tbuckley/cabot-search huggingface dataset:
AB0851 OBESITY AND RISK OF FRACTURE: DEPENDS ON THE BODY MASS INDEX AND TYPE OF FRACTURE
Authors: Jose Rosas, Catalina Cano, Ana Pons, Estíbaliz Ivars, José Miguel Senabre-Gallego, Gregorio Santos Soler, Esteban Salas-Heredia, José Antonio Bernal-Vidal, José Alberto García-Gómez, Xavier Barber
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Objectives</h3> To know the impact of obesity on the risk of fracture. <h3>Methods</h3> Observational study, during 2010-2018, of patients referred for bone densitometry (BMD), to the Bone Densitometry Unit of Rheumatology. BMD performed by Rheumatology nursing, collect several data (age, gender); osteoporosis (OP) risk factors: age of menopause, smoking and current alcohol intake, hip fracture parents, body mass index (BMI), diseases-drugs that reduce bone mass, fractures, treatment; BMD in lumbar spine (LS), femoral neck (FN); FRAX with BMD. BMI result was as WHO recommendations in kg/m<sup>2</sup>: Normal: 18.5-24.99; Obesity: ≥30; type I: 30-34.99, type II: 35.39.99, type III: ≥40. <h3>Results</h3> A first BMD in 6.943 postmenopausal women was done. 2.196 (32%) had normal BMI, low weight (BMI &lt;18.5 kg/m<sup>2</sup>) 103 (1.5%) patients, overweight (BMI 25-29.99 kg/m<sup>2</sup>) 2.643 (38%) and obesity 2.001 (29%). Obesity (BMI ≥30 kg/m<sup>2</sup>) vs normal BMI, are older (65±13 vs 61±13, p=0.005), lower current smokers (12% vs 27%) P &lt;0.0001), more treated for OP (37% vs 29%, p=0.002), higher percentage of fractures (44% vs 29%), especially distal radius (DR) (30% vs 11%), p&lt;0.001) and vertebral (19% vs 7%, p=0.002), lower mean T score in LS (-1.1±1.5 vs 1.8±1.5, p &lt;0.0001) and FN (-1.1±1.5 vs -1.6 ± 1.5, p&lt;0.0001) and lower mean FRAX hip fracture with BMD (1.9±3.6 vs 2.4±3.6, p &lt;0.0001). In table, obesity groups are compared with normal BMI. <h3>Conclusion</h3> In postmenopausal women referred for BMD, obese women vs normal BMI are 1. Older. 2. Overall, with higher percentage of fractures. 3. But, women with BMI≥ 40 kg/m<sup>2</sup> do not have a higher overall percentage of fracture, except in DR. <h3>Acknowledgement</h3> The study was supported with a research grant from the Association for Research in Rheumatology of Marina Baixa (AIRE-MB) <h3>Disclosure of Interests</h3> Jose Rosas Consultant for: Abbvie, Amgen, Bristol, Janssen, Lilly, Merck Sharp &amp; Dohme, Pfizer, UCB Pharma, Speakers bureau: Abbvie, Amgen, Bristol, Janssen, Lilly, Merck Sharp &amp; Dohme, Pfizer, UCB Pharma, Catalina Cano: None declared, Ana Pons: None declared, Estíbaliz Ivars: None declared, José Miguel Senabre-Gallego: None declared, Gregorio Santos Soler: None declared, Esteban Salas-Heredia: None declared, José Antonio Bernal-Vidal: None declared, José Alberto García-Gómez: None declared, Xavier Barber: None declared
Abstract 15: Repopulation of CA1 Region in the Hippocampus is Accompanied by Increased Diameter and Reduced Glial Scarring After 20 Weeks of Survival in an 8 Min Ventricular Fibrillation Cardiac Arrest Rat Model
Authors: Wolfgang Weihs, Florian Ettl, Ingrid A Magnet, Alexandra M Warenits, Harald Herkner, Michael Holzer, Andreas Janata, Sandra Högler
Journal: Circulation (2018)

Background: The CA1 region of hippocampus is specifically vulnerable to global ischemia and is depopulated 14 days after 8min ventricular fibrillation cardiac arrests (VF-CA) and conventional resuscitation in a rat model. We have previously reported on the pyramidal cell repopulation of the CA1 region after long term survival after cardiac arrest in two thirds of animals. (Circulation. 2014;130:A80) The aim of this study was to investigate the distribution of microglia and astrocytes in the CA1 region of rat hippocampus after CA and to measure its diameter. Methods: After 8 min of VF-CA male Sprague-Dawley rats received mechanical chest compressions for 2 min and epinephrine 20 μg/kg. The animals were defibrillated thereafter every 2 min to achieve return of spontaneous circulation. Animals surviving with favorable neurologic recovery were sacrificed 140 days after CA (n=12, 8 with neuronal repopulation (R), 4 without R (nonR)) and compared to 14 day survivors (n=6) and control animals (n=20). Results: Microglia cells/ 75000μm 2 were 6±3 in controls, 53±9 in 14d survivors (p&lt;0.001 vs controls), 12±4 in 140d-R and 19±12 in 140d-nonR. Astrocytes/75000μm 2 were 9±2 in controls, 15±3 in 14d survivors (p&lt;0.001 vs controls), 21±4 in 140d-R and 43±13 in 140d-nonR animals (p&lt;0.001 vs 140d-R). The hippocampal diameter (μm) was 543±36 in controls, 417±36 in 14d survivors (p&lt;0.001 vs controls), 462±39 in 140d-R and 306±86 in 140d-nonR animals (p&lt;0.001 vs 140d-R). Conclusions: The repopulation of pyramid cells in the CA1 that has taken place in two thirds of animals is accompanied by a significant increase in the diameter of the hippocampus and reduced astrocyte numbers compared to nonR-animals. Numbers of microglial cells are significantly increased after 14d survival removing cell debris after neuronal damage. This lifelong potential of the hippocampus for repair due to adult neurogenesis may open an additional late phase therapeutic window for CA recovery.
Abstract 13280: Genetic Variants Previously Associated with Brugada Syndrome in Newly Exome Data
Authors: Bjarke Risgaard, Reza Jabbari, Lena Refsgaard, Anders Holst, Stig Haunsø, Ahmad Sadjadieh, Bo Winkel, Morten Olesen, Jacob Tfelt-Hansen
Journal: Circulation (2012)

Introduction: Today, hundreds of variants in 13 genes have been associated with Brugada Syndrome (BrS), which is considered a monogenic disorder with a prevalence between 1:2.000 and 1:100.000. Unt...
Prevalence of vaping and smoking among adolescents in Canada, England, and the United States: repeat national cross sectional surveys
Authors: David Hammond, Jessica L Reid, Vicki L Rynard, Geoffrey T Fong, K Michael Cummings, Ann McNeill, Sara Hitchman, James F Thrasher, Maciej L Goniewicz, Maansi Bansal-Travers, Richard O’Connor, David Levy, Ron Borland, Christine M White
Journal: BMJ (2019)

To examine differences in vaping and smoking prevalence among adolescents in Canada, England, and the United States.
Abstract 10334: Activation of NAD(P)H Oxidase by Tryptophan-derived 3-hydroxykynurenine Accelerates Endothelial Apoptosis and Dysfunction in vivo
Authors: Qiongxin Wang, Ming-Hui Zou
Journal: Circulation (2013)

Background: The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism in mammals. The Trp-Kyn pathway is reported to regulate several fundamental biological processes, includi...
The compendium of self-enactable techniques to change and self-manage motivation and behaviour v.1.0
Authors: Keegan Knittle, Matti Heino, Marta M. Marques, Minna Stenius, Marguerite Beattie, Franziska Ehbrecht, Martin S. Hagger, Wendy Hardeman, Nelli Hankonen
Journal: Nature Human Behaviour (2020)
THU0572 RHEUMATOLOGICAL ASPECTS OF FORMS AND VARIANTS OF PANNICULITIS
Authors: Olga Egorova, Boris Belov, Svetlana Glukhova, S. Radenka-Lopovok
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Panniculitis (Pn) is a set of heterogeneous inflammatory diseases characterized by lesions of subcutaneous fat (SCF) and often accompanied with the defeat of the musculoskeletal system and internal organs. Depending on the etiology and histomorphological picture, Pn is divided into two forms: septal (SPn) and lobular panniculitis (LPn) with and without signs of vasculitis, which is reflected in the clinical picture of the disease. Often Pn is one of the symptoms of rheumatic diseases (Rd), it can lead to late diagnosis of the underlying disease. Objectives: to study the frequency of occurrence of forms and variants of Pn in rheumatological practice on the basis of long-term prospective observation <h3>Methods</h3> We examined 687 patients with Pn (613 women and 74 men, mean age 39.7±11.31 and 41.2±12.57 years, respectively) with the referral diagnosis of "Erythema Nodosum" (EN) or "Panniculitis", who were observed in the rheumatologic clinic in 2007-2017. In addition to general clinical examination, we determined serum concentrations of α-1 antitrypsin, amylase, lipase, ferritin, creatine phosphokinase, conducted a CT scan of the chest organs, immunological, TB tests and pathological study of skin biopsy from the node. <h3>Results</h3> As a result of application of the developed diagnostic algorithm, 430 patients (62.6%) were diagnosed with Spn and 249 patients (36.2%) - with LPn. In 9 cases (1%) (3 patients with SPn and 6 — with LPn), it was not possible to confirm the variant of Pn, despite the comprehensive examination. In 8 patients (1.1%) no Pn data were revealed, the following diagnoses were verified: 2 patients (25%) — discoid lupus and lipodystrophy, 1 (12.5%) — erysipelas, lichen, fixed erythema and keratoacanthoma. SPn in 94% of cases (400 patients) was presented by EN, in 4% (18) — by superficial migrating thrombophlebitis, in single cases (1-0%) — by eosinophilic fasciitis, skin nodular polyarteritis and scleroderma-Pn (2, 6 and 1 patients, respectively). In 28% of cases LPn was associated with systemic connective tissue lesions, in 27% with idiopathic lobular Pn (Weber — Christian panniculitis) (p&lt;0.002), in 32.92% with lipodermatosclerosis and in 14.28% with subcutaneous sarcoid. In a few cases Lpn was caused by lymphoproliferative (2,88%) and cancer (2,49%) diseases, calciphylaxis (2,05%), erythema Bazin (1.64%), cold Pn (0.82%) and alpha 1-antitrypsine failure (0.41%) Conclusion: the results confirm that patients with SPn were found twice as often as with LPn. Prenosological Pn was mainly associated with sarcoidosis, EN and Rd, which confirms the relevance of further research of Pn. <h3>Disclosure of Interests</h3> None declared
Antibody therapeutics and immunoregulation in cancer and autoimmune disease
Authors: Masahiro Yasunaga
Journal: Seminars in Cancer Biology (2019)

Cancer and autoimmune disease are closely related, and many therapeutic antibodies are widely used in clinics for the treatment of both diseases. Among them, the anti-CD20 antibody has proven to be effective against both lymphoid malignancy and autoimmune disease. Moreover, immune checkpoint blockade using the anti-PD1/PD-L1/CTLA4 antibody has improved the prognosis of patients with refractory solid tumors. At the same time, however, over-enhancement of immunoreaction can induce autoimmune reaction. Although anti-TNF antibody therapies represent a breakthrough in the treatment of autoimmune diseases, optimal management is required to control the serious associated issues, including development and progression of cancer, and it is becoming more and more important to control the immunoreaction. In addition, next-generation antibody therapeutics such as antibody-drug conjugates and bispecific antibodies, are anticipated to treat uncontrolled cancer and autoimmune disease. IL-7R signaling plays an important role in the development and progression of both lymphoid malignancy and autoimmune disease. In addition, abnormal homing activity and steroid resistance caused by IL-7R signaling may worsen prognosis. Therefore, anti-IL-7R targeting antibody therapies that enable suppression of such pathophysiological status have the potential to be beneficial for the treatment of both diseases. In this review, we discuss current antibody therapeutics in cancer and autoimmune disease, and describe a new therapeutic strategy for immunoregulation including IL-7R targeting antibodies.
PS1100 CONGENITAL FACTOR V DEFICIENCY FROM COMPOUND HETEROZYGOUS MUTATIONS WITH A NOVEL MUTATION C.2426DEL (P.PRO809HISFS<sup>∗</sup>2) IN THE F5 GENE
Authors: C.‐H. Park, M.‐S. Park, K.‐O. Lee, S.‐H. Kim, Y.S. Park, H.‐J. Kim
Journal: HemaSphere (2019)

Background: Congenital factor V deficiency (FVD) is a rare bleeding disorder characterized by low or undetectable plasma FV levels leading to mild to severe bleeding symptoms. Currently, more than 100 mutations have been reported in F5 . The majority of F5 mutations are missense mutations (61.5%), and small deletion and splicing mutations account for 18.5% and 11.9%, respectively. Aims: We herein report a patient with FVD from compound heterozygous mutations including a novel deleterious mutation. Methods: The patient was a 52‐year‐old man with prolonged PT and aPTT corrected by mixing test on preoperative screening. His past medical or family history was not remarkable. Factor assays revealed a markedly reduced FV activity at 7%. Other factors were not decreased. DNA sequencing analysis to detect F5 gene mutations was performed after obtaining written informed consent. Results: Two different heterozygous mutations in F5 were detected: a missense variant (c.286G&gt;C [p.Asp96His]) and a frameshift variant from small deletion (c.2426del [p.Pro809Hisfs ∗ 2]). The Asp96His was previously described missense mutation and Pro809Hisfs ∗ 2 was a novel deleterious mutation. Summary/Conclusion: We herein report an asymptomatic patient with FVD from compound heterozygous mutations of F5 including a novel frameshift mutation. As was the case in our patient, genotype‐phenotype correlations are poor in FVD, and molecular genetic test is necessary to confirm the diagnosis.
PB1989 SHORT‐TERM APPLICATION OF CAFFEIC ACID SPECIFICALLY PROMOTES EXPANSION OF HEMATOPOIETIC STEM CELLS
Authors: Y. Liu, R. Wang, Y. Liu, X. Liu, Y. Wang, M. Hou
Journal: HemaSphere (2019)

Background: Caffeic acid (CFA) is a commonly used medicine in China for treatment of various causes of thrombocytopenia and leukocytopenia, but the mechanism is unclear. Aims: To investigate the effect of CFA on umbilical cord blood hematopoietic stem cells (UCB–HSCs) in vitro and explore the differentiated effect of CFA on cell expansion and differentiation in various tissues in vivo . Methods: CD34 + HSCs were isolated from cord blood and cultured for expansion. After 7 days’ culture with CFA, the total cell number and proportion of CD34 + cells were detected. Differentiation ability was analyzed by colony formation assay and megakaryocytes inducing assay before and after expansion. Additionally, CD‐1 mice were administered with CFA or vehicle for 14 days and BrdU injection started from day 7. Blood cell count was examined every 3 days. The proportion in bone marrow nucleated cells and BrdU insertion rate of HSCs were detected by flow cytometry. Besides, the percentage and BrdU insertion rate of Lgr5 + stem cells in intestinal mucosa, Sca‐1 + cells in lung and CK‐18 + epithelial cells in kidney were also analyzed. Results: In HSC expansion tests, the mean number (4.40∗10^5/well) and proportion (60%) of CD34 + cell in CFA groups were significantly higher than controls (4.00∗10^5/well; 48%). In HSC colony formation assay and megakaryocytes inducing assay, there were no significant difference between CFA groups and control. In vivo , the mean proportion (1.59%) and BrdU insertion rate (5.18%) of HSCs in CFA groups were higher than control (0.65% and 2.24%). No statistical differences were observed in other tissues. Summary/Conclusion: CFA can promote expansion of UCB–HSCs. Administration of CFA for 14 days specifically increased the proportion and DNA synthesis rate of bone marrow HSC in mice. image
Abstract 11659: Mechanical Dyssynchrony is Predictive of Clinical Outcomes After Cardiac Resynchronization Therapy in Patients with Chronic Kidney Disease
Authors: Mohamed Ahmed, Josef Marek, Tetsuari Onishi, Toshinari Onishi, Stephanie C Haberman, David Schwartzman, John Gorcsan
Journal: Circulation (2012)

Background: Although cardiac resynchronization therapy (CRT) benefits many heart failure (HF) patients, about 1/3 are non-responders. Chronic kidney disease (CKD) has been identified as an importan...
PB1921 COMPREHENSIVE ANALYSIS OF MOLECULAR RESPONSE IN TUNISIAN CML PATIENTS FOR TREATMENT DISCONTINUATION
Authors: R. Frikha, M. Elloumi, H. Kamoun
Journal: HemaSphere (2019)

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by a balanced genetic translocation, t(9;22)(q34;q11.2) and the generation of a BCR‐ABL1 fusion oncogene. Assessment and monitoring of BCR‐ABL1 levels by quantitative PCR (qPCR) is essential for the management of CML patients treated with TKIs. Currently, deeper molecular response (DMR: BCR‐ABL1 ≤0,01% IS) is considered to be the gateway to treatment‐free remission, which is becoming a high‐priority goal of CML treatment. Thus, achieving deep molecular response is a requirement for a successful treatment discontinuation. Aims: This study was carried out to identify patients with chronic myeloid leukemia (CML) treated with TKI therapy in routine clinical practice in Tunisia potentially eligible for treatment discontinuation, based on a molecular response (MR) on the international scale (IS). Methods: It was a 2 years retrospective study of 114 CML patients who attended the hematology department at the Hospital University of Sfax, south of Tunisia. Quantitative assessment of the BCR‐ABL transcript was performed using the Cepheid Xpert BCR‐ABL ultra assay. Results: Most patients (67,5% i.e 77/114) had an optimal response according to the European LeukemiaNet 2013 guidelines. Among them; 58,4% were in deep molecular response at their last visit and had been receiving TKI for at least 4 years. Summary/Conclusion: Despite the limit of our study, the available real‐life molecular responses with TKI therapy should be considered to identify potentially CML patients eligible for discontinuation of TKI therapy.
FRI0010 TCR-CD3Z GENE EXPRESSION PROFILE IN A COHORT OF PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Abeer Abdelati, Rehab Elnemr, Ahmed Shaaban, Marwa Gamal
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Advances in understanding the pathogenesis of RA support the contribution of T cells in the disease process through the recognition of the arthritogenic antigen (Ag) and maintenance of chronic inflammatory response [1]. Previous gene association studies have demonstrated that CD247 gene expressions are associated with a variety of autoimmune disease. As regard Rheumatoid Arthritis (RA), this relationship has not been fully clarified yet. <h3>Objectives</h3> We aimed to evaluate the T-cell receptor-CD3 zeta chain (<i>TCR-CD3</i> ζ) gene expression profile in a cohort of patients with RA. <h3>Methods</h3> A case-control study on 150 consecutive RA patients diagnosed according to 2010 ACR/EULAR criteria and 150 matched healthy controls without family history of RA or other autoimmune diseases. RA patients with other autoimmune diseases, viral hepatitis B or C, malignancy or hematological disorders were excluded from the study. All participants were subjected to history taking, clinical examination, assessment of disease activity (in RA patients) using DAS-28 and HAQ, routine laboratory investigations, inflammatory markers level, serological tests, as well as molecular analysis for <i>TCR-CD3ζ</i> mRNA expression by quantitative real-time polymerase chain reaction. <h3>Results</h3> <i>TCR-CD3ζ</i> gene expression was significantly lower in RA cases than in healthy controls (p&lt;0.05)<i> (Table 1)</i>. Expression of <i>TCR-CD3ζ</i><b>revealed</b> a significant negative correlation with RA disease duration, RF, and ESR (p&lt;0.05) in RA cases. The level of<b><i>TCR-CD3ζ</i> also showed a significant lower expression in +ve RF patients than in –ve RF patients (p&lt;0.05). The AUC of <i>TCR-CD3ζ</i> level showed a moderate level of accuracy (AUC = 0.840, p=0.025) (<i>Figure 1),</i> and the calculated cutoff value (≤ 0.077) can precisely discriminate subjects with RA from those without RA with 93.5% sensitivity and 75% specificity(<i>Table 2</i>).</b> <h3>Conclusion</h3> Our results demonstrated a lower expression of TCR-CD3ζ in RA patients than in healthy controls. We suggested that CD247 gene down-regulation might contribute in the susceptibility to RA and help understanding the mechanisms responsible for deficient T-cell responses in RA patients. <h3>Reference</h3> [1] Wfeyand CM, Gaoronzy JJ. Pathogenesis of rheumatoid arthritis. Med Clin North Am 1997; 81:29–55. <h3>Disclosure of Interests</h3> None declared
Epigenetic signatures associated with imprinted paternally expressed genes in the Arabidopsis endosperm
Authors: Jordi Moreno-Romero, Gerardo Del Toro-De León, Vikash Kumar Yadav, Juan Santos-González, Claudia Köhler
Journal: Genome biology (2019)

Imprinted genes are epigenetically modified during gametogenesis and maintain the established epigenetic signatures after fertilization, causing parental-specific gene expression. In this study, we show that imprinted paternally expressed genes (PEGs) in the Arabidopsis endosperm are marked by an epigenetic signature of Polycomb Repressive Complex2 (PRC2)-mediated H3K27me3 together with heterochromatic H3K9me2 and CHG methylation, which specifically mark the silenced maternal alleles of PEGs. The co-occurrence of H3K27me3 and H3K9me2 on defined loci in the endosperm drastically differs from the strict separation of both pathways in vegetative tissues, revealing tissue-specific employment of repressive epigenetic pathways in plants. Based on the presence of this epigenetic signature on maternal alleles, we are able to predict known PEGs at high accuracy and identify several new PEGs that we confirm using INTACT-based transcriptomes generated in this study. The presence of the three repressive epigenetic marks, H3K27me3, H3K9me2, and CHG methylation on the maternal alleles in the endosperm serves as a specific epigenetic signature that allows prediction of genes with parental-specific gene expression. Our study reveals that there are substantially more PEGs than previously identified, indicating that paternal-specific gene expression is of higher functional relevance than currently estimated. The combined activity of PRC2-mediated H3K27me3 together with the heterochromatic H3K9me3 has also been reported to silence the maternal Xist locus in mammalian preimplantation embryos, suggesting convergent employment of both pathways during the evolution of genomic imprinting.