tbuckley/cabot-search huggingface dataset:
FRI0034 A LATIN-AMERICAN PREVENTIVE CARDIO-RHEUMA CLINIC: A CASE-CONTROL STUDY
Authors: Dionicio Ángel Galarza-Delgado, José Ramón Azpiri-López, Iris Jazmin Colunga-Pedraza, Marielva Castro-González, Karla Paola Cuéllar-Calderón, Ileana Cecilia Reynosa-Silva, Carolina Marlene Martínez-Flores, Guillermo Contreras, Cinthia Yaneth Guillen Gutiérrez, Guillermo Elizondo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> It has been described an increased prevalence of cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients. When compared with the general population, CVD mortality is 50% higher in RA (1). It is reported a 35.3% prevalence of CVD in Latin-American population with RA (2). Cardio-rheuma (CR) clinics were designed to enhance detection, prevention and treatment of CVD in patients with rheumatic conditions. Our clinic located in the University Hospital in Monterrey Mexico, is the first and only established in Latin-America since 2014. <h3>Objectives:</h3> To describe the characteristics of patients with RA attending to a Latin-American CR clinic and compare the findings by carotid ultrasound (US) and echocardiography to controls. <h3>Methods:</h3> Cross-sectional, observational, comparative study. RA patients aged 40 to 75 years that fulfilled the 2010 EULAR criteria and matched controls were included. Patients with prior atherosclerotic CVD and overlap syndromes were excluded. Clinical history, blood samples, physical exam, carotid US and echocardiography were performed. Carotid plaque (CP) was defined as a focal narrowing ≥0.5 mm of the surrounding lumen or a carotid intima media thickness (cIMT) ≥1.2 mm, and increased cIMT was defined as ≥0.9 mm. Transthoracic echocardiogram was performed and reviewed by 2 board-certified cardiologists. Differences were solved by consensus. Categorical variables are expressed as total number (%), and numerical variables as median (q25-q75). Chi square and Mann-Whitney U-test were used to compare groups and considered significant if p&lt;0.05. <h3>Results:</h3> A total of 336 RA patients and 144 controls were included (Table 1). Table 2 summarizes echocardiographic and carotid US findings; ejection fraction was higher in controls than RA patients, prevalence of bilateral CP and increased cIMT was significantly higher in RA patients. <h3>Conclusion:</h3> RA patients from this clinic had lower ejection fraction, more prevalence of cIMT and bilateral CP when compared to controls. It is important that rheumatologists perform a complete evaluation of their patients, in which cardiovascular assessment should be included. <h3>References:</h3> [1] Aviña-Zubieta JA, et al. 2008. Arthritis &amp; Rheumatism. [2] Sarmiento-Monroy JC, et al. 2012. Hindawi Publishing Corporation. <h3>Disclosure of Interests:</h3> None declared
SLiM 3: Forward Genetic Simulations Beyond the Wright–Fisher Model
Authors: Benjamin C Haller, Philipp W Messer
Journal: Molecular Biology and Evolution (2018)

With the desire to model population genetic processes under increasingly realistic scenarios, forward genetic simulations have become a critical part of the toolbox of modern evolutionary biology. The SLiM forward genetic simulation framework is one of the most powerful and widely used tools in this area. However, its foundation in the Wright–Fisher model has been found to pose an obstacle to implementing many types of models; it is difficult to adapt the Wright–Fisher model, with its many assumptions, to modeling ecologically realistic scenarios such as explicit space, overlapping generations, individual variation in reproduction, density-dependent population regulation, individual variation in dispersal or migration, local extinction and recolonization, mating between subpopulations, age structure, fitness-based survival and hard selection, emergent sex ratios, and so forth. In response to this need, we here introduce SLiM 3, which contains two key advancements aimed at abolishing these limitations. First, the new non-Wright–Fisher or "nonWF" model type provides a much more flexible foundation that allows the easy implementation of all of the above scenarios and many more. Second, SLiM 3 adds support for continuous space, including spatial interactions and spatial maps of environmental variables. We provide a conceptual overview of these new features, and present several example models to illustrate their use.
Adding intermittent pneumatic compression to UFH or LMWH did not reduce proximal DVT in critically ill patients
Authors: Michael J. Jacka
Journal: Annals of Internal Medicine (2019)

Source Citation Arabi YM, Al-Hameed F, Burns KEA, et al; Saudi Critical Care Trials Group. Adjunctive intermittent pneumatic compression for venous thromboprophylaxis. N Engl J Med. 2019;380:1305-15. 30779530
AB0941 SYSTEMIC LUPUS ERYTHEMATOSUS IN CHILDREN UNDER 6 YEARS OF AGE, EXPERIENCE IN A TERTIARY CENTER
Authors: EDITH ADRIANA BENITEZ VAZQUEZ, Maria Teresa Brana Ruiz, Luis Alberto Aparicio, Sofia Osorio Sagrero, Merari Gomez Cortes, Velka Cortez, Rocio Maldonado, Enrique Faugier Fuentes
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a rare entity in patients under 5 years old, depending on the ethnic group it has a prevalence of 3.3 to 24 per 100 000 children. Before puberty no difference in prevalence associated with gender was observed. In the pediatric age, SLE has a more aggressive course.<sup>1</sup> <h3>Objectives</h3> To describe the demographic and clinical characteristics of 6 patients under 6 years old diagnosed with SLE. <h3>Methods</h3> To describe the demographic and clinical characteristics of 6 patients under 6 years old with a diagnosis of SLE based on the 1997 ACR criteria at the Federico Gomez Children's Hospital of Mexico from June 2017 to January 2019. Table N°1. Demographic and clinical characteristics of patients under 6 years of age diagnosed with SLE. <h3>Results</h3> The diagnosis of SLE in patients under 5 years old is rare, the literature describes that in these patients there is greater renal, hematological and neuropsychiatric manifestations; We present the demographic and clinical characteristics of 6 patients under 6 years of age with a diagnosis of SLE based on criteria of ACR 1997; 4 of the patients presenting are male, in three of the cases the initial manifestation was non-erosive arthritis and skin manifestations (in two purpura and in one deep cutaneous lupus), in four of the cases lupus nephritis was presented; the average time between the onset of symptoms and the diagnosis was 8 months (range between 3 and 13 months). <h3>Conclusion</h3> The diagnosis of SLE in patients under 6 years old is rare, the initial manifestations may be nonspecific, which causes greater complexity to establish an opportune diagnosis. It is described that in lupus cases in pediatric patients there are clinical manifestations of greater severity and early diagnosis modifies the prognosis. The initial manifestations of SLE in patients younger than 6 years old in our series are similar to those described in the literature: arthritis and seizures, as well as the presentation associated with gender, with no difference in preschool age. <sup>2</sup> It has been described that the time elapsed from the onset of symptoms to the diagnosis is shorter at younger age of patient, however in our series the time of diagnosis was an average of 8 months, probably related to the low prevalence of the disease in this age group. <h3>References</h3> [1] Malattia C., Martinni A. (2013Jun). Paediatric-onset systemic lupus erythematosus. Best Pract Res Clin Rheumatol;27(3):351-62. [2] Jia Zhu., Fengqi Wu., Xiaolan Huang. (2013Jan). Age-related differences in the clinical characteristics of systemic lupus erythematosus in children. Rheumatol Int33:111–115. <h3>Disclosure of Interests</h3> None declared
PF230 THE RNA HELICASE DDX17 PROTECTS ACUTE MYELOID LEUKEMIA CELLS AGAINST DNA DAMAGE
Authors: P. Jagdhane, S. Garg, J. Xia, L. He, D. Misiak, O. Mortusewicz, T. Helleday, C. Müller‐Tidow, M. Koehn, C. Pabst
Journal: HemaSphere (2019)

Background: Alternative splicing (AS) is essentially regulated by RNA‐binding proteins (RBPs) and is one of many deregulated cellular processes in Acute Myeloid Leukemia (AML). The alternative usage of exons substantially increases the coding potential of mRNAs and frequently leads to the expression of tumor‐promoting mRNA variants in cancer modulating apoptosis, proliferation, invasion and migration of cancer cells. This underlines the great plasticity of AS in cancer and justifies the need to elucidate the function of nuclear RBPs in specific cancer types. We found that the RNA helicase DDX17 is significantly more highly expressed in primary human AML specimens with high versus low Leukemia Stem Cell (LSC) frequency. Aims: In this study, we aimed to understand the functional role of DDX17 in normal hematopoietic stem and progenitor cells (HSPCs) and in AML cells. In particular, we sought to determine whether DDX17 exerts its function in the hematopoietic system primarily via AS or AS‐unrelated mechanisms. Methods: We performed knockdown (KD) experiments using small hairpin (sh) RNAs to determine whether DDX17 was essential for primary human cord blood CD34+ HSPCs and leukemia cells. Furthermore, mRFP tagged DDX17 was overexpressed through lentiviral transduction to track protein localization by immunofluorescence (IF) imaging. Lentivirally transduced HSPCs and leukemia cells were analyzed in vitro for proliferative output, viability, immunophenotype, and colony formation potential. RNA sequencing (RNA‐Seq) was used to determine how DDX17 KD affected gene expression and alternative exon usage. Pull down experiments combined with mass spectrometry revealed binding partners in presence and absence of chemotherapeutic agents. Finally, we performed homologous recombination (HR) and drug sensitivity assays to determine the role of DDX17 in DNA damage. Results: Knockdown of DDX17 induced DNA damage and severely impaired the function of healthy HSPCs and TP53 wild type AML cells. TP53 null cells maintained their proliferative capacity during short term in vitro expansion in absence of DDX17, but were significantly sensitized towards DNA damaging agents. In line, overexpression of DDX17 protected the cells against double strand break (DSB) inducing drugs. IF imaging revealed direct recruitment of DDX17 to DNA damage sites, while RNA‐Seq showed suppression of multiple DNA repair genes. Summary/Conclusion: RNA‐Seq, IF imaging, proteomics, and HR assays suggest an essential role of DDX17 in DNA repair via different mechanisms including direct recruitment to DNA damage sites, alternative splicing, and regulation of DNA repair genes on the transcriptional level.
AB1395-HPR BURDEN IN CAREGIVERS OF PATIENTS WITH RHEUMATIC CONDITIONS
Authors: Diana Buitrago-Garcia, Laura Villarreal, Michael Cabrera, Pedro Santos-Moreno, Fernando Rodriguez
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic, disease that affects more than 1% of global population, it is a long term condition that causes pain and disability. Evidence had shown that most of the patients are moderately disabled, which brings the necessity of a caregiver to become the patients companion due to its chronic disease. The caregiving role can have an impact in the psychological and physical spheres of the caregivers life. <h3>Objectives</h3> The aim of this study was to explore demographical characteristics and caregiver burden through the Zarit Scale. <h3>Methods</h3> We conducted a cross sectional study in a meeting where caregivers in a rheumatoid arthritis specialized setting. We collected sociodemographic information, and applied the Zarit caregiver burden interview (ZBI) adapted to Spanish. The ZBI includes 22 questions which has 5 responses from 0 (never) to 4 (nearly always), where scores lower than 47 indicated little to no burden, 47 to 55 low burden and &gt;55 intense burden. We calculated means, and standard deviations for continuous variables and categorical variables were presented as rates. <h3>Results</h3> We applied a survey to 132 caregivers. Mean age was 52 years SD 19 and 72% were women, 78% of them were taking care of a patient with rheumatoid arthritis, 12% osteoarthrosis 2% lupus, 2% osteoporosis the remaining 6% were caregivers of patients with ankylosing spondylitis, fibromyalgia, Sjogren syndrome. Regarding the time as caregiver 48% of them had been carrying the task for less than a year, 16% between two and three years, 18% for more than three years, and 13% for more than four years 5% of them were temporarily caregivers. In our study 85% of caregivers were a family member while15% was a nurse or a non-related person. Zarit mean score was 38.2913, additionally 35% had a score higher than 41 points. See table 1. <h3>Conclusion</h3> In our study 93% of our patients reported to have moderate to severe burden; thus, it is important to develop strategies and explore the factors related to burden in caregivers in patient with rheumatoid arthritis. <h3>Disclosure of Interests:</h3> Diana Buitrago-Garcia: None declared, Laura Villarreal: None declared, Michael Cabrera: None declared, Pedro Santos-Moreno Grant/research support from: Dr Santos has received research grants from Janssen, Abbvie and UCB, Speakers bureau: Dr Santos has received speaker fees from Sanofi, Lilly, Bristol, Pfizer, Abbvie, Janssen and UCB, Fernando Rodriguez: None declared
Essential guidelines for computational method benchmarking
Authors: Lukas M. Weber, Wouter Saelens, Robrecht Cannoodt, Charlotte Soneson, Alexander Hapfelmeier, Paul P. Gardner, Anne-Laure Boulesteix, Yvan Saeys, Mark D. Robinson
Journal: Genome biology (2019)

In computational biology and other sciences, researchers are frequently faced with a choice between several computational methods for performing data analyses. Benchmarking studies aim to rigorously compare the performance of different methods using well-characterized benchmark datasets, to determine the strengths of each method or to provide recommendations regarding suitable choices of methods for an analysis. However, benchmarking studies must be carefully designed and implemented to provide accurate, unbiased, and informative results. Here, we summarize key practical guidelines and recommendations for performing high-quality benchmarking analyses, based on our experiences in computational biology.
PB1687 TRACKING HEMATOLOGIC MALIGNANCIES LETHALITY ASSOCIETED FACTORS IN OUAGADOUGOU (BURKINA FASO): TOWARDS A COOPERATION EUROPE - AFRICA
Authors: M. Kalo Roland, T. Solo, K. Jerome, S. Fabienne, B. Réné, Z. Alexandre, G. Oumar, D.Y. Joseph
Journal: HemaSphere (2019)

Background: Hematologic malignancies are a great public health problem in the World. These cancers of hematopoietic system are responsible for many deaths every year. But it exists some disparities in geographic repartition and in the lethality associated factors. Aims: The aim of this study was to describe a profil of major causes of deaths by hematologic malignancies in a West Africa’ country in order to establish the state of art and create a north south cooperation. Methods: We conducted a retrospective study from medical files of patients who was hospitalised or followed in external consultations in the department of Internal Medicine at University Hospital Yalgado Ouedraogo in Ouagadougou (Burkina Faso). The study period go from 1st January to 31th December 2016. Only patients over than 15 years old have been inclued. Results: The study population collected was 122 patients. Hematologic malignancies represented 80,33% (98/122) of patients. The annual incidence of hematologic malignancies was 8,16 cases. The mean age was 53,51 years [15 - 84]. The sex-ratio (M/W) was de 1,51. The repartition of frequences was : Acute Myeloid Leukemia (AML)= 2,04%, Acute Lymphoblastic Leukemia (ALL)= 6,12%, Myeloproliferative Syndroms (MS)= 10,20%, Lymphoproliferative Syndroms (LS)= 76,53%, Myelodysplasic Syndroms (MDS)= 5,11%. Infections was the most frequent etiology of death with 52,95% and the most lethal was pulmonary infection (29,42%). The range age [15-30 years[had the highest rate of lethaly (83,33%). The most lethal disease was ALL with 66,67%. The chemotherapy with poor survival was Bleomycin-CHOP with a lethality of 33,33%. Summary/Conclusion: The main associated factor to their lethality was infection and the worst prognosis's cancer was acute lymphoblastic leukemia. We hope that with a better partnership with developped countries and the sharing of experience we will improve our overall survival and the global prognosis of these diseases.
THU0235 INHIBITION OF EZH2 AMELIORATES LUPUS-LIKE DISEASE IN MRL/LPR MICE
Authors: Dallas Rohraff, Ye He, Evan Farkash, Mark Schonfeld, Eliza Tsou, Amr Sawalha
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> We previously revealed a role for EZH2 in inducing pro-inflammatory epigenetic changes in lupus CD4+ T cells. <h3>Objectives</h3> In this study, we sought to determine if inhibiting EZH2 ameliorates lupus-like disease in MRL/lpr mice. <h3>Methods</h3> EZH2 expression levels in multiple cell types in lupus patients were evaluated using flow cytometry and mRNA expression data. Inhibition of EZH2 in MRL/lpr mice was achieved by DZNep intraperitoneal administration using a preventative and a therapeutic treatment model. Effects of DZNep on animal survival, anti-dsDNA antibody production, proteinuria, renal histopathology, cytokine production, and T and B cell numbers and percentages were assessed. <h3>Results</h3> EZH2 expression levels were increased in whole blood, neutrophils, monocytes, B cells, and CD4+ T cells in lupus patients. In MRL/<i>lpr</i> mice, inhibiting EZH2 with DZNep treatment before or after disease onset improved survival and significantly reduced anti-dsDNA antibody production. DZNep-treated mice displayed a significant reduction in renal involvement, splenomegaly, and lymphadenopathy. Lymphoproliferation and numbers of double-negative T cells were significantly reduced in DZNep treated mice. Concentrations of circulating cytokines and chemokines, including TNF, IFN-γ, CCL2, RANTES/CCL5, IL-10, KC/CXCL1, IL-12, IL-12p40 and MIP-1β/CCL4 were decreased in DZNep treated mice. <h3>Conclusion</h3> EZH2 is upregulated in multiple cell types in lupus patients. Therapeutic inhibition of EZH2 abrogates lupus-like disease in MRL/lpr mice, suggesting that EZH2 inhibitors may be repurposed as a novel therapeutic option in lupus patients. <h3>Disclosure of Interests</h3> None declared
Abstract 15635: Consumption of Aspirin and Naproxen by Platelet Donors and the Quality of Platelet Transfusion
Authors: Xuanwen Li, Susanne Fries, Bruce S Sachais, Adam Cuker, Ian A Blair, Tilo Grosser
Journal: Circulation (2015)

Over-the-counter pain killers are amongst the most frequently consumed drugs world-wide. Individuals who self-report ingesting aspirin or aspirin containing drugs within the preceding 48-72 hours - depending on regional practice - are excluded from platelet donation, given the assumed platelet functional inhibition due to irreversible acetylation of platelet cyclooxygenase-1 (COX-1) by aspirin and the consequent suppression of thromboxane formation. Other nonsteroidal anti-inflammatory drugs, which bind COX-1 tightly enough to cause long acting platelet inhibition, such as naproxen, may also impact the quality of platelet preparations for transfusion but are not typically exclusionary. The prevalence of functionally relevant exposure of platelet donors to aspirin and naproxen is unknown. We used sensitive and specific mass spectrometry methods to quantitate the acetylation of platelet COX-1 by aspirin and platelet protein binding of naproxen in platelet transfusion units as indices of donor exposure to these drugs. Platelet thromboxane formation was assessed as a functional parameter. We screened single-donor apheresis platelet units transfused at the Hospital of the University of Pennsylvania. Over 30 % (71 out of 235) of the analyzed platelet units showed evidence of aspirin exposure ranging from residual COX-1 acetylation after an appropriate washout period to complete acetylation suggestive of recent aspirin exposure. Approximately 7% (16 out of 235) of the platelet units showed complete COX-1 acetylation and inhibition of thromboxane formation. More than 15% (22 out of 143) of analyzed platelet units showed high naproxen concentrations that were associated with depression of thromboxane formation. The prevalence of aspirin and naproxen consumption by platelet donors is as high as would be expected in the general population and results in transfusion of inhibited platelets with suppressed thromboxane formation.
Abstract 15515: Predicting Freedom From Interstage Death or Transplant After Stage I Palliation for Single Ventricle Heart Disease
Authors: Humera Ahmed, Lynn A Sleeper, Jeffrey Anderson, Katherine E Bates, Nancy S Ghanayem, Carole M Lannon, David W Brown
Journal: Circulation (2018)

Background: The Interstage period between Stage 1 palliation (S1P) and the Stage 2 procedure (S2P; i.e. Glenn or hemi-Fontan) is a time of high morbidity and mortality for infants with single ventr...
Tolerability and cardiac safety of neo/adjuvant trastuzumab-based chemotherapy regimens for HER2+ breast cancer: A single institution experience.
Authors: Potjana Jitawatanarat, Ellen Kossoff, Grazyna Riebandt, Ellis Glenn Levine, Tracey L. O'Connor, Kaweesak Chittawatanarat, Nuttapong Ngamphaiboon
Journal: Journal of Clinical Oncology (2013)

e11508 Background: Docetaxel/carboplatin/trastuzumab (H) (TCaH) and doxorubicin/cyclophosphamide/paclitaxel/H (AC-TH) and its variants are recommended by standard guidelines for neoadjuvant and adjuvant treatments for HER2+ breast cancer. Docetaxel/cyclophosphamide/H (TCyH) has also been used in clinical practice. Tolerability and cardiac safety among these regimens have not been well described. Methods: We retrospectively reviewed HER2+ early stage breast cancer who received neo/adjuvant H at RPCI between 2004-2011. Acute toxicities of different regimens (AC-TH and its variants, TCaH, TCyH) were evaluated. Cardiac events were defined as symptomatic congestive heart failure (CHF) and/or asymptomatic decline of ejection fraction (EF) that resulted in holding H. Results: 177 patients were identified (AC-TH=114, TCaH=39, TCyH=24). Patients who received AC-TH were younger, had less comorbidity, including cardiac history, and received less GCSF support. AC-TH regimens were associated with more febrile neutropenia (FN), grade 3-4 neutropenia, and dose delay (Table). Overall cardiac events were observed in 18% (anthracyclines 14% vs non-anthracyclines 9%; p=0.346). Termination of H was not significantly different between patients treated with anthracyclines (4%) vs non-anthracyclines (2%), nor was the CHF rate (4% vs 6%). Median absolute EF decline was also similar (5% vs 4%). After adjustment for age ≥65, cardiac history, baseline EF &lt;55%, and Charlson Comorbidity Index, patients treated with anthracyclines showed a trend toward increased cardiac events (OR 4.53, 95% CI 0.99-20.5; p=0.05) in multivariate analysis. Conclusions: Although physician selection of patients for trastuzumab directed therapy lessens overall toxicity, the acute toxicity and cardiac event rate among those considered the most fit remains considerable when an anthracycline is introduced. [Table: see text]
AB1338 PATIENT EDUCATION IN PSORIATIC ARTHRITIS: ADDRESSING AN UNMET NEED
Authors: Keziah Austin, Nia Jones, Roopa Prasad
Journal: Annals of the Rheumatic Diseases (2019)

Whitney U test) in both groups.In the VBC group time between decision to treat until funding approval obtained was measured and overall saving by all estimated drug cost was calculated.Results 122 patients were discussed at VBC -75 started a biologic (50 new, 25 switched) and 6 entered a clinical trial.The remaining 41 were agreed as unsuitable for a biologic table 1.