tbuckley/cabot-search huggingface dataset:
SAT0457 SjÖgren big data project, the first example of data sharing in autoimmune diseases: analysis of 10475 worldwide patients
Authors: S. Retamozo, N. Acar-Denizli, W. Fai Ng, M. Zeher, A. Rasmussen, T. Mandl, R. Seror, X. Li, C. Baldini, J.-E. Gottenberg, D. Danda, L. Quartuccio, A. Minniti, G. Hernandez-Molina, U. Kalyoncu, A.A. Kruize, S.-K. Kwok, M. Wahren-Herlenius, S. Praprotnik, D. Sene, E. Bartoloni, R. Solans, M. Rischmueller, Y. Suzuki, D. Isenberg, V. Valim, P. Wiland, G. Nordmark, G. Fraile, H. Bootsma, T. Nakamura, R. Giacomelli, V. Devauchelle-Pensec, B. Hofauer, M. Bombardieri, V. Fernandes Moça Trevisani, D. Hammenfors, S.G. Pasoto, T.A. Gheita, F. Atzeni, J. Morel, C. Vollenveider, P. Brito-Zerón, M. Ramos-Casals
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To take a "high-definition" picture of the main features of primary Sjögren syndrome (SjS) following a worldwide data-sharing cooperative merging of international clinical SjS databases. <h3>Methods</h3> The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014 including leading clinical centres in SjS of the 5 continents that shared a harmonised data architecture and conducted cooperative online efforts to refine collected data of primary SjS patients fulfilling the 2002 classification criteria. <h3>Results</h3> By January 2018, the participant centres had included 10 475 patients from 22 countries, including 7637 (73%) patients from Europe, 1420 (14%) from America, 1186 (11%) from Asia, 167 (1.4%) from Australia and 65 (0.6%) from Africa. The cohort included 9781 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years. The frequencies of fulfilment of the 2002 criteria were 92% for dry eye, 94% for dry mouth, 83% for abnormal ocular tests, 82% for positive minor salivary gland biopsy, 78% for abnormal oral diagnostic tests and 76% for positive anti-Ro/La antibodies. The frequency of positive immunological markers at diagnosis was 79% for ANA, 73% for anti-Ro, 49% for RF, 45% for anti-La, 13% for low C3 levels, 14% for low C4 levels and 7% for cryoglobulins. <h3>Conclusions</h3> International data sharing-based projects merging disperse clinical registries may be essential tools to increase current knowledge and to improve patient care in specific systemic autoimmune diseases. <h3>Disclosure of Interest</h3> None declared
Presence and diagnostic value of circulating tsncRNA for ovarian tumor
Authors: Eric Y. Peng, Yang Shu, Yuke Wu, Feier Zeng, Shuangyan Tan, Yun Deng, Yiqi Deng, Haining Chen, Lei Zhu, Heng Xu
Journal: Molecular Cancer (2018)

tRNA-derived small non-coding RNAs (tsncRNAs), a class of newly defined small non-coding RNA, have been considered to be involved in various cellular biological processes through regulating gene expression at both transcriptional and post-transcriptional level. However, the presence of circulating tsncRNAs and their diagnostic potential is largely unclear. In this study, we investigate the serum-derived public transcriptome data from ovarian tumor patients and non-cancer controls, and find that circulating tsncRNAs cover a high proportion of total small RNA and are non-random degradation products in serum (ranging from 2.5–29.4%), which are enriched in several specific types of related tRNA (e.g., Gly-tRNA). Particularly, four tsncRNAs are differentially expressed in serum from cancer patients compared to those from healthy controls, and can predict abnormal cell proliferation with high accuracy. Our results reveal the ubiquitous presence of circulating tsncRNAs in serum, and diagnostic potential of specific tsncRNAs for ovarian tumor.
Abstract 16650: Transcriptional Profiling of Single Human Heart Cells Reveals Subtypes of Ventricular Cardiomyocytes
Authors: Abha Bais, Niyatie Ammanamanchi, Jennifer Spaethling, Sangita Choudhury, Honghai Liu, Mugdha Khaladkar, Jocelyn D Mich-Basso, Stephen A Fisher, Junhyong Kim, James Eberwine, Dennis Kostka, Bernhard Kühn
Journal: Circulation (2016)

Regenerative strategies have the potential to transform the treatment of heart failure. Their success relies on a detailed molecular-genetic understanding of human cardiac cell development. Single-...
Subcutaneous injection of the Ad-sig-TAA/ecdCD40L adenoviral vector encoding a CD40ligand/tumor associated antigen secretory protein generates T cell dependent cellular immunity against tumor cell lines for up to one year
Authors: Yucheng Tang, Lixin Zhang, Jing Yuan, Hakan Akbulut, Jonathan Maynard, Phyllis-Jean Linton, Albert B. Deisseroth
Journal: Cancer Research (2004)

1234  T-cell tolerance to tumor associated antigens is commonly found in cancer patients. Dendritic cells are required to induce tumor-specific immunity because dendritic cells (DCs) can efficiently capture and present tumor antigens to result in the expansion and activation of tumor-specific cytotoxic T cells. We have studied ways of using adenoviral vectors for the simultaneous in vivo activation and loading of dendritic cells (DCs) with tumor associated antigens (TAA) continuously over a 10 day period. We found that the subcutaneous injection of an adenoviral vector (Ad-sig-TAA/ecdCD40L) which can secrete a fusion protein composed of a tumor associated antigen (TAA) and the extracellular domain (ecd) of the CD40 ligand (CD40L) could induce an antigen specific immune response against cancer cells brearing the TAA for up to one year. By using LDH release cytotoxicity assays, ELISOPT assays, and tetramer staining, we showed that subcutaneous injections of the Ad-sig-TAA/ecdCD40L vector increased the levels of TAA specific splenic T cells up to 250 fold, using the E7 foreign viral HPV antigen and the self MUC-1 TAA which is overexpressed on neoplastic epithelial cells. These injections induced a T cell dependent immune response for over a year which could prevent the growth of at least 5 X 105 TAA bearing cancer cells in 100% of the injected mice. These studies indicated that the Ad-sig-TAA/ecdCD40L vector injections were inducing antigen specific memory cells. In human MUC-1 transgenic mice which were transgenic for the human MUC-1 (hMUC-1) gene, and therefore anergic to the hMUC-1 antigen, vaccination with the Ad-sig-hMUC-1/ecdCD40L vector resulted in induction of an immune response to the hMUC-1 antigen positive tumor cells which overcame the anergy to the hMUC-1 antigen which exists in hMUC-1.Tg transgenic mice. The induction of the immune response was HLA restricted, was mediated by CD 8+ T cells, and involved activation of proliferation signal transduction pathways in the antigen specific T cells. No cytokine boosts were required to break tolerance to the TAA in 100% of the treated animals. These findings suggest that the Ad-sig-TAA/ecdCD40L vector injections may be of value in the treatment of the many epithelial malignancies in which the human MUC-1 gene is overexpressed.
A prospective study to determine survival outcome to CHOP-based therapy in patients with double expresser DLBCL: Single centre experience from India
Authors: V. Asati, K.C. Lakshmaiah, K. Govind Babu, D. Lokanath, L.A. Jacob, M.C. Suresh Babu, K.N. Lokesh, L.K. Rajeev, A.H. Rudresha, S.C. Smitha, G.V. Giri, D. Koppaka, A. Anand, R. Chethan, T. Chaudhuri, R. Patidar, A. Goyal, C.S. Premalata
Journal: Annals of Oncology (2018)
Potential Cardiovascular Disease Events Prevented with Adoption of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline
Authors: Adam P. Bress, Lisandro D. Colantonio, Richard S. Cooper, Holly Kramer, John N. Booth, Michelle C. Odden, Kirsten Bibbins-Domingo, Daichi Shimbo, Paul K. Whelton, Emily B. Levitan, George Howard, Brandon K. Bellows, Dawn Kleindorfer, Monika M. Safford, Paul Muntner, Andrew E. Moran
Journal: Circulation (2018)

Over 10 years, achieving and maintaining 2017 ACC/AHA guideline goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), and 1.4 million (UR, 0.6-2.0 million) cardiovascular disease (CVD) events compared with maintaining current blood pressure (BP) levels, achieving 2003 Seventh Joint National Committee Report goals, and achieving 2014 Eighth Joint National Committee goals, respectively. We estimated the number of cardiovascular disease events prevented and treatment-related serious adverse events incurred over 10 years among US adults with hypertension by achieving 2017 ACC/AHA guideline-recommended BP goals compared with (1) current BP levels, (2) achieving 2003 Seventh Joint National Committee Report BP goals, and (3) achieving 2014 Eighth Joint National Committee panel member report BP goals.
Prospective enterovirus D68 (EV-D68) surveillance from September 2015 to November 2018 indicates a current wave of activity in Wales
Authors: Simon Cottrell, Catherine Moore, Malorie Perry, Ember Hilvers, Chris Williams, Ananda Giri Shankar
Journal: Eurosurveillance (2018)

Since 7 June 2018, an enterovirus D-68 (EV-D68) season (the third since 2015) is ongoing in Wales, with 114 confirmed cases thus far. Median age of the 220 cases since 2015 is 2.5 years (2.5 years in intensive care cases), 94% were hospitalised, 17% (n = 38) in intensive care. All had respiratory symptoms; bronchiolitis symptoms were reported in 60 cases, severe respiratory symptoms in 23 and acute flaccid myelitis in two cases.
Reprocessing of flexible endoscopes and endoscopic accessories used in gastrointestinal endoscopy: Position Statement of the European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology Nurses and Associates (ESGENA) – Update 2018
Authors: Ulrike Beilenhoff, Holger Biering, Reinhard Blum, Jadranka Brljak, Monica Cimbro, Jean-Marc Dumonceau, Cesare Hassan, Michael Jung, Birgit Kampf, Christiane Neumann, Michael Pietsch, Lionel Pineau, Thierry Ponchon, Stanislav Rejchrt, Jean-François Rey, Verona Schmidt, Jayne Tillett, Jeanin van Hooft
Journal: Endoscopy (2018)

Abstract This Position Statement from the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastroenterology Nurses and Associates (ESGENA) sets standards for the reprocessing of flexible endoscopes and endoscopic devices used in gastroenterology. An expert working group of gastroenterologists, endoscopy nurses, chemists, microbiologists, and industry representatives provides updated recommendations on all aspects of reprocessing in order to maintain hygiene and infection control.
Investigation of expression of a system L neutral amino acid transporter LAT1 and its biological role in human glioma cells
Authors: Motoo Nagane, Keiichi Kobayashi, Promsuk Jutabha, Yoshikatsu Kanai, Hitoshi Endou, Yoshiaki Shiokawa
Journal: Cancer Research (2004)

1672   Objectives. Malignant tumor cells show an elevated proliferative activity which would require increased intracellular metabolism. LAT1, in the presence of its co-factor 4F2hc, constitutes the system L neurtral amino acid transporter which is responsible for cellular transport of most essential amino acids. Recent reports demonstrating increased expression of LAT1 in cancer cells prompted us to investigate its expression and biological roles in human glioma cells. Methods. Expression of LAT1 and 4F2hc was determined in 13 human glioma cell lines using Western blot and RT-PCR analyses. LAT1-positive glioma cells were treated with a system L inhibitor BCH, and their proliferation and apoptosis rates were examined by BrdU staining and TUNEL assay, respectively. LAT1-negative glioma cells were transfected with the plasmid encoding human LAT1 cDNA and the cells expressing high levels of LAT1 were subjected to in vitro growth assays, and were injected into nude mice subcutaneously as well. Amino acid uptake activity was measured using 14C-Leu. Results. Majority of glioma cell lines expressed LAT1 protein. All cell lines were positive for 4F2hc mRNA expression. BCH treatment resulted in significant reduction of proliferation in LAT1-positive LNZ308 cells, whereas it was ineffective in LAT1-negative LN319 cells. LNZ308 cells showed reduced proliferation and increased apoptosis upon BCH treatment, which were accompanied with changes of expression levels of cell-cycle regulators and caspase activation. Introduction of LAT1 did not affect growth rates in LN319 cells in vitro. However, LAT1 overexpression leading to 3.4-fold increase in amino acid uptake activity in U87MG cells resulted in enhanced tumorigenicity in vivo. Conclusions. LAT1 and its partner 4F2hc are expressed in majority of human glioma cells. Our results suggest that LAT1, the major component of the amino acid transport system, may play an important role in gliomagenesis and may be a novel potential therapeutic target for malignant gliomas.
Abstract 14345: Kaolin-containing Hemostatic Gauze Reduced The Re- bleeding Rate Following Catheter Ablation for Atrial Fibrillation
Authors: Yasuhiro Matsuda, Masaharu Masuda, Masashi Fujita, Osamu Iida, Shin Okamoto, Takayuki Ishihara, Kinonori Nanto, Takashi Kanda, Akihiro Sunaga, Takuya Tsujimura, Shota Okuno, koji Yanaka, Takuya Ohashi, Hiroyuki Kawai, Aki Tsuji, Yosuke Hata, Masaaki Uematsu
Journal: Circulation (2016)

Introduction: Hemostatic gauze containing kaolin, which promotes clotting cascade, has been used for hemostasis during surgery. However, efficacy of kaolin-containing hemostatic gauze (KG) in patie...
HER2 positive rates in invasive lobular breast carcinoma: A study amongst 1,095 consecutive Asian patients
Authors: G.J. Kee, R. Tan, R. Sultana, M.W.W. Zaw, W. Lian, K.T.B. Tan, R. Dent, F.Y. Wong, G.E. Lee
Journal: Annals of Oncology (2018)
Abstract 19372: Closure of Patent Foramen Ovale versus Medical Therapy After Cryptogenic Stroke: Meta Analysis of Randomized Controlled Clinical Trials
Authors: Usama Nasir, Waqas T Qureshi, Omer Shabbir, Abhishek Dutta, Mouaz Al-Mallah
Journal: Circulation (2017)

Background: Recurrence of stroke is common in patients with patent foramen ovale (PFO) and history of cryptogenic stroke and it is unclear if closure of PFO prevents recurrent ischemic stroke versu...
Authors reply: treatment strategy for necrotising pancreatitis
Authors: Ji Young Bang, Shyam Varadarajulu
Journal: Gut (2018)

We thank the authors for their interest in our randomised trial.1 2 First, the patient population: The treatment algorithm outlined in our study is different from the TENSION trial and other preceding trials from the Netherlands.3 In patients with large collections (>120 mm in size), the multigate technique was adopted (20% of patient cohort). In patients with persistent or ongoing systemic inflammatory response syndrome (SIRS) after initial drainage, a CT scan was obtained at 72 hours to assess treatment response. If there was <25% decrease in size …
Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2
Authors: Janine Schniering, Martina Benešová, Matthias Brunner, Stephanie Haller, Susan Cohrs, Thomas Frauenfelder, Bart Vrugt, Carol A Feghali-Bostwick, Roger Schibli, Oliver Distler, Cristina Mueller, Britta Maurer
Journal: Annals of the Rheumatic Diseases (2018)

Objective To evaluate integrin αvβ3 (alpha-v-beta-3)-targeted and somatostatin receptor 2 (SSTR2)-targeted nuclear imaging for the visualisation of interstitial lung disease (ILD). Methods The pulmonary expression of integrin αvβ3 and SSTR2 was analysed in patients with different forms of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. Single photon emission CT/CT (SPECT/CT) was performed on days 3, 7 and 14 after BLM instillation using the integrin αvβ3-targeting 177 Lu-DOTA-RGD and the SSTR2-targeting 177 Lu-DOTA-NOC radiotracer. The specific pulmonary accumulation of the radiotracers over time was assessed by in vivo and ex vivo SPECT/CT scans and by biodistribution studies. Results Expression of integrin αvβ3 and SSTR2 was substantially increased in human ILD regardless of the subtype. Similarly, in lungs of BLM-challenged mice, but not of controls, both imaging targets were stage-specifically overexpressed. While integrin αvβ3 was most abundantly upregulated on day 7, the inflammatory stage of BLM-induced lung fibrosis, SSTR2 expression peaked on day 14, the established fibrotic stage. In agreement with the findings on tissue level, targeted nuclear imaging using SPECT/CT specifically detected both imaging targets ex vivo and in vivo, and thus visualised different stages of experimental ILD. Conclusion Our preclinical proof-of-concept study suggests that specific visualisation of molecular processes in ILD by targeted nuclear imaging is feasible. If transferred into clinics, where imaging is considered an integral part of patients’ management, the additional information derived from specific imaging tools could represent a first step towards precision medicine in ILD.
New Strategies for the Management of Decompensated Cirrosis: Long‐Term Albumin Administration for Everyone?
Authors: Elsa Solà, Cristina Solé, Pere Ginès
Journal: Hepatology (2018)

Solà, Elsa M.D., Ph.D.; Solé, Cristina M.D.; Ginès, Pere M.D., Ph.D.Editor(s): Corey, Kathleen E.5; Malhi, Harmeet6 Author Information
Abstract 14602: Physical and Biophysical Coupling of the Cardiac Sodium Channel Involves 14-3-3
Authors: Jerome C Clatot, Malcolm Hoshi, Haiyan Liu, Xiaoping Wan, Krekwit Shinlapawittayatorn, Eckhard Ficker, Isabelle Deschênes
Journal: Circulation (2015)

Introduction: Mutations in SCN5A, the gene encoding for the cardiac sodium channel, produce alterations of the cardiac action potential that lead to life-threatening arrhythmias such as Long QT Syndrome (LQT3) and Brugada Syndrome (BrS). The conventional wisdom that sodium channels exist in complexes containing a single alpha-subunit has been challenged by the existence of dominant-negative (DN) mutations in BrS and the presence of polymorphisms that can restore trafficking and gating deficiencies of mutant channels in LQT and BrS. In fact, we have previously demonstrated that SCN5A subunits can interact with each other. Here we hypothesized that the physical and biophysical interactions between SCN5A alpha-subunits involve the partner protein 14-3-3, known to form dimers. Methods: SCN5A DN-BrS mutants and LQT3 gating deficient mutants were expressed in HEK293 cells and in commercially available iPS-derived cardiomyocytes, iCells©, in presence or absence of 14-3-3 inhibition. Resulting currents were measured using patch-clamp. Results: In order to investigate if the DN-effect seen by some BrS mutants is due to interaction of the sodium channel with the protein 14-3-3 which in turn would be involved in the alpha-alpha interaction, we expressed two different BrS DN-mutants in HEK293 cells with and without difopein, a specific 14-3-3 inhibitor. The presence of difopein abolished the DN-effect of both mutants. The DN-effect was also abolished when we mutated the putative 14-3-3 binding site on SCN5A and expressed the DN-mutants either in HEK293 cells or in iCells©. Inhibition of 14-3-3 also impaired the biophysical coupling observed in presence of SCN5A gating deficient mutants that affect either activation or inactivation of not only the mutants but also of the wild-type channel. Conclusions: Our results suggest that binding of 14-3-3 to the cardiac sodium channel alpha-subunit is involved in the alpha-alpha interaction and biophysical coupling of the channel. This study not only shifts paradigms in regards to sodium channel assembly and structure, but also puts forward the idea that physical and biophysical uncoupling of cardiac sodium channels could be a new therapy target for cardiac arrhythmias caused by SCN5A mutations.
Abstract 17662: Myeloperoxidase is a Potential Molecular Imaging and Therapeutic Target for the Identification and Stabilization of Unstable Atherosclerotic Plaque
Authors: Imran Rashid, Ghassan J Maghzal, Yung-Chih Chen, David Cheng, Jihan Talib, Christopher Stanley, Eva-Lotte Lindstedt, Erik Michaëlsson, Karlheinz Peter, Anthony J Kettle, Andre Bongers, Carl Power, Roland Stocker
Journal: Circulation (2017)

Introduction: Myeloperoxidase (Mpo) is a leukocyte enzyme that has been identified in culprit coronary atherosclerotic plaques following acute myocardial infarction (AMI). However, a causal relatio...
The Fragility Index in Randomized Clinical Trials as a Means of Optimizing Patient Care
Authors: Christopher J. Tignanelli, Lena M. Napolitano
Journal: JAMA Surgery (2018)

The Fragility Index (FI) is the minimum number of participants in a randomized clinical trial (RCT) whose status would have to change from a nonevent (not experiencing the primary end point) to an event (experiencing the primary end point) required to turn a statistically significant result to a nonsignificant result. The FI measures the robustness (or fragility) of the results of an RCT and is an important aid to the clinician's interpretation of RCT results. It has now been recognized that RCTs, which provide the foundation for treatment guideline recommendations, may not be robust.Most RCTs in surgery and general medicine are fragile (with a low FI score), in contrast to those in cardiac disease and heart failure, where most RCTs are robust (with high FI scores). For clinical trials of trauma, we identified that the median (interquartile range) FI score was 3 (1-8), which means that adding 3 events to the opposite treatment arm in a given RCT eliminated statistical significance. The median Fragility Quotient (the FI score divided by the total study sample size) was 0.016 (0.0043-0.0408).The provision of high-quality, evidence-based clinical care in surgery for optimal patient outcomes requires a foundation of robust clinical research evidence, and knowledge of the FI will assist in future surgical RCT design. We strongly recommend the routine reporting of FI scores for all future trauma and surgical RCTs to assist in appropriate and optimal decision making in the care of patients who have experienced trauma and/or need surgery. We also recommend the routine inclusion of the FI score in the development of clinical guidelines to assist the clinician in ascertaining whether guideline recommendations are robust. Surgeons should be aware to particularly exercise caution when considering a potential change in clinical practice based on RCTs with a low FI score.