tbuckley/cabot-search huggingface dataset:
PF621 REAL WORLD EXPERIENCE IN THE MANAGEMENT OF WALDENSTRÖM'S MACROGLOBULINAEMIA FROM ANALYSIS OF THE RORY MORRISON REGISTRY
Authors: J. Bomsztyk, S. D'Sa, H. McCarthy, D. El‐Sharkawi, H. Scorer, J. Kothari, G. Pratt, K. Cuthill, C. Kyriakou
Journal: HemaSphere (2019)

Background: Waldenström's Macroglobulinaemia (WM) is characterised by the presence of an IgM paraprotein and bone marrow infiltration by lymphoplasmacytic lymphoma (Owen et al. 2003); patients present in a variable manner (Castillo et al 2016). A variety of treatments are used at front line and relapse. Current guidelines advocate chemoimmunotherapy in both settings (Owen et al. 2014). Novel agents are also effective spurred on by biological discoveries, including the somatic mutations in MYD88 and CXCR4 genes, but their precise role remains to be determined. Ibrutinib became available in the UK in 2017 via the Cancer Drugs Fund (CDF) for WM in the relapsed setting (NICE TA491). Aims: To describe the natural history of WM, monitor usage and impact of treatments including emerging therapies on outcomes in the UK Methods: The Rory Morrison Registry (RMR) collects data from existing and new patients with WM &amp; related conditions from (so far) 14 centres across the UK using entry on to a web‐based platform. 701 patients are registered including 560 with a confirmed WM diagnosis. We describe treatment trends from across the UK at front line and first relapse. To facilitate analysis, we grouped the regimens. Results: 383 patients have received front line therapy with at least 29 different regimens since 1984, and 215 second line therapy with at least 32 different regimens. The most common categories were DRC (90 patients; 23%), Alkylator based (75, 20%), R‐Bendamustine (50; 13%) and CHOP‐based (42; 11%), Other (37, 10%), Purine analogue (PA)‐based therapy (35; 9%), Rituximab monotherapy (R‐mono) (34, 9%), Bortezomib‐based (17; 4%) and BTK inhibitors (3, 1%). The use of each treatment has noticeably changed over time (See graph). The peak treatment choices in the early 2000 s were Alkylator‐ or CHOP‐based therapies. This has been superseded by DRC (since 2007) and R‐Bendamustine (since 2011). There has been a stable role for R‐mono and PA‐based therapy. Regimens used at first relapse have been highly variable till 2017 when Ibrutinib became available. Treatments from 209 patients at first relapse since 1984 show that the most common category was ‘Other’ (52; 25%), followed by BTK Inhibitors (41; 21%), R‐mono (including maintenance rituximab) (22; 11%), Alkylator‐based (21; 10%), PA‐based (19; 9%), DRC (19, 9%), Bendamustine‐based (17, 8%), CHOP‐based (13; 6%) and Bortezomib‐based (5; 2%). Notably, since 2017, of the 58 patients having 2 nd line therapy 34 (58%) received BTK inhibitors. Summary/Conclusion: Observations from the Rory Morrison Registry demonstrate the evolving trends in WM treatment in the UK, including the emergence of DRC and R‐Bendamustine as standard frontline therapy and a preference for BTK inhibition as 2 nd line therapy, since their availability. Further analysis is planned to assess the ‘real world’ impact of the emerging treatments. image
Abstract 20276: Local Brain Atrophy in Parahippocampal Gyrus is Prominent in Insomniac Senile Heart Failure Patients Without Dementia
Authors: Tomomi Meguro, Yuko Meguro, Toshio Nagai
Journal: Circulation (2017)

Introduction: Heart failure (HF) patients with insomnia may have potential risk of cognitive impairment (CI) that attenuates the effect of treatment. Patients with CI have progressive local brain a...
Abstract 15514: Comparison of Mortality With Rotating Cutting Sheaths Versus Laser Sheaths for Transvenous Lead Extraction
Authors: Celso L Diaz, Xiaofan Guo, Isaac R Whitman, Gregory M Marcus, Cara N Pellegrini, Ramin E Beygui, Byron K Lee
Journal: Circulation (2017)

Introduction: Rotating cutting sheaths and laser sheaths are commonly used for transvenous lead extraction of cardiac implantable electronic devices. The difference in mortality associated with eac...
Abstract 13637: Depressive Symptoms, Antidepressants and Baroreflex Sensitivity. The Paris Prospective Study III
Authors: Jean-philippe Empana, Christof Prugger, Frederique Thomas, Catherine Guibout, Luca Zanolli, Bruno Pannier, Pierre Boutouyrie, Xavier Jouven
Journal: Circulation (2013)

Background: While depressive symptoms have been consistently associated with an increased risk of cardiovascular disease, the underlying mechanisms are unclear. Aims: To assess at the population le...
Comprehensive benchmarking and ensemble approaches for metagenomic classifiers
Authors: Alexa B. R. McIntyre, Rachid Ounit, Ebrahim Afshinnekoo, Robert J. Prill, Elizabeth Hénaff, Noah Alexander, Samuel S. Minot, David Danko, Jonathan Foox, Sofia Ahsanuddin, Scott Tighe, Nur A. Hasan, Poorani Subramanian, Kelly Moffat, Shawn Levy, Stefano Lonardi, Nick Greenfield, Rita R. Colwell, Gail L. Rosen, Christopher E. Mason
Journal: Genome biology (2017)

One of the main challenges in metagenomics is the identification of microorganisms in clinical and environmental samples. While an extensive and heterogeneous set of computational tools is available to classify microorganisms using whole-genome shotgun sequencing data, comprehensive comparisons of these methods are limited. In this study, we use the largest-to-date set of laboratory-generated and simulated controls across 846 species to evaluate the performance of 11 metagenomic classifiers. Tools were characterized on the basis of their ability to identify taxa at the genus, species, and strain levels, quantify relative abundances of taxa, and classify individual reads to the species level. Strikingly, the number of species identified by the 11 tools can differ by over three orders of magnitude on the same datasets. Various strategies can ameliorate taxonomic misclassification, including abundance filtering, ensemble approaches, and tool intersection. Nevertheless, these strategies were often insufficient to completely eliminate false positives from environmental samples, which are especially important where they concern medically relevant species. Overall, pairing tools with different classification strategies (k-mer, alignment, marker) can combine their respective advantages. This study provides positive and negative controls, titrated standards, and a guide for selecting tools for metagenomic analyses by comparing ranges of precision, accuracy, and recall. We show that proper experimental design and analysis parameters can reduce false positives, provide greater resolution of species in complex metagenomic samples, and improve the interpretation of results.
PB1647 EXPRESSION OF PHOSPHORYLATED AKT AND CLASS I PI3K ISOFORMS IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: M. Lourou, E. Papakonstanti, E. Yachnakis, E. Stiakaki
Journal: HemaSphere (2019)

Background : Acute lymphoblastic leukemia (ALL) is the most common neoplastic disease in children and represents 30% of all childhood malignancies. Although more than 80% of ALL cases are long term survivors, there is still a percentage of resistant or relapsed disease. The identification of genes and molecular pathways that are involved is crucial for targeted therapy design. The intracellular signaling pathway PI3K/AKT gets induced by growth factors and plays an important role in triggering many biological processes of the cell such as cell growth, metabolism, proliferation, survival, metabolism of insulin, protein synthesis and apoptosis. Recently it has been found that changes in the expression and mutations in many molecules of that pathway are involved in tumor genesis, which makes them an attractive target for cancer therapy. Aims: The study of the expression of the P110β, P110δ and P-Akt proteins in leukemic blasts of bone marrow from children with ALL at diagnosis and lymphomononuclear cells from children in remission, compared to the expression in lymphomononuclear cells from bone marrow of children with solid tumors without marrow involvement. Methods: Bone marrow mononuclear cells from 31 children with ALL at diagnosis, 25 children with ALL in remission and 20 children with solid tumors without bone marrow involvement was collected. Proteins were extracted and were analyzed with Western blot. The detection of P-Akt, P110β and P110δ was done with Thermo Scientific™ Pierce™ ECL Western Blotting Substrate,.The analysis of the results was performed with Image Lab and the statistical analysis with IBM SPSS Statistics version 25 (Kruskal-Wallis test and Mann-Whitney test). Results: The expression level of P-Akt in ALL diagnosis was significantly lower compared with ALL in remission (0.66 ± 0.21 vs 1.97 ± 0.41, p = 0.004) as well as with the solid tumors without bone marrow involvement (0.66 ± 0.21 vs 1.03 ± 0.25, p = 0.019). Additionally, the expression of P110δ estimated significantly lower in ALL diagnosis compared with ALL remission (0.92 ± 0.37 vs 1.52 ± 0.41, p = 0.012). On the other hand, there was no statistically significant difference of P110β expression values between ALL diagnosis, remission and solid tumors. Summary/Conclusion: P-Akt and P110δ expression was estimated decreased in ALL diagnosis although P110β expression was not found to be different between ALL diagnosis, ALL remission and solid tumors. Further studies are needed in order to clarify the relation of these proteins’ expression with other established prognostic factors and their role to the leukemia course, outcome and prognosis.
Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer
Authors: Katelyn M. Atkins, Bhupendra Rawal, Tafadzwa L. Chaunzwa, Nayan Lamba, Danielle S. Bitterman, Christopher L. Williams, David E. Kozono, Elizabeth H. Baldini, Aileen B. Chen, Paul L. Nguyen, Anthony V. D’Amico, Anju Nohria, Udo Hoffmann, Hugo J.W.L. Aerts, Raymond H. Mak
Journal: Journal of the American College of Cardiology (2019)

Radiotherapy-associated cardiac toxicity studies in patients with locally advanced non-small cell lung cancer (NSCLC) have been limited by small sample size and nonvalidated cardiac endpoints.The purpose of this analysis was to ascertain whether cardiac radiation dose is a predictor of major adverse cardiac events (MACE) and all-cause mortality (ACM).This retrospective analysis included 748 consecutive locally advanced NSCLC patients treated with thoracic radiotherapy. Fine and Gray and Cox regressions were used to identify predictors for MACE and ACM, adjusting for lung cancer and cardiovascular prognostic factors, including pre-existing coronary heart disease (CHD).After a median follow-up of 20.4 months, 77 patients developed ≥1 MACE (2-year cumulative incidence, 5.8%; 95% confidence interval [CI]: 4.3% to 7.7%), and 533 died. Mean radiation dose delivered to the heart (mean heart dose) was associated with a significantly increased risk of MACE (adjusted hazard ratio [HR]: 1.05/Gy; 95% CI: 1.02 to 1.08/Gy; p < 0.001) and ACM (adjusted HR: 1.02/Gy; 95% CI: 1.00 to 1.03/Gy; p = 0.007). Mean heart dose (≥10 Gy vs. <10 Gy) was associated with a significantly increased risk of ACM in CHD-negative patients (178 vs. 118 deaths; HR: 1.34; 95% CI: 1.06 to 1.69; p = 0.014) with 2-year estimates of 52.2% (95% CI: 46.1% to 58.5%) versus 40.0% (95% CI: 33.5% to 47.4%); but not among CHD-positive patients (112 vs. 82 deaths; HR: 0.94; 95% CI: 0.70 to 1.25; p = 0.66) with 2-year estimates of 54.6% (95% CI: 46.8% to 62.7%) versus 50.8% (95% CI: 41.5% to 60.9%), respectively (p for interaction = 0.028).Despite the competing risk of cancer-specific death in locally advanced NSCLC patients, cardiac radiation dose exposure is a modifiable cardiac risk factor for MACE and ACM, supporting the need for early recognition and treatment of cardiovascular events and more stringent avoidance of high cardiac radiotherapy dose.
DE-kupl: exhaustive capture of biological variation in RNA-seq data through k-mer decomposition
Authors: Jérôme Audoux, Nicolas Philippe, Rayan Chikhi, Mikaël Salson, Mélina Gallopin, Marc Gabriel, Jérémy Le Coz, Emilie Drouineau, Thérèse Commes, Daniel Gautheret
Journal: Genome biology (2017)

We introduce a k-mer-based computational protocol, DE-kupl, for capturing local RNA variation in a set of RNA-seq libraries, independently of a reference genome or transcriptome. DE-kupl extracts all k-mers with differential abundance directly from the raw data files. This enables the retrieval of virtually all variation present in an RNA-seq data set. This variation is subsequently assigned to biological events or entities such as differential long non-coding RNAs, splice and polyadenylation variants, introns, repeats, editing or mutation events, and exogenous RNA. Applying DE-kupl to human RNA-seq data sets identified multiple types of novel events, reproducibly across independent RNA-seq experiments.
Human Neural Tissues from Neural Stem Cells Using Conductive Biogel and Printed Polymer Microelectrode Arrays for 3D Electrical Stimulation
Authors: Eva Tomaskovic‐Crook, Peikai Zhang, Annika Ahtiainen, Heidi Kaisvuo, Chong‐Yong Lee, Stephen Beirne, Zaid Aqrawe, Darren Svirskis, Jari Hyttinen, Gordon G. Wallace, Jadranka Travas‐Sejdic, Jeremy M. Crook
Journal: Advanced Healthcare Materials (2019)

Abstract Electricity is important in the physiology and development of human tissues such as embryonic and fetal development, and tissue regeneration for wound healing. Accordingly, electrical stimulation (ES) is increasingly being applied to influence cell behavior and function for a biomimetic approach to in vitro cell culture and tissue engineering. Here, the application of conductive polymer (CP) poly(3,4‐ethylenedioxythiophene)‐polystyrenesulfonate (PEDOT:PSS) pillars is described, direct‐write printed in an array format, for 3D ES of maturing neural tissues that are derived from human neural stem cells (NSCs). NSCs are initially encapsulated within a conductive polysaccharide‐based biogel interfaced with the CP pillar microelectrode arrays (MEAs), followed by differentiation in situ to neurons and supporting neuroglia during stimulation. Electrochemical properties of the pillar electrodes and the biogel support their electrical performance. Remarkably, stimulated constructs are characterized by widespread tracts of high‐density mature neurons and enhanced maturation of functional neural networks. Formation of tissues using the 3D MEAs substantiates the platform for advanced clinically relevant neural tissue induction, with the system likely amendable to diverse cell types to create other neural and non‐neural tissues. The platform may be useful for both research and translation, including modeling tissue development, function and dysfunction, electroceuticals, drug screening, and regenerative medicine.
PF792 IDENTIFICATION OF REFERENCE GENES IN HUMAN TUMORS FOR TUMOR EDUCATED PLATELETS (TEPS) STUDY BASED ON RNA‐SEQ DATA
Authors: L. LUO, H. Luo
Journal: HemaSphere (2019)

Background: The previous studies have shown that Tumor Educated Platelets (TEPs) RNA may complement currently used biosources and biomolecules employed for liquid biopsy diagnosis. RT‐PCR is a regular method to measure gene expression levels to stage the patients and evaluate their prognosis. As there are little research on reference mRNA in platelets, especially in cancer. Aims: Our study is to find the proper internal controls for RT‐PCR in platelet study. Methods: Firstly, based on dataset GSE68086, we found 285 genes with relatively equal expression in 4 kinds of high incidence cancer (non‐small cell lung cancer (NSCLC), colorectal cancer (CC), breast cancer (BC) and liver cancer (LC)) and healthy control (HC). 95 genes left after screening with the criteria of mean&gt;1 and coefficient of variation (cv) &lt;1. Secondly, we gained 73 common reference genes from previous reported studies. Thirdly, we obtained 7 candidate reference genes (ACTB, B2 M, GAPDH, GNAS, OAZ1, PTMA and YWHAZ) after intersected the 95 genes and 73 genes. At last, we extracted total RNA from 1.5 ml blood in 30 unselected persons, including 6 NSCLC, 6 CC, 6 LC, 6 BC, and 6 HC, and performed RT‐PCR with equal quantity of RNA to measure the expression levels of the candidate reference genes. Results: All of 7 candidate reference genes performed well in 5 tested groups with a cv&lt;0.1. Both B2 M and GAPDH were the most stably expressed with a cv&lt;0.05, but the expression of B2 M was much higher than GAPDH in platelets. Summary/Conclusion: We have found 7 platelets mRNA with relatively same expression levels among several solid tumors and healthy people, which can be used as reference genes for mRNA measuring of platelets. Among them, B2 M may be the best reference control gene. image
AB0359 TREATING STRATEGY FOR ELDERLY RHEUMATOID ARTHRITIS PATIENT, ESPECIALLY WHOSE AGE IS MORE THAN 75
Authors: Ichiro Yoshii, Tatsumi Chijiwa, Naoya Sawada
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> A population of elderly rheumatoid arthritis (ERA) is increasing, probably due to treatment developed and simply elderly population increase. In aging, functional activity in daily life, immunity, especially T-cell function, and neural response decline and deteriorations become manifested. Treatment must not be same as that of young patient. <h3>Objectives</h3> To evaluate our treatment method and strategy for ERA. <h3>Methods</h3> From August 2010 to July 2015, 576 patient who have been treated in the institute continuously for more than 3 years were referred. In these, patients were classified in according with age at baseline (BL); younger than 65 (G-Y), from 65 to 74 (G-O), and no less than 75 (G-OO). Mean 28-joints disease activity score (DAS28), Health Assessment Questionnaire Disability Index (HAQ), Pain Score with visual analog scale (PS-VAS), drug administration history and dosage, were recorded. For ERA, we have adopted a treating strategy called "Touch Down Strategy", what configures three tactics; 1) From BL, methotrexate (MTX) 6mg/week or tacrolimus (TAC) 1.5mg/day administer. 2) Increase or maintain drug dosage until clinical remission is attained or start bDMARDs when remission is not attained in 3 months, and in case, glucocorticoid (GCS) administered with every other month interval. 3)When clinical remission is attained, GCS tapering started immediately and csDMARDs tapering considered. Tapering of bDMARDs is the last order. ERA patients were treated under these tactics. Monitored DAS28, HAQ score and PS-VAS were calculated for each group and compared with ANOVA with Bonferroni correction. <h3>Results</h3> HAQ at baseline demonstrated significantly higher in G-OO than the other groups. Prevalence of DAS28 remission were 76.4%, 89.6%, and 87.2%, while mean length from BL to DAS28 remission was 2.9, 2.5 and 4.0 months for G-Y, G-O, and G-OO, respectively. bDMARDs administration ratio was 19.8%, 20.6%, and 18.0%, while mean MTX dosage was 8.6mg, 8.6mg, and 7.4mg/week, for G-Y, G-O, and G-OO respectively. GCS administration ratio and mean dosage until DAS28 remission were 24.2% and 2.96mg, 38.0% and 2.41mg, and 42.6% and 2.71mg/day, while after remission 19.3% and 5.68mg, 21.1% and 4.58mg, and 26.4% and 2.14mg/day, for G-Y, G-O, and G-OO, respectively (Table). <h3>Conclusion</h3> Our Touch Down Strategy can work effective for ERA, especially for elderly ERA whose age is over 75 years old. Just by doing take care for risk of comorbidities, ERA can be well controlled their disease activity. <h3>Disclosure of Interests</h3> None declared
AB0638 ABSENCE OF LUNG INVOLVEMENT IN SYSTEMIC SCLEROSIS PATIENTS WITH SILICONE IMPLANTS
Authors: Yolanda Braun-Moscovici, Marius Braun, Doron Markovits, Alexandra Balbir-Gurman
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Although many cases have been reported for the last 3 decades, the correlation between silicone breast implants (SBI) and systemic sclerosis (SSc) is yet unclear. <h3>Objectives:</h3> To assess the prevalence of breast implants in a well characterized SSc cohort followed at a dedicated tertiary center and to define charcteristics that might differ between SSc patients with implants and those without. <h3>Methods:</h3> A prospectively maintained database was interrogated regarding the prevalence of breast implants and the disease characteristics. Female patients aged 20 to 55y (215 patients) followed at our center between 2003-2018 were included. SBI cases were identified and their characteristics tabulated. Each SBI patient was matched with 2 controls matched for age, disease duration and type of disease. We used descriptive statistics, multivariate comparisons and multivariate analysis for correlations. <h3>Results:</h3> 11 pts with SBI were found, 6 with diffuse (median age 37.5, range 32-55, median disease duration 3.5 y, range 1.5-8y, median mRSS 13.5, range 8-26) and 5 with limited SSC (median age 38,range 33-45, median disease duration 8y, range 3-22y, mRSS 2, range 2-5). The prevalence of SBI in the 20 to 55 y cohort is 5%, similar to the estimated prevalence in the general population. All had their implants instilled before the diagnosis of SSC (median 10y, range 4-13y). Four pts were first diagnosed with SSC within a year from diagnosis of silicon leakage. RNA polymerase 3 was positive in 3 patients, Scl70 in 3 others, anticentromere in 1 patient and 4 others were positive only for antinuclear antibody. There were no differences in the prevalence of digital ulcers, gastrointestinal involvement, skin score or the serologic profiles between the two groups. However, none of the SBI pts developed interstitial lung involvement, compared to 72% of the matched diffuse patients (p=0.001). There were neither renal crises in the SBI group (compared to 5 cases in the matched group) nor cardiac involvement. <h3>Conclusion:</h3> The temporal relation and the different clinical features might generate a theory that silicone might induce a particular type of SSC, as the idea that silicone protects against lung involvement seems unreasonable. We plan a further prospective study. <h3> Disclosure of interests:</h3> None declared