tbuckley/cabot-search huggingface dataset:
New Phylogenomic Analysis of the Enigmatic Phylum Telonemia Further Resolves the Eukaryote Tree of Life
Authors: Jürgen F H Strassert, Mahwash Jamy, Alexander P Mylnikov, Denis V Tikhonenkov, Fabien Burki
Journal: Molecular Biology and Evolution (2019)

The resolution of the broad-scale tree of eukaryotes is constantly improving, but the evolutionary origin of several major groups remains unknown. Resolving the phylogenetic position of these "orphan" groups is important, especially those that originated early in evolution, because they represent missing evolutionary links between established groups. Telonemia is one such orphan taxon for which little is known. The group is composed of molecularly diverse biflagellated protists, often prevalent although not abundant in aquatic environments. Telonemia has been hypothesized to represent a deeply diverging eukaryotic phylum but no consensus exists as to where it is placed in the tree. Here, we established cultures and report the phylogenomic analyses of three new transcriptome data sets for divergent telonemid lineages. All our phylogenetic reconstructions, based on 248 genes and using site-heterogeneous mixture models, robustly resolve the evolutionary origin of Telonemia as sister to the Sar supergroup. This grouping remains well supported when as few as 60% of the genes are randomly subsampled, thus is not sensitive to the sets of genes used but requires a minimal alignment length to recover enough phylogenetic signal. Telonemia occupies a crucial position in the tree to examine the origin of Sar, one of the most lineage-rich eukaryote supergroups. We propose the moniker "TSAR" to accommodate this new mega-assemblage in the phylogeny of eukaryotes.
OP0253 WORLDWIDE TRENDS IN MORTALITY OF SYSTEMIC LUPUS ERYTHEMATOSUS BETWEEN 2000 AND 2015: ANALYSIS OF THE WORLD HEALTH ORGANIZATION DATABASE
Authors: Marc Scherlinger, Jean Sibilia, Hervé Devilliers, Laurent Arnaud
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Although diagnosis, treatment and prevention strategies of Systemic Lupus Erythematosus (SLE) have further improved during the last two decades, the net benefit in term of global SLE-related mortality remains unknown. <h3>Objectives</h3> To describe the worldwide trends in SLE mortality between 2000 and 2015 using data of 125 countries from the World Health Organization (WHO) mortality database. To modelize SLE-related deaths taking into account temporal changes, geographical localization and country wealth. <h3>Methods</h3> We analyzed the WHO mortality database containing cause-specific mortality of participating countries. SLE-related deaths were identified using the international classification of disease 10 (ICD-10, code M32). In all countries which provided data between 2000 and 2015, sex-specific mortality rate was calculated for each year using the WHO reference population database. To have a better understanding of mortality fluctuations, countries were grouped geographically by continents and their nominal gross domestic product (GDP) per capita were retrieved from the United Nation database. A mixed regression model for repeated measures was used to take into account the time factor, GDP per capita and continent in SLE-related death. <h3>Results</h3> Between 2000 and 2015, a total of 97,008 SLE-related deaths occurred in 125 countries, which accounted for 0.021% of all deaths during the same period. World-wide, the overall mortality rate attributed to SLE remained stable (p=0.86) over the study years. However, we detected significant differences between continents (p=0.0006) with the mortality rate of Africa being significantly higher than that of Europe (p=0.004). There was a significant interaction between the continents and the study years (p=0.01) revealing a strong increase in the mortality rate attributed to SLE in Africa. We found a very strong association between SLE-attributed mortality and the GDP per capita (p&lt;0.0001). <h3>Conclusion</h3> We observed drastic differences in the evolution of SLE-related mortality due to country geographic localization, wealth and ethnic factors. SLE-related remained stable as a whole but strongly increased in the African continent. <h3>Disclosure of Interests</h3> Marc SCHERLINGER: None declared, Jean Sibilia: None declared, Hervé Devilliers: None declared, Laurent Arnaud Consultant for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugaï, and UCB., Paid instructor for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugaï, and UCB., Speakers bureau: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugaï, and UCB.
Comparison of methods that use whole genome data to estimate the heritability and genetic architecture of complex traits
Authors: Luke M. Evans, Rasool Tahmasbi, Scott I. Vrieze, Gonçalo R. Abecasis, Sayantan Das, Steven Gazal, Douglas W. Bjelland, Teresa R. de Candia, Michael E. Goddard, Benjamin M. Neale, Jian Yang, Peter M. Visscher, Matthew C. Keller
Journal: Nature Genetics (2018)
AB1047 DYNAMICS OF GROWTH AND BONE AGE IN CHILDREN WITH JIA DURING BIOLOGICAL THERAPY
Authors: Valentina Serayia
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In children with severe juvenile idiopathic arthritis (JIA), growth impairment is often accompanied by retardation of bone age. Dynamics of growth and bone during biological therapy is an important criterion for the effectiveness of treatment. <h3>Objectives</h3> To assess the effect of biological therapy on growth and bone age in children with JIA. <h3>Methods</h3> The study included 45 patients with JIA and (30 boys and 15 girls, mean age 12.2 ± 2.7 years; disease duration before the start of biological therapy 6.5 ± 3.3 years, 18 children with systemic JIA and 27 with polyarticular JIA). All children due to the ineffectiveness of standard therapy were transferred to biological therapy with TNF-α and IL-6 inhibitors. The study assessed growth SDS and bone age (according to x-ray imaging) before starting biological therapy (initialy) and after 24 months of therapy. <h3>Results</h3> Of the 45 children, the initial growth retardation marked in 13 children, all with systemic JIA (growth SDS -3.19 ± 0.36 (-6.67; -2.04)). All these children also showed a lag of bone age from the passport by 2.9 ± 0.5 years, which corresponded to growth retardation. During biological therapy, the growth retardation decreased within 24 months: growth SDS -2.73 ± 0.34 (-5.87; -1.17). The lag of bone age was maintained at 2.3 ± 1.5 years, which is comparable to the baseline (p = 0.053). In 32 children, the initial growth was within the normal range (growth SDS 0.12 ± 1.07 (-1.97; 1.76)); 8 children with sJIA, 24 with polyarticular JIA. In all these children, the lagging of bone age from the passport at the time of the start of biological therapy was not detected (deviation from the passport age at most 1 year). During biological therapy for 24 months, growth rates remained normal: growth SDS was 0.22 ± 0.99 (-1.58; 1.67). Indicators of bone age in all children were corresponding passport age. <h3>Conclusion</h3> In children with severe JIA and normal growth, the bone age is more likely to correspond to the passport age; during therapy with biological agents, there is no significant change in bone age in these children. In children with severe JIA, growth impairment and bone age may be observed, most likely in children with systemic JIA. During biological therapy, there is an improvement in growth, while the lagging of bone age from the passport remains, which indicates the preservation of growth potential and the possibility of achieving higher final growth. <h3>References</h3> [1] Uettwiller F, Perlbarg J, Pinto G, Bader-Meunier B, Mouy R, Compeyrot-Lacassagne S, Melki I, Wouters C, Prieur AM, Landais P, Polak M, Quartier P. Effect of biologic treatments on growth in children with juvenile idiopathic arthritis.//J Rheumatol. 2014 Jan;41(1):128-35 <h3>Acknowledgement</h3> The staff of children's rheumatology department of Pediatric Clinic of I.M.Sechenov First Moscow State Medical University <h3>Disclosure of Interests</h3> None declared
Racial Disparities and Trends in Pancreatic Cancer Incidence and Mortality in the United States
Authors: Anna Tavakkoli, Amit G. Singal, Akbar K. Waljee, B. Joseph Elmunzer, Sandi L. Pruitt, Thomas McKey, Joel H. Rubenstein, James M. Scheiman, Caitlin C. Murphy
Journal: Clinical Gastroenterology and Hepatology (2019)
PB2278 PRETREATMENT SERUM 25(OH) VITAMIN D AS PREDICTOR OF EVENT‐ FREE SURVIVAL IN LYMPHOID MALIGNANCIES
Authors: V. Djurasinovic, B. Mihaljevic, V. Vukovic, D. Antic, K. Tomic, V. Otasevic
Journal: HemaSphere (2019)

Background: Vitamin D was investigated as a prective factor in lymphoid malignancies recently. Aims: Assessment of 25(OH) vitamin D status in lymphoid malignacies before active treatment and its influence on event‐free survival (EFS). Methods: Study included 153 patients, median age 58(18‐84) years with diagnose: diffuse large B cell lymphoma‐70, Hodgkin lymphoma‐22, chronic lymphocitic leukemia‐21, follicular lymphoma‐20 and multiple myeloma‐20, who had pretreatment 25(OH) vitamin D level. Comorbidities were assessed by Cumulative comorbidity index (CIRS). Patients were treated with immunochemotherapy and followed for event‐free survival for median 38(2‐53) months.Event was defined as progression or death. Results: Pretreatment serum 25(OH) vitamin D was 34,4 ± 13,6 nmol/l, without significant difference between lymphoma subgroups (ANOVA p = 0,069). Multivariate Cox regression for EFS showed 25(OH)D&lt;25nmol/l (HR 2,732, 95%CI 1,37‐5,44), elevated LDH (HR 3,79, 95%CI 1,87‐7,66) and CIRS &gt; 3 (HR 2,88, 95%CI 1,43‐5,78) as significant parameters for EFS. Summary/Conclusion: Average pretreatment 25(OH)D level in lymphoid malignancies is low. Severe deficiency, 25(OH)D &lt;25nmol/l, is strong predictor of EFS in analysed group of patients.
S849 TNF‐α BLOCKADE CORRECTS THE MONOCYTE/MACROPHAGE IMBALANCE IN PRIMARY IMMUNE THROMBOCYTOPENIA (ITP)
Authors: Y. Zhao, X. Liu, G. Li, J. Peng, M. Hou
Journal: HemaSphere (2019)

Background: Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder. Deviation of monocyte/macrophage subsets plays an important role in the pathogenesis of ITP. TNF‐α blockade is widely used in many autoimmune diseases with satisfactory effects. However, the effect of TNF‐α blockade on monocyte/macrophage system in ITP remains unknown. Aims: Our study aimed to investigate whether TNF‐α could restore the disturbed balance of monocyte/macrophage subsets and be a potential therapeutic strategy for ITP. Methods: Plasma TNF‐α was detected by ELISA. The monocyte/macrophage subsets were analyzed using flow cytometry and immune fluorescence. Macrophage polarization was analyzed using western blot, q‐PCR, and flow cytometry. Phagocytic capacity of macrophages was measured by the engulfment of opsonized platelets. T‐cell priming ability of macrophages was determined through co‐culturing with CD4 + T cells and CD8 + T cells. We established a passive model of murine ITP. Platelet count was measured every other day. The retention of platelets in liver and spleen was assessed by the fluorescence intensity detected using the in vivo imaging system. Results: ITP patients manifested with an increased TNF‐α expression which was inversely correlated with platelet count. Moreover, the numbers of TNF‐α‐expressing macrophages in spleen and CD16 + monocytes were more than that of healthy controls. TNF‐α blockade inhibited M1 macrophage polarization by suppressing the NF‐κB signaling pathway, and dampened the phagocytic capacity and T‐cell priming ability of macrophages. Moreover, anti‐TNF‐α therapy reduced the number of non‐classical monocytes and M1 macrophages, ameliorated the retention of platelets in spleen and liver, and significantly increased the platelet count of ITP mice. Summary/Conclusion: Our study demonstrated that TNF‐α blockade could decrease the number and functions of pro‐inflammatory subsets of monocytes/macrophages by inhibiting NF‐κB signaling pathway, leading to remarkable attenuation of antibody‐mediated platelet destruction both in vitro and in vivo , thus might be a promising therapeutic strategy for the management of ITP. image
AB0829 OSTEOGENESIS IMPERFECTA : EVOLUTION OF THE BONE MINERAL DENSITY AND EVALUATION OF FRACTURE RISK UNDER BISPHOSPHONATES
Authors: Mohamed Amine El Achek, Mahbouba Jguirim, Amel Farhat, Saoussen Zrour, Ismail Bejia, Mongi Touzi, Naceur Bergaoui
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Osteogenesis imperfecta (OI), or Lobstein's disease, also known as 'Glass bone disease' is a rare genetic disorder predisposing to low bone mass with impaired bone microarchitecture and abnormal quality of bone material, causing fracture susceptibility and bone deformities. <h3>Objectives</h3> The main objective of our work was to study the clinical and para-clinical characteristics, and global management, of adult patients and children with OI in a rheumatology departement by comparing them with data from the littérature. The secondary objectives were to study the evolution of the bone mineral density and to evaluate the fracture incidence under treatement by Bisphosphonates. <h3>Methods</h3> This is a cross-sectional, observational, descriptive, analytical and monocentric study of subject with OI followed at Fattouma Bourguiba University Hospital in Monastir, Tunisia <h3>Results</h3> We collected 13 patients with OI, including 5 children and 8 adults. Seven patients were female and 6 were male, including 12 patients with type IB and one with type IIIB. Three adult patients had a family history of OI. For children, it was sporadic and the genetic survey did not reveal similar cases in the family. The mean age of clinical onset of the disease was 9 years and 3 months [0-33 years] with a mea nage at diagnosis of 15 years and 7 months [14 months- 40 years]. The clinical manifestations were dominated by osteo-articular symptoms. Chronic mechanical bone pain related to fractures was present in eight patients. Twelve patients had a history of fracture. These were repeated fractures without trauma or minimal traumain the majority of cases mainly in the lower limbs. The first fracture site was the femur associated with other fracture sites (there were no fractures in the pelvis, hands and skull). Deformities were observed in 7 patients, mainly in the limbs (6 patients), in the spine (2 patients) and in the thorax (1 patient). In our study the frequency of osteoporosis and/or osteopenia regardless of the mesured site and using the T-score value for women≤-2,5 and the Z-score≤-2 for children and men was 84,62%. All patients received Aredia treatment according to Glorieux's protocol with calcium and vitamin D supplementation. The treatment was also multidisciplinary. Bisphosphonate treatment was well tolerated for the majority of patients. There was a decrease in the number of fractures and also a densitometric gain objectivised for the majority of patients. <h3>Conclusion</h3> Our results confirm the efficacy of BP in patients with OI regardless of age group. Short-term adverse are rare and transient. <h3>Reference</h3> [1] R. Morello, Osteogenesis imperfecta and therapeutics, Matrix Biol. (2018). doi:10.1016/j.matbio.2018.03.010. <h3>Disclosure of Interests</h3> None declared
Abstract 18422: Comparable Diagnostic Utility of Instantaneous Wave-Free Ratio for Ischemia-Guided Revascularization Referenced to Fractional Flow Reserve: A PRISMA-Compliant Meta-Analysis of Clinical Studies
Authors: Rohit Maini, John C Moscona, Paul A Katigbak, Qusai A Saleh, Rohan Samson, Thierry H Lejemtel, Owen N Mogabgab, Nidal N Abi-Rafeh
Journal: Circulation (2017)

Introduction: Fractional flow reserve (FFR)-guided percutaneous coronary intervention improves clinical outcomes compared to angiographic-guided methods. However, hyperemic agents increase procedur...
FRI0021 ORAL HYGIENE STATUS IN RA PATIENTS AND PLACE OF RHEUMATOLOGIST IN THERAPEUTIC EDUCATION ON ORAL DENTAL HEALTH
Authors: saloua afilal, Hanan Rkain, Afaf Allaoui, Oum Keltoum Ennibi, Tahiri Latifa, Nada Alami, Fadoua Allali
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The relationship between oral hygiene and rheumatoid arthritis has been demonstrated by several studies. <h3>Objectives:</h3> To evaluate oral hygiene status in rheumatoid arthritis (RA) patients. To inform about the therapeutic education given by the rheumatologist on the importance of adequate oral hygiene in the management of RA <h3>Methods:</h3> This is a cross-sectional study that included 100 consecutive RA patients (89% female, mean age 46.7 years, median disease duration of 8 years, mean specialized care duration of 3 years). A questionnaire evaluating oral hygiene status was administered. It focused on following items: the daily frequency of brushing, the modalities of brushing, the use of other means of oral hygiene, the regular follow-up at a dentist's doctor and the place of the rheumatologist in therapeutic education on the oral dental hygiene status. <h3>Results:</h3> Table I illustrates the results of oral hygiene evaluation in RA patients. Table II illustrates the results of the place of oral hygiene information in rheumatologic management. <h3>Conclusion:</h3> This study illustrates the high prevalence of oral hygiene insufficiency in patients followed for RA. It also highlights poor therapeutic education given by the rheumatologist on the importance of adequate oral hygiene in the management of RA. <h3>Disclosure of Interests:</h3> None declared
AB0825 IMPACT OF AROMATASE INHIBITOR TREATMENT ON BONE MINERAL DENSITY AND PREVALENT VERTEBRAL FRACTURE
Authors: Cyrine Daldoul, Nejla El Amri, Sadok Laataoui, Khadija Baccouch, Imtinen Belaid, Hela Zeglaoui, Elyes Bouajina
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In recent years, despite the growing incidence of breast cancer, a reduction in mortality has been observed. Adjuvant therapy with aromatase inhibitors (AI) has contributed to a longer disease free survival. However these molecules induce a hyper bone remodeling, modifying the bone architecture and thus increasing the fracture risk. The new guidelines indicate extension of treatment duration up to 10 years. So special precautions must be established in order to avoid bone mineral density (BMD) decrease and to reduce fracture risk. <h3>Objectives</h3> The aim of this study was to evaluate the impact of AI treatment on BMD and to screen vertebral fracture (VF) in post menopausal women with breast cancer. <h3>Methods</h3> A clinical cross sectional study was carried between August 2018 and December 2018, including post-menopausal women with non-metastatic breast cancer. Each woman had an extensive medical history and physical examination. BMD was measured using dual energy X absorptiometry DeXa at femoral neck, total hip and at lumbar spine. We used the WHO criteria for the diagnosis of osteoporosis and osteopenia. Vertebral fractures were screened by performing a vertebral fracture (VFA) image. VF grade 1 were excluded. <h3>Results</h3> Thirty-six post-menopausal women were examined in our rheumatology department. The mean age was 59.5±10.38 years with an average body mass index (BMI) of 30.7 kg/m<sup>2</sup> [15.81-38.28].The average age of menopause was 45.5±5.25 years.The mean length of menopause was 14 years [2.1-31]. The mean duration of breast cancer follow-up was 71.7 months. 22 patients underwent chemotherapy and radiotherapy.Mean femoral neck BMD was 0.805 g/cm<sup>3</sup> [0.647-1.049 g/cm<sup>3</sup>] and the vertebral BMD was 1.003 g/cm<sup>3</sup> [0.739-1.314g/cm<sup>3</sup>].According to the WHO classification, 12 women (34.6%) had osteoporosis, 15 (42.3%) had osteopenia and 9 (19.2%) had normal BMD. 9 patients showed signs of osteoporosis at femoral neck and 8 had osteoporosis at lumbar spine. 10 subjects (27.8%) had VF identified by VFA, which were grade 2 and 3 in respectively 8 and 2 vertebra. No multiple VF were assessed. No statistically significant difference was found between women with and without VF for age, BMD value, and duration of follow-up or previous fragility fracture. We did not find a significant correlation between treatment length and BMD at either site: femoral neck (p=0.42), total hip (p=0.783) and lumbar spine (p=0.357). <h3>Conclusion</h3> This data has shown that approximately one-third of patients receiving AI treatment have at least one vertebral fracture, and 40% had osteoporosis. Therefore we need to screen bone mineral density and fracture in women under AI therapy. <h3>Disclosure of Interests</h3> None declared
FRI0182 FREQUENCY OF HYDROXYCHLOROQUINE RETINOPATHY IN THE HOPKINS LUPUS COHORT
Authors: Michelle A Petri, Marwa Elkhalifa, LI Jessica
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The Kaiser-Permanente study projected hydroxychloroquine (HCQ) retinopathy rates of 40% after 20 years of use (1). <h3>Objectives:</h3> We have prospectively followed SLE patients in the Hopkins lupus cohort to compare. <h3>Methods:</h3> Patients in the Hopkins cohort are seen quarterly for assessment of disease activity and lupus complications. Yearly ophthalmology examinations are requested. Patients, if insurance allows, are referred to the Wilmer Retina group. Four tests are performed: OCT, ERG, MP-1 and FAF. <h3>Results:</h3> Patients had a variety of retinal testing done, with optical coherence testing most frequent. Table 1 shows the concordance of a test abnormality with the retina expert opinion. The concordance of the test abnormality with the retina expert opinion showed the following sensitivity and specificity, respectively: OCT 93%, 84%; ERG 100%, 51%; MP1 100%, 70%; and FAF 83%, 76%. The frequency of retinopathy increased with years of HCQ use [number of retinopathies per total patients (percent frequency)]: 5 years or less, 1/103 (0.97%); 6-10 years, 2/109 (1.83%); 11-15 years, 3/91 (3.30%); 16-20 years, 11/96 (11.46%); and 21 or more years, 6/75 (8.00%). <h3>Conclusion:</h3> In agreement with the American Academy of Ophthalmology, OCT appears to be the optimum test for yearly monitoring (2). The frequency of retinopathy was much lower in our prospective study than estimated by the Kaiser-Permanente study. Our data also show the need for ophthalmologists with retinopathy expertise to interpret retina testing, as screening tests are frequently abnormal due to causes other than HCQ retinopathy. Stopping HCQ based on an abnormal test without confirmation from a retinopathy expert could needlessly deprive an SLE patient of an important medication. <h3>References:</h3> [1] Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol 2014;132:1453–1460. [2] Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 2016;123:1386–1394. <h3>Acknowledgement:</h3> The Hopkins Lupus Cohort was funded by NIH Grant R01-AR069572 <h3>Disclosure of Interests:</h3> Michelle A Petri Shareholder of: Pfizer, Merck, Grant/research support from: AstraZeneca, Exagen, Consultant for: Eli Lilly, GSK, Merck EMD Serono, Janssen, Amgen, Novartis, Quintiles, Exagen, Inova Diagnostics, AstraZeneca, Blackrock, Glenmark, UCB, and the Annenberg Center for Health Sciences, Marwa Elkhalifa: None declared, Jessica Li: None declared