bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of and Factors Associated With Increased Arterial Stiffness in Patients With Primary Sjögren's Syndrome
Authors: Sabio José Mario , Sánchez‐Berná Isabel , Martinez‐Bordonado Josefina , Vargas‐Hitos José Antonio , Navarrete‐Navarrete Nuria , Expósito Ruíz Manuela , Jiménez‐Alonso Juan 
Published: October 2014

ObjectiveTo compare the presence of subclinical atherosclerosis measured by means of pulse wave velocity (PWV) in women with primary Sjögren's syndrome (SS) versus a healthy age‐ and sex‐matched control group, and to identify factors independently associated with PWV in primary SS.MethodsForty‐four women with primary SS and 78 age‐matched healthy women without overt cardiovascular (CV) diseases were assessed for traditional and nontraditional CV risk factors. PWV was also performed. A linear regression analysis was used to identify factors independently associated with PWV in primary SS.ResultsWomen with primary SS had significantly higher PWV than controls (P = 0.030), and the frequency of increased PWV was significantly higher in this group (25% versus 8%; P = 0.013). The proportion of patients ages ≤50 years (ratio 4.6) with increased PWV was almost 2‐fold higher than those ages >50 years (ratio 2.4) with respect to controls. Positivity for anti‐SSB was more frequent in patients with normal PWV than in those with increased PWV (61% versus 18%; P = 0.034). Women with primary SS and increased PWV had lower levels of 25‐hydroxyvitamin D (25[OH]D; P = 0.047) than primary SS patients with normal PWV. In addition, 25(OH)D levels tended to correlate inversely with PWV in women with primary SS (P = 0.067), but not in controls (P = 0.97). In multivariate analysis, the Framingham Risk Score (FRS) and Sjögren's Syndrome Damage Index emerged as factors independently correlated with PWV.ConclusionWomen with primary SS had higher PWV than controls, but a similar FRS. The FRS and chronic damage were found to be independently associated with PWV.
Direct Assembly of Benzo[a]carbazole‐5‐carboxylates via a Diels–Alder Reaction with Arynes and 3‐Alkenylindoles
Authors: Tao Yuan , Zhang Fei , Tang Chen‐Yu , Wu Xin‐Yan , Sha Feng 
Published: October 2014

AbstractA concise and direct synthetic strategy for the construction of benzo[a]carbazole‐5‐carboxylates has been disclosed via the Diels–Alder reaction of arynes and 3‐alkenylindoles. The reaction is highly selective and affords the benzo[a]carbazole‐5‐carboxylates in good‐to‐excellent yields.
Access to Fluorine‐Containing Asparagine and Glutamine Analogues via Palladium‐Catalyzed Formate Reduction
Authors: Usuki Yoshinosuke , Wakamatsu Yosuke , Yabu Minoru , Iio Hideo 
Published: October 2014

AbstractA synthesis of fluorine‐containing asparagine and glutamine analogues via palladium‐catalyzed formate reduction of fluorinated carbonate esters is described. Primary amide moieties at the side‐chain of asparagine and glutamine were successfully replaced with fluoroolefins, which are proposed to be aprotic mimics for amides due to their electronic properties.
Mayflies (Ephemeroptera) as indicators of environmental changes in the past five decades: a case study from the Morava and Odra River Basins (Czech Republic)
Authors: Zedková Blanka , Rádková Vanda , Bojková Jindřiška , Soldán Tomáš , Zahrádková Světlana 
Published: October 2014

Abstract

Large‐scale and intensive human activities have caused widespread and profound changes in the diversity and structure of biological communities. Historical or long‐term data are an important tool for the quantification and understanding of temporal changes. A comparison of Ephemeroptera collected at 60 streams in the Morava and Odra river basins in two periods, 1955–1960 and 2006–2011, enabled an estimate of changes in their assemblages induced by various human pressures to be made.
The taxonomic composition of mayfly assemblages was substantially dissimilar between the two periods, although the changes were not associated with a decline in regional or local diversity. Only lowland rivers lost several of their original species, mostly habitat specialists. Species replacement, a leading driver of dissimilarity, caused shifts towards more simplified, less specialized assemblages in large rivers, and towards more pollution‐ and siltation‐tolerant assemblages in small rivers. The increase in cold‐water specialists and a stable share of generalists suggested the maintenance of a certain level of specialization in the assemblages of brooks.
The most marked change in the assemblage was associated with the impaired or bad water quality of rivers in the 1950s, which persisted or further deteriorated in the ensuing decades. Assemblages that were influenced by a slight deterioration or improvement in water quality were less altered, unless affected by other pressures (such as channel or discharge modifications).
The results indicate that the causes of changes in the assemblages are many and complex, although heavy pollution overrides other influences. Direct habitat loss or their degradation by siltation appear to be leading contributors to changes in assemblages. The results imply the need for the application of a catchment‐scale perspective for the restoration of streams and the conservation of the remaining well‐preserved stretches of lowland rivers.
Copyright © 2014 John Wiley & Sons, Ltd.
Combined Inhibition of Tumor Necrosis Factor α and Interleukin‐17 As a Therapeutic Opportunity in Rheumatoid Arthritis: Development and Characterization of a Novel Bispecific Antibody
Authors: Fischer Jens A. A. , Hueber Axel J. , Wilson Stacy , Galm Margarete , Baum Wolfgang , Kitson Christopher , Auer Johannes , Lorenz Stefan H. , Moelleken Jörg , Bader Martin , Tissot Alain C. , Tan Seng‐Lai , Seeber Stefan , Schett Georg 
Published: October 2014

ObjectiveRheumatoid arthritis therapies that are based on inhibition of a single cytokine, e.g., tumor necrosis factor α (TNFα) or interleukin‐6 (IL‐6), produce clinically meaningful responses in only about half of the treated patients. This study was undertaken to investigate whether combined inhibition of TNFα and IL‐17 has additive or synergistic effects in the suppression of mesenchymal cell activation in vitro and inflammation and tissue destruction in arthritis in vivo.MethodsCultures of human fibroblast‐like synoviocytes (FLS) were stimulated with TNFα, IL‐17, or a combination of both. Single/combined neutralizing antibodies against TNFα and IL‐17 were used to examine in vitro cytokine responses and in vivo development of arthritis and bone and cartilage destruction in TNFα‐transgenic mice. Bispecific anti–TNFα/IL‐17 antibodies were designed, and their potential to block cytokine responses in human FLS was tested.ResultsTNFα and IL‐17 had additive/synergistic effects in promoting production of IL‐6, IL‐8, and granulocyte colony‐stimulating factor, as well as matrix metalloproteinases, in FLS. Bispecific anti–TNFα/IL‐17 antibodies showed superior efficacy in blocking cytokine and chemokine responses in vitro. Furthermore, dual versus single inhibition of both cytokines using neutralizing antibodies was more effective in inhibiting the development of inflammation and bone and cartilage destruction in arthritic mice.ConclusionCombined blockade of TNFα and IL‐17 was more effective than single blockade in inhibiting cytokine, chemokine, and matrix enzyme responses from human mesenchymal cells and in blocking tissue destruction associated with arthritis, and additionally showed a positive impact on rebalance of bone homeostasis. Bispecific anti–TNFα/IL‐17 antibodies may have superior efficacy in the treatment of arthritis and may overcome the limited therapeutic responses obtained with single cytokine neutralization.
Transcription Factor Snail Regulates Tumor Necrosis Factor α–Mediated Synovial Fibroblast Activation in the Rheumatoid Joint
Authors: Chen Shih‐Yao , Shiau Ai‐Li , Li Yuan‐Tsung , Lin Chi‐Chen , Jou I‐Ming , Liu Ming‐Fei , Wu Chao‐Liang , Wang Chrong‐Reen 
Published: October 2014

ObjectiveThe transcription factor Snail is involved in various biologic functions. We hypothesized that this molecule regulates tumor necrosis factor α (TNFα)–mediated synovial fibroblast activation in the rheumatoid joint. The aim of this study was to examine the role of Snail in the expression of cadherin‐11 (Cad‐11) and myofibroblast markers, interleukin‐6 (IL‐6) production, and the invasive ability of cells.MethodsSynovium samples were obtained from patients with rheumatoid arthritis (RA) and from rats with collagen‐induced arthritis (CIA). Synovial fibroblasts were treated with TNFα or a Wnt signaling inducer, and the joints of rats with CIA were injected with a TNFα antagonist. Modulation of Snail expression in the synovial fibroblasts and joints was performed by lentiviral vector–mediated transfer of complementary DNA or short hairpin RNA.ResultsThe expression of Snail and Cad‐11 was higher in synovium and synovial fibroblasts from patients with RA compared with patients with osteoarthritis and was increased in rats with CIA. TNFα stimulation or activation of Wnt signaling up‐regulated the expression of Snail, Cad‐11, and α‐smooth muscle actin (α‐SMA) in synovial fibroblasts, and anti‐TNFα therapy down‐regulated the expression of Snail, Cad‐11, and α‐SMA in the joints of rats with CIA. Although synovial fibroblast transfectants in which Snail was overexpressed showed increased expression of Cad‐11 and α‐SMA and enhanced TNFα‐mediated invasive capacity and IL‐6 production, synovial fibroblast transfectants from rats with CIA in which Snail was silenced showed decreased expression and had the opposite effect on these functions. Normal joints in which Snail was overexpressed had hyperplastic synovium, with increased expression of Cad‐11, α‐SMA, and IL‐6. Silencing Snail expression ameliorated arthritis, with reduced Cad‐11 expression and reduced levels of extracellular matrix deposition in the joints of rats with CIA, whereas overexpression of Snail exacerbated arthritis, with increased Cad‐11 expression and increased levels of extracellular matrix deposition.ConclusionOur results demonstrate that Snail regulates TNFα‐mediated activation of synovial fibroblasts in the rheumatoid joint. These findings may contribute to the pharmacologic development of therapeutics targeting synovial fibroblasts in patients with RA.
Amelioration of Tissue Fibrosis by Toll‐like Receptor 4 Knockout in Murine Models of Systemic Sclerosis
Authors: Takahashi Takehiro , Asano Yoshihide , Ichimura Yohei , Toyama Tetsuo , Taniguchi Takashi , Noda Shinji , Akamata Kaname , Tada Yayoi , Sugaya Makoto , Kadono Takafumi , Sato Shinichi 
Published: October 2014

ObjectiveBleomycin‐induced fibrosis and the tight skin (TSK/+) mouse are well‐established experimental murine models of human systemic sclerosis (SSc). Growing evidence has demonstrated the pivotal role of Toll‐like receptors (TLRs) in several autoimmune inflammatory diseases, including SSc. This study was undertaken to determine the role of TLR‐4 in the fibrotic processes in these murine models.MethodsWe generated a murine model of bleomycin‐induced SSc using TLR‐4−/− mice and TLR‐4−/−;TSK/+ mice. The mechanisms by which TLR‐4 contributes to pathologic tissue fibrosis were investigated in these 2 models by histologic examination, hydroxyproline assay, enzyme‐linked immunosorbent assay, real‐time polymerase chain reaction, and flow cytometry.ResultsDermal and lung fibrosis was attenuated in bleomycin‐treated TLR‐4−/− mice compared with their wild‐type counterparts. Inflammatory cell infiltration, expression of various inflammatory cytokines, and pathologic angiogenesis induced by bleomycin treatment were suppressed with TLR‐4 deletion. Furthermore, the increased expression of interleukin‐6 (IL‐6) in fibroblasts, endothelial cells, and immune cells in response to bleomycin in vivo and to lipopolysaccharide in vitro was notably abrogated in the absence of TLR‐4. Moreover, TLR‐4 deletion was associated with alleviated B cell activation and skew toward a Th2/Th17 response against bleomycin treatment. Importantly, in TSK/+ mice, another SSc murine model, TLR‐4 abrogation attenuated hypodermal fibrosis.ConclusionThese results indicate the pivotal contribution of TLR‐4 to the pathologic tissue fibrosis of SSc murine models. Our results indicate the critical role of TLR‐4 signaling in the development of tissue fibrosis, suggesting that biomolecular TLR‐4 targeting might be a potential therapeutic approach to SSc.
Dual B Cell Immunotherapy Is Superior to Individual Anti‐CD20 Depletion or BAFF Blockade in Murine Models of Spontaneous or Accelerated Lupus
Authors: Lin WeiYu , Seshasayee Dhaya , Lee Wyne P. , Caplazi Patrick , McVay Sami , Suto Eric , Nguyen Allen , Lin Zhonghua , Sun Yonglian , DeForge Laura , Balazs Mercedesz , Martin Flavius , Zarrin Ali A. 
Published: October 2014

ObjectiveTo determine whether a combination of B cell depletion and BAFF blockade is more effective than monotherapy in treating models of spontaneous or accelerated systemic lupus erythematosus (SLE) in (NZB × NZW)F1 mice.MethodsClinical parameters such as disease progression–free survival, proteinuria, and renal injury were assessed in models of spontaneous, interferon‐α (IFNα)–accelerated, or pristane‐accelerated lupus in (NZB × NZW)F1 mice. Treatment arms included anti‐CD20 (B cell depletion), B lymphocyte stimulator receptor 3 fusion protein (BR‐3‐Fc) (BAFF blockade), the combination of anti‐CD20 and BR‐3‐Fc, isotype control, or cyclophosphamide. In models of spontaneous, IFNα‐accelerated, or pristane‐accelerated lupus, mice were treated for 24 weeks, 8 weeks, or 12 weeks, respectively. Peripheral and resident B cell subsets and various autoantibodies were examined.ResultsCompared to B cell depletion or BAFF blockade alone, combined therapy significantly improved disease manifestations in all 3 lupus models. In addition, marginal zone B cells, plasmablasts, and circulating and tissue plasma cells were decreased more effectively. Dual B cell immunotherapy also reduced multiple classes of pathogenic autoantibodies, consistent with its observed effectiveness in reducing immune complex–mediated renal injury.ConclusionDual immunotherapy via B cell depletion and BAFF blockade is more efficacious than single agent immunotherapy in murine SLE models, and this combination treatment is predicted to be an effective strategy for immunotherapy in human SLE.
Effect of Axial Ligands on the Molecular Configurations, Stability, Reactivity, and Photodynamic Activities of Silicon Phthalocyanines
Authors: Luan Liqiang , Ding Lanlan , Shi Jiawei , Fang Wenjuan , Ni Yuxing , Liu Wei 
Published: October 2014

AbstractTo demonstrate the effect of axial ligands on the structure–activity relationship, a series of axially substituted silicon phthalocyanines (SiPcs) have been synthesized with changes to the axial ligands. The reactivity of the axial ligand upon shielding by the phthalocyanine ring current, along with their stability, photophysical, and photodynamic therapy (PDT) activities were compared and evaluated for the first time. As revealed by single‐crystal XRD analysis, rotation of the axial OMe ligands was observed in SiPc 3, which resulted in two molecular configurations coexisting synchronously in both the solid and solution states and causing a split of the phthalocyanine α protons in the 1H NMR spectra that is significantly different from all SiPcs reported so far. The remarkable photostability, good singlet oxygen quantum yield, and efficient in vitro photodynamic activity synergistically show that compound 3 is one of the most promising photosensitizers for PDT.
Suppression of CCN formation by bromine chemistry in the remote marine atmosphere
Authors: Breider Thomas James , Chipperfield Martyn P. , Mann Graham W. , Woodhouse Matthew T. , Carslaw Ken S. 
Published: October 2014

AbstractUsing a global model, we investigate how bromine chemistry affects cloud condensation nuclei (CCN) formation in the remote marine atmosphere. Bromine increases dimethylsulphide (DMS) oxidation but lowers SO2 yield, leading to less sulphate aerosol. The effect is largest (3–7% decrease in total CCN and 15–30% decrease in CCN from DMS) over the summertime southern ocean, a region of strong bromine release from sea‐salt. DMS and bromine emissions have a coupled feedback effect on CCN. Increased DMS enhances the release of sea‐salt bromine through increased aerosol acidity. This enhanced bromine suppresses the CCN response to increased DMS by up to 30%.
Peptide and peptide nucleic acid syntheses using a DNA/RNA synthesizer
Authors: Pokharel Durga , Fueangfung Suntara , Zhang Mingcui , Fang Shiyue 
Published: October 2014

ABSTRACTThe use of an ABI 394 DNA/RNA synthesizer for peptide and peptide nucleic acid (PNA) syntheses is described. No additional physical part or software is needed for the application. A commercially available large DNA synthesis column was used, and only about half of its volume was filled with resin when the resin was fully swollen. With additional space in the top portion of the column, agitation of reaction mixture was achieved by bubbling argon from the bottom without losing solution. Removing solutions from column was achieved by flushing argon from top to bottom. Two peptide and two PNA sequences were synthesized. Good yields were obtained in all the cases. The method is easy to follow by researchers who are familiar with DNA/RNA synthesizer. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 487–493, 2014.
Development and validation of a simple and isocratic reversed‐phase HPLC method for the determination of rilpivirine from tablets, nanoparticles and HeLa cell lysates
Authors: Date Abhijit A. , Shibata Annemarie , Bruck Patrick , Destache Christopher J. 
Published: October 2014

AbstractIn the present investigation, a simple and isocratic HPLC‐UV method was developed and validated for determination of rilpivirine (RPV) from dosage forms (tablets and nanoparticles) and biological matrices like HeLa cell lysates. The separation and analysis of RPV was carried out under isocratic conditions using (a) a Gemini reversed‐phase C18 column (5 µm; 4.6 × 150 mm) maintained at 35°C, (b) a mobile phase consisting of a mixture of acetonitrile and 25 m m potassium dihydrogen phosphate (in the ratio 50:50 v/v) at a flow rate of 0.6 mL/min and (c) atazanavir as an internal standard. The total run time was 17 min and the analysis of RPV and internal standard was carried out at 290 nm. The method was found to be linear (r2 value > 0.998), specific, accurate and precise over the concentration range of 0.025–2 µg/mL. The lower limit of quantification was 0.025 µg/mL, the limit of detection was 0.008 µg/mL and the recovery of RPV was >90%. The stability of the RPV analytical method was confirmed at various conditions such as room temperature (24 h), −20°C (7 days), three freeze−thaw cycles and storage in an autosampler (4°C for 48 h). The method was successfully applied for the determination of RPV from conventional dosage forms like tablets, from polymeric nanoparticles and from biological matrices like HeLa cell lysates. Copyright © 2014 John Wiley & Sons, Ltd.
Stability‐indicating HPLC assay for lysine–proline–valine (KPV) in aqueous solutions and skin homogenates
Authors: Pawar Kasturi R. , Mulabagal Vanisree , Smith Forrest , Kolli Chandra S. , Rangari Vijaya K. , Babu R. Jayachandra 
Published: October 2014

AbstractA simple, sensitive and stability‐indicating high‐performance liquid chromatographic (HPLC) assay method was developed and validated for a bioactive peptide, lysine–proline–valine (KPV) in aqueous solutions and skin homogenates. Chromatographic separation was achieved on a reversed phase Phenomenex C18 column (4.6 × 250 mm, packed with 5 µm silica particles) with a gradient mobile phase consisting of 0.1% trifluoroacetic acid (TFA) in water (A) and 0.1% TFA in acetonitrile (B). The proposed HPLC method was validated with respect to accuracy, precision, linearity, repeatability, limit of detection (LOD) and limit of quantitation (LOQ). The calibration curve was linear with a correlation coefficient (r) of 0.9999. Relative standard deviation values of accuracy and precision experiments were <2. The LOD and LOQ of KPV were 0.01 and 0.25 µg/mL, respectively. Under stress conditions (acid, alkali and hydrogen peroxide) KPV yielded lys–pro–diketopiperazine as major degradation product, which was identified by flow injection MS analysis. The developed HPLC method was found to be efficient in separating the active peptide from its degradation products generated under various stress conditions. Also, the validated method was able to separate KPV from other peaks arising from endogenous components of the skin homogenate. Copyright © 2014 John Wiley & Sons, Ltd.
Simultaneous determination of erlotinib and its isomeric major metabolites in human plasma using isocratic liquid chromatography–tandem mass spectrometry and its clinical application
Authors: Ishida Takuya , Naito Takafumi , Kawakami Junichi 
Published: October 2014

AbstractThis study developed a method for the simultaneous determination of erlotinib and its isomeric major metabolites, OSI‐413 and OSI‐420, in human plasma using an isocratic liquid chromatography–tandem mass spectrometry. Plasma specimens deproteinized with acetonitrile were separated using a 3‐µm particle size octadecylsilyl column. The m/z values of the precursor and product ions for the analytes were as follows: erlotinib, 394.2/278.2; and OSI‐413 and OSI‐420, 380.2/278.2. The total run time was 21 min and no peaks interfering with the analytes and internal standard (d6‐erlotinib) in human plasma were observed. The calibration curves of erlotinib, OSI‐413 and OSI‐420 were linear over the concentration ranges of 10–3000, 2–500 and 2–100 ng/mL, respectively. The pretreatment recovery ratios were >86.1%. The intra‐ and inter‐assay precisions and accuracies were <12.7 and 89.0–108.9% for all analytes. This validated method was applied to the determination of plasma samples in lung cancer patients receiving 150 mg of oral erlotinib. The plasma concentration ranges of erlotinib, OSI‐413 and OSI‐420 were 373–2354, 15.7–379 and 2.5–43.6 ng/mL, respectively. In conclusion, the present method can be helpful for evaluating the plasma exposures of erlotinib and its major isomeric metabolites in clinical settings. Copyright © 2014 John Wiley & Sons, Ltd.
Collective Action and Social Change: Examining the Role of Representation in the Communication between Protesters and Third‐party Members
Authors: Batel Susana , Castro Paula 
Published: October 2014

AbstractWithin social psychology, it has been proposed that to understand how collective action creates social change, it is relevant to examine the role that other members of society can have on it. However, few studies have empirically examined that. We argue that for that task, it is useful, first, and as some authors have already argued, to go beyond the sole analysis of the two‐sided inter‐group relations creating collective action; and second, to articulate this with contributions from social representations theory, which recognises that to understand social change, we need to examine communicative practices, or how communication is used between collective action's actors and other actors to re‐present identities. We analyse the protests by a movement of residents from a Lisbon neighbourhood that protested against the transformation of a neighbourhood's convent. Besides discussing this transformation with local authorities and failing to achieve its aims through that, the protesters also discussed it with other citizens. The analysis of this debate shows that the arguments and actions they used change throughout time, from local to global, as the latter were the ones more endorsed by other citizens and thus those that could help the protesters to achieve their goals. Copyright © 2014 John Wiley & Sons, Ltd.