bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti–Endothelin Receptor Type A Autoantibodies in Systemic Lupus Erythematosus–Associated Pulmonary Arterial Hypertension
Authors: Guo Li , Li Mengtao , Chen Yi , Wang Qian , Tian Zhuang , Pan Shuming , Zeng Xiaofeng , Ye Shuang 
Published: May 2015

ObjectiveTo investigate the role of autoantibodies against endothelin 1 receptor type A (ETRA) in patients with systemic lupus erythematosus (SLE)–associated pulmonary arterial hypertension (PAH) and to examine the possibility that the pathogenesis of this disease is mediated by these autoantibodies.MethodsETRA autoantibodies in serum from patients with SLE‐associated PAH and serum from controls (SLE patients without PAH) were detected via a human ETRA epitope peptide–based enzyme‐linked immunosorbent assay. An exploratory cohort of patients with SLE‐associated PAH (n = 76) and an independent validation cohort of patients with SLE‐associated PAH confirmed by right‐sided heart catheterization (RHC) (n = 82) were enrolled. The clinical relevance of ETRA autoantibodies in SLE‐associated PAH was analyzed. The proliferation of vascular smooth muscle cells (SMCs) and the permeability of endothelial cells (ECs) were assessed in vitro in cells stimulated with polyclonal ETRA IgG autoantibodies. Expression of PAH‐related markers, i.e., serotonin transporter, platelet‐derived growth factor receptor β, vascular endothelial growth factor A, and platelet‐derived growth factor B was measured by quantitative polymerase chain reaction. In addition, a suboptimal dose of monocrotaline was used to induce PAH in rats, and the effect of ETRA autoantibodies in vivo was determined using a right ventricular hypertrophy index, pulmonary angiography, and laboratory parameters.ResultsETRA autoantibodies occurred more frequently in SLE‐associated PAH (41.5%) than in controls (17.1%). There was a significant correlation between ETRA autoantibody titers and pulmonary artery systolic pressure measured by echocardiography (r = 0.2978, P = 0.0038) or pulmonary artery systolic pressure measured by RHC (r = 0.2159, P = 0.0257) in SLE‐associated PAH. ETRA autoantibodies could promote SMC proliferation, disrupt the endothelial barrier, and up‐regulate expression of PAH‐related markers, which could be blocked in the presence of an endothelin receptor antagonist. ETRA autoantibodies aggravated right ventricular hypertrophy and vascular remodeling in vivo.ConclusionWe identified ETRA autoantibodies as a biomarker of mechanistic relevance in SLE. These autoantibodies may mediate PAH development in SLE.
The W620 Polymorphism in PTPN22 Disrupts Its Interaction With Peptidylarginine Deiminase Type 4 and Enhances Citrullination and NETosis
Authors: Chang Hui‐Hsin , Dwivedi Nishant , Nicholas Anthony P. , Ho I‐Cheng 
Published: May 2015

ObjectiveA C‐to‐T single‐nucleotide polymorphism (SNP) located at position 1858 of human protein tyrosine phosphatase PTPN22 complementary DNA carries the highest risk of rheumatoid arthritis (RA) among all non‐HLA genetic variants. This C1858T SNP converts an arginine (R620) to a tryptophan (W620), but it is unclear why it has such a strong impact on RA, a disease characterized by anti–citrullinated protein antibodies. The aim of this study was to test the hypothesis that PTPN22 regulates protein citrullination.MethodsThe level of citrullinated proteins in immune cells was quantified by Western blotting. The physical interaction between PTPN22 and peptidyl arginine deiminase type 4 (PAD‐4), which is one of the enzymes that catalyzes protein citrullination, was examined by coimmunoprecipitation. Neutrophils were collected from healthy donors carrying the C1858T SNP and healthy donors not carrying this SNP. The formation of neutrophil extracellular traps (NETs) was examined by immunocytochemistry.ResultsPTPN22 physically interacted with PAD‐4, and a deficiency in PTPN22 enhanced protein citrullination. This abnormality was reversed by exogenous wild‐type PTPN22 or catalytically dead mutant PTPN22. The R‐to‐W conversion rendered PTPN22 unable to interact with PAD‐4 and suppress citrullination. The C1858T SNP was associated with hypercitrullination in peripheral blood mononuclear cells and a heightened propensity for spontaneous formation of NETs, which is a PAD‐4–dependent process.ConclusionPTPN22 is an inhibitor of PAD‐4 and protein citrullination. This function of PTPN22 is independent of its phosphatase activity but requires R620. Our data not only establish a molecular link between PTPN22 and PAD‐4, but also suggest that the C1858T SNP increases the risk of RA by enhancing protein citrullination and spontaneous formation of NETs.
Brief Report: Association Between Pregnancy Outcomes and Death From Cardiovascular Causes in Parous Women With Systemic Lupus Erythematosus: A Study Using Swedish Population Registries
Authors: Soh May Ching , Nelson‐Piercy Catherine , Dib Fadia , Westgren Magnus , McCowan Lesley , Pasupathy Dharmintra 
Published: May 2015

ObjectiveTo determine if maternal placental syndromes (MPS) are associated with an increased risk of death from cardiovascular causes in women with systemic lupus erythematosus (SLE).MethodsBetween 1973 and 2011, women with SLE and a history of pregnancy were identified using linked Swedish population registries. The outcome was death from primarily cardiovascular causes, defined as death from acute coronary syndrome or coronary artery disease, stroke, or peripheral vascular disease. The exposure was MPS, defined as any hypertensive disorders in pregnancy, stillbirth, placental abruption, or delivery of a small‐for‐gestational‐age infant. The association of preterm delivery (delivery at <34 weeks of gestation) with death from cardiovascular causes was also explored. Risk of death from cardiovascular causes was determined using logistic regression, adjusting for the year of first delivery, duration of SLE, number of inpatient admissions, and cardiovascular risk factors.ResultsA total of 3,977 women with SLE had 7,410 pregnancies during the study interval. Death from primarily cardiovascular causes occurred in 44 of the 325 women who died (13.5%). The median age at death from cardiovascular causes was 54 years (interquartile range 48–58 years), and these women were more likely to have had hypertension and renal disease. MPS was associated with an increased risk of death from primarily cardiovascular causes (adjusted odds ratio [OR] 2.19 [95% confidence interval (95% CI) 1.14–4.22]), specifically, a history of placental abruption (adjusted OR 5.78 [95% CI 1.61–20.72]). Delivery at <34 weeks of gestation, particularly when combined with MPS, was also associated with an increased risk of death from primarily cardiovascular causes (adjusted OR 2.49 [95% CI 1.06–5.85]).ConclusionMPS in pregnancy is associated with a higher risk of death from primarily cardiovascular causes in women with SLE.
Adverse Events in Connective Tissue Disease–Associated Pulmonary Arterial Hypertension
Authors: Rhee Rennie L. , Gabler Nicole B. , Praestgaard Amy , Merkel Peter A. , Kawut Steven M. 
Published: May 2015

ObjectivePatients with connective tissue disease (CTD)–associated pulmonary arterial hypertension (PAH) have a poorer prognosis compared to those with idiopathic PAH, but little is known about the differences in treatment‐related adverse events (AEs) and serious adverse events (SAEs) between these groups. This study was undertaken to characterize these differences.MethodsIndividual patient‐level data from 10 randomized controlled trials of therapies for PAH were obtained from the US Food and Drug Administration. Patients diagnosed as having either CTD‐associated PAH or idiopathic PAH were included. A treatment‐by‐diagnosis interaction term was used to examine whether the effect of treatment on occurrence of AEs differed between patients with CTD‐associated PAH and those with idiopathic PAH. Studies were pooled using fixed‐effect models.ResultsThe study sample included 2,370 participants: 716 with CTD‐associated PAH and 1,654 with idiopathic PAH. In the active treatment group compared to the placebo group, the risk of AEs was higher among patients with CTD‐associated PAH than among those with idiopathic PAH (odds ratio [OR] 1.57, 95% confidence interval [95% CI] 1.00–2.47 versus OR 0.94, 95% CI 0.69–1.26; P for interaction = 0.061), but there was no difference in the risk of SAEs in analyses adjusted for age, race, sex, hemodynamic findings, and laboratory values. Despite the higher occurrence of AEs in patients with CTD‐associated PAH assigned to active therapy compared to those receiving placebo, the risk of drug discontinuation due to an AE was similar to that in patients with idiopathic PAH assigned to active therapy (P for interaction = 0.27).ConclusionPatients with CTD‐associated PAH experienced more treatment‐related AEs compared to those with idiopathic PAH in therapeutic clinical trials. These findings suggest that the overall benefit of advanced therapies for PAH may be attenuated by the greater frequency of AEs.
Inhibition of Inflammation and Bone Erosion by RNA Interference–Mediated Silencing of Heterogeneous Nuclear RNP A2/B1 in Two Experimental Models of Rheumatoid Arthritis
Authors: Herman Sonja , Fischer Anita , Presumey Jessy , Hoffmann Markus , Koenders Marije I. , Escriou Virginie , Apparailly Florence , Steiner Guenter 
Published: May 2015

ObjectiveThe nuclear protein heterogeneous nuclear RNP A2/B1 (hnRNP A2/B1) is involved in posttranscriptional regulation of gene expression. It is constitutively expressed in lymphoid organs and highly up‐regulated in the synovial tissue of patients with rheumatoid arthritis (RA), who may also generate autoantibodies to this protein. This study was undertaken to investigate the potential involvement of hnRNP A2/B1 in the pathogenesis of autoimmune arthritis, by silencing hnRNP A2/B1 expression in 2 animal models of RA.MethodsCollagen‐induced arthritis (CIA) and the K/BxN serum–transfer model were used as animal models of RA. Efficient silencing of hnRNP A2/B1 was achieved using a liposome‐based carrier system for delivery of small interfering RNAs. Expression of hnRNP A2/B1 was analyzed by flow cytometry, reverse transcription–quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The number of osteoclasts was determined by tartrate‐resistant acid phosphatase staining. Cytokine levels and anticollagen antibody levels were measured by enzyme‐linked immunosorbent assay.ResultsEfficient silencing of hnRNP A2/B1 was achieved in all lymphoid organs. In both experimental models, the incidence and severity of arthritis were largely reduced and bone erosion was not detectable as compared to the control groups. Down‐modulation of hnRNP A2/B1 significantly interfered with the production of proinflammatory cytokines from monocyte/macrophages, but not from T cells. Consistent with these findings, production of T cell cytokines was not impaired when cells were restimulated in vitro with type II collagen. Furthermore, levels of anticollagen antibodies were not affected by hnRNP A2/B1 silencing.ConclusionOur findings suggest that hnRNP A2/B1 has an important role in regulation of the innate immune system, especially at the level of monocyte/macrophage activation. Therefore, down‐modulation of hnRNP A2/B1 seems to affect primarily the effector phase of autoimmune arthritis.
Controllability of Semilinear Systems of Parabolic Equations with Delay on the State
Authors: Carrasco A. , Leiva Hugo , Merentes N. , Sanchez J. L. 
Published: May 2015

AbstractIn this paper we prove the approximate controllability of the following semilinear system parabolic equations with delay on the state variable

urn:x-wiley:asjc:media:asjc1162:asjc1162-math-0001
where Ω is a bounded domain in
is a n × n non diagonal matrix whose eigenvalues are semi‐simple with non negative real part, the control u belongs to
and B is a n × m matrix. Here τ≥0 is the maximum delay, which is supposed to be finite. We assume that the operator L:L2([−τ,0];Z)→Z is linear and bounded with
and the nonlinear function f:[0,r] × IRn×IRm→IRn is smooth and bounded.
A perspective perception on the applications of light‐emitting diodes
Authors: Nair Govind B. , Dhoble S. J. 
Published: May 2015

AbstractLight‐emitting diodes (LEDs) continue to penetrate the global market; their pervasiveness clearly being felt in such diverse fields as technological, socio‐economic and commercial interests. The multi‐billion dollar LED market is shared by various segments, including office and household lighting, street lighting, the automobile industry, traffic signals, backlighting for hand‐held devices, indoor and outdoor signs and indicators, medicine, communication systems, crop cultivation using artificial light and many more. The technological development of LEDs has undergone many phases in different parts of the world. From the early discovery of luminescence to the invention of highly efficient organic LEDs, researchers have worked with the prime purpose of improving the performance of luminaires. The need to infuse the market with more efficient and cheaper products has been prevalent from the start. LEDs are a result of this uncontrolled desire of researchers to develop superior products that would displace existing products in the market. To understand what led to the current prominence of LEDs, we give a brief historical overview of the field followed by a thorough discussion of the positive features of LEDs. This work includes the basic requirements, advantages and disadvantages of LEDs in a variety of applications. A brief description of the diverse applications of LED in fields such as lighting, indicators and displays, farming, medicine and communication is given. Considerable importance is placed on discussing the possible difficulties that must be overcome before using LEDs in commercial applications. Copyright © 2015 John Wiley & Sons, Ltd.
Resolving the contributions of two cooperative mechanisms to the DNA Binding of AGT
Authors: Melikishvili Manana , Fried Michael G. 
Published: May 2015

ABSTRACTThe O6‐alkylguanine DNA alkyltransferase (AGT) is a DNA repair enzyme that binds DNA with moderate cooperativity. This cooperativity is important for its search for alkylated bases. A structural model of the cooperative complex of AGT with DNA predicts short‐range interactions between nearest protein neighbors and long‐range interactions between proteins separated in the array. DNA substrates ranging from 11bp to 30bp allowed us to use differences in binding stoichiometry to resolve short‐ and long‐range protein contributions to the stability of AGT complexes. We found that the short‐range component of ΔG°coop was nearly independent of DNA length and protein packing density. In contrast the long‐range component oscillated with DNA length, with a period equal to the occluded binding site size (4bp). The amplitude of the long‐range component decayed from ∼−4 kcal/mole of interaction to ∼−1.2 kcal/mol of interaction as the size of cooperative unit increased from 4 to 7 proteins, suggesting a mechanism to limit the size of cooperative clusters. These features allow us to make testable predictions about AGT distributions and interactions with chromatin structures in vivo. © 2015 The Authors Biopolymers Published by Wiley Periodicals, Inc. Biopolymers 103: 509–516, 2015.
Modification of the degree of branching of a beta‐(1,3)‐glucan affects aggregation behavior and activity in an oxidative burst assay
Authors: Magee Andrew S. , Langeslay Ryan R. , Will Paul M. , Danielson Michael E. , Wurst Lindsay R. , Iiams Vanessa A. 
Published: May 2015

ABSTRACTScleroglucan is a β‐(1,3)‐glucan which is highly branched at the 6‐position with a single glucose residue. Acid hydrolysis of a high molecular weight scleroglucan gave a medium molecular weight, freely soluble material. Linkage analysis by the partially methylated alditol acetate method showed that the solubilized material had 30% branching. When the material was subjected to partial Smith degradations, the percent branching was reduced accordingly to 12% or 17%. After the percent branching was reduced, the average molecular weight of the samples increased considerably, indicating the assembly of higher ordered aggregate structures. An aggregate number distribution analysis was applied to confirm the higher aggregated structures. These aggregated structures gave the material significantly enhanced activity in an in vitro oxidative burst assay compared to the highly branched material. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 665–674, 2015.
Comparative pharmacokinetic profiles of five poorly soluble pulchinenosides in different formulations from Pulsatilla chinensis saponins extracts for enhanced bioavailability
Authors: Huang Jun , Liu Yali , Li Xiang , Song Yonggui , Li Wei , Liu Kuangyi , Su Dan , Feng Yulin , Yang Shilin 
Published: May 2015

AbstractPulsatilla chinensis, a traditional Chinese medicine (TCM), has been used for treating amoebic diseases, vaginal trichomoniasis and bacterial infections over a long history. Now growing attention has been attracted to its antitumor activities. The purpose of this work was to compare the pharmacokinetic profiles of pulchinenosides in different formulations and to improve their oral bioavailability. Extracts of P. chinensis saponins were prepared for PRS‐Na (salt forming), PRS‐HPβCD (hydroxypropyl‐β‐cyclodextrin inclusion complex), PRS‐O/W (oil‐in‐water emulsion) and PRS‐silica (micronization), respectively. A simpler and more durable LC‐MS/MS method was developed in this study for quantitative analysis of pulsatilla sapoin D, B7, B10, B11 and sapoin PD simultaneously. The four formulations enhanced saponins oral bioavailability to varying degrees, as PRS‐HPβCD > PRS‐silica > PRS‐O/W > PRS‐Na, which indicated that water‐soluble preparations can obviously improve the solubility of saponins, and are helpful to increase bioavailability. In particular, hydroxypropyl‐β‐cyclodextrin inclusion complex was the most effective way to promote absorption of saponins, raising the F values (bioavailability) >20 times. Therefore, P. chinensis saponin molecules can be slowly released by emulsion and micronization, which can avoid the enormous Cmax appearing in HPβCD, considering the pharmacokinetics profiles. However, appropriate pharmacokinetic parameters were observed in PRS‐Na, although the F value was minimum among the four preparations. Copyright © 2015 John Wiley & Sons, Ltd.
One‐year clinical outcomes after sirolimus‐eluting coronary stent implantation in diabetics enrolled in the worldwide e‐SELECT registry
Authors: Bartorelli Antonio L. , Egidy Assenza Gabriele , Abizaid Alexandre , Banning Adrian , Džavík Vladimír , Ellis Stephen , Gao Runlin , Holmes David , Ho Jeong Myung , Legrand Victor , Neumann Franz‐Josef , Spaulding Christian , Worthley Stephen G. , Urban Philip ,   for the e‐SELECT Investigators
Published: May 2015

BackgroundDiabetes mellitus has worse outcome after percutaneous coronary intervention.AimWe assessed stent thrombosis (ST), major adverse cardiac events (MACE), and major bleeding rates at 1 year after implantation of sirolimus‐eluting stents (SES) in patients with diabetes mellitus in a large multicenter registry.MethodsFrom May 2006 to April 2008, 15,147 unselected consecutive patients were enrolled at 320 centers in 56 countries in a prospective, observational registry after implantation of ≥ 1 SES. Source data were verified in 20% randomly chosen patients at > 100 sites. Adverse events were adjudicated by an independent Clinical Event Committee.ResultsComplete follow‐up at 1 year was obtained in 13,693 (92%) patients, 4,577 (30%) of whom were diabetics. Within diabetics, 1,238 (9%) were insulin‐treated diabetics (ITD). Diabetics were older (64 vs. 62 years, P < 0.001), with higher incidence of major coronary risk factors, co‐morbidities, and triple‐vessel coronary artery disease. Coronary lesions had smaller reference vessel diameter (2.88 ± 0.46 vs. 2.93 ± 0.45 mm, P < 0.001) and were more often heavily calcified (26.1% vs. 22.6%, P < 0.001). At 1 year, diabetics had higher MACE rate (6.8% vs. 3.9%, P < 0.001) driven by ITD (10.6% vs. 5.5%, P < 0.001). Finally, diabetics had significant increase in ST (1.7% vs. 0.7%, P < 0.001), principally owing to ITD (3.4% vs. 1.1%, P < 0.001). There was an overall low risk of major bleeding during follow‐up, without significant difference among subgroups.ConclusionsIn the e‐SELECT registry, diabetics represented 30% of patients undergoing SES implantation and had significantly more co‐morbidities and complex coronary lesions. Although 1‐year follow‐up documented good overall outcome in diabetics, higher ST and MACE rates were observed, mainly driven by ITD. © 2015 Wiley Periodicals, Inc.
When is rotational angiography superior to conventional single‐plane angiography for planning coronary angioplasty?
Authors: Morris Paul D. , Taylor Jane , Boutong Sara , Brett Sarah , Louis Amal , Heppenstall James , Morton Allison C. , Gunn Julian P. 
Published: May 2015

ObjectivesTo investigate the value of rotational coronary angiography (RoCA) in the context of percutaneous coronary intervention (PCI) planning.BackgroundAs a diagnostic tool, RoCA is associated with decreased patient irradiation and contrast use compared with conventional coronary angiography (CA) and provides superior appreciation of three‐dimensional anatomy. However, its value in PCI remains unknown.MethodsWe studied stable coronary artery disease assessment and PCI planning by interventional cardiologists. Patients underwent either RoCA or conventional CA pre‐PCI for planning. These were compared with the referral CA (all conventional) in terms of quantitative lesion assessment and operator confidence. An independent panel reanalyzed all parameters.ResultsSix operators performed 127 procedures (60 RoCA, 60 conventional CA, and 7 crossed‐over) and assessed 212 lesions. RoCA was associated with a reduction in the number of lesions judged to involve a bifurcation (23 vs. 30 lesions, P < 0.05) and a reduction in the assessment of vessel caliber (2.8 vs. 3.0 mm, P < 0.05). RoCA improved confidence assessing lesion length (P = 0.01), percentage stenosis (P = 0.02), tortuosity (P < 0.04), and proximity to a bifurcation (P = 0.03), particularly in left coronary artery cases. X‐ray dose, contrast agent volume, and procedure duration were not significantly different.ConclusionsCompared with conventional CA, RoCA augments quantitative lesion assessment, enhances confidence in the assessment of coronary artery disease and the precise details of the proposed procedure, but does not affect X‐ray dose, contrast agent volume, or procedure duration. © 2015 Wiley Periodicals, Inc.