bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Arterial Stiffness and Sexual Function after Adding on PCSK9 Inhibitor Treatment in Male Patients with Familial Hypercholesterolemia: A Single Lipid Center Real-World Experience
Authors: Scicali Roberto , Russo Giorgio Ivan , Di Mauro Marina , Manuele Flavia , Di Marco Grazia , Di Pino Antonino , Ferrara Viviana , Rabuazzo Agata Maria , Piro Salvatore , Morgia Giuseppe , Purrello Francesco
Published: November 2020

Familial hypercholesterolemia (FH) subjects have high low-density lipoprotein cholesterol (LDL-C) and may be at high risk of erectile dysfunction and atherosclerotic cardiovascular diseases. We evaluated the effect of PCSK9-i on sexual function evaluated by the Male Sexual Health Questionnaire (MSHQ) and the International Index of Erectile Function (IIEF-5) questionnaire and on pulse wave velocity (PWV) in FH male subjects. In this prospective observational study, we evaluated 30 FH male patients on high-intensity statins plus ezetimibe and with an LDL-C off-target. All patients added PCSK9-i treatment and obtained clinical assessment at baseline and after six months of PCSK9-i. As expected, LDL-C significantly decreased after adding-on PCSK9-i (−48.73%, p < 0.001). MSHQ and PWV significantly improved after adding-on PCSK9-i (for MSHQ 93.63 ± 6.28 vs. 105.41 ± 5.86, p < 0.05; for PWV 9.86 ± 1.51 vs. 7.7 ± 1.42, p < 0.05); no significant change of IIEF-5 was found. Finally, a simple regression showed that ∆ MSHQ was significantly associated with ∆ LDL-C and ∆ PWV (p value for both <0.05). In conclusion, PCSK9-i therapy significantly improves lipid profile, PWV, and sexual function in FH male patients; our results support the favorable function of PCSK9-i on these parameters.
Evaluation of Scalability and Degree of Fine-Tuning of Deep Convolutional Neural Networks for COVID-19 Screening on Chest X-ray Images Using Explainable Deep-Learning Algorithm
Authors: Lee Ki-Sun , Kim Jae Young , Jeon Eun-tae , Choi Won Suk , Kim Nan Hee , Lee Ki Yeol
Published: November 2020

According to recent studies, patients with COVID-19 have different feature characteristics on chest X-ray (CXR) than those with other lung diseases. This study aimed at evaluating the layer depths and degree of fine-tuning on transfer learning with a deep convolutional neural network (CNN)-based COVID-19 screening in CXR to identify efficient transfer learning strategies. The CXR images used in this study were collected from publicly available repositories, and the collected images were classified into three classes: COVID-19, pneumonia, and normal. To evaluate the effect of layer depths of the same CNN architecture, CNNs called VGG-16 and VGG-19 were used as backbone networks. Then, each backbone network was trained with different degrees of fine-tuning and comparatively evaluated. The experimental results showed the highest AUC value to be 0.950 concerning COVID-19 classification in the experimental group of a fine-tuned with only 2/5 blocks of the VGG16 backbone network. In conclusion, in the classification of medical images with a limited number of data, a deeper layer depth may not guarantee better results. In addition, even if the same pre-trained CNN architecture is used, an appropriate degree of fine-tuning can help to build an efficient deep learning model.
6th Fábos Conference on Landscape and Greenway Planning
Authors: Smardon Richard
Published: November 2020

This editorial is an overview of a Special Issue of Land entitled “Selected Papers from the6th Fábos Conference on Landscape and Greenway Planning: Adapting and Expanding Contracting Cities.” This Special Issue of land contains six papers—most of which were presented at the 6th Fábos Conference on Landscape and Greenway Planning (Fábos et al. 2019) held at the University of Massachusetts Amherst 28–30 March 2019.The Fábos conference theme was to explore the social and economic potential of linear green spaces in urban areas that are declining or expanding.
Excess Conductivity Analysis of Polycrystalline FeSe Samples with the Addition of Ag
Authors: Koblischka Michael Rudolf , Slimani Yassine , Koblischka-Veneva Anjela , Karwoth Thomas , Zeng XianLin , Hannachi Essia , Murakami Masato
Published: November 2020

Bulk FeSe superconductors of the iron-based (IBS) “11” family containing various additions of silver were thoroughly investigated concerning the microstructure using optical microscopy and electron microscopy (TEM and SEM). The measurements of electrical resistivity were performed through the four-point technique in the temperature interval T= 2–150 K. The Aslamazov–Larkin model was employed to analyze the fluctuation-induced conductivity (FIC) in all acquired measurements. In all studied products, we found that the FIC curves consist of five different regimes of fluctuation, viz. critical region (CR), three-dimensional (3D), two-dimensional (2D), one-dimensional (1D), and shortwave fluctuation (SWF) regimes. The critical current density (Jc), the lower and upper critical magnetic fields (Bc1 and Bc2), the coherence length along the c-axis at zero-temperature (ξc(0)), and further parameters were assessed with regards to the silver amount within the products. The analyses discloses a diminution in the resistivity and a great reduction in ξc(0) with Ag addition. The optimal silver doping amount is achieved for 7 wt.%, which yields the best superconducting transition and the greatest Jc value.
Evaluation of Cytotoxicity and Antibacterial Activity of a New Class of Silver Citrate-Based Compounds as Endodontic Irrigants
Authors: Generali Luigi , Bertoldi Carlo , Bidossi Alessandro , Cassinelli Clara , Morra Marco , Del Fabbro Massimo , Savadori Paolo , Ballal Nidambur Vasudev , Giardino Luciano
Published: November 2020

In the present study, the cytotoxicity and the antimicrobial activity of two silver citrate-based irrigant solutions were investigated. Cytotoxicity of various concentrations (0.25%, 0.5%, 1%, 2.5%, 5%) of both solutions (BioAKT and BioAKT Endo) was assessed on L-929 mouse fibroblasts using the MTT assay. For the quantitative analysis of components, an infrared (I.R.) spectroscopy was performed. The minimum inhibitory and minimal bactericidal concentrations (M.I.C. and M.B.C., respectively) were ascertained on Enterococcus faecalis strain ATCC 4083. For biofilm susceptibility after treatment with the irrigating agent, a minimum biofilm eradication concentration (M.B.E.C.) and confocal laser scanning microscope (C.L.S.M.) assays were performed. Quantification of E. faecalis cell biomass and percentage of live and dead cells in the biomass was appraised. Normality of data was analyzed using the D’Agostino & Pearson’s test and the Shapiro–Wilk test. Statistical analysis was performed using one-way analysis of variance (ANOVA) and Tukey’s test. Both silver citrate solutions showed mouse fibroblasts viability >70% when diluted to 0.25% and 0.5%. Conversely, at higher concentrations, they were extremely cytotoxic. F.T.-IR spectroscopy measurements of both liquids showed the same spectra, indicating similar chemical characteristics. No substantial contrast in antimicrobial activity was observed among the two silver citrate solutions by using broth microdilution methods, biofilm susceptibility (MBEC-HTP device), and biomass screening using confocal laser scanning microscopy (C.L.S.M.) technique. Both solutions, used as root canal irrigants, exhibited significant antimicrobial activity and low cytocompatibility at dilutions greater than 0.5%.
The Influence of Ball Burnishing on Friction in Lubricated Sliding
Authors: Swirad Slawomir , Pawlus Pawel
Published: November 2020

Ball burnishing treatment, using the Ecoroll system, of steel samples was conducted. In the experiment, the burnishing pressure was changed. After the treatments, measurements of the surface topographies of disc samples were conducted using a white light interferometer Talysurf CCI Lite. Tribological tests were carried out in a ball-on-disc configuration. After these tests, measurements of surface topographies of disc samples were repeated. Worn surfaces were also analyzed with a scanning electron microscope. It was found that as the result of burnishing, surface topography height of tested samples decreased. Ball burnishing led to a reduction in the frictional resistance. The highest friction reduction of more than 40% was achieved with a burnishing pressure of 20 MPa.
Non-Destructive Testing Mechanism for Pre-Stressed Steel Wire Using Acoustic Emission Monitoring
Authors: Thiyagarajan Jothi Saravanan
Published: November 2020

In this paper, the guided ultrasonic wave propagation characteristics in the axisymmetric pre-stressed viscoelastic waveguide for acoustic emission (AE) monitoring, using the semi-analytical finite element (SAFE) method, is studied broadly. For the numerical investigation, a single high-strength steel wire is considered. A comprehensive and in-depth study on the AE signal’s propagation characteristics is carried out based on the SAFE method. Both undamped and damped waveguides are considered for attaining SAFE solutions and presented in a detailed manner. The SAFE method for an axisymmetric cross-section in cylindrical coordinates analyzes the two main influencing factors of steel wire in a practical scenario: Material damping and initial tension. For the effect of initial stress, the calculation shows that the initial tensile stress can increase and decrease the energy velocity and attenuation factor of most modal waves above the cut-off frequency, and the effect is linear. Some longitudinal wave modes in the high-frequency region show their potential for AE monitoring as these modes have a low attenuation factor and small external surface vibration. By considering various states of initial stress in a damped waveguide, the effect of pre-stress on the dispersion characteristics is understood in a better manner. A non-destructive testing (NDT) mechanism for pre-stressed steel wire using AE monitoring is proposed for the health monitoring of structures.
Reasons for the Formation of Non-Fibrous Inclusions When Preparing Basalt Fibers by the Duplex Method
Authors: Elbakian Anri , Sága Milan , Sentyakov Boris , Kuric Ivan , Kopas Peter
Published: November 2020

Materials based on basalt fiber are widely used as thermal insulating material. These materials have a number of advantages, including their low thermal conductivity and fire resistance due to their natural composition. However, there is a significant drawback in that the material contain non-fibrous inclusions. The solution to this problem would significantly improve the working conditions of workers engaged in the production of materials from basalt fiber, as well as workers engaged in construction and installation works. In addition, the research will help to make completely new products, such as special fireproof paper and sterile medical materials. This article focuses on the reasons for the formation of non-fibrous inclusions in the production of this kind of material. The technology of producing canvases from superthin fiber in the duplex way is studied. The analysis of the production process is made. Certain technological and structural parameters of the influence on the formation of such inclusions are identified. Experiments are carried out and conclusions are drawn given formation of non-fibrous inclusions of various geometric shapes for various factors. A mathematical model of the process under consideration is built. The article draws conclusion on the application of these developments in the production cycle of creating materials based on basalt fiber.
Strategies in Forward Osmosis Membrane Substrate Fabrication and Modification: A Review
Authors: Suzaimi Nur Diyana , Goh Pei Sean , Ismail Ahmad Fauzi , Mamah Stanley Chinedu , Malek Nik Ahmad Nizam Nik , Lim Jun Wei , Wong Kar Chun , Hilal Nidal
Published: November 2020

Forward osmosis (FO) has been recognized as the preferred alternative membrane-based separation technology for conventional water treatment technologies due to its high energy efficiency and promising separation performances. FO has been widely explored in the fields of wastewater treatment, desalination, food industry and bio-products, and energy generation. The substrate of the typically used FO thin film composite membranes serves as a support for selective layer formation and can significantly affect the structural and physicochemical properties of the resultant selective layer. This signifies the importance of substrate exploration to fine-tune proper fabrication and modification in obtaining optimized substrate structure with regards to thickness, tortuosity, and porosity on the two sides. The ultimate goal of substrate modification is to obtain a thin and highly selective membrane with enhanced hydrophilicity, antifouling propensity, as well as long duration stability. This review focuses on the various strategies used for FO membrane substrate fabrication and modification. An overview of FO membranes is first presented. The extant strategies applied in FO membrane substrate fabrications and modifications in addition to efforts made to mitigate membrane fouling are extensively reviewed. Lastly, the future perspective regarding the strategies on different FO substrate layers in water treatment are highlighted.
Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders
Authors: Błaszczyk Janusz Wiesław
Published: November 2020

There is a growing body of evidencethat indicates that the aging of the brain results from the decline of energy metabolism. In particular, the neuronal metabolism of glucose declines steadily, resulting in a growing deficit of adenosine triphosphate (ATP) production—which, in turn, limits glucose access. This vicious circle of energy metabolism at the cellular level is evoked by a rising deficiency of nicotinamide adenine dinucleotide (NAD) in the mitochondrial salvage pathway and subsequent impairment of the Krebs cycle. A decreasing NAD level also impoverishes the activity of NAD-dependent enzymes that augments genetic errors and initiate processes of neuronal degeneration and death.This sequence of events is characteristic of several brain structures in which neurons have the highest energy metabolism. Neurons of the cerebral cortex and basal ganglia with long unmyelinated axons and these with numerous synaptic junctions are particularly prone to senescence and neurodegeneration. Unfortunately, functional deficits of neurodegeneration are initially well-compensated, therefore, clinical symptoms are recognized too late when the damages to the brain structures are already irreversible. Therefore, future treatment strategies in neurodegenerative disorders should focus on energy metabolism and compensation age-related NAD deficit in neurons. This review summarizes the complex interrelationships between metabolic processes on the systemic and cellular levels and provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.
New Technologies for Influenza Vaccines
Authors: Rockman Steven , Laurie Karen L. , Parkes Simone , Wheatley Adam , Barr Ian G.
Published: November 2020

Vaccine development has been hampered by the long lead times and the high cost required to reach the market. The 2020 pandemic, caused by a new coronavirus (SARS-CoV-2) that was first reported in late 2019, has seen unprecedented rapid activity to generate a vaccine, which belies the traditional vaccine development cycle. Critically, much of this progress has been leveraged off existing technologies, many of which had their beginnings in influenza vaccine development. This commentary outlines the most promising of the next generation of non-egg-based influenza vaccines including new manufacturing platforms, structure-based antigen design/computational biology, protein-based vaccines including recombinant technologies, nanoparticles, gene- and vector-based technologies, as well as an update on activities around a universal influenza vaccine.
Micro-Raman—A Tool for the Heavy Mineral Analysis of Gold Placer-Type Deposits (Pianu Valley, Romania)
Authors: Maftei Andreea Elena , Buzatu Andrei , Damian Gheorghe , Buzgar Nicolae , Dill Harald G. , Apopei Andrei Ionut
Published: November 2020

In the current study, different heavy minerals typical of gold placer deposits were identified by means of micro-Raman spectroscopy, and their chemical composition analyzed and discussed (garnet, kyanite, staurolite, zircon, allanite, monazite, xenotime, rutile, anatase, cassiterite, titanite, barite). Even complex solid solution series, such as those of garnets, can be deciphered with the aid of systematic trends observed in Raman line frequencies. The ν1 mode in garnets will shift from high to low frequencies as a function of the ionic radius of the X2+ cation, from Mg2+, to Fe2+ and Mn2+, while the presence of Ca2+ will make the band to be shifted strongly to even lower wavenumbers. This approach has successfully been taken to differentiate between polymorph triplets such as kyanite-sillimanite-andalusite and rutile-anatase-brookite. Minerals under consideration with high contents of REE, U and Th are affected by intensive metamictization, particularly zircon and titanite. Raman peak features, such as shape, symmetry and intensity, respond to this radiation damage of the lattice and enable fine-tuning of these heavy minerals, such as in the case of fluorite (fetid fluorite).
Rapid Quantification and Validation of Biomarker Scopoletin in Paederia foetida by qNMR and UV–Vis for Herbal Preparation
Authors: Tan Dai Chuan , Quek Alexandra , Kassim Nur Kartinee , Ismail Intan Safinar , Lee Joanna Jinling
Published: November 2020

Scopoletin has previously been reported as a biomarker for the standardization of Paederia foetida twigs. This study is the first report on the determination and quantification of scopoletin using quantitative nuclear magnetic resonance (qNMR) in the different extracts of Paederia foetida twigs. The validated qNMR method showed a good linearity (r2 = 0.9999), limit of detection (LOD) (0.009 mg/mL), and quantification (LOQ) (0.029 mg/mL), together with high stability (relative standard deviation (RSD) = 0.022%), high precision (RSD < 1%), and good recovery (94.08–108.45%). The quantification results of scopoletin concentration in chloroform extract using qNMR and microplate ultraviolet-visible (UV-vis) spectrophotometer was almost comparable. Therefore, the qNMR method is deemed accurate and reliable for quality control of Paederia foetida and other medicinal plants without extensive sample preparation.
Qualitative and Quantitative Analysis of Regional Cerebral Free Fatty Acids in Rats Using the Stable Isotope Labeling Liquid Chromatography–Mass Spectrometry Method
Authors: Hu Ting , Zhu Quanfei , Hu Yuning , Kamal Ghulam Mustafa , Feng Yuqi , Manyande Anne , Wang Jie , Xu Fuqiang
Published: November 2020

Free fatty acids serve as important bioactive molecules in the brain. They are involved in message transfer in the brain. There are many reports available in the literature regarding the role of cerebral fatty acids in message transfer; however, most of the studies are mainly focused on limited fatty acid species or only a few specific brain regions. To understand the relationship between cerebral functions and free fatty acids, it is necessary to investigate the distribution of the free fatty acids among different regions in the whole brain. In this study, free fatty acids were extracted from different brain regions and analyzed qualitatively and quantitatively using the stable isotopic labeling liquid chromatography–mass spectrometry approach. In total, 1008 potential free fatty acids were detected in the whole brain out of which 38 were found to be commonly present in all brain regions. Among different brain regions, the highest and the smallest amounts of potential free fatty acids were detected in the olfactory bulb and cerebellum, respectively. From a statistical point of view, 4-methyl-2-oxovaleric acid, cis-11, 14-eicosadienoic acid, tridecanoic acid, myristic acid, nonadecanoic acid, and arachidic acid were found to significantly vary among the four different brain regions (olfactory bulb, occipital lobe, hippocampus, and cerebellum). The variation in the composition of free fatty acids among different brain regions may be very important for investigating the relationship between free fatty acids and functions of cerebral regions.
Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol
Authors: Liu Yeju , You Yuyang , Lu Juan , Chen Xi , Yang Zhihong
Published: November 2020

Pterostilbene is a natural 3,5-dimethoxy analog of resveratrol. This stilbene compound has a strong bioactivity and exists widely in Dalbergia and Vaccinium spp. Besides natural extraction, pterostilbene can be obtained by biosynthesis. Pterostilbene has become popular because of its remarkable pharmacological activities, such as anti-tumor, anti-oxidation, anti-inflammation, and neuroprotection. Pterostilbene can be rapidly absorbed and is widely distributed in tissues, but it does not seriously accumulate in the body. Pterostilbene can easily pass through the blood-brain barrier because of its low molecular weight and good liposolubility. In this review, the studies performed in the last three years on resources, synthesis, bioactivity, and pharmacokinetics of pterostilbene are summarized. This review focuses on the effects of pterostilbene on certain diseases to explore its targets, explain the possible mechanism, and look for potential therapeutic applications.
AGS3 and Gαi3 Are Concomitantly Upregulated as Part of the Spindle Orientation Complex during Differentiation of Human Neural Progenitor Cells
Authors: Yip Jackson L. K. , Lee Maggie M. K. , Leung Crystal C. Y. , Tse Man K. , Cheung Annie S. T. , Wong Yung H.
Published: November 2020

Adult neurogenesis is modulated by many Gi-coupled receptors but the precise mechanism remains elusive. A key step for maintaining the population of neural stem cells in the adult is asymmetric cell division (ACD), a process which entails the formation of two evolutionarily conserved protein complexes that establish the cell polarity and spindle orientation. Since ACD is extremely difficult to monitor in stratified tissues such as the vertebrate brain, we employed human neural progenitor cell lines to examine the regulation of the polarity and spindle orientation complexes during neuronal differentiation. Several components of the spindle orientation complex, but not those of the polarity complex, were upregulated upon differentiation of ENStem-A and ReNcell VM neural progenitor cells. Increased expression of nuclear mitotic apparatus (NuMA), Gαi subunit, and activators of G protein signaling (AGS3 and LGN) coincided with the appearance of a neuronal marker (β-III tubulin) and the concomitant loss of neural progenitor cell markers (nestin and Sox-2). Co-immunoprecipitation assays demonstrated that both Gαi3 and NuMA were associated with AGS3 in differentiated ENStem-A cells. Interestingly, AGS3 appeared to preferentially interact with Gαi3 in ENStem-A cells, and this specificity for Gαi3 was recapitulated in co-immunoprecipitation experiments using HEK293 cells transiently overexpressing GST-tagged AGS3 and different Gαi subunits. Moreover, the binding of Gαi3 to AGS3 was suppressed by GTPγS and pertussis toxin. Disruption of AGS3/Gαi3 interaction by pertussis toxin indicates that AGS3 may recognize the same site on the Gα subunit as G protein-coupled receptors. Regulatory mechanisms controlling the formation of spindle orientation complex may provide novel means to manipulate ACD which in turn may have an impact on neurogenesis.
Drugs Repurposing Using QSAR, Docking and Molecular Dynamics for Possible Inhibitors of the SARS-CoV-2 Mpro Protease
Authors: Tejera Eduardo , Munteanu Cristian R. , López-Cortés Andrés , Cabrera-Andrade Alejandro , Pérez-Castillo Yunierkis
Published: November 2020

Wuhan, China was the epicenter of the first zoonotic transmission of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) in December 2019 and it is the causative agent of the novel human coronavirus disease 2019 (COVID-19). Almost from the beginning of the COVID-19 outbreak several attempts were made to predict possible drugs capable of inhibiting the virus replication. In the present work a drug repurposing study is performed to identify potential SARS-CoV-2 protease inhibitors. We created a Quantitative Structure–Activity Relationship (QSAR) model based on a machine learning strategy using hundreds of inhibitor molecules of the main protease (Mpro) of the SARS-CoV coronavirus. The QSAR model was used for virtual screening of a large list of drugs from the DrugBank database. The best 20 candidates were then evaluated in-silico against the Mpro of SARS-CoV-2 by using docking and molecular dynamics analyses. Docking was done by using the Gold software, and the free energies of binding were predicted with the MM-PBSA method as implemented in AMBER. Our results indicate that levothyroxine, amobarbital and ABP-700 are the best potential inhibitors of the SARS-CoV-2 virus through their binding to the Mpro enzyme. Five other compounds showed also a negative but small free energy of binding: nikethamide, nifurtimox, rebimastat, apomine and rebastinib.
Mineral Composition of Cereal and Cereal-Free Dry Dog Foods versus Nutritional Guidelines
Authors: Kazimierska Katarzyna , Biel Wioletta , Witkowicz Robert
Published: November 2020

The aims of the present work are to estimate the nutritional value and to evaluate and compare the levels of macroelements (Ca, P, K, Na, Mg), microelements (Fe, Zn, Mn, Cu), heavy metals (Co, Cd, Pb, Mo, Cr, Ni), and their ratios in extruded complete foods for adult dogs, their compatibility with nutritional guidelines, as well as food profile similarity. Basic composition was determined according to Association of Official Analytical Chemists (AOAC). Analyses for elements were performed using an atomic absorption spectrometer. All the evaluated dry dog foods met the minimum recommended levels for protein and fat. Eighteen tested dog foods (60%) did not meet at least one recommendation of nutritional guidelines. Four dog foods exceeded the legal limit of Fe and five foods exceeded the legal limit of Zn; in one of them, Zn level was almost twice higher. Dog foods with insect protein exceeded the legal limit for Mn content. Eight dog foods had an inappropriate Ca:P ratio. Heavy metals were below detection limit in all analyzed dog foods. The results seem to show the need for regular feed analyses of the elemental composition in raw materials before introducing supplementation and for the monitoring of the mineral composition of finished pet food.
In Vitro and In Silico Evaluation of Anticancer Activity of New Indole-Based 1,3,4-Oxadiazoles as EGFR and COX-2 Inhibitors
Authors: Sever Belgin , Altıntop Mehlika Dilek , Özdemir Ahmet , Akalın Çiftçi Gülşen , Ellakwa Doha E. , Tateishi Hiroshi , Radwan Mohamed O. , Ibrahim Mahmoud A. A. , Otsuka Masami , Fujita Mikako , Ciftci Halil I. , Ali Taha F. S.
Published: November 2020

Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are crucial targetable enzymes in cancer management. Therefore, herein, new 2-[(5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(thiazol/benzothiazol-2-yl)acetamides (2a–i) were designed and synthesized as EGFR and COX-2 inhibitors. The cytotoxic effects of compounds 2a–i on HCT116 human colorectal carcinoma, A549 human lung adenocarcinoma, and A375 human melanoma cell lines were determined using MTT assay. 2-[(5-((1H-Indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(6-ethoxybenzothiazol-2-yl)acetamide (2e) exhibited the most significant anticancer activity against HCT116, A549, and A375 cell lines with IC50 values of 6.43 ± 0.72 μM, 9.62 ± 1.14 μM, and 8.07 ± 1.36 μM, respectively, when compared with erlotinib (IC50 = 17.86 ± 3.22 μM, 19.41 ± 2.38 μM, and 23.81 ± 4.17 μM, respectively). Further mechanistic assays demonstrated that compound 2e enhanced apoptosis (28.35%) in HCT116 cells more significantly than erlotinib (7.42%) and caused notable EGFR inhibition with an IC50 value of 2.80 ± 0.52 μM when compared with erlotinib (IC50 = 0.04 ± 0.01 μM). However, compound 2e did not cause any significant COX-2 inhibition, indicating that this compound showed COX-independent anticancer activity. The molecular docking study of compound 2e emphasized that the benzothiazole ring of this compound occupied the allosteric pocket in the EGFR active site. In conclusion, compound 2e is a promising EGFR inhibitor that warrants further clinical investigations.
Carvone Decreases Melanin Content by Inhibiting Melanoma Cell Proliferation via the Cyclic Adenosine Monophosphate (cAMP) Pathway
Authors: Kang Wesuk , Choi Dabin , Park Soyoon , Park Taesun
Published: November 2020

Melanin, which determines the color of the skin and hair, is initially synthesized to protect the skin from ultraviolet light; however, excessive melanin pigmentation caused by abnormal cell proliferation can result in various melanocytic lesions. Cyclic adenosine monophosphate (cAMP) is known to regulate cell cycle progression and consequently to inhibit the division of abnormally proliferating cells. In this work, we aimed to test whether carvone, a scent compound from plants, inhibits proliferation and subsequently reduces melanin content of melanoma cells and to determine whether its beneficial effects are mediated by the cAMP pathway. We found that carvone decreases melanin content and inhibits melanoma cell proliferation in a concentration-dependent manner. Meanwhile, it inhibited the activation of cell cycle-associated proteins such as cyclin-dependent kinase 1 (CDK1). Of note, the beneficial effects of carvone were abrogated by cAMP inhibition. Our findings indicate potential benefits of carvone for the treatment of melanomas and presumably other hyperpigmentation-related dermatological disorders such as melasmas, lentigines, and excessive freckles.
Characterization of Chemically Activated Pyrolytic Carbon Black Derived from Waste Tires as a Candidate for Nanomaterial Precursor
Authors: González-González Reyna Berenice , González Lucy T. , Iglesias-González Sigfrido , González-González Everardo , Martinez-Chapa Sergio O. , Madou Marc , Alvarez Mario Moisés , Mendoza Alberto
Published: November 2020

Pyrolysis is a feasible solution for environmental problems related to the inadequate disposal of waste tires, as it leads to the recovery of pyrolytic products such as carbon black, liquid fuels and gases. The characteristics of pyrolytic carbon black can be enhanced through chemical activation in order to produce the required properties for its application. In the search to make the waste tire pyrolysis process profitable, new applications of the pyrolytic solid products have been explored, such as for the fabrication of energy-storage devices and precursor in the synthesis of nanomaterials. In this study, waste tires powder was chemically activated using acid (H2SO4) and/or alkali (KOH) to recover pyrolytic carbon black with different characteristics. H2SO4 removed surface impurities more thoroughly, improving the carbon black’s surface area, while KOH increased its oxygen content, which improved the carbon black’s stability in water suspension. Pyrolytic carbon black was fully characterized by elemental analysis, inductively coupled plasma–optical emission spectrometry (ICP-OES), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction (XRD), N2 adsorption/desorption, scanning electron microscopy–energy-dispersive X-ray spectroscopy (SEM-EDS), dynamic light scattering (DLS), and ζ potential measurement. In addition, the pyrolytic carbon black was used to explore its feasibility as a precursor for the synthesis of carbon dots; synthesized carbon dots were analyzed preliminarily by SEM and with a fluorescence microplate reader, revealing differences in their morphology and fluorescence intensity. The results presented in this study demonstrate the effect of the activating agent on pyrolytic carbon black from waste tires and provide evidence of the feasibility of using waste tires for the synthesis of nanomaterials such as carbon dots.
Effective Enrichment and Quantitative Determination of Trace Hg2+ Ions Using CdS-Decorated Cellulose Nanofibrils
Authors: Ahmad Hilal , Sharfan Ibtisam I. Bin , Khan Rais Ahmad , Alsalme Ali
Published: November 2020

Water pollution caused by metal contamination is of serious concern. Direct determination of trace metal ions in real water samples remains challenging. A sample preparation technique is a prerequisite before analysis. Herein, we report the facile water-based hydrothermal synthesis of cadmium sulfide nanoparticles on a cellulose nanofiber surface to prepare a new adsorbent material. Field emission scanning electron microscopy, high-resolution tunneling electron microscopy, elemental mapping and X-ray photoelectron microscopy were used to characterize the surface morphology, structural determination, elemental composition and nature of bonding. The nanoadsorbent (cadmium-sulfide-decorated cellulose nanofibrils (CNFs@CdS)) was employed for the solid-phase extraction and determination of trace Hg(II) from aqueous media. The experimental conditions were optimized systematically and the data show a good Hg(II) adsorption capacity of 126.0 mg g−1. The CNFs@CdS adsorbent shows the selective removal of Hg(II) accordingly to the hard and soft acid–base theory of metal–ligand interaction. A high preconcentration limit of 0.36 µg L−1 was obtained with a preconcentration factor of 580. The lowest level of trace Hg(II) concentration, which was quantitatively analyzed by the proposed method, was found to be 0.06 µg L−1. No significant interferences from the sample matrix were observed in the extraction of Hg(II). Analysis of the standard reference material (SRM 1641d) was carried out to validate the proposed methodology. Good agreement between the certified and observed values indicates the applicability of the developed methodology for the analysis of Hg(II) in tap water, river water and industrial wastewater samples.
Dietary Acid Load and Cardiometabolic Risk Factors—A Narrative Review
Authors: Ostrowska Joanna , Janiszewska Justyna , Szostak-Węgierek Dorota
Published: November 2020

The Western, diet rich in acidogenic foods (e.g., meat, fish and cheese) and low in alkaline foods (e.g., vegetables, fruits and legumes), is deemed to be a cause of endogenous acid production and elevated dietary acid load (DAL), which is a potential cause of metabolic acidosis. Multiple authors have suggested that such a dietary pattern increases the excretion of calcium and magnesium, as well as cortisol secretion. In addition, it is associated with decreased citrate excretion. All of these seem to increase blood pressure and insulin resistance and may contribute to the development of cardiometabolic disorders. However, there are inconsistencies in the results of the studies conducted. Therefore, this narrative literature review aims to present the outcomes of studies performed in recent years that investigated the association between DAL and the following cardiometabolic risk factors: blood pressure, hypertension, carbohydrate metabolism and lipid profile. Study outcomes are divided into (i) statistically significant positive association, (ii) statistically significant inverse association, and (iii) no statistically significant association.
PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression—A Randomized Controlled Trial
Authors: Reininghaus Eva Z. , Platzer Martina , Kohlhammer-Dohr Alexandra , Hamm Carlo , Mörkl Sabrina , Bengesser Susanne A. , Fellendorf Frederike T. , Lahousen-Luxenberger Theressa , Leitner-Afschar Birgitta , Schöggl Helmut , Amberger-Otti Daniela , Wurm Walter , Queissner Robert , Birner Armin , Falzberger Valerie S. , Painold Annamaria , Fitz Werner , Brunnmayr Martina , Rieger Alexandra , Wagner-Skacel Jolana , Maget Alexander , Unterweger Renate , Schwalsberger Karin , Reininghaus Bernd , Lenger Melanie , Bastiaanssen Thomaz F. S. , Dalkner Nina
Published: November 2020

Gut microbiota are suspected to affect brain functions and behavior as well as lowering inflammation status. Therefore, an effect on depression has already been suggested by recent research. The aim of this randomized double-blind controlled trial was to evaluate the effect of probiotic treatment in depressed individuals. Within inpatient care, 82 currently depressed individuals were randomly assigned to either receive a multistrain probiotic plus biotin treatment or biotin plus placebo for 28 days. Clinical symptoms as well as gut microbiome were analyzed at the begin of the study, after one and after four weeks. After 16S rRNA analysis, microbiome samples were bioinformatically explored using QIIME, SPSS, R and Piphillin. Both groups improved significantly regarding psychiatric symptoms. Ruminococcus gauvreauii and Coprococcus 3 were more abundant and β-diversity was higher in the probiotics group after 28 days. KEGG-analysis showed elevated inflammation-regulatory and metabolic pathways in the intervention group. The elevated abundance of potentially beneficial bacteria after probiotic treatment allows speculations on the functionality of probiotic treatment in depressed individuals. Furthermore, the finding of upregulated vitamin B6 and B7 synthesis underlines the connection between the quality of diet, gut microbiota and mental health through the regulation of metabolic functions, anti-inflammatory and anti-apoptotic properties. Concluding, four-week probiotic plus biotin supplementation, in inpatient individuals with a major depressive disorder diagnosis, showed an overall beneficial effect of clinical treatment. However, probiotic intervention compared to placebo only differed in microbial diversity profile, not in clinical outcome measures.
Dietary Patterns, Their Nutrients, and Associations with Socio-Demographic and Lifestyle Factors in Older New Zealand Adults
Authors: Mumme Karen , Conlon Cathryn , von Hurst Pamela , Jones Beatrix , Stonehouse Welma , Heath Anne-Louise M. , Coad Jane , Haskell-Ramsay Crystal , de Seymour Jamie , Beck Kathryn
Published: November 2020

Dietary patterns analyse combinations of foods eaten. This cross-sectional study identified dietary patterns and their nutrients. Associations between dietary patterns and socio-demographic and lifestyle factors were examined in older New Zealand adults. Dietary data (109-item food frequency questionnaire) from the Researching Eating, Activity and Cognitive Health (REACH) study (n = 367, 36% male, mean age = 70 years) were collapsed into 57 food groups. Using principal component analysis, three dietary patterns explained 18% of the variation in diet. Dietary pattern associations with sex, age, employment, living situation, education, deprivation score, physical activity, alcohol, and smoking, along with energy-adjusted nutrient intakes, were investigated using regression analysis. Higher ‘Mediterranean’ dietary pattern scores were associated with being female, higher physical activity, and higher education (p < 0.001, R2 = 0.07). Higher ‘Western’ pattern scores were associated with being male, higher alcohol intake, living with others, and secondary education (p < 0.001, R2 = 0.16). Higher ‘prudent’ pattern scores were associated with higher physical activity and lower alcohol intake (p < 0.001, R2 = 0.15). There were positive associations between beta-carotene equivalents, vitamin E, and folate and ‘Mediterranean’ dietary pattern scores (p < 0.0001, R2 ≥ 0.26); energy intake and ‘Western’ scores (p < 0.0001, R2 = 0.43); and fibre and carbohydrate and ‘prudent’ scores (p < 0.0001, R2 ≥ 0.25). Socio-demographic and lifestyle factors were associated with dietary patterns. Understanding relationships between these characteristics and dietary patterns can assist in health promotion.
Twenty Years of Equine Piroplasmosis Research: Global Distribution, Molecular Diagnosis, and Phylogeny
Authors: Tirosh-Levy Sharon , Gottlieb Yuval , Fry Lindsay M. , Knowles Donald P. , Steinman Amir
Published: November 2020

Equine piroplasmosis (EP), caused by the hemoparasites Theileria equi, Theileria haneyi, and Babesia caballi, is an important tick-borne disease of equines that is prevalent in most parts of the world. Infection may affect animal welfare and has economic impacts related to limitations in horse transport between endemic and non-endemic regions, reduced performance of sport horses and treatment costs. Here, we analyzed the epidemiological, serological, and molecular diagnostic data published in the last 20 years, and all DNA sequences submitted to GenBank database, to describe the current global prevalence of these parasites. We demonstrate that EP is endemic in most parts of the world, and that it is spreading into more temperate climates. We emphasize the importance of using DNA sequencing and genotyping to monitor the spread of parasites, and point to the necessity of further studies to improve genotypic characterization of newly recognized parasite species and strains, and their linkage to virulence.
First line Immunotherapy for Non-Small Cell Lung Cancer
Authors: Nasser Nicola J. , Gorenberg Miguel , Agbarya Abed
Published: November 2020

Immunotherapy for non-small cell lung cancer (NSCLC) is incorporated increasingly in first line treatments protocols. Multiple phase 3 studies have tested different medications targeting programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), with or without chemotherapy. The inclusion criteria differ between the various clinical trials, including the cut-off levels of PD-L1 expression on tumor cells, and the tumor histology (squamous or non-squamous). Patients with tumor expression levels of PD-L1 ≥ 50% are candidates for treatment with single agent Pembrolizumab or Atezolizumab. Patients with PD-L1 < 50% are candidates for immunotherapy with pembrolizumab as a single agent if PL-1 > 1%; immunotherapy doublet, Nivolumab and Ipilimumab, or single agent immunotherapy combined with chemotherapy. Here we review phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.
Investigation of Side Wall Roughness Effect on Optical Losses in a Multimode Si3N4 Waveguide Formed on a Quartz Substrate
Authors: Yakuhina Anastasia , Kadochkin Alexey , Svetukhin Vyacheslav , Gorelov Dmitry , Generalov Sergey , Amelichev Vladimir
Published: November 2020

This article presents the results of the study of the influence of the most significant parameters of the side wall roughness of an ultra-thin silicon nitride lightguide layer of multimode integrated optical waveguides with widths of 3 and 8 microns. The choice of the waveguide width was made due to the need to provide multimode operation for telecommunication wavelengths, which is necessary to ensure high integration density. Scattering in waveguide structures was measured by optical frequency domain reflectometry (OFDR) of a backscattering reflectometer. The finite difference time domain method (FDTD) was used to study the effect of roughness parameters on optical losses in fabricated waveguides, the roughness parameters that most strongly affect optical scattering were determined, and methods of its significant reduction were specified. The prospects for implementing such structures on a quartz substrate are justified.
Mitigation of Copper Stress in Maize by Inoculation with Paenibacillus polymyxa and Bacillus circulans
Authors: Abdel Latef Arafat Abdel Hamed , Zaid Abbu , Abo-Baker Abo-Baker Abd-Elmoniem , Salem Wesam , Abu Alhmad Mona Fawzy
Published: November 2020

Copper (Cu) is a micronutrient that assumes a principal role in plant growth and development. However, its excess concentration in soil is imperiling crop productivity. Inoculation with different bacterial strains in cereals could modify growth traits, photosynthetic effectiveness, and generation of strong antioxidant defense systems to make them more tolerant of Cu stress. Therefore, a pot study was designed to test plant growth-promoting rhizobacteria (PGPR) including Paenibacillus polymyxa and Bacillus circulans to Cu exposed maize (Zea mays L.) plants. Increasing Cu (100 to 500 µM of CuSO4) concentration decreased growth traits, photosynthetic pigments, soluble sugars, phosphorous (P) and potassium (K) contents, and the activity of catalase (CAT) but increased proline and malondialdehyde (MDA) content, the activity of peroxidase (POD) and Cu ions at root and shoot level. Moreover, the bacterial treatment also modulated the antioxidant capability in stress-free plants. Nevertheless, inoculation with P. polymyxa and B. circulans alleviated Cu-induced growth, photosynthetic pigments and mineral nutrient (P and K) on one hand and regulating the pools of osmolytes and antioxidant enzymes, whilst simultaneously reducing MDA and Cu root and shoot contents. These improved activities of antioxidant enzymes and the regulation of osmolytes content elicited by the blend of bacterial inoculation would have retained the ability of maize plants to confer resilience to Cu stress. This study further affirms that the application of two specific bacterial strains to maize plants proved very effective to ameliorate the Cu toxicity.
Thermoresponsive Polyoxazolines as Vectors for Transfection of Nucleic Acids
Authors: Haladjova Emi , Rangelov Stanislav , Tsvetanov Christo
Published: November 2020

Poly(2-oxazoline)s (POx) are an attractive platform for the development of non-viral gene delivery systems. The combination of POx moieties, exhibiting excellent biocompatibility, with DNA-binding polyethyleneimine (PEI) moieties into a single copolymer chain is a promising approach to balance toxicity and transfection efficiency. The versatility of POx in terms of type of substituent, copolymer composition, degree of polymerization, degree of hydrolysis, and chain architecture, as well as the introduction of stimuli-responsive properties, provides opportunities to finely tune the copolymer characteristics and physicochemical properties of the polyplexes to increase the biological performance. An overview of the current state of research in the POx–PEI-based gene delivery systems focusing particularly on thermosensitive POx is presented in this paper.
Biodeterioration of Untreated Polypropylene Microplastic Particles by Antarctic Bacteria
Authors: Habib Syahir , Iruthayam Anastasia , Abd Shukor Mohd Yunus , Alias Siti Aisyah , Smykla Jerzy , Yasid Nur Adeela
Published: November 2020

Microplastic pollution is globally recognised as a serious environmental threat due to its ubiquitous presence related primarily to improper dumping of plastic wastes. While most studies have focused on microplastic contamination in the marine ecosystem, microplastic pollution in the soil environment is generally little understood and often overlooked. The presence of microplastics affects the soil ecosystem by disrupting the soil fertility and quality, degrading the food web, and subsequently influencing both food security and human health. This study evaluates the growth and biodegradation potential of the Antarctic soil bacteria Pseudomonas sp. ADL15 and Rhodococcus sp. ADL36 on the polypropylene (PP) microplastics in Bushnell Haas (BH) medium for 40 days. The degradation was monitored based on the weight loss of PP microplastics, removal rate constant per day (K), and their half-life. The validity of the PP microplastics’ biodegradation was assessed through structural changes via Fourier transform infrared spectroscopy analyses. The weight loss percentage of the PP microplastics by ADL15 and ADL36 after 40 days was 17.3% and 7.3%, respectively. The optimal growth in the BH media infused with PP microplastics was on the 40th and 30th day for ADL15 and ADL36, respectively. The infrared spectroscopic analysis revealed significant changes in the PP microplastics’ functional groups following the incubation with Antarctic strains.