bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyridylimine Cobalt(II) and Nickel(II) Complex Functionalized Multiwalled Carbon Nanotubes and Their Catalytic Activities for Ethylene Oligomerization
Authors: Alshehri Saad M. , Ahamad Tansir , Aldalbahi Ali , Alhokbany Norah 
Published: April 2015

ABSTRACTMultiwalled carbon nanotubes (MWCNTs) were covalently functionalized with pyridylimine and its metal complexes. The synthesized compounds were characterized by several analytical techniques. The pyridylimine metal complex–functionalized multiwalled carbon nanotubes [Pyr‐M(II)‐MWCNTs] were evaluated as catalyst precursors for ethylene oligomerization with methylaluminoxane (MAO) used as an activator at different Al/M [M(II) = Co(II) and Ni(II)] ratios and at two different ethylene pressures. [Pyr‐Co(II)‐MWCNTs] (C1) and (Pyr‐Ni(II)‐MWCNTs] (C2) were isolated as solid materials in good yield. Complex C2 was found to be a more effective precatalyst than C1 in the presence of MAO. Thus, C2 exhibited a maximum catalytic activity of 1.89 × 106 g mol−1(Ni) h−1 bar−1 with an Al/Ni ratio of 2000:1 at room temperature with a 5‐atm pressure of ethylene, whereas C1 exhibited a maximum activity of 1.87 × 106 g mol−1(Co) h−1 bar−1 in a similar condition. When the Al/Co ratio was increased at a 1‐atm pressure of ethylene, the catalytic activity of the precatalyst increased and the process became more selective toward higher oligomers. The catalytic activity and selectivity with 1‐decene using C1 were 3.02 × 105 g mol−1(Co) h1 bar−1 and 72%, respectively, with 5 atm ethylene and an Al/Co ratio of 200:1.
Itraconazole and clarithromycin inhibit P‐glycoprotein activity in primary human sinonasal epithelial cells
Authors: Lam Allen , Hoang John D. , Singleton Amy , Han Xue , Bleier Benjamin S. 
Published: April 2015

BackgroundItraconazole and clarithromycin are clinically effective in the treatment of chronic rhinosinusitis (CRS) through incompletely understood anti‐inflammatory properties. P‐glycoprotein (P‐gp) is overexpressed in CRS and inhibition results in decreased inflammatory cytokine secretion. Both itraconazole and clarithromycin have also been shown to have P‐gp inhibitory properties in other tissues, suggesting a novel explanation for their immunomodulatory effects in CRS. The purpose of this study is to therefore confirm whether these drugs are capable of inhibiting P‐gp specifically in sinonasal epithelial cells.MethodsThis was an institutional review board (IRB)‐approved study in which primary sinonasal epithelial cells were cultured in 96‐well plates. A Calcein AM assay was used to quantify P‐gp inhibition as determined by an increase in intracellular fluorescence. A dose‐response curve was generated for itraconazole and clarithromycin (maximal concentration 100 μM) and compared to that of Zosuquidar, a highly specific known P‐gp inhibitor. Results were compared using a Student t test with a significance defined as p < 0.05.ResultsBoth itraconazole and clarithromycin demonstrated a dose‐response curve for P‐gp inhibition similar to that of Zosuquidar. The respective maximal inhibitory concentrations of Zosuquidar, itraconazole, and clarithromycin prior to induction of cytotoxicity were 0.31, 3.13, and 1.56 μM, respectively, as demonstrated by a statistically significant increase in total intracellular fluorescence (p < 0.05 in all groups).ConclusionBoth itraconazole and clarithromycin are capable of inhibiting sinonasal epithelial cell associated P‐gp. The anti‐inflammatory effects of these agents in CRS may be attributable, in part, to their heretofore unrecognized P‐gp modulatory properties.
Computed tomography imaging practice patterns in adult chronic rhinosinusitis: survey of the American Academy of Otolaryngology–Head and Neck Surgery and American Rhinologic Society membership
Authors: Batra Pete S. , Setzen Michael , Li Yan , Han Joseph K. , Setzen Gavin 
Published: April 2015

BackgroundThe objective of this study was to assess the current practice patterns of computed tomography (CT) imaging for diagnosis and management of adult chronic rhinosinusitis (CRS).MethodsA 29‐item, electronic, Web‐based physician survey was disseminated to the American Academy of Otolaryngology–Head and Neck Surgery (AAO‐HNS) and American Rhinologic Society (ARS) membership from November 2012 to January 2013.ResultsA total of 331 otolaryngologists completed the survey. Seventy‐five percent of respondents did not obtain confirmatory CT imaging prior to initiating medical therapy for CRS. A typical diagnostic scan was considered to be a 3‐mm coronal CT with or without 3‐mm axial images for 50.6% of participants. On average, the respondents obtained 1 (58.8%) or 2 (36.6%) CT scans prior to proceeding with sinus surgery. CT scanning was most commonly performed in a hospital radiology department (76.4%), followed by a free‐standing imaging center (44.5%). An in‐office CT scanner was owned by 24.5% of the respondents, mostly commonly a cone beam CT (74.0%) scanner. Most respondents (87.1%) did not experience problems with carriers denying ability to image or reimbursing for scans. Overall, 68.4% of the respondents were unaware of the dosage of radiation delivered by the scanner used for CT acquisition.ConclusionThis survey provides a snapshot of the current utility of CT imaging in the management paradigm for CRS. Given that most are unaware of the delivered radiation dose, this clearly represents an important area of improvement in the knowledge gap.
Outcomes of complete vs targeted approaches to endoscopic sinus surgery
Authors: DeConde Adam S. , Suh Jeffrey D. , Mace Jess C. , Alt Jeremiah A. , Smith Timothy L. 
Published: April 2015

BackgroundFunctional endoscopic sinus surgery (FESS) was historically predicated on targeted widening of narrow anatomic structures that caused postobstructive persistent sinus inflammation. It is now clear that chronic rhinosinusitis (CRS) is a multifactorial disease with subsets of patients which may require a more extensive surgical approach. This study compares quality‐of‐life (QOL) and disease severity outcomes after FESS based on the extent of surgical intervention.MethodsParticipants with CRS were prospectively enrolled into an ongoing, multi‐institutional, observational, cohort study. Surgical extent was determined by physician discretion. Participants undergoing bilateral frontal sinusotomy, ethmoidectomy, maxillary antrostomy, and sphenoidotomy were considered to have undergone “complete” surgery, whereas all other participants were categorized as receiving “targeted” surgery. Improvement was evaluated between surgical subgroups with at least 6‐month follow‐up using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and the Brief Smell Inventory Test (B‐SIT).ResultsA total of 311 participants met inclusion criteria with 147 subjects undergoing complete surgery and 164 targeted surgery. A higher prevalence of asthma, acetylsalicylic acid (ASA) sensitivity, nasal polyposis, and a history of prior sinus surgery (p ≤ 0.002) was present in participants undergoing complete surgery. Mean improvement in SNOT‐22 (28.1 ± 21.9 vs 21.9 ± 20.6; p = 0.011) and B‐SIT (0.8 ± 3.1 vs 0.2 ± 2.4; p = 0.005) was greater in subjects undergoing complete surgery. Regression models demonstrated a 5.9 ± 2.5 greater relative mean improvement on SNOT‐22 total scores with complete surgery over targeted approaches (p = 0.016).ConclusionComplete surgery was an independent predictor of greater postoperative SNOT‐22 score improvement, yet did not achieve clinical significance. Further study is needed to determine the optimal surgical extent.
Changes in Cytokines and Aggrecan ARGS Neoepitope in Synovial Fluid and Serum and in C‐Terminal Crosslinking Telopeptide of Type II Collagen and N‐Terminal Crosslinking Telopeptide of Type I Collagen in Urine Over Five Years After Anterior Cruciate Ligament Rupture: An Exploratory Analysis in the Knee Anterior Cruciate Ligament, Nonsurgical Versus Surgical Treatment Trial
Authors: Struglics André , Larsson Staffan , Kumahashi Nobuyuki , Frobell Richard , Lohmander L. Stefan 
Published: April 2015

ObjectiveTo prospectively monitor levels of proinflammatory cytokines and aggrecan ARGS neoepitope in synovial fluid and serum as well as levels of C‐terminal crosslinking telopeptide of type II collagen (CTX‐II) and N‐terminal crosslinking telopeptide of type I collagen (NTX‐I) in urine after acute anterior cruciate ligament (ACL) rupture.MethodsSynovial fluid, serum, and urine were collected from 121 adults on 6 occasions over 5 years after acute ACL injury. Reference samples were obtained from subjects without knee injury. Concentrations of interleukin‐6 (IL‐6), IL‐8, IL‐10, interferon‐γ (IFNγ), tumor necrosis factor (TNF), aggrecan ARGS neoepitope, CTX‐II, and NTX‐I were measured by enzyme‐linked immunosorbent assay.ResultsShortly after ACL injury, cytokine concentrations in synovial fluid were elevated 6‐fold (TNF) to 1,050‐fold (IL‐6) compared to reference levels, while concentrations of aggrecan ARGS neoepitope in synovial fluid and serum and CTX‐II in urine were elevated 1.4‐fold to 8‐fold. Thereafter, concentrations of cytokines and aggrecan ARGS neoepitope in synovial fluid decreased with different half‐lives (in years: IL‐6 0.9, IL‐8 2.2, IL‐10 2.3, IFNγ 3.1, TNF 3.6, aggrecan ARGS neoepitope 4.0). After 5 years, the TNF concentration in synovial fluid remained higher than the reference level. There was a correlation between the concentrations of aggrecan ARGS neoepitope in synovial fluid and serum (rs = 0.36). Concentrations of aggrecan ARGS neoepitope in synovial fluid and of CTX‐II and NTX‐I in urine were correlated with concentrations of cytokines in synovial fluid (rs = 0.41–0.49 and rs = 0.21–0.31, respectively).ConclusionAcute ACL injury induced highly increased levels of inflammatory cytokines in the joint, and these were associated with proteolysis of aggrecan and type II collagen. Cytokine levels remained increased up to 5 years after injury, indicative of extended local inflammation in the joint.
Large‐scale adenovirus and poxvirus‐vectored vaccine manufacturing to enable clinical trials
Authors: Kallel Héla , Kamen Amine A. 
Published: April 2015

AbstractEfforts to make vaccines against infectious diseases and immunotherapies for cancer have evolved to utilize a variety of heterologous expression systems such as viral vectors. These vectors are often attenuated or engineered to safely deliver genes encoding antigens of different pathogens. Adenovirus and poxvirus vectors are among the viral vectors that are most frequently used to develop prophylactic vaccines against infectious diseases as well as therapeutic cancer vaccines. This mini‐review describes the trends and processes in large‐scale production of adenovirus and poxvirus vectors to meet the needs of clinical applications. We briefly describe the general principles for the production and purification of adenovirus and poxvirus viral vectors. Currently, adenovirus and poxvirus vector manufacturing methods rely on well‐established cell culture technologies. Several improvements have been evaluated to increase the yield and to reduce the overall manufacturing cost, such as cultivation at high cell densities and continuous downstream processing. Additionally, advancements in vector characterization will greatly facilitate the development of novel vectored vaccine candidates.
The stage‐specific in vitro efficacy of a malaria antigen cocktail provides valuable insights into the development of effective multi‐stage vaccines
Authors: Spiegel Holger , Boes Alexander , Kastilan Robin , Kapelski Stephanie , Edgue Güven , Beiss Veronique , Chubodova Ivana , Scheuermayer Matthias , Pradel Gabriele , Schillberg Stefan , Reimann Andreas , Fischer Rainer 
Published: April 2015

AbstractMulticomponent vaccines targeting different stages of Plasmodium falciparum represent a promising, holistic concept towards better malaria vaccines. Additionally, an effective vaccine candidate should demonstrate cross‐strain specificity because many antigens are polymorphic, which can reduce vaccine efficacy. A cocktail of recombinant fusion proteins (VAMAX‐Mix) featuring three diversity‐covering variants of the blood‐stage antigen PfAMA1, each combined with the conserved sexual‐stage antigen Pfs25 and one of the pre‐erythrocytic‐stage antigens PfCSP_TSR or PfCelTOS, or the additional blood‐stage antigen PfMSP1_19, was produced in Pichia pastoris and used to immunize rabbits. The immune sera and purified IgG were used to perform various assays determining antigen specific titers and in vitro efficacy against different parasite stages and strains. In functional in vitro assays we observed robust inhibition of blood‐stage (up to 90%), and sexual‐stage parasites (up to 100%) and biased inhibition of pre‐erythrocytic parasites (0–40%). Cross‐strain blood‐stage efficacy was observed in erythrocyte invasion assays using four different P. falciparum strains. The quantification of antigen‐specific IgGs allowed the determination of specific IC50 values. The significant difference in antigen‐specific IC50 requirements, the direct correlation between antigen‐specific IgG and the relative quantitative representation of antigens within the cocktail, provide valuable implementations for future multi‐stage, multi‐component vaccine designs.
The Irony of Social Trust: Individual‐level and Contextual‐level Links with Protest Intention and Radical Right Support in Switzerland
Authors: Glaeser Stephanie 
Published: April 2015

AbstractThis research examines how social trust translates into dynamics of mobilisation for inclusion or exclusion in Swiss cantons by studying how social trust is linked to equality‐directed protest intention versus radical right support, comparing individual‐level and contextual‐level relationships. The study is based on data from the Swiss Household Panel collected between 2002 and 2008. The impact of individual‐level and contextual‐level social trust is analysed in three‐level regression models of repeated observations, nested in individuals who are nested in cantons. The results indicate complex patterns that depend on the level at which social trust is assessed and confirm the need for a contextualised view of social trust and social capital. For individuals, higher social trust is associated with higher protest intention and lower radical right support. However, in cantons characterised by higher rates of social trust, individuals are less likely to engage in protest actions and more likely to support the radical right. Further analyses show that canton‐level social trust is intertwined with other contextual factors, suggesting that in certain configurations, that is, combined with low levels of cultural and social diversity, climates of social trust may be linked to more restricted forms of solidarity and the persistence of inequality. Copyright © 2015 John Wiley & Sons, Ltd.
Enhancing Antibody Response against Small Molecular Hapten with Tobacco Mosaic Virus as a Polyvalent Carrier
Authors: Zhao Xia , Chen Limin , Luckanagul Jittima Amie , Zhang Xiaolei , Lin Yuan , Wang Qian 
Published: April 2015

AbstractVirus nanoparticles (VNPs) have been applied as carrier proteins for effective vaccine development. In this paper, we report the usage of tobacco mosaic virus (TMV) as a carrier for the display of the small molecule estriol (E3), a weakly immunogenic hapten. A highly efficient copper (I)‐catalyzed azide–alkyne cycloaddition reaction (CuAAC) was performed for the conjugation of E3 onto TMV capsid at tyrosine (Tyr) 139, by which the antigen density could be controlled. The immune properties of these constructs were evaluated in mice. We found that a strong and long‐term antibody response was elicited by conjugating a high density of small molecular haptens on TMV through an oligo(ethylene glycol) (OEG) linker, likely due to the effective activation of B‐cells. This study suggests that TMV can serve as a promising platform to induce strong humoral immune responses and that the optimized conjugation strategy was critical to produce high quality antibodies.
Aortic annulus and root characteristics in severe aortic stenosis due to bicuspid aortic valve and tricuspid aortic valves: Implications for transcatheter aortic valve therapies
Authors: Philip Femi , Faza Nadine Nadar , Schoenhagen Paul , Desai Milind Y. , Tuzcu E. Murat , Svensson Lars G. , Kapadia Samir R. 
Published: April 2015

BackgroundPatients with severe aortic stenosis due to BAV are excluded from transcatheter aortic valve replacement (TAVR) due to concern for asymmetric expansion and valve dysfunction. We sought to characterize the aortic root and annulus in bicuspid aortic valve (BAV) and tricuspid aortic valves (TAV).Methods and ResultsWe identified patients with severe AS who underwent multi‐detector computed tomographic (MDCT) imaging prior to surgical aortic valve replacement (SAVR, n = 200) for BAV and TAVR (n = 200) for TAV from 2010 to 2013. The presence of a BAV was confirmed on surgical and pathological review. Annulus measurements of the basal ring (short‐ and long‐axis, area‐derived diameter), coronary ostia height, sinus area (SA), sino‐tubular junction area (STJ), calcification and eccentricity index (EI, 1‐short axis/long axis) were made. Patients with TAV were older (78.8 years vs. 57.8 years, P = 0.04) than those with BAV. The aortic annulus area (5.21 ± 2.1 cm2 vs. 4.63 ± 2.0 cm2, P = 0.0001), sinus of Valsalva diameter (3.7 ± 0.9 cm vs. 3.1 ± 0.1 cm, P = 0.001) and ascending aorta diameter (3.5 ± 0.7 cm vs. 2.97 ± 0.6 cm, P = 0.001) were significantly larger with BAV. Bicuspid aortic annuli were significantly less elliptical (EI, 1.24 ± 0.1 vs. 1.29 ± 0.1, P = 0.006) and more circular (39% vs. 4%, P < 0.001) compared to the TAV annulus. There was more eccentric annular calcification in BAV vs. TAV (68% vs. 32%, P < 0.001). The mean distance from the aortic annulus to the left main coronary ostium was less than the right coronary ostium. Less than 10% of the BAV annuli would not fit a currently available valved stents.ConclusionBicuspid aortic valves have a larger annulus size, sinus of Valsalva and ascending aorta dimensions. In addition, the BAV aortic annuli appear circular and most will fit currently available commercial valved stents. © 2015 Wiley Periodicals, Inc.
A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine‐refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment
Authors: Cabanillas Maria E. , Schlumberger Martin , Jarzab Barbara , Martins Renato G. , Pacini Furio , Robinson Bruce , McCaffrey Judith C. , Shah Manisha H. , Bodenner Donald L. , Topliss Duncan , Andresen Corina , O'Brien James P. , Ren Min , Funahashi Yasuhiro , Allison Roger , Elisei Rossella , Newbold Kate , Licitra Lisa F. , Sherman Steven I. , Ball Douglas W. 
Published: April 2015

BACKGROUNDLenvatinib is an oral, multitargeted tyrosine kinase inhibitor of the vascular endothelial growth factor receptors 1 through 3 (VEGFR1‐VEGFR3), fibroblast growth factor receptors 1 through 4 (FGFR1‐FGFR4), platelet‐derived growth factor receptor α (PDGFRα), ret proto‐oncogene (RET), and v‐kit Hardy‐Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks implicated in tumor angiogenesis. Positive phase 1 results in solid tumors prompted a phase 2 trial in patients with advanced, radioiodine‐refractory, differentiated thyroid cancer (RR‐DTC).METHODSFifty‐eight patients with RR‐DTC who had disease progression during the previous 12 months received lenvatinib 24 mg once daily in 28‐day cycles until disease progression, unmanageable toxicity, withdrawal, or death. Previous VEGFR‐targeted therapy was permitted. The primary endpoint was the objective response rate (ORR) based on independent imaging review. Secondary endpoints included progression‐free survival (PFS) and safety. Serum levels of 51 circulating cytokines and angiogenic factors also were assessed.RESULTSAfter ≥14 months of follow‐up, patients had an ORR of 50% (95% confidence interval [CI], 37%‐63%) with only partial responses reported. The median time to response was 3.6 months, the median response duration was 12.7 months, and the median PFS was 12.6 months (95% CI, 9.9‐16.1 months). The ORR for patients who had received previous VEGF therapy (n = 17) was 59% (95% CI, 33%‐82%). Lower baseline levels of angiopoietin‐2 were suggestive of tumor response and longer PFS. Grade 3 and 4 treatment‐emergent adverse events, regardless of their relation to treatment, occurred in 72% of patients and most frequently included weight loss (12%), hypertension (10%), proteinuria (10%), and diarrhea (10%).CONCLUSIONSIn patients with and without prior exposure to VEGF therapy, the encouraging response rates, median time to response, and PFS for lenvatinib have prompted further investigation in a phase 3 trial. Cancer 2015;121:2749‐2756. © 2015 American Cancer Society
Solid‐Phase Synthesis of Trisubstituted Benzo[f][1,2,3]triazolo[1,5‐a][1,4]diazepin‐6(5H)‐ones and Their Sulfonyl Analogues under Mild Reaction Conditions
Authors: Fülöpová Veronika , Funk Petr , Popa Igor , McMaster Claire , Soural Miroslav 
Published: April 2015

AbstractThe solid‐phase synthesis of 4H‐benzo[f][1,2,3]triazolo[1,5‐a][1,4]diazepin‐6(5H)‐ones and 4,5‐dihydrobenzo[f][1,2,3]triazolo[5,1‐d][1,2,5]thiadiazepine 6,6‐dioxides under mild and catalyst‐free conditions is described. The seven‐step synthetic strategy is based on the preparation of polymer‐supported 4‐nitrobenzenesulfonamides and their alkylation with various propargyl derivatives. Cleavage of the 4‐nitrobenzenesulfonyl group from each of the key intermediates was followed by acylation with different 2‐azidobenzoic acids, leading to spontaneous intramolecular (Huisgen) 1,3‐dipolar cycloaddition. After cleavage from the polymer support, the target compounds were obtained in excellent crude purities and very good overall yields.
Ultrasensitive Determination of Vitamin B12 Using Disposable Graphite Screen‐Printed Electrodes and Anodic Adsorptive Voltammetry
Authors: Michopoulos Apostolos , Florou Ageliki B. , Prodromidis Mamas I. 
Published: April 2015

AbstractA facile, rapid and ultra‐sensitive method for the determination of vitamin B12 (cyanocobalamin) at the sub‐nanomolar concentration range by using low‐cost, disposable graphite screen‐printed electrodes is described. The method is based on the cathodic preconcentration of square planar vitamin B12s, as occurred due to the electro reduction of Co(III) center in vitamin B12a to Co(I), at −1.3 V versus Ag/AgCl/3 M KCl for 40 s. Then, an anodic square wave scan was applied and the height of the peak appeared at ca. −0.73 V versus Ag/AgCl/3 M KCl, due to the oxidation of Co(I) to Co(II) in the adsorbed molecule, was related to the concentration of the vitamin B12 in the sample. EDTA was found to serve as a key‐component of the electrolyte by eliminating the background signal caused by metal cations impurities contained in the electrolyte (0.1 M phosphate buffer in 0.1 M KCl, pH 3). It also blocks trace metals contained in real samples, thus eliminating their interference effect. The method was optimized to various working parameters and under the selected conditions the calibration curve was linear over the range 1×10−10–8×10−9 mol L−1 vitamin B12 (R2=0.994), while the limit of detection for a signal‐to‐noise ratio of 3 (7×10−11 mol L−1 vitamin B12) is the lowest value of any reported in the literature for the electrochemical determination of vitamin B12. The sensors were successfully applied to the determination of vitamin B12 in pharmaceutical products.