smith, Marie Camerota, Lynne M. Dansereau, Sheri A. Della Grotta, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

Importance: The ability to identify poor outcomes and treatable risk factors among very preterm infants remains challenging; improving early risk detection and intervention targets to potentially address developmental and behavioral delays is needed.

Objective: To determine associations between neonatal neurobehavior using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS), neonatal medical risk, and 2-year outcomes.

Design, Setting, and Participants: This multicenter cohort enrolled infants born at less than 30 weeks' gestation at 9 US university-affiliated NICUs. Enrollment was conducted from April 2014 to June 2016 with 2-year adjusted age follow-up assessment. Data were analyzed from December 2019 to …

Influence Of Cyp2d6 Genetic Variation On Adverse Events With Propafenone In The Pediatric And Young Adult Population., Sudeep D. Sunthankar, Prince J. Kannankeril, Andrea Gaedigk, Andrew E. Radbill, Frank A. Fish, Sara L. Van Driest

Manuscripts, Articles, Book Chapters and Other Papers

Propafenone is an antiarrhythmic drug metabolized primarily by cytochrome P450 2D6 (CYP2D6). In adults, propafenone adverse events (AEs) are associated with CYP2D6 poor metabolizer status; however, pediatric data are lacking. Subjects were tested for 10 CYP2D6 allelic variants and copy number status, and activity scores assigned to each genotype. Seventy-six individuals (median 0.3 [range 0-26] years old) were included. Propafenone AEs occurred in 29 (38%); 14 (18%) required drug discontinuation due to AE. The most common AEs were QRS (n = 10) and QTc (n = 6) prolongation. Those with AEs were older at the time of propafenone initiation (1.58 …

Molecular Characterization And Prospective Evaluation Of Pathologic Response And Outcomes With Neoadjuvant Therapy In Metaplastic Triple-Negative Breast Cancer, Clinton Yam, Nour Abuhadra, Ryan Sun, Beatriz E Adrada, Qing-Qing Ding, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Vicente Valero, Debu Tripathy, Senthilkumar Damodaran, Banu K Arun, Jennifer K Litton, Naoto T Ueno, Rashmi K Murthy, Bora Lim, Luis Baez, Xiaoxian Li, Aman U Buzdar, Gabriel N Hortobagyi, Alistair M Thompson, Elizabeth A Mittendorf, Gaiane M Rauch, Rosalind P Candelaria, Lei Huo, Stacy L Moulder, Jeffrey T Chang

Faculty, Staff and Student Publications

PURPOSE: Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer that is commonly triple-negative and poorly responsive to neoadjuvant therapy in retrospective studies.

EXPERIMENTAL DESIGN: To better define clinical outcomes and correlates of response, we analyzed the rate of pathologic complete response (pCR) to neoadjuvant therapy, survival outcomes, and genomic and transcriptomic profiles of the pretreatment tumors in a prospective clinical trial (NCT02276443). A total of 211 patients with triple-negative breast cancer (TNBC), including 39 with MpBC, received doxorubicin-cyclophosphamide-based neoadjuvant therapy.

RESULTS: Although not meeting the threshold for statistical significance, patients with MpBCs were less likely to experience …

Insurance Coverage And Respiratory Morbidities In Bronchopulmonary Dysplasia., Joseph M. Collaco, Michael C. Tracy, Catherine A. Sheils, Jessica L. Rice, Lawrence M. Rhein, Leif D. Nelin, Paul E. Moore, Winston M. Manimtim, Jonathan C. Levin, Khanh Lai, Lystra P. Hayden, Julie L. Fierro, Eric D. Austin, Stamatia Alexiou, Amit Agarwal, Natalie Villafranco, Roopa Siddaiah, Antonia P. Popova, Ioana A. Cristea, Christopher D. Baker, Manvi Bansal, Sharon A. Mcgrath-Morrow

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Preterm infants and young children with bronchopulmonary dysplasia (BPD) are at increased risk for acute care utilization and chronic respiratory symptoms during early life. Identifying risk factors for respiratory morbidities in the outpatient setting could decrease the burden of care. We hypothesized that public insurance coverage was associated with higher acute care usage and respiratory symptoms in preterm infants and children with BPD after initial neonatal intensive care unit (NICU) discharge.

METHODS: Subjects were recruited from BPD clinics at 10 tertiary care centers in the United States between 2018 and 2021. Demographics and clinical characteristics were obtained through chart …

Cholestasis Alters Brain Lipid And Bile Acid Composition And Compromises Motor Function In Neonatal Piglets, Nicole Lind Henriksen, Svend Høime Hansen, Matthew Domenic Lycas, Xiaoyu Pan, Thomas Eriksen, Lars Søndergaard Johansen, Richard R Sprenger, Christer Stenby Ejsing, Douglas G Burrin, Kerstin Skovgaard, Vibeke Brix Christensen, Thomas Thymann, Stanislava Pankratova

Faculty, Staff and Students Publications

Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more …

Onasemnogene Abeparvovec For Presymptomatic Infants With Two Copies Of Smn2 At Risk For Spinal Muscular Atrophy Type 1: The Phase Iii Spr1nt Trial, Kevin A Strauss, Craig M Zaidman, Et Al

2020-Current year OA Pubs

SPR1NT ( NCT03505099 ) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies of SMN2, expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric Neuromuscular Clinical Research natural-history cohort (n = 23). All 14 enrolled infants sat independently for ≥30 seconds at any visit ≤18 months (Bayley-III item #26; P < 0.001; 11 within the normal developmental window). All survived without permanent ventilation at 14 months as per protocol; 13 maintained body weight (≥3rd WHO percentile) through 18 months. No child used nutritional or respiratory support. No serious adverse events were considered related to treatment by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for children expected to develop SMA type 1, highlighting the urgency for universal newborn screening.

Onasemnogene Abeparvovec For Presymptomatic Infants With Three Copies Of Smn2 At Risk For Spinal Muscular Atrophy: The Phase Iii Spr1nt Trial, Kevin A Strauss, Craig M Zaidman, Et Al

2020-Current year OA Pubs

Most children with biallelic SMN1 deletions and three SMN2 copies develop spinal muscular atrophy (SMA) type 2. SPR1NT ( NCT03505099 ), a Phase III, multicenter, single-arm trial, investigated the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated within six postnatal weeks. Of 15 children with three SMN2 copies treated before symptom onset, all stood independently before 24 months (P < 0.0001; 14 within normal developmental window), and 14 walked independently (P < 0.0001; 11 within normal developmental window). All survived without permanent ventilation at 14 months; ten (67%) maintained body weight (≥3rd WHO percentile) without feeding support through 24 months; and none required nutritional or respiratory support. No serious adverse events were considered treatment-related by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for presymptomatic infants at risk of SMA type 2, underscoring the urgency of early identification and intervention.

Risk Of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage, Andrew J Durnford, Ridhima Guniganti, Akash P Kansagra, Gregory J Zipfel, Et Al

2020-Current year OA Pubs

BACKGROUND: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage.

METHODS: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time …

Caspase-1-Driven Neutrophil Pyroptosis And Its Role In Host Susceptibility To Pseudomonas Aeruginosa, Karin Santoni, Christine T. N. Pham, Et Al

2020-Current year OA Pubs

Multiple regulated neutrophil cell death programs contribute to host defense against infections. However, despite expressing all necessary inflammasome components, neutrophils are thought to be generally defective in Caspase-1-dependent pyroptosis. By screening different bacterial species, we found that several Pseudomonas aeruginosa (P. aeruginosa) strains trigger Caspase-1-dependent pyroptosis in human and murine neutrophils. Notably, deletion of Exotoxins U or S in P. aeruginosa enhanced neutrophil death to Caspase-1-dependent pyroptosis, suggesting that these exotoxins interfere with this pathway. Mechanistically, P. aeruginosa Flagellin activates the NLRC4 inflammasome, which supports Caspase-1-driven interleukin (IL)-1β secretion and Gasdermin D (GSDMD)-dependent neutrophil pyroptosis. Furthermore, P. aeruginosa-induced GSDMD activation …

Retrospective Analysis Of Pacritinib In Patients With Myelofibrosis And Severe Thrombocytopenia, Srdan Verstovsek, Ruben Mesa, Moshe Talpaz, Jean-Jacques Kiladjian, Claire N. Harrison, Stephen T. Oh, Alessandro M. Vannucchi, Raajit Rampal, Bart L. Scott, Sarah A. Buckley, Adam R. Craig, Karisse Roman-Torres, John O. Mascarenhas

2020-Current year OA Pubs

Thrombocytopenia is common in patients with myelofibrosis (MF) and is a well-established adverse prognostic factor. Both of the approved Janus kinase (JAK) inhibitors, ruxolitinib and fedratinib, can worsen thrombocytopenia and have not been evaluated in patients with severe thrombocytopenia (platelet counts <50×109/L). Pacritinib, a novel JAK2/interleukin-1 receptor-associated kinase 1 inhibitor, has been studied in two phase III trials (PERSIST-1 and PERSIST- 2), both of which enrolled patients with MF and severe thrombocytopenia. In order to better characterize treatment outcomes for this population with advanced disease, we present a retrospective analysis of efficacy and safety data in the 189 patients with severe thrombocytopenia treated in the PERSIST studies. The proportion of patients in the pacritinib group meeting efficacy endpoints was greater than in the BAT group for ≥35% spleen volume reduction (23% vs. 2%, P=0.0007), ≥50% modified Total Symptom Score reduction (25% vs. 8%, P=0.044), and self-reported symptom benefit ("much" or "very much" improved; 25% vs. 8%, P=0.016) at the primary analysis time point (week 24). The adverse event profile of pacritinib was manageable, and dose modification was rarely required. There was no excess in bleeding or death in pacritinib-treated patients. These results indicate that pacritinib is a promising treatment for patients with MF who lack safe and effective therapeutic options due to severe thrombocytopenia.

Single-Dose Intrathecal Dorsal Root Ganglia Toxicity Of Onasemnogene Abeparvovec In Cynomolgus Monkeys, Francis Fonyuy Tukov, Keith Mansfield, Mark Milton, Emily Meseck, Kelley Penraat, Deepa Chand, Andreas Hartmann

2020-Current year OA Pubs

Intravenous onasemnogene abeparvovec is approved for the treatment of spinal muscular atrophy in children < 2 years. For later-onset patients, intrathecal onasemnogene abeparvovec may be advantageous over intravenous administration. Recently, microscopic dorsal root ganglion (DRG) changes were observed in nonhuman primates (NHPs) following intrathecal onasemnogene abeparvovec administration. To characterize these DRG findings, two NHP studies evaluating intrathecal onasemnogene abeparvovec administration were conducted: a 12-month study with a 6-week interim cohort and a 13-week study with a 2-week interim cohort. The latter investigated the potential impact of prednisolone or rituximab plus everolimus on DRG toxicity. An additional 6-month, single-dose, intravenous NHP study conducted in parallel evaluated onasemnogene abeparvovec safety (including DRG toxicity) with or without prednisolone coadministration. Intrathecal onasemnogene abeparvovec administration was well tolerated and not associated with clinical observations. Microscopic onasemnogene abeparvovec-related changes were observed in the DRG and trigeminal ganglion (TG) and included mononuclear cell inflammation and/or neuronal degeneration, which was colocalized with high vector transcript expression at 6 weeks postdose. Incidence and severity of DRG changes were generally decreased after 52 weeks compared with 6 weeks postdose. Other onasemnogene abeparvovec-related microscopic findings of axonal degeneration, mononuclear cell infiltrates and/or gliosis in the spinal cord, dorsal spinal nerve root/spinal nerves, and/or peripheral nerves were absent or found at decreased incidences and/or severities after 52 weeks. DRG and/or TG microscopic findings following intravenous onasemnogene abeparvovec dosing included minimal to slight neuronal degeneration and mononuclear cell inflammation at 6 weeks and 6 months postdose. Nervous system microscopic findings following intrathecal onasemnogene abeparvovec (≥1.2 × 10

Ewi2 Prevents Egfr From Clustering And Endocytosis To Reduce Tumor Cell Movement And Proliferation, Chenying Fu, Jie Wang, Sandeep Pallikkuth, Yingjun Ding, Junxiong Chen, Jonathan D Wren, Yuchao Yang, Kwong-Kwok Wong, Hiroyasu Kameyama, Muralidharan Jayaraman, Anupama Munshi, Takemi Tanaka, Keith A Lidke, Xin A Zhang

Faculty, Staff and Student Publications

EWI2 is a transmembrane immunoglobulin superfamily (IgSF) protein that physically associates with tetraspanins and integrins. It inhibits cancer cells by influencing the interactions among membrane molecules including the tetraspanins and integrins. The present study revealed that, upon EWI2 silencing or ablation, the elevated movement and proliferation of cancer cells in vitro and increased cancer metastatic potential and malignancy in vivo are associated with (i) increases in clustering, endocytosis, and then activation of EGFR and (ii) enhancement of Erk MAP kinase signaling. These changes in signaling make cancer cells (i) undergo partial epithelial-to-mesenchymal (EMT) for more tumor progression and (ii) proliferate …

Structure Of A Vaccine-Induced, Germline-Encoded Human Antibody Defines A Neutralizing Epitope On The Sars-Cov-2 Spike N-Terminal Domain, Clara G Altomare, Daniel C Adelsberg, Juan Manuel Carreno, Iden A Sapse, Fatima Amanat, Ali H Ellebedy, Viviana Simon, Florian Krammer, Goran Bajic

Open Access Publications

Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs rational vaccine immunogen design. We isolated a germ line-encoded monoclonal antibody (mAb) from plasmablasts activated upon mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determined its structure in complex with the spike glycoprotein by electron cryomicroscopy (cryo-EM). We show that the mAb engages a previously uncharacterized neutralizing epitope on the spike N-terminal domain (NTD). The high-resolution structure reveals details of the intermolecular interactions and shows that the mAb inserts its heavy …

Gut Microbiome Alterations Associated With Diabetes In Mexican Americans In South Texas, Suet-Ying Kwan, Caroline M Sabotta, Aron Joon, Peng Wei, Lauren E Petty, Jennifer E Below, Xiaogang Wu, Jianhua Zhang, Robert R Jenq, Ernest T Hawk, Joseph B Mccormick, Susan P Fisher-Hoch, Laura Beretta

Faculty, Staff and Student Publications

Mexican Americans have a high prevalence of diabetes and burden of diabetes-related complications, highlighting the need for novel preventive strategies and noninvasive predictors of diabetes risk tailored to this population. Changes in the gut microbiome have the potential to predict diabetes. Here, we aimed to identify alterations in the gut microbiome associated with diabetes in the high-risk population of Mexican Americans in South Texas. Stool samples were collected from 216 subjects from the population-based Cameron County Hispanic Cohort. Among them, 75 had type 2 diabetes. Taxonomic and functional profiling of the stool samples were assessed by 16S and shotgun metagenomic …

Human Metapneumovirus Phosphoprotein Independently Drives Phase Separation And Recruits Nucleoprotein To Liquid-Like Bodies, Kerri Beth Boggs, Kearstin Edmonds, Nicolas Cifuentes-Munoz, Farah El Najjar, Conny Ossandón, Mckenna Roe, Chao Wu, Carole L Moncman, Trevor P Creamer, Gaya K Amarasinghe, Daisy W Leung, Rebecca Ellis Dutch

Open Access Publications

Human metapneumovirus (HMPV) inclusion bodies (IBs) are dynamic structures required for efficient viral replication and transcription. The minimum components needed to form IB-like structures in cells are the nucleoprotein (N) and the tetrameric phosphoprotein (P). HMPV P binds to the following two versions of the N protein in infected cells: N-terminal P residues interact with monomeric N (N

Aberrant Dna Hydroxymethylation Reshapes Transcription Factor Binding In Myeloid Neoplasms, Jia Li, Tingting Hong, Yue Wei, Lei Guo, Minjung Lee, Hui Yang, Caleb Class, Yaling Yang, Xiaoqiong Wang, Hua He, Stefan Siwko, M James You, Yubin Zhou, Guillermo Garcia-Manero, Yun Huang

Faculty, Staff and Student Publications

Epigenetic abnormalities in DNA hydroxymethylation (5hmC) have been detected in patients with myeloid neoplasms, suggesting that 5hmC might act as a valuable epigenetic mark to reflect the disease status of myeloid neoplasms. Here, we report systematic genome-wide mapping of the DNA hydroxymethylomes in over 70 patients with myeloid neoplasms. Our integrative analysis leads to the identification of distinct 5hmC signatures that can sensitively discriminate patients from healthy individuals. At the molecular level, we unveiled dynamic 5hmC changes within key transcription factor (e.g., the CEBP family) binding motifs that are essential for hematopoiesis and myeloid lineage specification. 5hmC redistribution was found …

Cancer Cells Dying From Ferroptosis Impede Dendritic Cell-Mediated Anti-Tumor Immunity, Bartosz Wiernicki, Sophia Maschalidi, Jonathan Pinney, Sandy Adjemian, Tom Vanden Berghe, Kodi S Ravichandran, Peter Vandenabeele

Open Access Publications

Immunogenic cell death significantly contributes to the success of anti-cancer therapies, but immunogenicity of different cell death modalities widely varies. Ferroptosis, a form of cell death that is characterized by iron accumulation and lipid peroxidation, has not yet been fully evaluated from this perspective. Here we present an inducible model of ferroptosis, distinguishing three phases in the process-'initial' associated with lipid peroxidation, 'intermediate' correlated with ATP release and 'terminal' recognized by HMGB1 release and loss of plasma membrane integrity-that serves as tool to study immune cell responses to ferroptotic cancer cells. Co-culturing ferroptotic cancer cells with dendritic cells (DC), reveals …

A Human Single-Neuron Dataset For Face Perception, Runnan Cao, Chujun Lin, Nicholas J Brandmeir, Shuo Wang

2020-Current year OA Pubs

The human amygdala and hippocampus have long been associated with face perception. Here, we present a dataset of single-neuron activity in the human amygdala and hippocampus during face perception. We recorded 2082 neurons from the human amygdala and hippocampus when neurosurgical patients with intractable epilepsy performed a one-back task using natural face stimuli, which mimics natural face perception. Specifically, our data include (1) single-neuron activity from the amygdala (996 neurons) and hippocampus (1086 neurons), (2) eye movements (gaze position and pupil), (3) psychological assessment of the patients, and (4) social trait judgment ratings from a subset of patients and a …

Dissociation Between Individual Differences In Self-Reported Pain Intensity And Underlying Fmri Brain Activation, M E Hoeppli, H Nahman-Averbuch, W A Hinkle, E Leon, J Peugh, M Lopez-Sola, C D King, K R Goldschneider, R C Coghill

Open Access Publications

Pain is an individual experience. Previous studies have highlighted changes in brain activation and morphology associated with within- and interindividual pain perception. In this study we sought to characterize brain mechanisms associated with between-individual differences in pain in a sample of healthy adolescent and adult participants (N = 101). Here we show that pain ratings varied widely across individuals and that individuals reported changes in pain evoked by small differences in stimulus intensity in a manner congruent with their pain sensitivity, further supporting the utility of subjective reporting as a measure of the true individual experience. Furthermore, brain activation related …

Effect Of Neoadjuvant Chemotherapy On Intraoperative Core Temperature In Patients With Breast Cancer: A Retrospective Cohort Study, Daniel B Zamler, Takashi Shingu, Laura M Kahn, Kristin Huntoon, Cynthia Kassab, Martina Ott, Katarzyna Tomczak, Jintan Liu, Yating Li, Ivy Lai, Rocio Zorilla-Veloz, Cassian Yee, Kunal Rai, Betty Ys Kim, Stephanie S Watowich, Amy B Heimberger, Giulio F Draetta, Jian Hu

Faculty, Staff and Student Publications

Novel therapeutic strategies targeting glioblastoma (GBM) often fail in the clinic, partly because preclinical models in which hypotheses are being tested do not recapitulate human disease. To address this challenge, we took advantage of our previously developed spontaneous Qk/Trp53/Pten (QPP) triple-knockout model of human GBM, comparing the immune microenvironment of QPP mice with that of patient-derived tumors to determine whether this model provides opportunity for gaining insights into tumor physiopathology and preclinical evaluation of therapeutic agents. Immune profiling analyses and single-cell sequencing of implanted and spontaneous tumors from QPP mice and from patients with glioma revealed intratumoral immune components that …

Immune Landscape Of A Genetically Engineered Murine Model Of Glioma Compared With Human Glioma, Daniel B Zamler, Takashi Shingu, Laura M Kahn, Kristin Huntoon, Cynthia Kassab, Martina Ott, Katarzyna Tomczak, Jintan Liu, Yating Li, Ivy Lai, Rocio Zorilla-Veloz, Cassian Yee, Kunal Rai, Betty Ys Kim, Stephanie S Watowich, Amy B Heimberger, Giulio F Draetta, Jian Hu

Faculty, Staff and Student Publications

Novel therapeutic strategies targeting glioblastoma (GBM) often fail in the clinic, partly because preclinical models in which hypotheses are being tested do not recapitulate human disease. To address this challenge, we took advantage of our previously developed spontaneous Qk/Trp53/Pten (QPP) triple-knockout model of human GBM, comparing the immune microenvironment of QPP mice with that of patient-derived tumors to determine whether this model provides opportunity for gaining insights into tumor physiopathology and preclinical evaluation of therapeutic agents. Immune profiling analyses and single-cell sequencing of implanted and spontaneous tumors from QPP mice and from patients with glioma revealed intratumoral immune components that …