bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ranolazine reduces repolarization heterogeneity in symptomatic patients with diabetes and non–flow‐limiting coronary artery stenosis
Authors: Evaristo Ederson , Stocco Fernando G. , Shah Nishant R. , Cheezum Michael K. , Hainer Jon , Foster Courtney , Nearing Bruce D. , Di Carli Marcelo , Verrier Richard L. 
Published: June 2017

BackgroundExperimental evidence suggests that ranolazine decreases susceptibility to ischemia‐induced arrhythmias independent of effects on coronary artery blood flow.ObjectiveIn symptomatic diabetic patients with non–flow‐limiting coronary artery stenosis with diffuse atherosclerosis and/or microvascular dysfunction, we explored whether ranolazine reduces T‐wave heterogeneity (TWH), an electrocardiographic (ECG) marker of arrhythmogenic repolarization abnormalities shown to predict sudden cardiac death.MethodsWe studied all 16 patients with analyzable ECG recordings during rest and exercise tolerance testing before and after 4 weeks of ranolazine in the double‐blind, crossover, placebo‐controlled RAND‐CFR trial (NCT01754259). TWH was quantified without knowledge of treatment assignment by second central moment analysis, which assesses the interlead splay of T waves in precordial leads about a mean waveform. Myocardial blood flow (MBF) was measured by positron emission tomography.ResultsAt baseline, prior to randomization, TWH during rest was 54 ± 7 μV and was not altered following placebo (47 ± 6 μV, p = .47) but was reduced by 28% (to 39 ± 5 μV, p = .002) after ranolazine. Ranolazine did not increase MBF at rest. Exercise increased TWH after placebo by 49% (to 70 ± 8 μV, p = .03). Ranolazine did not reduce TWH during exercise (to 75 ± 16 μV), and there were no differences among the groups (p = .95, ANOVA). TWH was not correlated with MBF at rest before (r2 = .07, p = .36) or after ranolazine (r2 = .23, p = .06).ConclusionsIn symptomatic diabetic patients with non‐flow‐limiting coronary artery stenosis with diffuse atherosclerosis and/or microvascular dysfunction, ranolazine reduced TWH at rest but not during exercise. Reduction in repolarization abnormalities appears to be independent of alterations in MBF.
Drugs for rare disorders
Authors: Cremers Serge , Aronson Jeffrey K. 
Published: June 2017

Estimates of the frequencies of rare disorders vary from country to country; the global average defined prevalence is 40 per 100 000 (0.04%). Some occur in only one or a few patients.However, collectively rare disorders are fairly common, affecting 6–8% of the US population, or about 30 million people, and a similar number in the European Union. Most of them affect children and most are genetically determined. Diagnosis can be difficult, partly because of variable presentations and partly because few clinicians have experience of individual rare disorders, although they may be assisted by searching databases.Relatively few rare disorders have specific pharmacological treatments (so‐called orphan drugs), partly because of difficulties in designing trials large enough to determine benefits and harms alike. Incentives have been introduced to encourage the development of orphan drugs, including tax credits and research aids, simplification of marketing authorization procedures and exemption from fees, and extended market exclusivity. Consequently, the number of applications for orphan drugs has grown, as have the costs of using them, so much so that treatments may not be cost‐effective. It has therefore been suggested that not‐for‐profit organizations that are socially motivated to reduce those costs should be tasked with producing them.A growing role for patient organizations, improved clinical and translational infrastructures, and developments in genetics have also contributed to successful drug development.The translational discipline of clinical pharmacology is an essential component in drug development, including orphan drugs. Clinical pharmacologists, skilled in basic pharmacology and its links to clinical medicine, can be involved at all stages. They can contribute to the delineation of genetic factors that determine clinical outcomes of pharmacological interventions, develop biomarkers, design and perform clinical trials, assist regulatory decision making, and conduct postmarketing surveillance and pharmacoepidemiological and pharmacoeconomic assessments.
Acute myeloid leukaemia genomics
Authors: Medinger Michael , Passweg Jakob R. 
Published: June 2017

SummaryAcute myeloid leukaemia (AML) is a biologically complex, molecularly and clinically heterogeneous disease. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, standard treatment options have not significantly changed during the past three decades. AML is characterized by multiple somatically acquired mutations that affect genes of different functional categories. Mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone. By contrast, mutations involving NPM1 or signalling molecules (e.g., FLT3, RAS gene family) are typically secondary events that occur later during leukaemogenesis. This review aims to provide an overview of advances in new prognostic markers, including targetable mutations that will probably guide the development and use of novel molecularly targeted therapies.
If You're Happy and You Know It: Positive Moods Reduce Age‐Related Differences in False Memory
Authors: Zhang Weiwei , Gross Julien , Hayne Harlene 
Published: June 2017

When tested in the Deese–Roediger–McDermott paradigm, children typically exhibit fewer false memories than do adolescents or adults. Here, participants’ moods and the valence of word lists were manipulated to explore the mechanism responsible for this developmental reversal in memory performance. Children (7‐ to 8‐year‐olds), adolescents (11‐ to 12‐year‐olds), and young adults (18‐ to 22‐year‐olds; N = 270) were assigned to one of three induced mood conditions and were presented with emotional word lists. In negative moods, adolescents and adults falsely recalled more negative information than did children, showing the typical developmental reversal effect. This effect, however, was eliminated when participants were in positive moods. The findings provide support for associative‐activation theory and have important implications for our understanding of the development of emotional false memories.
Tobacco education in UK dental schools: A survey of current practice
Authors: Holliday R. , Amin K. , Lawrence V. , Preshaw P. M. 
Published: June 2017

AbstractObjectiveTo investigate the current provision of tobacco education (tobacco use and cessation), assessment and e‐cigarette education in UK dental and dental hygiene and therapy (DHT) undergraduate programmes.Materials and MethodsThe study was conducted using a self‐administered questionnaire sent to all UK institutions training dental and DHT students during the academic year 2015/2016.ResultsTwenty‐five programmes returned completed questionnaires (response rate 68%). All programmes (100%) reported delivering tobacco education, delivered by multiple individuals in 78% of the programmes. Assessment of the theoretical and practical aspects of tobacco education was reported in 80% and 72% of the programmes, respectively. More formal teaching time was devoted to the theoretical aspects (100% >2 hours) rather than the practical aspects (76% > 2 hours) of tobacco education. All programmes expected their graduates to be clinically competent at discussing the health consequences of smoking, deliver a brief smoking cessation intervention, and referring patients to stop smoking services. The use of the National Centre for Smoking Cessation and Training “Very Brief Advice” (NCSCT VBA) training package was reported to be mandatory in 36%, and recommended, in 44% of programmes. Specialised stop smoking services delivered teaching in 40% of both dental and DHT training programmes whilst another 40% reported previous input from specialist smoking cessation services but not in 2015/2016. Most programmes reported delivery of teaching on electronic cigarettes, with 12% delivering a standalone lecture on this topic.ConclusionsTobacco education is an important component of dental training. Dental education programmes should remain responsive to a rapidly changing field and fully utilise the available resources.
Local environment and connectivity are the main drivers of diatom species composition and trait variation in a set of tropical reservoirs
Authors: Zorzal‐Almeida Stéfano , Soininen Janne , Bini Luis M. , Bicudo Denise C. 
Published: June 2017

Abstract

A metacommunity is defined as a set of local communities that are connected by dispersal and are controlled by environmental drivers operating at different spatial and temporal scales. Although diatom ecology has been studied extensively in temperate and lotic ecosystems, knowledge of tropical lentic systems is more limited.

We evaluated how planktonic and surface‐sediment diatom communities, including trait‐based communities, were structured by environmental, spatial and land‐use variables in tropical reservoirs. Diatoms were sampled in seven reservoirs (31 sites in total) in south‐east Brazil, from the surface sediment and the plankton in summer and winter.

Diatom communities responded primarily to a trophic gradient and secondarily to a light‐availability gradient. Connectivity was also a strong predictor, whereas land use had a weaker influence on community variation. Our results further suggested that surface‐sediment and planktonic diatom groups were structured by similar environmental variables. Trait‐based analysis also indicated that these communities were related to environmental and spatial factors.

We conclude that (1) trophic state, light availability and connectivity were the main drivers of diatoms in this set of tropical reservoirs, resulting in spatially structured communities; (2) patterns for surface‐sediment diatoms resembled both summer and winter diatom communities in the plankton; and (3) the effects of the explanatory variables (local environment, connectivity and land use) varied among the different biological datasets (i.e. when organised taxonomically, or according to growth morphology, cell size or trophic preference). We emphasize that studies in tropical reservoirs should take spatial variables into account, due to the connectivity of the sites.
Misdiagnosis of Spontaneous Intracranial Hypotension as a Risk Factor for Subdural Hematoma
Authors: Kim Youn‐Jung , Cho Hyun‐Young , Seo Dong‐Woo , Sohn Chang Hwan , Ahn Shin , Lee Yoon‐Seon , Kim Won Young , Lim Kyung Soo 
Published: June 2017

ObjectiveThis study aimed to evaluate the association between misdiagnosis of spontaneous intracranial hypotension (SIH) and subdural hematoma development.BackgroundAlthough SIH is more prevalent than expected and causes potentially life‐threatening complications including subdural hematoma (SDH), the association between misdiagnosis of SIH and SDH development is not yet evaluated.MethodsRetrospective observational study was conducted between January 1, 2005, and December 31, 2014. Adult patients with spontaneous intracranial hypotension (age ≥ 18 years) were enrolled.ResultsOf the 128 patients with SIH, 111 (86.7%) were in no SDH group and 17 (13.3%) were in SDH group. Their clinical presentation did not show significant different between the two groups, except age, the days from symptom onset to correct diagnosis, and the number of misdiagnoses. Age (odds ratio [OR], 1.15; 95% confidence interval [CI], 1.07‐1.23) and the number of times SIH was misdiagnosed (OR, 1.82; 95% CI, 1.03‐3.21) were independent risk factors for the development of SDH in SIH patients by multivariate logistic analysis. The clinical outcomes, including length of hospital stay and revisit rate, were similar in the two groups.ConclusionsThe number of times SIH was misdiagnosed was associated with the later development of SDH perhaps because of delay in correct diagnosis of SIH. Clinicians would prevent the later complication of SDH in SIH patients by increasing the awareness and a high index of suspicion of SIH.
Cleaning lateral morphological features of the root canal: the role of streaming and cavitation
Authors: Robinson J. P. , Macedo R. G. , Verhaagen B. , Versluis M. , Cooper P. R. , van der Sluis L. W. M. , Walmsley A. D. 
Published: June 2017

AbstractAimTo investigate the effects of ultrasonic activation file type, lateral canal location and irrigant on the removal of a biofilm‐mimicking hydrogel from a fabricated lateral canal. Additionally, the amount of cavitation and streaming was quantified for these parameters.MethodologyAn intracanal sonochemical dosimetry method was used to quantify the cavitation generated by an IrriSafe 25 mm length, size 25 file inside a root canal model filled with filtered degassed/saturated water or three different concentrations of NaOCl. Removal of a hydrogel, demonstrated previously to be an appropriate biofilm mimic, was recorded to measure the lateral canal cleaning rate from two different instruments (IrriSafe 25 mm length, size 25 andK21 mm length, size 15) activated with a P5 Suprasson (Satelec) at power P8.5 in degassed/saturated water or NaOCl. Removal rates were compared for significant differences using nonparametric Kruskal–Wallis and/or Mann–WhitneyU‐tests. Streaming was measured using high‐speed particle imaging velocimetry at 250 kfps, analysing both the oscillatory and steady flow inside the lateral canals.ResultsThere was no significant difference in amount of cavitation between tap water and oversaturated water (P = 0.538), although more cavitation was observed than in degassed water. The highest cavitation signal was generated with NaOCl solutions (1.0%, 4.5%, 9.0%) (P < 0.007) and increased with concentration (P < 0.014). The IrriSafe file outperformed significantly theK‐file in removing hydrogel (P < 0.05). Up to 64% of the total hydrogel volume was removed after 20 s. The IrriSafe file typically outperformed theK‐file in generating streaming. The oscillatory velocities were higher inside the lateral canal 3 mm compared to 6 mm fromWLand were higher for NaOCl than for saturated water, which in turn was higher than for degassed water.ConclusionsMeasurements of cavitation and acoustic streaming have provided insight into their contribution to cleaning. Significant differences in cleaning, cavitation and streaming were found depending on the file type and size, lateral canal location and irrigant used. In general, the IrriSafe file outperformed theK‐file, and NaOCl performed better than the other irrigants tested. The cavitation and streaming measurements revealed that both contributed to hydrogel removal and both play a significant role in root canal cleaning.
L'inadéquation horizontale et verticale entre compétences et emploi selon le pays et le domaine d'études
Authors: VERHAEST Dieter , SELLAMI Sana , van der VELDEN Rolf 
Published: June 2017

RésuméLes auteurs analysent les écarts dans les taux d'inadéquation entre compétences et emploi selon le pays et la discipline à partir de données sur l'insertion des jeunes diplômés en Europe et au Japon. S'agissant des pays, l'inadéquation ≪horizontale≫ (mauvaise spécialisation) diminue en cas de forte protection de l'emploi, d'assurance chômage généreuse et de système éducatif sélectif; l'inadéquation ≪verticale≫ (surqualification) dépend principalement des déséquilibres du marché du travail; et l'inadéquation ≪complète≫ (cumulative), sensible à toutes ces variables, est liée positivement avec la couverture de la négociation collective. Quant aux écarts entre disciplines, ils dépendent des caractéristiques de l'enseignement et des déséquilibres sur le marché du travail.
Imidacloprid is hydroxylated by Laodelphax striatellus CYP6AY3v2
Authors: Wang R. , Zhu Y. , Deng L. , Zhang H. , Wang Q. , Yin M. , Song P. , Elzaki M. E. A. , Han Z. , Wu M. 
Published: June 2017

AbstractLaodelphax striatellus (Fallén) is one of the most destructive pests of rice, and has developed high resistance to imidacloprid. Our previous work indicated a strong association between imidacloprid resistance and the overexpression of a cytochrome P450 gene CYP6AY3v2 in a L. striatellus imidacloprid resistant strain (Imid‐R). In this study, a transgenic Drosophila melanogaster line that overexpressed the L. striatellus CYP6AY3v2 gene was established and was found to confer increased levels of imidacloprid resistance. Furthermore, CYP6AY3v2 was co‐expressed with D. melanogaster cytochrome P450 reductase (CPR) in Spodoptera frugiperda 9 (SF9) cells. A carbon monoxide difference spectra analysis indicated that CYP6AY3v2 was expressed predominately in its cytochrome P450 (P450) form, which is indicative of a good‐quality functional enzyme. The recombinant CYP6AY3v2 protein efficiently catalysed the model substrate P‐nitroanisole to p‐nitrophenol with a maximum velocity (Vmax) of 60.78 ± 3.93 optical density (mOD)/min/mg protein. In addition, imidacloprid itself was metabolized by the recombinant CYP6AY3v2/nicotinamide adenine dinucleotide 2'‐phosphate reduced tetrasodium salt (NADPH) CPR microsomes in in vitro assays (catalytic constant (Kcat) = 0.34 pmol/min/pmol P450, michaelis constant (Km) = 41.98 μM), and imidacloprid depletion and metabolite peak formation were with a time dependence. The data provided direct evidence that CYP6AY3v2 is capable of hydroxylation of imidacloprid and conferring metabolic resistance in L. striatellus.
Finite element simulation for detecting the foreign body based on ultrasonic sensor
Authors: Mohd Khairi Mohd Taufiq , Ibrahim Sallehuddin , Md Yunus Mohd Amri , Faramarzi Mahdi , Abd Rahman Muhammad Abdul Illah , Gaya Muhammad Sani 
Published: June 2017

AbstractThis paper presents the design of an ultrasonic sensor for food quality and safety measurement which is modeled using two dimensions (2D) of finite element method (FEM). The measurement process was implemented by evaluating the presence of foreign body in a food container where the Comsol Multiphysics software was used to construct and conduct the design of modeling. This paper discussed briefly about the applied parameters in ultrasonic measurement which are acoustic impedance, attenuation coefficient, frequency and time of flight. Steel and glass are selected for foreign body's materials since these materials are occasionally present in foodstuffs during the manufacturing process. Some parameters such as frequency of ultrasonic sensor, the thickness of container wall and the size of foreign body were investigated and evaluated. The analysis process is based on the outcome of the total acoustic pressure and the time arrival of the receiving signal. The investigation only considered the ultrasonic transmission sensing mode. Two values of frequencies for ultrasonic sensor are being tested, that is, 45 kHz and 300 kHz. The results showed that the total acoustic pressure is reduced when the thickness of container wall and the size of foreign body are increased. For the 45 kHz frequency, the total acoustic pressures recorded were 1.210 Pa and 1.020 Pa for 0.5 mm and 0.9 mm of wall thickness, respectively. The data is obtained using 5 mm diameter of steel material containing as foreign body. The total acoustic pressure showed the same correlation for a frequency of 300 kHz where 0.658 Pa and 0.420 Pa were obtained for 0.5 mm and 0.9 mm of wall thickness respectively. The results revealed the same correlation for a glass material when it was used as a foreign body. The result shows that the finite elements method is very useful in designing an ultrasonic measurement system in food industry field especially in quality and safety food assessment.Practical applicationsFood quality is an important aspect for the food manufacturer. It is degraded for example if there is a foreign body in the foods product. It can cause the consumers to lose confidence of the manufacturer. Hence, a suitable sensor should be used to monitor the quality of the products is maintained. Ultrasonic sensors have attracted the attention of the food industry because it is cheap, fast response, and reliable. This paper presents an investigation using the two dimensional finite element method using Comsol Multiphysics software in order to detect the foreign body in a food container using an ultrasonic measurement system. The study demonstrates that the finite element method can assist in the design and development of an ultrasonic measurement system in the food industry field especially in the aspect of food safety and quality assurance.
Treatment of Sarcopenia with Bimagrumab: Results from a Phase II, Randomized, Controlled, Proof‐of‐Concept Study
Authors: Rooks Daniel , Praestgaard Jens , Hariry Sam , Laurent Didier , Petricoul Olivier , Perry Robert G. , Lach‐Trifilieff Estelle , Roubenoff Ronenn 
Published: June 2017

ObjectivesTo assess the effects of bimagrumab on skeletal muscle mass and function in older adults with sarcopenia and mobility limitations.DesignA 24‐week, randomized, double‐blind, placebo‐controlled, parallel‐arm, proof‐of‐concept study.SettingFive centers in the United States.ParticipantsCommunity‐dwelling adults (N = 40) aged 65 and older with gait speed between 0.4 and 1.0 m/s over 4 m and an appendicular skeletal muscle index of 7.25 kg/m2 or less for men and 5.67 kg/m2 or less for women.InterventionIntravenous bimagrumab 30 mg/kg (n = 19) or placebo (n = 21).MeasurementsChange from baseline in thigh muscle volume (TMV), subcutaneous and intermuscular fat, appendicular and total lean body mass, grip strength, gait speed, and 6‐minute walk distance (6MWD).ResultsThirty‐two (80%) participants completed the study. TMV increased by Week 2, was sustained throughout the treatment period, and remained above baseline at the end of study in bimagrumab‐treated participants, whereas there was no change with placebo treatment (Week 2: 5.15 ± 2.19% vs −0.34 ± 2.59%, P < .001; Week 4: 6.12 ± 2.56% vs 0.16 ± 3.42%, P < .001; Week 8: 8.01 ± 3.70% vs 0.35 ± 3.32%, P < .001; Week 16: 7.72 ± 5.31% vs 0.42 ± 5.14%, P < .001; Week 24: 4.80 ± 5.81% vs −1.01 ± 4.43%, P = .002). Participants with slower walking speed at baseline receiving bimagrumab had clinically meaningful and statistically significantly greater improvements in gait speed (mean 0.15 m/s, P = .009) and 6MWD (mean 82 m, P = .022) than those receiving placebo at Week 16. Adverse events in the bimagrumab group included muscle‐related symptoms, acne, and diarrhea, most of which were mild in severity and resolved by the end of study.ConclusionTreatment with bimagrumab over 16 weeks increased muscle mass and strength in older adults with sarcopenia and improved mobility in those with slow walking speed.