tbuckley/cabot-search huggingface dataset:
First malaria vaccine to be tested in pilot projects, WHO announces
Authors: Anne Gulland
Journal: BMJ (2016)

The world’s first malaria vaccine will be introduced in pilot projects in sub-Saharan Africa from 2018, the World Health Organisation (WHO) has said.

The vaccine, known as RTS,S acts against Plasmodium falciparum , the parasite associated with the highest rates of malaria complications and deaths, and the most common in sub-Saharan Africa.

After a phase 3 trial last year showed that the vaccine reduced the risk of clinical malaria by around 30% in infants and children,1 two WHO expert advisory committees advised that it be tested before being recommended for widespread use.2

WHO will announce which three …
Adoptive Transfer of Natural Killer (NK) Cells to Prevent Gvhd and Enhance GVT Effects After Allogeneic Hematopoietic Cell Transplantation (HCT): The Timing of Donor NK Cell Infusions Critically Impacts Transplant Outcome.
Authors: Andreas Lundqvist, Hisayuki Yokoyama, Richard W. Childs
Journal: Blood (2009)
From Interface to Solution: Integrating Immunoassay with Netlike Rolling Circle Amplification for Ultrasensitive Detection of Tumor Biomarker
Authors: Chang Feng, Bing Bo, Xiaoxia Mao, Hai Shi, Xiaoli Zhu, Genxi Li
Journal: Theranostics (2016)

Both the 3D solution and the 2D interface play important roles in bioanalysis.For the former, reactions can be carried out adequately; while for the latter, interfering substance can be eliminated simply through wash.It is a challenge to integrate the advantages of solution-based assays and the interface-based assays.Here, we report an immuno-NRCA (netlike rolling circle amplification) strategy, which integrates immunoassay with NRCA for the ultrasensitive detection of tumor biomarker, by taking the assay of a tumour marker as an example.In this strategy, immunoreactions occur on interface, while the target-induced signal amplification can be completed totally in solution.As a result, this system has the merits of both solution-and interface-based assays.The whole procedure of this novel strategy is similar to the conventional ELISA, inheriting the usability.But in comparison with ELISA, the performance is greatly improved.The detection limit can be lowered to 5.5 fg/L, making it possible to detect the target tumour marker in one drop of blood.Also, in comparison with established immuno-PCR method, which integrates immunoassay with the commonly used nucleic acid amplification approach, this system has no requirement for thermal cycler owing to the isothermal amplification, and it has the ability to retain the immunoreactivities.So, the new immunoassay method proposed in this study may have more feasible applications in the future.
The Protein Tyrosine Phosphatase STS-1 Interacts with Bcr-Abl and Impairs the Response of Philadelphia-Positive Acute Lymphoblastic Leukemia (ALL) to Tyrosine Kinase Inhibitors
Authors: Marcus Liebermann, Daniela Hoeller, Susanne Badura, Tamara Tesanovic, Hubert Serve, Martin Ruthardt, Oliver G. Ottmann
Journal: Blood (2010)
Public attitudes towards research participation during an infectious disease pandemic: a qualitative study across four European countries
Authors: Nina Gobat, Micaela Gal, Christopher C Butler, Nicholas A Francis, Sibyl Anthierens, Hilde Bastiaens, Maciek Godycki-ćwirko, Anna Kowalczyk, Mariona Pons-Vigués, Enriqueta Pujol-Ribera, Anna Berenguera, Helen Stanton, Angela Watkins, Kerenza Hood, Ronnie Moore, Prasanth Sukumar, Steve A R Webb, Alistair Nichol
Journal: The Lancet (2016)
The BCL-2 Antagonist ABT-737 Is Highly Effective on Primary Acute Lymphoblastic Leukemia Cells.
Authors: Maria Rosaria Ricciardi, Chiara Gregorj, Fabiana De Cave, Paola Bergamo, Samantha Decandia, Sara Santinelli, Antonella Vitale, Maria Teresa Petrucci, Michele Milella, Robert Foa, Agostino Tafuri
Journal: Blood (2007)
Reversible Transplantable Chronic Phase CML-Like Disease in SCLtTA/BCR-ABL Transgenic Mice.
Authors: Mirle Schemionek, Jörg Stypmann, Sven Hermann, Christian Elling, Nicole Bäumer, Tilmann Spieker, Joachim R. Göthert, Martin Stehling, Claudia S. Huettner, Michael Schäfers, Daniel G. Tenen, Wolfgang E. Berdel, Tessa L. Holyoake, Carsten Müller-Tidow, Hubert Serve, Steffen Koschmieder
Journal: Blood (2007)
AB0668 Effects of Infliximab Treatment in Terms of Metabolic Parameters and Insulin Resistance in Ankylosing Spondylitis Patients
Authors: A. Cefle, D.T. Karadag, M. Bilen, S.Y. Sener, O.O. Isik, A. Yazici
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Risk of cardiovascular mortality is increased in patients with ankylosing spondylitis (AS). Chronic inflammation plays a crucial role in the development of accelerated atherosclerosis. TNFa is a pro-inflammatory cytokine which may be a key mediator in the pathophysiology of atherogenesis. This cytokine reduces the activity of insulin and causes insulin resistance (IR). <h3>Objectives</h3> We assessed the effect of infliximab treatment on insulin sensitivity and metabolic parameters in patients with AS. <h3>Methods</h3> In this prospective study, 20 consecutive AS patients (11 men and 9 women, mean age 39±10 and mean disease duration 12±7 years) fulfilling the modified 1984 New York criteria for AS were investigated. All patients were treated with iv infliximab (5 mg/kg, 0, 2, 6. week and ewery 8 weeks). A complete biochemical profile was obtained before and after 24 weeks of infliximab therapy (BASDAI, BASFI, ESR, CRP, hsCRP, lipid parameters, fasting glucose, insulin, HbA1C, waist circumference, weight, BMI, blood pressure). No patients were taking medications known to affect glucose, lipid metabolism and blood pressure. The Homoeostasis Model Assessment of Insulin Resistance Index (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) were used to measure IR. <h3>Results</h3> After 24 weeks of infliximab treatment there was no statistically significant difference in fasting glucose levels, fasting insulin, HOMA-IR, QUICKI, HbA1C and blood pressure. Weight (84±18 vs. 87±16, p=0.002), body-mass index (29±6 vs. 30±5, p=0.001), waist circumference (101±12 vs. 104±11, p=0.014) and LDL level (112±42 vs. 127±36, p=0.014) increased significantly from baseline. <h3>Conclusions</h3> Infliximab treatment caused an increase in weight, BMI, waist circumference and LDL level but no change in IR. Cytokines associated with inflammation reduce appetite. Amelioration of anorexia with anti-TNF therapy may explain these results. Further studies are needed to clarify the role of factors that contribute to accelerated atherosclerosis in AS. <h3>Disclosure of Interest</h3> None declared
Budesonide/formoterol maintenance and reliever therapy in adolescent patients with asthma
Authors: Carin Jorup, Dan Lythgoe, Hans Bisgaard
Journal: European Respiratory Journal (2018)

Asthma control is often suboptimal in adolescents, but few studies have evaluated asthma treatments in this population. This post hoc analysis assessed the efficacy and safety of budesonide/formoterol (BUD/FORM) maintenance and reliever therapy (MART) for treatment of persistent asthma in adolescent (age 12–17 years) subgroups within six randomised, double-blind trials. The primary end-point was time to first severe exacerbation. Secondary end-points included number of severe exacerbations, asthma-related symptoms, night-time awakenings, morning peak expiratory flow, forced expiratory volume in 1 s, as-needed medication use and five-item asthma control questionnaire scores. In adolescents (n=1847), BUD/FORM MART was similar to or more effective than comparators across each of the studies in reducing the risk of a first severe exacerbation (hazard ratios (HR) BUD/FORM MART versus comparators 0.15–1.01; pooled HR 0.49, 95% CI 0.34–0.70), with comparable outcomes to the adult subgroups (n=12 197). Similar treatment benefits for BUD/FORM MART were observed for secondary end-points. As-needed medication use was lower with BUD/FORM MART than comparators, and BUD/FORM as-needed use was lower in adolescents than adults. Treatment was well tolerated. This analysis supports the use of BUD/FORM MART in adolescents with persistent asthma, its efficacy and safety being consistent with that reported for adults.
Impact of Balanced or Unbalanced Karyotype At Diagnosis On Prognosis of CML: Long-Term Observation From 1346 Patients of the Randomized CML Study IV
Authors: Alice Fabarius, Claudia Haferlach, Andreas Hochhaus, Martin C. Müller, Benjamin Hanfstein, Gudrun Göhring, Brigitte Schlegelberger, Martine Jotterrand, Ulrike Proetel, Wolf-Karsten Hofmann, Stefan W. Krause, Hermann Einsele, Jolanta Dengler, Christiane Falge, Lothar Kanz, Andreas Neubauer, Michael Kneba, Frank Stegelmann, Michael Pfreundschuh, Cornelius F. Waller, Karsten Spiekermann, Michael Lauseker, Markus Pfirrmann, Joerg Hasford, Rüdiger Hehlmann, Susanne Saussele
Journal: Blood (2012)
Fludarabine, cytarabine and Idarubicin (FLAI-5) with or without Gemtuzumab Ozogamicin Is an Effective and Well Tolerated Regimen for Younger AML Patients: Real Life Data from a Single Center Register
Authors: Fabio Guolo, Paola Minetto, Giordana Pastori, Livia Giannoni, Nicoletta Colombo, Raffaella Grasso, Francesco Trovato, Marcella Bado, Filippo Ballerini, Marino Clavio, Barbara Rebesco, Maurizio Miglino, Andrea Bacigalupo, Marco Gobbi, Roberto Lemoli
Journal: Blood (2014)
Treatement of New Cases of Acute Promyelocytic Leukemia by Arsenic Trioxide Whitout ATRA +/− Chemotherapy and Long Term Follow up of Patients
Authors: Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Seyed Hamidolah Ghaffari, Shahrbano Rostami, Mohamad Jahani, Rohollah Hosseini, Massoud Iravani, Seyed Asadollah Mossavi, Ali Khodabandeh, Babak Bahar, Eissa Baybordi, Mehrangiz Tootonchi, Ezat Eini, Zahra Nasri Moghadam, Fakhri Afshar, Parvin Radsafa
Journal: Blood (2008)
AB0915 A Low-Penetrance NLRP3 Variant in A NOD2 Carrier Possibly Worsens The Phenotype of Blau Syndrome
Authors: P. Galozzi, P. Sfriso, D. Basso, A. Scanu, F. Oliviero, M. Plebani, L. Punzi
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Blau syndrome (BS) is a rare autosomal dominant autoinflammatory syndrome that primarily affects skin, joints, and eyes, with varying severity of inflammation, and results from mutations in the <i>NOD2</i> gene<sup>1</sup>. NOD2 bears highly conserved residues and structural similarities to the NLRP3 protein, a key component of the inflammasome which mutations underlie some autoinflammatory disorders, named cryopyrinopathies. <h3>Objectives</h3> This study assessed the potential contribution of <i>NLRP3</i> mutations to the inflammatory BS phenotype in an Italian affected family carrying p.E383K <i>NOD2</i> mutation (Fig. 1). <h3>Methods</h3> Genomic DNA was isolated from blood samples of the four affected family members and sequence analyses of <i>NLRP3</i> were performed by an ABI 3730XL DNA sequencer (Applied Biosystems). A genotype/phenotype correlation of the carriers of <i>NLRP3</i> variations was also assessed. To explain the differences in inflammatory phenotype severity, peripheral blood mononuclear cells (PBMC) were isolated from patients and healthy subjects and their ability to activate NF-κB and inflammasome pathways was measured by an array-based assay (reverse phase protein array). <h3>Results</h3> A heterozygous genetic variant of <i>NLRP3</i> was found only in the proband9s sample. The p.V198M mutation was known in literature as a low-penetrance mutation associated with cryopyrinopathies in symptomatic patients (Infevers database data). The proband with combined mutations presented the worsened BS phenotype (severe chronic bilateral uveitis with glaucoma, cataracts and visual impairment), whereas the three subjects with only p.E383K variant had a much milder disease. Concerning the activation of NF-κB pathway, all BS patients have raised levels of signalling key molecules (phosphorylated NF-κB p&lt;0.05; phosphorylated IkB-α p&lt;0.05) compared to the controls. However, the components of inflammasome pathway presented a pattern of activation related to individual patients rather than to the whole disease. Enhanced level of cleaved caspase-1, the key component of inflammasome, was noticed only in proband PBMCs (p=0.03), potentially promoted by the additional presence of p.V198M <i>NLRP3</i> mutation. <h3>Conclusions</h3> Our data strongly suggest that severe phenotype in BS may result from co-existence with mutations in genes associated with other autoinflammatory diseases, and are consistent with recently reported findings in hereditary periodic fever syndromes<sup>2</sup>. The synergistic effect of dual mutations can also explain the differential activation of the inflammatory pathways and may lead to appropriate targeted drug development. <h3>References</h3> Sfriso P, Autoimm Rev. 2012 Touitou I, J Med Genet. 2013 <h3>Disclosure of Interest</h3> None declared
SP0052 How To Treat/manage fibromyalgia
Authors: D.A. Williams
Journal: Annals of the Rheumatic Diseases (2016)

Fibromyalgia (FM) is often associated with profound suffering on the part of patients and can be quite challenging to the clinician to treat/manage. This talk will provide demographic information about FM as well as a brief summary of current research supporting putative peripheral and central nervous system mechanisms underpinning this condition. Multiple approaches have been used to diagnose FM and these methods will be reviewed and clarified for a clinical audience. Multi-modal treatment is considered optimal for the long-term management of FM and a variety of pharmacological as well as non-pharmacological options are available. This talk will review some of the evidence supporting these options and will describe how best to craft a logical treatment plan taking into account the needs of the individual patient. <h3>Disclosure of Interest</h3> D. Williams Consultant for: Health Focus, Inc.
BRM Promoter Polymorphisms and Survival of Advanced Non–Small Cell Lung Cancer Patients in the Princess Margaret Cohort and CCTG BR.24 Trial
Authors: Geoffrey Liu, Sinead Cuffe, Shermi Liang, Abul Kalam Azad, Lu Cheng, Yonathan Brhane, Xin Qiu, David W. Cescon, Jeffrey Bruce, Zhuo Chen, Dangxiao Cheng, Devalben Patel, Brandon C. Tse, Scott A. Laurie, Glenwood Goss, Natasha B. Leighl, Rayjean Hung, Penelope A. Bradbury, Lesley Seymour, Frances A. Shepherd, Ming Sound Tsao, Bingshu E. Chen, Wei Xu, David N. Reisman
Journal: Clinical Cancer Research (2016)

Abstract Introduction: BRM, a key catalytic subunit of the SWI/SNF chromatin remodeling complex, is a putative tumor susceptibility gene that is silenced in 15% of non–small cell lung cancer (NSCLC). Two novel BRM promoter polymorphisms (BRM-741 and BRM-1321) are associated with reversible epigenetic silencing of BRM protein expression. Experimental Design: Advanced NSCLC patients from the Princess Margaret (PM) cohort study and from the CCTG BR.24 clinical trial were genotyped for BRM promoter polymorphisms. Associations of BRM variants with survival were assessed using log-rank tests, the method of Kaplan and Meier, and Cox proportional hazards models. Promoter swap, luciferase assays, and chromatin immunoprecipitation (ChIP) experiments evaluated polymorphism function. In silico analysis of publicly available gene expression datasets with outcome were performed. Results: Carrying the homozygous variants of both polymorphisms (“double homozygotes”, DH) when compared with those carrying the double wild-type was associated with worse overall survival, with an adjusted hazard ratios (aHR) of 2.74 (95% CI, 1.9–4.0). This was confirmed in the BR.24 trial (aHR, 8.97; 95% CI, 3.3–18.5). Lower BRM gene expression (by RNA-Seq or microarray) was associated with worse outcome (P &amp;lt; 0.04). ChIP and promoter swap experiments confirmed binding of MEF2D and HDAC9 only to homozygotes of each polymorphism, associated with reduced promoter activity in the DH. Conclusions: Epigenetic regulatory molecules bind to two BRM promoter sequence variants but not to their wild-type sequences. These variants are associated with adverse overall and progression-free survival. Decreased BRM gene expression, seen with these variants, is also associated with worse overall survival. Clin Cancer Res; 23(10); 2460–70. ©2016 AACR.
P150 Perceptions of asthma control in the uk – a cross sectional study comparing patient and hcp perceptions of asthma control with validated act scores
Authors: A Menzies-Gow, G Chiu
Journal: Thorax (2016)

<h3></h3> Uncontrolled asthma is a major health problem. Personal perceptions of asthma control often vary between patients and their treating physicians, and both may differ from actual control. This can be a major barrier in optimising patient asthma care. The aim of this cross-sectional survey was to provide UK-specific data on actual and perceived asthma control in a sample of adult (18–75 years) asthma patients attending routine asthma reviews in primary, secondary and tertiary settings. Differences between healthcare professionals’ (HCP) and patients’ perceived assessments of asthma control were evaluated via an online questionnaire and compared to a control – the validated Asthma Control Test (ACT) questionnaire, which was completed by the patient. Patients with a documented diagnosis of asthma who were taking medication (at least a short acting ß-agonist) were enrolled and consented by their HCP within a month of their last clinic appointment. Individuals with a history of an asthma exacerbation within prior 4 weeks; a diagnosis of another respiratory condition; or a smoking history &gt;10 pack years were excluded. Patients were grouped into BTS/SIGN treatment Steps 1–5. 260 patients were screened. 234 patients were eligible for the study: 33, 52, 50, 49 and 50 patients in Steps 1 to 5, respectively. Women composed 70% (164) of the study population. 47.4% of patients were aged 45–64 years. 164 patients (70%) were classed as non-smokers by HCPs. The ACT results suggest that asthma was only controlled in 54.7% of patients overall (defined as ACT score ≥20), with levels of uncontrolled asthma highest in Step 4–5 patients. This is in contrast to 84.2% of patients and 73.9% of HCPs who perceived that asthma was controlled. These data suggest a high level of uncontrolled asthma in UK asthma patients, especially Step 4–5 patients. A significant proportion of both patients and HCPs may have an incorrect perception of asthma control, representing a significant unmet medical need in terms of optimal asthma management. Overall, correct correlation of ACT score with perception of controlled or uncontrolled asthma only occurred in 67.9% of patients and 68.8% of HCPs. The poorest correlations occurred in Step 4–5 patients.
Abstract 1844: Genome wide analysis of AR-cell cycle interplay reveals novel functions in cancer
Authors: Christopher McNair, Jonathan Goodwin, Michael Augello, Alfonso Urbanucci, Matthew Schiewer, Clay Comstock, Adam Ertel, Liguo Wang, Qianben Wang, Ian Mills, Wei Li, Jason Carroll, Karen Knudsen
Journal: Cancer Research (2015)

Abstract The androgen receptor (AR) plays a vital role in prostate cancer (PCa) due in part to its ability to interact with cell cycle components in order to drive cell cycle transition. Numerous points of cross-talk have been identified, wherein specific components of the cell cycle machinery “feed back” to modulate AR function, and these interactions are thought to be altered in human malignancies. Despite these observations, the majority of genome wide analyses for AR have been performed in cells that have exited cell cycle (G0). Here, the cell cycle dependent AR transcriptome and cistrome was identified, revealing new and unexpected functions for AR in cycling tumor cells. In studies to be discussed, cells were arrested in 5 distinct phases of the cell cycle, stimulated with androgen, and AR activity assessed through gene expression and ChIP-Seq analyses. In AR binding analyses, significant overlap was seen with previously identified sites, but were accompanied by novel binding events that could be segregated into those that are specific to cycling cells and occur in all phases (“cell cycle common”) or show cell cycle stage specific binding (“phase exclusive”). Over 50% of the cell cycle common sites, and up to 95% of the phases exclusive sites were novel AR occupied sites. Additionally, using a “guilty by association” approach to determine potentially AR regulated genes from this novel cistromic data, it was determined that close to 50% of cell cycle common, and 70% of phase exclusive binding uncover novel candidates for AR regulation. Cistrome data was therefore overlaid with microarray data, to prioritize discovery of meaningful, cell cycle specific AR binding events. Analyses to be discussed reveal striking new insight into disease relevant AR function. In sum, these data rigorously demonstrate that AR acts in a cell cycle dependent manner, and that these functions of AR have a major impact on tumor cell phenotypes. Citation Format: Christopher McNair, Jonathan Goodwin, Michael Augello, Alfonso Urbanucci, Matthew Schiewer, Clay Comstock, Adam Ertel, Liguo Wang, Qianben Wang, Ian Mills, Wei Li, Jason Carroll, Karen Knudsen. Genome wide analysis of AR-cell cycle interplay reveals novel functions in cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1844. doi:10.1158/1538-7445.AM2015-1844
Highly Purified Hematopoietic Stem Cell Can Generate Cardiomyocytes Via Myeloid Progenitors through Cell Fusion.
Authors: Mitsuhiro Fukata, Fumihiko Ishikawa, Hideki Shimazu, Ryu Nakamura, Kazuya Shimoda, Koichi Akashi, Shultz D. Leonard, Mine Harada
Journal: Blood (2006)
Transplantation of Human Peripheral Blood CD34-Positive Cells in Combination with Ex Vivo Expanded Megakaryocytes Results in Fast Platelet Formation in NOD/SCID Mice.
Authors: Marloes R. Tijssen, Paula B. Van Hennik, Franca Di Summa, Peter L. Hordijk, Jaap Jan Zwaginga, C. Ellen Van der Schoot, Carlijn Voermans
Journal: Blood (2006)
PreSERVE-AMI
Authors: Arshed A. Quyyumi, Alejandro Vasquez, Dean J. Kereiakes, Marc Klapholz, Gary L. Schaer, Ahmed Abdel-Latif, Stephen Frohwein, Timothy D. Henry, Richard A. Schatz, Nabil Dib, Catalin Toma, Charles J. Davidson, Gregory W. Barsness, David M. Shavelle, Martin Cohen, Joseph Poole, Thomas Moss, Pamela Hyde, Anna Maria Kanakaraj, Vitaly Druker, Amy Chung, Candice Junge, Robert A. Preti, Robin L. Smith, David J. Mazzo, Andrew Pecora, Douglas W. Losordo
Journal: Circulation Research (2016)

Despite direct immediate intervention and therapy, ST-segment-elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death.