bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled by Established Basal Insulin
Authors: Riddle Matthew C. , Aronson Ronnie , Home Philip , Marre Michel , Niemoeller Elisabeth , Miossec Patrick , Ping Lin , Ye Jenny , Rosenstock Julio 
Published: April 2013

OBJECTIVE
To examine the efficacy and safety of adding the once-daily glucagon-like peptide-1 receptor agonist (GLP-1RA) lixisenatide to established basal insulin therapy alone or together with metformin, in people with type 2 diabetes and elevated glycated hemoglobin (HbA1c).

RESEARCH DESIGN AND METHODS
We conducted a double-blind, parallel-group, placebo-controlled trial. Patients (n = 495) with established basal insulin therapy but inadequate glycemic control were randomized to add lixisenatide 20 μg or placebo for 24 weeks. Basal insulin dosage was unchanged except to limit hypoglycemia. HbA1c reduction from baseline was the primary end point.

RESULTS
Mean duration of diabetes was 12.5 years, duration of insulin use was 3.1 years, insulin dosage was 55 units/day, and baseline HbA1c was 8.4%. With lixisenatide, the placebo-corrected change of HbA1c from baseline was –0.4% (95% CI –0.6 to –0.2; P = 0.0002), and mean HbA1c at end point was 7.8%. HbA1c &lt;7.0% (53 mmol/mol) was attained by more lixisenatide (28%) than placebo (12%; P &lt; 0.0001) participants. Lixisenatide reduced plasma glucose levels after a standardized breakfast (placebo-corrected reduction, –3.8 mmol/L; P &lt; 0.0001); seven-point glucose profiles showed a reduction persisting through the day. Reductions in body weight (placebo corrected, –1.3 kg; P &lt; 0.0001) and insulin dosage (–3.7 units/day; P = 0.012) were greater with lixisenatide. Main adverse events (AEs) with lixisenatide were gastrointestinal. Symptomatic hypoglycemia was 28% for lixisenatide and 22% for placebo; 4 of 328 subjects (1.2%) had severe hypoglycemia with lixisenatide vs. 0 of 167 with placebo.

CONCLUSIONS
By improving HbA1c and postprandial hyperglycemia without weight gain in type 2 diabetes with inadequate glycemic control despite stable basal insulin, lixisenatide may provide an alternative to rapid-acting insulin or other treatment options.
Five different columns in the analysis of basic drugs in hydrophilic interaction liquid chromatography
Authors: Jovanović Marko , Stojanović Biljana , Rakić Tijana , Malenović Anđelija , Ivanović Darko , Medenica Mirjana 
Published: April 2013

Abstract
Five different columns (two silica, two cyanopropyl and one diol) were investigated in hydrophilic interaction liquid chromatography (HILIC). For the assessment of columns behavior in HILIC mode, six basic drugs (lamotrigine, thioridazine, clozapine, chlorpheniramine, pheniramine and sulpiride) were chosen. The assessment of the influence of the concentration of organic modifier on analytes’ retention on each column was provided by fitting the retention data into theoretical models. Utilizing the statistical analysis, the selection of the model that provides better prediction of the retention behavior was enabled. Dual RP-HILIC mechanism was suggested on cyanopropyl and diol columns, therefore the transition points between the two mechanisms on these columns were calculated. Furthermore, in order to investigate the impact of three factors simultaneously on the retention behavior of the analyzed substances on Betasil Silica column, chemometrically-aided empirical models were built. The experiments were conducted according to the matrix of Box-Behnken design and on the basis of the retention data, six quadratic models were obtained and their adequacy was confirmed using ANOVA test. The obtained coefficients of quadratic models enabled the elucidation of both single factor and factor interactions influence. This was also graphically presented in 3D response surface plots.
Analytical considerations on the use of a fruit-specific and representative matrix in pesticide residue analysis by LC-ESI-MS/MS
Authors: Stachniuk Anna , Fornal Emilia 
Published: April 2013

Abstract
One of the quantification methods frequently applied to pesticide residue analysis in food by liquid chromatography — mass spectrometry (LC-MS) involves matrix-matched calibrations with a representative matrix used for all commodities belonging to one group. This approach, although very practical, is deemed to generate analytical errors. The effect of the application of a representative-matrix calibration curve on the pesticide quantification result was examined. Extractions of 56 pesticides from five soft fruits (strawberries, blackberries, raspberries, black currant and red currant) were carried out using QuEChERS method. Pesticide determinations were performed by LC-MS/MS in multiple reaction monitoring mode. Quantification difference functions and parameters were proposed and calculated. At the concentration of 0.05 mg kg−1 for ca. 90% of examined pesticides the quantification difference arising from the use of a representative matrix calibration curve (raspberries) instead of a specific fruit matrix calibration curve was below 20% for black and red currents, and below 30% and 35% in the case of strawberries and blackberries, respectively. The 25% difference limit was not exceeded for 51 pesticides in black and red currents, 46 pesticides in blackberries and 45 pesticides in strawberries. Quantification difference functions and parameters such as relative standard deviation of corrected process efficiencies were found to be helpful in data-driven decision-making on the applicability of a representative matrix; the former may be also used as a tool for data correction to ensure the reliability and accuracy of analyses.
Carbon nanotube-ionic liquid nanocomposite modified carbon-ceramic electrode for determination of dopamine in real samples
Authors: Majidi Mir , Baj Reza , Naseri Abdolhossein 
Published: April 2013

Abstract
Room temperature 1-butyl-3-methylimidazolium tetraflouroborate ([BMIM][BF4]) ionic liquid was employed for dispersion of multi walled carbon nanotubes (MWCNTs) and the formation of nanocomposite on the surface of a carbon-ceramic electrode. The surface of the modified electrode was characterized using scanning electron microscopy and electrochemical impedance spectroscopy. The modified electrode exhibited excellent electrochemical activity to oxidation of dopamine (DA); whereas electro oxidation of ascorbic acid (AA) was not seen and electro oxidation of uric acid (UA) appeared at a more positive potential than DA. The multi walled carbon nanotube-ionic liquid nanocomposite modified carbon-ceramic electrode was used for the selective determination of DA in the presence of high levels of AA and UA using differential pulse voltammetry. The calibration curve for DA was linear in the range of 3.00 to 130 µM with the detection limit (S/N=3) of 0.87 µM. The present electrode was successfully applied to the determination of DA in some commercial pharmaceutical samples and human blood serum.
Erratum to: “Comparative studies of Pd, Ru, Ni, Cu/ZnAl2O4 catalysts for the water gas shift reaction”
Authors: Mierczynski Pawel , Maniukiewicz Waldemar , Maniecki Tomasz 
Published: April 2013

Abstract
The original version of the article was published in Cent. Eur. J. Chem. 11(6) (2013) pp. 912–919. Unfortunately, the original version of this article contains a mistake in the Acknowledgement section. It should be written as “Partially financed from grant number 0680/B/H03/2011/40 and gratefully acknowledged. Paweł Mierczyński is a participant of START Programme.”
Cytotype coexistence leads to triploid hybrid production in a diploid–tetraploid contact zone of Chamerion angustifolium (Onagraceae)
Authors: Sabara Holly A. , Kron Paul , Husband Brian C. 
Published: April 2013

• Premise of the study: Polyploids are often geographically segregated from their diploid progenitors, but the extent of sympatry and the consequences for reproductive isolation and coexistence are rarely quantified.• Methods: In this study, we document the distribution and co‐occurrence of diploid and tetraploid Chamerion angustifolium among 57 populations within the diploid–tetraploid contact zone in the Canadian Rocky Mountains. Rates of hybrid mating in mixed‐ploidy populations were inferred from the frequency of triploid offspring in open‐pollinated seed families.• Key results: Twenty‐three of 57 populations sampled contained a single cytotype; 20 (87%) were tetraploid and three (13%) were diploid. Thirty‐four populations (60%) contained multiple ploidies. Diploid and tetraploid plants occurred in all mixed‐ploidy populations; triploids occurred in 13 populations and averaged 1.4% of plants per population. The proportion of tetraploids in a population was negatively related to elevation (partial regression: F = 27.2, P <0.0001) and latitude (partial regression: F = 17.4, P < 0.0001). Triploids were detected in seed from all eight mixed‐ploidy populations sampled ( = 3.7% of seed per population), comprising 7% of that expected with random mating (G = 2589.2, df = 1, P <0.0001, n = 2628), and were more often produced by diploid maternal parents than tetraploid parents.• Conclusions: Our results indicate that tetraploids regularly coexist with diploids in the contact zone and that this coexistence is likely promoted by both strong reproductive isolation and asymmetric intercytotype mating between diploid and tetraploid C. angustifolium.
SerpinB2 Is Critical to Th2 Immunity against Enteric Nematode Infection
Authors: Zhao Aiping , Yang Zhonghan , Sun Rex , Grinchuk Viktoryia , Netzel-Arnett Sarah , Anglin Ian E. , Driesbaugh Kathryn Hodge , Notari Luigi , Bohl Jennifer A. , Madden Kathleen B. , Urban Joseph F. , Antalis Toni M. , Shea-Donohue Terez 
Published: April 2013

Abstract
SerpinB2, a member of the serine protease inhibitor family, is expressed by macrophages and is significantly upregulated by inflammation. Recent studies implicated a role for SerpinB2 in the control of Th1 and Th2 immune responses, but the mechanisms of these effects are unknown. In this study, we used mice deficient in SerpinB2 (SerpinB2−/−) to investigate its role in the host response to the enteric nematode, Heligmosomoides bakeri. Nematode infection induced a STAT6-dependent increase in intestinal SerpinB2 expression. The H. bakeri–induced upregulation of IL-4 and IL-13 expression was attenuated in SerpinB2−/− mice coincident with an impaired worm clearance. In addition, lack of SerpinB2 in mice resulted in a loss of the H. bakeri–induced smooth muscle hypercontractility and a significant delay in infection-induced increase in mucosal permeability. Th2 immunity is generally linked to a CCL2-mediated increase in the infiltration of macrophages that develop into the alternatively activated phenotype (M2). In H. bakeri–infected SerpinB2−/− mice, there was an impaired infiltration and alternative activation of macrophages accompanied by a decrease in the intestinal CCL2 expression. Studies in macrophages isolated from SerpinB2−/− mice showed a reduced CCL2 expression, but normal M2 development, in response to stimulation of Th2 cytokines. These data demonstrate that the immune regulation of SerpinB2 expression plays a critical role in the development of Th2-mediated protective immunity against nematode infection by a mechanism involving CCL2 production and macrophage infiltration.
OX40L/Jagged1 Cosignaling by GM-CSF–Induced Bone Marrow-Derived Dendritic Cells Is Required for the Expansion of Functional Regulatory T Cells
Authors: Gopisetty Anupama , Bhattacharya Palash , Haddad Christine , Bruno Joseph C. , Vasu Chenthamarakshan , Miele Lucio , Prabhakar Bellur S. 
Published: April 2013

Abstract
Earlier, we had demonstrated that treatment with low dose of GM-CSF can prevent the development of experimental autoimmune thyroiditis (EAT), experimental autoimmune myasthenia gravis, and type 1 diabetes, and could also reverse ongoing EAT and experimental autoimmune myasthenia gravis. The protective effect was mediated through the induction of tolerogenic CD11C+CD8α− dendritic cells (DCs) and consequent expansion of Foxp3+ regulatory T cells (Tregs). Subsequently, we showed that GM-CSF acted specifically on bone marrow precursors and facilitated their differentiation into tolerogenic dendritic cells (DCs; GM-CSF–induced bone marrow-derived DCs [GM-BMDCs]), which directed Treg expansion in a contact-dependent manner. This novel mechanism of Treg expansion was independent of TCR-mediated signaling but required exogenous IL-2 and cosignaling from DC-bound OX40L. In this study, we observed that OX40L-mediated signaling by GM-BMDCs, although necessary, was not sufficient for Treg expansion and required signaling by Jagged1. Concurrent signaling induced by OX40L and Jagged1 via OX40 and Notch3 receptors expressed on Tregs was essential for the Treg expansion with sustained FoxP3 expression. Adoptive transfer of only OX40L+Jagged1+ BMDCs led to Treg expansion, increased production of IL-4 and IL-10, and suppression of EAT in the recipient mice. These results showed a critical role for OX40L- and Jagged1-induced cosignaling in GM-BMDC–induced Treg expansion.
Cord Factor and Peptidoglycan Recapitulate the Th17-Promoting Adjuvant Activity of Mycobacteria through Mincle/CARD9 Signaling and the Inflammasome
Authors: Shenderov Kevin , Barber Daniel L. , Mayer-Barber Katrin D. , Gurcha Sudagar S. , Jankovic Dragana , Feng Carl G. , Oland Sandy , Hieny Sara , Caspar Pat , Yamasaki Sho , Lin Xin , Ting Jenny P. -Y. , Trinchieri Giorgio , Besra Gurdyal S. , Cerundolo Vincenzo , Sher Alan 
Published: April 2013

Abstract
Although adjuvants are critical vaccine components, their modes of action are poorly understood. In this study, we investigated the mechanisms by which the heat-killed mycobacteria in CFA promote Th17 CD4+ T cell responses. We found that IL-17 secretion by CD4+ T cells following CFA immunization requires MyD88 and IL-1β/IL-1R signaling. Through measurement of Ag-specific responses after adoptive transfer of OTII cells, we confirmed that MyD88-dependent signaling controls Th17 differentiation rather than simply production of IL-17. Additional experiments showed that CFA-induced Th17 differentiation involves IL-1β processing by the inflammasome, as mice lacking caspase-1, ASC, or NLRP3 exhibit partially defective responses after immunization. Biochemical fractionation studies further revealed that peptidoglycan is the major component of heat-killed mycobacteria responsible for inflammasome activation. By assaying Il1b transcripts in the injection site skin of CFA-immunized mice, we found that signaling through the adaptor molecule caspase activation and recruitment domain 9 (CARD9) plays a major role in triggering pro–IL-1β expression. Moreover, we demonstrated that recognition of the mycobacterial glycolipid trehalose dimycolate (cord factor) by the C-type lectin receptor mincle partially explains this CARD9 requirement. Importantly, purified peptidoglycan and cord factor administered in mineral oil synergized to recapitulate the Th17-promoting activity of CFA, and, as expected, this response was diminished in caspase-1– and CARD9-deficient mice. Taken together, these findings suggest a general strategy for the rational design of Th17-skewing adjuvants by combining agonists of the CARD9 pathway with inflammasome activators.
TGF-β1 Limits the Onset of Innate Lung Inflammation by Promoting Mast Cell–Derived IL-6
Authors: Ganeshan Kirthana , Johnston Laura K. , Bryce Paul J. 
Published: April 2013

Abstract
TGF-β1 is an important suppressive mediator of inflammation, but it can also drive fibrosis and remodeling in the lung. In response to intratracheal LPS, neutrophils migrate into the lung, and TGF-β1 was suggested to protect against the ensuing injury. However, the mechanisms for this protective role remain unknown. Using a model of acute lung injury, we demonstrate that TGF-β1 decreases neutrophil numbers during the onset of injury. This was due to increased apoptosis rather than reduced migration. We demonstrate that TGF-β1 does not directly regulate neutrophil apoptosis but instead functions through IL-6 to promote neutrophil clearance. rIL-6 is sufficient to promote neutrophil apoptosis and reduce neutrophilia in bronchoalveolar lavage fluid, while IL-6 increases rapidly following LPS-induced injury. Mast cells are a critical source of IL-6, because mast cell–deficient mice exhibit increased neutrophil numbers that are reduced by reconstitution with wild-type, but not IL-6−/−, mast cells. Although IL-6 diminishes neutrophilia in mast cell–deficient mice, TGF-β1 is ineffective, suggesting that these effects were mast cell dependent. Taken together, our findings establish a novel pathway through which TGF-β1, likely derived from resident regulatory T cells, controls the severity and magnitude of early innate inflammation by promoting IL-6 from mast cells.
Buckling of 2D-FG Cylindrical Shells under Combined External Pressure and Axial Compression
Authors: Mohammadzadeh R. , Najafizadeh M. M. , Nejati M. 
Published: April 2013

AbstractThis paper presents the stability of two-dimensional functionally graded (2D-FG) cylindrical shells subjected to combined external pressure and axial compression loads, based on classical shell theory. The material properties of functionally graded cylindrical shell are graded in two directional (radial and axial) and determined by the rule of mixture. The Euler’s equation is employed to derive the stability equations, which are solved by GDQ method to obtain the critical mechanical buckling loads of the 2D-FG cylindrical shells. The effects of shell geometry, the mechanical properties distribution in radial and axial direction on the critical buckling load are studied and compared with a cylindrical shell made of 1D-FGM. The numerical results reveal that the 2D-FGM has a significant effect on the critical buckling load.
“New Year's Dream”: A Chinese Anarcho-cosmopolitan Utopia
Authors: Li Guangyi 
Published: April 2013

ABSTRACT
This article is an in-depth analysis of “New Year's Dream” (1904), a utopian story by Cai Yuanpei, one of the most prominent Chinese intellectuals in the twentieth century. In combination with the story's late Qing milieu, it explores how Cai Yuanpei maps his contemporary world and designs a better one. Based on detailed discussions of the linear progressive future history in the story, this article values “New Year's Dream” for its landmark importance in the transition of Chinese utopian thought and critically analyzes its theme of dual revolution—a national revolution leading to a world revolution, which is significant for our understanding of world utopianism and anarchism.
Ultrasound Guided FNAC for Evaluation of Neck Lumps to Improve Inadequacy Rates; A Complete Audit Cycle
Authors: Richard James Green  , Nick Dawe  , Debra Milne  , Ursula Schierle  , James W. Moor  
Published: April 2013

We present a completed audit cycle evaluating inadequacy rates in neck lump and thyroid fine needle aspiration cytology with and without ultrasound scan guidance. The first cycle of the audit was from January to July 2010 comparing free hand fine needle aspiration cytology (FNAC) with ultrasound guided fine needle aspiration cytology (USS+FNAC). Changes to practice were made, firstly all thyroid FNAC would be performed with USS+FNAC and a reduced threshold for referral for USS+FNAC for non-thyroid neck masses. The second audit cycle was completed sixteen months later to assess for an improvement in practice. 1st phase; 155 patients, 70 freehand, 85 USS+FNAC. 50% of the thyroid FNAC freehand were inadequate compared to 18% of the thyroid USS+FNAC. 2nd phase; 196 patients, USS+FNAC 134, freehand 62. Thyroid FNAC 105 (USS+FNAC-104, freehand-1). Inadequate USS+FNAC = 21/104 (20%). The completed audit cycle shows an increased proportion of thyroid FNACs performed by ultrasound guidance, improving from 82% to 99%, with an overall reduction of inadequate thyroid FNACs from 24% to 21%. There was a noticeable variability in the inadequacy rates from radiologist to radiologist with the head and neck senior radiologist demonstrating the lowest inadequacy rate at 9.6% in the second cycle. Although ultrasound guidance for FNAC is important for the reasons of increased sensitivity, specificity and accuracy, we have demonstrated that the operator experience and skill are just as important.
Controlled Growth of Porous α‐Fe2O3 Branches on β‐MnO2 Nanorods for Excellent Performance in Lithium‐Ion Batteries
Authors: Gu Xin , Chen Liang , Ju Zhicheng , Xu Huayun , Yang Jian , Qian Yitai 
Published: April 2013

AbstractHierarchical nanocomposites rationally designed in component and structure, are highly desirable for the development of lithium‐ion batteries, because they can take full advantages of different components and various structures to achieve superior electrochemical properties. Here, the branched nanocomposite with β‐MnO2 nanorods as the back‐bone and porous α‐Fe2O3 nanorods as the branches are synthesized by a high‐temperature annealing of FeOOH epitaxially grown on the β‐MnO2 nanorods. Since the β‐MnO2 nanorods grow along the four‐fold axis, the as‐produced branches of FeOOH and α‐Fe2O3 are aligned on their side in a nearly four‐fold symmetry. This synthetic process for the branched nanorods built by β‐MnO2/α‐Fe2O3 is characterized. The branched nanorods of β‐MnO2/α‐Fe2O3 present an excellent lithium‐storage performance. They exhibit a reversible specific capacity of 1028 mAh g−1 at a current density of 1000 mA g−1 up to 200 cycles, much higher than the building blocks alone. Even at 4000 mA g−1, the reversible capacity of the branched nanorods could be kept at 881 mAh g−1. The outstanding performances of the branched nanorods are attributed to the synergistic effect of different components and the hierarchical structure of the composite. The disclosure of the correlation between the electrochemical properties and the structure/component of the nanocomposites, would greatly benefit the rational design of the high‐performance nanocomposites for lithium ion batteries, in the future.
Upconversion Nanoparticles Conjugated with Gd3+‐DOTA and RGD for Targeted Dual‐Modality Imaging of Brain Tumor Xenografts
Authors: Jin Jiefu , Xu Zhenhua , Zhang Yue , Gu Yan‐Juan , Lam Michael Hon‐Wah , Wong Wing‐Tak 
Published: April 2013

AbstractGlioblastoma multiforme (GBM) is the most common and malignant form of primary brain tumors in human. Small molecular magnetic resonance imaging (MRI) contrast agents are used for GBM diagnosis. However, conventional contrast agents have several limitations, such as low T1 relaxivity, short circulation half lives and absence of tumor targeting. Herein, we develop an upconversion nanoprobe labeled with Gd3+‐DOTA and RGD (UCNP‐Gd‐RGD) for dual‐modality imaging of glioblastoma. The preparation of UCNP‐Gd‐RGD starts with amine‐functional upconversion nanoparticle core, followed by PEGylation, Gd3+DOTA conjugation and RGD labeling. The obtained UCNP‐Gd‐RGD has improved colloidal stability and reduced cytotoxicity compared with the UCNP core counterpart. Meanwhile, UCNP‐Gd‐RGD shows strong upconversion luminescence in deep‐red region and three times enhancement of T1 relaxivity over Gd3+DOTA. Due to the recognition between UCNP‐Gd‐RGD and integrin αvβ3 receptors, the nanoprobe specifically binds to U87MG cells, as evidenced by confocal microscopy and quantified by ICP‐MS. Furthermore, UCNP‐Gd‐RGD demonstrates a preferential retention in subcutaneous U87MG tumor xenograft as shown in both in vivo upconversion fluorescence/MR imaging studies and ex vivo analysis. UCNP‐Gd‐RGD, conjugated with numerous RGD peptide and T1 contrast enhancing molecules, is promising for MR imaging of glioblastoma and delineating the tumor boundary before surgery. In addition, NIR‐to‐red upconversion characteristic of UCNP‐Gd‐RGD facilitates its potential intra‐operative use for fluorescence‐guided tumor resection.