tbuckley/cabot-search huggingface dataset:
PB1765 CHARACTERISTICS OF ERYTHROLEUKEMIA ABOUT 10 CASES WITH REVIEW OF THE LITERATURE
Authors: T.F. Talbi, M.R. abbadi, Y. ghassoul, M. djilali, K. belateche, L. bouteldja, S. menouer, F.Z. ardjoun, S. belakhel, K. djouadi
Journal: HemaSphere (2019)

Background: Acute erythroblastic leukemia (AML‐M6) is a rare entity, accounting for 3‐4% of all LAs. There are two types: erythroleukemia and pure erythroid leukemia. It is most often manifested by signs of cytopenia and infiltration of extrahematopoietic tissues, and is more common in adults than in children with a poor prognosis. Aims: The objective of this study is to describe the clinical, biological and evolutionary aspects of erytholeukemia in a monocentric retrospective study. Methods: the diagnosis is based on a cytological examination of the blood smear (FS) and medullary (PMO) as well as the immunophenotypic examination. We calculated overall survival by Kaplan Meier method Results: n = 181 (evaluable), n = 10 patients with AML6 according to the FAB classification (5%). • The cytological study of FS and PMO + CMF results led to the diagnosis of erythroleukemia in 08 of our patients and pure erythroid leukemia in 2 patients. Mean age = 47 ± 21.77 years [0‐64]. Sex ratio = 1.5 (6H / 4F). Duration: 40 ± 35 days [01‐90]. Symptoms of bone marrow failure: PCM (100%), hemorrhagic syndrome: 3 cases (30%), infection: 04 cases (40%), splenomegaly: 04 cases (30%), mean WB = 84,300 ± 11.260 giga / l [125.000‐83.400], peripheral blast level (avg = 26 ± 23% [1‐65]), medullary blasts = average 49.5 ± 19% (08‐93) • mean hemoglobin level = 8.06 ± 1.09 g / dl [5‐10], platelets: 21‐151giga / l (avg: 65,900 ± 47,450 / mm3) n = 03 patients had severe thrombocytopenia at 13‐21‐39 giga / respectively (30%), pancytopenia found in n = 05 cases (50%), LDH level (mean) = 905 ± 896 IU / L [12‐2,900], n = 02 patients had 1 metabolic complication at diagnosis (hyperkalemia, hyponatremia). n = 8 patients received induction CT (3 + 7), n = 01 patient received only 2 aracytin‐associated antracycline injections. Newborn LAM, the newborn clinically presents: cutaneous and mucosal paleness and hepatosplenomegaly, on the biological plane: GB: 125giga / l, (EB = 64%, blast = 3%), HB = 10 g / dl, PLQ = 13gigal / l, PMO: infiltration by 68% of dystrophic EB, 08% of MB, the newborn t under aseptic vacuum The specific treatment has not yet been started. The complete remission is obtained (n = 04 cases (40%)) and n = 03 failures (30%), n = 01patient came out against medical advice; one induction death is listed (acute cardiac toxicity) • Overall survival = 27% (fig1) Summary/Conclusion: our data are similar to those of the literature: rare pathologic LAM6 (3‐5 / series, 05% in ours), exceptional in children. The signs of bone marrow failure are almost constant, 1 pancytopenia in 50%. Splenomegaly is found in 1/3 of the cases. The prognosis is reserved (overall survival = 25% at 05 years) from wherethe value of rapid diagnosis and adequate management image
Beyond Stability Constraints: A Biophysical Model of Enzyme Evolution with Selection on Stability and Activity
Authors: Julian Echave
Journal: Molecular Biology and Evolution (2018)

The rate of evolution varies among sites within proteins. In enzymes, two rate gradients are observed: rate decreases with increasing local packing and it increases with increasing distance from catalytic residues. The rate-packing gradient would be mainly due to stability constraints and is well reproduced by biophysical models with selection for protein stability. However, stability constraints are unlikely to account for the rate-distance gradient. Here, to explore the mechanistic underpinnings of the rate gradients observed in enzymes, I propose a stability-activity model of enzyme evolution, MSA. This model is based on a two-dimensional fitness function that depends on stability, quantified by ΔG, the enzyme's folding free energy, and activity, quantified by ΔG*, the activation energy barrier of the enzymatic reaction. I test MSA on a diverse data set of enzymes, comparing it with two simpler models: MS, which depends only on ΔG, and MA, which depends only on ΔG*. I found that MSA clearly outperforms both MS and MA and it accounts for both the rate-packing and rate-distance gradients. Thus, MSA captures the distribution of stability and activity constraints within enzymes, explaining the resulting patterns of rate variation among sites.
PB2450 DYE‐LIGAND CHROMATOGRAPHY AS AN ALTERNATIVE METHOD FOR OBTAINING THE FACTORS VIII/VON WILLEBRAND COMPLEX
Authors: N. Shurko, T. Danysh, V. Novak
Journal: HemaSphere (2019)

Background: A new dye‐ligand chromatographic procedure has been developed to produce a highly purified factors VIII/von Willebrand complex (FVIII/vWF) concentrate from plasma cryoprecipitate. Factor VIII (FVIII) and von Willebrand factor (vWF) circulate in the plasma as a non‐covalent protein complex FVIII/vWF. The levels of factor VIII in vivo are coordinately regulated with levels of vWF. Willebrand's disease together with hemophilia A are the most common heredity diseases of the hemostasis system. The concentrate of FVIII/vWF complex is used for the treatment of these diseases. The main method of obtaining of plasma concentrates of FVIII/vWF complex remains the method of ion‐exchange chromatography. With the use of ion exchange chromatography it is not possible to maintain the initial ratio because the elution of these two factors from the ion exchanger occurs at different ionic strength values. That is, the ion‐exchange chromatography method does not allow for the absolute yield of vWF together with FVIII. Aims: investigate the ratio of FVIII/vWF complex at various stages of the technology opurification of antihemophilic concentrate. Methods: Cryoprecipitation, ion‐exchange chromatography on DEAE‐Sepharose FAST FLOW; dye‐ligand affinity chromatography. Results: We development of a new method to obtain purified preparation of the complex FVIII/vWF, that inclused cryoprecipitation, ion‐exchange chromatography on DEAE‐Sepharose FAST FLOW and dye‐ligand affinity chromatography. The degree purification of FVIII was 95.3 times on the stage of ion‐exchange chromatography. The ratio FVIII/vWF has changed approximately twice (from 0.78 to 1.75) (Table 1). We used a buffer NaCl with an ionic strength of 0.3 M for co‐elution of FVIII and vWF. However, part of the vWF was eluted with the first fractions (0.15 M NaCl). The research demonstrated that the process of purification of the FVIII and vWF with dye‐ligand is due to the phenomenon of the negative affinity adsorption. This property we used in the technology of obtaining of FVIII/vWF complex. This property provides the output level of the relationship this provides the output level of the relationship (Table 1). Summary/Conclusion: It was established that at the stage of dye‐ligand chromatography, the loss from the initial activity of FVIII is practically absent and the original ratio of FVIII/vWF is saved. image
Vaccine safety: British are less sceptical than Europeans, but younger people need assurance
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The UK cannot afford to be complacent about vaccination rates despite higher public confidence in their safety than in many other European nations, global experts have warned.

Just under half of people surveyed in the UK (46%) strongly agreed that vaccines were safe. While this was significantly higher than in the rest of Europe (40%), it was some way below the global average of 61%, in a survey of more than 140 000 people in over 140 countries.1

Data from the Wellcome Global Monitor, the first global survey of its kind from the Wellcome Trust and the polling company Gallup, showed high overall global trust in doctors, nurses, and scientists, as well …
THU0541 ANTI-VACCINE ANTIBODY LEVELS IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS: PRELIMINARY DATA IN 90 PATIENTS
Authors: Natalia Lubimova, Olga Goleva, Irina Fridman, Lubov Sorokina, Rena Idrisova, Susanna Kharit, Mikhail Kostik
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Patients with juvenile idiopathic arthritis (JIA) may have lower protective levels of anti-vaccine antibodies (AVA) due to high inflammatory activity, interrupted or incomplete vaccination schedule, using of immune-modulating drugs, e.g. systemic corticosteroids (CS), methotrexate (MTX) and biologics [1]. <h3>Objectives</h3> The aim of our study was to evaluate levels of AVA in the patients with JIA. <h3>Methods</h3> We included data about 90 JIA (26 M and 64 F) aged from 2 to 17 years, who received scheduled vaccination before the age of 2 years and before JIA onset. In all patients the Ig G anti-measles (AM), anti-parotitis (AP), anti-hepatitis B (AHB), anti-diphtheria (AD) and anti-rubella (AR) AVA levels were detected with ELISA. In each patient we evaluate the type of the JIA (oligoarthritis – OA (n=38), polyarthritis – PA (n=36), systemic-SA (n=7) and enthesitis-related arthritis – ERA (n=10), routine disease activity and treatment. In healthy controls were measured anti-measles (n=40) and anti-parotitis (n=30) antibodies (AB) for comparison with JIA. <h3>Results</h3> The main demographic characteristics: age of inclusion in the study 11 (8-15) years, disease onset–6 (4-8) years, JIA duration–4 (2-7) years. The AM AB in JIA patients were 0.2 (0.0-0.5) IU/ml and in HC 0.3 (0.2-1.1) IU/ml (p=0.00002), despite the higher age of JIA patients than HC (p=0.0000001); AP AB were 2.6 (1.0-5.1) IU/ml vs 1.1 (0.0-4.9) IU/ml in JIA and HC, respectively (p=0.08). Protective levels of AM AB was detected in 50% of all JIA population, vs. HC – 87.5% (p=0.00005), AP–67.7% vs. 60% in HC (p=0.076), AHB – 54.4%, AD–50%, AR–97.8%. The main data related to vaccination status in the table. We have found correlation between JIA duration and levels AM AB (r=-0.27, p=0.015), AP AB (r=-0.22, p=0.039), AD AB (r=-0.27, p=0.015); MTX treatment with AM AB (r=-0.37, p=0.001), and AD AB (r=-0.29, p=0.007); treatment with biologics and AM AB (r=-0.25, p=0.018), and using more than one biologics with AR AB (r=-0.27, p=0.047). In the regression model only MTX had a negative impact on AM (r=-0.001) and AD AB level (p=0.01). <h3>Conclusion</h3> Children with JIA are in the risk of decreased level of AVA, especially in measles, diphtheria and parotitis. The measurements of AVA in the individual JIA vaccination schedule required. <h3>References</h3> [1] Toplak N, Avčin T. Long-term safety and efficacy of varicella vaccination in children with juvenile idiopathic arthritis treated with biologic therapy. Vaccine. 2015; 33(33):4056-9. <h3>Disclosure of Interests</h3> None declared
SP0164 ANA DIAGNOSTIC AND ANTIPHOSPHOLIPID SYNDROME (APS) AS INHERITED COAGULATION DISORDER
Authors: Thomas Dörner
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Use of ANA diagnostic is key for systemic autoimmune diseases. ANA is an overarching term and the underlying specificities are important for defined diagnosis of SLE, Sjögren"s, systemic sclerosis etc. Diagnostic algorithms of ANA and new semi-automated procedures are discussed in the context of case discussions. Subsequently, the value and limitations of the diagnostics of lupus anticoagulant and antiphospholipid antibodies as key serologic findings in antiphospholipid syndrome are discussed in the context of instructive cases. <h3>Disclosure of Interests:</h3> Thomas Dörner Grant/research support from: Eli Lilly, Janssen, Roche, UCB Pharma, Consultant for: Eli Lilly, Janssen, Roche, UCB Pharma, Speakers bureau: Eli Lilly, Janssen
AB1034 NO DIFFERENCES IN HEPATITIS B ANTIBODY POSITIVITY IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS ON BIOLOGICAL THERAPY
Authors: CICEK SUMEYRA OZDEMIR, Nihal Sahin, Aysenur Pac Kisaarslan, Meda Kondolot, Zubeyde Gunduz, Muammer Hakan Poyrazoglu, Ruhan DüŞünsel
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Biologic disease-modifying antirheumatic drugs (DMARDs) are frequently used in the treatment of juvenile idiopathic arthritis (JIA) resistant to nonbiologic DMARDs recently. There is a concern for their reducing the effectiveness of vaccines due to immunosuppresive effects. <h3>Objectives</h3> To evaluate hepatitis B antibody (anti-HBs) positivity and antibody titers between JIA patients on biologic DMARDs therapy and healthy conrols. <h3>Methods</h3> Anti-HBs antibody positivity and titers were compared between 88 patients with JIA on biologic DMARDs therapy followed in our clinic and 91 healthy controls aged 2-19 years. All participants were vaccinated according to the routine vaccination schedule in our country. <h3>Results</h3> Eighty-eight JIA patients included and fifty five (62,5%) patients were female. The median age of patients was 13,31 (4,07-18,08) years. The JIA subtypes were systemic JIA (10,2%), oligoarticular JIA (33%), poliarticular JIA (25%), entesitis related arthritis (26,1%), psoriatic JIA (3,4%), and undifferantiated JIA (2,3%). The median duration of biologic DMARDs was 31,995 (1,33-115) months. 54 patients were treated only with one anti-TNF (34 etanercept, 17 adalimumab), 16 patients were treated more than one TNF-alfa inhibitor. 18 patients were treated with more than one different group biologic DMARDs, and 7 of them had more than two biologic DMARD due to disease activity. Anti-HBs positivity was 67% in the JIA group and 54,9% in the control group, and no significant difference detected between the two groups (p=0,097). The anti-HBs titer was 12,95 (min-max: 2-1000) in the controls and 22,44 (2-1000) in the biological DMARDs. <h3>Conclusion</h3> Patients with JIA on biologic DMARDs had not lower anti-HBs positivity than healthy controls in our study. Further studies are required to understand the effects of biologic DMARDs on protective anti-HBs antibody levels. <h3>Disclosure of Interests</h3> None declared
Abstract 20060: miR-155 a Possible Mediator of Acute Oscillatory Shear Stress (OSS)-Induced Oxidative Stress, Inflammation & Vascular Dysfunction
Authors: Islam Mohamed, Sheena Thomas, Kimberly Rooney, Roy Sutliff, Nick Willett, Charles Searles
Journal: Circulation (2016)

Introduction: Shear stress forces play an integral role in dictating the endothelial cell (EC) response to changes in blood flow, induction of pro-inflammatory and oxidative stress and hence develo...
Abstract 13141: Cellular Microrna 449b Upregulation Sensitizes Ischemia/reperfusion Injury via Inhibition of Nrf-1, Increasing Ros Production and Apoptosis in the Diabetic Heart
Authors: Hang Wang, Wayne Lau, Erhe Gao, Walter Koch, Xin Ma, Yajing Wang
Journal: Circulation (2015)

Myocardial ischemic/reperfusion (MI/R) injury is significantly enhanced in diabetes by incompletely understood mechanisms. Recent clinical and experimental studies demonstrate that hypoadiponectinemia during diabetes enhances oxidative stress and exaggerates MI/R injury. However, molecular mechanisms responsible for hypoadiponectinemia-induced oxidative stress remain unknown. In a discovery-driven fashion, we determined the role of cardiac microRNAs in the MI/R response in adiponectin knockout (APNKO) mice. From 68 total miRNAs differentially expressed between APNKO and wild type (WT) mice, miRNA 449b was identified as the microRNA most relevant to oxidative stress and apoptosis. In cultured neonatal cardiomyocytes, miRNA 449b silencing inhibited hypoxia/reoxygenation-induced apoptosis, whereas miR-449b overexpression significantly increased oxidative stress and cardiomyocyte apoptosis. In APNKO mice, administration of anti-miR-449b decreased oxidative stress (-17.2±3.8%, p&lt;0.05), reduced caspase-3 activity (-21.3±4.2%, p&lt;0.05), attenuated myocardial apoptosis (-16.3±4.1%, p&lt;0.05), and improved myocardial function (1.4±0.3 fold). To identify the downstream molecule regulated by miRNA 449b, we integrated transcriptomics and proteomics data with computational annotation data, and identified Nrf-1 as a miRNA 449b target. A luciferase reporter gene assay demonstrated that miRNA 449b inhibited Nrf-1 expression via Nrf-1 mRNA 3’UTR region binding. Finally, we demonstrated that miRNA 449b was significantly upregulated, Nrf-1 expression was significantly decreased, and the anti-oxidative molecule metallothionein (MT) was significantly inhibited in the diabetic heart subjected to MI/R. Administration of anti-miR-449b in diabetic animals upregulated Nrf-1 and MT expression, reduced oxidative stress, and improved cardiac function (P&lt;0.01) after MI/R. Taken together, this study provides the first evidence that hypoadiponectinemia during diabetes causes cardiac miRNA-449b upregulation and subsequent downregulation of Nrf-1 and MT, thus enhancing oxidative stress and MI/R injury. MicroRNA 449b may represent a potential therapeutic target against diabetic heart disease.
Impact of transposable elements on genome structure and evolution in bread wheat
Authors: Thomas Wicker, Heidrun Gundlach, Manuel Spannagl, Cristobal Uauy, Philippa Borrill, Ricardo H. Ramírez-González, Romain De Oliveira, Klaus F. X. Mayer, Etienne Paux, Frédéric Choulet
Journal: Genome biology (2018)

Transposable elements (TEs) are major components of large plant genomes and main drivers of genome evolution. The most recent assembly of hexaploid bread wheat recovered the highly repetitive TE space in an almost complete chromosomal context and enabled a detailed view into the dynamics of TEs in the A, B, and D subgenomes. The overall TE content is very similar between the A, B, and D subgenomes, although we find no evidence for bursts of TE amplification after the polyploidization events. Despite the near-complete turnover of TEs since the subgenome lineages diverged from a common ancestor, 76% of TE families are still present in similar proportions in each subgenome. Moreover, spacing between syntenic genes is also conserved, even though syntenic TEs have been replaced by new insertions over time, suggesting that distances between genes, but not sequences, are under evolutionary constraints. The TE composition of the immediate gene vicinity differs from the core intergenic regions. We find the same TE families to be enriched or depleted near genes in all three subgenomes. Evaluations at the subfamily level of timed long terminal repeat-retrotransposon insertions highlight the independent evolution of the diploid A, B, and D lineages before polyploidization and cases of concerted proliferation in the AB tetraploid. Even though the intergenic space is changed by the TE turnover, an unexpected preservation is observed between the A, B, and D subgenomes for features like TE family proportions, gene spacing, and TE enrichment near genes.
Loss of PTEN Accelerates NKX3.1 Degradation to Promote Prostate Cancer Progression
Authors: Cai Bowen, Michael C. Ostrowski, Gustavo Leone, Edward P. Gelmann
Journal: Cancer Research (2019)

NKX3.1 is the most commonly deleted gene in prostate cancer and a gatekeeper suppressor. NKX3.1 is a growth suppressor, mediator of apoptosis, inducer of antioxidants, and enhancer of DNA repair. PTEN is a ubiquitous tumor suppressor that is often decreased in prostate cancer during tumor progression. Steady-state turnover of NKX3.1 is mediated by DYRK1B phosphorylation at NKX3.1 serine 185 that leads to polyubiquitination and proteasomal degradation. In this study, we show PTEN is an NKX3.1 phosphatase that protects NKX3.1 from degradation. PTEN specifically opposed phosphorylation at NKX3.1(S185) and prolonged NKX3.1 half-life. PTEN and NKX3.1 interacted primarily in the nucleus as loss of PTEN nuclear localization abrogated its ability to bind to and protect NKX3.1 from degradation. The effect of PTEN on NKX3.1 was mediated via rapid enzyme-substrate interaction. An effect of PTEN on Nkx3.1 gene transcription was seen in vitro, but not in vivo. In gene-targeted mice, Nkx3.1 expression significantly diminished shortly after loss of Pten expression in the prostate. Nkx3.1 loss primarily increased prostate epithelial cell proliferation in vivo. In these mice, Nkx3.1 mRNA was not affected by Pten expression. Thus, the prostate cancer suppressors PTEN and NKX3.1 interact and loss of PTEN is responsible, at least in part, for progressive loss of NKX3.1 that occurs during tumor progression. SIGNIFICANCE: PTEN functions as a phosphatase of NKX3.1, a gatekeeper suppressor of prostate cancer.
Bawa-Garba: legal advice to GMC was incorrect, chief executive acknowledges
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The head of the UK General Medical Council has acknowledged that the legal advice the regulator received during the Hadiza Bawa-Garba case was incorrect.

In an interview for a BBC documentary the GMC’s chief executive, Charlie Massey, said that if the same case arose now he would not have appealed the June 2017 tribunal verdict that decided to suspend Bawa-Garba but not to strike her off after the death …
AB0302 INTEREST OF THE SYSTEMATIC ELECTROCARDIOGRAM IN THE DETECTION OF CARDIAC INVOLVEMENT DURING SPONDYLOARTHROPATHIES AND RHEUMATOID ARTHRITIS
Authors: cédric Régis BOUMBA MAKAYA, Imane El Bouchti
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Cardiovascular risk is not uncommon in patients with chronic inflammatory rheumatism. <h3>Objectives</h3> The objective: To evaluate the interest of systematic electrocardiogram (ECG) as a tool for detecting cardiac abnormalities during spondyloarthropathies (SA) and rheumatoid arthritis (SA). <h3>Methods</h3> Consecutive patients suffering from SA, RA, hospitalized during the period from 2016 to 2017 and free from cardiovascular events were included. An ECG - 12-lead - was performed and interpreted by a cardiologist without the diagnosis. <h3>Results</h3> A total of 44 patients with SA were included (average duration 9 ± 8 years), 56 patients with RA (average duration 11 ± nine years). They were all asymptomatic on the cardiac level and without a cardiovascular history. The population was homogeneous, concerning the presence of the cardiovascular risk factors, except for the diabetes, more frequent in the RA groups. The proportions of extra systoles, atrioventricular blocks (2.2% in the SA group, 1.4% in the RA group), complete or incomplete left branch block (respectively: 0.7%, 0.6%), complete right limb block or left branch block (respectively: 0.8%, 2.7%) and abnormality suggestive of myocardial ischemia (5.2%, 10.8%) <h3>Conclusion</h3> In patients with no history of cardiovascular disease who are asymptomatic, performing a systematic ECG does not reveal the increased risk of specific cardiac complications related to these conditions in patients with SA and RA. <h3>References</h3> [1] Danesh J, Whincup P, Walker M, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ2000;321:199–204. [2] Bulkley BH, Roberts WC. Ankylosing spondylitis and aortic regurgitation. Circulation 1973;48:1014–27: [3] Nitter Hauge S, Otterstad JE. Characteristics of atrioventricular conduction disturbances in ankylosing spondylitis. Acta Med Scand 1981;210:197–200. [4] Brunner F, Kunz A, Weber U, et al. Ankylosing spondylitis and heart abnormalities. Clin Rheumatol 2006;25:24–9. [5] Yildirir A, Aksoyek S, Calguneri M, et al. QT dispersion as a predictor ofarrhythmic events in patients with ankylosing spondylitis. Rheumatology 2000;39:875–9 <h3>Disclosure of Interests</h3> None declared