tbuckley/cabot-search huggingface dataset:
Loss of Axin2 results in impaired heart valve maturation and subsequent myxomatous valve disease
Authors: Alexia Hulin, Vicky Moore, Jeanne M. James, Katherine E. Yutzey
Journal: Cardiovascular Research (2016)

Myxomatous valve disease (MVD) is the most common aetiology of primary mitral regurgitation. Recent studies suggest that defects in heart valve development can lead to heart valve disease in adults. Wnt/β-catenin signalling is active during heart valve development and has been reported in human MVD. The consequences of increased Wnt/β-catenin signalling due to Axin2 deficiency in postnatal valve remodelling and pathogenesis of MVD were determined. To investigate the role of Wnt/β-catenin signalling, we analysed heart valves from mice deficient in Axin2 (KO), a negative regulator of Wnt/β-catenin signalling. Axin2 KO mice display enlarged mitral and aortic valves (AoV) after birth with increased Wnt/β-catenin signalling and cell proliferation, whereas Sox9 expression and collagen deposition are decreased. At 2 months in Axin2 KO mice, the valve extracellular matrix (ECM) is stratified but distal AoV leaflets remain thickened and develop aortic insufficiency. Progressive myxomatous degeneration is apparent at 4 months with extensive ECM remodelling and focal aggrecan-rich areas, along with increased BMP signalling. Infiltration of inflammatory cells is also observed in Axin2 KO AoV prior to ECM remodelling. Overall, these features are consistent with the progression of human MVD. Finally, Axin2 expression is decreased and Wnt/β-catenin signalling is increased in myxomatous mitral valves in a murine model of Marfan syndrome, supporting the importance of Wnt/β-catenin signalling in the development of MVD. Altogether, these data indicate that Axin2 limits Wnt/β-catenin signalling after birth and allows proper heart valve maturation. Moreover, dysregulation of Wnt/β-catenin signalling resulting from loss of Axin2 leads to progressive MVD.
Studies of Murine Neutrophil and Macrophage Progenitors with Ectopic A-Type Lamins or Sun2 Expression Implicate the Importance of Nuclear Envelope Proteins in Myelopoiesis
Authors: Margery G.H. Pelletier, Krishnakumar Malu, Seda C. Babroudi, Richard M. Giadone, Peter Gaines
Journal: Blood (2014)
MASL1 Induces Erythroid Differentiation In Human Erythropoietin-Dependent CD34+ Cells Involving Raf/MEK/ERK Signaling Pathway
Authors: Chutima Kumkhaek, Wulin Aerbajinai, Wenli Liu, Jianqiong Zhu, Naoya Uchida, Matthew M Hsieh, John F Tisdale, Griffin P. Rodgers
Journal: Blood (2010)
THU0269 A Multitude of Downregulated miRNAs in Plasmacytoid Dcs of Sjögren's Syndrome Patients Indicates Numerous Dysregulated Signalling Pathways
Authors: M.R. Hillen, E. Chouri, S.L. Blokland, A.A. Kruize, F.P. Lafeber, M. Rossato, J.A. van Roon, T.R. Radstake
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Plasmacytoid dendritic cells (pDCs) are indicated to be key players in the pathogenesis of primary Sjögren9s syndrome (pSS) and important producers of type-1 interferon (IFN). This is based on their increased presence in pSS salivary glands, potential role in experimental animal models and the presence of an IFN signature in pSS patients, which is associated with disease activity measures. MicroRNAs (miRNA) are key regulators of cellular function and may play a pivotal role in pDC function. <h3>Objectives</h3> To unravel the role of miRNAs in pDCs of pSS patients, we investigated the expression of miRNA in these cells in pSS patients. <h3>Methods</h3> Two independent cohorts (discovery and validation) were established including a total of 30 pSS patients. 15 healthy controls (HC) were included as control group and divided over the two cohorts. CD304-expressing pDCs were isolated from peripheral blood using MACS and profiling of 758 miRNA was performed using the OpenArray platform in the donors included in the discovery cohort. miRNAs found to be differentially expressed in the discovery cohort were subsequently measured in an independent validation cohort. Experimentally supported targets of validated miRNAs were used to perform pathway enrichment. <h3>Results</h3> A total of 24 miRNAs were significantly downregulated in pSS patients versus HC in the discovery cohort (all p&lt;0.05 and &gt;2log fold difference). 15 miRNAs were selected to be measured in the validation cohort, ten of these miRNAs were subsequently validated (p&lt;0.05). Pathway enrichment indicated that these miRNAs are mainly involved in regulation of growth factor signalling and cell cycle (FDR corrected, p&lt;0.05), including MTOR and PI-3K pathways. We are currently studying the involvement of these miRNAs in pDC function by linking miRNA expression to RNA sequencing data and <i>in vitro</i> functional assays. <h3>Conclusions</h3> We here for the first time show differential expression of miRNAs in isolated pDCs of pSS patients. Considering the strong potential of miRNAs in regulation of cell function, these data suggest a significant contribution to pDC function. Further analysis of the pathways in which these miRNAs are involved will expand our understanding on the role of pDCs in pSS. <h3>Disclosure of Interest</h3> None declared
Pharmacologic Inhibition of JAK1/JAK2 Signaling Protects from Acute GvHD While Preserving Gvt in Mice
Authors: Cristiana Carniti, Silvia Gimondi, Antonio Vendramin, Camilla Recordati, Davide Confalonieri, Anisa Bermema, Paolo Corradini, Jacopo Mariotti
Journal: Blood (2014)
FRI0129 Association between Hearing Loss and Carotid Subclinical Atherosclerosis in Female Rheumatoid Arthritis Patients
Authors: G.-T. Kim, H.-S. Tag, E.-K. Park, S.-G. Lee, D.-W. Koo, S.-H. Kim, J.-W. Lee
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The incidence of hearing loss (HL) has been on the rise in patients with rheumatoid arthritis (RA). However, limited information exists regarding the pathogenic mechanisms of HL in RA patients<sup>1,2</sup>. <h3>Objectives</h3> This study sought to evaluate the prevalence and characteristics of HL in RA patients compared with a control group and to identify factors associated with the degree of HL in RA patients. <h3>Methods</h3> We enrolled 64 RA patients and 70 healthy controls in a prospective manner. Each subject was tested with pure tone audiometry including high frequencies ranging from 0.5 to 16 kHz. For each set of tests, mean values for air conduction at each frequency and tympanometric values were calculated to exclude middle ear disease. In the RA group, auto-antibodies, erythrocyte sedimentation rate, high-sensitivity C-reactive protein, and RA disease activity were measured, and carotid ultrasonography was performed for the detection of indicators of subclinical atherosclerosis, including arterial stiffness index beta (β-index) and carotid intima-media thickness (cIMT). <h3>Results</h3> The prevalence of HL was higher in the RA group than the control group (37.1% vs. 65.6%, p=0.001). The hearing threshold value difference between groups was significant at frequencies of 0.5, 1, 2, 4, and 8 kHz (p&lt;0.05). Age showed the strongest correlation to HL at all frequencies in RA patients (p&lt;0.01). cIMT was also strongly related to HL at all frequencies, whereas β-index was related to HL only at high frequencies (8, 12, and 16 kHz), acting as an early marker of HL (both p&lt;0.05). <h3>Conclusions</h3> HL was more prevalent in the RA group than the control group. cIMT and β-index were strongly correlated with HL in the RA group, which implies that subclinical atherosclerosis may play an important role in HL in RA patients. <h3>References</h3> Özkırış M, Kapusuz Z, Günaydın İ, Kubilay U, Pırtı İ, Saydam L. Does rheumatoid arthritis have an effect on audiovestibular tests? Eur Arch Otorhinolaryngol. 2014;271:1383–7 Pascual-Ramos V, Contreras-Yáñez I, Rivera-Hoyos P, Enríquez L, Ramírez-Anguiano J. Cumulative disease activity predicts incidental hearing impairment in patients with rheumatoid arthritis (RA). Clin Rheumatol. 2014;33:315–21. <h3>Disclosure of Interest</h3> None declared
AB0299 The Reasons for Withdrawal of Biological Dmards According To The Russian Registry of Patients with Rheumatoid Arthritis: Table 1.
Authors: A. Satybaldyev, D. Karateev, E. Nassonov, E. Luchikhina, G. Lukina, M. Nikolenko, M. Bilinskaya, M. Dmitrieva, L. Bogoderova, N. Lapkina, N. Chichasova, V. Sorotskaya, D. Abdulganieva, R. Mukhina, G. Gafurova, V. Mazurov, D. Chakieva, R. Samigullin
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Russian register of patients with inflammatory arthritis started in 2012 as a register of RA ("All-Russian register of Rheumatoid Artritis"- ARRA) now transformed into "Observational REgister of arthritis in cLinical practice" (OREL), including patients with rheumatoid arthritis (RA), psoriatic arthritis and adults with juvenile arthritis. (RA), psoriatic arthritis and adults with juvenile arthritis. <h3>Objectives</h3> To study reasons for withdrawal of biological DMARDs in patients with RA in clinical practice in Russia. <h3>Methods</h3> Data of 1398 pts with RA (286 men, 1112 women, medium age of 50,5 years), treated of biological DMARDs, were included in OREL registry from 01 Mar 2012 to 30 Mar 2015. <h3>Results</h3> 320 pts (22.8%) had withdrawals of biologics during this period. In 77 pts (23.4%) the reason for withdrawal was primary lack of efficacy or secondary loss of response; in 54 pts (16.9%) - adverse events (AE) or serious adverse events (SAE). In 80 pts (25.0%) biologic therapy has been stopped due to continuous remission; 109 pts (32.5%) had administrative reasons (lack of funding etc.). <h3>Conclusions</h3> Frequencies of withdrawals due to lack of efficacy or loss of response among biological DMARDs were comparable. Etanercept has been withdrawn due to long term remission more often than other biologics. Lack of funding is still an important cause of withdrawal of biological therapy of RA. <h3>Disclosure of Interest</h3> None declared
Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia
Authors: Suthesh Sivapalaratnam, Sarah K. Westbury, Jonathan C. Stephens, Daniel Greene, Kate Downes, Anne M. Kelly, Claire Lentaigne, William J. Astle, Eric G. Huizinga, Paquita Nurden, Sofia Papadia, Kathelijne Peerlinck, Christopher J. Penkett, David J. Perry, Catherine Roughley, Ilenia Simeoni, Kathleen Stirrups, Daniel P. Hart, R. Campbell Tait, Andrew D. Mumford, Michael A. Laffan, Kathleen Freson, Willem H. Ouwehand, Shinji Kunishima, Ernest Turro
Journal: Blood (2016)
¿ES NECESARIA UNA PRIMERA COLONOSCOPIA DE SEGUIMIENTO AL AÑO EN EL GRUPO DE PACIENTES CON ADENOMAS DE ALTO RIESGO TRAS UNA COLONOSCOPIA DE CALIDAD EN EL CRIBADO POBLACIONAL DEL CÁNCER COLORRECTAL?
Authors: Á Terán Lantarón, C Alonso Martín, P Ruiz Bueno, S Álvarez González, J López Arias María, C Rodríguez De Lope López, PL Fernández Gil, B Castro Senosiain, J De La Peña García
Journal: Endoscopy (2015)

Introducción: El seguimiento endoscópico post-polipectomía es básico para la reducción de la incidencia y mortalidad del cáncer colorrectal (CCR), sin embargo el intervalo de seguimiento se basa en una evidencia limitada. A diferencia de otras Guías Clínicas, la Europea de 2010 propone una primera colonoscopia de seguimiento (PCS) al año en sujetos con adenomas de alto riesgo (AAR). Este hecho tiene trascendencia para los pacientes así como para los sistemas sanitarios.
Clarithromycin Enhances tyrosine Kinase Inhibitor – Induced Cell Death by Inhibition of Late Stage Autophagy in Patients with Chronic Myeloid Leukemia At Diagnosis or with Resistant Stage of Disease
Authors: A. M. Carella, G. Beltrami, G. Pica, C. Ghiggi, D. Lovera, G. Cirmena, A. Garuti
Journal: Blood (2012)
HLA-DRB1*1101-Restricted T Cells from Two Unrelated Mild Hemophilia a Inhibitor Subjects with Missense Genotype R593C Respond to the Same Minimal Epitope.
Authors: Eddie A. James, Simon D. van Haren, Ruth A. Ettinger, Arthur R. Thompson, William W. Kwok, Jan Voorberg, Kathleen P. Pratt
Journal: Blood (2008)
AB0194 Anti-Cyclic Citrullinated Peptides Antibodies (Anti-CCP) in Cutaneo-Arthritic but Non-Pulmonic Case of Sarcoidosis
Authors: H. Al Attia, K. Al Kateeb, I.A. Khan
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Anti-CCP antibodies have a high predictive value in RA patients and associated with disease severity. They have also been detected in few conditions such as Palindromic rheumatism, Psoriatic arthritis, Sjogren9s syndrome and other rheumatic disorders. Sarcoidosis on the other hand is a chronic inflammatory and potentially multi-systemic disease which is classically forming non-caseating granuloma, is not characteristically associated with positive anti-CCP Abs. There is only one report in the previous English literature that has described 2 patients with pulmonic sarcoidosis who were tested positive for anti-CCP Abs. <h3>Case report</h3> For more than a year, this 52 year old smoker lady has been noticing the development of a rather painless papular rash into a nodular one over the extensor surface of the hands, mainly in the knuckles (figure 1). No specific diagnosis was offered to here in due course however, in the last few months she begun to experience polyarthralgia in the joints of the hands and mild stiffness. The initial impression by the dermatologist colleague was that of erythema elevatum diutinum Routine blood and biochemistry workups was runemarkable apart from an ESR of 29mm/HR and hypovitaminosis D but with normal serum total calcium of 10.1mg/dL (N 8.4–10.5). Tests for RF, ANF, ds DNA, ENAs, CPK and LDH were negative yet the ELISA test for anti- CCP was positive repeatedly but in rather low titre of 36.73 and 37.62 U/mL (N&lt;17).The CXR showed no enlarged hilar lymphadenopathy or interstitial lung changes (Figure 2), the hands X-ray showed osteopenia and narrowing of the PIP Joint of the left ring finger (figure3).The MRI of the left hand showed erosion in the head of the 5th metacarpal bone and minimal effusion in the first MPJ (Figure 4, a and b). The biopsy of one skin nodule revealed many loose well circumscribed islands of granulomas but without caseous necrosis consistent with cutaneous sarcoidosis. Both tuberculin skin test and Quantiferon TB Gold test were negative. Serum angiotensin converting enzyme was within normal values of 49 U/L (N 16–72).She was managed with hydroxychloroquine and pentoxifylline. <h3>Conclusions</h3> Sarcoidosis is capable of mimicking several rheumatic diseases. However, this case is unusual in the sense of being presented with cutaneo-arthritic sarcoidosis without any pulmonic disease. The presence of positive anti-CCP makes it the third reported case in the literature of such association and may also be reflecting an overlap syndrome of sarcoidosis-RA. <h3>Disclosure of Interest</h3> None declared
PTU-093a An Audit of Primary Prophylaxis Against Variceal Bleeding Amongst Patients with Cirrhosis
Authors: C Johnson, S Todd, S McPherson, S Masson
Journal: Gut (2016)

<h3>Introduction</h3> Variceal bleeding occurs in 30–50% of patients with portal hypertension with early mortality (within 6 weeks) after a first variceal bleed approaching 20%.<sup>1</sup> In 2015, the updated BSG guidelines recommend that all patients with cirrhosis should be screened for varices at diagnosis.<sup>1</sup> Primary prophylaxis with non-selective beta-blockers (NSBB) or variceal band ligation (VBL) should be offered to those with grade 2–3 oesophageal varices, or any varices with red signs. Appropriate endoscopic surveillance intervals are recommended for the others. Here, we aim to audit the implementation of these recommendations in our patient cohort. <h3>Methods</h3> Between January and March 2015, consecutive patients with cirrhosis who attended specialist liver clinics at our institution were included. Clinical, demographic and endoscopic data was collected retrospectively. <h3>Results</h3> 111 patients (50 alcohol-related liver disease [ARLD], 25 non-alcoholic steatohepatitis [NASH], 25 viral hepatitis and 11 others) were studied. The mean age was 61±12 and 68 (61%) were male. The Child’s-Pugh score was A: 93 (84%), B: 15 (14%) and C: 3 (2%). Upon diagnosis of cirrhosis, 64 (58%) patients underwent endoscopic variceal screening; varices were detected in 37 (34%). Variceal screening at diagnosis was higher amongst NASH (80%) and viral hepatitis (64%) than ARLD (43%). Amongst those with varices (n = 37), primary prophylaxis was warranted in 28 and given in 27 (96%). After initiation, NSBB were rarely titrated according to clinical response. Amongst those requiring interval variceal screening or surveillance (n = 70), 40 (57%) underwent correctly-timed endoscopy. This was higher amongst NASH (71%) and viral hepatitis (69%) than ARLD (24%). Variceal haemorrhage occurred in 7 (6%) patients, 3 (43%) of whom had never undergone any endoscopic screening. <h3>Conclusion</h3> Our results demonstrate room for greater adherence to the guidelines with regards to initial screening and subsequent surveillance endoscopy. Once varices are identified, primary prophylaxis is initiated in the majority of patients, though with little evidence of subsequent titration to clinical response. Varices screening and appropriate primary prophylaxis is a proposed quality indicator in cirrhosis care. In order to improve quality of care, we highlight the need to perform screening endoscopy at diagnosis, and to titrate primary prophylaxis after initiation. <h3>Reference</h3> 1 Tripathi D, <i>et al</i>. UK guidelines on the management of variceal haemorrhage in cirrhotic patients. <i>Gut</i> 2015;<b>0</b>:1–25. <h3>Disclosure of Interest</h3> None Declared
AB0633 Performance of The EULAR/ACR 2013 Classification Criteria in A Portuguese Systemic Sclerosis Population
Authors: R. Fonseca, D. Rosa-Gonçalves, F. Aguiar, T. Meirinhos, T. Martins-Rocha, E. Mariz, M. Bernardes, L. Costa
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The 19809s ACR classification criteria for systemic sclerosis (SSc) show low sensitivity, especially in early or mild forms. A new set of classification criteria has been developed by ACR/EULAR in 2013. Applicability of the new criteria in clinical practice remains to be shown. <h3>Objectives</h3> To evaluate the performance of both set of classification criteria for SSc in a Portuguese SSc population. <h3>Methods</h3> Cross-sectional study including consecutive patients with clinical diagnose of SSc (based on expert opinion) followed in our rheumatology department. Clinical and demographic characteristics were collected by consulting the clinical files and national data base – Reuma.pt. The two sets of criteria were applied to all patients, sensitivity was calculated and Kappa coefficient was used to evaluate the agreement between them. Patients not fulfilling the old but fulfilling the new criteria were compared with those that fulfilled ACR criteria using Mann-Whitney, qui-square and fisher test (SPSS 23.0). Significance level was set as &lt;0.05. <h3>Results</h3> 108 patients were included, 96 (88.9%) were female with mean age of 58.21 (±12.8) years and a median disease duration of 6 years (0–38). 96 (88.9%) had localized and 12 (11.1%) had diffuse disease form. The most prevalent criteria items were: Raynaud9s phenomenon (93.5%), sclerodactyly of the fingers (85.2%) and antinuclear antibodies (94.4%). For overall cohort, 53 patients (49.1%) fulfilled the old ACR criteria. These 53 patients and more 44 patients (97) fulfilled the new ACR/EULAR criteria, showing a sensitivity of 89.9% compared to 49.1% of the old ones. Kappa coefficient was 0.197 (p=0.01). In patients with localized forms, the sensitive of ACR/EULAR criteria was 88.5% compared with 43.8% of ACR 1980 criteria and Kappa coefficient was 0.183 (p=0.02). In diffuse forms, all 12 patients fulfilled both criteria set, showing an almost perfect agreement. Patients not fulfilling the old but fulfilling the new criteria presented more frequently with capillaroscopic abnormalities (p=0.04) and anticentromere antiboy (p=0.01), but low incidence of anti-Scl70 antibodies (p&lt;0.001) and interstitial lung disease (p&lt;0.001). <h3>Conclusions</h3> Our study confirmed a greater sensibility of the new ACR/EULAR 2013 criteria compared with ACR 1980 criteria, especially in mild and localized SSc disease forms. In our patients with SSc not fulfilling the old criteria, the presence of capillaroscopic abnormalities and anticentromere antibodies among the new set of classification criteria were of the utmost importance in their reclassification as SSc patients. The application of the new criteria in clinical scenario allows an early classification and timely management of more SSc patients, ensuring a better prognosis. <h3>Disclosure of Interest</h3> None declared
Organic Arsenic Lipid Derivatives Are More Potent and Less Toxic Than Inorganic Arsenic Trioxide in Preclinical Testing.
Authors: Xiaodong Cheng, Mirna Golemovic, Francis Giles, Ralph Zingaro, Ming-Zhang Gao, Emil J. Freireich, Michael Andreeff, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Blood (2004)
Clinical Phenotype of Myeloproliferative Neoplasms with Activating CBL-mutations Resembles Chronic Myelomonocytic Leukemia.
Authors: Juliana Popa, Susanne Schnittger, Philipp Erben, Tamara Weiss, Ayalew Tefferi, Eva M Kanders, Eva Lengfelder, Martin C. Müller, Torsten Haferlach, Andreas Hochhaus, Wolf-Karsten Hofmann, Andreas Reiter
Journal: Blood (2009)
GATA2 is a New Predisposition Gene for Familial Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
Authors: Hamish S Scott, Christopher N Hahn, Catherine L Carmichael, Ella J Wilkins, Chan-Eng Chong, Peter J Brautigan, Xiao-Chun Li, Milena Stankovic, Ming Lin, Amandine Carmagnac, Carolyn M Butcher, Kathryn L Friend, Paul G Ekert, Chung H Kok, Anna L Brown, Ian D Lewis, L. Bik To, Andrew E Timms, Jan Storek, Sarah Moore, Meryl Altree, Robert Escher, Peter G Bardy, Graeme K Suthers, Richard J D'Andrea, Marshall S Horwitz
Journal: Blood (2010)
Vascular Endothelial Growth Factor (VEGF) Expression by Neoplastic Hodgkin-Reed-Sternberg Cells Is An Independent Adverse Prognostic Factor for Relapse in Hodgkin Lymphoma.
Authors: Antonio Gutierrez, Francisco Mestre, Rafael Ramos, Jordi Martinez-Serra, Antonia Bautista, José Fuster, Pilar Lopez-Marti, Marta Casasus, Cristina Nicolau, Julio Rifa, Joan Besalduch, Juan Fernando Garcia, Jose Rodriguez
Journal: Blood (2009)
Role Of Interim,-PET In Poor Prognosis Young Patients With Diffuse Large B Cell Lymphoma At Diagnosis: Data From An Ancillary Study Of a Prospective Randomized Phase III Study (DLCL04) From the Fondazione Italiana Linfomi
Authors: Luigi Rigacci, Patrizia Pregno, Benedetta Puccini, Andrea Evangelista, Annalisa Chiappella, Gianluca Gaidano, Luca Nassi, Monica Balzarotti, Francesco Merli, Amalia De Renzo, Alessandro Levis, Michele Spina, Vincenzo Pavone, Roberto Freilone, Stefano Luminari, Giuseppe Rossi, Caterina Stelitano, Angelo Michele Carella, Alfonso Maria D'Arco, Pellegrino Musto, Alberto Bosi, Umberto Vitolo
Journal: Blood (2013)
Magnetic Nanoparticles Fe3O4 synergy with Adriamycin and Arsenic Trioxide Reverse Multidrug Resistance in Lymphoma in Vitro
Authors: Xiaohui Cai, Baoan Chen, Chunling Wang, Jian Cheng, Yu Zhang, Jiahua Ding, Jijiao Ning, Wen Bao, Guohua Xia
Journal: Blood (2012)
Increased Expression of Pro-Angiogenic and Decreased Expression of Osteogenic Genes by Multipotential Stromal Cells after Stimulation with Myeloma-Derived Microvesicles.
Authors: Anna Zebzda, Artur Jurczyszyn, Danuta Jarocha, Aleksander B. Skotnicki, Marcin Majka
Journal: Blood (2007)