tbuckley/cabot-search huggingface dataset:
AB0833 BONE TURNOVER MARKERS – DO THEY HAVE A ROLE AS PREDICTORS OF MORTALITY AND NEW FRACTURE IN PATIENTS WITH FRAGILITY HIP FRACTURE?
Authors: Miguel Guerra, Sara Ganhão, Francisca Aguiar, Raquel Ferreira, Teresa Martins-Rocha, Ana Filipa águeda, Georgina Terroso, Carlos Vaz, Lúcia Costa
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In Osteoporosis (OP), bone turnover markers (BTM) are potential monitors of drug adherence/efficacy as well as predictors of bone loss and fracture risk. However, without solid evidence, international guidelines still do not recommend their systematic measurement to assist treatment decision and follow-up. <h3>Objectives</h3> To evaluate the predictive value of baseline BTM (beta crosslaps – bCL; osteocalcin – OC) in the outcome (death and/or new fracture) of patients that suffered a fragility hip fracture (FHF). <h3>Methods</h3> Patients referred to a Fracture Liaison Service from March 2015 until March 2017 with a FHF were considered for this study. Clinical/demographic variables were collected, including: age at time of fracture, sex, serum OC and serum bCL at baseline and outcome (death, new fracture, lost to follow-up) until January 2018. Cox regression analysis was used to calculate hazard ratios (HR) for values of OC and bCL; p&lt;=0.05 was considered statistically significant. <h3>Results</h3> From a total of 522 patients, 218 presented a baseline measurement of OC and/or bCL and were included for analysis. Table 1 summarizes clinical and demographic characteristics of the sample. Twenty seven patients died (median days until death=457, min 160, max 1049) and 18 had a new fracture (median days until refracture 343.5, min 30, max 835); 129 patients maintained follow-up. Median serum bCL was 0.71 ng/ml (0.12-3.28, n=217) and median OC was 28.2 ng/ml (6.80-198.60, n=215). Through univariate analysis, higher bCL values predicted worse survival outcome (HR=3.09; 95% CI=1.14-8.39;p=0.026), even after adjustment for age/sex (HR=4.28; 95% CI=1.48-12.29;p=0.007); however, it did not predict higher risk of new fracture (HR=3.00;95%CI=0.85-10.68;p=0.089). Serum OC levels showed no statistically significant results, neither for mortality (HR=1.01; 95% CI=0.99-1.03;p=0.341) nor new fracture (HR=1.01;95%CI=0.99-1.04;p=0.057). <h3>Conclusion</h3> In this cohort, increased serum levels of bCL predicted higher mortality risk. These results support the value of BTM in OP, strengthening their potential as prognostic markers, besides treatment monitors. <h3>Reference</h3> [1] Glendenning P, Chubb SAP, Vasikaran S. Clin Chim Acta. 2018Jun;481:161-170. <h3>Disclosure of Interests</h3> None declared
Abstract 15366: Accurate Detection and Quantification of Atrial Fibrillation Using a Smartwatch With ECG Watchband
Authors: Jeremiah Wasserlauf, Cindy You, Ruchi Patel, David Albert, Rod S Passman
Journal: Circulation (2018)

Introduction: Atrial fibrillation (AF) burden and duration are related to stroke risk. A wearable device capable of accurate, long-term AF surveillance could be important for arrhythmia detection a...
Solithromycin versus ceftriaxone plus azithromycin for the treatment of uncomplicated genital gonorrhoea (SOLITAIRE-U): a randomised phase 3 non-inferiority trial
Authors: Marcus Y Chen, Anna McNulty, Ann Avery, David Whiley, Sepehr N Tabrizi, Dwight Hardy, Anita F Das, Ashley Nenninger, Christopher K Fairley, Jane S Hocking, Catriona S Bradshaw, Basil Donovan, Benjamin P Howden, David Oldach
Journal: The Lancet Infectious Diseases (2019)
Anagrelide Modulates Proplatelet Formation Resulting in Decreased Number and Increased Size of Platelets
Authors: Naohiro Miyashita, Masahiro Onozawa, Shota Yokoyama, Daisuke Hidaka, Koji Hayasaka, Shinji Kunishima, Takanori Teshima
Journal: HemaSphere (2019)

We retrospectively evaluated 48 essential thrombocythemia (ET) patients who were treated in our institute (male/female, 14/34, median age, 61.5 years). In 14 patients treated with anagrelide (ANA), the degree of platelet count reduction (median, -56.6%) was strongly correlated with increase of mean platelet volume (MPV) (median, +11.7%) (R = 0.777). This correlation was not observed in ET patients treated with hydroxycarbamide alone (R = 0.245). The change in size of platelets strongly suggested that ANA affected the final process of platelet production. Thus, we hypothesized that ANA modifies the process by which platelets are released from proplatelets. To verify the association in an in vitro setting, we compared MEG-01 cells treated with PMA ± ANA. The number of platelet-like particles (PLPs) was decreased (P < 0.05) and the size of PLPs estimated by using flow cytometry was significantly increased when MEG-01 cells were treated with PMA + ANA (P < 0.05 vs PMA alone), recapitulating the clinical findings. The cytoplasmic protrusions extending from MEG-01 cells were shorter and thicker and the number of proplatelets was decreased when MEG-01 cells were treated with PMA + ANA (P < 0.01 vs PMA alone). Western blotting analysis showed that ANA treatment resulted in increased phosphorylation of MLC2 and reduced phosphorylation of focal adhesion kinase (FAK). The morphological change of proplatelets were reversed by blebbistatin, a specific inhibitor of myosin II. These findings indicated that ANA modulates the FAK-RhoA-ROCK-MLC2-myosine IIA pathway and suppresses proplatelet maturation, leading to a decrease in platelet count and increase in MPV.
AB0187 CAN ARTIFICIAL INTELLIGENCE REPLACE MANUAL SEARCH FOR SYSTEMATIC LITERATURE REVIEW ON CUTANEOUS MANIFESTATIONS IN PRIMARY SJOGREN’S SYNDROME?
Authors: Laure Orgeolet, Nathan Foulquier, Laurent Misery, Pascal Redou, Jacques-Olivier Pers, Valerie Devauchelle-Pensec, Alain Saraux
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Manual systematic literature reviews are becoming increasingly challenging due to the sharp rise in publications. The task is particularly daunting when the study topic is complex. <h3>Objectives:</h3> The primary objective of this literature review was to compare manual and in-house computer software retrieval of publications on the cutaneous manifestations of primary Sjogren's Syndrome (pSS). The secondary objective was to evaluate the prevalence of cutaneous manifestations in pSS. <h3>Methods:</h3> We compared manual searching and searching with the in-house computer software BIBOT (1) designed for article retrieval and analysis. Both methods were used for a systematic literature review on a complex topic i.e., the cutaneous manifestations of pSS. Articles published in French or English between 1 January 1990 and 30 May 2018 were sought. <h3>Results:</h3> The manual search retrieved 855 articles and BIBOT 1042 articles. In all, 202 articles were then selecting by applying exclusion criteria. Among them, 155 were retrieved by both methods, 33 by manual search only, and 14 by BIBOT only. Further selection was performed by reading the 202 articles, of which 54 were deemed relevant, including 23 providing data on the prevalence of one or more cutaneous signs in a cohort of patients with pSS. Cohort sizes and the nature and prevalence of cutaneous manifestations varied across publications. In all, 52 cutaneous manifestations were reported, of which the most common were cutaneous vasculitis (561 patients), xerosis (651 patients), and annular erythema (215 patients). <h3>Conclusion:</h3> Agreement was good between the two methods. BIBOT was faster and automatically classified the articles in a chart. Combining the two methods retrieved the largest number of publications. The prevalence of cutaneous manifestations in patients with pSS varied considerably across studies. The advanced machine learning techniques used in artificial intelligence hold promise for literature reviews. <h3>References</h3> [1] Foulquier N, Redou P, Le Gal C, Rouvière B, Pers J-O, Saraux A. Pathogenesis-based treatments in primary Sjogren's syndrome using artificial intelligence and advanced machine learning techniques: a systematic literature review. Hum Vaccin Immunother2018;14:2553-2558. <h3>Disclosure of Interests:</h3> Laure Orgeolet: None declared, Nathan Foulquier: None declared, Laurent Misery: None declared, Pascal Redou: None declared, Jacques-Olivier Pers: None declared, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Alain Saraux Consultant for: Roche SAS, Speakers bureau: Chugai Pharma France
FRI0688 PREDICTORS OF EROSION AND JOINT SPACE NARROWING PROGRESSION IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS
Authors: Emil Rydell, Kristina Forslind, Jan-Åke Nilsson, Lennart T.H. Jacobsson, Carl Turesson
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Joint damage in rheumatoid arthritis (RA) includes erosions and joint space narrowing (JSN). Predictors of these processes, and the underlying mechanisms, require further study<sup>1</sup>. <h3>Objectives</h3> To investigate the relation between patient characteristics at RA diagnosis and progression of erosions and JSN, over 5 years. <h3>Methods</h3> Consecutive early RA patients (symptom duration &lt;12 months), recruited 1995-2005 from a defined area, managed according to usual care with no pre-specified treatment protocol, were followed through 5 years. Radiographs of hands and feet were scored in chronological order by a trained reader according to the modified Sharp-van der Heijde score (SHS), including separate erosion- and JSN scores. The relations between baseline variables and progression of erosion- and JSN scores over 5 years (log transformed), were assessed using linear regression. <h3>Results</h3> 233 early RA patients where included. Radiographs at baseline and 5 years were available for 162 patients. Results on predictors of rapid radiographic progression of the total SHS have been reported previously<sup>2</sup>. The median (interquartile) progression of erosion and JSN scores were 4 (0-8) and 8 (1-16), respectively. RF and anti-CPP predicted progression of erosions and JSN over 5 years, with stronger associations for erosions (Table 1). Baseline erosion- and JSN scores each predicted progression of JSN, while baseline JSN did not predict progression of erosions. In crude analyses, higher disease activity, CRP and ESR were associated with progression of both erosions and JSN, while statistically more robust for the former. Smoking and high levels of Cartilage Oligomeric Matrix Protein (COMP) (&gt;12 U/L) were both associated with progression of erosions ((B= 0.12, p= 0.016) and (B= 0.12, p= 0.02) respectively) but not JSN, in adjusted analyses (Table 1). Overweight or obesity (BMI &gt;25kg/m<sup>2</sup>) was associated with less progression of JSN (B= -0.14, p= 0.018, adjusted for RF, age and baseline JSN score). <h3>Conclusion</h3> RF, anti-CCP and markers of inflammation and disease activity predicted progression of erosions and JSN, in particular erosions. Development of erosions may predate cartilage damage leading to JSN. Smoking and high baseline levels of COMP predicted progression of erosions, but not JSN. Overweight and obesity may be associated with mechanisms that protect from JSN. <h3>References</h3> [1] Smolenet al, Ann Rheum Dis. 2009;68:1535-40.2 Rydell et al, Arthritis Res Ther. 2018;20:82. <h3>Disclosure of Interests</h3> Emil Rydell: None declared, Kristina Forslind: None declared, Jan-Åke Nilsson: None declared, Lennart T.H. Jacobsson Consultant for: LJ has received lecture and consulting fees from Pfizer, Abbvie, Novartis, Eli-Lily and Janssen, Carl Turesson: None declared
Ki-67 level in hormone reptor positive breast cancer patients: A retrospective review of 9,061 Korean women.
Authors: Jisun Kim, Wonshik Han, Yeon Hee Park, So Youn Jung, Eun Sook Lee, Jungsil Ro, Hyeong-Gon Moon, Soo Kyung Ahn, Jun Woo Lee, Min Kyoon Kim, Seock-Ah Im, Sae-Won Han, Tae-Yong Kim, Kyung-Hun Lee, In Ae Park, Dong Young Noh
Journal: Journal of Clinical Oncology (2013)

551 Background: Although young age breast cancer represents poor prognosis, no definitive explanation could have been made for the phenomenon. A tumor proliferation marker Ki67 is known to be a marker for both prognosis and prediction for chemotherapy responsiveness, and its level varies widely depending on the breast cancer subtype. This study was aimed to analyze Ki67 in relationship with age in hormone receptor positive breast cancer patients. Methods: We retrospectively reviewed 9061 consecutive cases of hormone receptor positive invasive breast cancer from data base at Seoul National University Hospital (SNUH) (between 2000 and 2012), Samsung Medical Center (SMC) (between 2004 and 2010), and National Cancer Center (NCC) (between 2001 and 2010) in Korea. Patients with estrogen receptor (ER) or progesterone receptor (PR) positive tumors were included irrespective of HER2 amplification. A multicenter data of Ki67 level identified by immunohistochemistry (IHC) and age at diagnosis were analyzed. Patients who underwent neoadjuvant systemic therapy were excluded. Results: Total 6222 cases from SNUH, 976 from SMC and 1863 from NCC were included. The three datasets were analyzed separately due to variable IHC methods in each institute. Mean ages were 49.30 years (range 20-86), 47.75 years (range 22-81) and 45.31 years (range 25-59), and mean Ki67 levels were 4.66% (range 1-100), 22.98% (range 1-97) and 14.58% (range 1-90), at SNUH, SMC, NCC respectively. Ki67 level was inversely proportional with age at diagnosis in all three datasets, and the level was significantly higher for patients &lt;40 years compared to ≥40 years (mean Ki67: 5.97 vs 4.41, p&lt;0.001; 28.60 vs 21.88, p&lt;0.001; 17.01 vs 14.03, p&lt;0.001, respectively). There was an inverse relation with age as well when Ki67 level was categorized into ‘&lt;10% vs ≥10% (p&lt;0.001)’, ‘&lt;20% vs ≥20% (p=0.03)’ and ‘&lt;14% vs ≥14% (p&lt;0.001)’ respectively. Conclusions: Despite the variability of assessing Ki67 expression, Ki67 level was significantly higher in young age hormone receptor positive breast cancer from all three analyses. This could partly explain the poor prognosis and substantial responsiveness to chemotherapy in this age group of patients.
Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies
Authors: Wei Zhou, Jonas B. Nielsen, Lars G. Fritsche, Rounak Dey, Maiken E. Gabrielsen, Brooke N. Wolford, Jonathon LeFaive, Peter VandeHaar, Sarah A. Gagliano, Aliya Gifford, Lisa A. Bastarache, Wei-Qi Wei, Joshua C. Denny, Maoxuan Lin, Kristian Hveem, Hyun Min Kang, Goncalo R. Abecasis, Cristen J. Willer, Seunggeun Lee
Journal: Nature Genetics (2018)
Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data
Authors: Ioanna Tachmazidou, Konstantinos Hatzikotoulas, Lorraine Southam, Jorge Esparza-Gordillo, Valeriia Haberland, Jie Zheng, Toby Johnson, Mine Koprulu, Eleni Zengini, Julia Steinberg, Jeremy M. Wilkinson, Sahir Bhatnagar, Joshua D. Hoffman, Natalie Buchan, Dániel Süveges, Laura Yerges-Armstrong, George Davey Smith, Tom R. Gaunt, Robert A. Scott, Linda C. McCarthy, Eleftheria Zeggini
Journal: Nature Genetics (2019)
Widespread natural variation of DNA methylation within angiosperms
Authors: Chad E. Niederhuth, Adam J. Bewick, Lexiang Ji, Magdy S. Alabady, Kyung Do Kim, Qing Li, Nicholas A. Rohr, Aditi Rambani, John M. Burke, Joshua A. Udall, Chiedozie Egesi, Jeremy Schmutz, Jane Grimwood, Scott A. Jackson, Nathan M. Springer, Robert J. Schmitz
Journal: Genome biology (2016)

DNA methylation is an important feature of plant epigenomes, involved in the formation of heterochromatin and affecting gene expression. Extensive variation of DNA methylation patterns within a species has been uncovered from studies of natural variation. However, the extent to which DNA methylation varies between flowering plant species is still unclear. To understand the variation in genomic patterning of DNA methylation across flowering plant species, we compared single base resolution DNA methylomes of 34 diverse angiosperm species.By analyzing whole-genome bisulfite sequencing data in a phylogenetic context, it becomes clear that there is extensive variation throughout angiosperms in gene body DNA methylation, euchromatic silencing of transposons and repeats, as well as silencing of heterochromatic transposons. The Brassicaceae have reduced CHG methylation levels and also reduced or loss of CG gene body methylation. The Poaceae are characterized by a lack or reduction of heterochromatic CHH methylation and enrichment of CHH methylation in genic regions. Furthermore, low levels of CHH methylation are observed in a number of species, especially in clonally propagated species.These results reveal the extent of variation in DNA methylation in angiosperms and show that DNA methylation patterns are broadly a reflection of the evolutionary and life histories of plant species.
SP0009 CARDIOVASCULAR RISK IN PSORIASIS AND PSORIATIC ARTHRITIS
Authors: Iain McInnes
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Psoriasis and psoriatic arthritis ar associated with increased cardiovascular and cardio metabolic risk. <h3>Objectives:</h3> To describe the prevalence and magnitude CV risk in psoriasis and psoriatic arthritis and to comment on the clinical therapeutic implications of this risk in our practice. <h3>Methods:</h3> Review of literature concerning CV risk and interpretation of the same. <h3>Results:</h3> MACE are elevated over time in people with psoriasis and PsA. The mechanisms driving this are currently unclear but likely include both the impact of traditional risk factors e.g. dyslipidaemia, hypertension, obesity and novel risk factors e.g. mediated via increased inflammatory burden. Increased vigilance is required to detect this risk and a low index of suspicion should be introduced in practice. Aggressive management of CV risk should improve outcomes. <h3>Conclusion:</h3> Recognising and treating factors mediating CV risk in psoriasis and psoriatic arthritis should comprise part of our routine clinical practice. <h3>Disclosure of Interests:</h3> Iain McInnes Grant/research support from: AstraZeneca, Celgene, Compugen, Novartis, Roche, UCB Pharma, Consultant for: AbbVie, Celgene, Galvani, Lilly, Novartis, Pfizer, UCB Pharma
PB1822 HIV‐ASSOCIATED LYMPHOMA: A REPORT OF 40 CASES AT YOPOUGON TEACHING HOSPITAL IN CÔTE D’IVOIRE
Authors: B. Kouakou, M. Diakité, A.D. Silué, D.L.V.S.C. Packo, Y.N. Atiméré, E. N’dhatz‐Comoé, I. Kamara, E.H.M. Chefou, R.‐P. Botti, N.C. Danho, A. Tolo‐Dièbkilé, G.K. Koffi, I. Sanogo
Journal: HemaSphere (2019)

Background: Lymphomas are a heterogeneous group of malignant haemopathies characterized by ganglionic and extra ganglionic infiltration of lymphoid cells. Their occurrence during the HIV infection had a specific clinical, therapeutic and evolutionary particularities. Aims: The aims of our study was to evaluate and compare the clinical, therapeutic and evolutionary aspects of HIV and none HIV patients. Methods: It was a descriptive and analytical case‐control study of patients with lymphoma followed at the department of clinical hematology at Yopougon Teaching Hospital from January 2014 to October 2016. The histology and immunohistochemistry was the diagnosis’ means to retain the diagnostic of lymphoma. The HIV test was performed by Western Blood. The variables of our study were the epidemiological, clinical, therapeutic and evolutionary aspects. Statistical analyzes were performed with épi info 351 and SPSS. The statistical test used was the ki2 test. Results: We collected 40 cases of lymphoma including 15 cases of HIV positive and 25 cases negative. The average age was 47 years with extremes of 27 and 65 years old. There was more male than female with a sex ratio of 2 for HIV positive and 3.16 for HIV negative. The reasons of consultation were dominated by polyadenopathies. The WHO performans status was stage 2 for 53.33% of HIV‐positive patient and stage 1 for 68% of HIV‐negative patients. Among HIV‐positive patients, 60% knew their status before the discovery of lymphoma and 53% already had opportunistic infections dominated by digestive and genital candida infection in 50% of cases. We noted 80% of aggressive lymphoma in the HIV‐positive patients with 26.6% Burkitt's lymphoma versus 68% aggressive lymphoma in the HIV‐negative patient. The lymph node localization was the most common with 66.6% for HIV‐positive patients and 84% for HIV‐negative patients. The breast localization was particularity observed with HIV positive patient. 86.6% of HIV‐positive patients have a bad prognosis against 16% for the HIV‐negative patients. For the treatment, the CHOP 21 protocol was the most used in both groups with 66.8% for HIV‐positive patients and 60% for HIV‐negative patients. The compliance was poor at 77% with HIV‐positive patients. The Median survival was 33 and 11 months, respectively, in the HIV‐negative and HIV‐positive patients. Summary/Conclusion: The prognosis of lymphoma with HIV remains pejorative in our country because often unknown before the diagnosis of lymphoma.
Clathrin-mediated Endocytosis of Alpha-1 Antitrypsin is Essential for its Protective Function in Islet Cell Survival
Authors: Jingjing Wang, Wenyu Gou, Do-sung Kim, Charlie Strange, Hongjun Wang
Journal: Theranostics (2019)

Cytokine-induced pancreatic β cell death plays a pivotal role in both type 1 and type 2 diabetes.Our previous study showed that alpha-1 antitrypsin (AAT) inhibits β cell death through the suppression of cytokine-induced c-Jun N-terminal kinase (JNK) activation in an islet transplantation model.The aim of this study was to further understand how AAT impacts β cells by studying AAT endocytosis in human islets and a βTC3 murine insulinoma cell line.Methods: In vitro, human islets and βTC3 cells were stimulated with cytokines in the presence or absence of chlorpromazine (CPZ), a drug that disrupts clathrin-mediated endocytosis.Western blot, real-time PCR and cell death ELISA were performed to investigate β cell death.The oxygen consumption rate (OCR) was measured on human islets.In vivo, islets were harvested from C57BL/6 donor mice treated with saline or human AAT and transplanted into the livers of syngeneic mice that had been rendered diabetic by streptozotocin (STZ).Islet graft survival and function were analyzed.Results: AAT was internalized by β cells in a time-and dose-dependent manner.AAT internalization was mediated by clathrin as treatment with CPZ, profoundly decreased AAT internalization, cytokine-induced JNK activation and the downstream upregulation of c-Jun mRNA expression.Similarly, addition of CPZ attenuated cytokine-induced caspase 9 cleavage (c-casp 9) and DNA fragmentation, which was suppressed by AAT.Treatment of donor mice with AAT produced AAT internalization in islets, and resulted in a higher percentage of recipients reaching normoglycemia after syngeneic intraportal islet transplantation.Conclusion: Our results suggest that AAT is internalized by β cells through clathrin-mediated endocytosis that leads to the suppression of caspase 9 activation.This process is required for the protective function of AAT in islets when challenged with proinflammatory cytokines or after islet transplantation.