Digital Commons Network^™

Effect Of Amoxicillin On The Gut Microbiome Of Children With Severe Acute Malnutrition In Madarounfa, Niger: A Retrospective Metagenomic Analysis Of A Placebo-Controlled Trial, Drew J Schwartz, Amy Langdon, Xiaoqing Sun, Céline Langendorf, Fatou Berthé, Rebecca F Grais, Indi Trehan, Sheila Isanaka, Gautam Dantas

2020-Current year OA Pubs

BACKGROUND: Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition.

METHODS: We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of …

Trapeziectomy With Ligament Reconstruction/ Suspensionplasty Compared To Suture Tape Suspensionplasty For The Surgical Treatment Of Advanced Thumb Carpometacarpal Osteoarthritis, Nishant Dwivedi, Ryan P Calfee, Lindley B Wall, Martin I Boyer, David Brogan, Christopher J Dy, Charles A Goldfarb

2020-Current year OA Pubs

PURPOSE: Trapeziectomy with tendon reconstruction/suspensionplasty (TRS) is the most commonly performed surgical procedure in the United States for treatment of thumb carpometacarpal (CMC) osteoarthritis (OA). Trapeziectomy with suture tape suspensionplasty (STS) has been used recently at the study institution as an alternative surgical treatment option with perceived benefits of earlier return to function and reduced operative time. The purpose of this study was to compare patient outcomes following TRS versus STS for treatment of thumb CMC OA.

METHODS: All patients who underwent primary, isolated TRS or STS for treatment of thumb CMC OA between 1/1/2014 and 9/1/2020 were analyzed. We …

Outcomes Of Therapy And Ulnar Nerve Transposition For Elbow Stiffness After Pediatric Medial Epicondyle Fractures, Emma R Payne, Lindley B Wall, Stacy Baker, Valeri Calhoun, Summer Roberts, Charles A Goldfarb

2020-Current year OA Pubs

PURPOSE: Following medial epicondyle fractures, a subset of pediatric patients has persistent limitations in elbow motion. This study soughted to understand the patient characteristics of this group and to assess the effectiveness of intensive therapy and ulnar nerve transposition in improving elbow range of motion and patient-reported outcomes.

METHODS: A cohort of 31 pediatric patients with stiffness after elbow trauma was narrowed to 8 pediatric patients (7 female) ranging in age from 9 to 14 years, who were diagnosed with medial epicondyle fractures and underwent intensive therapy and ulnar nerve transposition with or without elbow joint release. We collected demographic …

Obstetrics And Gynecology Clerkship Directors' Experiences Advising Residency Applicants, Helen K Morgan, Laura Baecher-Lind, Rashmi Bhargava, Susan Cox, Elise Everett, Angela Fleming, Scott Graziano, Chris Morosky, Celeste Royce, Tammy Sonn, Jill Sutton, Shireen Madani Sims

2020-Current year OA Pubs

BACKGROUND: The evolving landscape of application processes for obstetrics and gynecology residency applicants poses many challenges for applicants and advisors. The lack of data coordination among national groups creates crucial gaps in information for stakeholder groups.

OBJECTIVE: This study aimed to identify the current state of the advising milieu for obstetrics and gynecology residency applicants and their career advisors, the annual Association of Professors of Gynecology and Obstetrics survey focused on US clerkship directors' experiences advising students through these processes.

STUDY DESIGN: A 23-item anonymous survey was developed that asked respondents about demographics and outcomes for the students that they …

Bhlhe40 Mediates Cross-Talk Between Pathogenic Th17 Cells And Myeloid Cells During Experimental Autoimmune Encephalomyelitis, Melissa E Cook, Irina Shchukina, Chih-Chung Lin, Tara R Bradstreet, Elizabeth A Schwarzkopf, Nicholas N Jarjour, Ashlee M Webber, Konstantin Zaitsev, Maxim N Artyomov, Brian T Edelson

2020-Current year OA Pubs

TH17 cells are implicated in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). We previously reported that the transcription factor basic helix-loop-helix family member e40 (BHLHE40) marks cytokine-producing pathogenic TH cells during EAE, and that its expression in T cells is required for clinical disease. In this study, using dual reporter mice, we show BHLHE40 expression within TH1/17 and ex-TH17 cells following EAE induction. Il17a-Cre-mediated deletion of BHLHE40 in TH cells led to less severe EAE with reduced TH cell cytokine production. Characterization of the leukocytes in the CNS during EAE by single-cell RNA sequencing identified differences in …

Health-Related Quality-Of-Life In Treatment-Naive Cll/Sll Patients Treated With Zanubrutinib Versus Bendamustine Plus Rituximab, Paolo Ghia, Gisoo Barnes, Keri Yang, Constantine S Tam, Tadeusz Robak, Jennifer R Brown, Brad S Kahl, Tian Tian, Andy Szeto, Jason C Paik, Mazyar Shadman

2020-Current year OA Pubs

OBJECTIVE: Zanubrutinib is a highly selective, next-generation Bruton's tyrosine kinase inhibitor. In the phase 3 SEQUOIA trial (NCT03336333), treatment with zanubrutinib resulted in significantly improved progression-free survival compared to bendamustine plus rituximab (BR) in adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) without del(17p). The current analysis compared the effects of zanubrutinib versus BR on patients' health-related quality-of-life (HRQoL).

METHODS: In the SEQUOIA trial, patient-reported outcomes (PROs) were assessed at baseline and every 12 weeks (3 cycles) using the EORTC QLQ-C30 and EQ-5D-5L. Descriptive analyses were performed on all the questionnaires' scales and a mixed …

Both Horatio And Polonius: Innate Lymphoid Cells In Tissue Homeostasis And Repair, Intelly S Lee, Steven J Van Dyken

2020-Current year OA Pubs

Innate lymphoid cells (ILCs) have emerged as critical tissue-resident lymphocytes that coordinate responses to environmental stress and injury. Traditionally, their function was thought to mirror adaptive lymphocytes that respond to specific pathogens. However, recent work has uncovered a more central role for ILCs in maintaining homeostasis even in the absence of infection. ILCs are now better conceptualized as an environmental rheostat that helps maintain the local tissue setpoint during environmental challenge by integrating sensory stimuli to direct homeostatic barrier and repair programs. In this article, we trace the developmental origins of ILCs, relate how ILCs sense danger signals, and describe …

Iuphar Themed Review: Opioid Efficacy, Bias, And Selectivity, Nokomis Ramos-Gonzalez, Barnali Paul, Susruta Majumdar

2020-Current year OA Pubs

Drugs acting at the opioid receptor family are clinically used to treat chronic and acute pain, though they represent the second line of treatment behind GABA analogs, antidepressants and SSRI's. Within the opioid family mu and kappa opioid receptor are commonly targeted. However, activation of the mu opioid receptor has side effects of constipation, tolerance, dependence, euphoria, and respiratory depression; activation of the kappa opioid receptor leads to dysphoria and sedation. The side effects of mu opioid receptor activation have led to mu receptor drugs being widely abused with great overdose risk. For these reasons, newer safer opioid analgesics are …

Pigo-Cdg: A Case Study With A New Genotype, Expansion Of The Phenotype, Literature Review, And Nosological Considerations, Rodrigo Tzovenos Starosta, Nino Kerashvili, Cassandra Pruitt, Matthew J. Schultz, Suzanne W Boyer, Eva Morava, Maria Laura Duque Lasio, Dorothy K Grange

2020-Current year OA Pubs

The phosphatidylinositol glycan anchor biosynthesis class O protein (PIGO) enzyme is an important step in the biosynthesis of glycosylphosphatidylinositol (GPI), which is essential for the membrane anchoring of several proteins. Bi-allelic pathogenic variants in

Protective Effects Of Epigallocatechin-3-Gallate Counteracting The Chronic Hypobaric Hypoxia-Induced Myocardial Injury In Plain-Grown Rats At High Altitude, Haotian Chen, Chen Chen, Yuhui Qin, Lei Wang, Jie Zheng, Fabao Gao

2020-Current year OA Pubs

Exposure to hypobaric hypoxia (HH) environment causes stress to the body, especially the oxygen-consuming organs. Chronic HH conditions have adverse effects on the myocardium. Thus, we conducted this experiment and aim to evaluate such adverse effects and explore the therapeutic role of epigallocatechin-3-gallate (EGCG) in rats' heart under chronic HH conditions. For that purpose, we transported rats from plain to a real HH environment at high altitude for establishing the HH model. At high altitude, animals were treated with EGCG while the salidroside was used as the positive control. General physiological data were collected, and routine blood test results were …

Neonatal Brain Mri And Short-Term Outcomes After Acute Provoked Seizures, Yi Li, Renée A Shellhaas, Et Al.

2020-Current year OA Pubs

OBJECTIVE: We investigated how diagnosis and injury location on neonatal brain MRI following onset of acute provoked seizures was associated with short term outcome.

STUDY DESIGN: A multicenter cohort of neonates with acute provoked seizures enrolled in the Neonatal Seizure Registry. MRIs were centrally evaluated by a neuroradiologist for location of injury and radiologic diagnosis. Clinical outcomes were determined by chart review. Multivariate logistic regression was used to examine the association between MRI findings and outcomes.

RESULTS: Among 236 newborns with MRI at median age 4 days (IQR 3-8), 91% had abnormal MRI. Radiologic diagnoses of intracranial hemorrhage (OR 3.2 …

Type 2 Immunity In The Brain And Brain Borders, Tornike Mamuladze, Jonathan Kipnis

2020-Current year OA Pubs

Recent research in neuroimmunology has revolutionized our understanding of the intricate interactions between the immune system and the central nervous system (CNS). The CNS, an "immune-privileged organ", is now known to be intimately connected to the immune system through different cell types and cytokines. While type 2 immune responses have traditionally been associated with allergy and parasitic infections, emerging evidence suggests that these responses also play a crucial role in CNS homeostasis and disease pathogenesis. Type 2 immunity encompasses a delicate interplay among stroma, Th2 cells, innate lymphoid type 2 cells (ILC2s), mast cells, basophils, and the cytokines interleukin (IL)-4, …

Long Non-Coding Rna Snhg8 Drives Stress Granule Formation In Tauopathies, Reshma Bhagat, Miguel A Minaya, Arun Renganathan, Muneshwar Mehra, Jacob Marsh, Rita Martinez, Abdallah M Eteleeb, Alissa L Nana, Salvatore Spina, William W Seeley, Lea T Grinberg, Celeste M Karch

2020-Current year OA Pubs

Tauopathies are a heterogenous group of neurodegenerative disorders characterized by tau aggregation in the brain. In a subset of tauopathies, rare mutations in the MAPT gene, which encodes the tau protein, are sufficient to cause disease; however, the events downstream of MAPT mutations are poorly understood. Here, we investigate the role of long non-coding RNAs (lncRNAs), transcripts >200 nucleotides with low/no coding potential that regulate transcription and translation, and their role in tauopathy. Using stem cell derived neurons from patients carrying a MAPT p.P301L, IVS10 + 16, or p.R406W mutation and CRISPR-corrected isogenic controls, we identified transcriptomic changes that occur …

Modeling The Normal:Abnormal Spectrum Of Early Childhood Internalizing Behaviors: A Clinical-Developmental Approach For The Multidimensional Assessment Profiles Internalizing Dimensions, Lauren S Wakschlag, Phillip Sherlock, Courtney K Blackwell, James L Burns, Sheila Krogh-Jespersen, Richard C Gershon, David Cella, Kristin A Buss, Joan L Luby

2020-Current year OA Pubs

BACKGROUND: We expanded the Multidimensional Assessment Profiles (MAPS) Scales developmental specification model to characterize the normal:abnormal spectrum of internalizing (anxious and depressive) behaviors in early childhood via the MAPS-Internalizing (MAPS-INT) scale.

METHODS: The MAPS-INT item pool was generated based on clinical expertise and prior research. Analyses were conducted on a sub-sample of families (n = 183) from the diverse When to Worry early childhood sample.

RESULTS: Normal:abnormal descriptive patterns for both anxious and depressive behaviors were consistent with prior work: (1) extremes of normative variation are abnormal when very frequent; and (2) pathognomonic indicators that most children do not engage …

Cux1-Related Neurodevelopmental Disorder: Deep Insights Into Phenotype-Genotype Spectrum And Underlying Pathology, Henry Oppermann, Christina A Gurnett, Et Al.

2020-Current year OA Pubs

Heterozygous, pathogenic CUX1 variants are associated with global developmental delay or intellectual disability. This study delineates the clinical presentation in an extended cohort and investigates the molecular mechanism underlying the disorder in a Cux1

The Preserving Kidney Function In Children With Ckd (Preserve) Study: Rationale, Design, And Methods, Michelle R Denburg, Vikas Dharnidharka, Et Al.

2020-Current year OA Pubs

RATIONALE & OBJECTIVE: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management.

STUDY DESIGN: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]).

SETTING & PARTICIPANTS: PRESERVE will include …

Experimentally Induced Active And Quiet Sleep Engage Non-Overlapping Transcriptional Programs In Drosophila, Niki Anthoney, Lucy Tainton-Heap, Hang Luong, Eleni Notaras, Amber B Kewin, Qiongyi Zhao, Trent Perry, Philip Batterham, Paul J Shaw, Bruno Van Swinderen

2020-Current year OA Pubs

Sleep in mammals can be broadly classified into two different physiological categories: rapid eye movement (REM) sleep and slow-wave sleep (SWS), and accordingly REM and SWS are thought to achieve a different set of functions. The fruit fly

Evaluation Of The Efficacy And Safety Of Bempedoic Acid In Women And Men: Pooled Analyses From Phase 3 Trials, Anne C Goldberg, Maciej Banach, Alberico L Catapano, P Barton Duell, Lawrence A Leiter, Jeffrey C Hanselman, Lei Lei, G B John Mancini

2020-Current year OA Pubs

BACKGROUND AND AIMS: Sex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid.

METHODS: Patients were grouped into two pools: 1) atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) "on statins" and 2) "low-dose or no statin". Percent changes from baseline to at least week 12 in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed …

Novel Academic Tabletop 2022 (Nat22): A Dynamic Dice-Based Emergency Medicine Education Tool, Adam Heilmann, Jessica Pelletier, Collyn Murray, Alexander Croft

2020-Current year OA Pubs

Gamification is an effective teaching tool that improves engagement and knowledge retention. Tabletop role-playing games are dynamic games that use random chance and foster player/leader partnership. To date, there are no teaching tools that mimic dynamic or unpredictable patient presentations. This style of game may work well as a tool for medical education in a simulation-based modality. In this report, we document the rules, materials, and training required to reproduce a hybrid game created to combine facets of simulation and tabletop role-playing games (TRPGs) to create a dynamic medical education tool. After testing the game for flaws and fluidity of …

Cytokine Release Syndrome In Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: A Retrospective Study Analyzing Risks, Outcomes, And Healthcare Burden, Rushin Patel, Mrunal Patel, Fehmida Laxmidhar, Khushboo Lakhatariya, Darshil Patel, Zalak Patel, Safia Shaikh

2020-Current year OA Pubs

Background Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising immunotherapy for various malignancies. However, its use is associated with challenges, including cytokine release syndrome (CRS), a potentially severe complication. This retrospective study aims to analyze the risks, outcomes, and healthcare burden of CRS in patients undergoing CAR-T therapy. Method Data from the 2020 National Inpatient Sample (NIS) were utilized, comprising 415 CAR-T-related hospitalizations. They were categorized into those with CRS (n = 68) and those without CRS (n = 347). Baseline characteristics, including age, gender, race, income, insurance status, and comorbidities, were compared. Outcomes of interest included …

Scientific Document Development Standards For The Society Of Cardiovascular Computed Tomography (Scct): A Statement From The Scct Guidelines Committee, Lauren A Baldassarre, Lynne Koweek, Daniele Andreini, Kelley Branch, Dawn Brennaman, Ricardo P J Budde, Stacy De La O, Timothy Fairbairn, Sandeep S Hedgire, Jonathan R Weir-Mccall, Pam K Woodard, Dennis Wong, Marcus Y Chen, Scct Guidelines Committee

2020-Current year OA Pubs

The Society of Cardiovascular Computed Tomography (SCCT) is an international community of physicians, scientists and technologists advocating for research, education, and clinical excellence in the use of cardiovascular computed tomography (CCT). SCCT members are committed to improving health outcomes through effective use of CCT. The SCCT routinely authors, endorses, and jointly collaborates on scientific documents that reflect the best available evidence and expert consensus supported in practice of CCT. This paper outlines SCCT's methodology for developing scientific documents. It was formulated by members of the SCCT Guidelines Committee and approved by the SCCT Board of Directors.

Six-Month Outcomes Of Mechanical Thrombectomy For Treating Deep Vein Thrombosis: Analysis From The 500-Patient Clout Registry, Abdullah Shaikh, Vipul Khetarpaul, Et Al.

2020-Current year OA Pubs

PURPOSE: Mechanical thrombectomy for the treatment of deep vein thrombosis (DVT) is being increasingly utilized to reduce symptoms and prevent postthrombotic syndrome (PTS), but more data on clinical outcomes are needed. Mechanical thrombectomy was studied in the ClotTriever Outcomes (CLOUT) registry with 6-month full analysis outcomes reported herein.

MATERIALS AND METHODS: The CLOUT registry is a prospective, all-comer study that enrolled 500 lower extremity DVT patients across 43 US sites treated with mechanical thrombectomy using the ClotTriever System. Core-lab assessed Marder scores and physician-assessed venous patency by duplex ultrasound, PTS assessment using Villalta score, venous symptom severity, pain, and quality …

Assessing Cancer Risk In The Anterior Part Of The Prostate Using Micro-Ultrasound: Validation Of A Novel Distinct Protocol, Sandy Schaer, Arnas Rakauskas, Julien Dagher, Stefano La Rosa, Jake Pensa, Wayne Brisbane, Leonard Marks, Adam Kinnaird, Robert Abouassaly, Eric Klein, Lewis Thomas, Jean-Yves Meuwly, Pamela Parker, Beat Roth, Massimo Valerio

2020-Current year OA Pubs

PURPOSE: To develop and validate a micro-ultrasound risk score that predicts the likelihood of significant prostate cancer in the anterior zone.

METHODS: Patients were enrolled from three expert institutions familiar with micro-ultrasound. The study was conducted in two phases. First, the PRI-MUS anterior score was developed by assessing selected prostate videos from patients who subsequently underwent radical prostatectomy. Second, seven urology readers with varying levels of experience in micro-ultrasound examination evaluated prostate loops according to the PRI-MUS anterior score. Each reader watched the videos and recorded the likelihood of the presence of significant cancer in the anterior part of the …

T Cell Control Of Inflammaging, Irina Shchukina, Pavla Bohacova, Maxim N Artyomov

2020-Current year OA Pubs

T cells are a critical component of the immune system, found in abundance in blood, secondary lymphoid organs, and peripheral tissues. As individuals age, T cells are particularly susceptible to changes, making them one of the most affected immune subsets. These changes can have significant implications for age-related dysregulations, including the development of low-grade inflammation - a hallmark of aging known as inflammaging. In this review, we first present age-related changes in the functionality of the T cell compartment, including dysregulation of cytokine and chemokine production and cytotoxicity. Next, we discuss how these changes can contribute to the development and …

Hepatic Pyruvate And Alanine Metabolism Are Critical And Complementary For Maintenance Of Antioxidant Capacity And Resistance To Oxidative Insult, Nicole K H Yiew, Joel H Vazquez, Michael R Martino, Stefanie Kennon-Mcgill, Jake R Price, Felicia D Allard, Eric U Yee, Alexander J Layman, Laura P James, Kyle S Mccommis, Brian N Finck, Mitchell R Mcgill

2020-Current year OA Pubs

OBJECTIVE: Mitochondrial pyruvate is a critical intermediary metabolite in gluconeogenesis, lipogenesis, and NADH production. As a result, the mitochondrial pyruvate carrier (MPC) complex has emerged as a promising therapeutic target in metabolic diseases. Clinical trials are currently underway. However, recent in vitro data indicate that MPC inhibition diverts glutamine/glutamate away from glutathione synthesis and toward glutaminolysis to compensate for loss of pyruvate oxidation, possibly sensitizing cells to oxidative insult. Here, we explored this in vivo using the clinically relevant acetaminophen (APAP) overdose model of acute liver injury, which is driven by oxidative stress.

METHODS: We used pharmacological and genetic approaches …

Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 At 2 Children's Hospitals, Eric E Engstrom, Alexander S Plattner, J Chase Mcneil, Kristina G Hulten, Patrick J Reich, Mary G Boyle, James J Dunn, Stephanie A Fritz, Sheldon L Kaplan

2020-Current year OA Pubs

BACKGROUND: Invasive infections caused by

METHODS: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution.

RESULTS: I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In …

Humoral Immune Response To Covid-19 Mrna Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Ofatumumab, Amit Bar-Or, Rany Aburashed, Angel R Chinea, Barry A Hendin, Elisabeth Lucassen, Xiangyi Meng, James Stankiewicz, Mark J Tullman, Anne H Cross

2020-Current year OA Pubs

BACKGROUND: There are limited data available regarding the impact of ofatumumab, an anti-CD20 B-cell-depleting monoclonal antibody for relapsing multiple sclerosis (RMS), on vaccination response. The study objective was to assess humoral immune response (HIR) to non-live coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination in patients with RMS treated with ofatumumab.

METHODS: This was an open-label, single-arm, multicenter, prospective pilot study of patients with RMS aged 18-55 years who received 2 or 3 doses of a COVID-19 mRNA vaccine after ≥1 month of subcutaneous ofatumumab (20 mg/month) treatment. The primary endpoint was the proportion of patients achieving HIR, as defined …

Small Molecule Screen Identifies Pyrimethamine As An Inhibitor Of Nrf2-Driven Esophageal Hyperplasia, Chorlada Paiboonrungruang, Brittany Bowman, Julius Chembo, M Ben Major, Et Al.

2020-Current year OA Pubs

OBJECTIVE: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2

DESIGN: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays.

RESULTS: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as …

Operational Ontology For Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical And Research Use Of Real-World Data From Patients Treated For Cancer, Charles S Mayo, Walter Bosch, Et Al.

2020-Current year OA Pubs

PURPOSE: The ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), radiation oncology information systems, treatment planning systems, and other cancer care and outcomes databases. We sought to create a standardized ontology for clinical data, social determinants of health, and other radiation oncology concepts and interrelationships.

METHODS AND MATERIALS: The American Association of Physicists in Medicine's Big Data Science Committee was initiated in July 2019 to explore common ground from the stakeholders' collective experience of issues that typically compromise the formation of large inter- …

Steatosis Drives Monocyte-Derived Macrophage Accumulation In Human Metabolic Dysfunction-Associated Fatty Liver Disease, Mandy M Chan, Joseph W Beals, Marina Terekhova, Christina F Fu, Li He, Arick C Park, Gordon I Smith, Kathleen Byrnes, Wandy L Beatty, Shaina R Eckhouse, J Christopher Eagon, Daniel Ferguson, Brian N Finck, Samuel Klein, Maxim N Artyomov, Joel D Schilling, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common complication of obesity with a hallmark feature of hepatic steatosis. Recent data from animal models of MAFLD have demonstrated substantial changes in macrophage composition in the fatty liver. In humans, the relationship between liver macrophage heterogeneity and liver steatosis is less clear.

METHODS: Liver tissue from 21 participants was collected at time of bariatric surgery and analysed using flow cytometry, immunofluorescence, and H&E microscopy. Single-cell RNA sequencing was also conducted on a subset of samples (n = 3). Intrahepatic triglyceride content was assessed via MRI and tissue histology. …