bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Algorithmic Information Using Quantum Computing for Genomics Applications
Authors: Sarkar Aritra , Al-Ars Zaid , Bertels Koen
Published: March 2021

Inferring algorithmic structure in data is essential for discovering causal generative models. In this research, we present a quantum computing framework using the circuit model, for estimating algorithmic information metrics. The canonical computation model of the Turing machine is restricted in time and space resources, to make the target metrics computable under realistic assumptions. The universal prior distribution for the automata is obtained as a quantum superposition, which is further conditioned to estimate the metrics. Specific cases are explored where the quantum implementation offers polynomial advantage, in contrast to the exhaustive enumeration needed in the corresponding classical case. The unstructured output data and the computational irreducibility of Turing machines make this algorithm impossible to approximate using heuristics. Thus, exploring the space of program-output relations is one of the most promising problems for demonstrating quantum supremacy using Grover search that cannot be dequantized. Experimental use cases for quantum acceleration are developed for self-replicating programs and algorithmic complexity of short strings. With quantum computing hardware rapidly attaining technological maturity, we discuss how this framework will have significant advantage for various genomics applications in meta-biology, phylogenetic tree analysis, protein-protein interaction mapping and synthetic biology. This is the first time experimental algorithmic information theory is implemented using quantum computation. Our implementation on the Qiskit quantum programming platform is copy-left and is publicly available on GitHub.
Caulerpenyne Affects Bradykinin-Induced Intracellular Calcium Kinetics in LoVo Cells
Authors: Traina Giovanna
Published: March 2021

Sesquiterpene caulerpenyne (CYN) is the major metabolite present in green macroalgae Caulerpa taxifolia. This metabolite has been shown to be cytotoxic in some cell lines and was found to be active in various assays of pharmacological interest. In addition, it exerts antibiotic, antiviral, phytotoxic, antidyslipidemic, and antiproliferative activities. In the present study, we report that pretreatment with CYN decreases the bradykinin-induced calcium peak in human colon LoVo cells. We hypothesize that CYN pretreatment may adversely affect bradykinin-induced intracellular calcium increases. The data suggest that CYN, by reducing the increase in intracellular calcium, exerts an inhibitory role on calcium homeostasis and, likely, intercellular transmission.
Comparison of Thermal Characteristics and Fatty Acids Composition in Raw and Roasted Cocoa Beans from Peru (Criollo) and Ecuador (Forastero)
Authors: Ostrowska-Ligęza Ewa , Dolatowska-Żebrowska Karolina , Wirkowska-Wojdyła Magdalena , Bryś Joanna , Górska Agata
Published: March 2021

The aim of this research was to complete the characteristics of cocoa beans and cocoa butter extracted from two different Theobroma cacao species: Criollo originated from Peru and Forastero originated from Ecuador, both in the version of raw (unroasted) and roasted beans. Before extraction, the cocoa beans were characterized by proximate analysis. The determination of fatty acids composition was carried out by gas chromatography (GC). The positional distribution of fatty acids in the sn-2 positions of triacylglycerols (TAGs) was also determined. The thermogravimetric analyses (TGA/DTG) were performed under the nitrogen and oxygen atmosphere of roasted and unroasted cocoa beans. The kinetic information was helpful to assess the oxidative stability of cocoa butter. The cocoa butter extracted from unroasted Forastero from Ecuador had the highest values of oxidation activation energy Ea. The melting characteristics of cocoa butter extracted from roasted Criollo species were very similar to their unroasted versions. The same trend was not observed for Forastero species. TGA and DTG were revealed to be useful tools for the analysis of whole cocoa beans and the fats extracted from these cocoa beans.
Proportional Double Derivative Linear Quadratic Regulator Controller Using Improvised Grey Wolf Optimization Technique to Control Quadcopter
Authors: Shauqee Mohamad Norherman , Rajendran Parvathy , Suhadis Nurulasikin Mohd
Published: March 2021

A hybrid proportional double derivative and linear quadratic regulator (PD2-LQR) controller is designed for altitude (z) and attitude (roll, pitch, and yaw) control of a quadrotor vehicle. The derivation of a mathematical model of the quadrotor is formulated based on the Newton–Euler approach. An appropriate controller’s parameter must be obtained to obtain a superior control performance. Therefore, we exploit the advantages of the nature-inspired optimization algorithm called Grey Wolf Optimizer (GWO) to search for those optimal values. Hence, an improved version of GWO called IGWO is proposed and used instead of the original one. A comparative study with the conventional controllers, namely proportional derivative (PD), proportional integral derivative (PID), linear quadratic regulator (LQR), proportional linear quadratic regulator (P-LQR), proportional derivative and linear quadratic regulator (PD-LQR), PD2-LQR, and original GWO-based PD2-LQR, was undertaken to show the effectiveness of the proposed approach. An investigation of 20 different quadcopter models using the proposed hybrid controller is presented. Simulation results prove that the IGWO-based PD2-LQR controller can better track the desired reference input with shorter rise time and settling time, lower percentage overshoot, and minimal steady-state error and root mean square error (RMSE).
Enzymatic Synthesis of Glucose Fatty Acid Esters Using SCOs as Acyl Group-Donors and Their Biological Activities
Authors: El-Baz Hatim A. , Elazzazy Ahmed M. , Saleh Tamer S. , Dourou Marianna , Mahyoub Jazem A. , Baeshen Mohammed N. , Madian Hekmat R. , Aggelis George
Published: March 2021

Sugar fatty acid esters, especially glucose fatty acid esters (GEs), have broad applications in food, cosmetic and pharmaceutical industries. In this research, the fatty acid moieties derived from polyunsaturated fatty acids containing single-cell oils (SCOs) (i.e., those produced from Cunninghamella echinulata, Umbelopsis isabellina and Nannochloropsis gaditana, as well as from olive oil and an eicosapentaenoic acid (EPA) concentrate) were converted into GEs by enzymatic synthesis, using lipases as biocatalysts. The GE synthesis was monitored using thin-layer chromatography, FTIR and in situ NMR. It was found that GE synthesis carried out using immobilized Candida antarctica B lipase was very effective, reaching total conversion of reactants. It was shown that EPA-GEs were very effective against several pathogenic bacteria and their activity can be attributed to their high EPA content. Furthermore, C. echinulata-GEs were more effective against pathogens compared with U. isabellina-GEs, probably due to the presence of gamma linolenic acid (GLA) in the lipids of C. echinulata, which is known for its antimicrobial activity, in higher concentrations. C. echinulata-GEs also showed strong insecticidal activity against Aedes aegypti larvae, followed by EPA-GEs, olive oil-GEs and N. gaditana-GEs. All synthesized GEs induced apoptosis of the SKOV-3 ovarian cancer cell line, with the apoptotic rate increasing significantly after 48 h. A higher percentage of apoptosis was observed in the cells treated with EPA-GEs, followed by C. echinulata-GEs, U. isabellina-GEs and olive oil-GEs. We conclude that SCOs can be used in the synthesis of GEs with interesting biological properties.
Hybrid Equivalent Circuit/Finite Element/Boundary Element Modeling for Effective Analysis of an Acoustic Transducer Array with Flexible Surrounding Structures
Authors: Sim Min-Jung , Hong Chinsuk , Jeong Weui-Bong
Published: March 2021

Transducer arrays are commonly analyzed by the finite element method (FEM) with high accuracy, but it is costly, particularly when having flexible surrounding structures. In this study, we developed an equivalent circuit (EC)-based model of an array of transducers with flexible surrounding structures for effective analysis. The impedance matrix was first constructed by coupling the electrical, mechanical impedance, and the acoustic radiation impedance obtained by the EC method and finite element-boundary element (FE-BE) coupling method. The transfer matrix of far-field pressure to the transducer response was then constructed by the FE-BE coupling method, and finally the sound pressure of the external acoustic field was obtained. To verify the accuracy, the results of the proposed method were compared with those of the conventional FEM. To evaluate the efficiency of the proposed method, the reduction in the degrees of freedom (DOFs) of the proposed method from the conventional FEM analysis was investigated. The simulation results of the proposed method are highly accurate and efficient. The proposed method is expected to be useful for conceptual design.
Interoperability Reference Models for Applications of Artificial Intelligence in Medical Imaging
Authors: Kwon Oyun , Yoo Sun K.
Published: March 2021

Medical imaging is currently being applied in artificial intelligence and big data technologies in data formats. In order for medical imaging collected from different institutions and systems to be used for artificial intelligence data, interoperability is becoming a key element. Whilst interoperability is currently guaranteed through medical data standards, compliance to personal information protection laws, and other methods, a standard solution for measurement values is deemed to be necessary in order for further applications as artificial intelligence data. As a result, this study proposes a model for interoperability in medical data standards, personal information protection methods, and medical imaging measurements. This model applies Health Level Seven (HL7) and Digital Imaging and Communications in Medicine (DICOM) standards to medical imaging data standards and enables increased accessibility towards medical imaging data in the compliance of personal information protection laws through the use of de-identifying methods. This study focuses on offering a standard for the measurement values of standard materials that addresses uncertainty in measurements that pre-existing medical imaging measurement standards did not provide. The study finds that medical imaging data standards conform to pre-existing standards and also provide protection to personal information within any medical images through de-identifying methods. Moreover, it proposes a reference model that increases interoperability by composing a process that minimizes uncertainty using standard materials. The interoperability reference model is expected to assist artificial intelligence systems using medical imaging and further enhance the resilience of future health technologies and system development.
Gold-Modified Micellar Composites as Colorimetric Probes for the Determination of Low Molecular Weight Thiols in Biological Fluids Using Consumer Electronic Devices
Authors: Akrivi Elli A. , Vlessidis Athanasios G. , Giokas Dimosthenis L. , Kourkoumelis Nikolaos
Published: March 2021

This work describes a new, low-cost and simple-to-use method for the determination of free biothiols in biological fluids. The developed method utilizes the interaction of biothiols with gold ions, previously anchored on micellar assemblies through electrostatic interactions with the hydrophilic headgroup of cationic surfactant micelles. Specifically, the reaction of AuCl4− with the cationic surfactant cetyltrimethyl ammonium bromide (CTAB) produces an intense orange coloration, due to the ligand substitution reaction of the Br− for Cl− anions, followed by the coordination of the AuBr4− anions on the micelle surface through electrostatic interactions. When biothiols are added to the solution, they complex with the gold ions and disrupt the AuBr4−–CTAB complex, quenching the initial coloration and inducing a decrease in the light absorbance of the solution. Biothiols are assessed by monitoring their color quenching in an RGB color model, using a flatbed scanner operating in transmittance mode as an inexpensive microtiter plate photometer. The method was applied to determine the biothiol content in urine and blood plasma samples, with satisfactory recoveries (i.e., >67.3–123% using external calibration and 103.8–115% using standard addition calibration) and good reproducibility (RSD < 8.4%, n = 3).
Indentation Measurement in Thin Plates under Bending Using 3D Digital Image Correlation
Authors: Almazán-Lázaro Juan-Antonio , López-Alba Elías , Rubio-García Luis , Díaz-Garrido Francisco-Alberto
Published: March 2021

In the current paper, a novel experimental methodology to characterize the contact behavior on thin plates under bending is presented. The method is based on the experimental measurement of the indentation observed during contact experiments. Tests were conducted using aluminum thin plates and a steel sphere to evaluate the effect of thickness and bending during contact. For this purpose, a non-contact optical technique, 3D Digital Image Correlation (3D-DIC), has been employed to measure the out-of-plane displacements experienced at the rear face of the specimens (opposite where the contact is occurring). An indirect measurement of the experimental contact law is obtained for different plate thicknesses (2 mm, 3 mm, 4 mm, 5 mm and 6 mm) as the contact load increases. An energy balance performed during contact experiments made it possible to evaluate and quantify the applied energy to generate bending and contact deformation. When the specimen thickness increases from 2 mm to 6 mm, contact deformation reaches higher values from the total applied energy. In addition, it is also possible to evaluate the portion of the elastically recovered energy for contact and bending deformation during the unloading. It has been observed that thicker specimens show a lower elastic energy recovery due to bending and a higher elastic energy recovery due to contact. Results clearly show how the ratio between absorbed and applied energy changes as the specimen thickness increases, highlighting the relevance of the proposed method for the characterization of contact behavior in thin plates.
Evaluation of AI-Assisted Telemedicine Service Using a Mobile Pet Application
Authors: Hwang Sewoong , Song Yungyeong , Kim Jonghyuk
Published: March 2021

This study indirectly verifies the possibility of telemedicine for humans through a mobile application (app) targeting pets. It examined the perception of telemedicine services and the current status of the companion animal industry, the app platform, and its applied technology by industry domain, and four representative types of artificial intelligence (AI) technologies applicable in the medical field. A survey was conducted through an app implementing pet telemedicine, and hypotheses were established and statistically tested based on the adoption period of pets, health status, mobile service utilization (as an index measuring the ease of use of recent AI functions), and positive and negative perceptions of telemedicine services. As revealed by prospect theory, users with a negative perception of pet telemedicine tended to maintain negative perceptions about telemedicine for humans. This study proved that the severity of pet diseases and the ease of use of recent AI technologies act as a moderating effect on the perception of telemedicine services through the verification of reinforcement and additional hypotheses. It suggests a plan to overcome sanctions against telemedicine by utilizing AI technology. A positive effect on changing the medical paradigm to telemedicine and the improvement of the medical legal system were also observed.
Antimicrobial Activity of L-Lysine and Poly-L-Lysine with Pulsed Electric Fields
Authors: Švedienė Jurgita , Novickij Vitalij , Žalnėravičius Rokas , Raudonienė Vita , Markovskaja Svetlana , Novickij Jurij , Paškevičius Algimantas
Published: March 2021

For the first time, the possibility to use L-lysine (Lys) and poly-L-lysine (PLL) as additives with pulsed electric fields (PEF) for antimicrobial treatment is reported. The antimicrobial efficacy of Lys and PLL for Escherichia coli, Staphylococcus aureus, Trichophyton rubrum and Candida albicans was determined. Inactivation of microorganisms was also studied by combining Lys and PLL with PEF of 15 and 30 kV/cm. For PEF treatment, pulses of 0.5, 1, 10 or 100 μs were applied in a sequence of 10 to 5000 at 1 kHz frequency. The obtained results showed that 100 μs pulses were the most effective in combination with Lys and PLL for all microorganisms. Equivalent energy PEF bursts with a shorter duration of the pulse were less effective independently on PEF amplitude. Additionally, various treatment susceptibility patterns of microorganisms were determined and reported. In this study, the Gram-negative E. coli was the most treatment-resistant microorganism. Nevertheless, inactivation rates exceeding 2 log viability reduction were achieved for all analyzed yeast, fungi, and bacteria. This methodology could be used for drug-resistant microorganism’s new treatment development.
Potential Source Areas for Atmospheric Lead Reaching Ny-Ålesund from 2010 to 2018
Authors: Bazzano Andrea , Bertinetti Stefano , Ardini Francisco , Cappelletti David , Grotti Marco
Published: March 2021

Lead content, enrichment factors, and isotopic composition (208Pb/206Pb and 207Pb/206Pb) measured in atmospheric particulate matter (PM10) samples collected for nine years at Ny-Ålesund (Svalbard islands, Norwegian Arctic) during spring and summer are presented and discussed. The possible source areas (PSA) for particulate inferred from Pb isotope ratio values were compared to cluster analysis of back-trajectories. Results show that anthropogenic Pb dominates over natural crustal Pb, with a recurring higher influence in spring, compared to summer. Crustal Pb accounted for 5–16% of the measured Pb concentration. Anthropogenic Pb was affected by (i) a Central Asian PSA with Pb isotope signature compatible with ores smelted in the Rudny Altai region, at the Russian and Kazakhstan border, which accounted for 85% of the anthropogenic Pb concentration, and (ii) a weaker North American PSA, contributing for the remaining 15%. Central Asian PSA exerted an influence on 71–86% of spring samples, without any significant interannual variation. On the contrary, 59–87% of summer samples were influenced by the North American PSA, with higher contributions during 2015 and 2018. Back-trajectory analysis agreed on the seasonal difference in PSA and highlighted a possible increased influence for North American air masses during summer 2010 and 2018, but not for summer 2015.
Structural and Ultrastructural Morphological Evaluation of Giant Anteater (Myrmecophaga tridactyla) Prostate Gland
Authors: Moura Fernanda , Sampaio Letícia , Kobayashi Priscila , Laufer-Amorim Renee , Ferreira João Carlos , Watanabe Tatiane Terumi Negrão , Fonseca-Alves Carlos E.
Published: March 2021

The giant anteater (Myrmecophaga tridactyla) is a vulnerable species from Central and South America, and is considered possibly extinct in Belize, Guatemala, El Salvador, and Uruguay. Due to the species’ conservation and reproductive importance, this research aimed to characterize the morphology, histochemical, immunohistochemical, and ultrastructural feature of the giant anteater prostate gland. For this, we collected 11 giant anteater prostate glands and performed macroscopic, morphological, histochemical, immunohistochemical, and ultrastructural analysis. Nine prostate glands from an adult subject and two from young subjects were studied. Grossly, the adult giant anteater prostate gland is divided in two distinct zones; the central zones (composed mainly of ducts) and the peripheral zones (of acini formed by secretory cells). The secretory cells showed positive periodic acid–Schiff staining. Furthermore, the immunohistochemical characterization revealed a similar human prostate pattern, with p63 staining basal cells, uroplakin III (UPIII) superficial cells of prostatic urethra, androgen receptor (AR) expressing nucleus of secretory and stromal cells, and prostatic specific antigen (PSA) staining prostatic epithelial cells. Overall, our research provided an in-depth morphological description of the giant anteater’s prostate gland, providing valuable information for futures studies focused on giant anteater conservation.
Efficacy Assessment of Biosynthesized Copper Oxide Nanoparticles (CuO-NPs) on Stored Grain Insects and Their Impacts on Morphological and Physiological Traits of Wheat (Triticum aestivum L.) Plant
Authors: Badawy Ali A. , Abdelfattah Nilly A. H. , Salem Salem S. , Awad Mohamed F. , Fouda Amr
Published: March 2021

Herein, CuO-NPs were fabricated by harnessing metabolites of Aspergillus niger strain (G3-1) and characterized using UV–vis spectroscopy, XRD, TEM, SEM-EDX, FT-IR, and XPS. Spherical, crystallographic CuO-NPs were synthesized in sizes ranging from 14.0 to 47.4 nm, as indicated by TEM and XRD. EDX and XPS confirmed the presence of Cu and O with weight percentages of 62.96% and 22.93%, respectively, at varied bending energies. FT-IR spectra identified functional groups of metabolites that could act as reducing, capping, and stabilizing agents to the CuO-NPs. The insecticidal activity of CuO-NPs against wheat grain insects Sitophilus granarius and Rhyzopertha dominica was dose- and time-dependent. The mortality percentages due to NP treatment were 55–94.4% (S. granarius) and 70–90% (R. dominica). A botanical experiment was done in a randomized block design. Low CuO-NP concentration (50 ppm) caused significant increases in growth characteristics (shoot and root length, fresh and dry weight of shoot and root, and leaves number), photosynthetic pigments (total chlorophylls and carotenoids), and antioxidant enzymes of wheat plants. There was no significant change in carbohydrate or protein content. The use of CuO-NPs is a promising tool to control grain insects and enhance wheat growth performance.
The Era of Nanomaterials: A Safe Solution or a Risk for Marine Environmental Pollution?
Authors: Esposito Maria Consiglia , Corsi Ilaria , Russo Gian Luigi , Punta Carlo , Tosti Elisabetta , Gallo Alessandra
Published: March 2021

In recent years, the application of engineered nanomaterials (ENMs) in environmental remediation gained increasing attention. Due to their large surface area and high reactivity, ENMs offer the potential for the efficient removal of pollutants from environmental matrices with better performances compared to conventional techniques. However, their fate and safety upon environmental application, which can be associated with their release into the environment, are largely unknown. It is essential to develop systems that can predict ENM interactions with biological systems, their overall environmental and human health impact. Until now, Life-Cycle Assessment (LCA) tools have been employed to investigate ENMs potential environmental impact, from raw material production, design and to their final disposal. However, LCA studies focused on the environmental impact of the production phase lacking information on their environmental impact deriving from in situ employment. A recently developed eco-design framework aimed to fill this knowledge gap by using ecotoxicological tools that allow the assessment of potential hazards posed by ENMs to natural ecosystems and wildlife. In the present review, we illustrate the development of the eco-design framework and review the application of ecotoxicology as a valuable strategy to develop ecosafe ENMs for environmental remediation. Furthermore, we critically describe the currently available ENMs for marine environment remediation and discuss their pros and cons in safe environmental applications together with the need to balance benefits and risks promoting an environmentally safe nanoremediation (ecosafe) for the future.
Interferon Regulatory Factor 5 (IRF5) Gene Haplotypes Are Associated with Premature Coronary Artery Disease. Association of the IRF5 Polymorphisms with Cardiometabolic Parameters. The Genetics of Atherosclerotic Disease (GEA) Mexican Study
Authors: Posadas-Sánchez Rosalinda , Cardoso-Saldaña Guillermo , Fragoso José Manuel , Vargas-Alarcón Gilberto
Published: March 2021

Interferon regulatory factor 5 (IRF5) has an important role in the inflammatory process, a fundamental component of coronary artery disease (CAD). Thus, the objective of this study was to evaluate the association of IRF5 polymorphisms with the development of premature CAD (pCAD) and cardiometabolic parameters. IRF5 polymorphisms (rs1874330, rs3778754, rs3757386, rs3757385, rs3807134, rs3807135, and rs6968563) were determined in 1116 pCAD patients and 1003 controls. Polymorphism distribution was similar in patients and controls; however, the haplotype analysis showed five haplotypes with a different distribution. TGCGTCT (OR (odds ratio) = 1.248, p = 0005) and TCTGCCT (OR = 10.73, p < 0.0001) were associated with a high risk, whereas TCCGTCT (OR = 0.155, p < 0.0001), CGCTTTT (OR = 0.108, p < 0.0001), and TCCGCCT (OR = 0.014, p < 0.0001) were associated with a low risk of pCAD. Associations with aspartate aminotransferase, hypertriglyceridemia, magnesium deficiency, triglycerides/HDL-C index, LDL-C, and adiponectin levels were observed in pCAD patients. In controls, associations with hypoalphalipoproteinemia, non-HDL-C, apolipoprotein B, hyperuricemia, TNF-α, IL-6, IL-15, valvular calcification, and subclinical hypothyroidism were observed. In summary, five haplotypes were associated with pCAD, two with high risk and three with low risk. Some IRF5 polymorphisms were associated with cardiometabolic parameters in pCAD patients and control.
Agroindustrial Wastes as a Support for the Immobilization of Lipase from Thermomyces lanuginosus: Synthesis of Hexyl Laurate
Authors: K. de S. Lira Regiane , T. Zardini Rochele , C. C. de Carvalho Marcela , Wojcieszak Robert , G. F. Leite Selma , Itabaiana Ivaldo
Published: March 2021

As a consequence of intense industrialization in the last few decades, the amount of agro-industrial wastes has increasing, where new forms of valorization are crucial. In this work, five residual biomasses from Maranhão (Brazil) were investigated as supports for immobilization of lipase from Thermomyces lanuginosus (TLL). The new biocatalysts BM-TLL (babaçu mesocarp) and RH-TLL (rice husk) showed immobilization efficiencies >98% and hydrolytic activities of 5.331 U g−1 and 4.608 U g−1, respectively, against 142 U g−1 by Lipozyme® TL IM. High esterification activities were also found, with 141.4 U g−1 and 396.4 U g−1 from BM-TLL and RH-TLL, respectively, against 113.5 U g−1 by TL IM. Results of porosimetry, SEM, and BET demonstrated BM and RH supports are mesoporous materials with large hydrophobic area, allowing a mixture of hydrophobic adsorption and confinement, resulting in hyperactivation of TLL. These biocatalysts were applied in the production of hexyl laurate, where RH-TLL was able to generate 94% conversion in 4 h. Desorption with Triton X-100 and NaCl confirmed that new biocatalysts were more efficient with 5 times less protein than commercial TL IM. All results demonstrated that residual biomass was able to produce robust and stable biocatalysts containing immobilized TLL with better results than commercial preparations.
RNA-seq Characterization of Melanoma Phenotype Switch in 3D Collagen after p38 MAPK Inhibitor Treatment
Authors: Čermák Vladimír , Škarková Aneta , Merta Ladislav , Kolomazníková Veronika , Palušová Veronika , Uldrijan Stjepan , Rösel Daniel , Brábek Jan
Published: March 2021

Melanoma phenotype plasticity underlies tumour dissemination and resistance to therapy, yet its regulation is incompletely understood. In vivo switching between a more differentiated, proliferative phenotype and a dedifferentiated, invasive phenotype is directed by the tumour microenvironment. We found that treatment of partially dedifferentiated, invasive A375M2 cells with two structurally unrelated p38 MAPK inhibitors, SB2021920 and BIRB796, induces a phenotype switch in 3D collagen, as documented by increased expression of melanocyte differentiation markers and a loss of invasive phenotype markers. The phenotype is accompanied by morphological change corresponding to amoeboid–mesenchymal transition. We performed RNA sequencing with an Illumina HiSeq platform to fully characterise transcriptome changes underlying the switch. Gene expression results obtained with RNA-seq were validated by comparing them with RT-qPCR. Transcriptomic data generated in the study will extend the present understanding of phenotype plasticity in melanoma and its contribution to invasion and metastasis.
Evidence-Based View of Safety and Effectiveness of Prokineticin Receptors Antagonists during Pregnancy
Authors: Reynaud Deborah , Sergent Frederic , Abi Nahed Roland , Traboulsi Wael , Collet Constance , Marquette Christel , Hoffmann Pascale , Balboni Gianfranco , Zhou Qun-Yong , Murthi Padma , Benharouga Mohamed , Alfaidy Nadia
Published: March 2021

Endocrine gland derived vascular endothelial growth factor (EG-VEGF) is a canonical member of the prokineticin (PROKs) family. It acts via the two G-protein coupled receptors, namely PROKR1 and PROKR2. We have recently demonstrated that EG-VEGF is highly expressed in the human placenta; contributes to placental vascularization and growth and that its aberrant expression is associated with pregnancy pathologies including preeclampsia and fetal growth restriction. These findings strongly suggested that antagonization of its receptors may constitute a potential therapy for the pregnancy pathologies. Two specific antagonists of PROKR1 (PC7) and for PROKR2 (PKRA) were reported to reverse PROKs adverse effects in other systems. In the view of using these antagonists to treat pregnancy pathologies, a proof of concept study was designed to determine the biological significances of PC7 and PKRA in normal pregnancy outcome. PC7 and PKRA were tested independently or in combination in trophoblast cells and during early gestation in the gravid mouse. Both independent and combined treatments uncovered endogenous functions of EG-VEGF. The independent use of antagonists distinctively identified PROKR1 and PROKR2-mediated EG-VEGF signaling on trophoblast differentiation and invasion; thereby enhancing feto-placental growth and pregnancy outcome. Thus, our study provides evidence for the potential safe use of PC7 or PKRA to improve pregnancy outcome.
Recent Development toward the Next Clinical Practice of Primary Aldosteronism: A Literature Review
Authors: Tezuka Yuta , Yamazaki Yuto , Nakamura Yasuhiro , Sasano Hironobu , Satoh Fumitoshi
Published: March 2021

For the last seven decades, primary aldosteronism (PA) has been gradually recognized as a leading cause of secondary hypertension harboring increased risks of cardiovascular incidents compared to essential hypertension. Clinically, PA consists of two major subtypes, surgically curable and uncurable phenotypes, determined as unilateral or bilateral PA by adrenal venous sampling. In order to further optimize the treatment, surgery or medications, diagnostic procedures from screening to subtype differentiation is indispensable, while in the general clinical practice, the work-up rate is extremely low even in the patients with refractory hypertension because of the time-consuming and labor-intensive nature of the procedures. Therefore, a novel tool to simplify the diagnostic flow has been recently in enormous demand. In this review, we focus on recent progress in the following clinically important topics of PA: prevalence of PA and its subtypes, newly revealed histopathological classification of aldosterone-producing lesions, novel diagnostic biomarkers and prediction scores. More effective strategy to diagnose PA based on better understanding of its epidemiology and pathology should lead to early detection of PA and could decrease the cardiovascular and renal complications of the patients.
3D-PAD: Paper-Based Analytical Devices with Integrated Three-Dimensional Features
Authors: Ng James S. , Hashimoto Michinao
Published: March 2021

This paper describes the use of fused deposition modeling (FDM) printing to fabricate paper-based analytical devices (PAD) with three-dimensional (3D) features, which is termed as 3D-PAD. Material depositions followed by heat reflow is a standard approach for the fabrication of PAD. Such devices are primarily two-dimensional (2D) and can hold only a limited amount of liquid samples in the device. This constraint can pose problems when the sample consists of organic solvents that have low interfacial energies with the hydrophobic barriers. To overcome this limitation, we developed a method to fabricate PAD integrated with 3D features (vertical walls as an example) by FDM 3D printing. 3D-PADs were fabricated using two types of thermoplastics. One thermoplastic had a low melting point that formed hydrophobic barriers upon penetration, and another thermoplastic had a high melting point that maintained 3D features on the filter paper without reflowing. We used polycaprolactone (PCL) for the former, and polylactic acid (PLA) for the latter. Both PCL and PLA were printed with FDM without gaps at the interface, and the resulting paper-based devices possessed hydrophobic barriers consisting of PCL seamlessly integrated with vertical features consisting of PLA. We validated the capability of 3D-PAD to hold 30 μL of solvents (ethanol, isopropyl alcohol, and acetone), all of which would not be retained on conventional PADs fabricated with solid wax printers. To highlight the importance of containing an increased amount of liquid samples, a colorimetric assay for the formation of dimethylglyoxime (DMG)-Ni (II) was demonstrated using two volumes (10 μL and 30 μL) of solvent-based dimethylglyoxime (DMG). FDM printing of 3D-PAD enabled the facile construction of 3D structures integrated with PAD, which would find applications in paper-based chemical and biological assays requiring organic solvents.
Long-Term Trends of Hazel Grouse (Tetrastes bonasia) in the Bohemian Forest (Šumava), Czech Republic, 1972–2019
Authors: Klaus Siegfried , Ludwig Tobias
Published: March 2021

The population dynamics of Hazel Grouse were studied by presence/absence recording at stationary sites along fixed routes (110 km) in the central part of Šumava (Bohemian Forest, Czech Republic) from 1972 to 2019. The 100 km2 study area covered altitudes between 600 m (Rejštejn) and 1253 m above sea level (Mt. Sokol). Our database contained indices of Hazel Grouse occupancy: positive sites/visited sites for a yearly increasing number of Hazel Grouse occurrence sites (n = 134) for 48 years. We used a loglinear Poisson regression method to analyze the long-term population trend for Hazel Grouse in the study area. In the period from 1972 to 2006 we found a stable Hazel Grouse population (p = 0.83). From 2006–2007 to 2019, the population index dropped (−3.8% per year, p < 0.05). This decline is assumed to be influenced by habitat loss due to succession, resulting in older, more open forest stands, by strongly increasing forestry and windstorm “Kyrill”, followed by clear cutting, bark beetle damage, and the removal of pioneer trees in spruce plantations, which diminished buds and catkins, the dominant winter food of Hazel Grouse. The influence of disturbance by increasing tourist activities and/or predation is also discussed. Our results could help to optimize the conservation efforts for Hazel Grouse in the Bohemian Forest.
Displacement Demand for Nonlinear Static Analyses of Masonry Structures: Critical Review and Improved Formulations
Authors: Guerrini Gabriele , Kallioras Stylianos , Bracchi Stefano , Graziotti Francesco , Penna Andrea
Published: March 2021

This paper discusses different formulations for calculating earthquake-induced displacement demands to be associated with nonlinear static analysis procedures for the assessment of masonry structures. Focus is placed on systems with fundamental periods between 0.1 and 0.5 s, for which the inelastic displacement amplification is usually more pronounced. The accuracy of the predictive equations is assessed based on the results from nonlinear time-history analyses, carried out on single-degree-of-freedom oscillators with hysteretic force–displacement relationships representative of masonry structures. First, the study demonstrates some limitations of two established approaches based on the equivalent linearization concept: the capacity spectrum method of the Dutch guidelines NPR 9998-18, and its version outlined in FEMA 440, both of which overpredict maximum displacements. Two codified formulations relying on inelastic displacement spectra are also evaluated, namely the N2 method of Eurocode 8 and the displacement coefficient method of ASCE 41-17: the former proves to be significantly unconservative, while the latter is affected by excessive dispersion. A non-iterative procedure, using an equivalent linear system with calibrated optimal stiffness and equivalent viscous damping, is then proposed to overcome some of the problems identified earlier. A recently developed modified N2 formulation is shown to improve accuracy while limiting the dispersion of the predictions.
Properties of Cementitious Materials with Recycled Aggregate and Powder Both from Clay Brick Waste
Authors: Wu Huixia , Xiao Jianzhuang , Liang Chaofeng , Ma Zhiming
Published: March 2021

The utilization of recycled brick aggregate (RBA) and recycled brick powder (RBP) in cementitious materials helps the reclamation of clay brick waste in construction and demolition waste. This work studied the properties of cementitious materials with RBA as aggregate and RBP as supplementary cementitious material. The RBA has lower apparent density and higher water absorption than natural aggregate, and RBP with an irregular micro-structure contains high content of silicon and aluminum oxides and possesses excellent pozzolanic activity. Incorporating RBP decreases the fluidity and increases the setting time, but the incorporated RBP improves the pore structure and decreases the average pore diameter of cementitious materials, thereby decreasing the permeability. Utilizing RBA increases the drying shrinkage, while the incorporated RBP decreases the drying shrinkage of cementitious materials; the mortar with 50% RBA and 30% RBP has the lower drying shrinkage than the common mortar without RBA and RBP. Incorporating RBA and high-volume RBP decreases the mechanical strength, while there is no obvious decrease in the mechanical strength for the mortar with 50% RBA and 30% RBP. Moreover, the flexural strength to compressive strength ratio increases with RBA and RBP incorporating. Utilizing RBA increases the water transport, while the water transport properties decrease with the RBP incorporation; incorporating appropriate content of RBA and RBP can obtain the cementitious materials with low permeability. Particularly, a significant decrease in chloride ingress occurs with the substitution of RBP.
Pre-Clinical Evaluation of the Proteasome Inhibitor Ixazomib against Bortezomib-Resistant Leukemia Cells and Primary Acute Leukemia Cells
Authors: Roeten Margot S.F. , van Meerloo Johan , Kwidama Zinia J. , ter Huizen Giovanna , Segerink Wouter H. , Zweegman Sonja , Kaspers Gertjan J.L. , Jansen Gerrit , Cloos Jacqueline
Published: March 2021

At present, 20–30% of children with acute leukemia still relapse from current chemotherapy protocols, underscoring the unmet need for new treatment options, such as proteasome inhibition. Ixazomib (IXA) is an orally available proteasome inhibitor, with an improved safety profile compared to Bortezomib (BTZ). The mechanism of action (proteasome subunit inhibition, apoptosis induction) and growth inhibitory potential of IXA vs. BTZ were tested in vitro in human (BTZ-resistant) leukemia cell lines. Ex vivo activity of IXA vs. BTZ was analyzed in 15 acute lymphoblastic leukemia (ALL) and 9 acute myeloid leukemia (AML) primary pediatric patient samples. BTZ demonstrated more potent inhibitory effects on constitutive β5 and immunoproteasome β5i proteasome subunit activity; however, IXA more potently inhibited β1i subunit than BTZ (70% vs. 29% at 2.5 nM). In ALL/AML cell lines, IXA conveyed 50% growth inhibition at low nanomolar concentrations, but was ~10-fold less potent than BTZ. BTZ-resistant cells (150–160 fold) displayed similar (100-fold) cross-resistance to IXA. Finally, IXA and BTZ exhibited anti-leukemic effects for primary ex vivo ALL and AML cells; mean LC50 (nM) for IXA: 24 ± 11 and 30 ± 8, respectively, and mean LC50 for BTZ: 4.5 ± 1 and 11 ± 4, respectively. IXA has overlapping mechanisms of action with BTZ and showed anti-leukemic activity in primary leukemic cells, encouraging further pre-clinical in vivo evaluation.
Recent Updates on the Significance of KRAS Mutations in Colorectal Cancer Biology
Authors: László Loretta , Kurilla Anita , Takács Tamás , Kudlik Gyöngyi , Koprivanacz Kitti , Buday László , Vas Virag
Published: March 2021

The most commonly mutated isoform of RAS among all cancer subtypes is KRAS. In this review, we focus on the special role of KRAS mutations in colorectal cancer (CRC), aiming to collect recent data on KRAS-driven enhanced cell signalling, in vitro and in vivo research models, and CRC development-related processes such as metastasis and cancer stem cell formation. We attempt to cover the diverse nature of the effects of KRAS mutations on age-related CRC development. As the incidence of CRC is rising in young adults, we have reviewed the driving forces of ageing-dependent CRC.
Cell Surface GRP94 as a Novel Emerging Therapeutic Target for Monoclonal Antibody Cancer Therapy
Authors: Kim Ji Woong , Cho Yea Bin , Lee Sukmook
Published: March 2021

Glucose-regulated protein 94 (GRP94) is an endoplasmic reticulum (ER)-resident member of the heat shock protein 90 (HSP90) family. In physiological conditions, it plays a vital role in regulating biological functions, including chaperoning cellular proteins in the ER lumen, maintaining calcium homeostasis, and modulating immune system function. Recently, several reports have shown the functional role and clinical relevance of GRP94 overexpression in the progression and metastasis of several cancers. Therefore, the current review highlights GRP94’s physiological and pathophysiological roles in normal and cancer cells. Additionally, the unmet medical needs of small chemical inhibitors and the current development status of monoclonal antibodies specifically targeting GRP94 will be discussed to emphasize the importance of cell surface GRP94 as an emerging therapeutic target in monoclonal antibody therapy for cancer.
G Protein-Coupled Estrogen Receptor in Cancer and Stromal Cells: Functions and Novel Therapeutic Perspectives
Authors: Pepermans Richard A. , Sharma Geetanjali , Prossnitz Eric R.
Published: March 2021

Estrogen is involved in numerous physiological and pathophysiological systems. Its role in driving estrogen receptor-expressing breast cancers is well established, but it also has important roles in a number of other cancers, acting both on tumor cells directly as well as in the function of multiple cells of the tumor microenvironment, including fibroblasts, immune cells, and adipocytes, which can greatly impact carcinogenesis. One of its receptors, the G protein-coupled estrogen receptor (GPER), has gained much interest over the last decade in both health and disease. Increasing evidence shows that GPER contributes to clinically observed endocrine therapy resistance in breast cancer while also playing a complex role in a number of other cancers. Recent discoveries regarding the targeting of GPER in combination with immune checkpoint inhibition, particularly in melanoma, have led to the initiation of the first Phase I clinical trial for the GPER-selective agonist G-1. Furthermore, its functions in metabolism and corresponding pathophysiological states, such as obesity and diabetes, are becoming more evident and suggest additional therapeutic value in targeting GPER for both cancer and other diseases. Here, we highlight the roles of GPER in several cancers, as well as in metabolism and immune regulation, and discuss the therapeutic value of targeting this estrogen receptor as a potential treatment for cancer as well as contributing metabolic and inflammatory diseases and conditions.
Meconium Aspiration Syndrome: A Narrative Review
Authors: Monfredini Chiara , Cavallin Francesco , Villani Paolo Ernesto , Paterlini Giuseppe , Allais Benedetta , Trevisanuto Daniele
Published: March 2021

Meconium aspiration syndrome is a clinical condition characterized by respiratory failure occurring in neonates born through meconium-stained amniotic fluid. Worldwide, the incidence has declined in developed countries thanks to improved obstetric practices and perinatal care while challenges persist in developing countries. Despite the improved survival rate over the last decades, long-term morbidity among survivors remains a major concern. Since the 1960s, relevant changes have occurred in the perinatal and postnatal management of such patients but the most appropriate approach is still a matter of debate. This review offers an updated overview of the epidemiology, etiopathogenesis, diagnosis, management and prognosis of infants with meconium aspiration syndrome.
Renewable Biomass Utilization: A Way Forward to Establish Sustainable Chemical and Processing Industries
Authors: Guragain Yadhu N. , Vadlani Praveen V.
Published: March 2021

Lignocellulosic biomass feedstocks are promising alternatives to fossil fuels for meeting raw material needs of processing industries and helping transit from a linear to a circular economy and thereby meet the global sustainability criteria. The sugar platform route in the biochemical conversion process is one of the promising and extensively studied methods, which consists of four major conversion steps: pretreatment, hydrolysis, fermentation, and product purification. Each of these conversion steps has multiple challenges. Among them, the challenges associated with the pretreatment are the most significant for the overall process because this is the most expensive step in the sugar platform route and it significantly affects the efficiency of all subsequent steps on the sustainable valorization of each biomass component. However, the development of a universal pretreatment method to cater to all types of feedstock is nearly impossible due to the substantial variations in compositions and structures of biopolymers among these feedstocks. In this review, we have discussed some promising pretreatment methods, their processing and chemicals requirements, and the effect of biomass composition on deconstruction efficiencies. In addition, the global biomass resources availability and process intensification ideas for the lignocellulosic-based chemical industry have been discussed from a circularity and sustainability standpoint.
Special Issue “Anti-Adhesive Surfaces”
Authors: Carbone Giuseppe , Di Mundo Rosa
Published: March 2021

Research and review articles tackling the theme of antiadhesive surfaces are here collected [...]