tbuckley/cabot-search huggingface dataset:
Expressionof Sf3b1- K700Ein Murine B Cells Causes Pre-mRNA Splicing and Altered B Cell Differentiation and Function
Authors: Lili Wang, Rutendo Gambe, Jean Fan, Youzhong Wan, Angela N Brooks, Jing Sun, Esther A. Obeng, Donna S Neuberg, Matthew Meyerson, Mark D. Fleming, Benjamin L. Ebert, Ruben D. Carrasco, Catherine J Wu
Journal: Blood (2015)
Refractory Autoimmune Hemolytic Anemia Following Unrelated Cord Blood Transplantation for Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature.
Authors: Huilan Liu, Liangquan Geng, Juan Tong, Zuyi Wang, Zimin Sun, Wen Yao, Xiao Yuan, Jie Chen
Journal: Blood (2007)
FRI0231 Treatment with BI 655064 (Antagonistic Anti-CD40 Antibody) Modulates Biomarkers Associated with Rheumatoid Arthritis (RA): Table 1.
Authors: S. Visvanathan, M. Ramanujam, C. Schoelch, R. Vinisko, U. Mueller-Ladner, S. Padula, J.S. Fine, J. Steffgen
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Co-stimulation through the CD40- CD40L axis has been implicated in the pathogenesis of RA including T cell mediated responses, B cell driven autoantibodies, adhesion molecule expression, synovial hyperplasia, and pannus formation, in addition to the secretion of proinflammatory cytokines and MMPs. Circulating CD40L levels are elevated in RA patients versus healthy controls. BI 655064 is a humanized antagonistic anti-CD40 monoclonal antibody which blocks the CD40/ CD40L interaction in in vitro CD40L induced B cell and APC activation assays with IC50 of &lt;1nM. <h3>Objectives</h3> To characterize the effect of BI 655064 on cellular and protein biomarkers in RA patients with prior inadequate response to a stable dose MTX ≥15 mg over a 12 wk period of treatment. <h3>Methods</h3> In this double-blinded, randomized trial RA patients were treated with either 120 mg BI 655064 or placebo q1w for 12 wks as add-on to MTX. Inclusion criteria were ≥6 swollen and ≥6 tender joints, CRP &gt;8 mg/L or ESR&gt;28 mm/1h. The primary efficacy endpoint was ACR20 response at wk 12.Select biomarkers were assessed in whole blood and serum pre and post treatment with BI 655064. <h3>Results</h3> Treatment with BI 655064 resulted in minimal changes in median %CD19+ B cell population but larger median decreases in select %CD95+ activated B cell subsets, specifically class switched (CD19+IgD-CD27+CD95+), pre-switched (CD19+IgD+CD27+CD95+) and double negative (CD19+IgD-CD27-CD95+) cells and decreases in autoantibodies (IgG-RF and IgA-RF), total IgG and IgM levels in RA patients vs placebo at 12 wks. Median decreases in IL-6 levels (important for B cell and monocyte differentiation) and select bone resorption biomarkers (MMP-3 and RANKL) were also observed in the BI 655064 treated patients vs placebo through 12 wks. Baseline levels of IgG RF, IgM RF, TNFa and COMP correlated with improvement in swollen joint counts at 12 wks and IgA RF levels correlated with improvement in DAS-28 CRP scores at 12 wks in patients treated with BI 655064. <h3>Conclusions</h3> These results demonstrate that treatment of RA patients with BI 655064 decreases activated B cell subsets, inhibits the production of pathogenic autoantibodies, and reduces the level of circulaiting inflammatory and bone resorption biomarkers at 12 wks. Baseline levels of select biomarkers significantly correlated with clinical response to treatment with BI 655064 at 12 wks. <h3>Disclosure of Interest</h3> S. Visvanathan Employee of: Boehringer Ingelheim, M. Ramanujam Employee of: Boehringer Ingelheim, C. Schoelch Employee of: Boehringer Ingelheim, R. Vinisko Employee of: Boehringer Ingelheim, U. Mueller-Ladner Consultant for: Boehringer Ingelheim, S. Padula Employee of: Boehringer Ingelheim, J. Fine Employee of: Boehringer Ingelheim, J. Steffgen Employee of: Boehringer Ingelheim
OP0056 Association of IL-12P40 and IL-12P70 with Pathophysiology of Takayasu Arteritis
Authors: T. Nakajima, H. Yoshifuji, C. Terao, K. Kitagori, K. Murakami, R. Nakashima, Y. Imura, M. Tanaka, K. Ohmura, T. Mimori
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> We preliminarily found a SNP (rs6871626, A vs. C) in <i>IL-12B</i> region as a susceptibility gene to Takayasu arteritis (TAK) by genome-wide association study. <i>IL-12B</i> encodes IL-12p40 that is a component of both IL-12p70 and IL-23. The significance of IL-12p40 in pathophysiology of TAK has not been fully investigated yet. Moreover, there has been no consistent evidence about whether IL-12p70 or IL-23 is important in TAK. <h3>Objectives</h3> 1) To investigate the expression of IL-12p40 in patients with TAK, 2) reveal which is more important to pathophysiology of TAK, IL-12p70 or IL-23, and 3) examine the influence of SNP to the cytokine production. <h3>Methods</h3> We collected sera from 43 TAK patients and 19 healthy controls (HCs), and measured IL-12p40, IL-12p70 and IL-23 with ELISA. Next, we collected whole blood from 18 TAK patients and 12 HCs, and isolated monocytes with RosetteSep™. The monocytes were incubated with IL-6, IL-10 and GM-CSF, and then stimulated with INF-γ and LPS. Then we measured the cytokines in culture supernatant with ELISA. <h3>Results</h3> IL-12p40 and IL-12p70 in sera of TAK patients were significantly higher than those of HCs (p=0.031 and p&lt;0.001, respectively), whereas there were no differences in serum of IL-23 levels between TAK patients and HCs. IL-12p40 and IL-12p70 in sera of TAK patients whose allele at rs6871626 is AA or AC (defined as risk patients) were significantly higher than those of HCs (p=0.018 and p&lt;0.001, respectively), whereas there were no differences in serum IL-23 levels among risk patients, TAK patients with CC allele (defined as non-risk patients) and HCs. Supernatant IL-12p40 and IL-12p70 levels from monocytes of risk patients were significantly higher than those of non-risk patients (p=0.044 and p=0.032, respectively) or those of HCs (p=0.032 and p=0.0015, respectively). Supernatant IL-23 from monocytes of risk patients were significantly higher than those of non-risk patients (p=0.04). <h3>Conclusions</h3> IL-12p40 and IL-12p70 but not IL-23 may play an important role in pathophysiology of TAK, and the risk allele of rs6871626 could contribute to production of these cytokines. <h3>Disclosure of Interest</h3> None declared
HOXB7 Overexpression in Mesenchymal Cells Stimulates the Production of Pro-Angiogenic Molecules: Potential Role in Multiple Myeloma Associated Angiogenesis
Authors: Simona Colla, Nicola Giuliani, Paola Storti, Mirca Lazzaretti, Katia Todoerti, Gina Lisignoli, Luca Agnelli, Cristina Manferdini, Sabrina Bonomini, Luisa Galla, Marina Bolzoni, Cristina Mancini, Gabriella Sammarelli, Marcellina Mangoni, Giorgio Lambertenghi Deliliers, Antonino Neri, Vittorio Rizzoli
Journal: Blood (2008)
MiR-300 Acts As a Tumor Supressor in Ph+ Progenitors By Modulating the JAK2-SET/PP2A/β-Catenin Interplay
Authors: Giovannino Silvestri, Justin Ellis, Lorenzo Stramucci, Jason G Harb, Paolo Neviani, Guido Marcucci, Denis-Claude Roy, Peter Hokland, Dragana Milojkovic, Alistair Reid, Jane F. Apperley, Ferenc M Livak, Maria R. Baer, Rossana Trotta, Danilo Perrotti
Journal: Blood (2014)
Abstract 18939: Micro RNA-93 Promotes Macrophage M2 Polarization in Experimenal Peripheral Arterial Disease
Authors: Vijay C Ganta, Anna Kutateladze, Brian Annex, Norbert Leitinger
Journal: Circulation (2015)

Macrophages (MØ) were well known to play vital roles in promoting blood flow by arteriogenic induction in experimental Peripheral Arterial Disease (PAD). MØs depending on the cytokine milieu, exist in M1 or M2 polarization states (two extremes of polarization continuum). While M1-MØs are pro-inflammatory and anti-angiogenic, M2-MØs are anti-inflammatory and pro-angiogenic. We have previously demonstrated that Micro RNA-93 (Mir93) promotes angiogenesis and perfusion recovery in experimental PAD. However, the downstream mechanisms that operate in Mir93 mediated perfusion recovery in ischemic leg are not yet clear. In our current study we investigated the role of Mir93 in MØ polarization in vitro and in animal models of hind limb ischemic (HLI). We hypothesized that “Mir93 induction in ischemic muscle promotes M2-MØ polarization that improves tissue repair, survival and neovascularization in PAD” Mir93 mimic transfection in Raw264.7 (MØ cell line) significantly induced Arginase-1 (M1 marker) expression and decreased inducible Nitric oxide synthase (iNOS) (M2 marker) expression compared to negative mimic in qPCR analysis. Bone marrow derived macrophages (BMDM) from MCM7-KO (Mir93 deficient mice) express significantly higher levels of iNOS compared to littermates under hypoxia serum starvation. Monocytes isolated from the bone marrow of MCM7-KO ischemic legs express significantly higher levels of iNOS compared to littermates. Conditioned medium from Antagomir-93 treated Raw264.7 MØs and MCM7-KO BMDM significantly decreased HUVEC capillary like tube formation on matrigel compared to negative antagomir treated or littermates. Flow cytometry analysis showed that MCM7-KO mice had significantly higher levels of M1-MØs correlating with decreased capillary density compared to litter mate controls. P&lt;0.05 considered significant We conclude that Mir93 plays a crucial role in inducing MØ-M2 polarization. Increased Mir93 levels in ischemic hind limb promote M2-MØ polarization that helps in recovery of ischemic leg by tissue repair and neovascularization. Ongoing experiments are aimed to determine whether Mir93 deficient MØs can inhibit perfusion recovery in littermates and the downstream targets of Mir93 that regulate MØ polarization in HLI
Reply to Filippo Alongi, Rosario Mazzola, Dario Aiello and Matteo Salgarello's Letter to the Editor re: Re: Daniel E. Spratt, Hebert A. Vargas, Zachary S. Zumsteg, et al. Patterns of Lymph Node Failure after Dose-escalated Radiotherapy: Implications for Extended Pelvic Lymph Node Coverage. Eur Urol 2017;71:37–43. A Step Forward in the Era of Functional Imaging?
Authors: Daniel E. Spratt, Michael J. Zelefsky
Journal: European Urology (2016)
PWE-145 Incorporating Screening for Poor Prognosis Into Inpatient Management of Decompensated Cirrhosis
Authors: R Goddard, A Gopfert, G Connolly, B Hudson
Journal: Gut (2016)

<h3>Introduction</h3> The Lancet standing commission on liver disease recently highlighted the importance of palliative care in advanced liver disease. The end of life care strategy (DoH, 2008) noted many patients do not die in a place of their choosing, and that difficulties exist amongst physicians in identifying the dying process. Optimal provision and co-ordination of palliative care relies on timely recognition of poor prognosis. 90% of patients who die from liver disease are admitted to hospital at least once in the previous year. Hospital admission presents an important opportunity to assess prognosis and explore patients’ understanding of their risk of dying and preferences for care. This quality improvement project aimed to create a clinical framework through which screening for poor prognosis could be integrated into the routine inpatient management of patients with decompensated cirrhosis. <h3>Methods</h3> An inpatient Poor Prognosis Screening Tool (PPST - incorporating assessment of disease severity, WHO performance status, frequency of admission, and suitability for transplantation) was developed at University Hospitals Bristol in 2013. Based on retrospective data, a positive PPST screen predicted death at 1 year with a sensitivity of 81%. Initial audit identified infrequent use of the existing PPST (18.1%). A series of 5 quality improvement cycles (plan-do-study-act) were completed with input from consultants, junior medical and nursing staff at each stage. Ease of use and incorporation into routine practice were used as primary objectives. <h3>Results</h3> The weekly ward MDT was identified as a point where the PPST could be routinely incorporated. Following feedback from junior staff the PPST was simplified and embedded into a weekly written MDT proforma. Guidance for completion were streamlined and made accessible by printing on the reverse of the proforma. Following feedback from nursing staff the proforma sheet was coloured, allowing key discussions and decisions to be easily identified on subsequent admissions. Consultants chairing the MDT incorporated the PPST into the standard weekly discussion of each patient. Repeat audits demonstrated that PPST use had become routine with completion rates of 66–94% for patients with decompensated cirrhosis. <h3>Conclusion</h3> Assuming MDT agreement, a positive PPST screen triggers a consultant led poor prognosis discussion with the patient, a poor prognosis letter to the GP, and involvement of the palliative medicine team to assist with symptom control and advance care planning. Through incorporation of the PPST into the routine care of patients with decompensation, identification of patients with end-stage disease has improved. Better access to appropriate services and support, and improved co-ordination of community care can be subsequently afforded to appropriate patients. <h3>Disclosure of Interest</h3> None Declared
Axonal Degeneration Is Regulated by a Transcriptional Program that Coordinates Expression of Pro- and Anti-degenerative Factors
Authors: Maya Maor-Nof, Erez Romi, Hadas Sar Shalom, Valeria Ulisse, Calanit Raanan, Aviv Nof, Dena Leshkowitz, Roland Lang, Avraham Yaron
Journal: Neuron (2016)
Reduced Intensity Conditioning Regimens in Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis patients.
Authors: Andrei A. Novik, Alexey N. Kuznetsov, Vladimir Y Melnichenko, Denis A Fedorenko, Andrey Kartashov, Ruslana V Kruglina, Tatiana I Ionova, Kira Kurbatova, Gary J Gorodokin
Journal: Blood (2009)
A Phase II Feasibility Study of Prophylactic White Cell Transfusions for the Prevention of Infection in AML Patients Undergoing Induction Therapy
Authors: Courtney D. DiNardo, Fleur M. Aung, Fernando Martinez, Naval Daver, Tapan Kadia, Nitin Jain, Elias Jabbour, Naveen Pemmaraju, Virgil M Reddy, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi, Hagop M. Kantarjian, Benjamin Lichtiger, Emil J. Freireich
Journal: Blood (2014)
Adults with Acute Lymphoblastic Leukemia and T(1;19) Abnormality Have a Favorable Outcome with Hyper-CVAD Chemotherapy
Authors: Ravin Jain Garg, Hagop M Kantarjian, D. A Thomas, Stefan Faderl, Farhad Ravandi, Denise Lovshe, Sherry Pierce, Susan O’Brien
Journal: Blood (2008)
SAT0350 Functional Characterisation of Takayasu Arteritis Vascular Lesions by MR and FDG-PET/CT Provides Non-Redundant Information over Clinical Assessment
Authors: E. Tombetti, E. Tombolini, E. Incerti, A. Salerno, G. Benedetti, M. Papa, L. Gianolli, M.G. Sabbadini, F. De Cobelli, A.A. Manfredi, M. Picchio, E. Baldissera
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Disease activity (DA) assessment in Takayasu arteritis (TA) is an unresolved enigma as systemic inflammation and current activity measures poorly correlate with arterial progression. Morphological imaging, e.g. with morphological magnetic resonance (MR) sequencies, is the goal standard to evaluate arterial progression after its occurrence, and it is not clear whether functional characterisation of the lesions (e.g. contrast enhancement at MR or fluorodesoxyglucose [FDG] uptake at FDG-PET/CT [PET]) can predict arterial progression before its occlusion. We are prospectively following 60 TA patients with functional and morphological imaging to understand the predictors of arterial progression. Here we present the baseline assessment of the first 47 patients. <h3>Objectives</h3> to verify if activity measures, and functional lesion characterisation with PET or MR provide independent information. <h3>Methods</h3> Cross-sectional analysis of 47 TA patients according to ACR criteria followed at our Institution and undergoing closely related MR, PET and clinical evaluation. DA was evaluated with NIH criteria, indian Takayasu activity score (ITAS2010) and physician global assessment (PGA). At MR, arterial lesions were characterized by length, thickness and percentage of stenosis. Contrast to noise ratio (CNR) was calculated, when technically possible. Each vascular lesion uptake large enough to be evaluated by PET was evaluated with a quantitative (SUV<sub>max</sub>) method. Per patients and per lesion analyses were performed. <h3>Results</h3> The median interval between MR and PET was 24 days. TA was active in 25, 17 and 35 patients according to NIH criteria, ITAS2010 and PGA (including active and grumbling disease). In total, MR identified 333 arterial lesions (median lesion N per patient 6, IQR 1–15). At the “per patient” analysis, median CNR<sub>max</sub> at MR was 12,43 (IQR 0,00–54,29). CNR<sub>max</sub> did not correlate with acute-phase markers nor activity measures, except for ITAS-CRP (rho 0.300, p=0,038). PET showed significant uptake in 18 patients. Meadian SUV<sub>max</sub> was 1,19 (IQR 0,00–9,00). SUVmax did not correlate with activity measures. At the “per lesions” analysis, 56 lesions had positive uptake in PET. There was no correlation between the degree of enhancement at MR and of FDG uptake at PET (rho 0,094, p=0,529). <h3>Conclusions</h3> Current activity measures, mainly based on systemic inflammation, and functional characterisation of the arterial lesions by MR and FDG-PET provide independent information in TA. The prospective part of this study will clarify the clinical relevance and the predictive values for progression of these different pieces of information. <h3>Disclosure of Interest</h3> None declared
Recurrent Innovation at Genes Required for Telomere Integrity in<i>Drosophila</i>
Authors: Yuh Chwen G Lee, Courtney Leek, Mia T Levine
Journal: Molecular Biology and Evolution (2016)

Telomeres are nucleoprotein complexes at the ends of linear chromosomes. These specialized structures ensure genome integrity and faithful chromosome inheritance. Recurrent addition of repetitive, telomere-specific DNA elements to chromosome ends combats end-attrition, while specialized telomere-associated proteins protect naked, double-stranded chromosome ends from promiscuous repair into end-to-end fusions. Although telomere length homeostasis and end-protection are ubiquitous across eukaryotes, there is sporadic but building evidence that the molecular machinery supporting these essential processes evolves rapidly. Nevertheless, no global analysis of the evolutionary forces that shape these fast-evolving proteins has been performed on any eukaryote. The abundant population and comparative genomic resources of Drosophila melanogaster and its close relatives offer us a unique opportunity to fill this gap. Here we leverage population genetics, molecular evolution, and phylogenomics to define the scope and evolutionary mechanisms driving fast evolution of genes required for telomere integrity. We uncover evidence of pervasive positive selection across multiple evolutionary timescales. We also document prolific expansion, turnover, and expression evolution in gene families founded by telomeric proteins. Motivated by the mutant phenotypes and molecular roles of these fast-evolving genes, we put forward four alternative, but not mutually exclusive, models of intra-genomic conflict that may play out at very termini of eukaryotic chromosomes. Our findings set the stage for investigating both the genetic causes and functional consequences of telomere protein evolution in Drosophila and beyond.
PTH-043 A Comparative Study of Risk Assessment Scores for Acute Upper GI Bleeds, in Predicting Need &amp; Time for Intervention
Authors: SAA Gardezi, C Tibbatts, A Foliaki, L Chase
Journal: Gut (2016)

<h3>Introduction</h3> While managing patients with acute upper GI bleed (AUGIB) a simple numerical score can be helpful to identify high risk groups &amp; need for intervention as recommended by NICE.Recent NCEPOD report for AUGIB reported that only 32% patients had a Pre-endoscopy risk assessment performed. Two commonly used scoring systems in UK are GBS (Glasgow Blatchford score) and RCS (Rockall score). Recent comparisons have shown that the GBS was superior in identifying need for hospital-based intervention<sup>1</sup> while RCS was better in predicting mortality.<sup>2</sup> <h3>Methods</h3> We conducted a retrospective study of 893 patients, admitted to the hospital and treated in endoscopy unit of Cardiff &amp; Vale health board between September 2010 to September 2013 with AUGIB. We calculated the GBS and pre &amp; post endoscopy RCS for each and compared several outcomes. <h3>Results</h3> Overall, GI bleed related mortality was only 3.1% in our study, with chronic liver disease being one of the main risk factor. GBS was superior in identifying patients suitable for safe discharge with outpatient management. The GBS was also better at predicting the need for endoscopic intervention. Our study also found that very early endoscopy (ie &lt; 6 hours) compared to rapid endoscopy (6–24 hours), did not improve survival in the highest risk patients (ie GBS &gt; 10), and in fact had a significantly worse mortality rate of 28% versus 7.4% . <h3>Conclusion</h3> The GBS score is superior to the pre-endoscopy Rockall in rationalising need &amp; timeliness of intervention. The post-Rockall score is shown to be the better predictor of mortality. This study also reinforced the importance of access to rapid endoscopic intervention within 24 hours, but did not demonstrate the need for very early gastroscopy. <h3>References</h3> 1 Camellini L, <i>et al</i>. <i>Dig Liver Dis</i>. 2004;<b>36</b>(4):271–7. 2 Rockall TA, <i>et.al</i>. <i>Gut</i>. 1996;<b>38</b>(3):316–21. <h3>Disclosure of Interest</h3> None Declared
A Complex T(10;11) MLL-AF10 Translocation with Duplication of the Rearranged Chromosome 10 in a Patient Affected with An AML M2
Authors: Paolo Bernasconi, Irene Dambruoso, Marina Boni, Rita Zappatore, Paola Maria Cavigliano, Marilena Caresana, Cesare Astori, Carlo Castagnola, Mario Lazzarino
Journal: Blood (2008)
Strong Inhibition of Alloreaction by Newly Generated Tolerogenic Dendritic Cells by Psoralen Plus UVA Treatment.
Authors: Hideaki Maeba, Ryosei Nishimura, Rie Kuroda, Raita Araki, Shintaro Mase, Yasuhiro Ikawa, Akihiro Yachie, Shoichi Koizumi
Journal: Blood (2009)