bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Regulatory Non-Coding RNAs in Aggressive Thyroid Cancer: Prospective Applications of Neural Network Analysis
Authors: Iesato Asumi , Nucera Carmelo
Published: May 2021

Thyroid cancer (TC) is the most common endocrine malignancy. Most TCs have a favorable prognosis, whereas anaplastic thyroid carcinoma (ATC) is a lethal form of cancer. Different genetic and epigenetic alterations have been identified in aggressive forms of TC such as ATC. Non-coding RNAs (ncRNAs) represent functional regulatory molecules that control chromatin reprogramming, including transcriptional and post-transcriptional mechanisms. Intriguingly, they also play an important role as coordinators of complex gene regulatory networks (GRNs) in cancer. GRN analysis can model molecular regulation in different species. Neural networks are robust computing systems for learning and modeling the dynamics or dependencies between genes, and are used for the reconstruction of large data sets. Canonical network motifs are coordinated by ncRNAs through gene production from each transcript as well as through the generation of a single transcript that gives rise to multiple functional products by post-transcriptional modifications. In non-canonical network motifs, ncRNAs interact through binding to proteins and/or protein complexes and regulate their functions. This article overviews the potential role of ncRNAs GRNs in TC. It also suggests prospective applications of deep neural network analysis to predict ncRNA molecular language for early detection and to determine the prognosis of TC. Validation of these analyses may help in the design of more effective and precise targeted therapies against aggressive TC.
New Cardenolides from Biotransformation of Gitoxigenin by the Endophytic Fungus Alternaria eureka 1E1BL1: Characterization and Cytotoxic Activities
Authors: Bedir Erdal , Karakoyun Çiğdem , Doğan Gamze , Kuru Gülten , Küçüksolak Melis , Yusufoğlu Hasan
Published: May 2021

Microbial biotransformation is an important tool in drug discovery and for metabolism studies. To expand our bioactive natural product library via modification and to identify possible mammalian metabolites, a cytotoxic cardenolide (gitoxigenin) was biotransformed using the endophytic fungus Alternaria eureka 1E1BL1. Initially, oleandrin was isolated from the dried leaves of Nerium oleander L. and subjected to an acid-catalysed hydrolysis to obtain the substrate gitoxigenin (yield; ~25%). After 21 days of incubation, five new cardenolides 1, 3, 4, 6, and 8 and three previously- identified compounds 2, 5 and 7 were isolated using chromatographic methods. Structural elucidations were accomplished through 1D/2D NMR, HR-ESI-MS and FT-IR analysis. A. eureka catalyzed oxygenation, oxidation, epimerization and dimethyl acetal formation reactions on the substrate. Cytotoxicity of the metabolites were evaluated using MTT cell viability method, whereas doxorubicin and oleandrin were used as positive controls. Biotransformation products displayed less cytotoxicity than the substrate. The new metabolite 8 exhibited the highest activity with IC50 values of 8.25, 1.95 and 3.4 µM against A549, PANC-1 and MIA PaCa-2 cells, respectively, without causing toxicity on healthy cell lines (MRC-5 and HEK-293) up to concentration of 10 µM. Our results suggest that A. eureka is an effective biocatalyst for modifying cardenolide-type secondary metabolites.
Anti-Melanogenic Properties of Velutin and Its Analogs
Authors: Jung Se-Hui , Heo Hee-Young , Choe Jung-Won , Kim Jaehyun , Lee Kooyeon
Published: May 2021

Velutin, one of the flavones contained in natural plants, has various beneficial activities, such as skin whitening, as well as anti-inflammatory, anti-allergic, antioxidant, and antimicrobial activities. However, the relationship between the structure of velutin and its anti-melanogenesis activity is not yet investigated. In this study, we obtained 12 velutin derivatives substituted at C5, C7, C3′, and C4′ of the flavone backbone with hydrogen, hydroxyl, and methoxy functionalities by chemical synthesis, to perform SAR analysis of velutin structural analogues. The SAR study revealed that the substitution of functional groups at C5, C7, C3′, and C4′ of the flavone backbone affects biological activities related to melanin synthesis. The coexistence of hydroxyl and methoxy at the C5 and C7 position is essential for inhibiting tyrosinase activity. However, 1,2-diol compounds substituted at C3′ and C4′ of flavone backbone induce apoptosis of melanoma cells. Further, substitution at C3′ and C4′ with methoxy or hydrogen is essential for inhibiting melanogenesis. Thus, this study would be helpful for the development of natural-derived functional materials to regulate melanin synthesis.
Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach
Authors: Saddique Furqan Ahmad , Aslam Sana , Ahmad Matloob , Ashfaq Usman Ali , Muddassar Muhammad , Sultan Sadia , Taj Saman , Hussain Muzammil , Sung Lee Dae , Zaki Magdi E. A.
Published: May 2021

Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 μM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 μM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.
TAK1/AP-1-Targeted Anti-Inflammatory Effects of Barringtonia augusta Methanol Extract
Authors: Ha Anh Thu , Kim Mi-Yeon , Cho Jae Youl
Published: May 2021

Barringtonia augusta methanol extract (Ba-ME) is a folk medicine found in the wetlands of Thailand that acts through an anti-inflammatory mechanism that is not understood fully. Here, we examine how the methanol extract of Barringtonia augusta (B. augusta) can suppress the activator protein 1 (AP-1) signaling pathway and study the activities of Ba-ME in the lipopolysaccharide (LPS)-treated RAW264.7 macrophage cell line and an LPS-induced peritonitis mouse model. Non-toxic concentrations of Ba-ME downregulated the mRNA expression of cytokines, such as cyclooxygenase and chemokine ligand 12, in LPS-stimulated RAW264.7 cells. Transfection experiments with the AP-1-Luc construct, HEK293T cells, and luciferase assays were used to assess whether Ba-ME suppressed the AP-1 functional activation. A Western blot assay confirmed that C-Jun N-terminal kinase is a direct pharmacological target of Ba-ME action. The anti-inflammatory effect of Ba-ME, which functions by β-activated kinase 1 (TAK1) inhibition, was confirmed by using an overexpression strategy and a cellular thermal shift assay. In vivo experiments in a mouse model of LPS-induced peritonitis showed the anti-inflammatory effect of Ba-ME on LPS-stimulated macrophages and acute inflammatory mouse models. We conclude that Ba-ME is a promising anti-inflammatory drug targeting TAK1 in the AP-1 pathway.
Ligand-Dependent Conformational Transitions in Molecular Dynamics Trajectories of GPCRs Revealed by a New Machine Learning Rare Event Detection Protocol
Authors: Plante Ambrose , Weinstein Harel
Published: May 2021

Central among the tools and approaches used for ligand discovery and design are Molecular Dynamics (MD) simulations, which follow the dynamic changes in molecular structure in response to the environmental condition, interactions with other proteins, and the effects of ligand binding. The need for, and successes of, MD simulations in providing this type of essential information are well documented, but so are the challenges presented by the size of the resulting datasets encoding the desired information. The difficulty of extracting information on mechanistically important state-to-state transitions in response to ligand binding and other interactions is compounded by these being rare events in the MD trajectories of complex molecular machines, such as G-protein-coupled receptors (GPCRs). To address this problem, we have developed a protocol for the efficient detection of such events. We show that the novel Rare Event Detection (RED) protocol reveals functionally relevant and pharmacologically discriminating responses to the binding of different ligands to the 5-HT2AR orthosteric site in terms of clearly defined, structurally coherent, and temporally ordered conformational transitions. This information from the RED protocol offers new insights into specific ligand-determined functional mechanisms encoded in the MD trajectories, which opens a new and rigorously reproducible path to understanding drug activity with application in drug discovery.
Calcium Alginate Beads with Entrapped Iron Oxide Magnetic Nanoparticles Functionalized with Methionine—A Versatile Adsorbent for Arsenic Removal
Authors: Lilhare Surbhi , Mathew Sunitha B. , Singh Ajaya K. , Carabineiro Sónia A. C.
Published: May 2021

A novel beads adsorbent, consisting of calcium alginate entrapped on magnetic nanoparticles functionalized with methionine (MFMNABs), was developed for effective elimination of arsenic from water. The material was characterized by FT-IR (Fourier Transform Infrared Spectroscopy), SEM (Scanning Electron Microscopic), XRD (X-ray Diffraction) and TEM (Transmission Electron Microscopy). The arsenic removal capacity of the material was studied by altering variables such as pH of the solution, contact time, adsorbent dose and adsorbate concentration. The maximal removal of As(III) was 99.56% under optimal conditions with an equilibrium time of 110 min and pH 7.0–7.5. The adsorption followed a second order kinetics and data best fitted the Langmuir isotherm with a correlation coefficient of R2 = 0.9890 and adsorption capacity (qm) of 6.6533 mg/g. The thermodynamic study showed entropy change (∆S) and enthalpy change (∆H) to be 34.32 J mol−1 K and 5.25 kJ mol−1, respectively. This study proved that it was feasible to treat an As(III) solution with MFMNABs. The synthesized adsorbent was cost-effective, environmentally friendly and versatile, compared to other adsorbents. The adsorption study was carried by low cost spectrophotometric method using N- bromosuccinimide and rhodamine-B developed in our laboratory.
A New Method for Dispersing Pristine Carbon Nanotubes Using Regularly Arranged S-Layer Proteins
Authors: Breitwieser Andreas , Sleytr Uwe B. , Pum Dietmar
Published: May 2021

Homogeneous and stable dispersions of functionalized carbon nanotubes (CNTs) in aqueous solutions are imperative for a wide range of applications, especially in life and medical sciences. Various covalent and non-covalent approaches were published to separate the bundles into individual tubes. In this context, this work demonstrates the non-covalent modification and dispersion of pristine multi-walled carbon nanotubes (MWNTs) using two S-layer proteins, namely, SbpA from Lysinibacillus sphaericus CCM2177 and SbsB from Geobacillus stearothermophilus PV72/p2. Both the S-layer proteins coated the MWNTs completely. Furthermore, it was shown that SbpA can form caps at the ends of MWNTs. Reassembly experiments involving a mixture of both S-layer proteins in the same solution showed that the MWNTs were primarily coated with SbsB, whereas SbpA formed self-assembled layers. The dispersibility of the pristine nanotubes coated with SbpA was determined by zeta potential measurements (−24.4 +/− 0.6 mV, pH = 7). Finally, the SbpA-coated MWNTs were silicified with tetramethoxysilane (TMOS) using a mild biogenic approach. As expected, the thickness of the silica layer could be controlled by the reaction time and was 6.3 +/− 1.25 nm after 5 min and 25.0 +/− 5.9 nm after 15 min. Since S-layer proteins have already demonstrated their capability to bind (bio)molecules in dense packing or to act as catalytic sites in biomineralization processes, the successful coating of pristine MWNTs has great potential in the development of new materials, such as biosensor architectures.
Airborne Coronaviruses: Observations from Veterinary Experience
Authors: Pozzi Paolo , Soggiu Alessio , Bonizzi Luigi , Elkin Nati , Zecconi Alfonso
Published: May 2021

The virus responsible for the pandemic that has affected 152 countries worldwide is a new strain of coronavirus (CoV), which belongs to a family of viruses widespread in many animal species, including birds, and mammals including humans. Indeed, CoVs are known in veterinary medicine affecting several species, and causing respiratory and/or enteric, systemic diseases and reproductive disease in poultry. Animal diseases caused by CoV may be considered from the following different perspectives: livestock and poultry CoVs cause mainly “population disease”; while in companion animals they are a source of mainly “individual/single subject disease”. Therefore, respiratory CoV diseases in high-density, large populations of livestock or poultry may be a suitable example for the current SARS-CoV-2/COVID-19 pandemic. In this review we describe some strategies applied in veterinary medicine to control CoV and discuss if they may help to develop practical and useful strategies to control the SARS-CoV-2/COVID-19 pandemic.
The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions
Authors: Hahn Martina , Roll Sibylle C.
Published: May 2021

Drug interactions are a well-known cause of adverse drug events, and drug interaction databases can help the clinician to recognize and avoid such interactions and their adverse events. However, not every interaction leads to an adverse drug event. This is because the clinical relevance of drug–drug interactions also depends on the genetic profile of the patient. If inhibitors or inducers of drug metabolising enzymes (e.g., CYP and UGT) are added to the drug therapy, phenoconcversion can occur. This leads to a genetic phenotype that mismatches the observable phenotype. Drug–drug–gene and drug–gene–gene interactions influence the toxicity and/or ineffectivness of the drug therapy. To date, there have been limited published studies on the impact of genetic variations on drug–drug interactions. This review discusses the current evidence of drug–drug–gene interactions, as well as drug–gene–gene interactions. Phenoconversion is explained, the and methods to calculate the phenotypes are described. Clinical recommendations are given regarding the integratation of the PGx results in the assessment of the relevance of drug interactions in the future.
The Influence of Manganese on Growth Processes of Hordeum L. (Poaceae) Seedlings
Authors: Tkachenko Kirill , Kosareva Irina , Frontasyeva Marina
Published: May 2021

Manganese, as one of the xenobionts, belongs to the group of heavy metals, which, in high concentrations, can negatively affect the development of plants. In small concentrations, it is necessary for plants for normal growth and development. It is present in soils and is available to plants to varying degrees. In acidic soils, it often acts as a toxic element, and plants do not develop well and can even die. Screening major crops for manganese tolerance is essential. Based on the analysis of the collection of barley (Hordeum L., Poaceae), the N.I. Vavilov All-Russian Institute of Plant Genetic Resources (VIR) presented data that manganese-tolerant varieties and samples are concentrated in western and northern countries with a wide distribution of soils with low pH levels and high contents of mobile manganese. It follows from the diagnostic results that the maximum number of barley genotypes resistant to manganese is concentrated in Sweden, Finland, the northwestern and northern regions of the CIS countries, and the Russian Federation. In most cases, the samples tolerant to Al showed resistance to Mn as well, which is of great interest for further study of the mechanisms of plant resistance to these stressors. As a rule, samples from the northern territories—zones of distribution of acidic soils—were highly resistant. In this case, the role of the species belonging to the sample was leveled out. The highlighted areas (Scandinavia (Finland, Sweden), northern and northwestern regions of Russia, Belarus, and the Baltic countries) are sources of germplasm valuable for selection for acid resistance of barley.
Comparison of Different Semi-Automated Bioreactors for In Vitro Propagation of Taro (Colocasia esculenta L. Schott)
Authors: Mancilla-Álvarez Eucario , Pérez-Sato Juan Antonio , Núñez-Pastrana Rosalía , Spinoso-Castillo José L. , Bello-Bello Jericó J.
Published: May 2021

Taro is important for its nutritional content, medicinal use, and bioethanol production. The aim of the present study was to compare different semi-automated bioreactors (SABs) during in vitro multiplication of C. esculenta. The SABs used were temporary immersion bioreactors (TIBs), SETIS™ bioreactors and ebb-and-flow bioreactors; semi-solid culture medium was used as a control treatment. At 30 d of culture, different developmental variables, determination of chlorophyll, stomatal content, and survival percentage during acclimatization were evaluated. SABs increased the shoot multiplication rate relative to the semi-solid medium; however, the SETIS™ bioreactor showed the highest shoot production, with 36 shoots per explant, and the highest chlorophyll content. The stomatal index was higher in the semi-solid medium compared to the SABs, while the percentage of closed stomata was higher in the SABs than in the semi-solid culture medium. The survival rate during acclimatization showed no differences among the culture systems assessed, obtaining survival rates higher than 99%. In conclusion, the SETIS™ bioreactor showed the highest multiplication rate; however, other bioreactor alternatives are available for semi-automation and cost reduction for micropropagation of C. esculenta.
Antiproliferative Activity of Triterpenoid and Steroid Compounds from Ethyl Acetate Extract of Calotropis gigantea Root Bark against P388 Murine Leukemia Cell Lines
Authors: Hasballah Kartini , Sarong Murniana , Rusly Renzavaldy , Fitria Herdina , Maida Dewi Rara , Iqhrammullah Muhammad
Published: May 2021

Calotropis gigantea has been known to produce bioactive secondary metabolites with antiproliferative activities against cancer cells. Herein, we extracted the secondary metabolites using ethyl acetate from its root bark and further tested its antiproliferative activities against P388 murine leukemia cell lines. The subfractions from the ethyl acetate extract was obtained from Vacuum Liquid Column Chromatography (VLCC), and followed by Gravity Column Chromatography (GCC). The subfraction C2 and D1 were identified to contain triterpenoids and steroids with the most potent cytotoxicity against Brine Shrimp Lethality Test (BSLT). A 3-(4,5-dimethylthiazol-2-yl) -2-5 diphenyl tetrazolium bromide (MTT) assay suggested that ethyl acetate extract has the highest antiproliferative activities against P388 murine leukemia cell lines (IC50 = 21.79 μg/mL), as opposed to subfraction C2 (IC50 = 50.64 µg/mL) and subfraction D1 (IC50 = 49.33 µg/mL). The compound identified in subfraction C2 and D1 are taraxerol acetate and calotropone, respectively. Though taraxerol acetate and calotropone were active in inhibiting the leukemic cell lines, their IC50s were lower than the ethyl acetate extract, which is probably due to the synergism of the secondary metabolites.
Opening the “Black Box” of University Entrepreneurial Intention in the Era of the COVID-19 Pandemic
Authors: Gomes Sofia , Sousa Marlene , Santos Tânia , Oliveira José , Oliveira Márcio , Lopes João M.
Published: May 2021

This research aims to study the determinants of entrepreneurial intention in academia and compare the outcomes from two different moments, before and during the COVID-19 pandemic. For this purpose, a quantitative methodology was used, whereby a questionnaire was given to higher education students in these two chronological moments. From the obtained results, it was possible to ascertain that, given the motivational dimension, the attitude towards behavior and perceived behavioral control are having a positive impact on entrepreneurial intentions during the pandemic and that subjective norms have a negative impact on entrepreneurial intentions. This relationship of influences is unchanged, either before or during the pandemic. Regarding the environmental dimension, both of the variables under analysis are having a negative impact on entrepreneurial intention during the pandemic period, which corresponds to an aggravation or loss of positive influences when compared to the context before the pandemic, and the next assessment had a positive impact on entrepreneurial intentions. On the theoretical contributions, the findings are very important, as they strengthen the literature on entrepreneurial intentions, and in specific contexts of social and economic instability. As for practical contributions, this research suggests actions to agents with an important intervention role in the community, one of these agents is Higher Education Institutions, which play a determining role by creating a positive environment to support their students’ entrepreneurial intent. This research is original, as far as we are informed, and it is the first to study entrepreneurial intention in academia during the COVID-19 pandemic in the Portuguese context. Moreover, we suggest that the obtained results should be succeeded by further studies to confirm the evolutionary trends now identified on the subject under analysis.
Geoenvironmental Implications and Biocenosis of Freshwater Lakes in the Arid Zone of East Kazakhstan
Authors: Samarkhanov Talant N. , Myrzagaliyeva Anar B. , Chlachula Jiri , Kushnikova Ludmila B. , Czerniawska Jolanta , Nigmetzhanov Sayan B.
Published: May 2021

Steppe and semi-desert lakes of Central Asia represent unique and still poorly known aquatic ecosystems. The paper provides summaries of multi-proxy environmental and biological investigations of the previously unexplored ground of Sibe lakes in the naturally pristine zone of East Kazakhstan, and of their contributions to people. Data on the taxonomic composition of zooplankton and zoobenthos of these freshwater lacustrine basins are presented in terms of the species’ frequency of occurrence; the abundance of the aquatic biomass and the analyzed water geochemical variables insofar as they are dependent and correlative. The qualitative and quantitative records display variability in the biocenosis diversity due to the lakes’ geochemistry and hydrology differences—some lakes being oligotrophic and others being moderately trophic. In the latter case, the lakes characterized by an increased macrozoobenthos biomass are favourable for local ichthyofauna. Sapro-biological analysis reveals the predominance of β-saprobic species in the zooplankton composition pointing to slight or moderate pollution of surface waters due to natural biotic substances. This observation is in agreement with differences in the water quality of solitary lakes. The uneven distributions of benthic invertebrates (in terms of taxonomy and species populations) in the water bodies suggest specific hydro-ecological conditions that predetermine the structure of the lakes’ biocenosis. The littoral part of the lakes is characterized by the highest abundance of zooplankton and benthic fauna. The Sibe lakes are an example of an autonomous functioning of the lacustrine basins in the upland arid steppe zone, which is characterized by pronounced climate “continentality” and a high level of the sub-aquatic flora and fauna endemism. The present results are relevant to the understanding of the ecosystems’ dynamics and the modern anthropogenic impacts upon the pristine parkland-steppe landscapes of Central Asia, with implications for regional nature protection and sustainable eco-recreation.
Optimized Factor Approximants and Critical Index
Authors: Gluzman Simon
Published: May 2021

Based on expansions with only two coefficients and known critical points, we consider a minimal model of critical phenomena. The method of analysis is both based on and inspired with the symmetry properties of functional self-similarity relation between the consecutive functional approximations. Factor approximants are applied together with various natural optimization conditions of non-perturbative nature. The role of control parameter is played by the critical index by itself. The minimal derivative condition imposed on critical amplitude appears to bring the most reasonable, uniquely defined results. The minimal difference condition also imposed on amplitudes produces upper and lower bound on the critical index. While one of the bounds is close to the result from the minimal difference condition, the second bound is determined by the non-optimized factor approximant. One would expect that for the minimal derivative condition to work well, the bounds determined by the minimal difference condition should be not too wide. In this sense the technique of optimization presented above is self-consistent, since it automatically supplies the solution and the bounds. In the case of effective viscosity of passive suspensions the bounds could be found that are too wide to make any sense from either of the solutions. Other optimization conditions imposed on the factor approximants, lead to better estimates for the critical index for the effective viscosity. The optimization is based on equating two explicit expressions following from two different definitions of the critical index, while optimization parameter is introduced as the trial third-order coefficient in the expansion.
ROS Cocktails as an Adjuvant for Personalized Antitumor Vaccination?
Authors: Clemen Ramona , Bekeschus Sander
Published: May 2021

Cancer is the second leading cause of death worldwide. Today, the critical role of the immune system in tumor control is undisputed. Checkpoint antibody immunotherapy augments existing antitumor T cell activity with durable clinical responses in many tumor entities. Despite the presence of tumor-associated antigens and neoantigens, many patients have an insufficient repertoires of antitumor T cells. Autologous tumor vaccinations aim at alleviating this defect, but clinical success is modest. Loading tumor material into autologous dendritic cells followed by their laboratory expansion and therapeutic vaccination is promising, both conceptually and clinically. However, this process is laborious, time-consuming, costly, and hence less likely to solve the global cancer crisis. Therefore, it is proposed to re-focus on personalized anticancer vaccinations to enhance the immunogenicity of autologous therapeutic tumor vaccines. Recent work re-established the idea of using the alarming agents of the immune system, oxidative modifications, as an intrinsic adjuvant to broaden the antitumor T cell receptor repertoire in cancer patients. The key novelty is the use of gas plasma, a multi-reactive oxygen and nitrogen species-generating technology, for diversifying oxidative protein modifications in a, so far, unparalleled manner. This significant innovation has been successfully used in proof-of-concept studies and awaits broader recognition and implementation to explore its chances and limitations of providing affordable personalized anticancer vaccines in the future. Such multidisciplinary advance is timely, as the current COVID-19 crisis is inexorably reflecting the utmost importance of innovative and effective vaccinations in modern times.
Quality Verification with a Cluster−Controlled Manufacturing System to Generate Monocyte−Derived Dendritic Cells
Authors: Kawaguchi Haruhiko , Sakamoto Takuya , Koya Terutsugu , Togi Misa , Date Ippei , Watanabe Asuka , Yoshida Kenichi , Kato Tomohisa , Nakamura Yuka , Ishigaki Yasuhito , Shimodaira Shigetaka
Published: May 2021

Dendritic cell (DC) vaccines for cancer immunotherapy have been actively developed to improve clinical efficacy. In our previous report, monocyte−derived DCs induced by interleukin (IL)−4 with a low−adherence dish (low−adherent IL-4−DCs: la−IL-4−DCs) improved the yield and viability, as well as relatively prolonged survival in vitro, compared to IL-4−DCs developed using an adherent culture protocol. However, la−IL-4−DCs exhibit remarkable cluster formation and display heterogeneous immature phenotypes. Therefore, cluster formation in la−IL-4−DCs needs to be optimized for the clinical development of DC vaccines. In this study, we examined the effects of cluster control in the generation of mature IL-4−DCs, using cell culture vessels and measuring spheroid formation, survival, cytokine secretion, and gene expression of IL-4−DCs. Mature IL-4−DCs in cell culture vessels (cluster−controlled IL-4−DCs: cc−IL-4−DCs) displayed increased levels of CD80, CD86, and CD40 compared with that of la−IL-4−DCs. cc−IL-4−DCs induced antigen−specific cytotoxic T lymphocytes (CTLs) with a human leukocyte antigen (HLA)−restricted melanoma antigen recognized by T cells 1 (MART−1) peptide. Additionally, cc−IL-4−DCs produced higher levels of IFN−γ, possessing the CTL induction. Furthermore, DNA microarrays revealed the upregulation of BCL2A1, a pro−survival gene. According to these findings, the cc−IL-4−DCs are useful for generating homogeneous and functional IL-4−DCs that would be expected to promote long−lasting effects in DC vaccines.
Sow Vaccination with a Protein Fragment against Virulent Glaesserella (Haemophilus) parasuis Modulates Immunity Traits in Their Offspring
Authors: López-Serrano Sergi , Neila-Ibáñez Carlos , Costa-Hurtado Mar , Mahmmod Yasser , Martínez-Martínez Jorge , Galindo-Cardiel Iván José , Darji Ayub , Rodríguez Fernando , Sibila Marina , Aragon Virginia
Published: May 2021

Glaesserella (Haemophilus) parasuis, an early colonizer of the nasal cavity in piglets, is a highly heterogeneous species, comprising both commensal and virulent strains. Virulent G. parasuis strains can cause fibrinous polyserositis called Glässer’s disease. Colostrum is a source of passive immunity for young piglets. When vaccinating sows, protective antibodies are transferred to their offspring through the colostrum. Here, sow vaccination was performed with a protein fragment, F4, from the outer membrane trimeric autotransporters VtaAs exclusively found in virulent G. parasuis. Piglets were allowed to suckle for 3 weeks, following which a challenge with two virulent strains of G. parasuis was performed. A group of nonvaccinated sows and their piglets were included as a control. Antibodies against F4 were confirmed using ELISA in the vaccinated sows and their offspring before the G. parasuis challenge. Compared to the control group, F4-vaccination also resulted in an increased level of serum TGF-β both in vaccinated sows and in their offspring at early time points of life. After the challenge, a lower body temperature and a higher weight were observed in the group of piglets from vaccinated sows. One piglet from the non-vaccinated group succumbed to the infection, but no other significant differences in clinical signs were noticed. At necropsy, performed 2 weeks after the virulent challenge, the level of surfactant protein D (SP-D) in bronchoalveolar lavage was higher in the piglets from vaccinated sows. Vaccination did not inhibit the nasal colonization of the piglets by the challenge strains.
Mental reactions of doctors against the background of the SARS-CoV-2 pandemic (message 1)
Authors: Kinkulkina Marina Arkadievna , Gardanova Zhanna Robertovna , Novikov Vladimir Vladimirovich , Khritinin Dmitriy Fedorovich
Published: May 2021

The article considers various mental reactions of doctors against the background of the SARS-CoV-2 pandemic, based on a brief scientific analysis of the literature and experimental psychological research methods. It has been found that currently, the impact of the SARS-CoV-2 pandemic on medical workers causes a complex of mental reactions (from anosognosia to severe anxiety and depressive disorders) and is accompanied by an increase in general anxiety. This pilot study showed the need for further analysis of the problem under consideration.
Features of modern approaches to the diagnosis and treatment of insomnia
Authors: Khritinin Dmitry Fedorovich , Sumarokova M. A. , Schukina E. P.
Published: May 2021

Currently, insomnia is not only a medical, but also a social as well as an economic problem. Sleep disorders increase the risk of somatic, neurological and mental illnesses. The shift schedule has a significant impact on the employee’s health, increasing the risk of developing such disorders as metabolic syndrome, arterial hypertension and other. As a result of sleep disturbances, lipid peroxidation processes may intensify, which can lead to the disorders described above. Therefore, the prevention and treatment of sleep disorders is an important aspect of chronic diseases diagnostics. In our opinion, it is crucial to study possible sleep disorders for their timely correction. The article discusses the features of drug and non-drug treatment of sleep disorders, as well as approaches to the primary and secondary prevention of insomnia. It is recommended to begin the treatment of sleep disorders with cognitive-behavioral therapy. Cognitive-behavioral therapy for insomnia typically includes psycho-education, training in relaxation techniques, stimulation limitation method, sleep limitation therapy, and cognitive therapy. When developing recreational activities for employees with a shift work schedule, attention should be paid to work and rest regimes, prevention of fatigue and obesity, and the sleep disorders treatment. Training in sleep hygiene and improving its compliance in the target groups is regarded as a method of non-pharmacological treatment of sleep disorders and a means of primary and secondary prevention of insomnia. In our opinion, further research on the features of the prevention and treatment of insomnia in various population groups is needed. Effective primary and secondary prevention of sleep disorders will reduce the risks of developing neurological, somatic and mental diseases and significantly improve the quality of life.
Modern principles of the diagnosis and conservative treatment of Cushing disease
Authors: Abdali Ashraf , Astafeva Ludmila , Kalinin Pavel , Trunin Yuriy , Chernov I. V. , Сhmutin G. E. , Badshahzar Abdali , Sherzad GulSharif , Keith Simfukwe
Published: May 2021

Cushing disease is a severe neuro-endocrinological disorder caused by hypersecretion of ACTH from a benign lesion of hypophyseal gland which is clinically represented by symptoms of hypercortisolism. Cushing disease is associated with an increased risk of cardiovascular and metabolic disorders, psychological complications, osteoporosis and infectious diseases which bring about an increased mortality rate. The article considers the clinical and diagnostic aspects of Cushing disease in accordance to the modern international protocols and recommendations along with the modern principles of conservative treatment.
Syntactic Annotation in the I3rab Dependency Treebank
Authors: Halabi Dana , Awajan Arafat , Fayyoumi Ebaa
Published: May 2021

Arabic dependency parsers have a poor performance compared to parsers of other languages. Recently the impact of annotation at lexical level of dependency treebank on the overall performance of the dependency parses has been extensively investigated. This paper focuses on the impact of coarse-grained and fine-grained dependency relations on the performance of Arabic dependency parsers. Moreover, this paper introduces the annotation rules for I3rab dependency treebank. Experimentally, the obtained results showed that having an appropriate set of dependency relations improves the performance of an Arabic dependency parser up to 27.55%.
Multi-Spectral Hybrid Invariant Moments Fusion Technique for Face Identification
Authors: Hamandi Shaymaa , Rahma Abdul Monem , Hassan Rehab
Published: May 2021

For reliable face identification, the fusion process of multi-spectral vision features produces robust classification systems, this paper exploits the power of thermal facial image invariant moments features fused with the visible facial image invariant moments features to propose a new multi-spectral hybrid invariant moment fusion system for face identification. And employs Feed-forward neural network to train the moments' features and make decisions. The evaluation system uses databases of visible thermal pairs face images CARL and UTK-IRIS databases and gives an accuracy reaches 99%.
Evaluation of cone beam computed tomography imaging in placed dental implants: comparison between multiplanar reconstruction and parasagittal images / Avaliação de imagens de tomografia computadorizada de feixe cônico em implantes instalados: comparação entre reconstrução multiplanar e imagens parassagitais
Authors: Chagas Mariana Murai , Silva Maria Alves Garcia , Cavalcanti Marcelo Gusmão Paraiso
Published: May 2021

This study aimed to compare multiplanar reconstruction (MPR) to parasagittal images of cone-beam computed tomography (CBCT) for localizing placed dental implants concerning adjacent anatomical structures (nasal fossa floor, maxillary sinus, inferior alveolar canal and nasopalatine canal).The CBCT exams of 164 placed implants were analyzed. All tomographic images were imported to Imaging Studio software to create parasagittal image templates. The images were randomized and analyzed by two oral and maxillofacial radiologists who classified whether or not there was perforation of the anatomical structure in question.According to Kappa coefficient of agreement, the results including, all anatomical structures for inter-observer assessment was 0.81 and for intra-observer assessment, 0.79 for observer one and 0.89 for observer two. For each anatomical structure, the agreement ranged from 'substantial' to 'almost perfect' (nasal fossa floor 0.72, nasopalatine canal 0.92, maxillary sinus 0.81, and inferior alveolar canal 0.81).  Based on our findings, there was substantial to almost perfect agreement when comparing MPR and parasagittal images of CBCT regarding of implant position relationship with anatomical structures. Since both modalities did not differ in implant position, and the MPR represents the complete and original volume that enables analysis in three dimensions, they can be the first-choice imaging modality to analyze placed dental implants.
CINEMATOGRAFIA DIGITAL E FOTÔNICA
Authors: Gomide João Victor Boechat
Published: May 2021

Nesse artigo é destacado o impacto que o surgimento e o desenvolvimento da fotônica provocou na produção audiovisual. O registro e a distribuição da imagem digital só foram possíveis pelos avanços da fotônica. A mudança de paradigma que ocorreu em todas as áreas que utilizam imagens, principalmente ao longo das três últimas décadas, e na cinematografia, com a substituição dos formatos até então dominantes, em filme ou analógico, pelos formatos digitais, está intimamente relacionado com os avanços da Ciência da Luz. A investigação científica e as invenções da fotônica geraram os sensores de semicondutor para a captura da imagem, os lasers, para fazer sua digitalização, e as fibras óticas, para distribuí-la em tempo real, e provocaram uma revolução na forma em que a imagem é capturada, processada, armazenada e distribuída. Esse artigo discute as razões do abandono dos formatos em filme e analógico, como isso foi possível, e compara os fluxos de trabalho químico e digital, tomando como ponto de partida a experiência visual provocada pela imagem cinematográfica. As críticas do diretor Quentin Tarantino são apresentadas e sua o seu filme, The Hateful Eight, é usado como um exemplo da polêmica gerada pelo abandono inexorável da película. Novas perspectivas estão se abrindo hoje, com a conexão 5G e a possibilidade de se enviar as imagens diretamente para as nuvens de armazenamento.
Controls at the starting point for preventing accidents in the road transport of dangerous products / Controles no ponto de partida para prevenção de acidentes no transporte rodoviário de produtos perigosos
Authors: Cabral Ana Beatriz Paes Barretto , Bezerra Marcelo Roberto Ventura Dias de Mattos , Novo Jean Marcel de Faria
Published: May 2021

This article discusses activities related to the prevention of road accidents with dangerous products that precede trips by tank truck drivers. The Brazilian normative framework (laws, decrees, and norms), the Haddon Matrix as a systemic prevention model, and the premises of the Olho Vivo nas Estradas Program of the Brazilian Chemical Industry Association constitute the conceptual bases of the research. The empirical approach consists of semi-structured interviews with drivers of a fuel distributor who travel along the BR-116. The results indicate that the company has training practices and disclosure of recent accidents. The workgroup dominates the normative knowledge and preventive procedures, being the main concern of the interviewees with the carelessness practiced by drivers who travel the roads in all types of vehicles (trucks, automobiles, motorcycles).
Abordagem inicial da criança com Insuficiência Respiratória
Authors: Germano Letícia Geovanna Ramos , de Oliveira Kessia Karina Alves , de Freitas Maria Beatriz Mariz Maia de Freitas , Pinto Millena Maria Maciel , de Arruda Isabela Tatiana Sales , de Souza Alysson Kennedy Pereira , de Souza Daniela Heitzmann Amaral Valentin , de Arruda Isabela Tatiana Sales
Published: May 2021

Na população pediátrica, a principal causa de mortalidade é o comprometimento do sistema respiratório, logo, o conhecimento da abordagem inicial da criança com insuficiência respiratória é fundamental, tendo em vista que essa por sua vez auxilia no diagnóstico e tratamento precoce da IR. O nosso objetivo foi discutir a fisiopatologia da insuficiência respiratória na criança, os aspectos do diagnóstico diferencial e do tratamento. A falha de oxigenação no aparelho respiratório pode ser provocada por alteração de difusão na membrana alveolocapilar ou, mais classicamente, pela relação desigual entre a ventilação alveolar e o fluxo sanguíneo alveolar. Os mecanismos fisiopatológicos que levam à insuficiência respiratória podem se dividir em falha de oxigenação e falha de ventilação. O tratamento varia dependendo do caso do paciente, ele compreende a permeabilização das vias aéreas, a ventilação assistida e a oxigenoterapia, a manutenção da circulação adequada pela fluidoterapia e uso de drogas vasoativas. É premente que que a insuficiência respiratória aguda seja diagnosticada precocemente na infância para que se possa reestabelecer sua oxigenação e a ventilação dessa criança de maneira adequada levando a reversão desse quadro clínico.
Diagonally Compressed TNAZ - A DFT Treatment
Authors: Türker Lemi
Published: May 2021

TNAZ is an insensitive explosive material having a 4-membered azetidine ring system which has three nitro groups substituted, one of them is a nitramine type. In the present density functional treatise at the level of B3LYP/6-311++G(d,p), the 4-membered ring of TNAZ is compressed diagonally either along the X- or Y-axis direction. Various properties (including energies, quantum chemical and spectral etc.) in the perturbed systems have been searched and discussed.
Teacher Moments: A digital clinical simulation platform with extensible AI architecture
Authors: Hillaire Garron , Waldron Rick , Murray Chas , Dutt Ritam , Marvez Gabrielle R , Larke Laura R. , Rose Carolyn , Reich Justin
Published: May 2021

Teacher Moments is an open source platform that allows the authoring of simulations used for education which we recently revised to integrate intelligent coaching agents. The initial simulation development for Teacher Moments focused on teacher education, but the platform is actively used for professional development with nurses, psychologists, police officers, judges, and attorneys. Simulations can range in complexity from single-user simulations to multi-user role-play simulations. Single-user simulations provide opportunities for participants to respond using text or audio inputs while multiuser simulations extend those response types to include chat functionality. To support participant learning, Teacher Moments simulations can now be configured to include intelligent coaching agents that review participant inputs, identify salient patterns in text or speech, and respond with feedback and coaching supports. Teacher Moments can be configured to incorporate text or audio binary classifiers or include conversational agents into the chat feature. Once a classifier is configured there is functionality to dynamically display content based on audio or text classification when authoring the simulation. In addition, conversational agents can interject comments into the chat directed at either a particular participant or to all participants in a chat. Finally, there is a new integrated labeling component that supports collecting binary labels from participants for text or audio data, which can be used either to validate the accuracy of a classifier or to establish training data for a classifier. In this demo, we will: 1) highlight GitHub repositories designed to support the deployment of classifiers that can be integrated into Teacher Moments; 2) demonstrate a conversational agent integrated into the chat feature to provide intelligent supports; 3) illustrate how binary classification can trigger the dynamic display of content providing options for dynamic learning supports; and 4) demonstrate how the labeling component can be used for either validation of a classifier or collection of training data.
ANALYSIS OF MICROFLORA IN MODERN OUTPATIENT CLINIC
Authors: Pahomov Mikhail , Morozov Artyom , Sergeev Alexey , Mokhov, Evgeny , Sergeev Nikolay , Askerov Elshad
Published: May 2021

Antibiotic resistance is a global problem of modern medicine. In the research a microflora of out-patient department visitors in 2018–2019 was examined. It was revealed that the most often microbes were Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli. The dynamics of bacterial resistance to antibiotics was also analyzed. The multiple bacterial resistance to antibiotics were detected. The data show a rapid resistance genes spread among non-hospital strains, which necessitates constant monitoring of antibiotic sensitivity in order to develop the right tactics to combat antibiotic resistance.