bluuebunny/crossref_metadata_2025 huggingface dataset:
Smart Learning Technologization in the Economy 5.0—The Polish Perspective
Authors: Sułkowski Łukasz , Kolasińska-Morawska Katarzyna , Seliga Robert , Morawski Paweł
Published: June 2021

Contemporary higher education is gradually transforming. Meetings of teachers and students from lecture halls are increasingly moving into the digital space of the Internet, adopting the formula of distance learning. The advent of Society 5.0 and Economy 5.0 will imply further changes. The necessity to integrate the real and virtual world, increased demand for information, limited time resources, and the need to combine professional work with education will cause higher education, in order to prepare future citizens to function in the area of sharing resources, to be forced to further adaptive transformations. The subject of this article is the analysis of the impact of technology on changes in higher education with an indication of the model of future paths of education in the Economy 5.0 trend. The source of the article was exploratory research of secondary sources, including books, articles, and reports, which were subjected to a critical analysis of the content. The obtained results made it possible to design and implement an explanatory study among students based on the CAWI methodology. The collected material became the basis for the authors to prepare a proposal for a model of future educational paths in accordance with the Economy 5.0 trend in which the flexibility of place and time, customization of the offer, cooperation, adaptability of teaching methods and instruments, and the proactive role of the teacher as a mentor and trainer constitute a set of set guidelines in the teaching model of the future. This model will be able to be used by universities and training institutions in the field of professionalization of the management of teaching and organizational processes.
Formation of the Optimal Load of High School Students Using a Genetic Algorithm and a Neural Network
Authors: Dogadina Elena Petrovna , Smirnov Michael Viktorovich , Osipov Aleksey Viktorovich , Suvorov Stanislav Vadimovich
Published: June 2021

The problem of the effectiveness of teaching can be successfully solved only if the high quality of lessons is supported by well-organized homework of students. The question of homework occupies one of the main places in educational activities since this question is directly related to the health of the child. A competent approach to minimizing the time for completing homework, taking into account the maximum efficiency obtained from the learning process, can preserve the health of students to some extent. The article describes a method for obtaining the most comfortable results of the process of completing homework, which are a Pareto set. This method is implemented using a genetic algorithm and queuing theory, and the selection of homework is carried out on the basis of intellectual analysis of the text of tasks and is a scale of a certain range. The proposed algorithm successfully obtains the solutions of the Pareto set and minimizes the efforts of school students while achieving the maximum efficiency of the educational process to preserve their health. Compared with other known algorithms, the results obtained show that the proposed algorithm demonstrates fairly accurate optimization characteristics presented in the form of a Pareto set. Furthermore, combining a genetic algorithm, queuing theory apparatus, and a neural network makes it possible to model the studied subject area more accurately.
P-Norm Attention Deep CORAL: Extending Correlation Alignment Using Attention and the P-Norm Loss Function
Authors: Wang Zhi-Yong , Kang Dae-Ki
Published: June 2021

CORrelation ALignment (CORAL) is an unsupervised domain adaptation method that uses a linear transformation to align the covariances of source and target domains. Deep CORAL extends CORAL with a nonlinear transformation using a deep neural network and adds CORAL loss as a part of the total loss to align the covariances of source and target domains. However, there are still two problems to be solved in Deep CORAL: features extracted from AlexNet are not always a good representation of the original data, as well as joint training combined with both the classification and CORAL loss may not be efficient enough to align the distribution of the source and target domain. In this paper, we proposed two strategies: attention to improve the quality of feature maps and the p-norm loss function to align the distribution of the source and target features, further reducing the offset caused by the classification loss function. Experiments on the Office-31 dataset indicate that our proposed methodologies improved Deep CORAL in terms of performance.
Influence of Intermittent Parathyroid Hormone (PTH) Administration on the Outcomes of Orthodontic Tooth Movement—A Systematic Review
Authors: Khurshid Zohaib , Asiri Faris Yahya
Published: June 2021

Objective: The aim of this review is to summarize the effects of local and systemic PTH administration on periodontal tissues during orthodontic tooth movement. Materials and methods: An electronic search was conducted on the following databases: PubMed/MEDLINE, Google Scholar, SCOPUS and Embase. On PubMed/MEDLINE, the Medical Subject Headings (MeSH) keywords used were: “orthodontic tooth movement” OR (“tooth” (All Fields) AND “tooth movement” (All Fields)) OR “tooth movement” (All Fields)) AND (“parathyroid hormone”); all studies included using CONSORT. Results: After elimination of duplicates and articles not meeting our inclusion criteria, seven animal studies were included in this review. Although the majority of the studies suggest that PTH may a have a favorable outcome on OTM, most studies were found to have several sources of bias. Conclusion: Animal studies with minimal bias and long-term clinical studies are needed to ascertain the efficacy of intermittent PTH administration in improving the rate and retention of OTM.
Force–Time Characteristics of Dynamic and Isometric Muscle Actions: Association with Muscle Architecture in Female Athletes
Authors: Gaspari Vasiliki , Bogdanis Gregory C. , Panidi Ioli , Giannakopoulou Georgia , Terzis Gerasimos , Kotsala Helen , Donti Anastasia , Donti Olyvia
Published: June 2021

The association between force–time characteristics of isometric leg press (ILP) and countermovement jump (CMJ) with vastus lateralis (VL) muscle architecture, was examined in 19 female athletes (aged 23.2 ± 5.4 years). Peak force (PF), average rate of force development (ARFD) and rate of force development (RFD) at different time epochs were calculated from the force–time curve, as well as CMJ jump height and power. Significant correlations were found between ILP-PF and CMJ power (r = 0.658, p < 0.01), while both variables were correlated with VL thickness and fascicle length (r = 0.471 to 0.648, p < 0.05). Significant correlations were also observed between ILP-RFD epochs and VL fascicle length (r = 0.565 to 0.646, p < 0.05) and between CMJ height with VL thickness (r = 0.523, p < 0.05). Furthermore, positive correlations were found between ILP and CMJ in ARFD (r = 0.625, p < 0.01) and RFD epochs (r = 0.464 to 0.566, p < 0.05). ILP-PF and muscle thickness accounted for 52.8% (p = 0.002) of the variance in CMJ power. These results suggest that isometric force time characteristics are associated with power generation during dynamic muscle actions. Furthermore, VL muscle thickness and fascicle length are associated with rapid force production in female athletes, irrespective of the type of muscle action.
Internal Mechanics of a Subject-Specific Wrist in the Sagittal versus Dart-Throwing Motion Plane in Adult and Elder Models: Finite Element Analyses
Authors: Mahpari Vered , Levanon Yafa , Kaufman-Cohen Yael , Zilberman Meital , Portnoy Sigal
Published: June 2021

Introduction: Most of the wrist motions occur in a diagonal plane of motion, termed the dart-throwing motion (DTM) plane; it is thought to be more stable compared with movement in the sagittal plane. However, the effect of the altered carpus motion during DTM on the stress distribution at the radiocarpal joint has yet to be explored. Aim: To calculate and compare the stresses between the radius and two carpal bones (the scaphoid and the lunate) in two wrist positions, extension and radial extension (position in DTM), and between an adult and an elder model. Methods: A healthy wrist of a 40-year-old female was scanned using Magnetic Resonance Imaging in two wrist positions (extension, radial extension). The scans were transformed into three-dimensional models and meshed. Finite element (FE) analyses in each position of the wrist were conducted for both adult and elder models, which were differentiated by the mechanical properties of the ligaments. The distal surfaces of the carpal bones articulating with the metacarpals were loaded by physically accurate tendon forces for each wrist position. Results: The von Mises, shear stresses and contact stresses were higher in the extension model compared with the radial-extension model and were higher for the radius-scaphoid interface in the adult model compared with the elder model. In the radius-scaphoid interface, the stress differences between the two wrist positions were smaller in the elder model (11.5% to 22.5%) compared with the adult model (33.6–41.5%). During radial extension, the contact area at the radius-lunate interface was increased, more so in the adult model (222.2%) compared with the elder model (127.9%), while the contact area at the radius-scaphoid was not affected by the position of the wrist in the adult model (100.9%) but decreased in the elder model (50.2%) during radial extension. Conclusion: The reduced stresses during radial extension might provide an explanation to our frequent use of this movement pattern, as the reduced stresses decrease the risk of overuse injury. Our results suggest that this conclusion is relevant to both adults and elder individuals.
The Italian National Beekeeping Registry (BDNA) as a Tool to Identify Areas Suitable for Controlled Mating of Honey Bees in Italy
Authors: Mutinelli Franco , Mazzucato Matteo , Barbujani Marco , Carpana Emanuele , Di Salvo Vincenzo , Gardi Tiziano , Greco Daniele , Bonizzoni Luca , Benvenuti Massimo , Casarotto Claudia , Bortolotti Laura , Costa Cecilia
Published: June 2021

Honey bee mating is difficult to control as it occurs in flight, several kilometers away from the hive of origin of both queens and drones. In recent years, there has been an increase in the introduction into Italy of queen bees and swarms originating from interracial crossings (especially those known as “Buckfast”), or belonging to non-native subspecies. Consequently, there is a strong need to establish areas suitable for controlled mating. The Italian national beekeeping registry (BDNA) has been recently set up to monitor the position of apiaries and movement of hives, with the purpose of economic and sanitary protection and improvement of bee heritage and food safety. The BDNA was, thus, deemed a suitable tool to explore the availability of areas that could be used as mating stations. Specific criteria, such as not be classified as wetlands, altitude below 1500 m a.s.l., distance of at least 6000 m from an apiary, and distance of at least 1500 m from the national terrestrial border, were selected for defining the mating stations. Furthermore, all the remaining Italian national territory was considered suitable for settlement of mating stations, including towns, industrial settlements, and roads. Based on these criteria, the following methodological framework was applied: (1) collection of the required data (i.e., apiaries coordinates, geospatial data on soil classification, geospatial data on terrain altitude, Italian boundary geospatial data); (2) calculation for the excluded areas according with the criteria listed above; (3) calculation of the mating areas by means of the difference between the entire Italian territory and the excluded areas. The database of BDNA was used to identify them. Appropriate databases and software were used to exclude the areas of the Italian national territory that did not fulfill the established criteria. In this paper, we report the procedure applied to identify on maps the areas suitable for controlled mating of queen bees in the Italian national territory based on data currently available in the BDNA.
Fractional Order Processing of Satellite Images
Authors: Henriques Manuel , Valério Duarte , Melicio Rui
Published: June 2021

Nowadays, satellite images are used in many applications, and their automatic processing is vital. Conventional integer grey-scale edge detection algorithms are often used for this. This study shows that the use of color-based, fractional order edge detection may enhance the results obtained using conventional techniques in satellite images. It also shows that it is possible to find a fixed set of parameters, allowing automatic detection while maintaining high performance.
Evolution of Water-in-Oil Droplets in T-Junction Microchannel by Micro-PIV
Authors: Ringkai Hawa , Tamrin Khairul Fikri , Sheikh Nadeem Ahmed , Mohamaddan Shahrol
Published: June 2021

Water-in-oil droplets have huge importance in chemical and biotechnology applications, despite their difficulty being produced in microfluidics. Moreover, existing studies focus more on the different shape of microchannels instead of their size, which is one of the critical factors that can influence flow characteristics of the droplets. Therefore, the present work aims to study the behaviours of water-in-oil droplets at the interfacial surface in an offset T-junction microchannel, having different radiuses, using micro-PIV software. Food-grade palm olein and distilled water seeded with polystyrene microspheres particles were used as working fluids, and their captured images showing their generated droplets’ behaviours focused on the junction of the respective microfluidic channel, i.e., radiuses of 400 µm, 500 µm, 750 µm and 1000 µm, were analysed via PIVlab. The increasing in the radius of the offset T-junction microchannel leads to the increase in the cross-sectional area and the decrease in the distilled water phase’s velocity. The experimental velocity of the water droplet is in agreement with theoretical values, having a minimal difference as low as 0.004 mm/s for the case of the microchannel with a radius of 750 µm. In summary, a small increase in the channel’s size yields a significant increase in the overall flow of a liquid.
Static Magnetic Fields Effects on Polysaccharides Production by Different Microalgae Strains
Authors: Deamici Kricelle M. , de Morais Michele G. , Santos Lucielen O. , Muylaert Koenraad , Gardarin Christine , Costa Jorge Alberto V. , Laroche Céline
Published: June 2021

Microalgae are able to produce many valuable biomolecules, such as polysaccharides, that presents a large diversity of biochemical structures and functions as antioxidant, antifungal, anticancer, among others. Static magnetic fields (SMF) influence the metabolism of microorganisms and has been shown as an alternative to increase microalgae biomass, yield and compounds production. Especially, some studies have highlighted that SMF application could enhance carbohydrate content. This study aimed to evaluate different conditions of SMF on Spirulina and Chlorella in indoor and outdoor conditions, in order to confirm the influence of SMF on polysaccharides production, evaluating which polysaccharidic fraction could be enhanced by SMF and highlighting a possible modification in EPS composition. Starch from Chlorella and exopolysaccharides (EPS) from Spirulina were quantified and characterized. SMF increased the starch content in Chorella fusca biomass. EPS productions from A. platensis and Spirulina sp. were not significantly increased, and global composition appeared similar to the controls (constituted basically of 80–86% neutral sugars and 13–19% uronic acids). However, the monosaccharide composition analysis revealed a significant modification of composition, i.e., the amount of fucose, arabinose, rhamnose, galactose and glucuronic acid was increased, while the glucose content was decreased. SMF application led to significant modification of polysaccharides production and this study demonstrate that combining the outdoor conditions with SMF, the starch content and EPS composition was positively affected.
The Possibility to Recreate the Shapes of Objects on the Basis of Printer Vibration in the Additive Printing Process
Authors: Stańczak Andrzej , Kubiak Ireneusz , Przybysz Artur , Witenberg Anna
Published: June 2021

Information protection is an important safety issue in many human activity fields. Technological advances and related ubiquitous computerization bring new challenges in this area. In particular, the problem concerns the protection of devices against non-invasive acquisition processed information in ICT systems. It is known that, e.g., VGA, DVI/HDMI interfaces or laser printer formatter systems that process visual signals are the effective sources of compromising electromagnetic emanations. The emission safety of the more and more commonly used 3D printers is less known. In many cases, the disclosure of information about printed objects might constitute an infringement of the state/industrial/commercial secret, copyright, patent protection, etc. In order to analyze the existing threat, a selected printer using FDM technology was tested. During the tests, simple objects were printed to identify the operation of the stepper motor and the movements of the printer head and the printer platform, which are sources of emissions in the secondary channels. The analyses performed focused on finding the correlation between the recorded vibration signals and the printer head movements when an object was printed. It was shown that the analysis of the registered sensitive signal runtimes and their spectrograms allowed to recreate the printed object shape. Three simple objects (a trihedron, a tube and a tetrahedron) were selected for testing because they include elements that allow the four major movements of the printer head to be easily recognized: along the X axis, along the Y axis, along an arc and diagonally (between the X and Y axes). The paper presents the test results and their analyses.
Analyzing Precision and Efficiency of Global Navigation Satellite System-Derived Height Determination for Coastal and Island Areas
Authors: Lee Jisun , Kwon Jay Hyoun , Lee Yong
Published: June 2021

The global navigation satellite system (GNSS)-derived height determination technique is applied in the field of surveying owing to the broad use of GNSS and the development of precise local geoid models. In Korea, this technique was officially adopted in 2020 for public surveying, such as urban facility mapping; it is also treated as an efficient way to unify the vertical datum of the inland and island areas of Korea. Here, GNSS surveying was conducted on 19 stations located in Korea’s coastal regions and islands, and GNSS-derived elevations were determined. When each GNSS-derived elevation was compared with elevations from spirit leveling, all stations showed differences of less than 3 cm when GNSS surveying was conducted for 4 h/day over two days; they were smaller than 5 cm with 2 h of surveying. These differences meet the standards of GNSS-derived elevations in Korea. In addition, GNSS-derived elevations were compared with those obtained via sea-crossing leveling in two regions, showing differences smaller than 1 cm. Sea-crossing leveling takes longer than GNSS-derived height determination, and its accuracy can be significantly affected by various environments, such as sea fog. Thus, GNSS-derived height determination represents a practical and useful technique.
Theoretical Chemistry and the Calculation of the Atmospheric State
Authors: Tuck Adrian F.
Published: June 2021

Theoretical chemists have been actively engaged for some time in processes such as ozone photodissociation, overtone photodissociation in nitric acid, pernitric acid, sulphuric acid, clusters and in small organic acids. The last of these have shown very different behaviours in the gas phase, liquid phase and importantly at the air–water interface in aqueous aerosols. The founder of molecular dynamics, B J Alder, pointed out long ago that hydrodynamic behaviour emerged when the symmetry of a random, thermalised population of hard spheres—billiard balls—was broken by a flux of energetic molecules. Despite this, efforts over two centuries to solve turbulence by finding top-down solutions to the Navier–Stokes equation have failed. It is time for theoretical chemistry to try a bottom-up solution. Gibbs free energy that drives the circulation arises from the entropy difference between the incoming low-entropy beam of visible and ultraviolet photons and the outgoing higher-entropy flux of infrared photons over the whole 4π solid angle. The role of the most energetic molecules with the highest velocities will affect the rovibrational line shapes of water, carbon dioxide and ozone in the far wings, where there is the largest effect on radiative transfer and hence on calculations of atmospheric temperature. The atmospheric state is determined by the interaction of radiation, chemistry and fluid dynamics on the microscopic scale, with propagation through the mesoscale to the macroscale. It will take theoretical chemistry to simulate that accurately. A challenging programme of research for theoretical chemistry is proposed, involving ab initio simulation by molecular dynamics of an air volume, starting in the upper stratosphere. The aim is to obtain scaling exponents for turbulence, providing a physical method for upscaling in numerical models. Turbulence affects chemistry, radiation and fluid dynamics at a fundamental, molecular level and is thus of basic concern to theoretical chemistry as it applies to the atmosphere, which consists of molecules in motion.
Contribution of Aerosol Sources to Health Impacts
Authors: Contini Daniele , Lin Ying-Hsuan , Hänninen Otto , Viana Mar
Published: June 2021

Atmospheric aerosol is one of the major leading environmental risk factors for human health worldwide, potentially causing several million premature deaths per year [...]
Calculation of Electron Impact Single Ionization TDCS of Tungsten Atoms at 200, 500 and 1000 eV
Authors: Purohit Ghanshyam
Published: June 2021

We report triple differential cross-sections (TDCSs) for the electron impact single ionization of tungsten atoms for the ionization taking place from the outer sub shells of tungsten atoms, viz. W (6s), W (5d), W (5p) and W (4f). The study of the electron-induced processes such as ionization, excitation, autoionization from tungsten and its charged states is strongly required to diagnose and model the fusion plasma in magnetic devices such as Tokamaks. Particularly, the cross-section data are important to understand the electron spectroscopy involved in the fusion plasma. In the present study, we report TDCS results for the ionization of W atoms at 200, 500 and 1000 eV projectile energy at different values of scattered electron angles. It was observed that the trends of TDCSs for W (5d) are significantly different from the trends of TDCSs for W (6s), W (5p) and W (4f). It was further observed that the TDCS for W atoms has sensitive dependence on value of momentum transfer and projectile energy.
Characterization of Tumor-Associated Macrophages and the Immune Microenvironment in Limited-Stage Neuroendocrine-High and -Low Small Cell Lung Cancer
Authors: Dora David , Rivard Christopher , Yu Hui , Pickard Shivaun Lueke , Laszlo Viktoria , Harko Tunde , Megyesfalvi Zsolt , Dinya Elek , Gerdan Csongor , Szegvari Gabor , Hirsch Fred R. , Dome Balazs , Lohinai Zoltan
Published: June 2021

This study aims to characterize tumor-infiltrating macrophages (TAMs), myeloid-derived suppressor cells (MDSC), and the related molecular milieu regulating anti-tumor immunity in limited-stage neuroendocrine (NE)-high and NE-low small cell lung cancer. Primary tumors and matched lymph node (LN) metastases of 32 resected, early-stage SCLC patients were analyzed by immunohistochemistry (IHC) with antibodies against pan-macrophage marker CD68, M2-macrophage marker CD163, and MDSC marker CD33. Area-adjusted cell counting on TMAs showed that TAMs are the most abundant cell type in the TME, and their number in tumor nests exceeds the number of CD3 + T-cells (64% vs. 38% in NE-low and 71% vs. 18% in NE-high). Furthermore, the ratio of CD163-expressing M2-polarized TAMs in tumor nests was significantly higher in NE-low vs. NE-high tumors (70% vs. 31%). TAM density shows a strong positive correlation with CD45 and CD3 in tumor nests, but not in the stroma. fGSEA analysis on a targeted RNAseq oncological panel of 2560 genes showed that NE-high tumors exhibited increased enrichment in pathways related to cell proliferation, whereas in NE-low tumors, immune response pathways were significantly upregulated. Interestingly, we identified a subset of NE-high tumors representing an immune-oasis phenotype, but with a different gene expression profile compared to NE-low tumors. In contrast, we found that a limited subgroup of NE-low tumors is immune-deserted and express distinct cellular pathways from NE-high tumors. Furthermore, we identified potential molecular targets based on our expression data in NE-low and immune-oasis tumor subsets, including CD70, ANXA1, ITGB6, TP63, IFI27, YBX3 and CXCR2.
New Insights on Leptospira Infections in a Canine Population from North Sardinia, Italy: A Sero-Epidemiological Study
Authors: Piredda Ivana , Ponti Maria Nicoletta , Piras Angela , Palmas Bruna , Pintore Pierangela , Pedditzi Aureliana , Chisu Valentina
Published: June 2021

Leptospirosis is a widespread zoonosis recognized as a re-emerging infectious disease in a wide variety of animal species, including humans and dogs. No data exist regarding the presence of Leptospira species in the canine population of Sardinia Island. This study reports the first sero-survey for leptospirosis in kennel and owned dogs from six areas of the north of Sardinia. Sera from 1296 dogs were tested by microscopic agglutination test (MAT) specific for nine different serovars that are known to be well widespread in the Mediterranean environment. Moreover, kidney homogenates from rodents collected from the study area were also analyzed by LipL32 real-time PCR and multi-locus sequence type (MLST) on the basis of the analysis of seven concatenated loci. A total of 13% of the examined sera (95%CI: 11–15) tested positive for one or more serovars of Leptospira MAT detected; antibodies for serogroup Icterohaemorrhagiae (57%; 95%CI: 49–65) were the most common, followed by serovars Bratislava (22%; 95%CI: 16–28), Canicola (14%; 95%CI: 9–19), and Grippotyphosa (7%; 95%CI: 3–11). MLST analyses on isolates from rodents identified L. interrogans and L. borgpetersenii genomospecies. Different serovars belonging to pathogenic Leptospira serogroups are circulating in dogs from the island. Moreover, data obtained from rodents, indicated that rodents likely act as reservoir of spirochetes. Further sero-epidemiological studies are needed in order to obtain data from other collection sites in Sardinia and to increase the information on Leptospira species circulating in this area.
SARS-CoV-2 and Skin: The Pathologist’s Point of View
Authors: Cazzato Gerardo , Mazzia Giulia , Cimmino Antonietta , Colagrande Anna , Sablone Sara , Lettini Teresa , Rossi Roberta , Santarella Nadia , Elia Rossella , Nacchiero Eleonora , Maruccia Michele , Marzullo Andrea , Maiorano Eugenio , Giudice Giuseppe , Ingravallo Giuseppe , Resta Leonardo
Published: June 2021

The SARS-CoV-2 pandemic has dramatically changed our lives and habits. In just a few months, the most advanced and efficient health systems in the world have been overwhelmed by an infectious disease that has caused 3.26 million deaths and more than 156 million cases worldwide. Although the lung is the most frequently affected organ, the skin has also resulted in being a target body district, so much so as to suggest it may be a real “sentinel” of COVID-19 disease. Here we present 17 cases of skin manifestations studied and analyzed in recent months in our Department; immunohistochemical investigations were carried out on samples for the S1 spike-protein of SARS-CoV-2, as well as electron microscopy investigations showing evidence of virions within the constituent cells of the eccrine sweat glands and the endothelium of small blood vessels. Finally, we conduct a brief review of the COVID-related skin manifestations, confirmed by immunohistochemistry and/or electron microscopy, described in the literature.
Folding and Stability of Ankyrin Repeats Control Biological Protein Function
Authors: Kumar Amit , Balbach Jochen
Published: June 2021

Ankyrin repeat proteins are found in all three kingdoms of life. Fundamentally, these proteins are involved in protein-protein interaction in order to activate or suppress biological processes. The basic architecture of these proteins comprises repeating modules forming elongated structures. Due to the lack of long-range interactions, a graded stability among the repeats is the generic properties of this protein family determining both protein folding and biological function. Protein folding intermediates were frequently found to be key for the biological functions of repeat proteins. In this review, we discuss most recent findings addressing this close relation for ankyrin repeat proteins including DARPins, Notch receptor ankyrin repeat domain, IκBα inhibitor of NFκB, and CDK inhibitor p19INK4d. The role of local folding and unfolding and gradual stability of individual repeats will be discussed during protein folding, protein-protein interactions, and post-translational modifications. The conformational changes of these repeats function as molecular switches for biological regulation, a versatile property for modern drug discovery.
Effective Diagnosis of Foot-And-Mouth Disease Virus (FMDV) Serotypes O and A Based on Optical and Electrochemical Dual-Modal Detection
Authors: Hwang Yun-Jung , Lee Kyung-Kwan , Kim Jong-Won , Chung Kwang-Hyo , Kim Sang-Jick , Yun Wan-Soo , Lee Chang-Soo
Published: June 2021

Foot-and-mouth disease virus (FMDV) is a highly contagious disease that affects cloven-hoofed animals. The traditional diagnostic methods for FMDV have several drawbacks such as cross-reactivity, low sensitivity, and low selectivity. To overcome these drawbacks, we present an optical and electrochemical dual-modal approach for the specific detection of FMDV serotypes O and A by utilizing a magnetic nanoparticle labeling technique with resorufin β-d-glucopyranoside (res-β-glc) and β-glucosidase (β-glc), without the use of typical lateral flow assay or polymerase chain reaction. FMDV serotypes O and A were reacted with pan-FMDV antibodies that recognize all seven FMDV serotypes (O, A, C, Asia 1, SAT 1, SAT 2, and SAT 3). The antigen–antibody complex was then immobilized on magnetic nanoparticles and reacted with β-glc-conjugated FMDV type O or type A antibodies. Subsequently, the addition of res-β-glc resulted in the release of fluorescent resorufin and glucose owing to catalytic hydrolysis by β-glc. The detection limit of fluorescent signals using a fluorescence spectrophotometer was estimated to be log(6.7) and log(5.9) copies/mL for FMDV type O and A, respectively, while that of electrochemical signals using a glucometer was estimated to be log(6.9) and log(6.1) copies/mL for FMDV type O and A, respectively. Compared with a commercially available lateral flow assay diagnostic kit for immunochromatographic detection of FMDV type O and A, this dual-modal detection platform offers approximately four-fold greater sensitivity. This highly sensitive and accurate dual-modal detection method can be used for effective disease diagnosis and treatment, and will find application in the early-stage diagnosis of viral diseases and next-generation diagnostic platforms.
Exploring the Connection between Porphyromonas gingivalis and Neurodegenerative Diseases: A Pilot Quantitative Study on the Bacterium Abundance in Oral Cavity and the Amount of Antibodies in Serum
Authors: Franciotti Raffaella , Pignatelli Pamela , Carrarini Claudia , Romei Federica Maria , Mastrippolito Martina , Gentile Antonella , Mancinelli Rosa , Fulle Stefania , Piattelli Adriano , Onofrj Marco , Curia Maria Cristina
Published: June 2021

Recent studies support the hypothesis that microbes can seed some Alzheimer’s disease (AD) cases, leading to inflammation and overproduction of amyloid peptides. Porphyromonas gingivalis (Pg) is a keystone pathogen of chronic periodontitis and has been identified as risk factor for the development and progression of AD. The present preliminary study aimed to quantify Pg abundance in neurodegenerative disease (ND) patients compared with neurologic patients without neurodegenerative disorders (no-ND) and healthy controls (HC) to determine possible association between Pg abundance and neurodegenerative process. Pg was quantified on DNA extracted from the oral samples of 49 patients and 29 HC by quantitative polymerase chain reaction (qPCR). Anti-Pg antibodies were also detected on patient serum samples by enzyme-linked immunosorbent assays (ELISA). The Pg abundance in the oral cavity was significantly different among groups (p = 0.004). It was higher in ND than no-ND (p = 0.010) and HC (p = 0.008). The Pg abundance was correlated with the antibodies (p = 0.001) with different slopes between ND and no-ND (p = 0.037). Pg abundance was not correlated with oral indices and comorbidities. These results extend our understanding of the association between oral pathogens and AD to other neurodegenerative processes, confirming the hypothesis that oral pathogens can induce an antibody systemic response, influencing the progression of the disease.
Glycine Receptors in Spinal Nociceptive Control—An Update
Authors: Zeilhofer Hanns Ulrich , Werynska Karolina , Gingras Jacinthe , Yévenes Gonzalo E.
Published: June 2021

Diminished inhibitory control of spinal nociception is one of the major culprits of chronic pain states. Restoring proper synaptic inhibition is a well-established rational therapeutic approach explored by several pharmaceutical companies. A particular challenge arises from the need for site-specific intervention to avoid deleterious side effects such as sedation, addiction, or impaired motor control, which would arise from wide-range facilitation of inhibition. Specific targeting of glycinergic inhibition, which dominates in the spinal cord and parts of the hindbrain, may help reduce these side effects. Selective targeting of the α3 subtype of glycine receptors (GlyRs), which is highly enriched in the superficial layers of the spinal dorsal horn, a key site of nociceptive processing, may help to further narrow down pharmacological intervention on the nociceptive system and increase tolerability. This review provides an update on the physiological properties and functions of α3 subtype GlyRs and on the present state of related drug discovery programs.
Pulsed Electric Field (PEF) Enhances Iron Uptake by the Yeast Saccharomyces cerevisiae
Authors: Nowosad Karolina , Sujka Monika , Pankiewicz Urszula , Miklavčič Damijan , Arczewska Marta
Published: June 2021

The aim of the study was to investigate the influence of a pulsed electric field (PEF) on the level of iron ion accumulation in Saccharomyces cerevisiae cells and to select PEF conditions optimal for the highest uptake of this element. Iron ions were accumulated most efficiently when their source was iron (III) nitrate. When the following conditions of PEF treatment were used: voltage 1500 V, pulse width 10 μs, treatment time 20 min, and a number of pulses 1200, accumulation of iron ions in the cells from a 20 h-culture reached a maximum value of 48.01 mg/g dry mass. Application of the optimal PEF conditions thus increased iron accumulation in cells by 157% as compared to the sample enriched with iron without PEF. The second derivative of the FTIR spectra of iron-loaded and -unloaded yeast cells allowed us to determine the functional groups which may be involved in metal ion binding. The exposure of cells to PEF treatment only slightly influenced the biomass and cell viability. However, iron-enriched yeast (both with or without PEF) showed lower fermentative activity than a control sample. Thus obtained yeast biomass containing a high amount of incorporated iron may serve as an alternative to pharmacological supplementation in the state of iron deficiency.
Promising Activities of Marine Natural Products against Hematopoietic Malignancies
Authors: Saide Assunta , Damiano Sara , Ciarcia Roberto , Lauritano Chiara
Published: June 2021

According to the WHO classification of tumors, more than 150 typologies of hematopoietic and lymphoid tumors exist, and most of them remain incurable diseases that require innovative approaches to improve therapeutic outcome and avoid side effects. Marine organisms represent a reservoir of novel bioactive metabolites, but they are still less studied compared to their terrestrial counterparts. This review is focused on marine natural products with anticancer activity against hematological tumors, highlighting recent advances and possible perspectives. Until now, there are five commercially available marine-derived compounds for the treatment of various hematopoietic cancers (e.g., leukemia and lymphoma), two molecules in clinical trials, and series of compounds and/or extracts from marine micro- and macroorganisms which have shown promising properties. In addition, the mechanisms of action of several active compounds and extracts are still unknown and require further study. The continuous upgrading of omics technologies has also allowed identifying enzymes with possible bioactivity (e.g., l-asparaginase is currently used for the treatment of leukemia) or the enzymes involved in the synthesis of bioactive secondary metabolites which can be the target of heterologous expression and genetic engineering.
Identification of MicroRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer
Authors: Martínez-González Luis , Sánchez-Conde Victor , González-Cabezuelo Jose , Antunez-Rodríguez Alba , Andrés-León Eduardo , Robles-Fernandez Inmaculada , Lorente Jose , Vázquez-Alonso Fernando , Alvarez-Cubero María
Published: June 2021

MiRNAs play a relevant role in PC (prostate cancer) by the regulation in the expression of several pathways’ AR (androgen receptor), cellular cycle, apoptosis, MET (mesenchymal epithelium transition), or metastasis. Here, we report the role of several miRNAs’ expression patterns, such as miR-93-5p, miR-23c, miR-210-3p, miR-221-3p, miR-592, miR-141, miR-375, and miR-130b, with relevance in processes like cell proliferation and MET. Using Trizol® extraction protocol and TaqMan™ specific probes for amplification, we performed miRNAs’ analysis of 159 PC fresh tissues and 60 plasmas from peripheral blood samples. We had clinical data from all samples including PSA, Gleason, TNM, and D’Amico risk. Moreover, a bioinformatic analysis in TCGA (The Cancer Genome Atlas) was included to analyze the effect of the most relevant miRNAs according to aggressiveness in an extensive cohort (n = 531). We found that miR-210-3p, miR-23c, miR-592, and miR-93-5p are the most suitable biomarkers for PC aggressiveness and diagnosis, respectively. In fact, according with our results, miR-93-5p seems the most promising non-invasive biomarker for PC. To sum up, miR-210-3p, miR-23c, miR-592, and miR-93-5p miRNAs are suggested to be potential biomarkers for PC risk stratification that could be included in non-invasive strategies such as liquid biopsy in precision medicine for PC management.
Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin
Authors: Štorkánová Hana , Štorkánová Lenka , Navrátilová Adéla , Bečvář Viktor , Hulejová Hana , Oreská Sabína , Heřmánková Barbora , Špiritović Maja , Bečvář Radim , Pavelka Karel , Vencovský Jiří , Distler Jörg H. W. , Šenolt Ladislav , Tomčík Michal
Published: June 2021

Our previous study demonstrated that heat shock protein 90 (Hsp90) is overexpressed in the involved skin of patients with systemic sclerosis (SSc) and in experimental dermal fibrosis. Pharmacological inhibition of Hsp90 prevented the stimulatory effects of transforming growth factor-beta on collagen synthesis and the development of dermal fibrosis in three preclinical models of SSc. In the next step of the preclinical analysis, herein, we aimed to evaluate the efficacy of an Hsp90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in the treatment of established experimental dermal fibrosis induced by bleomycin. Treatment with 17-DMAG demonstrated potent antifibrotic and anti-inflammatory properties: it decreased dermal thickening, collagen content, myofibroblast count, expression of transforming growth factor beta receptors, and pSmad3-positive cell counts, as well as leukocyte infiltration and systemic levels of crucial cytokines/chemokines involved in the pathogenesis of SSc, compared to vehicle-treated mice. 17-DMAG effectively prevented further progression and may induce regression of established bleomycin-induced dermal fibrosis to an extent comparable to nintedanib. These findings provide further evidence of the vital role of Hsp90 in the pathophysiology of SSc and characterize it as a potential target for the treatment of fibrosis with translational implications due to the availability of several Hsp90 inhibitors in clinical trials for other indications.
The Role of Single Nucleotide Variants of NOS1, NOS2, and NOS3 Genes in the Development of the Phenotype of Migraine and Arterial Hypertension
Authors: Moskaleva Polina V. , Shnayder Natalya A. , Petrova Marina M. , Kaskaeva Daria S. , Gavrilyuk Oksana A. , Radostev Sergey V. , Garganeeva Natalia P. , Sharavii Victoria B. , Vaiman Elena E. , Nasyrova Regina F.
Published: June 2021

Migraine (M) and arterial hypertension (AH) are very common diseases. Today, there are a number of studies confirming and explaining their comorbidity. We searched PubMed, Springer, Scopus, Web of Science, Clinicalkeys, and Google Scholar databases for full-text English publications over the past 15 years using keywords and their combinations. The present review provides a synthesis of information about single nucleotide variants (SNVs) of NOS1, NOS2, and NOS3 genes involved in the development of M and essential AH. The results of studies we have discussed in this review are contradictory, which might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical environments. Despite a high prevalence of the M and AH phenotype, its genetic markers have not yet been sufficiently studied. Specifically, there are separate molecular genetic studies aimed to identify SNVs of NOS1, NOS2, and NOS3 genes responsible for the development of M and those responsible for the development of AH. However, these SNVs have not been studied in patients with the phenotype of M and AH. In this review, we identify the SNVs that would be the most interesting to study in this aspect. Understanding the role of environmental factors and genetic predictors will contribute to a better diagnostics and exploration of new approaches to pathogenetic and disease-modifying treatment of the M and AH phenotype.
Vitamin D Intake and the Risk of Colorectal Cancer: An Updated Meta-Analysis and Systematic Review of Case-Control and Prospective Cohort Studies
Authors: Boughanem Hatim , Canudas Silvia , Hernandez-Alonso Pablo , Becerra-Tomás Nerea , Babio Nancy , Salas-Salvadó Jordi , Macias-Gonzalez Manuel
Published: June 2021

Obesity, a sedentary lifestyle, high red meat consumption and alcohol, and tobacco are considered the driving factors behind colorectal cancer (CRC) worldwide. Both diet and lifestyle are recognized to play an important role in the prevention of CRC. Forty years later, the vitamin D–cancer hypothesis is considered consistent. However, the relationship between low vitamin D intake and CRC is still controversial. The aim of this meta-analysis is to determine the associations between Vitamin D intake and CRC. MEDLINE-PubMed and Cochrane databases were searched up to May 2020 for studies evaluating the association between vitamin D intake (from foods and supplements) and CRC. Two reviewers, working independently, screened all titles and abstracts to identify the studies that met the inclusion criteria (case-control or prospective cohort (PC) studies published in English). Data were pooled by the generic inverse variance method using a random or fixed effect model. Heterogeneity was identified using the Cochran Q-test and quantified by the I2 statistic. A total of 31 original studies were included for the quantitative meta-analysis, comprising a total 47.540 cases and 70.567 controls in case-control studies, and a total of 14.676 CRC-incident cases (out of 808.130 subjects in PC studies) from 17 countries. A significant 25% lower risk was reported comparing the highest vs. the lowest dietary vitamin D consumption and CRC risk (odds ratio (95% confidence interval): 0.75 (0.67; 0.85)) in case-control studies, whereas a non-significant association was reported in case of prospective studies (hazard ratio (95% confidence interval): 0.94 (0.79; 1.11). The present meta-analysis demonstrates that high dietary vitamin D is associated to CRC prevention. However, larger and high-quality prospective studies and clinical trials are warranted to confirm this association.
Neutrophil-to-Lymphocyte Ratio as a Biomarker Predicting Overall Survival after Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma
Authors: Chu Hee Ho , Kim Jin Hyoung , Shim Ju Hyun , Gwon Dong Il , Ko Heung-Kyu , Shin Ji Hoon , Ko Gi-Young , Yoon Hyun-Ki , Kim Nayoung
Published: June 2021

The clinical impact of neutrophil-to-lymphocyte ratio (NLR) in predicting outcomes in hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE) remain unclear, and additional large-scale studies are required. This retrospective study evaluated outcomes in treatment-naïve patients who received TACE as first-line treatment for intermediate-stage HCC between 2008 and 2017. Patients who underwent TACE before and after 2013 were assigned to the development (n = 495) and validation (n = 436) cohorts, respectively. Multivariable Cox analysis identified six factors predictive of outcome, including NLR, which were used to create models predictive of overall survival (OS) in the development cohort. Risk scores of 0–3, 4–7, and 8–12 were defined as low, intermediate, and high risk, respectively. Median OS times in the low-, medium-, and high-risk groups in the validation cohort were 48.1, 24.3, and 9.7 months, respectively (p < 0.001). Application to the validation cohort of time-dependent ROC curves for models predictive of OS showed AUC values of 0.72 and 0.70 at 3 and 5 years, respectively. Multivariable logistic regression analysis found that NLR ≥ 3 was a significant predictor (odds ratio, 3.4; p < 0.001) of disease progression 6 months after TACE. Higher baseline NLR was predictive of poor prognosis in patients who underwent TACE for intermediate-stage HCC.
Neutrophil Extracellular Traps in Tumor Metastasis: Pathological Functions and Clinical Applications
Authors: Chen Qian , Zhang Lu , Li Xiang , Zhuo Wei
Published: June 2021

Neutrophil extracellular trap (NET) formation is an ability of neutrophils to capture and kill pathogens by releasing chromatin scaffolds, along with associated cytotoxic enzymes and proteases, into the extracellular space. NETs are usually stimulated by pathogenic microorganisms and their products, surgical pressure or hypoxia. Interestingly, a number of recent studies suggest that tumor cells can induce NET formation, which in turn confers tumor cell malignancy. Notably, emerging studies indicate that NETs are involved in enhancing local invasion, increasing vascular permeability and facilitating immune escape and colonization, thus promoting tumor metastasis. In this article, we review the pivotal roles of NETs in the tumor metastasis cascade. We also recapitulate the potential of NETs as a cancer prognostic biomarker and therapeutic target.