bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating Soluble Urokinase-Type Plasminogen Activator Receptor Levels Reflect Renal Function in Newly Diagnosed Patients with Multiple Myeloma Treated with Bortezomib-Based Induction
Authors: Terpos Evangelos , Ntanasis-Stathopoulos Ioannis , Papassotiriou Gerasimos-Petros , Kastritis Efstathios , Margeli Alexandra , Kanellias Nikolaos , Eleutherakis-Papaiakovou Evangelos , Migkou Magdalini , Fotiou Despina , Roussou Maria , Gavriatopoulou Maria , Malandrakis Panagiotis , Psimenou Erasmia , Papassotiriou Ioannis , Dimopoulos Meletios A.
Published: October 2020

(1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated in the pathogenesis of kidney disease in different disease settings. The aim of this study was to investigate a possible link between suPAR circulating levels and renal impairment (RI) in newly diagnosed patients with symptomatic multiple myeloma (NDMM) before and after frontline therapy with bortezomib-based regimens. (2) Methods: We studied 47 NDMM patients (57% males, median age 69.5 years) before the administration of anti-myeloma treatment and at best response to bortezomib-based therapy. suPAR was measured in the serum of all patients and of 24 healthy matched controls, using an immuno-enzymatic assay (ViroGates, Denmark). (3) Results: suPAR levels were elevated in NDMM patients at diagnosis compared to healthy individuals (p < 0.001). suPAR levels strongly correlated with disease stage (p-ANOVA < 0.001). suPAR levels both at diagnosis and at best response negatively correlated with estimated glomerular filtration rate (eGFR) values (p < 0.001). Interestingly, no significance changes in suPAR levels were observed at best response compared to baseline values (p = 0.31) among 18 responding patients with baseline eGFR < 50 mL/min/1.73 m2. (4) Conclusions: SuPAR levels reflect renal function in NDMM patients treated with bortezomib-based induction. Responders may have elevated circulating suPAR levels, possibly reflecting persistent kidney damage, despite their renal response.
Effect Sizes, Power, and Biases in Intelligence Research: A Meta-Meta-Analysis
Authors: Nuijten Michèle B. , van Assen Marcel A. L. M. , Augusteijn Hilde E. M. , Crompvoets Elise A. V. , Wicherts Jelte M.
Published: October 2020

In this meta-study, we analyzed 2442 effect sizes from 131 meta-analyses in intelligence research, published from 1984 to 2014, to estimate the average effect size, median power, and evidence for bias. We found that the average effect size in intelligence research was a Pearson’s correlation of 0.26, and the median sample size was 60. Furthermore, across primary studies, we found a median power of 11.9% to detect a small effect, 54.5% to detect a medium effect, and 93.9% to detect a large effect. We documented differences in average effect size and median estimated power between different types of intelligence studies (correlational studies, studies of group differences, experiments, toxicology, and behavior genetics). On average, across all meta-analyses (but not in every meta-analysis), we found evidence for small-study effects, potentially indicating publication bias and overestimated effects. We found no differences in small-study effects between different study types. We also found no convincing evidence for the decline effect, US effect, or citation bias across meta-analyses. We concluded that intelligence research does show signs of low power and publication bias, but that these problems seem less severe than in many other scientific fields.
Interannual Variability of Winter Sea Levels Induced by Local Wind Stress in the Northeast Asian Marginal Seas: 1993–2017
Authors: Han MyeongHee , Nam SungHyun , Cho Yang-Ki , Kang Hyoun-Woo , Jeong Kwang-Young , Lee Eunil
Published: October 2020

The interannual variability of winter sea levels averaged over the northeast Asian marginal seas, consisting of the Yellow Sea, East China Sea, and the East Sea (ES), was investigated. The spatial-mean sea level in winter observed using satellite altimetry shows significant interannual variations with a long-term rising trend of 3.88 mm y−1 during 1993–2017, with relatively high (Period H) and low (Period L) sea level anomalies. These anomalies correlate with the patterns of the East Asian winter monsoon at interannual timescales. The atmospheric pressure difference between the Sea of Okhotsk (SO) and ES around the Soya Strait is large during Period H. Ekman transport increases due to enhanced southeastward wind stress and results in a horizontal mass convergence that yields positive sea level anomalies during Period H. In contrast, the wind-induced transport is enhanced in the southern ES rather than in the southern SO resulting in horizontal mass divergence and negative anomalies in the spatial-mean winter sea level during Period L. Our results highlight the important roles of local wind forcing and Ekman dynamics in inducing interannual winter sea level variability in the region indicating the high predictive ability of atmospheric pressure anomalies around the Soya Strait.
Human Factor in Navigation: Overview of Cognitive Load Measurement during Simulated Navigational Tasks
Authors: Žagar Dejan , Svetina Matija , Košir Andrej , Dimc Franc
Published: October 2020

This paper is intended to give an overview of the experiments to evaluate the cognitive load of the officer on watch (OOW) during a collision avoidance maneuver in a full-mission simulator. The main goal is to investigate the possibilities of recording the biometric parameters of an OOW during a simulated collision avoidance maneuver. Potentially dangerous navigation errors known as human erroneous action (HEA) are induced by excessive cognitive load. Despite modern navigational aids on the ship’s bridge, investigators of maritime incidents typically link the reason for incidents at sea with human factors, including high cognitive load. During the experimental tasks on the bridge, the biometric parameters of the OOW are recorded. Statistical tools are used to visualize the data and evaluate the cognitive load of the OOW. Biometric peaks of the OOW typically occur either during the collision avoidance maneuver or when the OOW has been exposed to disturbing factors that increase reaction time and cause potentially dangerous navigation. Assessing the cognitive load of OOWs in the simulator is challenging for several reasons: e.g., the environmental conditions of the simulator, the type of task to be simulated, and even the type of sensor used. After careful study of the available literature, an original experimental design using non-invasive biometric sensors is proposed.
A Novel Secreted Cysteine-Rich Anionic (Sca) Protein from the Citrus Postharvest Pathogen Penicillium digitatum Enhances Virulence and Modulates the Activity of the Antifungal Protein B (AfpB)
Authors: Garrigues Sandra , Marcos Jose F. , Manzanares Paloma , Gandía Mónica
Published: October 2020

Antifungal proteins (AFPs) from ascomycete fungi could help the development of antimycotics. However, little is known about their biological role or functional interactions with other fungal biomolecules. We previously reported that AfpB from the postharvest pathogen Penicillium digitatum cannot be detected in the parental fungus yet is abundantly produced biotechnologically. While aiming to detect AfpB, we identified a conserved and novel small Secreted Cysteine-rich Anionic (Sca) protein, encoded by the gene PDIG_23520 from P. digitatum CECT 20796. The sca gene is expressed during culture and early during citrus fruit infection. Both null mutant (Δsca) and Sca overproducer (Scaop) strains show no phenotypic differences from the wild type. Sca is not antimicrobial but potentiates P. digitatum growth when added in high amounts and enhances the in vitro antifungal activity of AfpB. The Scaop strain shows increased incidence of infection in citrus fruit, similar to the addition of purified Sca to the wild-type inoculum. Sca compensates and overcomes the protective effect of AfpB and the antifungal protein PeAfpA from the apple pathogen Penicillium expansum in fruit inoculations. Our study shows that Sca is a novel protein that enhances the growth and virulence of its parental fungus and modulates the activity of AFPs.
Chromoblastomycosis in an Endemic Area of Brazil: A Clinical-Epidemiological Analysis and a Worldwide Haplotype Network
Authors: Santos Daniel Wagner C. L. , Vicente Vania Aparecida , Weiss Vinicius Almir , de Hoog G. Sybren , Gomes Renata R. , Batista Edith M. M. , Marques Sirlei Garcia , Queiroz-Telles Flávio de , Colombo Arnaldo Lopes , Azevedo Conceição de Maria Pedrozo e Silva de
Published: October 2020

Chromoblastomycosis (CBM) is a neglected implantation mycosis prevalent in tropical climate zones, considered an occupational disease that affects impoverished rural populations. This retrospective study described clinical aspects of CBM in a hyperendemic area in Brazil and constructed a worldwide haplotype network of Fonsecaea spp. strains. The variables were collected from medical records using a standard report form, reporting 191 patients with CBM from Maranhão, Brazil. The mean age was 56.1 years, 168 (88%) patients were male and predominantly farmers (85.8%). The mean time of evolution of the disease until diagnosis was 9.4 years. Lower limbs (81.2%) and upper limbs (14.2%) were the main sites affected. Most patients exhibited verrucous (55%) and infiltrative plaque (48.2%). Fonsecaea spp. were identified in 136 cases and a haplotype network constructed with ITS sequences of 185 global strains revealed a total of 59 haplotypes exhibiting high haplotypic and low nucleotide diversities. No correlation was observed between the different haplotypes of Fonsecaea species and dermatological patterns, severity of disease or geographic distribution inside Maranhão. Data from this area contributed to better understanding the epidemiology of CBM. For the first time, a robust haplotype network with Fonsecaea strains reveals an evolutionary history with a recent population expansion.
Multivariate Analysis of Fecal Metabolites from Children with Autism Spectrum Disorder and Gastrointestinal Symptoms before and after Microbiota Transfer Therapy
Authors: Qureshi Fatir , Adams James , Hanagan Kathryn , Kang Dae-Wook , Krajmalnik-Brown Rosa , Hahn Juergen
Published: October 2020

Fecal microbiota transplant (FMT) holds significant promise for patients with Autism Spectrum Disorder (ASD) and gastrointestinal (GI) symptoms. Prior work has demonstrated that plasma metabolite profiles of children with ASD become more similar to those of their typically developing (TD) peers following this treatment. This work measures the concentration of 669 biochemical compounds in feces of a cohort of 18 ASD and 20 TD children using ultrahigh performance liquid chromatography-tandem mass spectroscopy. Subsequent measurements were taken from the ASD cohort over the course of 10-week Microbiota Transfer Therapy (MTT) and 8 weeks after completion of this treatment. Univariate and multivariate statistical analysis techniques were used to characterize differences in metabolites before, during, and after treatment. Using Fisher Discriminant Analysis (FDA), it was possible to attain multivariate metabolite models capable of achieving a sensitivity of 94% and a specificity of 95% after cross-validation. Observations made following MTT indicate that the fecal metabolite profiles become more like those of the TD cohort. There was an 82–88% decrease in the median difference of the ASD and TD group for the panel metabolites, and among the top fifty most discriminating individual metabolites, 96% report more comparable values following treatment. Thus, these findings are similar, although less pronounced, as those determined using plasma metabolites.
Nonstandard Analysis, Deformation Quantization and Some Logical Aspects of (Non)Commutative Algebraic Geometry
Authors: Kanel-Belov Alexei , Chilikov Alexei , Ivanov-Pogodaev Ilya , Malev Sergey , Plotkin Eugeny , Yu Jie-Tai , Zhang Wenchao
Published: October 2020

This paper surveys results related to well-known works of B. Plotkin and V. Remeslennikov on the edge of algebra, logic and geometry. We start from a brief review of the paper and motivations. The first sections deal with model theory. In the first part of the second section we describe the geometric equivalence, the elementary equivalence, and the isotypicity of algebras. We look at these notions from the positions of universal algebraic geometry and make emphasis on the cases of the first order rigidity. In this setting Plotkin’s problem on the structure of automorphisms of (auto)endomorphisms of free objects, and auto-equivalence of categories is pretty natural and important. The second part of the second section is dedicated to particular cases of Plotkin’s problem. The last part of the second section is devoted to Plotkin’s problem for automorphisms of the group of polynomial symplectomorphisms. This setting has applications to mathematical physics through the use of model theory (non-standard analysis) in the studying of homomorphisms between groups of symplectomorphisms and automorphisms of the Weyl algebra. The last sections deal with algorithmic problems for noncommutative and commutative algebraic geometry.The first part of it is devoted to the Gröbner basis in non-commutative situation. Despite the existence of an algorithm for checking equalities, the zero divisors and nilpotency problems are algorithmically unsolvable. The second part of the last section is connected with the problem of embedding of algebraic varieties; a sketch of the proof of its algorithmic undecidability over a field of characteristic zero is given.
Risk of Interruption of Doctoral Studies and Mental Health in PhD Students
Authors: González-Betancor Sara M. , Dorta-González Pablo
Published: October 2020

PhD students report a higher prevalence of mental illness symptoms than highly educated individuals in the general population. This situation presents a serious problem for universities. Thus, the knowledge about this phenomenon is of great importance in decision-making. In this paper we use the Nature PhD survey 2019 and estimate several binomial logistic regression models to analyze the risk of interrupting doctoral studies. This risk is measured through the desire of change in either the supervisor or the area of expertise, or the wish of not pursue a PhD. Among the explanatory factors, we focus on the influence of anxiety/depression, discrimination, and bullying. As control variables we use demographic characteristics and others related with the doctoral program. Insufficient contact time with supervisors, and exceeding time spent studying crossing the 50-h week barrier, are risk factors of PhD studies interruption, but the most decisive risk factor is poor mental health. Universities should therefore foster an environment of well-being, which allows the development of autonomy and resilience of their PhD students or, when necessary, which fosters the development of conflict resolution skills.
Implementation of Adjusted Fuzzy AHP Method in the Assessment for Reuse of Industrial Buildings
Authors: Milošević Dušan M. , Milošević Mimica R. , Simjanović Dušan J.
Published: October 2020

With rapid economic development and restructuring, the number of old or obsolete buildings is growing in large cities. Construction practice has actively focused in recent decades on the regeneration of brownfield areas and creating opportunities for their cost-effective and sustainable reuse. Some of the buildings could be identified as-built industrial heritage whose purpose could be modified and used differently. Adaptive reuse can make a major contribution to sustainable development by reducing construction waste and saving natural resources. In the reuse management process, the problem is how to deal with multiple criteria that are imposed as factors in assessing the reuse of a building. Using the adjusted fuzzy analytical hierarchy process (FAHP), we explore the potential for the adaptation and new use of industrial buildings in the former area of Electronic Industry Nis (EI Nis) in Serbia. The standard FAHP, in which we determine the weights of each sub-criterion based on the expert’s evaluation, we adjusted for use when no pairwise comparison of existing alternatives was available. Multiple criteria evaluation was performed by applying many criteria and sub-criteria, taking into account the different spatial and physical performance of buildings, as well as their locational indicators. A case study is used to demonstrate the application of the method and show its effectiveness.
A New Hybrid MCDM Model for Personnel Selection Based on a Novel Grey PIPRECIA and Grey OCRA Methods
Authors: Ulutaş Alptekin , Popovic Gabrijela , Stanujkic Dragisa , Karabasevic Darjan , Zavadskas Edmundas Kazimieras , Turskis Zenonas
Published: October 2020

People represent one of the most significant resources of an organization, and therefore, personnel selection is one of the problems that organizations have increasingly been facing. The criteria that influence the final decision are usually opposing, so the application of multiple-criteria decision-making methods (MCDM) represents a suitable way for the facilitation of the given process. Additionally, the decision environment is characterized by the vagueness and uncertainty and, because of that, it is very hard to express the criteria over the exact crisp numbers. To acknowledge the unpredictability and obscurity of the available information important for the selection of the optimal candidate, a hybrid grey MCDM model for personnel selection is proposed in this paper. As an extension of the PIPRECIA method, the novel Grey Pivot Pairwise Relative Criteria Importance Assessment—the PIPRECIA-G method—is proposed and used for the determination of criteria importance. The PIPRECIA-G method preserved the good features of the PIPRECIA, but its superiority is reflected in its ability to deal with input data that are vague and grey. For the final ranking of the considered alternative candidates, the OCRA-G method is used. Basing the decision process and candidate selection on the two grey extended MCDM methods contributes to the increase of the reliability and confidence in the performed selection.
Multiple Periodic Solutions and Fractal Attractors of Differential Equations with n-Valued Impulses
Authors: Andres Jan
Published: October 2020

Ordinary differential equations with n-valued impulses are examined via the associated Poincaré translation operators from three perspectives: (i) the lower estimate of the number of periodic solutions on the compact subsets of Euclidean spaces and, in particular, on tori; (ii) weakly locally stable (i.e., non-ejective in the sense of Browder) invariant sets; (iii) fractal attractors determined implicitly by the generating vector fields, jointly with Devaney’s chaos on these attractors of the related shift dynamical systems. For (i), the multiplicity criteria can be effectively expressed in terms of the Nielsen numbers of the impulsive maps. For (ii) and (iii), the invariant sets and attractors can be obtained as the fixed points of topologically conjugated operators to induced impulsive maps in the hyperspaces of the compact subsets of the original basic spaces, endowed with the Hausdorff metric. Five illustrative examples of the main theorems are supplied about multiple periodic solutions (Examples 1–3) and fractal attractors (Examples 4 and 5).
Ticagrelor as an Alternative Antiplatelet Therapy in Cardiac Patients Non-Sensitive to Aspirin
Authors: Khan Hamzah , Gallant Reid , Jain Shubha , Al-Omran Mohammed , De Mestral Charles , Greco Elisa , Wheatcroft Mark , Alazonni Ashraf , Abdin Rawand , Rand Margaret L. , Ni Heyu , Qadura Mohammad
Published: October 2020

Background and Objectives: Aspirin (acetylsalicylic acid—ASA) is a first-line antiplatelet therapy provided to patients with coronary artery disease (CAD). However, it has been demonstrated that 20–30% of these patients are non-sensitive to their ASA therapy. ASA non-sensitivity is a phenomenon where low-dose ASA (81–325 mg) does not completely inhibit arachidonic-acid-induced platelet aggregation, putting patients at risk of adverse cardio-thrombotic events. Ticagrelor is a P2Y12 receptor inhibitor and alternative antiplatelet that has been approved to reduce the risk of stroke, myocardial infarction, and overall cardiovascular-related death. In this study, we aimed to identify ASA non-sensitive patients and evaluate if they would be sensitive to ticagrelor. Materials and Methods: For this pilot study, thirty-eight patients with CAD taking 81 mg ASA were recruited. Blood samples were collected from each patient and platelet rich plasma (PRP) from each sample was isolated. Light-transmission aggregometry (LTA) was used to determine baseline ASA sensitivity in each patient using 0.5 mg/mL arachidonic acid as a platelet agonist. Patients with ≥20% maximal platelet aggregation after activation were considered ASA non-sensitive. Fresh PRP samples from all patients were then spiked with a clinical dosage of ticagrelor (3 μM—approximately equivalent to a loading dose of 180 mg ticagrelor). Sensitivity was determined using LTA and 5 μM ADP as a platelet agonist. Patients with ≥46% maximal platelet aggregation were considered ticagrelor non-sensitive. Results: Of the 38 CAD patients taking 81 mg ASA, 32% (12/38) were non-sensitive to their 81 mg ASA therapy. All 38 of the recruited patients (100%) were sensitive to ticagrelor ex vivo. In conclusion, we were able to identify ASA non-sensitivity using LTA and determine that ASA non-sensitive patients were sensitive to ticagrelor. Conclusions: Our results suggest that ticagrelor is a promising alternative therapy for patients who are non-sensitive to ASA.
Stress–Corrosion Cracking of AISI 316L Stainless Steel in Seawater Environments: Effect of Surface Machining
Authors: Ren Zhe , Ernst Frank
Published: October 2020

To understand the effect of surface machining on the resistance of AISI 316L to SCC (stress–corrosion cracking) in marine environments, we tested nuts surface-machined by different methods in a seawater-spraying chamber. Two forms of cracks were observed: on the machined surface and underneath it. On the surface, cracks connected with the pitting sites were observed to propagate perpendicular to the hoop-stress direction, identifying them as stress–corrosion cracks. Under the surface, catastrophic transgranular cracks developed, likely driven by hydrogen embrittlement caused by the chloride-concentrating level of humidity in the testing environment. Under constant testing conditions, significantly different SCC resistance was observed depending on how the nuts had been machined. Statistical evaluation of the nut surface-crack density indicates that machining by a “form” tool yields a crack density one order of magnitude lower than machining by a “single-point” tool. Microstructural analysis of form-tool-machined nuts revealed a homogeneous deformed subsurface zone with nanosized grains, leading to enhanced surface hardness. Apparently, the reduced grain size and/or the associated mechanical hardening improve resistance to SCC. The nanograin subsurface zone was not observed on nuts machined by a single-point tool. Surface roughness measurements indicate that single-point-tool-machined nuts have a rougher surface than form-tool machined nuts. Apparently, surface roughness reduces SCC resistance by increasing the susceptibility to etch attack in Cl--rich solutions. The results of X-ray diffractometry and transmission electron microscopy diffractometry indicate that machining with either tool generates a small volume fraction (< 0.01) of strain-induced martensite. However, considering the small volume fraction and absence of martensite in regions of cracking, martensite is not primarily responsible for SCC in marine environments.
Solidification and Precipitation Microstructure Simulation of a Hypereutectic Al–Mn–Fe–Si Alloy in Semi-Quantitative Phase-Field Modeling with Experimental Aid
Authors: Park Jiwon , Oh Chang-Seok , Kang Joo-Hee , Jung Jae-Gil , Lee Jung-Moo
Published: October 2020

In this study, microstructural evolution during solidification of a hypereutectic Al–Mn–Fe–Si alloy was investigated using semi-quantitative two-/three-dimensional phase-field modeling. The formation of facetted Al6Mn precipitates and the temperature evolution during solidification were simulated and experimentally validated. The temperature evolution obtained from the phase-field simulation, which was balanced between extracted heat and latent heat release, was compared to the thermal profile of the specimen measured during casting to validate the semi-quantitative phase-field simulation. The casting microstructure, grain morphology, and solute distribution of the specimen were analyzed using electron backscatter diffraction and energy-dispersive spectroscopy and compared with the simulated microstructure. The simulation results identified the different Fe to Mn ratios in Al6(Mnx,Fe1−x) precipitates that formed during different solidification stages and were confirmed by energy-dispersive spectroscopy. The precipitates formed in the late solidification stage were more enriched with Fe than the primary precipitate due to solute segregation in the interdendritic channel. The semi-quantitative model facilitated a direct comparison between the simulation and experimental observations.
Development of a New PM Tool Steel for Optimization of Cold Working of Advanced High-Strength Steels
Authors: Mussa Abdulbaset , Krakhmalev Pavel , Şelte Aydın , Bergström Jens
Published: October 2020

In the present study, Uddeholm Vancron SuperClean cold work tool steel was investigated concerning wear resistance and fatigue strength, using laboratory and semi-industrial tests. The Uddeholm Vancron SuperClean was designed with the help of ThermoCalc calculations to contain a high amount of a carbonitride phase, which was suggested to improve tribological performance of this tool steel. In order to investigate the tested steel, galling tests with a slider-on flat-surface tribotester and semi-industrial punching tests were performed on an advanced high-strength steel, CP1180HD. Uddeholm Vanadis 8 SuperClean containing only a carbide phase and Uddeholm Vancron 40 containing a mixture of carbides and carbonitrides were also tested to compare the performance of the tool steels. The microstructure and wear mechanisms were characterized with scanning electron microscopy. It was found that the carbonitrides presented in Uddeholm Vancron SuperClean improved its resistance to material transfer and galling. Semi-industrial punching tests also confirmed that Uddeholm Vancron SuperClean cold work tool steel also possesses enhanced resistance to chipping and fatigue crack nucleation, which confirms the beneficial role of the carbonitride phase in wear resistance of cold work tool steel.
Vaccines against Meningococcal Diseases
Authors: Pizza Mariagrazia , Bekkat-Berkani Rafik , Rappuoli Rino
Published: October 2020

Neisseria meningitidis is the main cause of meningitis and sepsis, potentially life-threatening conditions. Thanks to advancements in vaccine development, vaccines are now available for five out of six meningococcal disease-causing serogroups (A, B, C, W, and Y). Vaccination programs with monovalent meningococcal serogroup C (MenC) conjugate vaccines in Europe have successfully decreased MenC disease and carriage. The use of a monovalent MenA conjugate vaccine in the African meningitis belt has led to a near elimination of MenA disease. Due to the emergence of non-vaccine serogroups, recommendations have gradually shifted, in many countries, from monovalent conjugate vaccines to quadrivalent MenACWY conjugate vaccines to provide broader protection. Recent real-world effectiveness of broad-coverage, protein-based MenB vaccines has been reassuring. Vaccines are also used to control meningococcal outbreaks. Despite major improvements, meningococcal disease remains a global public health concern. Further research into changing epidemiology is needed. Ongoing efforts are being made to develop next-generation, pentavalent vaccines including a MenACWYX conjugate vaccine and a MenACWY conjugate vaccine combined with MenB, which are expected to contribute to the global control of meningitis.
Actions of FTY720 (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-Lymphocytes
Authors: Chang Wei-Ting , Liu Ping-Yen , Wu Sheng-Nan
Published: October 2020

FTY720 (fingolimod), a modulator of sphingosine-1-phosphate receptors, is known to produce the immunomodulatory actions and to be beneficial for treating the relapsing multiple sclerosis. However, whether it exerts any effects on membrane ion currents in immune cells remains largely unknown. Herein, the effects of FTY720 on ionic currents in Jurkat T-lymphocytes were investigated. Cell exposure to FTY720 suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in a time- and concentration-dependent manner with an IC50 value of 1.51 μM. Increasing the FTY720 concentration not only decreased the IK(DR) amplitude but also accelerated the inactivation time course of the current. By using the minimal reaction scheme, the effect of FTY720 on IK(DR) inactivation was estimated with a dissociation constant of 3.14 μM. FTY720 also shifted the inactivation curve of IK(DR) to a hyperpolarized potential with no change in the slope factor, and recovery from IK(DR) became slow during the exposure to this compound. Cumulative inactivation for IK(DR) in response to repetitive depolarizations was enhanced in the presence of FTY720. In SEW2871-treated cells, FTY720-induced inhibition of IK(DR) was attenuated. This compound also exerted a stimulatory action on the activity of intermediate-conductance Ca2+-activated K+ channels in Jurkat T-lymphocytes. However, in NSC-34 neuronal cells, FTY720 did not modify the inactivation kinetics of KV3.1-encoded IK(DR), although it suppressed IK(DR) amplitude in these cells. Collectively, the perturbations by FTY720 on different types of K+ channels may contribute to the functional activities of immune cells, if similar findings appear in vivo.
Phytochemical Identification, Acute, and Sub-Acute Oral Toxicity Studies of the Foliar Extract of Withania frutescens
Authors: EL Moussaoui Abdelfattah , Bourhia Mohammed , Jawhari Fatima Zahra , Mechchate Hamza , Slighoua Meryem , Bari Ahmed , Ullah Riaz , Mahmood Hafiz Majid , Ali Syed Saeed , Ibenmoussa Samir , Bousta Dalila , Bari Amina
Published: October 2020

Withania frutescens (W. frutescens) is a medicinal plant widely used to treat several diseases. This work aims to study phytochemical composition as well as acute and subacute toxicity of W. frutescens hydroethanolic extract in mice. The phytochemical composition of W. frutescens extract was performed using gas chromatographic analysis. Acute toxicity was studied in vivo with oral administration of single doses 400 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was studied with the administration of repeated doses of 400 mg/kg/day and 2000 mg/kg/day for 28 days. Phytochemical analysis of W. frutescens hydro-ethanolic extract confirmed the presence of interesting chemical compounds. Acute toxicity results showed no toxic symptoms in mice treated with an increasing dose up to a maximum of 2000 mg/kg. Alongside acute toxicity, subacute data showed no clinical symptoms nor biochemical or histological alteration in mice treated with an increasing dose up to a maximum of 2000 mg/kg compared to the control group (p < 0.05). This study shows no toxic effects in animals treated with W. frutescens extract, and, therefore, this plant can be considered safe in animals up to 2000 mg/kg under both acute and subacute toxicity conditions.
Volatile Phenols—Important Contributors to the Aroma of Plant-Derived Foods
Authors: Schieber Andreas , Wüst Matthias
Published: October 2020

Volatile phenols like phenylpropanoid and benzoid compounds originate from the aromatic amino acid phenylalanine, which is biosynthesized via the shikimate/arogenate pathway. These volatile compounds contribute to the aroma of a number of economically important plant-derived foods like herbs, spices and fruits. The sequestration of numerous phenylpropanoid and benzoid compounds as glycosides occurs widely in fruits, and this pool represents an important source of flavor that can be released during storage and processing. Therefore, this review will provide an overview of the biosynthesis of free and glycosylated phenylpropanoid and benzoid compounds and their reactions during food processing, which both lead to the generation of odor-active volatile phenols in plant-derived foods.
Synthesis of New Imidazopyridine Nucleoside Derivatives Designed as Maribavir Analogues
Authors: Papadakis Georgios , Gerasi Maria , Snoeck Robert , Marakos Panagiotis , Andrei Graciela , Lougiakis Nikolaos , Pouli Nicole
Published: October 2020

The strong inhibition of Human Cytomegalovirus (HCMV) replication by benzimidazole nucleosides, like Triciribine and Maribavir, has prompted us to expand the structure–activity relationships of the benzimidazole series, using as a central core the imidazo[4,5-b]pyridine scaffold. We have thus synthesized a number of novel amino substituted imidazopyridine nucleoside derivatives, which can be considered as 4-(or 7)-aza-d-isosters of Maribavir and have evaluated their potential antiviral activity. The target compounds were synthesized upon glycosylation of suitably substituted 2-aminoimidazopyridines, which were prepared in six steps starting from 2-amino-6-chloropyridine. Even if the new compounds possessed only a slight structural modification when compared to the original drug, they were not endowed with interesting antiviral activity. Even so, three derivatives showed promising cytotoxic potential.
New Mesoporous Silica-Supported Organocatalysts Based on (2S)-(1,2,4-Triazol-3-yl)-Proline: Efficient, Reusable, and Heterogeneous Catalysts for the Asymmetric Aldol Reaction
Authors: Sánchez-Antonio Omar , Romero-Sedglach Kevin A. , Vázquez-Orta Erika C. , Juaristi Eusebio
Published: October 2020

Novel organocatalytic systems based on the recently developed (S)-proline derivative (2S)-[5-(benzylthio)-4-phenyl-(1,2,4-triazol)-3-yl]-pyrrolidine supported on mesoporous silica were prepared and their efficiency was assessed in the asymmetric aldol reaction. These materials were fully characterized by FT-IR, MS, XRD, and SEM microscopy, gathering relevant information regarding composition, morphology, and organocatalyst distribution in the doped silica. Careful optimization of the reaction conditions required for their application as catalysts in asymmetric aldol reactions between ketones and aldehydes afforded the anticipated aldol products with excellent yields and moderate diastereo- and enantioselectivities. The recommended experimental protocol is simple, fast, and efficient providing the enantioenriched aldol product, usually without the need of a special work-up or purification protocol. This approach constitutes a remarkable improvement in the field of heterogeneous (S)-proline-based organocatalysis; in particular, the solid-phase silica-bonded catalytic systems described herein allow for a substantial reduction in solvent usage. Furthermore, the supported system described here can be recovered, reactivated, and reused several times with limited loss in catalytic efficiency relative to freshly synthesized organocatalysts.
New Sustainable Process for Hesperidin Isolation and Anti-Ageing Effects of Hesperidin Nanocrystals
Authors: Stanisic Danijela , Liu Leticia H. B. , dos Santos Roney V. , Costa Amanda F. , Durán Nelson , Tasic Ljubica
Published: October 2020

Hesperidin, a secondary orange (Citrus sinensis) metabolite, was extracted from orange bagasse. No organic solvents or additional energy consumption were used in the clean and sustainable process. Hesperidin purity was approximately 98% and had a yield of 1%. Hesperidin is a known supplement due to antioxidant, chelating, and anti-ageing properties. Herein, hesperidin application to eliminate dark eye circles, which are sensitive and thin skin regions, was studied. In addition, the proposed method for its aqueous extraction was especially important for human consumption. Further, the most effective methods for hesperidin nanonization were explored, after which the nanoemulsions were incorporated into a cream formulation that was formulated for a tropical climate. Silky cream formulations (oil in water) were tested in vitro on artificial 3D skin from cultured cells extracted from skin residues after plastic surgery. The proposed in vitro assay avoided tests of the different formulations in human volunteers and animals. It was shown that one of the nanonized hesperidin formulations was the most skin-friendly and might be used in cosmetics.
Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease
Authors: Mocanu Cosmin Stefan , Jureschi Monica , Drochioiu Gabi
Published: October 2020

Aluminium (Al) is clearly neurotoxic and considerable evidence exists that Al may play a role in the aetiology or pathogenesis of Alzheimer’s disease (AD). Nevertheless, the link between AD pathology and Al is still open to debate. Therefore, we investigated here the interaction of aluminium ions with two Aβ peptide fragments and their analogues. First, we synthesised by the Fmoc/tBu solid-phase peptide synthesis (SPPS) strategy using an automated peptide synthesiser two new peptides starting from the Aβ(1–16) native peptide fragment. For this purpose, the three histidine residues (H6, H13, and H14) of the Aβ(1–16) peptide were replaced by three alanine and three serine residues to form the modified peptides Aβ(1–16)A36,13,14 and Aβ(1–16)S36,13,14 (primary structures: H-1DAEFRADSGYEVAAQK16-NH2 and H-1DAEFRSDSGYEVSSQK16-NH2). In addition, the Aβ(9–16) peptide fragment (H-9GYEVHHQK16-NH2) and its glycine analogues, namely Aβ(9–16)G110, (H-9GGEVHHQK16-NH2), Aβ(9–16)G213,14 (H-9GYEVGGQK16-NH2), and Aβ(9–16)G310,13,14 (H-9GGEVGGQK16-NH2), were manually synthesised in order to study Al binding to more specific amino acid residues. Both the peptides and the corresponding complexes with aluminium were comparatively investigated by mass spectrometry (MS), circular dichroism spectroscopy (CD), atomic force microscopy (AFM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR). Al–peptide molecular ions and Al-fragment ions were unambiguously identified in the MS and MS/MS spectra. AFM images showed dramatic changes in the film morphology of peptides upon Al binding. Our findings from the investigation of N-terminal 1-16 and even 9-16 normal and modified sequences of Aβ peptides suggest that they have the capability to be involved in aluminium ion binding associated with AD.
Effect of Increasing the Dietary Protein Content of Breakfast on Subjective Appetite, Short-Term Food Intake and Diet-Induced Thermogenesis in Children
Authors: Bellissimo Nick , Fansabedian Tammy , Wong Vincent , Totosy de Zepetnek Julia , Brett Neil , Schwartz Alexander , Cassin Stephanie , Suitor Katherine , Rousseau Dérick
Published: October 2020

Dietary protein affects energy balance by decreasing food intake (FI) and increasing energy expenditure through diet-induced thermogenesis (DIT) in adults. Our objective was to investigate the effects of increasing the dietary protein in an isocaloric breakfast on subjective appetite, FI, blood glucose, and DIT in 9–14 y children. Two randomized repeated measures designs were used. In experiment 1, 17 children (9 boys, 8 girls) consumed isocaloric meals (450 kcal) on four separate mornings containing: 7 g (control), 15 g (low protein, LP), 30 g (medium protein, MP) or 45 g (high protein, HP) of protein. Blood glucose and subjective appetite were measured at baseline and regular intervals for 4 h, and FI was measured at 4 h. In experiment 2, 9 children (6 boys, 3 girls) consumed the control or HP breakfast on two separate mornings, and both DIT and subjective appetite were determined over 5 h. In experiment 1, all dietary protein treatments suppressed subjective appetite compared to control (p < 0.001), and the HP breakfast suppressed FI compared with the LP breakfast and control (p < 0.05). In experiment 2, DIT was higher after HP than control (p < 0.05). In conclusion, increasing the dietary protein content of breakfast had favorable effects on satiety, FI, and DIT in children.
The Anti-Obesogenic Effect of Lean Fish Species Is Influenced by the Fatty Acid Composition in Fish Fillets
Authors: Fjære Even , Myrmel Lene Secher , Dybing Karianne , Kuda Ondrej , Holbech Jensen Benjamin Anderschou , Rossmeisl Martin , Frøyland Livar , Kristiansen Karsten , Madsen Lise
Published: October 2020

Fillets from marine fish species contain n-3 polyunsaturated fatty acids (PUFAs) in the form of phospholipids (PLs). To investigate the importance of PL-bound n-3 PUFAs in mediating the anti-obesogenic effect of lean seafood, we compared the anti-obesogenic properties of fillets from cod with fillets from pangasius, a fresh water fish with a very low content of PL-bound n-3 PUFAs. We prepared high-fat/high-protein diets using chicken, cod and pangasius as the protein sources, and fed male C57BL/6J mice these diets for 12 weeks. Mice fed the diet containing cod gained less adipose tissue mass and had smaller white adipocytes than mice fed the chicken-containing diet, whereas mice fed the pangasius-containing diet were in between mice fed the chicken-containing diet and mice fed the cod-containing diet. Of note, mice fed the pangasius-containing diet exhibited reduced glucose tolerance compared to mice fed the cod-containing diet. Although the sum of marine n-3 PUFAs comprised less than 2% of the total fatty acids in the cod-containing diet, this was sufficient to significantly increase the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) in mouse tissues and enhance production of n-3 PUFA-derived lipid mediators as compared with mice fed pangasius or chicken.
Decision-Making Process in Comprehensive Medication Management Services: From the Understanding to the Development of a Theoretical Model
Authors: Oliveira Isabela Viana , Nascimento Yone de Almeida , Ramalho-de-Oliveira Djenane
Published: October 2020

In Comprehensive medication management (CMM), the practitioner applies a decision-making method to assess patients’ pharmacotherapy in order to identify and solve drug therapy problems. Grounded theory was used to understand how pharmacists make clinical decisions when providing CMM service. Data collection included individual semi structured interviews with 11 pharmacists, observation of clinical case discussions and CMM consultations provided by the participating pharmacists. Two main categories emerged: 1. Understanding the rational method of decision-making: the foundation of the patient care process. 2. Balancing the care equation: the objective and the subjective, which includes a theoretical proposal explaining the pharmacists’ decision-making process and the factors that can modify this process. The pharmacotherapy knowledge should guide the anamnesis. Thus, the professional can evaluate the indication, effectiveness, safety and convenience of medications used by the patient. After exploring patients’ medication experiences, pharmacists can follow two courses of action: helping the patient overcome barriers to medication use; or matching the pharmacotherapy to the patient’s routine. Professional autonomy and absence of the patient at the time of the decision were some factors that influenced the pharmacist’s decision. Findings provide a broad understanding of pharmacists’ decision-making process during the care of patients using medications. It can be applied as a basis for educational interventions to train professionals on decision-making.
The P–T Probability Framework for Semantic Communication, Falsification, Confirmation, and Bayesian Reasoning
Authors: Lu Chenguang
Published: October 2020

Many researchers want to unify probability and logic by defining logical probability or probabilistic logic reasonably. This paper tries to unify statistics and logic so that we can use both statistical probability and logical probability at the same time. For this purpose, this paper proposes the P–T probability framework, which is assembled with Shannon’s statistical probability framework for communication, Kolmogorov’s probability axioms for logical probability, and Zadeh’s membership functions used as truth functions. Two kinds of probabilities are connected by an extended Bayes’ theorem, with which we can convert a likelihood function and a truth function from one to another. Hence, we can train truth functions (in logic) by sampling distributions (in statistics). This probability framework was developed in the author’s long-term studies on semantic information, statistical learning, and color vision. This paper first proposes the P–T probability framework and explains different probabilities in it by its applications to semantic information theory. Then, this framework and the semantic information methods are applied to statistical learning, statistical mechanics, hypothesis evaluation (including falsification), confirmation, and Bayesian reasoning. Theoretical applications illustrate the reasonability and practicability of this framework. This framework is helpful for interpretable AI. To interpret neural networks, we need further study.