tbuckley/cabot-search huggingface dataset:
THU0052 Fibroblast-like synoviocytes from rheumatoid arthritis patients are more invasive than from osteoarthritis in an in vitro system: correlation with growth characteristics and expression of mmp-1, mmp-3 and mmp-10
Authors: TC Tolboom, E Pieterman, WH Vd Laan, AL Huidekoper, RG Nelissen, FC Breedveld, TW Huizinga
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Fibroblast-like synoviocytes (FLS) are involved in joint destruction. In this study the invasiveness in a transwell system in vitro was correlated with origin of synoviocytes. Moreover the relation between invasive growth of FLS in the transwell system and growth characteristics and expression of MMP 1-14, 17, 19, cathepsin K, TIMP-1 and -2 was determined. <h3>Methods</h3> FLS were derived from 56 patients (30 rheumatoid arthritis (RA), 17 osteoarthritis (OA), 9 avascular necrosis (AVN) or fractures). Invasive growth of FLS through a collagen matrix was measured in a transwell system coated with matrigel. The number of cells grown through the matrix and the transwell membrane were counted. Growth rate was determined by counting of FLS after seven days of culturing. Expression of MMP’s, cathepsin-K and TIMP’s was investigated using RT-PCR and related to expression of a household gene, beta-actin. <h3>Results</h3> FLS from RA invaded more easily in vitro than FLS from OA and AVN (median: RA: 4788 (cells grown through matrix and transwell membrane), OA: 1875; p &lt;0.001 and AVN: 1530; p = 0.014 respectively). The median rate of proliferation of RA FLS was 0.27 per day compared to OA 0.22 per day (p = 0.012) and AVN and fractures 0.25 per day (RA versus AVN: p = 0.242; OA versus AVN: p = 0.553), but there was no correlation between rate of proliferation and invasive growth in vitro. FLS that expressed MMP-1, MMP-3 or MMP-10 were significantly more invasive (median number of invasive cells: 3835, 4248, 4990, respectively) than cells that did not express MMP-1, MMP-3 or MMP-10 (1605, p = 0.03; 1970, p = 0.004; 2360, p = 0.012, respectively). Expression of the other MMP’s, cathepsin-K and TIMP’s did not show a significant relationship with invasive growth. Expression of MMP-9 showed a trend with higher expression in more invasive cells (p = 0.066). There was also a significant relationship between the expression of MMP-1 and MMP-9 and a diagnosis of RA (both p = 0.013). <h3>Conclusion</h3> FLS of RA invade more easily in a matrigel matrix than OA FLS. This is not due to a greater rate of proliferation of RA FLS than OA FLS, although FLS from RA patients have a 25% higher rate of proliferation than FLS from OA patients. A significant relationship exists between the expression of MMP-1, MMP-3 and MMP-10 and invisive growth in a matrigel transwell system and this relationship was nearly significant for MMP-9. FLS of RA patients expressed significantly more often MMP-1 and MMP-9 than FLS from OA patients.
THU0321 URINARY T CELLS IDENTIFY ACTIVE RENAL ANCA ASSOCIATED VASCULITIS
Authors: J. Sonnemann, J. Klocke, M. Bieringer, S. Elitok, P. Enghard, A. D. Salama, A. Schreiber
Journal: Annals of the Rheumatic Diseases (2020)

Background: ANCA-associated vasculitis (AAV) causes necrotizing crescentic glomerulonephritis (NCGN) which is a major contributor to morbidity and mortality in AAV. Since therapy relies on cytotoxic agents with potentially severe adverse effects, a reliable non-invasive biomarker of disease activity is needed to determine the right balance between over- and undertreatment. Using the urine space as a window into the local inflammatory milieu of the kidney, quantification of urinary leukocytes using flow cytometry has become an upcoming marker of various other inflammatory kidney diseases. As recent studies have illuminated the emerging role of T regulatory (Treg) and Th17 cells in the pathogenesis of AAV, these could represent a viable non-invasive biomarker more closely displaying the underlying pathogenic processes than metabolites or epiphenomena of inflammation. Objectives: To quantify urinary T cells in active renal AAV and asses their biomarker characteristics. Methods: Using flow cytometry, T-lymphocytes and their subsets were quantified in peripheral blood and urine samples from patients with active AAV with or without NCGN, in stable remission with previous NCGN and healthy controls. Concentrations of urinary soluble metabolites and cytokines (Monocyte-attracting protein 1 (MCP-1), sCD163, sCD25 and C5a) were measured using Multiplex analysis. Results were verified in a separate validation cohort. Results: Patients with renal active AAV (n = 30) showed significantly higher urinary cell counts of total T cells, CD4+, CD8+, Treg and Th17 subsets than disease (n = 21) and healthy controls (n = 8). Patients with active renal AAV also showed a significantly higher percentage of Tregs in urine than in blood. While Tregs allowed a robust discrimination between active renal AAV and disease controls (receiver operator characteristics (ROC): area under the curve (AUC) 0.93, sensitivity 79%, specificity 95%) quantification of all T cells proved to be slightly more accurate (ROC: AUC 0.95, sensitivity 92%, specificity 95%). Soluble markers showed a slightly inferior discrimination (MCP-1 ROC: AUC 0.90, sensitivity 60%, specificity 100%, sCD163 ROC: AUC 0.92, sensitivity 96%, specificity 85%) while sCD25 and C5a were far less accurate. Conclusion: Urinary T cells are significantly elevated in active renal AAV and the increased frequency of Tregs in urine suggests active migration into inflamed glomeruli and thereby the urine rather than mere bleeding of ruptured capillaries. These cells show great potential for a non-invasive biomarker close to the local inflammatory milieu. Particularly the total count of urinary T cells showed slightly superior biomarker characteristics than previously established soluble markers. Further studies are needed to confirm these results and show potential prognostic value of these cellular markers. Disclosure of Interests: None declared
Microbial translocation in type 2 diabetes: when bacterial invaders overcome host defence in human obesity
Authors: Benjamin AH Jensen, Andre Marette
Journal: Gut (2020)

Metabolic endotoxemia, characterised by systemic influx of bacterial components, impairs lipid handling and glucoregulation.1 Early preclinical studies showed that high fat diet feeding facilitates bacterial translocation to metabolic tissues coinciding with dendritic cell (DC)-mediated inflammation.2 This process was aggravated in mice lacking either the canonical adaptor for inflammatory signalling pathways downstream of Toll-like receptor (TLR) families, MyD882 or the intracellular microbial pattern recognition receptor, NOD2.3 The first conceptual evidence for bacterial translocation in human type 2 diabetes (T2D) was reported in 2011 when Amar et al showed that 16S rDNA gene content in blood was associated with future T2D risk.4 These seminal papers pioneered the concept of bacterial translocation in metabolic diseases. Yet, it remains intensely debated whether bacterial translocation to extraintestinal tissues is a true phenomenon or a result of spurious data, as it is notoriously difficult to robustly distinguish biologically relevant bacterial DNA sequences in very low microbial biomass tissues from environmental contaminants.5 6 Indeed, low bacteria:host cell ratio obviously increases the risk of contamination during surgical procedures, biobanking and wet-laboratory processing of tissue samples. This has revivified the tenet that internal organs are sterile and casted doubt on emerging reports of tissue microbial signatures in a number of diseases, arguing that such findings may be confounded by sample contamination.

In GUT, Massier et al challenge again the dogma of sterile internal organs …
Screening for Anxiety in Adolescent and Adult Women
Authors: Heidi D. Nelson, Amy Cantor, Miranda Pappas, Chandler Weeks
Journal: Annals of Internal Medicine (2020)

Background: Anxiety disorders are infrequently recognized during routine health care even though they are common in adolescent girls and adult women. Purpose: To evaluate evidence on the effectiveness of screening for anxiety disorders in primary care in improving symptoms, function, and quality of life; harms of screening; accuracy of screening instruments; and effectiveness and harms of treatments. Data Sources: English-language searches of Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Health and Psychosocial Instruments (1 January 1996 to 4 November 2019); ClinicalTrials.gov (November 2019); and reference lists of studies and reviews. Study Selection: Studies that enrolled adolescent girls and adult women not currently diagnosed with anxiety disorders, including pregnant or postpartum women, and compared clinical outcomes and harms between women who were and were not screened; diagnostic accuracy studies of screening instruments; and systematic reviews of randomized trials of behavioral and pharmacologic treatments. Data Extraction: Dual extraction and quality assessment of individual studies. Data Synthesis: No studies evaluated the overall effectiveness or harms of screening. Thirty-three studies and 2 systematic reviews (171 studies; 112 574 participants) evaluated the diagnostic accuracy of 27 screening instruments and their variations against a clinical diagnosis or other instruments. Most demonstrated moderate to high accuracy for adults (Generalized Anxiety Disorder scale: sensitivity, 70% to 97%; specificity, 50% to 89%), pregnant and postpartum women (Edinburgh Postnatal Depression Scale: sensitivity, 74%; specificity, 64%), and adolescents (Screen for Child Anxiety Related Emotional Disorders: sensitivity, 64% to 74%; specificity, 64% to 73%). Anxiety symptoms improved with cognitive behavioral therapy (246 randomized controlled trials; 17 209 participants) and antianxiety medications (126 randomized controlled trials; 8225 participants). Limitation: Limited data on long-term harms of treatment and no treatment trials in pregnant or postpartum women. Conclusion: Evidence on the overall effectiveness and harms of screening for anxiety is insufficient. Most screening instruments are moderately to highly accurate. Behavioral therapies and antianxiety medications effectively improve anxiety symptoms. Primary Funding Source: Health Resources and Services Administration.
用量強化多剤化学療法と手術を用いた小児期にリスクの高い肝芽腫の治療奏効:SIOPEL-3HR試験の最終結果 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Zsiros Jozsef, Maibach Rudolf, Shafford Elizabeth, Brugieres Laurence, Brock Penelope, Czauderna Piotr, Roebuck Derek, Childs Margaret, Zimmermann Arthur, Laithier Veronique, Otte Jean-Bernard, DE Camargo Beatriz, Mackinlay Gordon, Scopinaro Marcelo, Aronson Daniel, Plaschkes Jack, Perilongo Giorgio
Journal: Journal of Clinical Oncology (2010)
Pisotriquetral arthritis: ‘forgotten’ joint in ultrasound imaging of the wrist
Authors: Andrea Becciolini, Alarico Ariani, Marco Becciolini
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the study of Di Matteo et al ,1 which highlighted the association between ultrasound (US)-detected subclinical synovitis and bone erosion with the development of inflammatory arthritis. We agree with the authors that the second and fifth metacarpophalangeal joints and the fifth metatarsophalangeal joints are the most frequent site of US-detected bone erosion.2 However, MRI studies have reported that in rheumatoid arthritis (RA), carpal joints were affected by synovitis and erosions more frequently than metacarpophalangeal joints.3 4 The ulnar aspect of the radiocarpal joint and the pisotriquetral joint (PTJ) are the most involved by synovitis.5 Moreover, triquetrum is among the most frequent erosion-affected bone3 and, according to a recent MRI investigation, seems to be …
Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology
Authors: Wei Hu, Cong Liu, Zhuo-Yue Bi, Qun Zhou, Han Zhang, Lin-Lin Li, Jian Zhang, Wei Zhu, Yang-Yi-Yan Song, Feng Zhang, Hui-Min Yang, Yong-Yi Bi, Qi-Qiang He, Gong-Jun Tan, Cheng-Cao Sun, De-Jia Li
Journal: Molecular Cancer (2020)

Abstract Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.
Reliability of methods to estimate the fraction of inspired oxygen in patients with acute respiratory failure breathing through non-rebreather reservoir bag oxygen mask
Authors: Rémi Coudroy, Jean-Pierre Frat, Christophe Girault, Arnaud W Thille
Journal: Thorax (2020)

Severity of hypoxaemia can be assessed using the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (FiO 2 ). However, in patients breathing through non-rebreather reservoir bag oxygen mask, accuracy of bedside FiO 2 estimation methods remains to be tested. In a post-hoc analysis of a multicentre clinical trial, three FiO 2 estimation methods were compared with FiO 2 measured with a portable oxygen analyser introduced in the oxygen mask. Among 262 patients analysed, mean (SD) measured FiO 2 was 65% (13). The 3%-formula (21% + oxygen flow rate in L/min × 3) was the most accurate method to estimate FiO 2 . Other methods overestimated FiO 2 and hypoxaemia severity, so they should be avoided.
Spermine promotes pulmonary vascular remodelling and its synthase is a therapeutic target for pulmonary arterial hypertension
Authors: Yang-Yang He, Yi Yan, Xin Jiang, Jun-Han Zhao, Zhe Wang, Tao Wu, Yong Wang, Shan-Shan Guo, Jue Ye, Tian-Yu Lian, Xi-Qi Xu, Jin-Lan Zhang, Kai Sun, Fu-Hua Peng, Yu-Ping Zhou, Yi-Min Mao, Xue Zhang, Ji-Wang Chen, Shu-Yang Zhang, Zhi-Cheng Jing
Journal: European Respiratory Journal (2020)

Pathological mechanisms of pulmonary arterial hypertension (PAH) remain largely unexplored. Effective treatment of PAH remains a challenge. The aim of this study was to discover the underlying mechanism of PAH through functional metabolomics and to help develop new strategies for prevention and treatment of PAH.Metabolomic profiling of plasma in patients with idiopathic PAH was evaluated through high-performance liquid chromatography mass spectrometry, with spermine identified to be the most significant and validated in another independent cohort. The roles of spermine and spermine synthase were examined in pulmonary arterial smooth muscle cells (PASMCs) and rodent models of pulmonary hypertension.Using targeted metabolomics, plasma spermine levels were found to be higher in patients with idiopathic PAH compared to healthy controls. Spermine administration promoted proliferation and migration of PASMCs and exacerbated vascular remodelling in rodent models of pulmonary hypertension. The spermine-mediated deteriorative effect can be attributed to a corresponding upregulation of its synthase in the pathological process. Inhibition of spermine synthase in vitro suppressed platelet-derived growth factor-BB-mediated proliferation of PASMCs, and in vivo attenuated monocrotaline-mediated pulmonary hypertension in rats.Plasma spermine promotes pulmonary vascular remodelling. Inhibiting spermine synthesis could be a therapeutic strategy for PAH.
Considerations on biologicals for patients with allergic disease in times of the COVID‐19 pandemic: An EAACI statement
Authors: Alessandra Vultaggio, Ioana Agache, Cezmi A. Akdis, Mubeccel Akdis, Sevim Bavbek, Apostolos Bossios, Jean Bousquet, Onur Boyman, Adam M. Chaker, Susan Chan, Alexia Chatzipetrou, Wojciech Feleszko, Davide Firinu, Marek Jutel, Paula Kauppi, Ludger Klimek, Antonios Kolios, Akash Kothari, Marek L. Kowalski, Andrea Matucci, Oscar Palomares, Oliver Pfaar, Barbara Rogala, Eva Untersmayr, Thomas Eiwegger
Journal: Allergy (2020)

The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.
Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study
Authors: Marian Knight, Kathryn Bunch, Nicola Vousden, Edward Morris, Nigel Simpson, Chris Gale, Patrick O’Brien, Maria Quigley, Peter Brocklehurst, Jennifer J Kurinczuk
Journal: BMJ (2020)

Abstract Objectives To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants. Design Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS). Setting All 194 obstetric units in the UK. Participants 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020. Main outcome measures Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission. Results The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth. Conclusions Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation. Study registration ISRCTN 40092247.
A Single Factor Underlies the Metabolic Syndrome
Authors: Manel Pladevall, Bonita Singal, L. Keoki Williams, Carlos Brotons, Heidi Guyer, Josep Sadurni, Carles Falces, Manuel Serrano-Rios, Rafael Gabriel, Jonathan E. Shaw, Paul Z. Zimmet, Steven Haffner
Journal: Diabetes Care (2006)

OBJECTIVE—Confirmatory factor analysis (CFA) was used to test the hypothesis that the components of the metabolic syndrome are manifestations of a single common factor. RESEARCH DESIGN AND METHODS—Three different datasets were used to test and validate the model. The Spanish and Mauritian studies included 207 men and 203 women and 1,411 men and 1,650 women, respectively. A third analytical dataset including 847 men was obtained from a previously published CFA of a U.S. population. The one-factor model included the metabolic syndrome core components (central obesity, insulin resistance, blood pressure, and lipid measurements). We also tested an expanded one-factor model that included uric acid and leptin levels. Finally, we used CFA to compare the goodness of fit of one-factor models with the fit of two previously published four-factor models. RESULTS—The simplest one-factor model showed the best goodness-of-fit indexes (comparative fit index 1, root mean-square error of approximation 0.00). Comparisons of one-factor with four-factor models in the three datasets favored the one-factor model structure. The selection of variables to represent the different metabolic syndrome components and model specification explained why previous exploratory and confirmatory factor analysis, respectively, failed to identify a single factor for the metabolic syndrome. CONCLUSIONS—These analyses support the current clinical definition of the metabolic syndrome, as well as the existence of a single factor that links all of the core components.
False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications
Authors: Steven Woloshin, Neeraj Patel, Aaron S Kesselheim
Journal: New England Journal of Medicine (2020)

False Negative Tests for SARS-CoV-2 Infection Diagnostic testing for SARS-CoV-2 will help in safely reopening the country, but only if tests are highly accurate. Several steps need to be taken by m...