tbuckley/cabot-search huggingface dataset:
The Salmonella Effector SteD Mediates MARCH8-Dependent Ubiquitination of MHC II Molecules and Inhibits T Cell Activation
Authors: Ethel Bayer-Santos, Charlotte H. Durkin, Luciano A. Rigano, Andreas Kupz, Eric Alix, Ondrej Cerny, Elliott Jennings, Mei Liu, Aindrias S. Ryan, Nicolas Lapaque, Stefan H.E. Kaufmann, David W. Holden
Journal: Cell Host & Microbe (2016)

The SPI-2 type III secretion system (T3SS) of intracellular Salmonella enterica translocates effector proteins into mammalian cells. Infection of antigen-presenting cells results in SPI-2 T3SS-dependent ubiquitination and reduction of surface-localized mature MHC class II (mMHCII). We identify the effector SteD as required and sufficient for this process. In Mel Juso cells, SteD localized to the Golgi network and vesicles containing the E3 ubiquitin ligase MARCH8 and mMHCII. SteD caused MARCH8-dependent ubiquitination and depletion of surface mMHCII. One of two transmembrane domains and the C-terminal cytoplasmic region of SteD mediated binding to MARCH8 and mMHCII, respectively. Infection of dendritic cells resulted in SteD-dependent depletion of surface MHCII, the co-stimulatory molecule B7.2, and suppression of T cell activation. SteD also accounted for suppression of T cell activation during Salmonella infection of mice. We propose that SteD is an adaptor, forcing inappropriate ubiquitination of mMHCII by MARCH8 and thereby suppressing T cell activation.
The Novel, Investigational NEDD8-Activating Enzyme Inhibitor MLN4924 In Adult Patients with Acute Myeloid Leukemia (AML) or High-Grade Myelodysplastic Syndromes (MDS): A Phase 1 Study
Authors: Ronan T Swords, Harry P Erba, Daniel J DeAngelo, Peter G Smith, Michael D Pickard, Bruce J. Dezube, Francis J. Giles, Bruno C. Medeiros
Journal: Blood (2010)
Self‐Renewal of Bone Marrow Stem Cells by Nanovesicles Engineered from Embryonic Stem Cells
Authors: Wonju Jo, Dayeong Jeong, Junho Kim, Jaesung Park
Journal: Advanced Healthcare Materials (2016)

Extracellular vesicles can enhance cell proliferation by stimulating signal transduction and delivering genetic materials, and thus may have applications in regenerative medicine and other therapeutic applications. The processes employed to isolate extracellular vesicles, however, are complex and achieve low yield. To overcome these obstacles, a large-scale, micropore device for generating extracellular vesicle-mimetic nanovesicles that have characteristics similar to those of extracellular vesicles is fabricated. The nanovesicles are generated through the self-assembly capability of cell membrane fragments in an aqueous solution. The nanovesicles enhance the proliferation of murine mesenchymal stem cells (MSCs), stimulate the signal pathway related to cell proliferation, and do not influence the characteristics of murine MSCs. Therefore, these nanovesicles could provide stable MSCs for regenerative medicine and other therapeutic applications.
AB0335 Prevalence of Residual Inflammation in Rheumatoid Arthritis Patient after One Year of Adalimumab Therapy: Table 1.
Authors: Y.-C. Chen, J.-F. Chen, T.-T.C. Tien-Tsai Cheng
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Studies have previously demonstrated that ultrasound detected power Doppler (PD) activity (implying active synovial inflammation) may be present in a proportion of patients in clinical remission<sup>1,2</sup> and this can be used to accurately predict subsequent radiographic structural progression.<sup>3</sup> It may be hypothesised that such continued subclinical inflammation despite apparent remission as determined by traditional criteria may trigger a subsequent disease flare. <h3>Objectives</h3> Our study aimed to determine subclinical joint inflammation in patients with rheumatoid arthritis by power Doppler ultrasound in patients with rheumatoid arthritis at 12 months of adalimumab therapy. <h3>Methods</h3> Patients with RA who had received adalimumab therapy were enrolled. Patients underwent clinical, laboratory, and ultrasonographic assessment with power Doppler assessment of bilateral elbows (posterior recess), wrists (radio-carpal), second and third MCP joints (dorsal recess), MCP II and III, PIP II and III (dorsal recess), knee, ankle and MTPII and MTP V joint at 12th month. <h3>Results</h3> Power Doppler ultrasound was performed in 62 patients (87 females and 18 males; mean age: 57.09±9.96 years). The mean baseline DAS28 were 8.13±9.52. Baseline PD score (mean ±SD) were 0.852 ±1.051 and after 12 month of adalimumab therapy, the PD score decreased to 0.23±0.42. Ultrasound was performed 12th month at various parts, with the mean GS score: most prominent at right wrist (.810±.924) and left wrist (.774±.909) (Table).Logistical regression confirmed diabetes, positive anti-CCP, high DAS28 had more sonographic inflammation, while hypertension and positive rheumatoid factor (RF) had less sonographic inflammation. MTX, glucocorticoid and cyclosporin therapy had increased inflammation. <h3>Conclusions</h3> Our data confirm the evidence that even after 1 year of biological therapy, there were still persistent subclinical synovitis, more severe at wrist joints. Baseline high DAS28 and high PD activity had more prone to residual inflammation. So we recommended serial ultrasound follow up of PD ultrasound in patients with rheumatoid arthritis after adalimumab therapy. <h3>References</h3> Saleem B, et al. Arthritis Rheum. 2009;60(7):1915–22. Brown AK, et al. Arthritis Rheum. 2006;54(12):3761–73. Brown AK, et al. Arthritis Rheum. 2008;58(10):2958–67. <h3>Disclosure of Interest</h3> None declared
PTU-030 Number of Significant Polyps Detected Per Six Minutes of Withdrawal Time at Colonoscopy (SP6): A New Measure of Colonoscopy Efficiency and Quality: Abstract PTU-030 Table 1
Authors: R Rameshshanker, A Wilson, Z Tsiamoulos, P Tekkis, BP Saunders
Journal: Gut (2016)

<h3>Introduction</h3> There is an increasing focus on quality, safety and efficiency of colonoscopy procedures. Colonoscopic efficiency could be defined as the ability to detect clinically relevant pathologies with a minimum expenditure of time and effort without compromising the safety of the procedure. Adenoma Detection Rate (ADR) is considered as a surrogate marker for quality of colonoscopic examination. However, ADR does not take into account sessile serrated polyps/adenomas (SSP/A) or the efficiency of detection. We therefore propose a new measure of colonoscopy efficiency the SP6 that can be used to evaluate both individual endoscopist’s performance and to compare different detection interventions. Our objective was to assess the SP6 for an individual colonoscopist during standard and Endocuff –assisted colonoscopy (EAC) <h3>Methods</h3> A prospective service evaluation of screening colonoscopies was performed by an experienced endoscopist between October 2014 and September 2015. For consecutive colonoscopies, patient demographics and procedural data were collected. <h3>Results</h3> 96 patients had screening colonoscopy during this period. The median age was 65 years (55–74 years). A distal disposable attachment such as Endocuff Vision<sup>TM</sup> was used at the endoscopists’ discretion. 49 patients had Endocuff Vision-assisted colonoscopy and the remainder had standard colonoscopy. Figure 1 summarises the main findings. There was no significant difference in caecal intubation time and withdrawal time between the two groups. Both ADR and SP6 were significantly improved and SP6 demonstrated that EAC appears to significantly improve colonoscopy efficiency with approximately twice as many pre-cancerous lesions detected and removed per 6 minutes of withdrawal time (1.11 vs 0.6, p = 0.004). <h3>Conclusion</h3> From this preliminary data an SP6 (colonoscopy efficiency metric) appeared significantly higher when Endocuff Vision<sup>TM</sup> is used. An SP6 &gt;1 can be achieved in the context of bowel cancer screening FOBT positive colonoscopy and may act as a new benchmark to demonstrate high quality examinations. <h3>Disclosure of Interest</h3> None Declared
OP0037 First Pilot Study of An Implantable Loop Recorder (ILR) in Systemic Sclerosis Detects Significant Cardiac Arrhythmias with CMR Abnormalities: Table 1.
Authors: L.-A. Bissell, R. Dumitru, B. Erhayiem, G. Fent, J.P. Greenwood, S. Plein, J. Andrews, L. Graham, M.H. Buch
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> SSc-cardiomyopathy associated conduction abnormalities carry a poor prognosis, but their pathogenesis is unclear. Early detection to prevent complications is essential. ILRs are well-established in cardiology practice. <h3>Objectives</h3> To determine the spectrum of cardiac conduction abnormalities (CCA) using the REVEAL® ILR &amp; their association with CMR in patients (pts) with SSc with no known cardiac disease. <h3>Methods</h3> 20 pts with (ACR/EULAR criteria) SSc, with no diabetes &amp;/or more than 1 cardiovascular (CV) risk factor, were assessed for SSc/CV profile &amp; comprehensive CV assessment performed, inc. 3T delayed enhancement-CMR (reported by CMR-cardiologists) &amp; ILR insertion. ILR data was downloaded 3 monthly +/− at pt request if indicated. One yr data is reported. CMR compared to 30 healthy controls. <h3>Results</h3> ILR data was available for 19 pts; 63% female, 84% Caucasian; mean (SD) age 53 (12)yrs, time from 1st non-RP symptom 9 (8)yrs; 32% dcSSc, 32% ACA+ve, 21% Scl70+ve, 54% palpitations hx, 42% known ILD, 11% DU hx, 0% pulmonary hypertension. Ten (52%) pts had ILR abnormalities; 4 with dcSSc, 3 ACA+ve, 3 Scl70+ve, 6 with palpitations hx, 4 known ILD, 3 DU hx. Subanalysis; 8 (42%) pts had supraventricular ectopics (SVE), 2 (11%) with ventricular ectopics (VE), 4 (21%) with arrhythmias of which 1 atrial flutter, 1 SVT, 1 VT &amp; 1 complete heart block (CHB). Of the 4 pts with arrhythmias; 2 had dcSSc, 1 ACA+ve, 1 Scl70, 3 palpitations hx, 2 known ILD, 2 DU hx. Pt with CHB (dcSSc) had few SVE/VEs &amp; 3 couplets on 24hr ECG 6 weeks previous. CMR data was available for 15 SSc pts (DE in 14; 1 pt claustrophobic, no IV access in 2, 1 CMR abandoned due to pacemaker insertion for CHB). Trend towards lower LVmass &amp; distensibility (ie greater arterial stiffness) &amp; higher extracellular volume (ECV, fibrosis marker) seen in pts with ILR abnormalities (p&gt;0.05). Trend for higher ECV in those with SVE [unadj. mean difference (diff.) (95%CI) 1.1 (-2.5, 4.7)% p0.513], VE [0.7 (-4.9, 6.3)% p0.789] &amp; arrhythmias [1.8 (-3.7, 7.3)% p0.486]. ECV was higher in SSc vs. controls; mean diff. 4.9 (3.2, 6.6)% p&lt;0.001 R<sup>2</sup> 0.568, adj. for age/sex; with trend for lower LV mass &amp; distensibility. <h3>Conclusions</h3> This first ILR in SSc study demonstrates its utility in the incidental detection of CCA, including serious cardiac arrhythmias &amp; suggests associated CMR abnormalities. These data support the need for identification of pts at risk that would benefit from ILR &amp; provide insights into the pathogenesis of SSc-cardiomyopathy <h3>Disclosure of Interest</h3> None declared
Azacitidine (AZA) Combined with Idarubicin in Higher Risk MDS - Results of a Phase I/II Study By the Groupe Francophone Des Myelodysplasies (GFM)
Authors: Marie Sebert, Aspasia Stamatoullas, Thorsten Braun, Jacques Delaunay, Benoît de Renzis, Ramzi Jeddi, Balkis Meddeb, Mathilde Hunault Berger, Benedicte Samey, Fatiha Chermat, Sylvie Chevret, Cendrine Chaffaut, Pierre Fenaux, Lionel Ades
Journal: Blood (2015)
FRI0378 National Audit of Vasculitis Inpatient Comorbidities and Mortality from 2005-14
Authors: L. Harty, S. Burns, D. Jayne
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Incidence of inpatient (inpt) events, comorbidities and age of death for Irish vasculitis patients is currently unknown <h3>Objectives</h3> Establish mortalitity &amp; comorbidities in Irish vasculitis inpts <h3>Methods</h3> The HIPE system was evaluated from 57 Irish hospitals between 2005–2014 for vasculitis inpt episodes (not individual patients) based on ICD10. Age, length of stay (LOS), gender and admitting indication and mortality were recorded. Results are shown as totals, % &amp; median (IQR). The Mann–Whitney U test and χ<sup>2</sup> were employed <h3>Results</h3> 5,841 vasculitis inpt records were reviewed with median annual admissions of 601 (601–622). 2,229 inpt admissions had large vessel vasculitis (LVV – Takayasu9s &amp; GCA) whose median age was 75yrs (66–81), LOS 6 days (3–13) and 68% were female. 3612 inpt admissions had small &amp; medium vessel vasculitis (SMVV –GPA, eGPA, MPA, PAN, Behcet9s, Goodpastures, Necrotizing &amp; Juvenile Vasculitis) with a median age 58yrs (42–70), LOS 6 days (2–13) and 48% were female. MPA, eGPA and GPA admissions were more common for men whereas GCA, Takayasu9s and Behcets admissions were more common for women (<i>table 1).</i> 58% LVV inpts &amp; 50% SMVV inpts were admitted for systemic inflammation (p&lt;0.001). Infection was the next most common cause for admission (14% SMVV &amp; 10% LVV, p&lt;0.001). Ischaemic events were the 3rd most common reason for admission in LVV (7% v 3%, p&lt;0.001) whereas renal failure was for SMVV (8% v 1%, p&lt;0.001). Symptoms without a diagnosis were the 4th most common reason for admission (7% LVV &amp; 5% SMVV, p=0.002). <i>Figure 1.</i> Admission for cancer occurred in mean 2.5% and all other diagnoses accounted for &lt;2% each. A greater percentage of SMVV inpts died than LVV inpts (4.1% v 2.7%, p=0.006) and they died younger (71yr (61–79) v 82 (76–86), p&lt;0.001). Infection accounted for 28% of all deaths without difference between LVV and SMVV (p=0.5). More SMVV inpts died due to disease activity than LVV inpts (19% v 6%; p=0.03) and from renal failure (12% v 1%, p=0.05). More LVV inpts died from vascular infarction than SMVV (19% LVV v 6% SMVV; p&lt;0.001). Male GPA inpts died younger than female (69yrs (62–78) v 79yrs (68–82); p=0.02). <h3>Conclusions</h3> Around 600 vasculitis admissions occurred each year across the 57 hospitals directing the need for a concentrated number of centres of excellence to facilitate expert care, research and education. Small vessel vasculitis admissions were more common for men and large vessel and Behcet9s for women. Despite advances in therapy systemic autoimmune disease and infection prevailed as causes for admission and death in vasculitis inpts, with greater mortality in SMVV from disease activity and renal failure and from vascular infarction in LVV. There is a need for improved diagnostic tests. <h3>Disclosure of Interest</h3> None declared
OC-013 Endoscopic Full-Thickness Resection (eFTR) in the Colon with the FTRD System: The First UK Experience
Authors: I Rahman, P Boger, S Ishaq, N Suzuki, S Green, A Kawesha, P Patel
Journal: Gut (2016)

<h3>Introduction</h3> Standard endoscopic resection of non-lifting adenomas and subepithelial tumours are challenging and pose significant risks of adverse events. Various methods for full thickness resection of these lesions have been trialled, but have been fraught with difficulties. Here we report a simple technique for colonic resections using a novel endoscopic full thickness resection (eFTR) device. <h3>Methods</h3> Data on consecutive patients who underwent eFTR at 3 UK institutions from April 2014 – January 2015 were prospectively analysed. The procedure was undertaken using the, over-the-scope, full thickness resection device (FTRD). Main outcome measures were technical success, total procedure times, histological confirmation of full thickness, R0 resection and adverse events. <h3>Results</h3> A total of 11 patients underwent eFTR, of which 5 were non-lifting adenomas, 4 T1 polyps and 2 subepithelial tumours. Procedure was technically successful in 82% (9/11) cases. The median age was 76 years (range 64–93 yrs), median procedure time was 40 minutes (range 22–60 mins) with a median specimen size of 22 mm (range 15–25 mm). Histology confirmed full thickness resection in all cases, with a R0 resection in 89% (8/9) cases. At 3 month endoscopic follow the anastomotic clip was still in situ in 3 cases. In 1 case (known R1 resection) a small 5 mm area of residual adenoma was noted which was successfully treated by conventional endoscopic means. There were no cases of immediate or delayed bleeding or perforation. <h3>Conclusion</h3> eFTR using the FTRD system is a promising, simple technique to facilitate full thickness resections in the colon that may avoid the need for surgery in some selected cases. Further studies are now required to fully evaluate its efficacy. <h3>Disclosure of Interest</h3> None Declared
Lysosomal Glycohydrolase Activities in Dendritic Cells: Is It a Function of Hematopoietic Stem Cells Differentiation Process?.
Authors: Anna C. Berardi, Pamela Manieri, Elisa Ciraci, Roberto Tribuzi, Ilaria Di Girolamo, Cristina Cavalieri, Giancarlo Isacchi, Carla Emiliani, Gianfranco Bottazzo, Aldo Orlacchio, Sabata Martino
Journal: Blood (2004)
Low-Dose Decitabine (DAC), Alone or in Combination with All-Trans Retinoic Acid (ATRA), Is An Active First-Line Treatment in Older AML Patients of All Cytogenetic Risk Groups: Final Results of the FR00331 Multicenter Phase II Study.
Authors: Michael Lübbert, Björn H. Rüter, Mathias Schmid, Rainer Claus, Ulrich Germing, Volker Rethwisch, Arnold Ganser, Uwe Platzbecker, Oliver Galm, Wolfram Brugger, Gerhard Heil, Björn Hackanson, Barbara Deschler, Pierre W Wijermans, Claudia Schmoor, Hartmut Döhner
Journal: Blood (2009)
Single or Multiple HLA-A, B, C or DRB1 Mismatches Limit Success of Unrelated Donor Bone Marrow Transplantation.
Authors: Stephanie J. Lee, John Klein, Michael Haagenson, Lee Ann Baxter-Lowe, Dennis Confer, Mary Eapen, Marcelo Fernandez-Vina, Neal Flomenberg, Mary Horowitz, Carolyn Hurley, Harriet Noreen, Machteld Oudshoorn, Effie Petersdorf, Michelle Setterholm, Stephen Spellman, Daniel Weisdorf, Thomas M. Williams, Claudio Anasetti
Journal: Blood (2006)
Combined Epigenetic Therapy with the Novel Histone Methyl Transferase EZH2 Inhibitor 3-Deazaneplanocin and Histone Deacetylase Inhibitor Panobinostat Exerts Synergistic Activity against Human Mantle Cell Lymphoma Cells
Authors: Warren Fiskus, Yongchao Wang, Anand Jillella, Pace Johnston, Rajeshree Joshi, Rekha Rao, Eduardo Sotomayor, Jianguo Tao, Peter Atadja, Victor Marqez, Kapil N. Bhalla
Journal: Blood (2008)
Molecular and Cellular Mechanisms for Fetal Hemoglobin Induction by Hydroxyureain Normal Erythroid Progenitors.
Authors: S. Likousi, G. Paterakis, D. Koumbi, A. Tserga, M. Papadakis, D. Kletsas, M. Katelani, E. Fibach, V. Merianou, P. Kollia
Journal: Blood (2004)
AB1024 Health-Related Quality of Life in Different Musculoskeletal Disorders: A Comparison among The Conditions and with A Selected Sample of Healthy Individuals Using SF-36 Questionnaire, EQ-5D and SQ-6D Utility Values
Authors: M. Di Carlo, F. Salaffi, M. Carotti, A. Ciapetti, M. Gutierrez
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Given the high prevalence of musculoskeletal (MSK) disorders, there is a need to determine which conditions have the greatest impact on health-related quality of life (HRQoL). <h3>Objectives</h3> To compare the HRQoL scores of the Medical Outcomes Study Short-Form 36 Health Survey (SF-36) and of the two widely used indirect utility instruments, the EuroQol Five Dimensions questionnaire (EQ-5D) and the Short-Form Six Dimensions questionnaire (SF-6D) among 14 different MSK disorders and to compare them with the results of a selecting sample of healthy controls. <h3>Methods</h3> 2,633 patients participated to this study. MSK disorders were classified into five diagnostic groups: inflammatory rheumatic diseases (IRD), connective tissue disorders (CTD), symptomatic peripheral osteoarthritis (SPOA), soft tissue disorders (STD) and osteoporosis (OP). IRD were further classified into 3 subgroups: rheumatoid arthritis (RA) (n=572), peripheral psoriatic arthritis (PsA) (n=150) and ankylosing spondylitis (AS) (n=251). CTD were classified into sistemic sclerosis (SSc) (n=75), sistemic lupus erythematosus (SLE) (n=83) and Sjogren sindrome (SS) (n=50). SPOA included symptomatic knee (n=176), hip (n=136 patients), and hand OA (n=87). The STD group included fibromyalgia (FM) (n=226 patients), low back pain (n=141) and shoulder tendinitis/adhesive capsulitis (n=112 patients). The OP group included 172 women who had vertebral fractures due to osteoporosis, and a group of 402 asymptomatic osteoporotic women without vertebral fractures. For comparison were used 649 healthy controls. The HRQoL was evaluated with the SF-36, using physical (PCS) and mental (MCS) component scales and EQ-5D. The SF-6D utility values were calculated from SF-36 by using a definite scoring function. <h3>Results</h3> The five major rheumatic disease groups, compared to healthy people, significantly impaired all eight health concepts of the SF-36 (p&lt;0.0001). Similar results were found for EQ-5D, EQ-VAS and SF-6D. The patients with IRD have poorer self-reported health status than those without arthritis in all domains of living, but particularly with respect to scales measuring aspects of physical functioning or mobility, role limitation due to physical health problems and usual activities, and bodily pain. RA had the largest negative impact on HRQoL at the individual level, followed by FM, vertebral fractures due to OP, OA of the hip, and SSc. <h3>Conclusions</h3> Our results indicates that MSK conditions have a clearly detrimental effect on the HRQoL, and physical domain is more impaired than mental and social ones. These findings may help clinical decision making and priority setting for management of individuals with MSK diseases. <h3>Disclosure of Interest</h3> None declared