tbuckley/cabot-search huggingface dataset:
Low RUNX3 expression alters dendritic cell function in patients with systemic sclerosis and contributes to enhanced fibrosis
Authors: Alsya J Affandi, Tiago Carvalheiro, Andrea Ottria, Jasper CA Broen, Lara Bossini-Castillo, Ralph G Tieland, Lenny van Bon, Eleni Chouri, Marzia Rossato, Jorre S Mertens, Samuel Garcia, Aridaman Pandit, Laurie MG de Kroon, Romy B Christmann, Javier Martin, Joel AG van Roon, Timothy RDJ Radstake, Wioleta Marut
Journal: Annals of the Rheumatic Diseases (2019)

Systemic sclerosis (SSc) is an autoimmune disease with unknown pathogenesis manifested by inflammation, vasculopathy and fibrosis in skin and internal organs. Type I interferon signature found in SSc propelled us to study plasmacytoid dendritic cells (pDCs) in this disease. We aimed to identify candidate pathways underlying pDC aberrancies in SSc and to validate its function on pDC biology.In total, 1193 patients with SSc were compared with 1387 healthy donors and 8 patients with localised scleroderma. PCR-based transcription factor profiling and methylation status analyses, single nucleotide polymorphism genotyping by sequencing and flow cytometry analysis were performed in pDCs isolated from the circulation of healthy controls or patients with SSc. pDCs were also cultured under hypoxia, inhibitors of methylation and hypoxia-inducible factors and runt-related transcription factor 3 (RUNX3) levels were determined. To study Runx3 function, Itgax-Cre:Runx3f/f mice were used in in vitro functional assay and bleomycin-induced SSc skin inflammation and fibrosis model.Here, we show downregulation of transcription factor RUNX3 in SSc pDCs. A higher methylation status of the RUNX3 gene, which is associated with polymorphism rs6672420, correlates with lower RUNX3 expression and SSc susceptibility. Hypoxia is another factor that decreases RUNX3 level in pDC. Mouse pDCs deficient of Runx3 show enhanced maturation markers on CpG stimulation. In vivo, deletion of Runx3 in dendritic cell leads to spontaneous induction of skin fibrosis in untreated mice and increased severity of bleomycin-induced skin fibrosis.We show at least two pathways potentially causing low RUNX3 level in SSc pDCs, and we demonstrate the detrimental effect of loss of Runx3 in SSc model further underscoring the role of pDCs in this disease.
AB0832 The effects of anti-tnf biological agents in patients with spondyloarthritis: a comparative study
Authors: F. Essafi, O. Saidane, I. Mahmoud, A. Ben Tekaya, R. Tekaya, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> The aim of the present study was to compare the efficacy of three anti-TNF agents (adalimumab, infliximab and etanercept) in patients with spondyloarthritis (SpA) at 24 weeks. <h3>Methods</h3> We achieved a retrospective descriptive and comparative monocentric study, on 49 patients, with SpA including ankylosing spondylitis (AS), psoriatic arthritis (PsA), enteropathic arthritis (EA), reactive arthritis (ReA) and undifferentiated spondyloarthritis (uSpA) (according to Amor criteria, <sup>ASAS 2009</sup> and CASPAR criteria), during 12 years (2004–2015). The patients were treated with at least one anti-TNF, during at least 6 months. Disease activity was assessed by the BASDAI, ASDAS, ESR and CRP. To compare mean differences between time points (week 0 versus week 24), a Wilcoxon test was applied. To compare efficacy between the 3 anti-TNF, a Mann-Whitney test was applied. <h3>Results</h3> Twenty three patients (47%) had AS, 13 patients (27%) had PsA and 11 patients (22%) had EA. One patient had an uSpA, and 1 patient had a ReA. The mean age was 42,81 years±11,77. The median age at disease onset was 29,41 years±11,29. The mean disease duration was 10,16 years. Nineteen patients received etanercept (ETN), 18 infliximab (IFX) and 12 adalimumab (ADA). At six Months, the 3 anti-TNF showed improvement in the disease activity scores: BASDAI (p&lt;0,0001), ASDAS CRP (p&lt;0,0001), ESR (p&lt;0,0001) and CRP (p&lt;0,0001). Sixty two percent of the patients have reached BASDAI 50 response at 6 months. At week 24, patients on ETN achieved more frequently a significant reduction of BASDAI (−5,13 vs −2,53; p=0,004), ESR (−52,69 vs −16,64; p=0,006) and CRP (−36,7 vs −21,34; p=0,009) than IFX. The efficacy comparison between ETN and ADA showed ETN superiority concerning BASDAI (−5,13 vs −2,04; p=0,004) and ASDAS CRP (−3,03 vs −1,4; p=0,006). The comparison ADA vs IFX had shown no significant efficacy differences. <h3>Conclusions</h3> Our results showed a BASDAI 50 response in 62% of patients. The comparison between the three biologics was consistent with a better efficacy of the ETN. <h3>Disclosure of Interest</h3> None declared
Hematogenous Extramedullary Relapse in Multiple Myeloma - A Multicenter Retrospective Study in 127 Patients
Authors: Irit Avivi, Yael C Cohen, Gabor Mikala, Laurent Garderet, Mor Seny Gueye, David S Jayabalan, Sophia Glickman, Ruben Niesvizky, Alessandro Gozzetti, Katarzyna Wiśniewska-Piąty, Anna Waszczuk-Gajda, Lidia Usnarska-Zubkiewicz, Iwona Hus, Renata Guzicka Kazmierczak, Jakub Radocha, Vibor Milunovic, Julio Dávila, Massimo Gentile, Anna Suska, Sarah Goldman-Mazur, Jorge J. Castillo, Artur Jurczyszyn
Journal: Blood (2018)
Abstract P066: Shot-term Exposure to Ambient Air Pollution and Circulating Biomarkers of Systemic Inflammation: The Framingham Heart Study
Authors: Wenyuan Li, Elissa H Wilker, Kirsten S Dorans, Mary B Rice, Petter L Ljungman, Joel Schwartz, Brent A Coull, Petros Koutrakis, Diane R Gold, Emelia J Benjamin, Ramachandran S Vasan, Murray A Mittleman
Journal: Circulation (2017)

Introduction: Exposure to air pollution has been positively associated with systemic inflammation. However, few large scale studies were conducted in regions with low levels of air pollution. We therefore studied the associations of air pollution with systemic inflammation biomarkers among participants in the Framingham Offspring and Third Generation cohorts in Greater Boston area. Methods: We measured C-reactive protein (CRP), fibrinogen, interleukin 6 (IL6), and tumor necrosis factor receptor 2 (TNFR2) in 3943 participants living within 50 km of a central site monitor in Boston. We calculated the 1-, 2-, 3-, 5-, and 7-day moving averages of fine particulate matter (PM 2.5 ), black carbon (BC), sulfate (SO 4 2- ), nitrogen oxides (NO x ), and ozone (O 3 ) prior to the exam visits. We used linear mixed effects models and linear regression models to evaluate repeated measures and cross-sectional associations respectively, adjusting for age, sex, individual and area level measures of socioeconomic position, lifestyle and clinical factors, time trend, and weather. We examined effect modification by age (&gt;/≤ 65 years), sex, and diabetes history. Results: The mean age was 53(±14) years and 54% were women. PM 2.5 , BC, and SO 4 2- were positively associated with CRP across multiple moving averages, and were statistically significant at 5-day moving averages: a 5 μg/m 3 higher PM 2.5 or a 0.5 μg/m 3 higher BC was associated with 3.9% (95% CI: 0.5, 7.3) or 5.3% (95% CI: 0.1, 10.9) higher CRP, respectively. Positive associations were observed for PM 2.5 , BC, and NO x with IL6; and for BC, SO 4 2- , and O 3 with TNFR2. SO 4 2- and O 3 were negatively associated with fibrinogen. Associations of BC and NO x with CRP and of BC with IL6 were of a larger magnitude among participants with diabetes than those without. Conclusions: In a region in compliance with current US-EPA regulation, we find positive associations of short-term exposure to ambient air pollution with CRP, IL6 and TNFR2 but not for fibrinogen.
SAT0162 Where should we seek for subclinical synovitis using ultrasound in rheumatoid arthritis?
Authors: W. Hamdi, M. Sellami, H. Riahi, D. Kaffel, K. Maatallah, M. Chelli-Bouaziz, M. F. Ladeb, M. M. Kchir
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> The role of ultrasound imaging (US) in rheumatoid arthritis (RA) management is fundamental by sharpen diagnosis, predicting prognosis, monitoring disease activity and identifying remission. The detection of subclinical synovitis and articular inflammatory changes represent the real advantages of this technology. However, joint US is time-consuming, thus identifying the area of subclinical synovitis should be useful to overcome this difficulty. <h3>Objectives:</h3> We aimed to assess the most profitable joint locations in detecting subclinical synovitis in RA. <h3>Methods:</h3> We performed a cross-sectional study of one hundred patients with inflammatory joint pain or synovitis for more than 6 weeks and less than 2 years. All patients were free of conventional or biological DMARD's at inclusion. An experienced radiologist performed the MSUS scan of 22 joints (2 wrists, 10 metacarpophalangeal joints MCP and 10 proximal interphalangeal joints PIP) unaware of clinical and biological findings. MSUS was performed using a Philips HD11. The used frequency ranged from 15 to 17 MHz and we used a Power Doppler (PD). After US assessment, patients were classified as having RA according to ACR/EULAR 2010 criteria. <h3>Results:</h3> We enrolled 100 patients (77 women and 23 men) with a mean age of 51.8 years [16–77]. Fifty-five patients (55%) fulfilled the ACR/EULAR 2010 criteria for the diagnosis of RA. The mean disease duration was 10.96 months [2–24]. Rheumatoid factor and ACPA were positive in 53% and 25% cases respectively. The mean disease activity score at the time of study was 5.36 [1.36–8.61]. A clinical wrist synovitis was found in 92 cases (46%). In the 54 wrists with no clinical synovitis, a total number of US wrist synovitis was detected at 30 (15%) radioulnar (of which half was Doppler +), 91 (45.5%) radiocarpal (of which 60% was Doppler +) and 105 (52.5%) intercarpal joints (of which 67% was Doppler +). Concerning the MCP and PIP joints, the most frequent location of subclinical synovitis were 1st MCP in 51 cases (25.5%), 4th MCP in 49 cases (24.5%), 5th MCP in 50 of cases (25%),1st PIP in 24 cases (12%) and 5th PIP in 22 cases (11%). <h3>Conclusions:</h3> Our study highlighted the low sensitivity of physical examination of synovitis in hand and wrist joints, especially in some locations. We showed the most frequent location for detecting subclinical synovitis were radiocarpal and intercarpal joint, 1st-4th -5th MCP and 1st-5th PIP. About half of those subclinical synovitis were Doppler +. <h3>Disclosure of Interest:</h3> None declared
Mitochondrial miRNA Determines Chemoresistance by Reprogramming Metabolism and Regulating Mitochondrial Transcription
Authors: Song Fan, Tian Tian, Weixiong Chen, Xiaobin Lv, Xinyuan Lei, Hanqing Zhang, Sheng Sun, Lei Cai, Guokai Pan, Lile He, Zhanpeng Ou, Xinyu Lin, Xinhui Wang, Matthew Francis Perez, Zhiming Tu, Soldano Ferrone, Bakhos A. Tannous, Jinsong Li
Journal: Cancer Research (2019)

Abstract miRNAs that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNAs (mitomiR). mitomiRs have been shown to modulate the translational activity of the mitochondrial genome, yet their role in mitochondrial DNA (mtDNA) transcription remains to be determined. Here we report that the mitomiR-2392 regulates chemoresistance in tongue squamous cell carcinoma (TSCC) cells by reprogramming metabolism via downregulation of oxidative phosphorylation and upregulation of glycolysis. These effects were mediated through partial inhibition of mtDNA transcription by mitomiR-2392 rather than through translational regulation. This repression required specific miRNA–mtDNA base pairing and Argonaute 2. mitomiR-2392 recognized target sequences in the H-strand and partially inhibited polycistronic mtDNA transcription in a cell-specific manner. A retrospective analysis of TSCC patient tumors revealed a significant association of miR-2392 and regulated mitochondrial gene expression with chemosensitivity and overall survival. The clinical relevance of targeted mitochondrial genes was consistently validated by The Cancer Genome Atlas RNA sequencing in multiple types of cancer. Our study revealed for the first time the role of mitomiR in mtDNA transcription and its contribution to the molecular basis of tumor cell metabolism and chemoresistance. Significance: These findings uncover a novel mechanism by which mitomiRNA regulates mitochondrial transcription and provide rationale for use of mitomiRNA and mtDNA-encoded genes to predict chemosensitivity and patient clinical prognosis.
Preventing Neonatal Group B <i>Streptococcus</i> Disease
Authors: Sagori Mukhopadhyay, Karen M. Puopolo
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Potential Predictors of Induction Failure and Complete Remission Duration in FLT3-ITD Mutated Acute Myeloid Leukemia
Authors: Fevzi Yalniz, Hagop M. Kantarjian, Gautam Borthakur, Tapan M. Kadia, Naval G. Daver, Naveen Pemmaraju, Marina Y. Konopleva, Guillermo Garcia-Manero, Koichi Takahashi, Courtney D. DiNardo, Prithviraj Bose, Michael Andreeff, Farhad Ravandi, Jorge E. Cortes
Journal: Blood (2018)
Early Prophylaxis Provides Continued Joint Protection in Severe Hemophilia A: Results of the Joint Outcome Continuation Study
Authors: Beth Boulden Warren, Dianne Thornhill, Jill Stein, Michael Fadell, Sharon Funk, Heidi D. Lane, Carolyn M. Bennett, Amy Shapiro, Michael Recht, Marilyn J Manco-Johnson
Journal: Blood (2018)
AB0042 Essential oil extracted from chamaecyparis obtusa attenuates the severity of collagen-induced arthritis
Authors: J. Lee, Y. Park, C.-H. Yoon
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> <i>Chamaecyparis obtusa</i> (<i>C. obtusa</i>) is a tropical tree species found in Japan and the southern region of South Korea. Although the biological activities of essential oil extracted from <i>C. obtusa</i> (EOCO) are not yet fully understood, essential oil has been shown to have antibacterial activities and anti-inflammatory effects. <h3>Objectives</h3> We investigated the effect of essential oil extracted from <i>Chamaecyparis obtusa</i> on the development of collagen-induced arthritis (CIA), a well-characterised preclinical model of human RA. <h3>Methods</h3> DBA1/J mice were injected intraperitoneally with EOCO dissolved in dimethyl sulfoxide (DMSO) 3 times a week for 5 weeks after type II collagen (CII) immunisation. Arthritis severity was evaluated by clinical and histological parameters. Serum anti-CII antibody levels were assayed by ELISA. Iinterleukin-17 (IL-17) expressions in the joints were determined by immunohistochemistry. Effect of EOCO on Th17 cells and natural killer (NK) cells was analysed using flow cytometry. <h3>Results</h3> EOCO markedly reduced the clinical and histological severity of CIA. Serum anti-CII antibody levels and the expression of IL-17 in the joints were significantly lower in mice treated with EOCO than those treated with DMSO alone. EOCO inhibited the differentiation of Th17 cells in total splenocytes, not in isolated CD4<sup>+</sup> T cells, from mice. EOCO increased the production of granzyme B and perforin in NK cells. <h3>Conclusions</h3> Our data demonstrate a protective effect of EOCO on the development of CIA through the inhibition of Th17 cell differentiation. This effect may be related with NK cell activity enhanced by EOCO. <h3>References</h3> [1] Hong EJ, Na KJ, Choi IG, Choi KC, Jeung EB. Antibacterial and antifungal effects of essential oils from coniferous trees. Biol Pharm Bull2004;27:863–6. [2] An BS, Kang JH, Yang H, Jung EM, Kang HS, Choi IG, et al. Anti-inflammatory effects of essentia oils from Chamaecyparis obtusa via the cyclooxygenase-2 pathway in rats. Mol Med Rep2013;8:255–9. <h3>Acknowledgements</h3> This study was carried out with the support of 'Forest Science and Technology Projects (Project No. S111114L020100)' provided by Korea Forest Service. <h3>Disclosure of Interest</h3> None declared
SAT0722-HPR The validity and test-retest reliability of the turkish patient specific functional scalein chronic neck pain patients
Authors: G. Yalcinkaya, B. Kara, M.N. Arda
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Current clinical guidelines recommend to use both clinical and self-reported measurements for evaluation of chronic neck pain. Among the self-reported outcomes, Neck Disability Index (NDI) and Patient Specific Functional Scale (PSFS) are the most widely used and recommended instruments.<sup>1</sup> Although, NDI was validated in Turkish language before, but no validation study related to the PSFS was detected in the literature. <h3>Objectives</h3> The purpose of our study was to determine the validity and reliability of PSFS which was not validated in Turkish language previously. <h3>Methods</h3> The PSFS has been translated into Turkish (PSFS-T) according to "translation-backward translation" method as recommended in the guidelines. Demographic data, PSFS-T, and NDI were recorded at the initial assessment. For the test-retest reliability analysis, the first 30 patients were called by phone. Intraclass correlation coefficient (ICC) was established for reliability analyses. The correlations between PSFS-T and NDI was examined for the validity analysis. <h3>Results</h3> The final form was completed by 110 chronic neck pain patients (F:77, M:33). The mean age of patients was 44±14 and the average duration of pain was 43±49 months. Test retest reliability of PSFS-T was found good level (ICC: 0.85). The relationship between PSFS-T and NDI was found moderate level (p&lt;0.05, rho:−0.578). Furthermore, reading books/newspapers, cleaning and carrying heavy things were reported by Turkish neck patients as the first three activities which are the most problematic for their daily activities of life. <h3>Conclusions</h3> PSFS-T is a valid and reliable method of measuring outcome in patients with neck pain. Future studies should focus on the validity and reliability of PSFS-T in different populations. <h3>Reference</h3> [1] Blanpied PR, Gross AR, Elliott JM, Devaney LL, Clewley D, Walton DM, et al. Neck Pain: Revision 2017: Clinical Practice Guidelines Linked to the International Classification of Functioning, Disability and Health From the Orthopaedic Section of the American Physical Therapy Association. Journal of Orthopaedic &amp; Sports Physical Therapy2017;47(7):A1-A83. <h3>Disclosure of Interest</h3> None declared
A Novel Chimeric Antigen Receptor T Cells Therapy Strategy That Dual Targeting CD19 and CD123 to Treat Relapsed Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Sanfang Tu, Lan Deng, Rui Huang, Xuan Zhou, Jilong Yang, Weijun Zhou, Meifang Li, Chunyan Yue, Shaojie Wu, Zhenling Guo, Lung-Ji Chang, Yuhua Li
Journal: Blood (2018)
Circulating Tumor Cells: Come Together, Right Now, Over Metastasis
Authors: Paulo Rodrigues, Sakari Vanharanta
Journal: Cancer Discovery (2019)

Abstract Summary: Circulating tumor cells (CTC) are the source of metastases, but only an infinitesimal fraction of them eventually succeed in colonizing a distant organ. New results show that CD44-dependent aggregation in the circulation provides CTCs with cancer stem cell–like characteristics, suggesting an explanation for the low metastatic efficiency of CTCs, but also avenues for therapeutic intervention. See related article by Liu et al., p. 96.
SP0019 Ucan and printo aligned to link bed and bedside: perspective from the benchside
Authors: S.J. Vastert
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> In the past 2 decades we have gained important insights on the mechanisms of disease and therapy in children with Juvenile Idiopathic Arthritis (JIA). These insights have resulted in several game-changing therapeutic modalities in several subtypes of JIA. In for example systemic JIA, we have learned that the systemic inflammatory mechanisms at onset of this disease, are primarily driven by innate immune cells and their inflammatory cascades. Both IL-1 and IL-6 blockade in sJIA have resulted in high response rates of sJIA patients. Additional progress still has to be made in efficacy, cost reduction, minimization of side effects and taper and stop strategies of maintenance drugs. To ensure that the right goals are set, patients (and/or their parents in paediatric disease) should be involved in important research questions and goals. In addition, if we really aim to take the next step in improving the outcome and life of our patients, clinical innovations need to go hand in hand with basic discoveries to really affect care for patients. Current clinical trials rely on the recognition of clinical phenotypes and have strict inclusion criteria. In these trials with more or less homogenous patient cohorts, response rates to a specific treatment are evaluated and compared to placebo or current standard therapeutics. This has resulted in the registration of multiple biologic therapies for various JIA subtypes and to significantly improved response rates and disease outcomes for most JIA patients. However, still a major question in clinical practice remains: which biological to start in which patient and when. Agreement on several consensus treatment plans in clinical practice for different subtypes of JIA, will help in comparing responses to registered therapeutics. However, to book further progress in the care for JIA patients, what we really need is a more molecular based set of classification criteria, or disease taxonomy, of JIA subtypes and (sets of) biomarkers for disease course/therapy response and biomarkers to assess subclinical disease activity. These criteria and biomarkers will enable informed decisions on the start as well as tapering/stop of maintenance therapy. Such a classification, as well as the discovery and validation of novel/promising biomarkers are likely to be developed in collaborative cohort studies with new onset JIA patients that are prospectively followed and sampled over time. Facilitating the translation from bench to bedside is crucial for addressing the major current challenges in JIA management. When successful, it will set new standards for safe, targeted and personalised medicine in JIA. <h3>Disclosure of Interest</h3> S. Vastert Grant/research support from: from SOBI in collaboration with ZonMW, rational pharmacotherapy program
Rogues and Regulation of Germline Editing
Authors: R. Alta Charo
Journal: New England Journal of Medicine (2019)

Interview with Dr. George Daley on the prospects for using genome editing to prevent genetic diseases. (10:11)Download Calling for a moratorium on germline editing won't stop rogue actors. Instead, an "ecosystem" approach to regulation might minimize premature, unwarranted, or dangerous research and complement efforts to develop a consensus about acceptable and unacceptable uses.