bluuebunny/crossref_metadata_2025 huggingface dataset:
New Tetrahydroacridine Hybrids with Dichlorobenzoic Acid Moiety Demonstrating Multifunctional Potential for the Treatment of Alzheimer’s Disease
Authors: Czarnecka Kamila , Girek Małgorzata , Wójtowicz Przemysław , Kręcisz Paweł , Skibiński Robert , Jończyk Jakub , Łątka Kamil , Bajda Marek , Walczak Anna , Galita Grzegorz , Kabziński Jacek , Majsterek Ireneusz , Szymczyk Piotr , Szymański Paweł
Published: May 2020

A series of new tetrahydroacridine and 3,5-dichlorobenzoic acid hybrids with different spacers were designed, synthesized, and evaluated for their ability to inhibit both cholinesterase enzymes. Compounds 3a, 3b, 3f, and 3g exhibited selective butyrylcholinesterase (EqBuChE) inhibition with IC50 values ranging from 24 to 607 nM. Among them, compound 3b was the most active (IC50 = 24 nM). Additionally, 3c (IC50 for EeAChE = 25 nM and IC50 for EqBuChE = 123 nM) displayed dual cholinesterase inhibitory activity and was the most active compound against acetylcholinesterase (AChE). Active compound 3c was also tested for the ability to inhibit Aβ aggregation. Theoretical physicochemical properties of the compounds were calculated using ACD Labs Percepta and Chemaxon. A Lineweaver–Burk plot and docking study showed that 3c targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, 3c appears to possess neuroprotective activity and could be considered a free-radical scavenger. In addition, 3c did not cause DNA damage and was found to be less toxic than tacrine after oral administration; it also demonstrated little inhibitory activity towards hyaluronidase (HYAL), which may indicate that it possesses anti-inflammatory properties. The screening for new in vivo interactions between 3c and known receptors was realized by yeast three-hybrid technology (Y3H).
Photodegradation of Antibiotics by Noncovalent Porphyrin-Functionalized TiO2 in Water for the Bacterial Antibiotic Resistance Risk Management
Authors: Gaeta Massimiliano , Sanfilippo Giuseppe , Fraix Aurore , Sortino Giuseppe , Barcellona Matteo , Oliveri Conti Gea , Fragalà Maria Elena , Ferrante Margherita , Purrello Roberto , D’Urso Alessandro
Published: May 2020

Antibiotics represent essential drugs to contrast the insurgence of bacterial infections in humans and animals. Their extensive use in livestock farming, including aquaculture, has improved production performances and food safety. However, their overuse can implicate a risk of water pollution and related antimicrobial resistance. Consequently, innovative strategies for successfully removing antibiotic contaminants have to be advanced to protect human health. Among them, photodegradation TiO2-driven under solar irradiation appears not only as a promising method, but also a sustainable pathway. Hence, we evaluated several composite TiO2 powders with H2TCPP, CuTCPP, ZnTCPP, and SnT4 porphyrin for this scope in order to explore the effect of porphyrins sensitization on titanium dioxide. The synthesis was realized through a fully non-covalent functionalization in water at room conditions. The efficacy of obtained composite materials was also tested in photodegrading oxolinic acid and oxytetracycline in aqueous solution at micromolar concentrations. Under simulated solar irradiation, TiO2 functionalized with CuTCPP has shown encouraging results in the removal of oxytetracycline from water, by opening the way as new approaches to struggle against antibiotic’s pollution and, finally, to represent a new valuable tool of public health.
Effectiveness of Workplace Yoga Interventions to Reduce Perceived Stress in Employees: A Systematic Review and Meta-Analysis
Authors: Della Valle Elisabetta , Palermi Stefano , Aloe Irene , Marcantonio Roberto , Spera Rocco , Montagnani Stefania , Sirico Felice
Published: May 2020

Work-related stress represents a relevant public health issue and solution strategies are mandatory. Yoga is a common approach to manage stress and its effectiveness has been extensively confirmed. Therefore, this study aims systematically to review the effectiveness of Yoga interventions carried out at workplace on work-related stress among employees and to assess their impact quantitatively. Springerlink, MEDLINE, PubMed, CINAHL, Web of Science, Scopus, Cochrane CENTRAL and PEDro databases were searched. Clinical trials comparing workplace Yoga interventions to control groups, and evaluating perceived stress as outcome measure, were assessed for eligibility. All forms and styles of Yoga were considered for the analysis. Out of 3392 initially identified, 6 studies were included in the meta-analysis; 266 participants practicing Yoga interventions at worksite were compared to 221 subjects in control group. Included studies showed “some concerns” about different domains of source of bias. Quantitative analysis showed an overall effect size of −0.67 [95% confidence interval (CI): −0.86, −0.49] in favor of Yoga intervention in reducing stress outcome measures. Hence, workplace Yoga interventions were more effective when compared to no treatment in work-related stress management. Further high-quality studies are needed to improve the validity of these results and to specify more characteristics of the Yoga intervention, such as style, volume, and frequency.
Intelligent Marine Robotics Modelling, Simulation and Applications
Authors: Chin Cheng Siong , Cui Rongxin
Published: May 2020

Creating this inaugural Special Issue on Intelligent Marine Robotics Modelling, Simulation, and Applications is important due to the rapid technological advancement and the aim to reduce human involvement via artificial intelligence [...]
Data Imputation in Wireless Sensor Networks Using a Machine Learning-Based Virtual Sensor
Authors: Matusowsky Michael , Ramotsoela Daniel T. , Abu-Mahfouz Adnan M.
Published: May 2020

Data integrity in wireless sensor networks (WSN) is very important because incorrect or missing values could result in the system making suboptimal or catastrophic decisions. Data imputation allows for a system to counteract the effect of data loss by substituting faulty or missing sensor values with system-defined virtual values. This paper proposes a virtual sensor system that uses multi-layer perceptrons (MLP) to impute sensor values in a WSN. The MLP was trained using a genetic algorithm which efficiently reached an optimal solution for each sensor node. The system was able to successfully identify and replace physical sensor nodes that were disconnected from the network with corresponding virtual sensors. The virtual sensors imputed values with very high accuracies when compared to the physical sensor values.
Comparative Study of SPA Mud from “Bacino Idrominerario Omogeneo dei Colli Euganei (B.I.O.C.E.)–Italy” and Industrially Optimized Mud for Skin Applications
Authors: Bergamaschi Beatrice , Marzola Laura , Radice Matteo , Manfredini Stefano , Baldini Erika , Vicentini Chiara Beatrice , Marrocchino Elena , Molesini Sonia , Ziosi Paola , Vaccaro Carmela , Vertuani Silvia
Published: May 2020

The term “Salus per aquam (SPA) therapies” refers to therapeutic pathways that includes mud therapy. The therapeutic efficacy of a peloid depends on its chemical and mineralogical composition, as well as its technological properties. Considering the increasing use of clay-based products, it becomes essential to characterize peloids from a qualitative and quantitative point of view. Therefore, this research project aimed to develop a protocol that allows characterization of the chemical-physical composition of sludges collected from different areas of the Homogeneous Euganean Hills Hydromineral Basin (B.I.O.C.E.). The study established a comparative study both between different matrices and between the same matrices at different maturation times, including also a comparison with an industrialized product, that can be used at home, which maintains the characteristics of a natural mud. This research was developed studying the pH, grain size distribution, and chemical and mineralogical composition. Peloids are characterized by a neutral/basic pH and are divided into two categories from a granulometric point of view: The chemical composition allowed observation of numerous correlations between oxides present in the samples and to quantify the presence of heavy metals. Mineralogical analysis made it possible to identify and compare the composition of each sample, also according to the maturation time. Thanks to the methods adopted, important correlations were achieved.
Microstructure and Properties of the Copper Alloyed with Ag and Ti Powders Using Fiber Laser
Authors: Krupiński Mariusz , Smolarczyk Paulina Ewelina , Bonek Mirosław
Published: May 2020

The scope of the work covers the development of the relationship between the chemical composition of surface-modified copper and the diffusion of alloy elements as well as the microstructure and mechanical properties. This article presents the impact of laser alloying with titanium and silver powders on the microstructure and mechanical properties of copper. In order to investigate the phenomena occurring during the laser alloying process, microstructural studies were performed using scanning electron microscopy (SEM), optical microscopy, and energy dispersive x-ray spectroscopic (EDS) analysis of the chemical composition in micro-areas. In addition, to test the properties of the resulting alloy, abrasion resistance, hardness measurement at low loading force, and conductivity measurements were performed. As a result of alloying with Ag and Ti powders, three distinct zones were indeed recognized: re-melting zone (RZ), diffusion zone (DZ), and heat affected zone (HAZ). The surface modification that results from laser alloying increases the hardness as well as the abrasion resistance of the material. Overall, it was found that laser alloying with Ti powder increased the strength of the copper surface layer due to the formation of intermetallic phases (Cu3Ti2). It was also found that laser alloying with Ag powder changed the mechanical properties of the surface layer due to the solid solution strengthening.
A Study on Microstructure, Residual Stresses and Stress Corrosion Cracking of Repair Welding on 304 Stainless Steel: Part II-Effects of Reinforcement Height
Authors: Hu Xiaodong , Jiang Hao-Yong , Luo Yun , Jin Qiang , Peng Wei , Yi Chun-Mei
Published: May 2020

The repair reinforcement height is an important parameter of repair welding, which may have a great influence on structural integrity. In this paper, the effects of repair welding reinforcement height on the microstructure, microhardness, residual stresses and stress corrosion cracking (SCC) behavior of a 304 stainless steel-repaired joint were investigated by experimentation and simulation. With an increase of the repair weld reinforcement height, the δ ferrite content in weld and fusion zone is obviously reduced, and the ferrite shape is gradually changed from the skeleton to the worm shape. With the increase of repair welding reinforcement height, the microhardness and residual stresses decrease gradually. The tensile strength and elongation for higher repair weld reinforcement height are larger than those with lower repair weld reinforcement height. The higher the repair weld reinforcement height, the harder it is for SCC to occur. The repair welding in 304 stainless steel is recommended to be repaired no more than two times.
A Novel Approach to the Analysis of Under Sleeper Pads (USP) Applied in the Ballasted Track Structures
Authors: Zbiciak Artur , Kraśkiewicz Cezary , Al Sabouni-Zawadzka Anna , Pełczyński Jan , Dudziak Sławomir
Published: May 2020

The present paper is dedicated to the analysis of under sleeper pads (USP), which are resilient elements used in ballasted track systems as vibration isolators. Four types of USP are considered. The authors present the results of laboratory tests, which are then used as input values for the finite element (FE) and mechanical model of the structure. A special focus is put on the description of an original four-degree-of-freedom (4DoF) mechanical model of the system that includes a fractional rheological model of USP. Using the proposed approaches, the dynamic characteristics of under sleeper pads are determined, and conclusions on vibration isolation effectiveness are drawn.
Application of a Prototype Thermoplastic Treatment Line in Order to Design a Thermal Treatment Process of Forgings with the Use of the Heat from the Forging Process
Authors: Hawryluk Marek , Gronostajski Zbigniew , Zwierzchowski Maciej , Jabłoński Paweł , Barełkowski Artur , Krawczyk Jakub , Jaśkiewicz Karol , Rychlik Marcin
Published: May 2020

The global production of die forgings is an important branch of the motor industry for obvious reasons, resulting from the very good mechanical properties of the forged products. The expectations of the recipients, beside the implementation of the forging process, include also a range of supplementary procedures, such as finishing treatment including shot blasting, thermal treatment, and machining, in order to ensure the proper quality of the provided semi-product or the ready detail for the assembly line. Especially important in the aspect of the operational properties of the products is the thermal treatment of the forgings, which can be implemented in many variants, depending on the expected results. Unfortunately, a treatment of this type, realized separately after the forging process, is very time and energy-consuming; additionally, it significantly raises the production costs due to the increased energy consumption resulting from the necessity of repeated heating of the forgings for such thermal treatment. The article reviews the most frequently applied (separately, after the forging process) thermal treatments for die forgings together with the devices/lines assigned for them, as well as presents an alternative (thermoplastic) method of forging production with the use of the forging heat. The paper also presents a prototype semi-industrial controlled cooling line developed by the authors, which allows the development of the assumed heat treatment of forgings directly after forging with the use of forging heat, together with sample results of conducted tests.
Equilibria and Stability of One Class of Positive Dynamic Systems with Entropy Operator: Application to Investment Dynamics Modeling
Authors: Popkov Yuri S.
Published: May 2020

Dynamical systems with entropy operator (DSEO) form a special class of dynamical systems whose nonlinear properties are described by the perturbed mathematical programming problem with entropy objective functions. A subclass of DSEO is the system with positive state coordinates (PDSEO), which are used as mathematical models of the spatiotemporal evolution of demographic and economic processes, dynamic image restoration procedures in computer tomography and machine learning. A mathematical model of the PDSEO with a connectivity parameter characterizing the influence of the entropy operator on the dynamic properties of the system is constructed. PDSEO can have positive stationary states of various classes depending on the number of positive components in the state vector. Classes with p positive components of the state vector ( p ≤ n , where n is the order of the system) are considered. The framework of formal power series and the method of successive approximations for the formation of existence conditions of stationary states are developed. The conditions of existence are obtained in the form of relations between the parameters of the system. We used the method of differential Bellman inequalities to study the stability of classes of stationary states in a limited region of phase space. The parametric conditions of instability of the zero stationary state and p positive stationary states depending on the connectivity parameter are obtained. The framework of formal power series and the method of successive approximations for the formation of existence conditions and classification of stationary states are developed. The stability conditions “in large” stationary states are obtained, based on the method of differential Bellman inequalities. The developed methods of existence, classification and stability are illustrated by the analysis of the dynamic properties of the economic model with stochastic investment exchange. Positive stationary states characterize the profitability of economic subsystems. The conditions of profitability and their stability for all subsystems in the system and their various groups are obtained.
The Buttressed Walls Problem: An Application of a Hybrid Clustering Particle Swarm Optimization Algorithm
Authors: García José , Martí José V. , Yepes Víctor
Published: May 2020

The design of reinforced earth retaining walls is a combinatorial optimization problem of interest due to practical applications regarding the cost savings involved in the design and the optimization in the amount of CO 2 emissions generated in its construction. On the other hand, this problem presents important challenges in computational complexity since it involves 32 design variables; therefore we have in the order of 10 20 possible combinations. In this article, we propose a hybrid algorithm in which the particle swarm optimization method is integrated that solves optimization problems in continuous spaces with the db-scan clustering technique, with the aim of addressing the combinatorial problem of the design of reinforced earth retaining walls. This algorithm optimizes two objective functions: the carbon emissions embedded and the economic cost of reinforced concrete walls. To assess the contribution of the db-scan operator in the optimization process, a random operator was designed. The best solutions, the averages, and the interquartile ranges of the obtained distributions are compared. The db-scan algorithm was then compared with a hybrid version that uses k-means as the discretization method and with a discrete implementation of the harmony search algorithm. The results indicate that the db-scan operator significantly improves the quality of the solutions and that the proposed metaheuristic shows competitive results with respect to the harmony search algorithm.
A Semantic Framework to Debug Parallel Lazy Functional Languages
Authors: de la Encina Alberto , Hidalgo-Herrero Mercedes , Llana Luis , Rubio Fernando
Published: May 2020

It is not easy to debug lazy functional programs. The reason is that laziness and higher-order complicates basic debugging strategies. Although there exist several debuggers for sequential lazy languages, dealing with parallel languages is much harder. In this case, it is important to implement debugging platforms for parallel extensions, but it is also important to provide theoretical foundations to simplify the task of understanding the debugging process. In this work, we deal with the debugging process in two parallel languages that extend the lazy language Haskell. In particular, we provide an operational semantics that allows us to reason about our parallel extension of the sequential debugger Hood. In addition, we show how we can use it to analyze the amount of speculative work done by the processes, so that it can be used to optimize their use of resources.
Combining DEA and ARIMA Models for Partner Selection in the Supply Chain of Vietnam’s Construction Industry
Authors: Nguyen Han-Khanh
Published: May 2020

The competition between enterprises in the construction market is fierce. If enterprises are unable to afford financial and technological capabilities, they could go bankrupt. Therefore, the implementation of alliances between businesses can help increase their competitiveness. In this study, the authors simultaneously used data envelopment analysis (DEA), the Grey model (GM (1,1)), and autoregressive integrated moving average (ARIMA) to choose a suitable strategic partner to boost the strength of each business and cut the cost of transportation and personnel in an attempt to help managers come up with suitable solutions, offer sustainability, and develop creative management. The results show that the chosen solution improves the business efficiency of construction businesses and offers cost savings on materials, production, and transportation. Management agencies can use the results of this study to propose suitable orientations, strengthen decision-making, and ensure strategic planning to develop the construction sector in Vietnam.
Submuscular and Pre-pectoral ADM Assisted Immediate Breast Reconstruction: A Literature Review
Authors: Cuomo Roberto
Published: May 2020

Background and objectives: Breast cancer treatment has deeply changed in the last fifty years. Acellular dermal matrices (ADMs) were introduced for breast reconstruction, with encouraging results, but with conflicting reports too. The present paper aims to summarize the current data on breast reconstruction using acellular dermal matrices. Materials and Methods: We reviewed the literature regarding the use of ADM-assisted implant-based breast reconstruction. Results: The main techniques were analyzed and described. Conclusions: Several authors have recently reported positive results. Nevertheless, an increased complications’ rate has been reported by other authors. Higher cost compared to not-ADM-assisted breast reconstruction is another concern.
New Bactericide Orthodonthic Archwire: NiTi with Silver Nanoparticles
Authors: Gil F. Javier , Espinar-Escalona Eduardo , Clusellas Nuria , Fernandez-Bozal Javier , Artes-Ribas Montserrat , Puigdollers Andreu
Published: May 2020

A potential new bactericide treatment for NiTi orthodontic archwires based in the electrodeposition of silver nanoparticles on the surface was studied. Twenty-five archwires were treated by electrodeposition, obtaining nanoparticles of silver embedded on the archwire surface. These were evaluated in order to investigate the possible changes on the superelastic characteristics (critical temperatures and stresses), the nickel ion release, and the bacteria culture behavior. The chemical composition was analyzed by Energy Dispersive X-Ray Spectroscopy-microanalysis; the singular temperatures of the martensitic transformation were obtained by a flow calorimeter. Induced martensitic transformation stresses were obtained by mechanical testing apparatus. Nickel ion release was analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) equipment using artificial saliva solution at 37 °C. Bacterial tests were studied with the most used oral bacterial strains: Streptococcus sanguinis and Lactobacillus salivarius. NiTi samples were immersed in bacterial suspensions for 2 h at 37 °C. Adhered bacteria were separated and seeded on agar plates: Tood-Hewitt (TH) and Man-Rogosa-Sharpe (MRS) for S. sanguinis and for L.salivarius, respectively. These were then incubated at 37 °C for 1 day and the colonies were analyzed. The results showed that the transformation temperatures and the critical stresses have not statistically significant differences. Likewise, nickel ion release at different immersion times in saliva at 37 °C does not present changes between the original and treated with silver nanoparticles archwires. Bacteria culture results showed that the reduction of the bacteria due to the presence to the nanoparticles of silver is higher than 90%. Consequently, the new treatment with nanoparticles of silver could be a good candidate as bactericidic orthodontic archwire.
A Microfluidic Diagnostic Device Capable of Autonomous Sample Mixing and Dispensing for the Simultaneous Genetic Detection of Multiple Plant Viruses
Authors: Natsuhara Daigo , Takishita Keisuke , Tanaka Kisuke , Kage Azusa , Suzuki Ryoji , Mizukami Yuko , Saka Norikuni , Nagai Moeto , Shibata Takayuki
Published: May 2020

As an efficient approach to risk management in agriculture, the elimination of losses due to plant diseases and insect pests is one of the most important and urgent technological challenges for improving the crop yield. Therefore, we have developed a polydimethylsiloxane (PDMS)-based microfluidic device for the multiplex genetic diagnosis of plant diseases and pests. It offers unique features, such as rapid detection, portability, simplicity, and the low-cost genetic diagnosis of a wide variety of plant viruses. In this study, to realize such a diagnostic device, we developed a method for the autonomous dispensing of fluid into a microchamber array, which was integrated with a set of three passive stop valves with different burst pressures (referred to as phaseguides) to facilitate precise fluid handling. Additionally, we estimated the mixing efficiencies of several types of passive mixers (referred to as chaotic mixers), which were integrated into a microchannel, through experimental and computational analyses. We first demonstrated the ability of the fabricated diagnostic devices to detect DNA-based plant viruses from an infected tomato crop based on the loop-mediated isothermal amplification (LAMP) method. Moreover, we demonstrated the simultaneous detection of RNA-based plant viruses, which can infect cucurbits, by using the reverse transcription LAMP (RT-LAMP) method. The multiplex RT-LAMP assays revealed that multiple RNA viruses extracted from diseased cucumber leaves were successfully detected within 60 min, without any cross-contamination between reaction microchambers, on our diagnostic device.
Neospora caninum: Differential Proteome of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294
Authors: Winzer Pablo , Müller Joachim , Imhof Dennis , Ritler Dominic , Uldry Anne-Christine , Braga-Lagache Sophie , Heller Manfred , Ojo Kayode K. , Van Voorhis Wesley C. , Ortega-Mora Luis-Miguel , Hemphill Andrew
Published: May 2020

Background: the apicomplexan parasite Neospora caninum causes important reproductive problems in farm animals, most notably in cattle. After infection via oocysts or tissue cysts, rapidly dividing tachyzoites infect various tissues and organs, and in immunocompetent hosts, they differentiate into slowly dividing bradyzoites, which form tissue cysts and constitute a resting stage persisting within infected tissues. Bumped kinase inhibitors (BKIs) of calcium dependent protein kinase 1 are promising drug candidates for the treatment of Neospora infections. BKI-1294 exposure of cell cultures infected with N. caninum tachyzoites results in the formation of massive multinucleated complexes (MNCs) containing numerous newly formed zoites, which remain viable for extended periods of time under drug pressure in vitro. MNC and tachyzoites exhibit considerable antigenic and structural differences. Methods: Using shotgun mass spectrometry, we compared the proteomes of tachyzoites to BKI-1294 induced MNCs, and analyzed the mRNA expression levels of selected genes in both stages. Results: More than half of the identified proteins are downregulated in MNCs as compared to tachyzoites. Only 12 proteins are upregulated, the majority of them containing SAG1 related sequence (SRS) domains, and some also known to be expressed in bradyzoites Conclusions: MNCs exhibit a proteome different from tachyzoites, share some bradyzoite-like features, but may constitute a third stage, which remains viable and ensures survival under adverse conditions such as drug pressure. We propose the term “baryzoites” for this stage (from Greek βαρυσ = massive, bulky, heavy, inert).
Applications of Graphene and Its Derivatives in the Upstream Oil and Gas Industry: A Systematic Review
Authors: Fu Lipei , Liao Kaili , Tang Bo , Jiang Lujun , Huang Weiqiu
Published: May 2020

Graphene and its derivatives, with their unique two-dimensional structures and excellent physical and chemical properties, have been an international research hotspot both in the research community and industry. However, in application-oriented research in the oil and gas industry they have only drawn attention in the past several years. Their excellent optical, electrical, thermal and mechanical performance make them great candidates for use in oil and gas exploration, drilling, production, and transportation. Combined with the actual requirements for well working fluids, chemical enhanced oil recovery, heavy oil recovery, profile control and water shutoff, tracers, oily wastewater treatment, pipeline corrosion prevention treatment, and tools and apparatus, etc., this paper introduces the behavior in water and toxicity to organisms of graphene and its derivatives in detail, and comprehensively reviews the research progress of graphene materials in the upstream oil and gas industry. Based on this, suggestions were put forward for the future research. This work is useful to the in-depth mechanism research and application scope broadening research in the upstream oil and gas industry.
Iron Oxide Nanoparticles as Carriers for DOX and Magnetic Hyperthermia after Intratumoral Application into Breast Cancer in Mice: Impact and Future Perspectives
Authors: Piehler Susann , Dähring Heidi , Grandke Julia , Göring Julia , Couleaud Pierre , Aires Antonio , Cortajarena Aitziber L. , Courty José , Latorre Alfonso , Somoza Álvaro , Teichgräber Ulf , Hilger Ingrid
Published: May 2020

There is still a need for improving the treatment of breast cancer with doxorubicin (DOX). In this paper, we functionalized magnetic nanoparticles (MNPs) with DOX and studied the DOX-induced antitumor effects in breast cancer cells (BT474) in the presence of magnetic hyperthermia (43 °C, 1 h). We show that i) intratumoral application of DOX-functionalized MNPs (at least at a concentration of 9.6 nmol DOX/100 mm3 tumor volume) combined with magnetic hyperthermia favors tumor regression in vivo, and there is evidence for an increased effect compared to magnetic hyperthermia alone or to the intratumoral application of free DOX and ii) the presence of the pseudopeptide NucAnt (N6L) on the MNP surface might well be beneficial in its function as carrier for MNP internalization into breast cancer cells in vitro, which could further augment the possibility of the induction of intracellular heating spots and cell death in the future.
Pancreatic Cancer and Cachexia—Metabolic Mechanisms and Novel Insights
Authors: Poulia Kalliopi Anna , Sarantis Panagiotis , Antoniadou Dimitra , Koustas Evangelos , Papadimitropoulou Adriana , Papavassiliou Athanasios G. , Karamouzis Michalis V.
Published: May 2020

Cachexia is a major characteristic of multiple non-malignant diseases, advanced and metastatic cancers and it is highly prevalent in pancreatic cancer, affecting almost 70%–80% of the patients. Cancer cachexia is a multifactorial condition accompanied by compromised appetite and changes in body composition, i.e., loss of fat. It is associated with lower effectiveness of treatment, compromised quality of life, and higher mortality. Understanding the complex pathways underlying the pathophysiology of cancer cachexia, new therapeutic targets will be unraveled. The interplay between tumor and host factors, such as cytokines, holds a central role in cachexia pathophysiology. Cytokines are possibly responsible for anorexia, hypermetabolism, muscle proteolysis, and apoptosis. In particular, cachexia in pancreatic cancer might be the result of the surgical removal of pancreas parts. In recent years, many studies have been carried out to identify an effective treatment algorithm for cachexia. Choosing the most appropriate treatment, the clinical effect and the risk of adverse effects should be taken under consideration. The purpose of this review is to highlight the pathophysiological mechanisms as well as the current ways of cachexia treatment in the pharmaceutical and the nutrition field.
An Experimental Comparison of the Impact of ‘Warning’ and ‘Health Star Rating’ FoP Labels on Adolescents’ Choice of Breakfast Cereals in New Zealand
Authors: Hamlin Robert , Hamlin Benjamin
Published: May 2020

This research investigated the performance of the red, octagonal Vienna Convention traffic ‘STOP’ sign as a front of pack (FoP) warning nutritional label. While the Vienna Convention traffic light system is an established FoP label, the potential of the ‘STOP’ sign in the role has not been investigated. The performance of the ‘STOP’ label was compared with that of a single star (low nutritional value) Australasian Health Star Rating (HSR) label using a fractionally replicated Latin square design. The labels were presented on choice diads of cold breakfast cereal packets. The sample of 240 adolescents aged 16–18 was drawn from a secondary school in the South Island of New Zealand. A large and significant main effect was observed at the p < 0.01 level for the difference between the ’STOP’ sign and the control condition (no nutritional FoP label), and at p < 0.05 for the difference between the HSR and the ‘STOP’ label. There was no significant difference between the HSR FoP and the control condition. A significant non-additivity (interaction) (p < 0.01) was also observed via the fractional replication. The results indicate that the Vienna Convention ‘STOP’ sign is worthy of further research with regard to its potential as an FoP nutritional label.
Valid Assessment of Carbohydrate Intolerance and the Need for a Distinction to Carbohydrate Malabsorption. Comment on “Roles of Lactose and Fructose Malabsorption and Dietary Outcomes in Children Presenting with Chronic Abdominal Pain.” Nutrients 2019, 11, 3063
Authors: Hammer Karin , Hammer Johann
Published: May 2020

We have read with interest the recent paper by Posovszky and Roesler et al [...]
The Gluten Free Diet’s Impact on Growth in Children with Celiac Disease in Two Different Countries
Authors: Sansotta Naire , Guandalini Stefano , Romano Simone , Amirikian Karine , Cipolli Marco , Tridello Gloria , Barzaghi Silvia , Jericho Hilary
Published: May 2020

The effects of gluten free diet (GFD) on body mass index (BMI) and growth parameters in pediatric patients with celiac disease (CD) and their dependence on different socio-cultural environments are poorly known. We conducted an international retrospective study on celiac patients diagnosed at the University of Verona, Italy, and at the University of Chicago, Chicago, IL, USA, as underweight. A total of 140 celiac children and 140 controls (mean age 8.4 years) were enrolled in Chicago; 125 celiac children and 125 controls (mean age 7.3 years, NS) in Verona. At time of diagnosis, Italian celiac children had a weight slightly lower (p = 0.060) and a BMI z-score significantly (p < 0.001) lower than their American counterparts. On GFD, Italian celiac children showed an increased prevalence of both underweight (19%) as well as overweight (9%), while American children showed a decrease prevalence of overweight/obese. We concluded that while the GFD had a similar impact on growth of celiac children in both countries, the BMI z-score rose more in American than in Italian celiac children. Additionally, in Italy, there was an alarming increase in the proportion of celiac children becoming underweight. We speculate that lifestyle and cultural differences may explain the observed variations.
Metabolic Impacts of Confinement during the COVID-19 Pandemic Due to Modified Diet and Physical Activity Habits
Authors: Martinez-Ferran María , de la Guía-Galipienso Fernando , Sanchis-Gomar Fabián , Pareja-Galeano Helios
Published: May 2020

While the detrimental effects of a chronic positive energy balance due to a sedentary lifestyle have been well established, the impacts of a short period of abruptly reduced physical activity and overeating arising from strict confinement due to the COVID-19 pandemic will soon start to emerge. To reasonably anticipate major consequences according to the available evidence, we hereby review the literature for studies that have explored the health impacts of several weeks of a reduction in physical activity and daily step-count combined with modified eating habits. These studies identify as main metabolic consequences increases in insulin resistance, total body fat, abdominal fat and inflammatory cytokines. All these factors have been strongly associated with the development of metabolic syndrome, which in turn increases the risk of multiple chronic diseases. A plausible mechanism involved in these impacts could be a positive energy balance promoted by maintaining usual dietary intake while reducing energy expenditure. This means that just as calorie intake restriction could help mitigate the deleterious impacts of a bout of physical inactivity, overeating under conditions of home confinement is very likely to exacerbate these consequences. Moreover, hypertension, diabetes, and cardiovascular disease have been identified as potential risk factors for more severely ill patients with COVID-19. Thus, adequate control of metabolic disorders could be important to reduce the risk of severe COVID-19.
A Brief Overview of Restricted Mean Survival Time Estimators and Associated Variances
Authors: Nemes Szilárd , Bülow Erik , Gustavsson Andreas
Published: May 2020

Restricted Mean Survival Time ( R M S T ) experiences a renaissance and is advocated as a model-free, easy to interpret alternative to proportional hazards regression and hazard rates with implication in causal inference. Estimation of R M S T and associated variance is mainly done by numerical integration of Kaplan–Meier curves. In this paper we briefly review the two main alternatives to the Kaplan–Meier method; analysis based on pseudo-observations, and the flexible parametric survival method. Using computer simulations, we assess the efficacy of the three methods compared to a fully parametric approach where the distribution of survival times is known. Thereafter, the three methods are directly compared without any distributional assumption for the survival data. Generally, flexible parametric survival methods outperform both competitors, however the differences are small.
Evidence of the Mechanism by Which Polyomaviruses Exploit the Extracellular Vesicle Delivery System during Infection
Authors: Giannecchini Simone
Published: May 2020

Increasing evidence suggests that human viruses can hijack extracellular vesicles (EVs) to deliver proteins, mRNAs, microRNAs (miRNAs) and whole viral particles during viral persistence in the host. Human polyomavirus (PyV) miRNAs, which downregulate large T-antigen expression and target host factors, help the virus escape immune elimination and may have roles in the success of viral persistence/replication and the development of diseases. In this context, several investigations have detected PyV miRNAs in EVs obtained from cell culture supernatants after viral infection, demonstrating the ability of these vesicles to deliver miRNAs to uninfected cells, potentially counteracting new viral infection. Additionally, PyV miRNAs have been identified in EVs derived from the biological fluids of clinical samples obtained from patients with or at risk of severe PyV-associated diseases and from asymptomatic control healthy subjects. Interestingly, PyV miRNAs were found to be circulating in blood, urine, cerebrospinal fluid, and saliva samples from patients despite their PyV DNA status. Recently, the association between EVs and PyV viral particles was reported, demonstrating the ability of PyV viral particles to enter the cell without natural receptor-mediated entry and evade antibody-mediated neutralization or to be neutralized at a step different from that of the neutralization of naked whole viral particles. All these data point toward a potential role of the association between PyVs with EVs in viral persistence, suggesting that further work to define the implication of this interaction in viral reactivation is warranted.
The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation
Authors: George Parakkal Jovvian , Tai Wanbo , Du Lanying , Lustigman Sara
Published: May 2020

Vaccination is one of the most successful strategies to prevent human infectious diseases. Combinatorial adjuvants have gained increasing interest as they can stimulate multiple immune pathways and enhance the vaccine efficacy of subunit vaccines. We investigated the adjuvanticity of Aluminum (alum) in combination with rASP-1, a protein adjuvant, using the Middle East respiratory syndrome coronavirus MERS-CoV receptor-binding-domain (RBD) vaccine antigen. A highly enhanced anti-MERS-CoV neutralizing antibody response was induced when mice were immunized with rASP-1 and the alum-adjuvanted RBD vaccine in two separate injection sites as compared to mice immunized with RBD + rASP-1 + alum formulated into a single inoculum. The antibodies produced also significantly inhibited the binding of RBD to its cell-associated receptor. Moreover, immunization with rASP-1 co-administered with the alum-adjuvanted RBD vaccine in separate sites resulted in an enhanced frequency of TfH and GC B cells within the draining lymph nodes, both of which were positively associated with the titers of the neutralizing antibody response related to anti-MERS-CoV protective immunity. Our findings not only indicate that this unique combinatorial adjuvanted RBD vaccine regimen improved the immunogenicity of RBD, but also point to the importance of utilizing combinatorial adjuvants for the induction of synergistic protective immune responses.
Chimeric Vaccines Designed by Immunoinformatics-Activated Polyfunctional and Memory T Cells That Trigger Protection against Experimental Visceral Leishmaniasis
Authors: Brito Rory Cristiane Fortes De , Ruiz Jeronimo Conceição , Cardoso Jamille Mirelle de Oliveira , Ostolin Thais Lopes Valentim Di Paschoale , Reis Levi Eduardo Soares , Mathias Fernando Augusto Siqueira , Aguiar-Soares Rodrigo Dian de Oliveira , Roatt Bruno Mendes , Corrêa-Oliveira Rodrigo , Resende Daniela de Melo , Reis Alexandre Barbosa
Published: May 2020

Many vaccine candidates against visceral leishmaniasis (VL) have been proposed; however, to date, none of them have been efficacious for the human or canine disease. On this basis, the design of leishmaniasis vaccines has been constantly changing, and the use of approaches to select specific epitopes seems to be crucial in this scenario. The ability to predict T cell-specific epitopes makes immunoinformatics an even more necessary approach, as in VL an efficient immune response against the parasite is triggered by T lymphocytes in response to Leishmania spp. immunogenic antigens. Moreover, the success of vaccines depends on the capacity to generate long-lasting memory and polyfunctional cells that are able to eliminate the parasite. In this sense, our study used a combination of different approaches to develop potential chimera candidate vaccines against VL. The first point was to identify the most immunogenic epitopes of Leishmania infantum proteins and construct chimeras composed of Major histocompatibility complex (MHC) class I and II epitopes. For this, we used immunoinformatics features. Following this, we validated these chimeras in a murine model in a thorough memory study and multifunctionality of T cells that contribute to a better elucidation of the immunological protective mechanisms of polyepitope vaccines (chimera A and B) using multicolor flow cytometry. Our results showed that in silico-designed chimeras can elicit polyfunctional T cells producing T helper (Th)1 cytokines, a strong immune response against Leishmania antigen, and the generation of central and effector memory T cells in the spleen cells of vaccinated animals that was able to reduce the parasite burden in this organ. These findings contribute two potential candidate vaccines against VL that can be used in further studies, and help in this complex field of vaccine development against this challenging parasite.
The challenge of pain identification, assessment, and management in people with dementia: a qualitative study
Authors: Bullock Laurna , Chew-Graham Carolyn A , Bedson John , Bartlam Bernadette , Campbell Paul
Published: May 2020

Background

Painful conditions are common in older adults, including people with dementia. The symptoms associated with dementia (for example, diminished language capacity, memory impairment, and behavioural changes), however, may lead to the suboptimal identification, assessment, and management of pain. Research has yet to qualitatively explore pain management for community-dwelling people with dementia.

Aim

To explore pain identification, assessment, and management for community-dwelling people with dementia.

Design & setting

A qualitative study was undertaken, set in England.

Method

Semi-structured interviews took place with people with dementia, family caregivers, GPs, and old-age psychiatrists. Data were analysed thematically.

Results

Interviews were conducted with eight people with dementia, nine family caregivers, nine GPs, and five old-age psychiatrists. Three themes were identified that related to pain identification and assessment: gathering information to identify pain; the importance of knowing the person; and the use of pain assessment tools. A further three themes were identified that related to pain management: non-drug strategies; concerns related to analgesic medications; and responsibility of the caregiver to manage pain.

Conclusion

Identifying and assessing the pain experienced by people with dementia was challenging. Most people with dementia, family caregivers, and healthcare professionals supported non-drug strategies to manage pain. The minimal concerns associated with non-drug strategies contrasted the multifactorial concerns associated with analgesic treatment for people with dementia. Given the complexity of pain identification, assessment, and management, primary care should work together with family caregivers and community services, with case finding for pain being considered in all assessment and management plans.
Determinantes de salud en la población de Tiquipa y Chiluyo en Bolivia
Authors: Cori Aruquipa Karina Mayra
Published: May 2020

Introducción: La salud y la enfermedad están determinadas por varios factores la exposición ambiental, vivienda, educación y nivel socioeconómico, mismos que fueron expuestos en 1974 cuando se publicó el informe Lalonde. Bolivia no queda al margen, por lo que se realizan políticas de salud y campañas para poder combatir los problemas. Los determinantes de la salud son aquellos factores que ejercen influencia sobre la salud de las personas e influyen en diferentes niveles de organización, determinando el estado de salud de la población. Objetivo: Establecer los determinantes de la salud de las comunidades de Tiquipa y Chiluyo del sector de Chojasivi en el año 2018. Métodos: Se realizó un estudio descriptivo, cuantitativo, transversal y retrospectivo. Resultados: la comunidad de Chiluyo cuenta con 62 familias y una población de 241 personas, la comunidad de Tiquipa consta de 76 familias con 266 habitantes. Las familias tienen una condición de vida en un rango de riesgo medio, con una cobertura en sus necesidades básicas. Conclusión: Los determinantes que fueron evaluados demuestran que son familias que habitan en una vivienda propia que solventan solo las necesidades básicas con una alimentación promedio y con una educación deficiente.