bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of major amputation in patients with intermittent claudication undergoing early revascularization
Authors: Golledge J , Moxon J V , Rowbotham S , Pinchbeck J , Yip L , Velu R , Quigley F , Jenkins J , Morris D R 
Published: March 2018

Abstract

Background
Revascularization is being used increasingly for the treatment of intermittent claudication and yet few studies have reported the long-term outcomes of this strategy. The aim of this study was to compare the long-term outcome of patients with intermittent claudication who underwent revascularization compared with a group initially treated without revascularization.

Methods
Patients with symptoms of intermittent claudication and a diagnosis of peripheral arterial disease were recruited from outpatient clinics at three hospitals in Queensland, Australia. Based on variation in the practices of different vascular specialists, patients were either treated by early revascularization or received initial conservative treatment. Patients were followed in outpatient clinics using linked hospital admission record data. The primary outcome was the requirement for major amputation. Kaplan–Meier curves, Cox regression and competing risks analyses were used to compare major amputation rates.

Results
Some 456 patients were recruited; 178 (39·0 per cent) underwent early revascularization and 278 (61·0 per cent) had initial conservative treatment. Patients were followed for a mean(s.d.) of 5·00(3·37) years. The estimated 5-year major amputation rate was 6·2 and 0·7 per cent in patients undergoing early revascularization and initial conservative treatment respectively (P = 0·003). Early revascularization was associated with an increased requirement for major amputation in models adjusted for other risk factors (relative risk 5·40 to 4·22 in different models).

Conclusion
Patients presenting with intermittent claudication who underwent early revascularization appeared to be at higher risk of amputation than those who had initial conservative treatment.
Polymorphism of regulatory region of GHRL gene (‐2531C>T) as a promising predictive factor for radiotherapy‐induced oral mucositis in patients with head neck cancer
Authors: Brzozowska Anna , Homa‐Mlak Iwona , Mlak Radosław , Gołębiowski Paweł , Mazurek Marcin , Ciesielka Marzanna , Małecka‐Massalska Teresa 
Published: March 2018

AbstractBackgroundThe purpose of this study was to investigate the relationship between single nucleotide polymorphisms (SNP; rs1629816) in the regulatory region (c.‐2531C>T) of the ghrelin (GHRL) gene and the occurrence and severity of oral mucositis caused by radiotherapy (RT) in patients with head and neck cancer.MethodsOral mucositis in 65 patients with head and neck cancer who underwent irradiation were assessed according to Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) scale. The DNA from patients with head and neck cancer was isolated from whole blood. The genotypes were determined using the minisequencing method (SNaPshot PCR).ResultsThe frequency of occurrence of the GHRL gene (c.‐2531C>T, rs1629816) genotypes were as follows: AA = 21.5%; GA = 40%; and GG = 38.5%. In case of AA genotype, there was a 7‐fold decrease of the risk of occurrence of oral mucositis (of grades 2 and 3) in the sixth week of RT (AA vs GA or GG, respectively: 17.9% vs 82.1% patients; odds ratio [OR] 0.14; 95% confidence interval [CI] 0.02‐0.98; P = .0481). No statistically significant differences were observed between the volume of oral cavity contours (V30, V40, and V50) depending on the GHRL genotype in patients with head and neck cancer.ConclusionThe study results have demonstrated an association between the AA genotype of the GHRL gene and the risk of more severe oral mucositis attributed to RT in patients with head and neck cancer.
Sobolev's inequality for Riesz potentials of functions in grand Musielak–Orlicz–Morrey spaces over nondoubling metric measure spaces
Authors: Ohno Takao , Shimomura Tetsu 
Published: March 2018

AbstractIn this paper we are concerned with Sobolev's inequality for Riesz potentials of functions in grand Musielak–Orlicz–Morrey spaces over nondoubling metric measure spaces.
Inverse generating function approach for the preconditioning of Toeplitz‐block systems
Authors: Schneider F. S. , Pisarenco M. 
Published: March 2018

SummaryAs proposed by R. H. Chan and M. K. Ng (1993), linear systems of the form T [ f ]x=b, where T [ f ] denotes the n×n Toeplitz matrix generated by the function f, can be solved using iterative solvers with
as a preconditioner. This article aims at generalizing this approach to the case of Toeplitz‐block matrices and matrix‐valued generating functions F. We prove that if F is Hermitian positive definite, most eigenvalues of the preconditioned matrix T [F−1]T[F] are clustered around one. Numerical experiments demonstrate the performance of this preconditioner.
An engineering model for wind turbines under yawed conditions derived from high fidelity models
Authors: Rahimi Hamid , Martinez Garcia Andrea , Stoevesandt Bernhard , Peinke Joachim , Schepers Gerard 
Published: March 2018

AbstractThis work presents a significantly improved engineering model for the prediction of the loads in yawed flow. The newly developed model focuses on the so‐called skewed wake effect. This effect leads to an azimuthal variation of the axial induction velocity which depends on the yaw angle, tip speed ratio, wind speed, and radial position. The azimuthal variation of the induced velocities leads to a variation in blade loads, which is important for the prediction of fatigue loads and determines the yawing moment which can be stabilizing or destabilizing and is among others important for passively yawed turbines. The paper puts particular emphasis on the contribution of the root vorticity to the azimuthal variation of induced velocity. Current widely used models typically only take into account the skewed wake effect without the contribution of root vorticity, i.e., leading to a significant different radial dependency of the skewed wake effects. The new model is derived from computational fluid dynamics of 3 multimegawatt‐class wind turbines, namely the NREL 5MW and two 10‐MW turbines designed in the EU projects AVATAR and INNWIND.EU. Simulations were performed by means of an actuator line model. The proposed model is validated with results from a fully resolved computational fluid dynamics model, a free vortex wake code and actuator line model simulations for different wind turbines and yaw angles. The obtained results indicate that in many cases, the new model considerably improves the prediction of the azimuthal variation of axial induction factor and the resulting variation in blade loads and consequent yawing moment.
European Legal Framework for Algorithmic and High Frequency Trading (Mifid 2 and MAR)
Authors: ČUK Tilen , VAN WAEYENBERGE Arnaud 
Published: March 2018

AbstractAlgorithmic and high frequency trading use computer algorithms to execute strategies and the confluence of trends in computer hardware, programming, mathematical modelling, and financial innovation have pushed the limits of trading speed to unprecedented levels. Algorithms are fast and automatically spread disruptions through the financial system. Over the last decade, the ensuing systemic risk called for new regulations. This article attempts an early assessment of the new European legal framework (Mifid 2 and Market Abuse Regime) intended to tackle the technological risks of the modern trading paradigm.
Time and age trends in morning and evening protein intakes of German children and adolescents
Authors: Roßbach Sarah , Diederichs Tanja , Herder Christian , Buyken Anette E. , Alexy Ute 
Published: March 2018

AbstractThe present study describes time and age trends in morning and evening protein intakes and sources among German children and adolescents from 1985 to 2014. A total of 9757 three-day weighed dietary records of 1246 3- to 18-year-old participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study were analysed using polynomial mixed-effects regression models. Morning protein intake increased over the study period by approximately 1 % of morning energy intake (linear trend P < 0·0001), with the youngest and the oldest children having the highest protein intake (linear, quadratic trend P < 0·0001). Evening protein intake increased over time by approximately 2 % of evening energy intake in girls (linear trend P < 0·0001) and 1 % of evening energy intake in boys (quadratic trend P = 0·0313), with decreasing intake with age (girls: linear trend P < 0·0001; boys: linear trend P = 0·0963). Time trends were largely due to increases in protein from ‘starchy foods’. In conclusion, morning and evening protein intakes increased modestly between 1985 and 2014; these increases were, however, not accompanied by increases in traditional protein sources (i.e. meat or dairy products).
Statistical modelling of the surface mass-balance variability of the Morteratsch glacier, Switzerland: strong control of early melting season meteorological conditions
Authors: ZEKOLLARI HARRY , HUYBRECHTS PHILIPPE 
Published: March 2018

ABSTRACTIn this study we analyse a 15-year long time series of surface mass-balance (SMB) measurements performed between 2001 and 2016 in the ablation zone of the Morteratsch glacier complex (Engadine, Switzerland). For a better understanding of the SMB variability and its causes, multiple linear regressions analyses are performed with temperature and precipitation series from nearby meteorological stations. Up to 85% of the observed SMB variance can be explained by the mean May–June–July temperature and the total precipitation from October to March. A new method is presented where the contribution of each month's individual temperature and precipitation to the SMB can be examined in a total sample of 224 (16.8 million) combinations. More than 90% of the observed SMB can be explained with particular combinations, in which the May–June–July temperature is the most recurrent, followed by October temperature. The role of precipitation is less pronounced, but autumn, winter and spring precipitation are always more important than summer precipitation. Our results indicate that the length of the ice ablation season is of larger importance than its intensity to explain year-to-year variations. The widely used June–July–August temperature index may not always be the best option to describe SMB variability through statistical correlation.
Biological concepts in recurrentPlasmodium vivaxmalaria
Authors: Markus Miles B. 
Published: March 2018

AbstractA curious aspect of the evolution of the hypnozoite theory of malarial relapse is its transmogrification from theory into ‘fact’, this being of historical, linguistic, scientific and sociological interest. As far as it goes, the hypnozoite explanation for relapse is almost certainly correct. I contend, however, that many of the genotypically homologous, non-reinfection, relapse-likePlasmodium vivaxrecurrences that researchers ascribe to hypnozoite activation are probably hypnozoite-independent. Indeed, some malariologists are starting to recognize that homologousP. vivaxrecurrences have most likely been overattributed to activation of hypnozoites. Hitherto identified, non-hypnozoite, possible plasmodial sources of recurrence that must be considered, besides circulating erythrocytic stages, include parasites in splenic dendritic cells, other cells in the spleen (in addition to infected erythrocytes there), bone marrow (importantly) and the skin. I argue that we need to take into account the possibility of a dual or multiple extra-vascular origin ofP. vivaxnon-reinfection recurrences, not arbitrarily discount it. The existence of aP. vivaxreservoir(s) is a topical subject and one of practical importance for malaria eradication. Pertinent drug-associated matters are also discussed, as is the dormancy-related significance of clues provided by blood-stage-induced malarial infection.
Effect of New Synthetic Heparin Mimetics on Whole Blood Thrombin Generation In Vivo and In Vitro in Rats
Authors: Hérault J.P. , Bernat A. , Gaich C. , Herbert J.M. 
Published: March 2018

SummaryThe effect of new heparin mimetics (synthetic oligosaccharides) was studied in vitro with regard to thrombin generation (TG) in rat platelet rich plasma (PRP) and whole blood (WB) and in vivo on stasis-induced venous thrombosis in the rat.TG in PRP and in WB was highly dependent on platelet count and strongly influenced by the haematocrit. The peak of TG appeared to be significantly higher in WB than in PRP whereas the endogenous thrombin potential (ETP) was not significantly different under either condition.The effect of hirudin, the synthetic pentasaccharide SR90107/ Org31540 (SP) and heparin were measured on TG in PRP and WB. We then compared the effect of two new synthetic heparin mimetics (SR121903A and SanOrg123781) with potent and comparable antithrombin (AT) mediated activity against factor Xa and thrombin. These two compounds were made of a pentasaccharide with a high affinity to AT, prolonged at the non-reducing end by an oligosaccharide chain recognised by thrombin. In SR121903A, the charge density and charge distribution was analogous to that of heparin whereas in SanOrg123781 the charges were only located on the last 5 saccharides of the non-reducing end of the molecule. In PRP and in WB, SR121903A acted on the lag time and on the AUC whereas SanOrg123781 inhibited thrombin formation with no effect on the lag time. SanOrg123781 was more potent in inhibiting TG than SR121903A. This difference was due to the structures of the compounds that differed in their ability to be neutralised by platelet factor 4. The antithrombotic effect of the two compounds was examined in a venous thrombosis model in rats. We observed that SanOrg123781 was more active than SR121903A and heparin.Taken together, these results indicate that the activity of oligosaccharides is greatly influenced by the global charge density of the molecule and show that SanOrg123781 is a potent and promising antithrombotic drug candidate.
Substitution of Gly-548 to Ala in the Substrate Binding Pocket of Prothrombin Perijá Leads to the Loss of Thrombin Proteolytic Activity
Authors: Sekine Osamu , Ebisawa Kazuyoshi , Umeyama Hideaki , Iwahana Hiroyuki , Ruiz-Sáez Arlette , de Bosch Norma , Matsuda Michio , Sugo Teruko 
Published: March 2018

SummaryProthrombin Perijá is a dysprothrombin derived from a homozygous patient that manifests low thrombin activity upon activation in a onestage assay. Purified prothrombin Perijá showed normal appearance on SDS-PAGE, and was cleaved normally to form α-thrombin by the prothrombinase complex. The activated form, thrombin Perijá, however, did not show any proteolytic activity towards native substrates, fibrinogen, protein C or various synthetic substrates for α-thrombin, but it was able to bind to antithrombin III, although the binding capacity was markedly reduced even in the presence of heparin. Thrombin Perijá showed full reactivity toward a small inhibitor, DFP, indicating that the molecular defect is in the substrate binding site in the thrombin molecule but not in the active site itself. By DNA sequence analysis of the patient prothrombin gene, we identified a G to C mutation at nucleotide 20016 in exon 14, which predicts a Gly-548 to Ala substitution in the prothrombin Perijá molecule. The structural modeling of thrombin Perijá suggests that Ala-548 is located close to the limb of the cavity wall of the substrate binding pocket, and that the methyl group blocks protrusion of the guanidino group of Arg into the cavity. This steric hindrance may well inhibit the access of Arg-containing substrates to the catalytic Ser-525 leading to the loss of proteolytic activity.
Molecular Modeling of the Seven Tandem Leucine-Rich Repeats within the Ligand-Binding Region of Platelet Glycoprotein Ibα
Authors: Whisstock James , Shen Yang , López José , Andrews Robert , Berndt Michael 
Published: March 2018

SummaryPlatelet glycoprotein (GP)Ib-IX-V mediates von Willebrand Factor (vWF)-dependent adhesion to vascular subendothelium at high shear in (patho)physiological thrombus formation. The ligand-binding domain of GPIb-IX-V is within the N-terminal 282 residues of GPIbα, that contains seven tandem leucine-rich repeats (Leu36–Ala200). Repeats 2–4 are critical for vWF binding. In this study, we have built molecular models of the seven leucine-rich repeats of human, canine and mouse GPIbα, providing novel insights into the species-specific interaction between human vWF and its receptor. Interestingly, a major difference between the models was a large negatively charged patch on the concave face of human, but not canine, repeats 2–4. In addition, five individual mutations within the leucine-rich repeats of GPIbα associated with the bleeding disorder Bernard-Soulier syndrome, that result in dysfunctional vWF binding, were mapped to the model of human GPIbα. This provides the basis for relating these genetic lesions to abnormal function of the receptor.
A Defect in Collagen Receptor-Ca2+ Signaling System in Platelets from Cattle with Chediak-Higashi Syndrome
Authors: Shiraishi Mitsuya , Kawashima Sachiko , Moroi Masaaki , Shin Yangchol , Morita Takashi , Horii Yoichiro , Ikeda Masahiro , Ito Katsuaki 
Published: March 2018

SummaryDecreased platelet aggregation to collagen is a cause for bleeding diathesis of Chediak-Higashi syndrome (CHS). We investigated whether the collagen receptor-Ca2+ signaling system was impaired in platelets from cattle affected with CHS. A collagen-induced increase in cytosolic Ca2+ ([Ca2+]i) was depressed in CHS platelets, which was accompanied by a decrease in the production of inositol 1,4,5-trisphosphate. When the influences of endogenous arachidonic acid metabolites and ADP were excluded, convulxin or collagen-related peptide, which are specific agonists for the collagen receptor GPVI, increased [Ca2+]i in both normal and CHS platelets. In contrast, rhodocytin, which was thought to activate another collagen receptor GPIa/IIa, increased [Ca2+]i in CHS platelets to a lesser extent than in normal ones. Cytochalasin D, an actin polymerization inhibitor, depressed the response to collagen or rhodocytin but not the response to convulxin. Adhesion of CHS platelets to acid soluble type I collagen, which was mediated by GPIa/IIa, was similar to that of normal platelets. These results suggest that a defect in the rhodocytin-sensitive pathway is responsible for decreasing the response to collagen in CHS platelets. It remains to be determined which receptor is associated with the mechanism.
Protein C Global Assay in the Evaluation of Women with Idiopathic Pregnancy Loss
Authors: Sarig Galit , Lanir Naomi , Hoffman Ron , Brenner Benjamin 
Published: March 2018

SummarySince the majority of thrombophilic defects in women with pregnancy loss are in the protein C pathway, we have prospectively determined the diagnostic value of a protein C global assay in 60 consecutive women with pregnancy loss compared to 61 controls. Protein C activation time normalized ratio (PCAT-NR) in pregnancy loss women was significantly lower than controls (0.74 ± 0.16 vs. 0.99 ± 0.2; P <0.0001). PCAT-NR lower than cut off level of 0.8 were found in 42/60 (70%) of PL women compared to 7/61 (11%) of controls (OR = 18.0, 95% CI: 6.3-53.4, P < 0.0001).Cut-off level of 0.8 successfully identified all pregnancy loss women with abnormality in the protein C pathway (12 factor V Leiden, 7 APC-Resistance without factor V Leiden, 15 low levels of protein S and 1 of protein C). Moreover, PCAT-NR below 0.8 was documented in 15/29 (52%) of PL women without thrombophilic risk factor compared to 3/55 (5%) of controls (OR = 18.6, 95% CI: 4.2-95.2, P <0.0001).These results suggest that ProC Global may be useful as a screening test for protein C pathway abnormalities and may serve as a new thrombophilic risk factor in women with pregnancy loss.
Characterization of the Binding of Urokinase-Type Plasminogen Activator to the Asialoglycoprotein Receptor
Authors: van der Kaaden M. E. , Groeneveld E. , Barrett-Bergshoeff M. M. , van Berkel Th. J. C. , Kuiper J. , Rijken D. C. 
Published: March 2018

SummaryIn order to study the role of the asialoglycoprotein receptor (ASGPr) in the rapid plasma clearance of urokinase-type plasminogen activator (u-PA), a microtiter plate binding assay was developed using ASGPr purified from rat liver extracts. Urinary two-chain u-PA bound to immobilized ASGPr in a saturable manner with an EC50 of 0.2 µM. Binding was inhibited by rabbit antibodies against the ASGPr. In line with the known carbohydrate specificity of the ASGPr, GalNAc proved to be the most effective inhibitor from a series of monosaccharides, followed by Gal and Fuc, whereas GlcNAc was ineffective. The N-linked oligosaccharides of urinary u-PA do not terminate with the common Gal-GlcNAc element, but with a GalNAc-GlcNAc element which is partially sulfated. Sulfated forms of u-PA were separated from non-sulfated forms by using the lectin Wisteria floribunda agglutinin. Only the non-sulfated forms of u-PA (30% of the total) appeared to bind to the ASGPr. From different u-PA preparations used for thrombolytic therapy only urinary u-PA and u-PA produced by kidney cell cultures strongly bound to the ASGPr, whereas (recombinant) u-PA expressed in mouse myeloma cells, Chinese hamster ovary cells or E. coli scarcely bound to the receptor. It is concluded that u-PA bearing non-sulfated GalNAc-GlcNAc elements is specifically recognized by the ASGPr present on liver cells.
The −33T → C Polymorphism in Intron 7 of the TFPI Gene Influences the Risk of Venous Thromboembolism, Independently of the Factor V Leiden and Prothrombin Mutations
Authors: Borgel Delphine , Fumeron Frédéric , Moatti Didier , Alhenc-Gelas Martine , Grandchamp Bernard , Aiach Martine , Emmerich Joseph , Ameziane Nejma , Seguin Cendrine , de Prost Dominique 
Published: March 2018

SummaryWe have previously identified, in intron 7 of the TFPI gene, a T to C single-base polymorphism (−33T→C) which is strongly associated with total circulating TFPI antigen levels. Here we examined the influence of this polymorphism on the risk of venous thromboembolism. The polymorphism was identified in the PATHROS study population (330 cases with venous thromboembolism and 826 controls). The CC genotype was found in 6.4% of cases and 10.2% of controls (age-adjusted odds ratio 0.6; 95% CI 0.3–0.9; p = 0.03). This protective effect persisted after adjustment for oral contraception and the factor V Leiden and prothrombin gene polymorphisms. In 171 controls and 49 cases in whom blood was taken at least three months after the thrombotic event, the CC genotype was associated with significantly higher total TFPI levels than the TT genotype. These results suggest that the CC genotype of the TFPI intron 7 polymorphism is an independent protective factor for venous thromboembolism, an effect probably mediated by increased TFPI levels.