bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation and Effectiveness of Policies Adopted to Enable Breastfeeding in the Philippines Are Limited by Structural and Individual Barriers
Authors: Samaniego Jyn Allec R. , Maramag Cherry C. , Castro Mary Christine , Zambrano Paul , Nguyen Tuan T. , Datu-Sanguyo Janice , Cashin Jennifer , Mathisen Roger , Weissman Amy
Published: September 2022

The Philippines has adopted policies to protect, promote, and support breastfeeding on par with global standards, yet the impact of these policies is not well understood. This study assesses the adequacy and potential impact of breastfeeding policies, as well as the perceptions of stakeholders of their effectiveness and how to address implementation barriers. This mixed methods study entailed a desk review of policies and documents and in-depth interviews with 100 caregivers, employees, employers, health workers, and policymakers in the Greater Manila Area. Although the Philippines has a comprehensive breastfeeding policy framework, its effectiveness was limited by structural and individual barriers. Structural barriers included inconsistent breastfeeding promotion, limited access of mothers to skilled counseling, limited workplace breastfeeding support, gaps in legal provisions, weak monitoring and enforcement of the Philippine Milk Code, and the short duration and limited coverage of maternity leave. Individual barriers included knowledge and skills gaps, misconceptions, and low self-confidence among mothers due to insufficient support to address breastfeeding problems, misconceptions in the community that undermine breastfeeding, limited knowledge and skills of health workers, and insufficient support extended to mothers by household members. Breastfeeding policies in the Philippines are consistent with global standards, but actions to address structural and individual barriers are needed to enhance their effectiveness for improving breastfeeding practices.
Critical Players and Therapeutic Targets in Chronic Itch
Authors: Yang Hua , Chen Weiwei , Zhu Renkai , Wang Jiafu , Meng Jianghui
Published: September 2022

Chronic itch is one of the most prominent clinical characteristics of diverse systematic diseases. It is a devastating sensation in pathological diseases. Despite its importance, there are no FDA-labelled drugs specifically geared toward chronic itch. The associated complex pathogenesis and diverse causes escalate chronic itch to being one of the top challenges in healthcare. Humanized antibodies against IL-13, IL-4, and IL-31 proved effective in treatment of itch-associated atopic dermatitis but remain to be validated in chronic itch. There are still no satisfactory anti-itch therapeutics available toward itch-related neuropeptides including GRP, BNP, SST, CGRP, and SP. The newly identified potential itch targets including OSM, NMB, glutamate, periostin, and Serpin E1 have opened new avenues for therapeutic development. Proof-of-principle studies have been successfully performed on antagonists against these proteins and their receptors in itch treatment in animal models. Their translational interventions in humans need to be evaluated. It is of great importance to summarize and compare the newly emerging knowledge on chronic itch and its pathways to promote the development of novel anti-itch therapeutics. The goal of this review is to analyze the different physiologies and pathophysiologies of itch mediators, whilst assessing their suitability as new targets and discussing future therapeutic development.
Clostridium novyi’s Alpha-Toxin Changes Proteome and Phosphoproteome of HEp-2 Cells
Authors: Schweitzer Theresa , Genth Harald , Pich Andreas
Published: September 2022

C. novyi type A produces the alpha-toxin (TcnA) that belongs to the large clostridial glucosylating toxins (LCGTs) and is able to modify small GTPases by N-acetylglucosamination on conserved threonine residues. In contrast, other LCGTs including Clostridioides difficile toxin A and toxin B (TcdA; TcdB) modify small GTPases by mono-o-glucosylation. Both modifications inactivate the GTPases and cause strong effects on GTPase-dependent signal transduction pathways and the consequent reorganization of the actin cytoskeleton leading to cell rounding and finally cell death. However, the effect of TcnA on target cells is largely unexplored. Therefore, we performed a comprehensive screening approach of TcnA treated HEp-2 cells and analyzed their proteome and their phosphoproteome using LC-MS-based methods. With this data-dependent acquisition (DDA) approach, 5086 proteins and 9427 phosphosites could be identified and quantified. Of these, 35 proteins were found to be significantly altered after toxin treatment, and 1832 phosphosites were responsive to TcnA treatment. By analyzing the TcnA-induced proteomic effects of HEp-2 cells, 23 common signaling pathways were identified to be altered, including Actin Cytoskeleton Signaling, Epithelial Adherens Junction Signaling, and Signaling by Rho Family GTPases. All these pathways are also regulated after application of TcdA or TcdB of C. difficile. After TcnA treatment the regulation on phosphorylation level was much stronger compared to the proteome level, in terms of both strength of regulation and the number of regulated phosphosites. Interestingly, various signaling pathways such as Signaling by Rho Family GTPases or Integrin Signaling were activated on proteome level while being inhibited on phosphorylation level or vice versa as observed for the Role of BRCA1 in DNA Damage Response. ZIP kinase, as well as Calmodulin-dependent protein kinases IV & II, were observed as activated while Aurora-A kinase and CDK kinases tended to be inhibited in cells treated with TcnA based on their substrate regulation pattern.
Matrix Vesicle-Mediated Mineralization and Osteocytic Regulation of Bone Mineralization
Authors: Hasegawa Tomoka , Hongo Hiromi , Yamamoto Tomomaya , Abe Miki , Yoshino Hirona , Haraguchi-Kitakamae Mai , Ishizu Hotaka , Shimizu Tomohiro , Iwasaki Norimasa , Amizuka Norio
Published: September 2022

Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by osteoblasts, and thereafter, bone mineral density gradually increases during secondary mineralization. Nearby extracellular phosphate ions (PO43−) flow into the vesicles via membrane transporters and enzymes located on the vesicles’ membranes, while calcium ions (Ca2+), abundant in the tissue fluid, are also transported into the vesicles. The accumulation of Ca2+ and PO43− in the matrix vesicles induces crystal nucleation and growth. The calcium phosphate crystals grow radially within the vesicle, penetrate the vesicle’s membrane, and continue to grow outside the vesicle, ultimately forming mineralized nodules. The mineralized nodules then attach to collagen fibrils, mineralizing them from the contact sites (i.e., collagen mineralization). Afterward, the bone mineral density gradually increases during the secondary mineralization process. The mechanisms of this phenomenon remain unclear, but osteocytes may play a key role; it is assumed that osteocytes enable the transport of Ca2+ and PO43− through the canaliculi of the osteocyte network, as well as regulate the mineralization of the surrounding bone matrix via the Phex/SIBLINGs axis. Thus, bone mineralization is biologically regulated by osteoblasts and osteocytes.
Preparation and Properties of Double-Crosslinked Hydroxyapatite Composite Hydrogels
Authors: Zhao Benbo , Zhao Mingda , Li Liming , Sun Shixiong , Yu Heping , Cheng Yuan , Yang Yuedi , Fan Yujiang , Sun Yong
Published: September 2022

Natural polymer hydrogels have good mechanical properties and biocompatibility. This study designed hydroxyapatite-enhanced photo-oxidized double-crosslinked hydrogels. Hyaluronic acid (HA) and gelatin (Gel) were modified with methacrylate anhydride. The catechin group was further introduced into the HA chain inspired by the adhesion chemistry of marine mussels. Hence, the double-crosslinked hydrogel (HG) was formed by the photo-crosslinking of double bonds and the oxidative-crosslinking of catechins. Moreover, hydroxyapatite was introduced into HG to form hydroxyapatite-enhanced hydrogels (HGH). The results indicate that, with an increase in crosslinking network density, the stiffness of hydrogels became higher; these hydrogels have more of a compact pore structure, their anti-degradation property is improved, and swelling property is reduced. The introduction of hydroxyapatite greatly improved the mechanical properties of hydrogels, but there is no change in the stability and crosslinking network structure of hydrogels. These inorganic phase-enhanced hydrogels were expected to be applied to tissue engineering scaffolds.
Genomic Dissection and Diurnal Expression Analysis Reveal the Essential Roles of the PRR Gene Family in Geographical Adaptation of Soybean
Authors: Wang Peiguo , Wang Liwei , Zhang Lixin , Wu Tingting , Sun Baiquan , Zhang Junquan , Sapey Enoch , Yuan Shan , Jiang Bingjun , Chen Fulu , Wu Cunxiang , Hou Wensheng , Sun Shi , Bai Jiangping , Han Tianfu
Published: September 2022

Pseudo-response regulator (PRR) family members serve as key components of the core clock of the circadian clock, and play important roles in photoperiodic flowering, stress tolerance, growth, and the development of plants. In this study, 14 soybean PRR genes were identified, and classified into three groups according to phylogenetic analysis and structural characteristics. Real-time quantitative PCR analysis revealed that 13 GmPRRs exhibited obvious rhythmic expression under long-day (LD) and short-day (SD) conditions, and the expression of 12 GmPRRs was higher under LD in leaves. To evaluate the effects of natural variations in GmPRR alleles on soybean adaptation, we examined the sequences of GmPRRs among 207 varieties collected across China and the US, investigated the flowering phenotypes in six environments, and analyzed the geographical distributions of the major haplotypes. The results showed that a majority of non-synonymous mutations in the coding region were associated with flowering time, and we found that the nonsense mutations resulting in deletion of the CCT domain were related to early flowering. Haplotype analysis demonstrated that the haplotypes associated with early flowering were mostly distributed in Northeast China, while the haplotypes associated with late flowering were mostly cultivated in the lower latitudes of China. Our study of PRR family genes in soybean provides not only an important guide for characterizing the circadian clock-controlled flowering pathway but also a theoretical basis and opportunities to breed varieties with adaptation to specific regions and farming systems.
The Role of Ergosterol and Sphingolipids in the Localization and Activity of Candida albicans’ Multidrug Transporter Cdr1p and Plasma Membrane ATPase Pma1p
Authors: Urbanek Aneta K. , Muraszko Jakub , Derkacz Daria , Łukaszewicz Marcin , Bernat Przemysław , Krasowska Anna
Published: September 2022

Opportunistic pathogen Candida albicans causes systemic infections named candidiasis. Due to the increasing number of multi-drug resistant clinical isolates of Candida sp., currently employed antifungals (e.g., azoles) are insufficient for combating fungal infection. One of the resistance mechanisms toward azoles is increased expression of plasma membrane (PM) transporters (e.g., Cdr1p), and such an effect was observed in C. albicans clinical isolates. At the same time, it has been proven that a decrease in PMs sphingolipids (SLs) content correlates with altered sensitivity to azoles and diminished Cdr1p levels. This indicates an important role for SL in maintaining the properties of PM and gaining resistance to antifungal agents. Here, we prove using a novel spot variation fluorescence correlation spectroscopy (svFCS) technique that CaCdr1p localizes in detergent resistant microdomains (DRMs). Immunoblot analysis confirmed the localization of CaCdr1p in DRMs fraction in both the C. albicans WT and erg11Δ/Δ strains after 14 and 24 h of culture. We also show that the C. albicanserg11Δ/Δ strain is more sensitive to the inhibitor of SLs synthesis; aureobasidin A (AbA). AbA treatment leads to a diminished amount of SLs in C. albicans WT and erg11Δ/Δ PM, while, for C. albicanserg11Δ/Δ, the general levels of mannose-inositol-P-ceramide and inositol-P-ceramide are significantly lower than for the C. albicans WT strain. Simultaneously, the level of ergosterol in the C. albicans WT strain after adding of AbA remains unchanged, compared to the control conditions. Analysis of PM permeabilization revealed that treatment with AbA correlates with the disruption of PM integrity in C. albicanserg11Δ/Δ but not in the C. albicans WT strain. Additionally, in the C. albicans WT strain, we observed lower activity of H+-ATPase, correlated with the delocalization of both CaCdr1p and CaPma1p.
Recent Advances in Molecular Improvement for Potato Tuber Traits
Authors: Ahmad Daraz , Zhang Zhongwei , Rasheed Haroon , Xu Xiaoyong , Bao Jinsong
Published: September 2022

Potato is an important crop due to its nutritional value and high yield potential. Improving the quality and quantity of tubers remains one of the most important breeding objectives. Genetic mapping helps to identify suitable markers for use in the molecular breeding, and combined with transgenic approaches provides an efficient way for gaining desirable traits. The advanced plant breeding tools and molecular techniques, e.g., TALENS, CRISPR-Cas9, RNAi, and cisgenesis, have been successfully used to improve the yield and nutritional value of potatoes in an increasing world population scenario. The emerging methods like genome editing tools can avoid incorporating transgene to keep the food more secure. Multiple success cases have been documented in genome editing literature. Recent advances in potato breeding and transgenic approaches to improve tuber quality and quantity have been summarized in this review.
Lateral Flow Immunoassay Based on Time-Resolved Fluorescence Microspheres for Rapid and Quantitative Screening CA199 in Human Serum
Authors: Jiao Xueshima , Peng Tao , Liang Zhanwei , Hu Yalin , Meng Bo , Zhao Yang , Xie Jie , Gong Xiaoyun , Jiang You , Fang Xiang , Yu Xiaoping , Dai Xinhua
Published: September 2022

Carbohydrate antigen 199 (CA199) is a serum biomarker which has certain value and significance in the diagnosis, prognosis, treatment, and postoperative monitoring of cancer. In this study, a lateral flow immunoassay based on europium (III) polystyrene time-resolved fluorescence microspheres (TRFM-based LFIA), integrated with a portable fluorescence reader, has been successfully establish for rapid and quantitative analysis of CA199 in human serum. Briefly, time-resolved fluorescence microspheres (TRFMs) were conjugated with antibody I (Ab1) against CA199 as detection probes, and antibody II (Ab2) was coated as capture element, and a “TRFMs-Ab1-CA199-Ab2” sandwich format would form when CA199 was detected by the TRFM-based LFIA. Under the optimal parameters, the detection limit of the TRFM-based LFIA for visible quantitation with the help of an ultraviolet light was 4.125 U/mL, which was four times lower than that of LFIA based on gold nanoparticles. Additionally, the fluorescence ratio is well linearly correlated with the CA199 concentration (0.00–66.0 U/mL) and logarithmic concentration (66.0–264.0 U/mL) for quantitative detection. Serum samples from 10 healthy people and 10 liver cancer patients were tested to confirm the performances of the point-of-care application of the TRFM-based LFIA, 20.0 U/mL of CA199 in human serum was defined as the threshold for distinguishing healthy people from liver cancer patients with an accuracy of about 60%. The establishment of TRFM-based LFIA will provide a sensitive, convenient, and efficient technical support for rapid screening of CA199 in cancer diagnosis and prognosis.
Preparation of Porous Ellipsoidal Bismuth Oxyhalide Microspheres and Their Photocatalytic Performances
Authors: Luo Bing , Wu Canfeng , Zhang Fuzeng , Wang Tingting , Yao Yingbang
Published: September 2022

Well-dispersed and uniform porous ellipsoidal-shaped bismuth oxyhalides (nominal composition: 80%BiOCl/20%BiOI) microspheres were obtained by a facile solvothermal method, in which process the use of polyvinylpyrrolidone (PVP) as template agent was found to be crucial. At 150 °C, elliptical porous particles with a particle size of 0.79 μm were formed. Instead of forming solid solutions, the study of X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM) shows that the prepared 80%BiOCl/20%BiOI microspheres are composite of BiOCl and BiOI in nature and the obtained crystallite size is about 5.6 nm. The optical bandgap of 80%BiOCl/20%BiOI was measured to be 2.93 eV, which is between the bandgap values of BiOCl and BiOI. The 80%BiOCl/20%BiOI microspheres were able to decompose various organic dyes (rhodamine B-RhB, methyl orange-MO, methylene blue-MB, methyl violet-MV) under an illuminated condition with the degradation rate in the order of RhB > MB > MV > MO, and 98% of RhB can be degraded in 90 min. Radical scavenger tests showed that photogenerated holes are the main active species for the photocatalytic decomposition of all of the tested organic dyes. Our results show that the obtained porous ellipsoidal-shaped 80%BiOCl/20%BiOI microspheres are promising for the degradation of various organic pollutants under the illumination of visible light.
Significance or Scatter—Statistical Evaluation of Rapid Chloride Migration Test Results for Sprayable Cement Mortar
Authors: Ullmann Stefan , Nordsiek Sven , Lowke Dirk
Published: September 2022

In order to evaluate the influence of certain experimental or material-related conditions on results of the rapid chloride migration test (RCM test), statistical tests within and between samples are necessary. Thus, it needs to be clear which scatter a sample or a population of results is already subjected to without external influences due to the test method itself. So far, however, literature values for the appropriate statistical variable (coefficient of variation, CoV) explicitly valid for mortar or fine-grained concrete, e.g., for concrete repair, are missing. Therefore, we suggest a specific mortar CoV based on our own results of RCM tests performed on a cement-rich, sprayable mortar based on ordinary Portland cement. For the evaluation of external influences on a sample in comparison to a reference sample, we developed a significance criterion based on a statistical hypothesis test. The sensitivity and the reliability of this criterion is demonstrated on various results from RCM tests on mortar specimens, according to the test specifications and with deliberately chosen deviations from it. In addition, we point out the parameters included in the calculation of the rapid chloride migration coefficient that are the most sensitive to unintentional errors.
Experimental Verification of Theoretical Stress-Strain Model for Compressed Concrete Considering Post-Peak Stage
Authors: Iskhakov Iakov , Frolov Ilya , Ribakov Yuri
Published: September 2022

The theoretical stress-strain model for compressed composite cement materials’ behavior without empirical coefficients was proposed by Iskhakov in 2018. This model includes the following main parameters describing concrete behavior: stresses and strains corresponding to the border between the elastic and non-elastic behavior stages of a concrete specimen, ultimate elastic strains, and stresses and strains at the end of the post-peak region. Particular attention is focused on the descending branch of the stress-strain diagram, as well as on the analysis of concrete elastic and plastic potentials. These potentials are important for assessing the dynamic response of the concrete element section, as well as for concrete creep analysis. The present research is aimed at experimental verification of the above-mentioned theoretical model. The obtained experimental results are in good agreement with the theoretical ones, which confirms the model’s accuracy and enables a significant reduction in the empirical coefficients number in compressed reinforced concrete elements design. This, in turn, represents the scientific novelty of this study.
Effects of Isothermal Temperature on Dislocation Density in Bainite Transformation of 4140 Steel
Authors: Zhu Jian , Barber Gary , Sun Xichen
Published: September 2022

To relate the bainitic microstructures to the mechanical properties of steel, the average dislocation density needs to be determined. Using X-ray diffraction and diffraction line broadening analysis, this research quantifies the average dislocation density in the four bainite phase matrices, (upper bainite, upper and lower bainite mixture, lower bainite, lower bainite and martensite mixture), which are transformed in a wide range of isothermal temperatures. The effects of isothermal temperatures on the average dislocation density are assessed for different thermal dynamic driving forces in terms of activation energy and cooling rate. It is found that as isothermal holding temperature is increased, the dislocation density in the bainite matrix decreases from 1.55 × 1017 to 8.33 × 1015 (m−2) due to the reduction in the plastic deformation in the austenite in the transformation. At the same time, the activation energy required decreases only after passing the martensite and lower bainite mixed phase. A new method for better estimating the average dislocation density in bainitic steel is also proposed.
Investigation of the Efficiency of Shielding Gamma and Electron Radiation Using Glasses Based on TeO2-WO3-Bi2O3-MoO3-SiO to Protect Electronic Circuits from the Negative Effects of Ionizing Radiation
Authors: Kozlovskiy Artem , Shlimas Dmitriy I. , Zdorovets Maxim V. , Popova Elena , Elsts Edgars , Popov Anatoli I.
Published: September 2022

This article considers the effect of MoO3 and SiO additives in telluride glasses on the shielding characteristics and protection of electronic microcircuits operating under conditions of increased radiation background or cosmic radiation. MoO3 and SiO dopants were chosen because their properties, including their insulating characteristics, make it possible to avoid breakdown processes caused by radiation damage. The relevance of the study consists in the proposed method of using protective glasses to protect the most important components of electronic circuits from the negative effects of ionizing radiation, which can cause failures or lead to destabilization of the electronics. Evaluation of the shielding efficiency of gamma and electron radiation was carried out using a standard method for determining the change in the threshold voltage (∆U) value of microcircuits placed behind the shield and subjected to irradiation with various doses. It was established that an increase in the content of MoO3 and SiO in the glass structure led to an increase of up to 90% in the gamma radiation shielding efficiency, while maintaining the stability of microcircuit performance under prolonged exposure to ionizing radiation. The results obtained allow us to conclude that the use of protective glasses based on TeO2–WO3–Bi2O3–MoO3–SiO is highly promising for creating local protection for the main components of microcircuits and semiconductor devices operating under conditions of increased background radiation or cosmic radiation.
Investigation on the Fatigue Crack Propagation of Medium-Entropy Alloys with Heterogeneous Microstructures
Authors: Liu Yang , Jiang Ping , Duan Guihua , Wang Jing , Zhou Lingling , Xie Jijia
Published: September 2022

The behavior and the mechanism of fatigue crack propagation in CrCoNi medium-entropy alloys (MEAs) with heterogeneous microstructures were investigated in this paper. After cold-rolling and recrystallization annealing at different temperatures and times, five sets of heterostructured specimens were acquired with different recrystallization levels. Then, the structure characterizations of these five sets of specimens were carried out by nanoindentation testing and electron back-scatter diffraction (EBSD) mapping. Finally, the fatigue crack propagation tests were conducted on single edge crack specimens of these different heterogeneous microstructures. The experimental results indicate that the crack propagation rates of specimens with partial recrystallization microstructures are higher than those with complete recrystallization microstructures, and the effect on fatigue crack thresholds of these specimens is the opposite. The fatigue cracks grow along the slip planes or twin boundaries in recrystallization grains (RGs), which induced crack deflections and the roughness-induced crack closure effect. For this reason, the area percentage of recrystallization and the grain size of RGs have a great effect on the value of the fatigue crack growth threshold.
Influence of Nitrogen Fertilizer on the Antioxidative Potential of Basil Varieties (Ocimum basilicum L.)
Authors: Hęś Marzanna , Golcz Anna , Gramza-Michałowska Anna , Jędrusek-Golińska Anna , Dziedzic Krzysztof , Mildner-Szkudlarz Sylwia
Published: September 2022

Total phenolic content (TPC) in extracts of basil depended on the cultivar and type of fertilization used in cultivation. TPC was determined spectrophotometrically with the Folin–Ciocalteu reagent. The antioxidant activity of extracts was analyzed by scavenging of DPPH and ABTS radicals, on the basis of metal chelating ability (MetChel) and ferric reducing antioxidant power (FRAP). The greatest TPC was determined in the purple cultivars—141.35 and 165.44 mg gallic acid/g d.m. for fertilized with ammonium nitrate (NH4NO3) and ammonium sulfate ((NH4)2SO4), respectively. Their extracts had the greatest antioxidant capacity in the majority of the methods used. The results varied depending on the modelling system used. The amount of polyphenols in individual basil cultivars differed significantly (p < 0.05) depending on the fertilization used in the culture. Regarding TPC, DPPH, ABTS, FRAP, and MetChel variables, we observed a significant effect for the applied cultivation. In the case of MetChel factor, lower results of all investigated basil species were observed for cultivation with ammonium sulfate. PCA demonstrated in the present study shows that Sweet and Cinnamon Basil samples cultivated with ammonium nitrate create a separated group. We recommend cultivation with ammonium sulfate fertilizers for these varieties of basil. The high content of phenolic compounds demonstrated in Sweet and Cinnamon Basil cultivated with ammonium sulfate, and thus associated antioxidant activity, indicates that it can constitute a valuable source for bioactive compounds in a balanced diet.
Synthesis of thia-Michael-Type Adducts between Naphthoquinones and N-Acetyl-L-Cysteine and Their Biological Activity
Authors: Micheletti Gabriele , Boga Carla , Zalambani Chiara , Farruggia Giovanna , Esposito Erika , Fiori Jessica , Rizzardi Nicola , Taddei Paola , Di Foggia Michele , Calonghi Natalia
Published: September 2022

A series of naphthoquinones, namely, 1,4-naphthoquinone, menadione, plumbagin, juglone, naphthazarin, and lawsone, were reacted with N-acetyl-L-cysteine, and except for lawsone, which did not react, the related adducts were obtained. After the tuning of the solvent and reaction conditions, the reaction products were isolated as almost pure from the complex reaction mixture via simple filtration and were fully characterized. Therefore, the aim of this work was to evaluate whether the antitumor activity of new compounds of 1,4-naphthoquinone derivatives leads to an increase in ROS in tumor cell lines of cervical carcinoma (HeLa), neuroblastoma (SH-SY5Y), and osteosarcoma (SaOS2, U2OS) and in normal dermal fibroblast (HDFa). The MTT assay was used to assay cell viability, the DCF-DA fluorescent probe to evaluate ROS induction, and cell-cycle analysis to measure the antiproliferative effect. Compounds 8, 9, and 12 showed a certain degree of cytotoxicity towards all the malignant cell lines tested, while compound 11 showed biological activity at higher IC50 values. Compounds 8 and 11 induced increases in ROS generation after 1 h of exposure, while after 48 h of treatment, only 8 induced an increase in ROS formation in HeLa cells. Cell-cycle analysis showed that compound 8 caused an increase in the number of G0/G1-phase cells in the HeLa experiment, while for the U2OS and SH-SY5Y cell lines, it led to an accumulation of S-phase cells. Therefore, these novel 1,4-naphthoquinone derivatives may be useful as antitumoral agents in the treatment of different cancers.
Scalable (Enantioselective) Syntheses of Novel 3-Methylated Analogs of Pazinaclone, (S)-PD172938 and Related Biologically Relevant Isoindolinones
Authors: Di Mola Antonia , Nicastro Giorgia , Serusi Lorenzo , Filosa Rosanna , Waser Mario , Massa Antonio
Published: September 2022

Herein, we report the application of an efficient and practical K2CO3 promoted cascade reaction of 2-acetylbenzonitrile in the synthesis of novel 3-methylated analogs of Pazinaclone and PD172938, belonging to isoindolinones heterocyclic class bearing a tetrasubstituted stereocenter. Organocatalytic asymmetric synthesis of the key intermediate and its transformation into highly enantioenriched 3-methylated analog of (S)-PD172938 was also developed. These achievements can be of particular interest also for medicinal chemistry, since the methyl group is a very useful structural modification in the rational design of new and more effective bioactive compounds.
Antidepressant Low Doses of Ketamine and Melatonin in Combination Produce Additive Neurogenesis in Human Olfactory Neuronal Precursors
Authors: Estrada-Reyes Rosa , Quero-Chávez Daniel B. , Alarcón-Elizalde Salvador , Cercós Montserrat G. , Trueta Citlali , Constantino-Jonapa Luis A. , Oikawa-Sala Julián , Argueta Jesús , Cruz-Garduño Ricardo , Dubocovich Margarita L. , Benítez-King Gloria A.
Published: September 2022

Melatonin (MEL), an indolamine with diverse functions in the brain, has been shown to produce antidepressant-like effects, presumably through stimulating neurogenesis. We recently showed that the combination of MEL with ketamine (KET), an NMDA receptor antagonist, has robust antidepressant-like effects in mice, at doses that, by themselves, are non-effective and have no adverse effects. Here, we show that the KET/MEL combination increases neurogenesis in a clone derived from human olfactory neuronal precursors, a translational pre-clinical model for effects in the human CNS. Neurogenesis was assessed by the formation of cell clusters > 50 µm in diameter, positively stained for nestin, doublecortin, BrdU and Ki67, markers of progenitor cells, neurogenesis, and proliferation. FGF, EGF and BDNF growth factors increased the number of cell clusters in cultured, cloned ONPs. Similarly, KET or MEL increased the number of clusters in a dose-dependent manner. The KET/MEL combination further increased the formation of clusters, with a maximal effect obtained after a triple administration schedule. Our results show that the combination of KET/MEL, at subeffective doses that do not produce adverse effects, stimulate neurogenesis in human neuronal precursors. Moreover, the mechanism by which the combination elicits neurogenesis is meditated by melatonin receptors, CaM Kinase II and CaM antagonism. This could have clinical advantages for the fast treatment of depression.
A Design Framework of Exploration, Segmentation, Navigation, and Instruction (ESNI) for the Lifecycle of Intelligent Mobile Agents as a Method for Mapping an Unknown Built Environment
Authors: Chu Junchi , Tang Xueyun , Shen Xiwei
Published: September 2022

Recent work on intelligent agents is a popular topic among the artificial intelligence community and robotic system design. The complexity of designing a framework as a guide for intelligent agents in an unknown built environment suggests a pressing need for the development of autonomous agents. However, most of the existing intelligent mobile agent design focus on the achievement of agent’s specific practicality and ignore the systematic integration. Furthermore, there are only few studies focus on how the agent can utilize the information collected in unknown build environment to produce a learning pipeline for fundamental task prototype. The hierarchical framework is a combination of different individual modules that support a type of functionality by applying algorithms and each module is sequentially connected as a prerequisite for the next module. The proposed framework proved the effectiveness of ESNI system integration in the experiment section by evaluating the results in the testing environment. By a series of comparative simulations, the agent can quickly build the knowledge representation of the unknown environment, plan the actions accordingly, and perform some basic tasks sequentially. In addition, we discussed some common failures and limitations of the proposed framework.
Technologies for the Instrumental Evaluation of Physical Function in Persons Affected by Chronic Obstructive Pulmonary Disease: A Systematic Review
Authors: Zucchelli Alberto , Pancera Simone , Bianchi Luca Nicola Cesare , Marengoni Alessandra , Lopomo Nicola Francesco
Published: September 2022

Several systems, sensors, and devices are now available for the instrumental evaluation of physical function in persons with Chronic Obstructive Pulmonary Disease (COPD). We aimed to systematically review the literature about such technologies. The literature search was conducted in all major scientific databases, including articles published between January 2001 and April 2022. Studies reporting measures derived from the instrumental assessment of physical function in individuals with COPD were included and were divided into application and validation studies. The quality of validation studies was assessed with the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) risk of bias tool. From 8752 articles retrieved, 21 application and 4 validation studies were included in the systematic review. Most application studies employed accelerometers, gait analysis systems, instrumented mattresses, or force plates to evaluate walking. Surface electro-myography or near-infrared spectroscopy were employed in four studies. Validation studies were heterogeneous and presented a risk of bias ranging from inadequate to doubtful. A variety of data regarding physical function can be retrieved from technologies used in COPD studies. However, a general lack of standardization and limitations in study design and sample size hinder the implementation of the instrumental evaluation of function in clinical practice.
Sign Language Recognition Method Based on Palm Definition Model and Multiple Classification
Authors: Amangeldy Nurzada , Kudubayeva Saule , Kassymova Akmaral , Karipzhanova Ardak , Razakhova Bibigul , Kuralov Serikbay
Published: September 2022

Technologies for pattern recognition are used in various fields. One of the most relevant and important directions is the use of pattern recognition technology, such as gesture recognition, in socially significant tasks, to develop automatic sign language interpretation systems in real time. More than 5% of the world’s population—about 430 million people, including 34 million children—are deaf-mute and not always able to use the services of a living sign language interpreter. Almost 80% of people with a disabling hearing loss live in low- and middle-income countries. The development of low-cost systems of automatic sign language interpretation, without the use of expensive sensors and unique cameras, would improve the lives of people with disabilities, contributing to their unhindered integration into society. To this end, in order to find an optimal solution to the problem, this article analyzes suitable methods of gesture recognition in the context of their use in automatic gesture recognition systems, to further determine the most optimal methods. From the analysis, an algorithm based on the palm definition model and linear models for recognizing the shapes of numbers and letters of the Kazakh sign language are proposed. The advantage of the proposed algorithm is that it fully recognizes 41 letters of the 42 in the Kazakh sign alphabet. Until this time, only Russian letters in the Kazakh alphabet have been recognized. In addition, a unified function has been integrated into our system to configure the frame depth map mode, which has improved recognition performance and can be used to create a multimodal database of video data of gesture words for the gesture recognition system.
Intra-Rater Reliability of Shear Wave Elastography for the Quantification of Respiratory Muscles in Adolescent Athletes
Authors: Pałac Małgorzata , Linek Paweł
Published: September 2022

The aim of this study was to assess the intra-rater reliability and agreement of diaphragm and intercostal muscle elasticity and thickness during tidal breathing. The diaphragm and intercostal muscle parameters were measured using shear wave elastography in adolescent athletes. To calculate intra-rater reliability, intraclass correlation coefficient (ICC) and Bland–Altman statistics were used. The reliability/agreement for one-day both muscle measurements (regardless of probe orientation) were at least moderate. During the seven-day interval between measurements, the reliability of a single measurement depended on the measured parameter, transducer orientation, respiratory phase, and muscle. Excellent reliability was found for diaphragm shear modulus at the peak of tidal expiration in transverse probe position (ICC3.1 = 0.91–0.96; ICC3.2 = 0.95), and from poor to excellent reliability for the intercostal muscle thickness at the peak of tidal inspiration with the longitudinal probe position (ICC3.1 = 0.26–0.95; ICC3.2 = 0.15). The overall reliability/agreement of the analysed data was higher for the diaphragm measurements (than the intercostal muscles) regardless of the respiratory phase and probe position. It is difficult to identify a more appropriate probe position to examine these muscles. The shear modulus/thickness of the diaphragm and intercostal muscles demonstrated good reliability/agreement so this appears to be a promising technique for their examination in athletes.
Comprehensive Analysis of Network Slicing for the Developing Commercial Needs and Networking Challenges
Authors: Zahoor Sumbal , Ahmad Ishtiaq , Othman Mohamed Tahar Ben , Mamoon Ali , Rehman Ateeq Ur , Shafiq Muhammad , Hamam Habib
Published: September 2022

Network slicing (NS) is one of the most prominent next-generation wireless cellular technology use cases, promising to unlock the core benefits of 5G network architecture by allowing communication service providers (CSPs) and operators to construct scalable and customized logical networks. This, in turn, enables telcos to reach the full potential of their infrastructure by offering customers tailored networking solutions that meet their specific needs, which is critical in an era where no two businesses have the same requirements. This article presents a commercial overview of NS, as well as the need for a slicing automation and orchestration framework. Furthermore, it will address the current NS project objectives along with the complex functional execution of NS code flow. A summary of activities in important standards development groups and industrial forums relevant to artificial intelligence (AI) and machine learning (ML) is also provided. Finally, we identify various open research problems and potential answers to provide future guidance.
Non-Invasive Data Acquisition and IoT Solution for Human Vital Signs Monitoring: Applications, Limitations and Future Prospects
Authors: Salem Mahmoud , Elkaseer Ahmed , El-Maddah Islam A. M. , Youssef Khaled Y. , Scholz Steffen G. , Mohamed Hoda K.
Published: September 2022

The rapid development of technology has brought about a revolution in healthcare stimulating a wide range of smart and autonomous applications in homes, clinics, surgeries and hospitals. Smart healthcare opens the opportunity for a qualitative advance in the relations between healthcare providers and end-users for the provision of healthcare such as enabling doctors to diagnose remotely while optimizing the accuracy of the diagnosis and maximizing the benefits of treatment by enabling close patient monitoring. This paper presents a comprehensive review of non-invasive vital data acquisition and the Internet of Things in healthcare informatics and thus reports the challenges in healthcare informatics and suggests future work that would lead to solutions to address the open challenges in IoT and non-invasive vital data acquisition. In particular, the conducted review has revealed that there has been a daunting challenge in the development of multi-frequency vital IoT systems, and addressing this issue will help enable the vital IoT node to be reachable by the broker in multiple area ranges. Furthermore, the utilization of multi-camera systems has proven its high potential to increase the accuracy of vital data acquisition, but the implementation of such systems has not been fully developed with unfilled gaps to be bridged. Moreover, the application of deep learning to the real-time analysis of vital data on the node/edge side will enable optimal, instant offline decision making. Finally, the synergistic integration of reliable power management and energy harvesting systems into non-invasive data acquisition has been omitted so far, and the successful implementation of such systems will lead to a smart, robust, sustainable and self-powered healthcare system.
XGBLoc: XGBoost-Based Indoor Localization in Multi-Building Multi-Floor Environments
Authors: Singh Navneet , Choe Sangho , Punmiya Rajiv , Kaur Navneesh
Published: September 2022

Location-based indoor applications with high quality of services require a reliable, accurate, and low-cost position prediction for target device(s). The widespread availability of WiFi received signal strength indicator (RSSI) makes it a suitable candidate for indoor localization. However, traditional WiFi RSSI fingerprinting schemes perform poorly due to dynamic indoor mobile channel conditions including multipath fading, non-line-of-sight path loss, and so forth. Recently, machine learning (ML) or deep learning (DL)-based fingerprinting schemes are often used as an alternative, overcoming such issues. This paper presents an extreme gradient boosting-based ML indoor localization scheme, simply termed as XGBLoc, that accurately classifies (or detects) the positions of mobile devices in multi-floor multi-building indoor environments. XGBLoc not only effectively reduces the RSSI dataset dimensionality but trains itself using structured synthetic labels (also termed as relational labels), rather than conventional independent labels, that classify such complex and hierarchical indoor environments well. We numerically evaluate the proposed scheme on the publicly available datasets and prove its superiority over existing ML or DL-based schemes in terms of classification and regression performance.
Legal regulation of the use of distributed ledger technologies in financial sector of Singapore
Authors: Alekseenko Aleksandr P
Published: September 2022

Singapore is one of the leading countries in digitalization and blockchain technology. Since 2016, Singapore has implemented the Ubin project to create a national digital currency. In 2019, Singapore passed the Payment Services Act. The paper aims to analyze Singapore's legislation and MAS policies and identify approaches that can be used to improve legislation in other states. To meet that aim, the general scientific techniques and methods of scientific cognition, such as analysis, synthesis, deduction, induction, system-structural and formal-logical approaches are utilised. Based on the analysis, it is concluded that Singapore extends the provisions of securities legislation to digital tokens, which have the characteristics of securities or futures. Digital tokens, which are cryptocurrencies, are regulated by the Payment Services Act containing criteria to distinguish payment tokens from other virtual objects. Using this approach minimizes difficulties in regulating the circulation of, for example, bitcoins. In addition, MAS has developed a set of rules enshrining requirements for cryptocurrency exchanges, which reduces the risks of fraud and money laundering using cryptocurrencies. The paper also analyses MAS reports on developing a state's digital currency. The paper concludes that other states can use Singapore's experience to shape or modernize their legislation.
Tensions, Power, and Commitment:
Authors: Carlström Charlotta
Published: September 2022

Experiences of being LGBTQ1 within Swedish free-church environments have not been highlighted to any great extent. In the autumn of 2020, I participated, as an observing researcher, in a study group consisting of LGBTQ persons and LGBTQ allies focusing on LGBTQ in the Christian free-church environment. The discussions took their point of departure in the question how we ensure that congregations are a welcoming and safe place for LGBTQ people. This article is based on the conversations that took place during these meetings. In the articleI will examine how power relations and tensions were described and investigate how LGBTQ persons and their allies handle and challenge them. The results of the investigation show that free-church contexts are permeated with hegemonic heteronormativity, the structural power of which operates both visibly and covertly. The participants talk about unlivable compromises, emanating from membership always being conditional and subject to certain terms for LGBTQ persons. The participants narrated their experiences, ranging from subtle com- ments or silences to ostracism and exclusion. All participants testified to the existence of various forms of conversion efforts in contemporary free church environments and recounted examples of how they had been pressured in prayer and pastoral care and conversations in which they had been silenced or told that it is possible to change one’s sexual orientation or identity.
Methodology of Surzhyk
Authors: Beketova Masha
Published: September 2022

SPEAKING AND WRITING normative English well seems to be crucial not only in the Anglophone countries, but also in other countries for those, who aspire to work academically. This paper aims to look carefully, how the Western and Anglophone-Centered knowledge production forces young scholars into reproducing imperial and colonial schemes while adjusting themselves to those rules, and what alternatives are there.
Semiotics of advertisment
Authors: Lytvynenko Аlla , Zavіalova Olha , Kalashnyk Mariya , Varadi Natalia , Enska Olena
Published: September 2022

The purpose of the article is to clarify the main trends in modern research on the semiotics of advertising. The peculiarities of semiotic models of modern media advertising as a kind of visualized marketing communication are highlighted and the prospects of formation of semiotics of advertising as an autonomous direction in the stream of semiotics as a general discipline are determined. Modern advertising is interpreted as an artifact of mass culture. It is a cultural product of the postmodern aesthetics, which is special in terms of semantics and semiotics. The article proposes to consider it as a separate direction in the context of semiotics as a science. The presented research is mostly theoretical and generalizing.

The authors used the logical method of integrative cognition to analyze the approaches to interpreting the semiotics in the advertisement field and the descriptive analysis to show how signs transformation influences on the final perception of advertising text. The main thesis of the article is the need to consider the semiotics of advertising as an excellent signing system.