A Survey on Metamorphic Testing

A test oracle determines whether a test execution reveals a fault, often by comparing the observed program output to the expected output. This is not always practical, for example when a program's input-output relation is complex and difficult to capture formally. Metamorphic testing provides an alternative, where correctness is not determined by checking an individual concrete output, but by applying a transformation to a test input and observing how the program output “morphs” into a different one as a result. Since the introduction of such metamorphic relations in 1998, many contributions on metamorphic testing have been made, and the technique has seen successful applications in a variety of domains, ranging from web services to computer graphics. This article provides a comprehensive survey on metamorphic testing: It summarises the research results and application areas, and analyses common practice in empirical studies of metamorphic testing as well as the main open challenges

Kinetics of antibodies in sera, saliva, and urine samples from adult patients with primary or secondary dengue 3 virus infections

SummaryObjectivesThe kinetics of three serological markers (IgM, IgA, and IgG) in serum, saliva, and urine samples from adult patients with primary or secondary dengue infection were studied.DesignSerum, saliva, and urine samples were collected from 22 patients with clinical and confirmed dengue 3 virus infection during the outbreak in Havana City in 2001. They were tested by capture IgM (MAC-ELISA), IgA (AAC-ELISA), and IgE (EAC-ELISA) and IgG ELISA inhibition method (EIM) to detect specific dengue antibodies.ResultsSimilar kinetics were observed in IgM, IgA, and IgG antibodies in saliva and IgA and IgG in urine samples from secondary cases compared with kinetics in serum samples, although the values were lower. No IgG antibody was detected in saliva and urine samples in primary cases and IgM antibody was not detected in urine samples from either primary or secondary infection. All secondary cases were positive for IgG in saliva and urine samples at day 7. The kinetics of specific IgE antibodies in primary and secondary cases were different.ConclusionsThe kinetics of three serological markers (IgM, IgA, and IgG) in serum, saliva, and urine samples from adult patients with primary or secondary dengue 3 virus infection were studied for the first time, showing its behavior and usefulness in dengue virus diagnosis. The specific IgE could play a role as a serological marker in secondary infections

Architectural plasticity of human BRCA2-RAD51 complexes in DNA break repair

The tumor suppressor BRCA2 is a large multifunctional protein mutated in 50-60% of familial breast cancers. BRCA2 interacts with many partners and includes multiple regions with potentially disordered structure. In homology directed DNA repair BRCA2 delivers RAD51 to DNA resulting in removal of RPA and assembly of a RAD51 nucleoprotein filame

Tritordeum breads are well tolerated with preference over gluten-free breads in non-celiac wheat-sensitive patients and its consumption induce changes in gut bacteria

BACKGROUND The ingestion of wheat and other cereals are related to several gut disorders. The specific components responsible for non-celiac wheat-sensitivity (NCWS) may include gluten and other compounds. Tritordeum is a new cereal derived from crossing durum wheat with a wild barley species, which differs from bread wheat in its gluten composition. In the present work, we examined the response of NCWS patients to tritordeum bread Gastrointestinal symptoms as well as tritordeum acceptability, gluten immunogenic peptides excretion, and the composition and structure of the intestinal microbiota were evaluated. RESULTS Gastrointestinal symptoms of the subjects showed no significant change between the gluten-free bread and the tritordeum bread. Participating subjects rated tritordeum bread higher than the gluten-free bread. Analysis of the bacterial gut microbiota indicated that tritordeum consumption does not alter the global structure and composition of the intestinal microbiota, and only a few changes in some butyrate-producing bacteria were observed. CONCLUSIONS All the results derived from acceptability, biochemical and microbiological tests suggest that tritordeum may be tolerated by a sub-set of NCWS sufferers who do not require strict exclusion of gluten from their diet. (c) 2020 Society of Chemical Industry

The role of disulfide bond replacements in analogues of the Tarantula toxin ProTx-II and their effects on inhibition of the voltage-gated sodium ion channel Nav1.7

Spider venom toxins, such as Protoxin-II (ProTx-II), have recently received much attention as selective Nav1.7 channel blockers, with potential to be developed as leads for the treatment of chronic nocioceptive pain. ProTx-II is a 30-amino acid peptide with three disulfide bonds that has been reported to adopt a well-defined inhibitory cystine knot (ICK) scaffold structure. Potential drawbacks with such peptides include poor pharmacodynamics and potential scrambling of the disulfide bonds in vivo. In order to address these issues, in the present study we report the solid-phase synthesis of lanthionine-bridged analogues of ProTx-II, in which one of the three disulfide bridges is replaced with a thioether linkage, and evaluate the biological properties of these analogues. We have also investigated the folding and disulfide bridging patterns arising from different methods of oxidation of the linear peptide precursor. Finally, we report the X-ray crystal structure of ProTx-II to atomic resolution; to our knowledge this is the first crystal structure of an ICK spider venom peptide not bound to a substrate

Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse

CYP2C19*2 and CYP2C19*17 might influence tamoxifen metabolism and clinical outcome. Our aim was to investigate the effect of CYP2C19 genotypes on tamoxifen concentrations and metabolic ratios (MRs) and breast cancer recurrence in a large cohort of Caucasian women. Genetic variants (CYP2D6 and CYP2C19 genotypes), tamoxifen and metabolites concentrations, baseline characteristics, and breast cancer recurrence from the CYPTAM study (NTR1509) were used. CYP2C19*2 and CYP2C19*17 genotypes were evaluated as alleles and as groups based on CYP2D6 genotypes (high, intermediate and low activity). Log-rank test and Kaplan-Meier analysis were used to evaluate differences in recurrence defined as relapse-free survival (RFS). Classification tree analyses (CTAs) were conducted to assess the levels of interactions per polymorphism (CYP2D6 and CYP2C19 genotypes) on endoxifen concentrations. No differences in mean concentrations and MRs were observed when comparing CYP2C19 genotypes (CYP2C19*1/*1; CYP2C19*1/*2; CYP2C19*2/*2; CYP2C19*1/*17; CYP2C19*17/*17; CYP2C19*2/*17). Only significant differences (p value<0.05) in mean concentrations and MRs were observed when comparing tamoxifen activity groups (high, intermediate and low activity). A log-rank test did not find an association across CYP2C19 genotypes (p value 0.898). CTAs showed a significant relationship between CYP2D6 and endoxifen (p value<0.0001), but no association with CYP2C19 genotypes was found. CYP2C19 polymorphisms do not have a significant impact on tamoxifen metabolism or breast cancer relapse.Personalised Therapeutic

Efectividad del aceite esencial de orégano mexicano de República Dominicana (Lippia graveolens) contra plagas del maíz (Sitophilus zeamais y Fusarium verticillioides)

The insecticidal and antifungal properties of Mexican oregano (Lippia graveolens) essential oil from the Dominican Republic were investigated under laboratory conditions against two main pests of stored grains: Sitophilus zeamais and Fusarium verticillioides. Although oregano essential oil at 600 ?l/l air did not result in a significant mortality of S. zeamais after 24 hours of exposure by fumigation, this essential oil was a powerful acetylcholinesterase (AChE) inhibitor in vitro. One of the main components of oregano essential oil, p-cymene, presented fumigant toxicity and AChE inhibition activity against the maize weevil. The L. graveolens essential oil antifungal activity against F. verticillioides was evaluated at 50, 100 and 200 ?l/l, and it was found that growth parameters were affected by the presence of oregano essential oil in the media, whereas FB1 production was not inhibited. The results demonstrate that oregano essential oil and p-cymene can be used as alternatives to synthetic pesticides against F. verticillioides and S. zeamais, respectively.Se estudiaron en condiciones de laboratorio las propiedades insecticidas y fungicidas del aceite esencial de orégano mexicano (Lippia graveolens) de República Dominicana contra dos plagas principales de granos almacenados: Sitophilus zeamais y Fusarium verticillioides. Aunque el aceite esencial de orégano a 600 ?l/l de aire no resultó en una mortalidad significativa de S. zeamais después de 24 horas de exposición a la fumigación, fue un potente inhibidor de la acetilcolinesterasa (AChE) in vitro. El p-cimeno, uno de los principales componentes del aceite esencial, presentó actividad fumigante y de inhibición de la AChE contra el gorgojo del maíz. Además se evaluó la actividad antifúngica frente a F. verticillioides a 50, 100 y 200 ?l/l y se encontró que los parámetros de crecimiento del hongo fueron afectados por la presencia del aceite esencial de orégano en el medio, mientras que la producción de fumonisina B1 (FB1) no se inhibió. Los resultados demuestran que el aceite esencial de orégano y el p-cimeno se pueden usar como alternativas a los pesticidas sintéticos contra F. verticillioides y S. zeamais, respectivamente

PrevenBox: Evaluation of concomitant use of preventive medications with OnabotulinumtoxinA in migraine

P114 Background: OnabotulinumtoxinA is an effective, tolerable and safepreventive treatment for chronic migraine (CM). Other than a reduc-tion in headache frequency or disability, in CM the withdrawal ofconcomitant preventive medication indicates treatment effectivenessand quality of life improvement. Objective: To characterize the change in the use of oral preventivemedication after treatment with OnabotulinumtoxinA in patientswith migraine. Methods: This is a multicentre study. We consecutively included pa-tients with migraine (ICHD-3) that were on preventive treatment withOnabotulinumtoxinA. We retrospectively collected demographic data, diagnosis of migraine, frequency and intensity changes, number ofcycle and OnabotulinumtoxinA dose. In addition, we listed the initialand current preventive treatment (number of drugs and group) andthe number and cycle of medications withdrawn. We performed aunivariate and logistic regression analysis. Results: We included 542 patients: 87.6% women, mean age 47.6 ±11.7 years. A 89.3% had chronic migraine and 10.8% had high fre-quency episodic migraine. The mean reduction in frequency aftertreatment was 13.4±8.2 headache days/month. At baseline, a 91.3%took other preventives and during treatment with Onabotulinumtox-inA a 58.6% withdrew at least one drug, 25.8% stopped completelyall oral preventive drugs. Factors associated with withdrawal were:being male, having >50% response in frequency and intensity, thenumber of infiltrations and a shorter chronification period until thefirst OnabotulinumtoxinA administration (p <0.05). The multivariateanalysis showed that a better response in intensity (OR:1.8 [1.4-2.2], p<0.001), a greater number of infiltrations (OR:1.1 [1.0-1.2], p<0.001)and a shorter chronification period (OR:0.994 [0.992-0.997], p<0.001)were predictors of withdrawal. The ROC curve, showed that 6 Onabo-tulinumtoxinA cycles was the cut-off point that better predicted oralpreventive medication withdrawal (p <0.001). Conclusions: Treatment with OnabotulinumtoxinA reduces the use ofother preventive medications for migraine. The highest probability ofwithdrawal occurs after 6 cycles of treatment

The relative age effect on physical fitness in preschool children

The aim of the present study was to investigate the existence of a relative age effect (RAE) on physical fitness of preschoolers. Anthropometry and physical fitness were assessed in 3147 children (3–5 years old) using the PREFIT battery. Based on the birth year, participants were divided into 3year groups (3-, 4- and 5-years). Within each year group, 4quarter groups were created: quarter 1, preschoolers born from January to March; quarter 2, from April to June; quarter 3, from July to September; quarter 4, from October to December. The MANCOVA analysis revealed a main effect of year group (Wilks’ ¿ = 0.383; F10, 5996 = 369.64; p &lt; 0.001, ¿p 2 = 0.381) and of quarter (Wilks’ ¿ = 0.874; F15, 8276.6 = 27.67; p &lt; 0.001; ¿p 2 = 0.044) over the whole battery of tests. To the best of our knowledge, this is the first study to report the existence of RAE at the preschool stage. In general, performance improved as the relative age increased (i.e., those born in quarter 1 performed better than those in the other quarters). Individualization strategies should be addressed within the same academic year not only in elementary or secondary years but also in preschoolers