tbuckley/cabot-search huggingface dataset:
SAT0132 LONG-TERM SAFETY, IMMUNOGENICITY AND EFFICACY IN RANDOMIZED, DOUBLE-BLIND, AND OPEN-LABEL EXTENSION STUDIES COMPARING FKB327, AN ADALIMUMAB BIOSIMILAR, WITH THE ADALIMUMAB REFERENCE PRODUCT IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS
Authors: Rieke Alten, Mark C. Genovese, Rafael Muniz, Herbert Kellner
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> FKB327 is a biosimilar of adalimumab reference product (RP). Studies with adalimumab biosimilars have shown no increase in safety signals or immunogenicity versus RPs studied at 52 weeks. <h3>Objectives</h3> To study the long-term safety, immunogenicity and efficacy of FKB327 compared with Adalimumab RP in a randomized double blind (DB) phase 3 study in patients (pts) with active rheumatoid arthritis (RA) inadequately controlled with methotrexate (MTX) and in a subsequent randomized, open-label extension (OLE) study with treatment switching assessed long-term safety, efficacy, PK, and immunogenicity. <h3>Methods</h3> Pts aged ≥18 years with moderate-to-severe, active RA (2010 ACR/EULAR criteria) for ≥3 months and receiving a stable dose of MTX were randomized 1:1 to FKB327 or RP (40 mg subcutaneously [SQ]) every other week with MTX. In the OLE study, pts who completed the DB study with clinical response and no serious adverse events (AEs) were rerandomized in a 2:1 ratio to FKB327 or RP. All pts received FKB327 through week 76 (Period 2). The primary end point was safety; the secondary end point was efficacy. Pooled data for up to 2 years were analyzed to assess long-term safety. Incidence rates of treatment-emergent AEs were adjusted by overall exposure to enable safety comparison of FKB327 and RP. <h3>Results</h3> Of 728 pts in the DB study, 645 were enrolled in the OLE; of those, 572 and 515 pts completed periods 1 and 2, respectively. Safety results from the pooled data were comparable between treatment sequences. Mean serum drug concentrations appeared to be in steady–state in all treatment sequences in Period 1 and comparable among sequences in Period 2. The proportion of pts with positive antidrug antibody (ADA) status in Period 1 was comparable between treatment sequences, and the majority of patients with positive ADA status had neutralizing activity. The mean proportion of patients achieving an ACR20 response remained stable between studies and was similar for all treatment sequences. <h3>Conclusion</h3> The safety, immunogenicity, and efficacy of FKB327 were maintained over long-term treatment and after switching between the biosimilar and RP. <h3>Disclosure of Interests</h3> Rieke Alten Grant/research support from: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, Mark C. Genovese Grant/research support from: Sanofi/Genzyme, Genentech/Roche, RPharm, Consultant for: Sanofi/Genzyme, Genentech/Roche, RPharm, Yasumasa Arai Employee of: I am an employee of Fujifilm Kyowa Kirin Biologics., Rafael Muniz Shareholder of: Employee of Mylan, Consultant for: Employee of Mylan, Employee of: Employee of Mylan, Herbert Kellner Grant/research support from: Roche, Consultant for: Roche
I-Boost: an integrative boosting approach for predicting survival time with multiple genomics platforms
Authors: Kin Yau Wong, Cheng Fan, Maki Tanioka, Joel S. Parker, Andrew B. Nobel, Donglin Zeng, Dan-Yu Lin, Charles M. Perou
Journal: Genome biology (2019)

We propose a statistical boosting method, termed I-Boost, to integrate multiple types of high-dimensional genomics data with clinical data for predicting survival time. I-Boost provides substantially higher prediction accuracy than existing methods. By applying I-Boost to The Cancer Genome Atlas, we show that the integration of multiple genomics platforms with clinical variables improves the prediction of survival time over the use of clinical variables alone; gene expression values are typically more prognostic of survival time than other genomics data types; and gene modules/signatures are at least as prognostic as the collection of individual gene expression data.
Scotland agrees on new opt-out organ donation system
Authors: Bryan Christie
Journal: BMJ (2019)

Scotland has decided to follow Wales and England in introducing an opt-out system of organ and tissue donation in an attempt to increase the number of lifesaving transplant operations.

The Scottish parliament has approved the Human Tissue (Authorisation) (Scotland) Bill, which will result in all people over 16 being deemed to be organ donors unless they opt out. Currently, people have to opt in by registering their willingness to have their organs used after their death.

Scotland has the UK’s highest proportion of people on the organ donor …
Abstract 19049: Feasibility of Simulation-Based Prediction of Optimal Ventricular Tachycardia (VT) Ablation Targets in Patients With ICD Artifact Burden
Authors: Adityo Prakosa, Plamen Nikolov, Sohail Zahid, Esra G Ipek, Saman Nazarian, Natalia A Trayanova
Journal: Circulation (2016)

Introduction: We recently developed methodology to predict infarct-related VTs and the optimal ablation targets using personalized ventricular models reconstructed from LGE MRI scans. However, most...
Exploration of gene expression networks that regulate cell-cell interaction during angiogenesis by transcript profiling in an in vitro angiogenesis co-culture model
Authors: Yuefeng Chen, Tao Wei, Frank Lawrence, Wayne E. Evans, Xiaoling Xia, Lei Yan, Jonathan M. Yingling, Jianyong Shou
Journal: Cancer Research (2006)

139   Angiogenesis is a complex biological process involving cell-cell interactions between the vessel forming endothelial cells and the host microenvironment. The molecular networks that govern cell-cell communication during angiogenesis are not well understood. We established an in vitro HUVEC/dermal fibroblast co-culture system to mimick the angiogenic microenvironment and used it as a model system to explore gene regulation networks that control angiogenesis. Establishment of optimal and suboptimal combinations of fibroblasts and HUVEC cells enabled comparison of networks that contribute to efficient angiogenic cord formation in this model system. To validate the model, we assayed a variety of pro-angiogenic (e.g. VEGF) and anti-angiogenic factors (e.g. KDR inhibitors). The expected biological effects were observed for these factors in our co-culture system. Neonatal human dermal fibroblasts at low passage provided a supportive environment for efficient cord formation by co-cultured HUVEC cells. However, adult human dermal fibroblasts at high passage were less permissive for cord formation. In addition, HUVEC cells gradually lost their VEGF responsiveness and capacity for cord formation when serially passaged in vitro. We performed complementary microarray analysis on both HUVEC cells and different supporting dermal fibroblast cells to elucidate the gene expression networks that regulate angiogenesis. A number of pro-angiogenic and anti-angiogenic factors are differentially expressed in the supportive neonatal fibroblasts compared to the less supportive adult dermal fibroblasts. For example, Spondin 1, an extracellular matrix protein that promotes neurite outgrowth and inhibits angiogenesis, was found to be over expressed in the adult fibroblasts by more than 50-fold. Coherent analysis revealed twelve statistically significant Gene Ontology (GO) categories as differentially regulated by the two fibroblast populations. These include blood vessel morphogenesis, vasculature development, cell matrix adhesion and cell migration. The vast majority of genes from this analysis are implicated in the regulation of angiogenesis. Ingenuity pathway analysis also indicated the involvement of several conical signaling pathways such as the Integrin pathway and the PDGF signaling pathway. In depth pathway analysis is being utilized to examine the interaction and integration of these signaling pathways to enable a comprehensive understanding of gene regulation networks that are involved in angiogenesis control in this in vitro co-culture model system.
AB1228 ACCESS TO RHEUMATOLOGIC TREATMENTS AND AUTOIMMUNE CONDITIONS IN LATIN AMERICA
Authors: Genessis Maldonado, Daniella Cobeña, Enrique Soriano, Letty Moreno, Carlos Rios
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> <h3>Objectives:</h3> To know the availability of treatment for rheumatologic and autoimmune conditions in Latin America, according to rheumatologists in the region. <h3>Methods:</h3> A digital survey was created using Google Forms, it was approved and endorsed by the scientific committee of PANLAR, and later sent to the different Rheumatology associations of the region. The data was analyzed in the statistical program SPSS v.23. <h3>Results:</h3> 456 surveys were filled by rheumatologists from 23 countries. The majority were females (54%). The mean age was 47.18 ± 11.79 [25-78] years. 91% reported access to DMARDs, methotrexate 95%, azathioprine 94%, cyclophosphamide 92%, hydroxychloroquine 92%, leflunomide 90%, mycophenolate mofetil 90%, sulfazalasin 88%, cyclosporine 80%, tacrolimus 64%, chloroquine 60%. 85% have access to biological therapy: adalimumab (78%), etarnercept (83%), rituximab (81%), infliximab (74%), tocilizumab (73%), abatacept (67%), golimumab (63%), certolizumab (59%), secukinumab (55%), ustekinumab (44%), certolizumab (59%), belimumab (47%), canakinumab (22%), sarilumab (15%), ixekizumab (12%), anakinra (10%) and rilonacept (3%). 58% have access to biosimilar drugs: rituximab (27%), infliximab (24%), etanercept (18%) and adalimumab (4%). 61% have access to small molecules such as: tofacitinib 62%, baricitinib 18% and ruxolutinib 1%. Regarding the survey by each country 95% reported access to DMARDs: between 80-100% (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Dominican Republic). 70% of the countries reported access to biological therapy between 80-100% (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Panama, Paraguay, Puerto Rico, Uruguay.) 15% did not have access to biosimilar therapy (Cuba, Honduras and Uruguay). 30% have access to therapy with small molecules between 80 -100% (Argentina, Guatemala, Honduras, Panama, Paraguay and Dominican Republic), 25% did not have access to small molecules (Cuba, Uruguay and Venezuela). <h3>Conclusion:</h3> It is evident that most Latin American countries have access to drugs focused on rheumatic diseases, however, there are substantial differences in countries that do not have access to all therapies. In addition, newer treatment as small molecules are less accessible to the region. <h3> Disclosure of Interests:</h3> None declared
AB0378 AN UPDATE AND SYSTEMATIC REVIEW ON USING BIOLOGICALS DURING PREGNANCY IN INFLAMMATORY AUTOIMMUNE DISEASES
Authors: Nafise Ghalandari, Radboud Dolhain, Johanna Hazes, Eugène van Puijenbroek, Manavi Kapur, Hubertina Johanna Maria Josephina Crijns
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The effects of biologicals on reproduction are unknown. Therefore pregnancy during biologicals use is discouraged. However biologicals are frequently prescribed in patients of childbearing potential and many patients become pregnant while using these drugs. <h3>Objectives</h3> In 2015 EULAR published a broad review article on this matter. Our aim was to update the data based on newly published articles. <h3>Methods</h3> A search was conducted at 18/10/2017 and then 21/11/2018 in Embase, Medline Ovid, Web Of Science, Cochrane CENTRAL and Google Scholar with specific search terms for each database. Articles were excluded based on title/abstract (double blind, two researchers, NG and HJMJC) and then full text (one researcher, NG). A chart was made based on outcomes of interest(see Table1). The references of included articles were reviewed to include and minimize the missing articles. <h3>Results</h3> Totally 137 articles were included (79 articles at first round, 51 articles at second round and 7 found after screening the references of the included articles). A descriptive analysis was performed to sum up the data on each separate biological and all the biologicals together. The results are shown in Table1. It should be notified that due to heterogeneity of the data the calculated percentages are up to individual interpretations and cannot be compared to each other. <h3>Conclusion</h3> From 2015 onwards, there have been many articles published regarding use of biologicals during pregnancy. Despite limitations of our study, such as heterogeneity in being prospective or retrospective and quality of the included articles, no alarm is raised concerning safety issues. <h3>Disclosure of Interests</h3> Nafise Ghalandari: None declared, Radboud Dolhain Grant/research support from: UCB Pharma B.V, Johanna Hazes: None declared, Eugène van Puijenbroek: None declared, Manavi Kapur: None declared, Hubertina Johanna Maria Josephina Crijns: None declared
AB0569 THE EFFECT OF CUTANEOUS AND MUSCULOSKELETAL SYMPTOMS ON QUALITY OF LIFE IN PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN RENAISSANCE COHORT
Authors: Lyubov Vorobyova, Elena Aseeva, Sergey Solovyev
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Cutaneous and musculoskeletal symptoms is one of the most frequent clinical complaints of patients with systemic lupus erythematosus(SLE) and has been found to occur in up to 70%-95% of patients during the course of the disease. For these reasons, SLE can affect different aspects of the patient's life, leading to an impairment of HRQOL. <h3>Objectives:</h3> The aim of the current study was to assess the effect of cutaneous and musculoskeletal symptoms on HRQoL in a cohort of patients with systemic lupus erythematosus in Russian Federation (RENAISSANCE). <h3>Methods:</h3> Consecutive patients who fulfilled SLICC 2012 criteria for SLE were recruited. Health-related quality of life (HRQoL) was assessed by the validated specific questionnaires LupusQoL-Russian. Disease activity was evaluated by the SLEDAI-2K, and chronic damage by the Systemic Lupus International Collaborating Clinics Damage Index score (SDI). <h3>Results:</h3> 328 Russian SLE patients were enrolled in the study (M/F 30/298, mean age 34.4±11.5 years, mean disease duration 106.3±97.9 months; mean SLEDAI 2K 9.6±8.0; mean SDI 0.2±0.6. Musculoskeletal symptoms were observed in 142 patients, cutaneous and mucosal lesion symptoms -147 patients, respectively. When comparing HRQOL in patients with lesions skin and mucousal revealed (Table 1) significant decline HRQoL on the scales "Planning" (58.5 ± 28.9), "Intimate Relationships" (65.9 ± 32.1), "Burden to other" (52.9 ± 26) and "Body Image" (57.4 ± 29.1) of the LupusQol questionnaire compared with the patients without skin and mucosal lesions (p≤0.002; p≤0.001; p≤0.03; p≤0,0001 respectively). When evaluating HRQoL in patients with SLE and musculoskeletal symptoms (Table 2) reduction of almost all scales LupusQoL. <h3>Conclusion:</h3> Cutaneous and musculoskeletal symptoms in SLE patients were associated with significantly poorer HRQoL. <h3>Disclosure of Interests:</h3> None declared
AB0531 OBESITY INCREASES THE INCIDENCE OF NEW-ONSET LUPUS NEPHRITIS AND ORGAN DAMAGE DURING FOLLOW-UP IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Shin-Seok Lee, Ji-Hyoun Kang, Sung-Eun Choi, Haimuzi Xu, Dong-Jin Park
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> <h3>Objectives</h3> This study investigated the detrimental effects of obesity on clinical manifestations, disease activity, and organ damage in Korean patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> We obtained data on 393 SLE patients from the Korean Lupus Network registry. Demographic variables, clinical manifestations, laboratory findings, Physician Global Assessment (PGA), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 and Systemic Lupus International Collaborating Clinics Group (SLICC) damage index scores were recorded at the time of enrollment. The tests were repeated annually for 3 consecutive years. We divided the patients into groups according to their body mass index (BMI) using the Asia-Pacific classification (normal, BMI &lt; 23; overweight, 23 ≤ BMI &lt;25; obese, BMI ≥ 25). Univariate and multivariate analyses were performed to assess the impact of obesity on clinical outcomes. <h3>Results</h3> Of the 393 patients, 59 (15.0%) were obese at the time of enrollment. Obese patients had more comorbidities, such as diabetes (<i>P</i>=0.002), hypertension (<i>P</i>=0.005), hyperlipidemia (<i>P</i>=0.005), and pulmonary hypertension (<i>P</i>=0.036) than non-obese patients. Nephritis at enrollment and newly developed nephritis during follow-up were more common in obese patients than in non-obese patients (<i>P</i>=0.002 and <i>P</i>=0.002, respectively). In addition, obese patients had higher daily and cumulative prednisolone doses (<i>P</i>=0.010 and <i>P</i>=0.010, respectively) and higher rates of intravenous cyclophosphamide (<i>P</i>=0.008), mycophenolate (<i>P</i>=0.030), tacrolimus (<i>P</i>=0.007), and cyclosporine (<i>P</i>=0.019) use than non-obese patients. Furthermore, the PGA and SLICC damage index scores were higher in obese patients than in non-obese patients (<i>P</i>=0.017 and <i>P</i>=0.039, respectively) for all 3 consecutive years. In the multivariate analysis, obesity was significantly associated with male gender (OR = 0.141, 95% CI: 0.047–0.419, <i>P</i>&lt;0.001), newly developed nephritis (OR = 2.741, 95% CI: 1.080–6.957, <i>P</i>=0.034), and annual increase in SDI (OR = 2.185, 95% CI: 1.229–3.885, <i>P</i>=0.008). <h3>Conclusion</h3> Obese SLE patients had a higher incidence of newly developed nephritis and cumulative organ damage than non-obese patients. Therefore, lifestyle modifications, including those aimed at weight loss, should be recommended for these patients to improve their clinical outcomes. <h3>Disclosure of Interests</h3> None declared
Abstract 12801: Epigallocatechin Gallate Attenuates the Progression of Heart Failure Induced by Heart/muscle-specific Deletion Of Mn-SOD in Mice Through Scavenging Free Radicals and Improving the Cardiac Chronic Inflammation
Authors: Jun-ichi Oyama, Hiroshi Komoda, Koichi Node, Naoki Makino
Journal: Circulation (2012)

Background- Heart failure involves a robust inflammatory response, but the involvement of oxidative stress in mediating cardiac remodeling remains incompletely defined.MnSOD is one of the important...
Genomic signatures accompanying the dietary shift to phytophagy in polyphagan beetles
Authors: Mathieu Seppey, Panagiotis Ioannidis, Brent C. Emerson, Camille Pitteloud, Marc Robinson-Rechavi, Julien Roux, Hermes E. Escalona, Duane D. McKenna, Bernhard Misof, Seunggwan Shin, Xin Zhou, Robert M. Waterhouse, Nadir Alvarez
Journal: Genome biology (2019)

The diversity and evolutionary success of beetles (Coleoptera) are proposed to be related to the diversity of plants on which they feed. Indeed, the largest beetle suborder, Polyphaga, mostly includes plant eaters among its approximately 315,000 species. In particular, plants defend themselves with a diversity of specialized toxic chemicals. These may impose selective pressures that drive genomic diversification and speciation in phytophagous beetles. However, evidence of changes in beetle gene repertoires driven by such interactions remains largely anecdotal and without explicit hypothesis testing.We explore the genomic consequences of beetle-plant trophic interactions by performing comparative gene family analyses across 18 species representative of the two most species-rich beetle suborders. We contrast the gene contents of species from the mostly plant-eating suborder Polyphaga with those of the mainly predatory Adephaga. We find gene repertoire evolution to be more dynamic, with significantly more adaptive lineage-specific expansions, in the more speciose Polyphaga. Testing the specific hypothesis of adaptation to plant feeding, we identify families of enzymes putatively involved in beetle-plant interactions that underwent adaptive expansions in Polyphaga. There is notable support for the selection hypothesis on large gene families for glutathione S-transferase and carboxylesterase detoxification enzymes.Our explicit modeling of the evolution of gene repertoires across 18 species identifies putative adaptive lineage-specific gene family expansions that accompany the dietary shift towards plants in beetles. These genomic signatures support the popular hypothesis of a key role for interactions with plant chemical defenses, and for plant feeding in general, in driving beetle diversification.
CIDR: Ultrafast and accurate clustering through imputation for single-cell RNA-seq data
Authors: Peijie Lin, Michael Troup, Joshua W. K. Ho
Journal: Genome biology (2017)

Most existing dimensionality reduction and clustering packages for single-cell RNA-seq (scRNA-seq) data deal with dropouts by heavy modeling and computational machinery. Here, we introduce CIDR (Clustering through Imputation and Dimensionality Reduction), an ultrafast algorithm that uses a novel yet very simple implicit imputation approach to alleviate the impact of dropouts in scRNA-seq data in a principled manner. Using a range of simulated and real data, we show that CIDR improves the standard principal component analysis and outperforms the state-of-the-art methods, namely t-SNE, ZIFA, and RaceID, in terms of clustering accuracy. CIDR typically completes within seconds when processing a data set of hundreds of cells and minutes for a data set of thousands of cells. CIDR can be downloaded at https://github.com/VCCRI/CIDR .
Abstract 17156: A Randomized Placebo-phase Clinical Trial With the Monoclonal Antibody Alirocumab Demonstrates Reductions in Low-density Lipoprotein Cholesterol in Patients With Proprotein Convertase Subtilisin/Kexin Type 9 Gain-of-Function Mutations
Authors: Paul N Hopkins, Gary D Swergold, Scott Mellis, Eric Bruckert, Gérald Luc, Johanna Mendoza, Yunling Du, Michel Krempf
Journal: Circulation (2013)

Background: Autosomal dominant hypercholesterolemia (ADH) is characterized by inherited high serum LDL cholesterol (LDL-C) levels and early onset cardiovascular disease. ADH causes include mutation...