bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of insulin degludec versus sitagliptin in patients with type 2 diabetes uncontrolled on oral antidiabetic agents
Authors: Philis‐Tsimikas A. , Del Prato S. , Satman I. , Bhargava A. , Dharmalingam M. , Skjøth T. V. , Rasmussen S. , Garber A. J. 
Published: April 2013

AimThe efficacy and safety of insulin degludec (IDeg), a new basal insulin with an ultra‐long duration of action, was compared to sitagliptin (Sita) in a 26‐week, open‐label trial.MethodsInsulin‐naïve subjects with type 2 diabetes [n = 458, age: 56 years, diabetes duration: 7.7 years, glycosylated haemoglobin (HbA1c): 8.9% (74 mmol/mol)] were randomized (1 : 1) to once‐daily IDeg or Sita (100 mg orally) as add‐on to stable treatment with 1 or 2 oral antidiabetic drugs (OADs).ResultsSuperiority of IDeg to Sita in improving HbA1c and fasting plasma glucose (FPG) was confirmed [estimated treatment difference (ETD) IDeg–Sita for HbA1c: −0.43%‐points [95% confidence interval (CI): −0.61; −0.24, p < 0.0001] and for FPG: −2.17 mmol/l (95% CI: −2.59; −1.74, p < 0.0001)]. HbA1c < 7% (<53 mmol/mol) was achieved by 41% (IDeg) versus 28% (Sita) of patients, estimated odds ratio IDeg/Sita: 1.60 (95% CI: 1.04; 2.47, p = 0.034). There was no statistically significant difference in the rate of nocturnal confirmed hypoglycaemia between IDeg and Sita [0.52 vs. 0.30 episodes/patient‐year, estimated rate ratio (ERR): IDeg/Sita: 1.93 (95% CI: 0.90; 4.10, p = 0.09)]. Rates of overall confirmed hypoglycaemia were higher with IDeg than with Sita [3.1 vs. 1.3 episodes/patient‐year, ERR IDeg/Sita: 3.81 (95% CI: 2.40; 6.05, p < 0.0001)]. IDeg was associated with a greater change in body weight than Sita [ETD IDeg–Sita: 2.75 kg (95% CI: 1.97; 3.54, p < 0.0001)]. The overall rates of adverse events were low and similar for both groups.ConclusionsIn patients unable to achieve good glycaemic control on OAD(s), treatment intensification with IDeg offers an effective, well‐tolerated alternative to the addition of a second or third OAD.
Clinical high‐risk state does not predict later psychosis in a delinquent adolescent population
Authors: Manninen Marko , Lindgren Maija , Therman Sebastian , Huttunen Matti , Ebeling Hanna , Moilanen Irma , Suvisaari Jaana 
Published: April 2013

AbstractAimAdolescents with severe disruptive behaviour have an elevated risk for adult psychosis. We investigated whether the Structured Interview for Prodromal Syndromes (SIPS) is a useful psychosis risk‐screening tool for adolescents with disruptive behaviour.MethodFifty‐three adolescents residing in a reform school due to severe behavioural problems were interviewed with SIPS to ascertain clinical high‐risk (CHR) state. CHR status was compared to self‐reported psychiatric problems, and to registry data on hospital treatments for mental health disorders during a 5‐year follow‐up time.ResultsCHR was associated with self‐reported internalizing problems and thought problems. It failed to predict psychoses but was associated with hospital treatment for mood and conduct disorders.ConclusionThe SIPS interview has limited power for predicting psychosis among adolescents with severe behavioural problems. However, SIPS appears to be useful for screening and predicting other psychiatric problems.
The Illusion of Exclusivity
Authors: McHugh Conor 
Published: April 2013

AbstractIt is widely held that when you are deliberating about whether to believe some propositionp, only considerations relevant to the truth ofpcan be taken into account as reasons bearing on whether to believepand motivate you accordingly. This thesis ofexclusivityhas significance for debates about the nature of belief, about control of belief, and about certain forms of evidentialism. In this paper I distinguish a strong and a weak version of exclusivity. I provide reason to think that strong exclusivity is an illusion and that weak exclusivity may also be an illusion. I describe a number of cases in which exclusivity seems not to hold, and I show how an illusion of exclusivity may be generated by a rather different feature of doxastic deliberation, which I calldemandingness.
Assessment of cognitive function in adult patients with hemorrhagic moyamoya disease who received no surgical revascularization
Authors: Su S.‐H. , Hai J. , Zhang L. , Yu F. , Wu Y.‐F. 
Published: April 2013

Background and purposeDue to controversial surgical treatment for hemorrhagic moyamoya disease (MMD), a large proportion of these patients chose conservative treatment. The aim of this study was to assess cognitive function in adult patients with hemorrhagic MMD who received no surgical revascularization.MethodsTwenty‐six adult hemorrhagic MMD patients with only intraventricular hemorrhage (IVH) confirmed by positive computed tomography and magnetic resonance imaging scan, 20 patients with spontaneous IVH whose digital subtraction angiography results were negative, and 30 healthy controls were identified and matched for age, gender, education background and living area. Cognitive function was evaluated by Montreal Cognitive Assessment (MoCA). The non‐parametric test was used for comparisons among the three groups.ResultsNo patient was confirmed cognitive dysfunction at the initial screening. Twenty‐four (92%) cases presented mild cognitive impairment (MCI) after 1 year. All the cases demonstrated MCI after 2 years. The difference between cases and healthy controls was statistically significant at the second screening (P = 0.000) and the third screening (P = 0.000), as was that between cases and patients with spontaneous IVH at the second screening (P = 0.000) and the third screening (P = 0.000). In addition, there were significant decreases in all MoCA subscores (P = 0.000) with special regards to delayed recall, visual space and executive function in cases compared with the other two groups. Moreover, significant differences were found in the subgroups of smoking (P = 0.021) and Suzuki angiographic classification of MMD (P = 0.030).ConclusionsCognitive impairment is a long‐term complication for adult hemorrhagic MMD patients who underwent conservative treatment.
Somatotropic axis resistance and ghrelin in critically ill foals
Authors: Barsnick R. J. I. M. , Hurcombe S. D. A. , Dembek K. , Frazer M. L. , Slovis N. M. , Saville W. J. A. , Toribio R. E. 
Published: April 2013

SummaryReasons for performing studyResistance to the somatotropic axis and increases in ghrelin concentrations have been documented in critically ill human patients, but limited information exists in healthy or sick foals.ObjectivesTo investigate components of the somatotropic axis (ghrelin, growth hormone and insulin‐like growth factor‐1 [IGF‐1]) with regard to energy metabolism (glucose and triglycerides), severity of disease and survival in critically ill equine neonates. It was hypothesised that ghrelin and growth hormone would increase andIGF‐1 would decrease in proportion to severity of disease, supporting somatotropic axis resistance, which would be associated with severity of disease and mortality in sick foals.Study designProspective multicentre cross‐sectional study.MethodsBlood samples were collected at admission from 44 septic, 62 sick nonseptic (SNS) and 19 healthy foals, all aged <7 days. Foals with positive blood cultures or sepsis scores ≥12 were considered septic, foals with sepsis scores of 5–11 were classified asSNS. Data were analysed by nonparametric methods and multivariate logistic regression.ResultsSeptic foals had higher ghrelin, growth hormone and triglyceride and lowerIGF‐1 and glucose concentrations than healthy foals (P<0.01). Sick nonseptic foals had higher growth hormone and triglycerides and lowerIGF‐1 concentrations than healthy foals (P<0.05). Growth hormone:IGF‐1 ratio was higher in septic andSNSfoals than healthy foals (P<0.05). Hormone concentrations were not different between septic nonsurvivors (n = 14) and survivors (n = 30), but the growth hormone:IGF‐1 ratio was lower in nonsurvivors (P= 0.043).ConclusionsSomatotropic axis resistance, characterised by a high growth hormone:IGF‐1 ratio, was frequent in sick foals, associated with the energy status (hypoglycaemia, hypertriglyceridaemia) and with mortality in septic foals.Potential relevanceA functional somatotropic axis appears to be important for foal survival during sepsis. Somatotropic resistance is likely to contribute to severity of disease, a catabolic state and likelihood of recovery.
Participation of central imidazoline binding sites in antinociceptive effect of ethanol and nicotine in rats
Authors: Aglawe Manish Manohar , Taksande Brijesh Gulabrao , Kuldhariya Sharvari Shambabu , Chopde Chandrabhan Tukaram , Umekar Milind Janrao , Kotagale Nandkishor Ramdas 
Published: April 2013

AbstractDespite synergistic morbidity and mortality, concomitant consumption of alcohol and tobacco is increasing, and their antinociceptive effect has been linked with co‐abuse. Present study was designed to investigate the role of imidazoline binding sites in the antinociceptive effect of nicotine, ethanol, and their combination. Separate group of male Sprague–Dawley rats (200–250 g) were treated with different doses of alcohol (0.50–2 g/kg, i.p.) or nicotine (0.25–1 mg/kg, i.p.), and their combination evaluated in tail flick test. Influence of endogenous imidazoline binding site ligands, agonist, and antagonists were determined by their prior treatment with effective or subeffective doses of either ethanol or nicotine. Ethanol, nicotine, or their subeffective dose combination exhibited significant antinociceptive effects in dose‐dependent manner. Antinociceptive effect of ethanol and nicotine was significantly augmented by intracerebroventricular (i.c.v.) administration of endogenous imidazoline receptor ligands, harmane (25 μg/rat, i.c.v.) and agmatine (10 μg/rat, i.c.v.), as well as imidazoline I1/α2 adrenergic receptor agonist, clonidine (2 μg/rat, i.c.v.), I1 agonist moxonidine (25 μg/rat, i.c.v.), and imidazoline I2 agonist, 2‐BFI (10 μg/rat, i.c.v.). Conversely, antinociception elicited by ethanol or nicotine or their subeffective dose combination was antagonized by pretreatment with imidazoline I1 antagonist, efaroxan (10 μg/rat, i.c.v.), and I2 antagonist, idazoxan (4 μg/rat, i.c.v.), at their per se ineffective doses. These findings project imidazoline binding ligands as important therapeutic molecules for central antinociceptive activity as well as may reduce the co‐abuse potential of alcohol and nicotine.
Reporter‐based screening and selection of enzymes
Authors: van Rossum Teunke , Kengen Servé W. M. , van der Oost John 
Published: April 2013

The biotech industry is continuously seeking for new or improved biocatalysts. The success of these efforts is often hampered by the lack of an efficient screening assay. Thus, to be able to extend the number of enzymes available for industrial applications, high‐throughput screening and selection methods are required. In the last few years an impressive range of screening and selection strategies has been developed. In this review, we will mainly focus on in vivo reporter systems in which the activity of a reporter is controlled by the activity of an enzyme of interest. Different mechanisms can be distinguished: (a) binding of the product of the enzymatic reaction to a transcriptional regulator and thereby turning on transcription of the reporter; (b) direct modification of a transcriptional regulator by the enzyme resulting in expression of the reporter; (c) binding of the product to a regulatory riboswitch or ribozyme, resulting in translation of the reporter; and (d) direct modification of the reporter by the enzyme, altering the reporter's activity. The choice for either a selection or a screening strategy depends on the type of reporter, e.g. providing antibiotic resistance (selection) or transmitting a fluorescent signal (screening). Although developing the specificity of each of these reporter‐based selection or screening systems towards a certain enzymatic reaction is not yet straightforward, their adjustable modular design appears to be a promise for general applicability in the near future.
Evolutionary and mechanistic insights into substrate and product accommodation of CTP:phosphocholine cytidylyltransferase from Plasmodium falciparum
Authors: Nagy Gergely N. , Marton Lívia , Krámos Balázs , Oláh Julianna , Révész Ágnes , Vékey Károly , Delsuc Frédéric , Hunyadi‐Gulyás Éva , Medzihradszky Katalin F. , Lavigne Marina , Vial Henri , Cerdan Rachel , Vértessy Beáta G. 
Published: April 2013

The enzyme CTP:phosphocholine cytidylyltransferase (CCT) is essential in the lipid biosynthesis of Plasmodia (Haemosporida), presenting a promising antimalarial target. Here, we identified two independent gene duplication events of CCT within Apicomplexa and characterized a truncated construct of Plasmodium falciparum CCT that forms a dimer resembling the molecular architecture of CCT enzymes from other sources. Based on biophysical and enzyme kinetics methods, our data show that the CDP‐choline product of the CCT enzymatic reaction binds to the enzyme considerably stronger than either substrate (CTP or choline phosphate). Interestingly, in the presence of Mg2+, considered to be a cofactor of the enzyme, the binding of the CTP substrate is attenuated by a factor of 5. The weaker binding of CTP:Mg2+, similarly to the related enzyme family of aminoacyl tRNA synthetases, suggests that, with lack of Mg2+, positively charged side chain(s) of CCT may contribute to CTP accommodation. Thermodynamic investigations by isothermal titration calorimetry and fluorescent spectroscopy studies indicate that accommodation of the choline phosphate moiety in the CCT active site is different when it appears on its own as one of the substrates or when it is linked to the CDP‐choline product. A tryptophan residue within the active site is identified as a useful internal fluorescence sensor of enzyme–ligand binding. Results indicate that the catalytic mechanism of Plasmodium falciparum CCT may involve conformational changes affecting the choline subsite of the enzyme.DatabaseModel data are available in the Protein Model DataBase (PMDB) under the accession number PM0078718 (PfCCT(528–795)) and PM0078719 (PfCCT MΔK)Structured digital abstract

PfCCT M&#x0394;K and PfCCT M&#x0394;K bind by mass spectrometry studies of complexes (View interaction)

PfCCT M&#x0394;K and PfCCT M&#x0394;K bind by comigration in gel electrophoresis (View interaction)

PfCCT M&#x0394;K and PfCCT M&#x0394;K bind by molecular sieving (View interaction)
Analysis of mechanical properties and its associated fracture surfaces in dual‐phase austempered ductile iron
Authors: Basso A. , Sikora J. , Martínez R. 
Published: April 2013

ABSTRACTThis work aims at evaluating the fracture surfaces of tensile samples taken from a new kind of ductile iron referred to as ‘dual‐phase Austempered Ductile Iron (ADI)’, a material composed of ausferrite (regular ADI microstructure) and free (or allotriomorphic) ferrite. The tensile fracture surface characteristics and tensile properties of eight dual‐phase ADI microstructures, containing different relative quantities of ferrite and ausferrite, were studied in an alloyed ductile cast iron. Additionally, samples with fully ferritic and fully ausferritic (ADI) matrices were produced to be used as reference. Ferritic–pearlitic ductile irons (DI) were evaluated as well. For dual‐phase ADI microstructures, when the amount of ausferrite increases, tensile strength, yield stress and hardness do so too. Interesting combinations of strength and elongation until failure were found. The mechanisms of fracture that characterise DI under static uniaxial loading at room temperature are nucleation, growth and coalescence of microvoids. The fracture surface of fully ferritic DI exhibited an irregular topography with dimples and large deformation of the nodular cavities, characteristic of ductile fracture. Microstructures with small percentages of ausferrite (less than 20%) yielded better mechanical properties in relation to fully ferritic matrices. These microstructures presented regions of quasi‐cleavage fracture around last‐to‐freeze zones, related to the presence of ausferrite in those areas. As the amount of ausferrite increased, a decrease in nodular cavities deformation and a flatter fracture surface topography were noticed, which were ascribed to a higher amount of quasi‐cleavage zones. By means of a special thermal cycle, microstructures with pearlitic matrices containing a continuous and well‐defined net of allotriomorphic ferrite, located at the grain boundaries of recrystallised austenite, were obtained. The results of the mechanical tests leading to these microstructures revealed a significant enhancement of mechanical properties with respect to completely pearlitic matrices. The topographies of the fracture surfaces revealed a flat aspect and slightly or undeformed nodular cavities, as a result of high amount of pearlite. Still isolated dimple patterns associated to ferritic regions were observed.
Kinking of an interface crack in an orthotropic bimaterial
Authors: Cui C. B. , Beom H. G. , Jang H. S. , Fang Q.‐Z. , Li H. M. 
Published: April 2013

ABSTRACTWe investigated the asymptotic problem of a kinked interface crack in an orthotropic bimaterial under in‐plane loading conditions. The stress intensity factors at the tip of the kinked interface crack are described in terms of the stress intensity factors of the interface crack prior to the kink combined with a dimensionless matrix function. Using a modified Stroh formalism and an orthotropy rescaling technique, the matrix function was obtained from the solutions of the corresponding problem in transformed bimaterial. The effects of orthotropic and bimaterial parameters on the matrix function were examined. A reduction in the number of dependent material parameters on the matrix function was made using the modified Stroh formalism. Moreover, the explicit dependence of one orthotropic parameter on the matrix function was determined using an orthotropic rescaling technique. The effects of the other material parameters on the matrix function were numerically examined. The energy release rate was obtained for a kinked interface crack in an orthotropic bimaterial.
A simple method to analyse the notch sensitivity of specimens in fatigue tests
Authors: Hu X. A. , Yang X. G. , Wang J. K. , Shi D. Q. , Huang J. 
Published: April 2013

ABSTRACTA simple method to analyse the notch sensitivity of specimens in fatigue tests is presented. The parameter m, which can be used to measure the notch sensitivity, the nominal stress and the stress concentration factor (Kt) are used to establish the method. In order to verify the feasibility of the method, notch fatigue test results from our group and literatures were collected. The results reveal that an optimal value of parameter m does exist for each material. Life predictions indicated that the model is able to describe the life evolution for notched specimens under high cycle fatigue and low cycle fatigue tests. Because the geometry effect is accounted for Kt, the method is suitable for the conditions when the notch geometries and the absolute dimensions are similar to the tested specimens.
Crack tip stress distribution and stress intensity factor in shape memory alloys
Authors: Maletta Carmine , Sgambitterra Emanuele , Furgiuele Franco 
Published: April 2013

ABSTRACTThe crack tip stress‐induced martensitic transformation and the resulting stress distribution in a nickel–titanium (NiTi)‐based shape memory alloy have been analysed. In particular, the effects of temperature, within the stress‐induced transformation regime, in single edge crack specimens have been studied by a recent analytical model, finite element simulations and experimental measurements. The results of the analytical model have been compared with those obtained from finite element simulations, carried out by using a special constitutive model for shape memory alloys, and good agreements have been observed. Furthermore, full field numerical results have been used to better understand the evolution of the volume fraction of martensite in the crack tip region. Finally, experimental measurements have been carried out, by using single edge crack specimens obtained from commercially available NiTi sheets by electro‐discharge machining. The results have been analysed by linear elastic fracture mechanics theory, and the analytical model has been used to calculate modified stress‐intensity factors for shape memory alloys. A slightly increase of the critical stress‐intensity factor has been observed with increasing the testing temperature, and this result is in accordance with the model calculations, which indicate a toughening effect, i.e. a reduction of the crack tip stress intensity factor.
Biotic interactions mediate the expansion of black mangrove (Avicennia germinans) into salt marshes under climate change
Authors: Guo Hongyu , Zhang Yihui , Lan Zhenjiang , Pennings Steven C. 
Published: April 2013

AbstractMany species are expanding their distributions to higher latitudes due to global warming. Understanding the mechanisms underlying these distribution shifts is critical for better understanding the impacts of climate changes. The climate envelope approach is widely used to model and predict species distribution shifts with changing climates. Biotic interactions between species, however, may also influence species distributions, and a better understanding of biotic interactions could improve predictions based solely on climate envelope models. Along the northern Gulf of Mexico coast, USA, subtropical black mangrove (Avicennia germinans) at the northern limit of its distribution grows sympatrically with temperate salt marsh plants in Florida, Louisiana, and Texas. In recent decades, freeze‐free winters have led to an expansion of black mangrove into salt marshes. We examined how biotic interactions between black mangrove and salt marsh vegetation along the Texas coast varied across (i) a latitudinal gradient (associated with a winter‐temperature gradient); (ii) the elevational gradient within each marsh (which creates different marsh habitats); and (iii) different life history stages of black mangroves (seedlings vs. juvenile trees). Each of these variables affected the strength or nature of biotic interactions between black mangrove and salt marsh vegetation: (i) Salt marsh vegetation facilitated black mangrove seedlings at their high‐latitude distribution limit, but inhibited black mangrove seedlings at lower latitudes; (ii) mangroves performed well at intermediate elevations, but grew and survived poorly in high‐ and low‐marsh habitats; and (iii) the effect of salt marsh vegetation on black mangroves switched from negative to neutral as black mangroves grew from seedlings into juvenile trees. These results indicate that the expansion of black mangroves is mediated by complex biotic interactions. A better understanding of the impacts of climate change on ecological communities requires incorporating context‐dependent biotic interactions into species range models.