tbuckley/cabot-search huggingface dataset:
Abstract 15589: Mitochondrial Metabolites Predict Cardiovascular Outcomes and Heart Failure in People With Type 2 Diabetes Mellitus and Vascular Disease: A Tecos Substudy
Authors: Jessica A Regan, Jennifer Green, Lauren K Truby, Maggie Nguyen, Stephanie Giamberardino, Robert J Mentz, Robert W McGarrah, Yinggan Zheng, John B Buse, Darren K McGuire, eberhard standl, Paul W Armstrong, Rury R Holman, Eric D Peterson, Svati H Shah
Journal: Circulation (2020)

Introduction: People with type 2 diabetes mellitus (DM) have a large burden of cardiovascular (CV) morbidity and mortality, but the likelihood of these outcomes varies and existing risk calculators do not fully capture risk for individuals. Hypothesis: Circulating metabolites characterizing mitochondrial dysfunction may be novel predictors for CV outcomes. Methods: We performed targeted mass-spectrometry metabolite profiling (45 acylcarnitines, 15 amino acids) on baseline plasma samples from 568 cases (498 with major adverse cardiac events (MACE) and 131 with incident hospitalization for heart failure (hHF)) and 568 matched controls (without events) from the patients assigned to placebo in Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Matching was based on history of HF, coronary artery disease, BMI, hemoglobin A1C, creatinine, low-density lipoprotein cholesterol, fasting status and ejection fraction. Principal components analysis (PCA) was used for dimensionality reduction, and conditional logistic regression to determine association of PCA factors with MACE or hHF and for individual metabolites within significant factors (false discovery rate q&lt;0.05) Results: Of 12 PCA-derived metabolite factors, three were associated significantly with MACE or hHF; these factors were composed of: 1) short-chain dicarboxylacylcarnitines and long chain acylcarnitines (OR 1.50, q=0.03); 2) medium chain acylcarnitines (OR 1.28, q=0.001); 3) C5:1 and one medium-chain dicarboxylacylcarnitine (OR 1.17, q=0.03). Of these three factors, none were significantly associated with the individual components of MACE. Ten individual metabolites, including short- and medium-chain dicarboxylacylcarnitines and medium- and long-chain acylcarnitines, remained significantly associated with MACE (q&lt;0.05). Two metabolites, one short-chain dicarboxylacylcarnitine and one medium-chain acylcarnitine were associated with hHF (q&lt;0.05). Conclusions: Metabolites reporting on dysregulated mitochondrial fatty acid oxidation and endoplasmic reticulum stress are elevated in individuals with DM who progress to MACE and/or hHF. These biomarkers may improve CV risk prediction in DM patients and help highlight emerging risk mechanisms.
The aryl hydrocarbon receptor as a mediator of host-microbiota interplay
Authors: Fangcong Dong, Gary H. Perdew
Journal: Gut Microbes (2020)

Increasing evidence suggests a significant role for microbiota dependent metabolites and co-metabolites, acting as aryl hydrocarbon receptor (AHR) ligands, to facilitate bidirectional communication between the host and the microbiota and thus modulate physiology. Such communication is particularly evident within the gastrointestinal tract. Through binding to or activating the AHR, these metabolites play fundamental roles in various physiological processes and likely contribute to the maintenance of intestinal homeostasis. In recent years, tryptophan metabolites were screened to identify physiologically relevant AHR ligands or activators. The discovery of specific microbiota-derived indole-based metabolites as AHR ligands may provide insight concerning how these metabolites affect interactions between gut microbiota and host intestinal homeostasis and how this relates to chronic GI disease and overall health. A greater understanding of the mechanisms that modulate the production of such metabolites and associated AHR activity may be utilized to effectively treat inflammatory diseases and promote human health. Here, we review microbiota-derived AHR ligands generated from tryptophan that modulate host-gut microbiota interactions and discuss possible intervention strategies for potential therapies in the future.
Correspondence on ‘Risk of systemic lupus erythematosus after immune thrombocytopenia and autoimmune haemolytic anaemia: a nationwide French study’
Authors: Julien Maquet, Margaux Lafaurie, Laurent Sailler, Maryse Lapeyre-Mestre, Guillaume Moulis
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the articles by Zhu et al 1 and Mo et al 2 studying the risk of new systemic lupus erythematosus (SLE) diagnosis after immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) diagnoses in the Taiwanese National Health Database. Zhu et al observed 34 SLE cases among 723 patients with incident ITP between 2000 and 2013. The 1-year and 5-year cumulative incidences were 1.9% and 4.8%, respectively.1 Mo et al reported the diagnosis of 117 SLE during the follow-up of 731 patients with incident AIHA between 2005 and 2012. The 1-year and 5-year cumulative incidences were 11.3% and 17.3%, respectively.2

In the present study, we estimated the risk of new SLE after incident ITP or AIHA in the entire French general population. FAITH and AHEAD cohorts3 are the French nationwide cohorts of adult patients with incident primary ITP and AIHA, respectively. These cohorts are built using validated algorithms in the French health database ( Systeme National des Donnees de Sante ), which links sociodemographic, out-hospital and in-hospital data for the entire French population (>66 million inhabitants).4 SLE was defined by the date of first in-hospital or chronic disease (the …
Effect of providing free glasses on children's educational outcomes in China: The "Seeing is Learning" cluster-randomized controlled trial
Authors: Xiaochen Ma, Zhongqiang Zhou, Hongmei Yi, Xiaopeng Pang, Yaojiang Shi, Qianyun Chen, Mirjam E. Meltzer, Saskia le Cessie, Mingguang He, Scott Rozelle, Yizhi Liu, Nathan Congdon
Journal: BMJ (2014)
EPEN-42. MOLECULAR PROFILING REVEALS DISTINCT SUBGROUPS OF PEDIATRIC SPINAL EPENDYMOMA
Authors: Omar Ahmad, Rebecca Chapman, Lisa Storer, Li Luo, Linda Resar, Kenneth Cohen, Richard Grundy, Anbarasu Lourdusamy
Journal: Neuro-Oncology (2020)

Abstract Paediatric spinal ependymomas are important, albeit uncommon, malignant central nervous system tumours. Unlike adults, children with these tumours are likely to experience a more aggressive disease course, with a higher rate of local failure and a higher rate of metastases. The clinical and molecular factors underlying these differences remain poorly characterized. We analyzed spinal ependymoma (SEPN) tumour samples from 27 paediatric patients (female: 11, male: 15; age range: 4–18 years) using genome-wide DNA methylation profiling, copy-number analysis, as well as transcriptome profiling. Using DNA methylation profiles, two distinct unsupervised consensus-clustering approaches, hierarchical clustering and non-negative matrix factorization reliably identified two subgroups. These subgroups were designated as Myxopapillary ependymomas (SP-MPE) and spinal ependymomas (SP-EPN) based on the online Classifier tool (MNP2.0). The genome-wide copy-number analysis showed differences in numbers and pattern of copy-number alterations between these groups. The gain of chromosome 20 (39%) followed by loss of chromosomes 6 (28%), 10 (28%), and 13 (28%) were detected in the SP-MPE group, whereas loss of chromosome 22 was frequent (60%) in the SP-EPN group. Transcriptomics analysis showed that genes associated with oxidative phosphorylation, TCA cycle components, electron transport, and Interferon-gamma production characterize the SP-MPE group whereas potassium ion import and regulation of astrocyte differentiation characterize the SP-EPN group. Western blot analysis validated the increased protein expression of oxidative phosphorylation complexes in SP-MPE. With this study, we provide a foundation for further molecular characterization of pediatric SEPN subgroups. Our results suggest that mitochondrial oxidative phosphorylation may drive the regulation of energy metabolism of SP-MPE tumours.
Trends in Use and Perceptions of Nicotine Vaping Among US Youth From 2017 to 2020
Authors: Richard Miech, Adam Leventhal, Lloyd Johnston, Patrick M. O’Malley, Megan E. Patrick, Jessica Barrington-Trimis
Journal: JAMA Pediatrics (2020)

US adolescent nicotine vaping increased at a record pace from 2017 to 2019, prompting new national policies to reduce access to flavors of vaping products preferred by youth.To estimate prevalence, perceived harm, and accessibility of nicotine vaping products among US adolescents from 2017 to 2020.This survey study includes data from Monitoring the Future, which conducted annual, cross-sectional, school-based, nationally representative surveys from 2017 to 2020 of 10th- and 12th-grade students (results pooled grades, n = 94 320) about vaping and other topics.Prevalence of self-reported nicotine vaping; vaping brand and flavor used most often; perceived risk of nicotine vaping; and perceived ease of getting vaping devices, nicotine solutions for vaping, and flavored solutions.In 2020, Monitoring the Future surveyed 8660 students in 10th and 12th grade, of whom 50.6% (95% CI, 47%-54%) were female, 13% (95% CI, 8%-21%) were non-Hispanic Black, 29% (95% CI, 21%-40%) were Hispanic, and 53% (95% CI, 42%-63%) were non-Hispanic White. Nicotine vaping prevalence in 2020 was 22% (95% CI, 19%-25%) for past 30-day use, 32% (95% CI, 28%-37%) for past 12-month use, and 41% (95% CI, 37%-46%) for lifetime use; these levels did not significantly change from 2019. Daily nicotine vaping (use on ≥20 days of the last 30 days) significantly declined from 9% (95% CI, 8%-10%) to 7% (95% CI, 6%-9%) over 2019 to 2020. JUUL brand prevalence in the past 30 days decreased from 20% (95% CI, 18%-22%) in 2019 to 13% (95% CI, 11%-15%) in 2020, while use of other brands increased. Among youth who vaped in the past 30 days in 2020, the most often used flavor was fruit at 59% (95% CI, 55%-63%), followed by mint at 27% (95% CI, 24%-30%) and menthol at 7% (95% CI, 5%-9%); significantly fewer reported easy access to vaping devices and nicotine solutions compared with 2019; and 80% (95% CI, 75%-84%) reported they could easily get a vaping flavor other than tobacco or menthol. Among all youth, perceived risk of both occasional and regular nicotine vaping increased from 2019 to 2020.Increasing US adolescent nicotine vaping trends from 2017 to 2019 halted in 2020, including a decline in daily vaping. Decreases in perceived accessibility of some vaping products, as well as increases in perceived risk of nicotine vaping, occurred from 2019 to 2020. Yet, adolescent nicotine vaping remains highly prevalent, flavors remain highly accessible, and declines in JUUL use were countered by increased use of other brands.
Rugby players plan negligence claim for chronic traumatic encephalopathy
Authors: Clare Dyer
Journal: BMJ (2020)

Eight former rugby players with early onset dementia are planning to launch negligence claims against World Rugby, the Rugby Football Union, and the Welsh Rugby Union over the effects of concussion and repeated blows to the head.

All of the players, who include the World Cup winner Steve Thompson and the former Wales international Alix Popham, are under 45 and blame their condition on brain injuries sustained while playing rugby. Thompson, 43, says that he cannot remember winning the World Cup for England in 2003 or even being in Australia for the tournament.

All eight have a …
Intranasal vaccination with a lentiviral vector protects against SARS-CoV-2 in preclinical animal models
Authors: Min-Wen Ku, Maryline Bourgine, Pierre Authié, Jodie Lopez, Kirill Nemirov, Fanny Moncoq, Amandine Noirat, Benjamin Vesin, Fabien Nevo, Catherine Blanc, Philippe Souque, Houda Tabbal, Emeline Simon, David Hardy, Marine Le Dudal, Françoise Guinet, Laurence Fiette, Hugo Mouquet, François Anna, Annette Martin, Nicolas Escriou, Laleh Majlessi, Pierre Charneau
Journal: Cell Host & Microbe (2020)
EPID-12. TEMPORAL AND GLOBAL GEOGRAPHIC VARIATION IN THE INCIDENCE OF PEDIATRIC CNS TUMORS, 1998–2012
Authors: Karina Ribeiro, Sidnei Epelman
Journal: Neuro-Oncology (2020)

Abstract AIMS To describe the temporal and geographic variation in the incidence of pediatric CNS malignancies worldwide, presenting analyses by sex, period, region, and histological subtype between 1998 and 2012. METHODS Data were extracted from volumes IX to XI of the Cancer Incidence in 5 Continents, covering the periods 1998–2002 (1), 2003–2007 (2), and 2008–2012 (3). We pooled data from 44 countries, classifying them into 6 regions (Africa (AF), Asia (AS), Oceania (O), Europe (E), Central/South America (CSA), North America (NA)). Age-standardized incidence rates (ASIR per million, 0–19 years) were calculated and temporal variation was evaluated using incidence rate ratios (IRR) (95% CI). RESULTS The highest incidence (Period 3) was observed in NA (34.0 and 30.2 for males and females, respectively). Astrocytic tumors were predominant in all regions, with percentages ranging between 24.5% (E, females) and 45.6% (NA, females). Increasing trends (Period 3 x 1) were observed in AS (IRR=1.15, 95% CI 1.06–1.25), CSA (IRR=1.25, 95% CI 1.01–1.55), and NA (IRR=1.05, 95% CI 1.03–1.07), for males and in AS (IRR=1.15, 95% CI 1.05–1.26) and NA (IRR=1.08, 95% CI 1.06–1.11) for females. Geographic discrepancies in time-trends were observed for astrocytomas, ependymomas, medulloblastomas, other embryonal tumors, and other specified tumors. Reductions in the incidence of unspecified tumors from period 1 to 3 were noted in E, AS, and NA, ranging from -20% (E, females) to -66% (AS, females). CONCLUSIONS Heterogeneous trends and improvement in the registration of histological types were noted. Geographic variation can help to raise hypotheses to investigate etiologic factors.
Two Cases of Decreased 123I-Metaiodobenzylguanidine Lung Uptake in Metaiodobenzylguanidine Scintigraphy While Taking Selective Serotonin Reuptake Inhibitor/Serotonin Noradrenaline Reuptake Inhibitor
Authors: Shinobu Adaniya, Miwako Takahashi, Keitaro Koyama, Kenichiro Ogane, Toshimitsu Momose
Journal: Clinical Nuclear Medicine (2020)

Abstract 123 I-metaiodobenzylguanidine scintigraphy is used to differentiate Lewy body disease from other neurodegenerative disorders. We identified 2 cases with remarkably changed pulmonary uptake between 2 metaiodobenzylguanidine scintigraphies; pulmonary uptake was reduced when patients were taking selective serotonin reuptake inhibitor/serotonin noradrenaline reuptake inhibitor and preserved during the medication-naive or withdrawal state, suggesting that pulmonary uptake involves not only the noradrenaline transporter, but also the serotonin transporter. Pulmonary accumulation may affect the heart-to-mediastinum ratio as the region of interest on the planner image is usually placed on the heart and includes part of the lung. Therefore, we should pay attention to the medication state of patients with decreased pulmonary uptake.
EPCO-25. AN IMMUNOMETHYLOMIC PLATFORM INTEGRATING SYSTEMIC IMMUNE PROFILES AND EPIGENETIC AGE IN NEURO-ONCOLOGY
Authors: Annette Molinaro, John Wiencke, Gayathri Warrier, JiYoon Lee, Devin Koestler, Helen Hansen, Terri Rice, Paige Bracci, Lucie McCoy, Lucas Salas, Brock Christensen, Margaret Wrensch, Karl Kelsey, Jennie Taylor, Jennifer Clarke
Journal: Neuro-Oncology (2020)

Abstract Lineage-specific DNA methylation marks differentiate leukocyte cell types while individual biological aging mechanisms impact other methylation alterations. Human glioma incidence and survival times have been shown to be associated with aberrant immune profiles and have a strong dependency on age. Here we developed a single epigenetic analysis framework to evaluate both immune cell fractions and epigenetic age in peripheral blood. We examined these measures in archived blood from 197 triple-negative glioma patients (TNG; IDH wildtype, 1p19q intact and TERT wildtype) and 312 frequency-matched controls from the SF Bay Area Adult Glioma Study (AGS). Significant differences were observed with TNG cases having lower CD4 and CD8 T cell, natural killer, and B cell fractions, and higher neutrophil fractions than controls. TNG cases were significantly older than controls in two of three epigenetic age estimates; however, there was no difference in epigenetic age acceleration once immune cell proportions were considered. For the TNG cases, we augmented results from several machine learning methods to delineate risk groups of TNG patients with significantly different overall survival. We compared survival models built by recursive partitioning, random forest, and elastic net methods. The final model was chosen by repeated bootstrap sampling via the Brier score loss function and validated in an independent set of 72 IDH-mutant only or TERT-mutant only glioma patients also from the AGS. The final model indicated important interactions between immune cell fractions (including CD4 and CD8 T cells and neutrophils) and treatment, age, and dexamethasone status when adjusted for the main effects of epigenetic age, glioblastoma status, and the neutrophil-to-lymphocyte ratio. The capacity of immunomethylomics to capture diverse, clinically relevant information and the simplicity of its implementation make this a powerful tool for personalized patient evaluation in the neuro-oncology clinic.
LINC-09. TREATMENT AND OUTCOME IN CHILDREN WITH LOW-GRADE GLIOMAS IN WESTERN MEXICO: EXPERIENCE AT HOSPITAL CIVIL DE GUADALAJARA
Authors: Regina M Navarro-Martin del Campo, Erika Casillas-Toral, Ana L Orozco-Alvarado, Fernando Sanchez-Zubieta, Luis A Arredondo-Navarro, Lorelai Gutierrez-Oliva
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Brain tumors are the most common solid tumors in childhood, 35% of them being low-grade gliomas (LGGs). Few data is available regard LGGs in low-and-middle-income countries. This study evaluates LGGs in a tertiary center in Mexico. DESIGN: A retrospective review of clinical files of 105 children diagnosed with LGG other than optic nerve glioma from 2007 to 2019 was done. RESULTS Median age at diagnosis was 7.2 years (from 5 months to 18 years). Male to female ratio was 0.75:1. WHO Grade I represented 68% of the cases. Anatomic sites were: posterior fossa (41%), supratentorial (43.5 %), spinal (8.5%), subependymal (6 %) and pineal (1%). Ten percent of patients had a diagnosed phacomatosis. Treatment was observation without surgery in 3.8%, surgery followed by observation in 49.5%, only chemotherapy in 2.8%, only radiotherapy in 6.7%, and surgery combined with chemotherapy or radiotherapy in 37.2% of cases. Among patients who had surgical intervention, 40% achieved gross total resection, 44% subtotal resection and 16% only biopsy. One or more recurrences were found in 20 % of patients. The 5 and 10-year overall survival (OS) was 83% and 73% respectively. The 5 and 10-year progression-free survival (PFS) was 66 % and 44 % respectively. CONCLUSIONS In this series the OS were lower compared with countries with high income, reflecting the need to improve surgery, since only 40% achieved complete resection that is a determining factor for the prognosis. We observed a decrease in OS until 10-year follow and the PFS was even lower due to recurrence/progression.
Response to: ‘Correspondence on ‘Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities’’ by Rönnelid<i>et al</i>
Authors: Sindhu R Johnson, Martin Aringer
Journal: Annals of the Rheumatic Diseases (2020)

We thank Ronnelid et al for their comments on our paper, ‘Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes, and ethnicities.’1

In 2019, the authors comparatively evaluated the ‘diagnostic accuracy’ of the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) criteria2 3 against the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. In referring to their paper,4 we stated that it is inappropriate to evaluate the 2019 EULAR/ACR criteria as diagnostic criteria. Ronnelid et al now point out that diagnostic use of the criteria was not their intention. They make the point that they used the term diagnostic, as diagnostic sensitivity …
Dual Angiotensin Receptor-Neprilysin Inhibition With Sacubitril/Valsartan Attenuates Systolic Dysfunction in Experimental Doxorubicin-Induced Cardiotoxicity
Authors: Nabil E. Boutagy, Attila Feher, Daniel Pfau, Zhao Liu, Nicole M. Guerrera, Lisa A. Freeburg, Sydney J. Womack, Abigail C. Hoenes, Caroline Zeiss, Lawrence H. Young, Francis G. Spinale, Albert J. Sinusas
Journal: JACC CardioOncology (2020)

Doxorubicin (DOX) induces cardiotoxicity in part by activation of matrix metalloproteinases (MMPs). Sacubitril/valsartan (Sac/Val) exerts additive cardioprotective actions over renin-angiotensin-aldosterone inhibitors in preclinical models of myocardial infarction and in heart failure patients. We hypothesized that Sac/Val would be more cardioprotective than Val in a rodent model of progressive DOX-induced cardiotoxicity, and this benefit would be associated with modulation of MMP activation. We sought to investigate the efficacy of Sac/Val for the treatment of anthracycline-induced cardiotoxicity. Male Wistar rats received DOX intraperitoneally (15 mg/kg cumulative) or saline over 3 weeks. Following the first treatment, control animals were gavaged daily with water (n = 25), while DOX-treated animals were gavaged daily with water (n = 25), Val (31 mg/kg; n = 25) or Sac/Val (68 mg/kg; n = 25) for either 4 or 6 weeks. Echocardiography was performed at baseline, and 4 and 6 weeks after DOX initiation. In addition, myocardial MMP activity was assessed with 99mTc-RP805, and cardiotoxicity severity was assessed by histology at these time points in a subgroup of animals. Left ventricular ejection fraction decreased by 10% at 6 weeks in DOX and DOX + Val rats (both p < 0.05), while this reduction was attenuated in DOX + Sac/Val rats. MMP activity was increased at 6 weeks by 76% in DOX-alone rats, and tended to increase in DOX + Val rats (36%; p = 0.051) but was similar in DOX + Sac/Val rats as compared with time-matched control animals. Both therapies attenuated histological evidence of cellular toxicity and fibrosis (p < 0.05). Sac/Val offers greater protection against left ventricular remodeling and dysfunction compared with standard angiotensin receptor blocker therapy in a rodent model of progressive DOX-induced cardiotoxicity.