tbuckley/cabot-search huggingface dataset:
Controllable Autocatalytic Cleavage-Mediated Fluorescence Recovery for Homogeneous Sensing of Alkyladenine DNA Glycosylase from Human Cancer Cells
Authors: Li-Juan Wang, Ming-Li Luo, Xiao-Yun Yang, Xiao-Fang Li, Yanxia Wu, Chun-Yang Zhang
Journal: Theranostics (2019)

DNA alkylation and oxidation are two most common forms of cytotoxic damage with the characteristics of mutagenic and carcinogenic.Human alkyladenine DNA glycosylase (hAAG) is the only glycosylase known to repair a wide variety of alkylative and oxidative DNA lesions.However, few approaches are capable of real-time monitoring hAAG activity.Methods: Herein, we develop a facile fluorescent strategy for homogeneous and sensitive sensing of hAAG activity based on the controllable autocatalytic cleavage-mediated fluorescence recovery.The presence of hAAG enables the cleavage of hairpin probe 1 (HP1) at the damaged 2′-deoxyinosine site by AP endonuclease 1 (APE1), forming a DNA duplex.The trigger 1 built in the resultant DNA duplex may hybridize with hairpin probe 2 (HP2) to induce the T7 exonuclease (T7 exo)-catalyzed recycling cleavage of HP2 (Cycle I) to release trigger 2. The trigger 2 can further hybridize with the signal probe (a fluorophore (FAM) and a quencher (BHQ1) modified at its 5′ and 3′ ends) to induce the subsequent recycling cleavage of signal probes (Cycle II) to liberate FAM molecules.Through two-recycling autocatalytic cleavage processes, large amounts of fluorophore molecules (i.e., FAM) are liberated from the FAM-BHQ1 fluorescence resonance energy transfer (FRET) pair, leading to the amplified fluorescence recovery.Results: Taking advantage of the high accuracy of in vivo DNA repair mechanism, the high specificity of T7 exo-catalyzed mononucleotides hydrolysis, and the high efficiency of autocatalytic recycling amplification, this strategy exhibits high sensitivity with a detection limit of 4.9 × 10 -6 U/μL and a large dynamic range of 4 orders of magnitude from 1 × 10 -5 to 0.1 U/μL, and it can further accurately evaluate the enzyme kinetic parameters, screen the potential inhibitors, and even quantify the hAAG activity from 1 cancer cell. Conclusion:The proposed strategy can provide a facile and universal platform for the monitoring of DNA damage-related repair enzymes, holding great potential for DNA repair-related biochemical research, clinical diagnosis, drug discovery, and cancer therapy.
Abstract 13169: Validation of an Artificial Intelligence Algorithm for Diagnostic Prediction of Coronary Disease in Patients With Acute Thoracic Pain: Comparison With an Human Intelligence Model
Authors: Yasmin F Lacerda, Gabriela O Bagano, Daniel Lopes, Vitor C Correia, Leticia L Fonseca, Thiago M Souza, Lara Q Kertzman, Fernanda O Lopes, Luiza M Lino, Pedro H Filgueiras, Marcia M Rabelo, Luis C Correia
Journal: Circulation (2018)

Introduction: The evolution of computers ability to process information has enabled algorithms capable of translation an infinity of patterns into probabilities. The accuracy of this artificial int...
Abstract 15948: Decreasing the Rate of Thromboembolism During Cardiac Radiofrequency Ablation: A Novel “Hood” Prototype Device
Authors: Omar Yasin, Alan Sugrue, Vaibhav Vaidya, Anas Abudan, Ameesh Isath, Deepak Padmanabhan, Suraj Kapa, Samuel Asirvatham
Journal: Circulation (2018)

Introduction: Radiofrequency (RF) catheter ablation is an effective treatment modality for cardiac arrhythmias. Left-sided (systemic) ablation poses a risk for thromboembolic events, such as stroke...
AB0080 THE INHIBITION OF IL-25 TO THE EFFECT OF IL-17 TO ERK1/2 AND MMP–3 IN RHEUMATOID ARTHRITIS FIBROBLAST-LIKE SYNOVIALCYTES
Authors: Lu Jinyue, Feng Yuchen, Kang Guorong, Zhang Hui, Shen HaiLi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a common chronic systemic autoimmune diseases characterized by the inflammation in joint and synovium. Synovitis leads to the destruction of cartilage and bone in joint subsequently joint dysfunction and even disability eventually.Recently, IL-25 has been found to play a role in regulating inflammation through Th1 and Th17 responses in inflammatory diseases<sup>[</sup><i><sup>3</sup></i><sup>]</sup>, However, the function to fibroblast-like synoviocytes and its signaling pathway are not clear. This study aims to probe the effects of IL-25 on the expression of ERK1/2 and MMP-3 in RA fibroblast-like synoviocytes. <h3>Objectives:</h3> To study the function of IL - 25 for rheumatoid arthritis (RA) fibroblast - like synoviocytes(FLS) differentiation as well as to the effects on the expression of extracellular regulating protein kinase (ERK) and matrix metalloproteinases-3 (MMP-3). <h3>Methods:</h3> The differences on ERK1/2 and MMP-3 protein levels were tested in RA-FLS and healthy controls, then IL-17A (10ng/ml), different concentrations of IL-25 (0.01, 0.1, 1 and 10ng/ml) and IL-17A(10ng/ml) to co-stimulate the RA-FLS for 24 hours respectively.The expression of ERK1/2 and MMP-3 protein were detected by the Wesern blot. The results were expressed by ±<i>s</i>, <i>t</i> test was used for the comparison between different groups. <h3>Results:</h3> The expression of ERK1/2 (1.71±0.17) and MMP-3 (0.50±0.13) proteins in RA-FLS was higher than the healthy controls (0.50±0.15, 0.17±0.05)(t=-9.13,P&lt;0.001and t=-4.10,P&lt;0.05), because of the stimulation of IL-17A, the expression of ERK1/2 (0.77±0.22) and MMP-3 (0.59±0.13) proteins in RA-FLS were increased compared with untreated groups (0.18±0.35, 0.04±0.03)(t=-4.69,P&lt;0.01 and t=-7.47,P&lt;0.01).with the increasion of the concentration on IL-25, the level of ERK1/2 (0.54±0.26, 0.48±0.18, 0.48±0.23, 0.23±0.06)and MMP-3 (0.58±0.09, 0.59±0.14, 0.21±0.04, 0.04±0.02)in RA-FLS which stimulated by IL-17A was decreased slowly (t=4.22,P&lt;0.05 and t=4.95,P&lt;0.01 and t=7.47,P&lt;0.01). <h3>Conclusion:</h3> IL-25 can inhibit the stimulation of IL-17A on ERK1/2 and MMP-3 fractionally,which imply that it may take part in the development of RA through this pathway and may play as a target for the RA treatment on IL-17A. <h3>Disclosure of Interests:</h3> None declared
SP0003 NSAIDS – HOW TO OPTIMALLY USE THEM? (SAFETY OF NSAIDS)
Authors: Victoria Navarro-Compán
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The management of patients with axial spondyloarthritis (axSpA) requires a combination of non-pharmacological and pharmacological treatment modalities. Among pharmacological treatment, nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line drug. NSAIDs have shown to be efficacious to reduce symptoms and signs in patients with axSpA. Nevertheless, NSAIDs are not exepmt of side effects especially when administered chronically, as in patients with axSpA. These include gastrointestinal, cardiovascular and nephrological side effects. In addition, some situations may influence on the prescription of NSAIDs, such as the presence of some extrarheumatolgical manifestations of the disease (inflammatory bowel disease), comorbidities and family planning-decisions including pregnancy and breastfeeding. Therefore, it is essential taking risk and benefits of NSAIDs use to properly manage patients with axSpA. During this presentation, the optimal usage of NSAIDs in patients with axSpA will be analysed and discussed, taken into account all the possible side effects and the context of the patient. <h3>Disclosure of Interests</h3> None declared
PB1942 DOES STEPWISE DOSE ESCALATION METHOD OF NILOTINIB FOR CML IMPROVE MR4.5 AND TREATMENT FREE REMISSION?
Authors: K. Mayama, K. Yamaguchi, S. Yamashita, T. Ebina, T. Tachita, K. Kamata, K. Yamagata, Y. Tamai, H. Takami, S. Fukuda, K. Ota, T. Fujii, T. Akagi, K. Kubo
Journal: HemaSphere (2019)

Background: Every TKI has it's unique adverse events (AEs) and AEs drive therapeutic outcome down in patient with CML-CP. Treatment completion rate(TCR), complete molecular response(MR4.5), and treatment free remission(TFR) were examined. Aims: We conducted this study aiming at improving TCR, MR4.5, and TFR by stepwise dose escalation method of nilotinib. Methods: TCR, MR4.5, and TFR (6, 12, and 18 months) were examined by stepwise dose escalation method of nilotinib (4-Stepwise method, i.e., 150mg-14day, 300mg-14day, 450mg-14day, 600mg-2years) in imatinib experienced or newly diagnosed patient with CML-CP. Results: 25 cases were enrolled in this study and all patient were received this method. Consequently, all patients achieved 600 mg, TCR was 100% by the method. 22 cases (88%) achieved MR4.5, and all of them transferred to treatment discontinuation phase. 7 cases out of 22 lost MMR in non-treatment period, and all of them remained in the CP phase and were administered nilotinib again. TFR at 6, 12, 18 months were 86%(19/22), 75%(15/20), 79%(15/19), respectively. NK cell activity at before treatment, one of important biomarker, showed a significant difference between not achieved MR4.5 group and achieved MR4.5 group(P = 0.04).Summary/Conclusion: In this study, our stepwise dose escalation method of nilotinib (4-Stepwise method, i.e., 150mg-14day, 300mg-14day, 450mg-14day, 600mg-2years) will make good use of improving therapeutic outcome. TCR was 100%. 22 out of 25 cases (88%) achieved MR4.5, and all of them were transferred to treatment discontinuation phase. 7 out of 22 cases lost MMR, TFR at 6, 12, 18 months were 86%(19/22), 75%(15/20), 79%(15/19), respectively. NK cell activity at before treatment, showed a significant difference between not achieved MR4.5 group and achieved MR4.5 group(P = 0.04).
Abstract 14167: Clinical Characteristics of Subjects With Different Levels of Systemic Erythrocyte-bound Apolipoprotein B
Authors: Marijke A de Vries, Boudewijn Klop, Noëlle van der Meulen, Gert-Jan M van de Geijn, Lenneke Prinzen, Ellen van der Zwan, Erwin Birnie, Manuel Castro Cabezas
Journal: Circulation (2015)

Introduction: The level of apolipoprotein (apo) B-containing lipoproteins in plasma is positively associated with cardiovascular risk. We have previously demonstrated that apo B bound to circulating erythrocytes (ery-apoB) may protect against atherosclerosis. We evaluated the clinical characteristics of subjects with different levels of ery-apoB. Methods: Ery-apoB was measured by flow cytometry in subjects with (n=177) and without (n=208) cardiovascular disease (CVD), and expressed as mean fluorescent intensity in arbitrary units (au). The number of criteria for metabolic syndrome as outlined by the NCEP was scored. Carotid intima media thickness (cIMT) was measured using B-mode ultrasound. Data are given as median (IQR). Results: Ery-apoB was lower in patients with CVD than in controls (0.80 (0.40-1.40) and 0.90 (0.46-1.79) au, respectively, p=0.039). Ery-apoB was inversely associated with cIMT, waist circumference, plasma triglycerides, C-reactive protein and complement C3, and was positively associated with HDL-cholesterol. Ery-apoB was similar in men and women. The number of criteria for the metabolic syndrome was closely associated with ery-apoB, in a dose-depending manner. Median ery-apoB decreased with increasing number of metabolic syndrome criteria (Kruskall Wallis test, p=0.02). Furthermore, ery-apoB was almost 3-fold higher in subjects with blood group O than in subjects with a non-O blood group (1.40 (0.75-2.15) and 0.50 (0.10-0.95) au, respectively, p&lt;0.001). No correlation between ery-apoB and plasma apo B was found, and ery-apoB was unrelated to statin use. Discontinuation of statin use did not affect ery-apoB (n=54). Conclusion: Apo B bound to circulating erythrocytes is associated with several characteristics of the metabolic syndrome, inflammation and ABO blood group. These data provide novel insight into the mechanisms involved in the binding of atherogenic lipoproteins to erythrocytes.
Open Source Brain: A Collaborative Resource for Visualizing, Analyzing, Simulating, and Developing Standardized Models of Neurons and Circuits
Authors: Padraig Gleeson, Matteo Cantarelli, Boris Marin, Adrian Quintana, Matt Earnshaw, Sadra Sadeh, Eugenio Piasini, Justas Birgiolas, Robert C. Cannon, N. Alex Cayco-Gajic, Sharon Crook, Andrew P. Davison, Salvador Dura-Bernal, András Ecker, Michael L. Hines, Giovanni Idili, Frederic Lanore, Stephen D. Larson, William W. Lytton, Amitava Majumdar, Robert A. McDougal, Subhashini Sivagnanam, Sergio Solinas, Rokas Stanislovas, Sacha J. van Albada, Werner van Geit, R. Angus Silver
Journal: Neuron (2019)

Computational models are powerful tools for exploring the properties of complex biological systems. In neuroscience, data-driven models of neural circuits that span multiple scales are increasingly being used to understand brain function in health and disease. But their adoption and reuse has been limited by the specialist knowledge required to evaluate and use them. To address this, we have developed Open Source Brain, a platform for sharing, viewing, analyzing, and simulating standardized models from different brain regions and species. Model structure and parameters can be automatically visualized and their dynamical properties explored through browser-based simulations. Infrastructure and tools for collaborative interaction, development, and testing are also provided. We demonstrate how existing components can be reused by constructing new models of inhibition-stabilized cortical networks that match recent experimental results. These features of Open Source Brain improve the accessibility, transparency, and reproducibility of models and facilitate their reuse by the wider community.
THU0705-HPR PELVIC FLOOR AND SEXUAL DYSFUNCTION IN WOMEN WITH SJOGREN SYNDROME
Authors: Alime Buyuk Gonen, S. Yaprak Cetin, Ayse Ayan
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Sjogren syndrome (SS) is a systemic autoimmune disease causing secretory gland dysfunction. This leads to dryness of the mainly salivary and lacrimal glands such as the mouth, eyes, nose, larynx, and vagina. The disease overwhelmingly affects middle aged women. These women have symptoms of decreased lacrimal and salivary gland function which usually precede involvement of other exocrine glands such as the upper airway, the gastrointestinal tract and the external genitalia (dyspareunia). Although genital tract symptoms are common in patients with sjogren, such as vulvar and vaginal dryness, dyspareunia, and pruritus, their pelvic floor health and functions have been rarely evaluated. <h3>Objectives:</h3> The aim of study was investigation of pelvic floor and sexual dysfunction in patients with SS. <h3>Methods:</h3> 23 patients with SS with an average age of 49.00±8.71 were included in the study. Pelvic floor dysfunction of patients with SS were evaluated by the Pelvic Floor Impact Questtionare-7 (PFIQ-7) and Pelvic Floor Distress Inventory-20 (PFDI-20) and sexual dysfunction were evaluated by Pelvic Organ Prolapsed/Urinary Incontinence Sexual Questionnaire (PISQ-12). <h3>Results:</h3> PFIQ-7 total score was 27.14±27.73 (UIQ-7: 17.07±17.88, CRAIQ-7: 7.43±10.14, POPIQ-7: 2.32±5.00);, PFDI-20 total score was 116.36±34.00 (POPDI-6:31.48±8.29, CRADI-8: 35.59±15.73, UDI-6:49.00±16.56) and PISQ-12 total score was 16.78±5.71. <h3>Conclusion:</h3> According to the results of the study, patients with SS had pelvic floor dysfunction and sexual dysfunction. This study showed that pelvic floor and sexual functions of patients with SS have been negatively affected. Therefore these functions need to be routinely assessed by health professionals. Further studies need to recommend pelvic health physiotherapy and educational programme about pelvic floor dysfunction. <h3>References:</h3> [1] Both, T., Dalm, V. A., van Hagen, P. M., &amp; van Daele, P. L. (2017). Reviewing primary Sjögren's syndrome: beyond the dryness-From pathophysiology to diagnosis and treatment. International journal of medical sciences, 14(3), 191. [2] Mavragani, C. P., &amp; Moutsopoulos, H. M. (2010). The geoepidemiology of Sjögren's syndrome. Autoimmunity reviews, 9(5), A305-A310. [3] Maddali Bongi S, Del Rosso A, Orlandi M, et al. Gynaecological symptoms and sexual disability in women with primary Sjogren's syndrome and sicca syndrome. Clin Exp Rheumatol 2013;31:683–90 [4] Priori, R., Minniti, A., Derme, M., Antonazzo, B., Brancatisano, F., Ghirini, S.,. .. &amp; Framarino-dei-Malatesta, M. (2015). Quality of sexual life in women with primary Sjögren syndrome. The Journal of rheumatology, jrheum-141475. <h3>Disclosure of Interests:</h3> None declared
Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study
Authors: Stephanie W Lo, Rebecca A Gladstone, Andries J van Tonder, John A Lees, Mignon du Plessis, Rachel Benisty, Noga Givon-Lavi, Paulina A Hawkins, Jennifer E Cornick, Brenda Kwambana-Adams, Pierra Y Law, Pak Leung Ho, Martin Antonio, Dean B Everett, Ron Dagan, Anne von Gottberg, Keith P Klugman, Lesley McGee, Robert F Breiman, Stephen D Bentley, Abdullah W Brooks, Alejandra Corso, Alexander Davydov, Alison Maguire, Andrew Pollard, Anmol Kiran, Anna Skoczynska, Benild Moiane, Bernard Beall, Betuel Sigauque, David Aanensen, Deborah Lehmann, Diego Faccone, Ebenezer Foster-Nyarko, Ebrima Bojang, Ekaterina Egorova, Elena Voropaeva, Eric Sampane-Donkor, Ewa Sadowy, Godfrey Bigogo, Helio Mucavele, Houria Belabbès, Idrissa Diawara, Jennifer Moïsi, Jennifer Verani, Jeremy Keenan, Jyothish N Nair Thulasee Bhai, Kedibone M Ndlangisa, Khalid Zerouali, K L Ravikumar, Leonid Titov, Linda De Gouveia, Maaike Alaerts, Margaret Ip, Maria Cristina de Cunto Brandileone, Md Hasanuzzaman, Metka Paragi, Michele Nurse-Lucas, Mushal Ali, Naima Elmdaghri, Nicholas Croucher, Nicole Wolter, Nurit Porat, Özgen Köseoglu Eser, Patrick E Akpaka, Paul Turner, Paula Gagetti, Peggy-Estelle Tientcheu, Philip E Carter, Rafal Mostowy, Rama Kandasamy, Rebecca Ford, Rebecca Henderson, Roly Malaker, Sadia Shakoor, Samanta Cristine Grassi Almeida, Samir K Saha, Sanjay Doiphode, Shabir A Madhi, Shamala Devi Sekaran, Somporn Srifuengfung, Stephen Obaro, Stuart C Clarke, Susan A Nzenze, Tamara Kastrin, Theresa J Ochoa, Veeraraghavan Balaji, Waleria Hryniewicz, Yulia Urban
Journal: The Lancet Infectious Diseases (2019)

Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits.
A Genetically Encoded Fluorescent Sensor for Rapid and Specific In Vivo Detection of Norepinephrine
Authors: Jiesi Feng, Changmei Zhang, Julieta E. Lischinsky, Miao Jing, Jingheng Zhou, Huan Wang, Yajun Zhang, Ao Dong, Zhaofa Wu, Hao Wu, Weiyu Chen, Peng Zhang, Jing Zou, S. Andrew Hires, J. Julius Zhu, Guohong Cui, Dayu Lin, Jiulin Du, Yulong Li
Journal: Neuron (2019)
Morphological classification of pancreatic ductal adenocarcinoma that predicts molecular subtypes and correlates with clinical outcome
Authors: Sangeetha N Kalimuthu, Gavin W Wilson, Robert C Grant, Matthew Seto, Grainne O’Kane, Rajkumar Vajpeyi, Faiyaz Notta, Steven Gallinger, Runjan Chetty
Journal: Gut (2019)

Transcriptional analyses have identified several distinct molecular subtypes in pancreatic ductal adenocarcinoma (PDAC) that have prognostic and potential therapeutic significance. However, to date, an indepth, clinicomorphological correlation of these molecular subtypes has not been performed. We sought to identify specific morphological patterns to compare with known molecular subtypes, interrogate their biological significance, and furthermore reappraise the current grading system in PDAC.We first assessed 86 primary, chemotherapy-naive PDAC resection specimens with matched RNA-Seq data for specific, reproducible morphological patterns. Differential expression was applied to the gene expression data using the morphological features. We next compared the differentially expressed gene signatures with previously published molecular subtypes. Overall survival (OS) was correlated with the morphological and molecular subtypes.We identified four morphological patterns that segregated into two components ('gland forming' and 'non-gland forming') based on the presence/absence of well-formed glands. A morphological cut-off (≥40% 'non-gland forming') was established using RNA-Seq data, which identified two groups (A and B) with gene signatures that correlated with known molecular subtypes. There was a significant difference in OS between the groups. The morphological groups remained significantly prognostic within cancers that were moderately differentiated and classified as 'classical' using RNA-Seq.Our study has demonstrated that PDACs can be morphologically classified into distinct and biologically relevant categories which predict known molecular subtypes. These results provide the basis for an improved taxonomy of PDAC, which may lend itself to future treatment strategies and the development of deep learning models.
The promise of discovering population-specific disease-associated genes in South Asia
Authors: Nathan Nakatsuka, Priya Moorjani, Niraj Rai, Biswanath Sarkar, Arti Tandon, Nick Patterson, Gandham SriLakshmi Bhavani, Katta Mohan Girisha, Mohammed S Mustak, Sudha Srinivasan, Amit Kaushik, Saadi Abdul Vahab, Sujatha M Jagadeesh, Kapaettu Satyamoorthy, Lalji Singh, David Reich, Kumarasamy Thangaraj
Journal: Nature Genetics (2017)