bluuebunny/crossref_metadata_2025 huggingface dataset:
From Supply Chain 4.0 to Supply Chain 5.0: Findings from a Systematic Literature Review and Research Directions
Authors: Frederico Guilherme F.
Published: July 2021

The main purpose of this paper is to present what the Industry 5.0 phenomenon means in the supply chain context. A systematic literature review method was used to get evidence from the current knowledge linked to this theme. The results have evidenced a strong gap related to Industry 5.0 approaches for the supply chain field. Forty-one (41) publications, including conference and journal papers, have been found in the literature. Nineteen (19) words, which were grouped in four (4) clusters, have been identified in the data analysis. This was the basis to form the four (4) constructs of Industry 5.0: Industry Strategy, Innovation and Technologies, Society and Sustainability, and Transition Issues. Then, an alignment with the supply chain context was proposed, being the basis for the incipient Supply Chain 5.0 framework and its research agenda. Industry 5.0 is still in an embryonic and ideal stage. The literature is scarce and many other concepts and discoveries are going to emerge. Although this literature review is based on few available sources, it provides insightful and novel concepts related to Industry 5.0 in the supply chain context. Moreover, it presents a clear set of constructs and a structured research agenda to encourage researchers in deploying further conceptual and empirical works linked to the subject herein explored. Organizations’ leadership, policymakers, and other practitioners involved in supply chains, and mainly those currently working with Industry 4.0 initiatives, can benefit from this research by having clear guidance regarding the dimensions needed to structurally design and implement an Industry 5.0 strategy. This article adds valuable insights to researchers and practitioners, by approaching the newest and revolutionary concept of the Industry 5.0 phenomenon in the supply chain context, which is still an unexplored theme.
Efficient Implementations of Sieving and Enumeration Algorithms for Lattice-Based Cryptography
Authors: Satılmış Hami , Akleylek Sedat , Lee Cheng-Chi
Published: July 2021

The security of lattice-based cryptosystems is based on solving hard lattice problems such as the shortest vector problem (SVP) and the closest vector problem (CVP). Various cryptanalysis algorithms such as (Pro)GaussSieve, HashSieve, ENUM, and BKZ have been proposed to solve these hard problems. Several implementations of these algorithms have been developed. On the other hand, the implementations of these algorithms are expected to be efficient in terms of run time and memory space. In this paper, a modular software package/library containing efficient implementations of GaussSieve, ProGaussSieve, HashSieve, and BKZ algorithms is developed. These implementations are considered efficient in terms of run time. While constructing this software library, some modifications to the algorithms are made to increase the performance. Then, the run times of these implementations are compared with the others. According to the experimental results, the proposed GaussSieve, ProGaussSieve, and HashSieve implementations are at least 70%, 75%, and 49% more efficient than previous ones, respectively.
Effective Pedagogy of Guiding Undergraduate Engineering Students Solving First-Order Ordinary Differential Equations
Authors: Guo William , Li Wei , Tisdell Christopher C.
Published: July 2021

An alternative pedagogical design is discussed that aims to guide engineering students to solve first-order ordinary differential equations (ODEs), and is based on students’ learning weaknesses identified from previous teaching and learning activities. This approach supported student’s self-enrichment through exploration of relevant resources in ODEs, and guided students towards the choice of their own effective ways for solving ODEs for different problems. This paper presents the practices on designing and delivering solution techniques for first-order linear ODEs using this approach for more than 400 undergraduate engineering students at a regional university in Australia during 2014–2017. The timeline involved initial experimentation in 2014 and 2015, followed by refinements to the pedagogy based on student’s feedback. The refined pedagogy was then used for the advanced mathematics course in 2016 and 2017. Significant improvements were made in student’s learning outcomes in effectively and accurately solving the first-order linear ODEs over this period.
Strength Enhancement of Superduplex Stainless Steel Using Thermomechanical Processing
Authors: Lakhdari M. A. , Krajcarz F. , Mithieux J. D. , Van Landeghem H. P. , Veron M.
Published: July 2021

The impact of microstructure evolution on mechanical properties in superduplex stainless steel UNS S32750 (EN 1.4410) was investigated. To this end, different thermomechanical treatments were carried out in order to obtain clearly distinct duplex microstructures. Optical microscopy and scanning electron microscopy, together with texture measurements, were used to characterize the morphology and the preferred orientations of ferrite and austenite in all microstructures. Additionally, the mechanical properties were assessed by tensile tests with digital image correlation. Phase morphology was not found to significantly affect the mechanical properties and neither were phase volume fractions within 13% of the 50/50 ratio. Austenite texture was the same combined Goss/Brass texture regardless of thermomechanical processing, while ferrite texture was mainly described by α-fiber orientations. Ferrite texture and average phase spacing were found to have a notable effect on mechanical properties. One of the original microstructures of superduplex stainless steel obtained here shows a strength improvement by the order of 120 MPa over the industrial material.
Doxorubicin Anticancer Drug Monitoring by ds-DNA-Based Electrochemical Biosensor in Clinical Samples
Authors: Hassani Moghadam Firouzeh , Taher Mohammad A. , Karimi-Maleh Hassan
Published: July 2021

In this research, glassy carbon electrode (GCE) amplified with single-wall carbon nanotubes (SWCNTs) and ds-DNA was fabricated and utilized for voltammetric sensing of doxorubicin with a low detection limit. In this technique, the reduction in guanine signal of ds-DNA in the presence of doxorubicin (DOX) was chosen as an analytical factor. The molecular docking study revealed that the doxorubicin drug interacted with DNA through intercalation mode, which was in agreement with obtained experimental results. The DOX detection performance of ds-DNA/SWCNTs/GCE was assessed at a concentration range of 1.0 nM–20.0 µM. The detection limit was found to be 0.6 nM that was comparable and even better (in many cases) than that of previous electrochemical reported sensors. In the final step, the ds-DNA/SWCNTs/GCE showed powerful ability for determination of the DOX in injection samples with acceptable recovery data.
Characterization of Two α-l-Arabinofuranosidases from Acetivibrio mesophilus and Their Synergistic Effect in Degradation of Arabinose-Containing Substrates
Authors: Liu Yajing , Vanderhaeghen Sonja , Feiler Werner , Angelov Angel , Baudrexl Melanie , Zverlov Vladimir , Liebl Wolfgang
Published: July 2021

Arabinofuranosidases are important accessory enzymes involved in the degradation of arabinose-containing poly- and oligosaccharides. Two arabinofuranosidases from the recently described novel anaerobic cellulolytic bacterium Acetivibrio mesophilus, designated AmAraf51 and AmAraf43, were heterologously expressed in Escherichia coli and biochemically characterized. AmAraf51 not only removed arabinose moieties at O-3, O-2 and terminal O-5 positions of arabinose-containing oligosaccharides, but also exhibited exo-β-xylosidase side activity. In comparison, AmAraf43 preferably cleaved 1,3-linkages from arabinosyl disubstitutions. AmAraf51 and AmAraf43 demonstrated maximum activity at 70 °C and 57 °C, respectively. Judging from the genetic context and substrate specificity, AmAraf51 may decompose internalized arabino/xylo-oligosaccharides. The embedding of the AmAraf43 gene between genes for several putative xylanolytic enzymes, along with its enzymatic properties suggests that AmAraf43 cleaves arabinose decorations from heteroxylans extracellularly. The enzymes revealed completely converse activity profiles towards arabinan/arabinoxylan: AmAraf51 displayed strong activity on arabinan, while AmAraf43 prefers arabinoxylan. AmAraf51 dramatically stimulated the saccharification level of wheat arabinoxylan (WAX-RS) and sugar beet arabinan when administered along with xylanase M_Xyn10 or arabinanase PpAbn43, respectively. For WAX-RS degradation, the yield of arabinose and xylose was boosted 13.77-fold and 4.96-fold, respectively. The bifunctional activity, thermostability and high catalytic efficiency make AmAraf51 an interesting candidate for industrial applications.
Analysis of 56,348 Genomes Identifies the Relationship between Antibiotic and Metal Resistance and the Spread of Multidrug-Resistant Non-Typhoidal Salmonella
Authors: Fenske Gavin J. , Scaria Joy
Published: July 2021

Salmonella enterica is common foodborne pathogen that generates both enteric and systemic infections in hosts. Antibiotic resistance is common is certain serovars of the pathogen and of great concern to public health. Recent reports have documented the co-occurrence of metal resistance with antibiotic resistance in one serovar of S. enterica. Therefore, we sought to identify possible co-occurrence in a large genomic dataset. Genome assemblies of 56,348 strains of S. enterica comprising 20 major serovars were downloaded from NCBI. The downloaded assemblies were quality controlled and in silico serotyped to ensure consistency and avoid improper annotation from public databases. Metal and antibiotic resistance genes were identified in the genomes as well as plasmid replicons. Co-occurrent genes were identified by constructing a co-occurrence matrix and grouping said matrix using k-means clustering. Three groups of co-occurrent genes were identified using k-means clustering. Group 1 was comprised of the pco and sil operons that confer resistance to copper and silver, respectively. Group 1 was distributed across four serovars. Group 2 contained the majority of the genes and little to no co-occurrence was observed. Metal and antibiotic co-occurrence was identified in group 3 that contained genes conferring resistance to: arsenic, mercury, beta-lactams, sulfonamides, and tetracyclines. Group 3 genes were also associated with an IncQ1 class plasmid replicon. Metal and antibiotic co-occurrence from group 3 genes is mostly isolated to one clade of S. enterica I 4,[5],12:i:-.
Analysis and Reconstitution of the Menaquinone Biosynthesis Pathway in Lactiplantibacillus plantarum and Lentilactibacillus buchneri
Authors: Watthanasakphuban Nisit , Virginia Ludovika Jessica , Haltrich Dietmar , Peterbauer Clemens
Published: July 2021

In Lactococcus lactis and some other lactic acid bacteria, respiratory metabolism has been reported upon supplementation with only heme, leading to enhanced biomass formation, reduced acidification, resistance to oxygen, and improved long-term storage. Genes encoding a complete respiratory chain with all components were found in genomes of L. lactis and Leuconostoc mesenteroides, but menaquinone biosynthesis was found to be incomplete in Lactobacillaceae (except L. mesenteroides). Lactiplantibacillus plantarum has only two genes (menA, menG) encoding enzymes in the biosynthetic pathway (out of eight), and Lentilactobacillus buchneri has only four (menA, menB, menE, and menG). We constructed knock-out strains of L. lactis defective in menA, menB, menE, and menG (encoding the last steps in the pathway) and complemented these by expression of the extant genes from Lactipl. plantarum and Lent. buchneri to verify their functionality. Three of the Lactipl. plantarum biosynthesis genes, lpmenA1, lpmenG1, and lpmenG2, as well as lbmenB and lbmenG from Lent. buchneri, reconstituted menaquinone production and respiratory growth in the deficient L. lactis strains when supplemented with heme. We then reconstituted the incomplete menaquinone biosynthesis pathway in Lactipl. plantarum by expressing six genes from L. lactis homologous to the missing genes in a synthetic operon with two inducible promoters. Higher biomass formation was observed in Lactipl. plantarum carrying this operon, with an OD600 increase from 3.0 to 5.0 upon induction.
Common and Rare Hematological Manifestations and Adverse Drug Events during Treatment of Active TB: A State of Art
Authors: Minardi Maria Letizia , Fato Ilenia , Di Gennaro Francesco , Mosti Silvia , Mastrobattista Annelisa , Cerva Carlotta , Libertone Raffaella , Saracino Annalisa , Goletti Delia , Girardi Enrico , Andreoni Massimo , Palmieri Fabrizio , Gualano Gina
Published: July 2021

Background: Tuberculosis (TB) can seriously affect the hematopoietic system, with involvement of both myeloid and lymphoid cell lines as well as plasma components. These hematological changes act as a marker for the diagnosis, prognosis and response to therapy. Methods: We searched PubMed, Scopus, Google Scholar, EMBASE, Cochrane Library and WHO websites from 1950 to May 2021 for papers on the interaction between TB and common and rare hematological manifestation. Results: Hematological reactions in patients with TB are possible in both young and old women and men but seem more frequent in the elderly, and they can be predictors of both diagnosis and worse outcome for TB, regardless of whether it is pulmonary, extra pulmonary or miliary. Even anti-TB therapies can cause hematological adverse events, among which some are serious and rare and can compromise the patient’s recovery pathway to completing treatment. Conclusion: Hematological screening and follow-up, including complete blood count and coagulation, are always necessary both at the diagnosis of TB and during antitubercular treatment in order to monitor hematological parameters. Short therapy regimens for multidrug-resistant TB (MDR-TB) may also be useful for reducing hematological toxicity, especially in contexts where this cannot be monitored. Close monitoring of drug interactions and hematological adverse events is always recommended.
Production Technologies of Ancient Bricks from Padua, Italy: Changing Colors and Resistance over Time
Authors: Pérez-Monserrat Elena Mercedes , Maritan Lara , Garbin Enrico , Cultrone Giuseppe
Published: July 2021

Representative and very uneven texturally bricks having yellow/beige or pale or dark red colors from the Renaissance walls (16th century) of Padua, Northeast Italy, were studied by means of colorimetric, petrographic (MOP), chemical (XRF), mineralogical (PXRD) and microstructural analysis (FESEM-EDS). Starting from the color measurements of the ceramic bodies, the manufacturing technologies and their influence on the physical behavior and durability of the bricks were established. The porous system was characterized by means of hygric tests and mercury intrusion porosimetry; the compactness and structural anisotropy were defined through ultrasound velocity; the uniaxial compressive strength was determined; and durability to salt crystallization and frost action of the bricks was assessed. Mg- and Ca-rich illitic clays fired at temperatures ≥900 °C were used to manufacture the beige hue bodies, while the pale red bricks were made out with Ca- and Fe-rich illitic clays fired at 850–900 °C. A lower carbonate content on the base clays and a lower firing temperature were the main causes responsible for the changing colors from beige to red hue. The increase of the red color was associated to higher silicate inclusions content and lower development of reaction rims around grains. The low sintering degree achieved yielded highly porous bodies with diverse porous systems, leading to differential physical performance and durability of the bricks that may turn out beneficial for the conservation of the historic walls.
U-Pb Detrital Zircon Ages and Geochemical Features of the Jingxing Formation, (Qamdo Basin, Tibet: Implications): Inferences for the Metallogenic Model of the East Tethys Evaporite
Authors: Han Wenhua , Ma Haizhou , Fang Weixuan , Cheng Huaide , Li Yongshou , Li Binkai , Miao Weiliang , Hai Qinyu
Published: July 2021

Qamdo basin is located between the suture zone of Jinsha River (Ailao Mountains) and that of Ban Gong Lake (Nujiang) in the eastern Tethys. Part of the Jingxing Formation is deposited in the southwest of the basin. In this study, two profiles were investigated from the north and south of Qamdo basin. The characteristics of detrital zircon LA-ICP-MS U-Pb age, and the main and trace elements of sandstone were analyzed. The characteristics of major and trace elements showed that the tectonic setting of the study area is mainly composed of a relatively stable active continental margin and a passive continental margin, showing characteristics of a continental island arc. The weathering degree of Jingxing Formation in the Qamdo area is lower than that in the Lanping-Simao area, which may be closer to the origin. The age distribution characteristics of detrital zircon grains indicate that the Qiangtang Block, Youjiang basin, and Yangtze area jointly constitute the provenance of the Qamdo-Lanping-Simao basin. Both basins may be part of a large marine basin with unified water conservancy connection before evaporite deposition. Metamorphic seawater from the Qamdo basin may migrate to the Lanping-Simao basin and even the Khorat basin, where evaporite was deposited.
Structure–Activity Relationships of the Antimalarial Agent Artemisinin 10. Synthesis and Antimalarial Activity of Enantiomers of rac-5β-Hydroxy-d-Secoartemisinin and Analogs: Implications Regarding the Mechanism of Action
Authors: Jahan Mohamed , Leon Francisco , Fronczek Frank R. , Elokely Khaled M. , Rimoldi John , Khan Shabana I. , Avery Mitchell A.
Published: July 2021

An efficient synthesis of rac-6-desmethyl-5β–hydroxy-d-secoartemisinin 2, a tricyclic analog of R-(+)-artemisinin 1, was accomplished and the racemate was resolved into the (+)-2b and (−)-2a enantiomers via their Mosher Ester diastereomers. Antimalarial activity resided with only the artemisinin-like enantiomer R-(−)-2a. Several new compounds 9–16, 19a, 19b, 22 and 29 were synthesized from rac-2 but the C-5 secondary hydroxyl group was surprisingly unreactive. For example, the formation of carbamates and Mitsunobu reactions were unsuccessful. In order to assess the unusual reactivity of 2, a single crystal X-ray crystallographic analysis revealed a close intramolecular hydrogen bond from the C-5 alcohol to the oxepane ether oxygen (O-11). All products were tested in vitro against the W-2 and D-6 strains of Plasmodium falciparum. Several of the analogs had moderate activity in comparison to the natural product 1. Iron (II) bromide-promoted rearrangement of 2 gave, in 50% yield, the ring-contracted tetrahydrofuran 22, while the 5-ketone 15 provided a monocyclic methyl ketone 29 (50%). Neither 22 nor 29 possessed in vitro antimalarial activity. These results have implications in regard to the antimalarial mechanism of action of artemisinin.
LP1 and LP2: Dual-Target MOPr/DOPr Ligands as Drug Candidates for Persistent Pain Relief
Authors: Pasquinucci Lorella , Parenti Carmela , Georgoussi Zafiroula , Reina Lorena , Tomarchio Emilia , Turnaturi Rita
Published: July 2021

Although persistent pain is estimated to affect about 20% of the adult population, current treatments have poor results. Polypharmacology, which is the administration of more than one drug targeting on two or more different sites of action, represents a prominent therapeutic approach for the clinical management of persistent pain. Thus, in the drug discovery process the “one-molecule-multiple targets” strategy nowadays is highly recognized. Indeed, multitarget ligands displaying a better antinociceptive activity with fewer side effects, combined with favorable pharmacokinetic and pharmacodynamic characteristics, have already been shown. Multitarget ligands possessing non-opioid/opioid and opioid/opioid mechanisms of action are considered as potential drug candidates for the management of various pain conditions. In particular, dual-target MOPr (mu opioid peptide receptor)/DOPr (delta opioid peptide receptor) ligands exhibit an improved antinociceptive profile associated with a reduced tolerance-inducing capability. The benzomorphan-based compounds LP1 and LP2 belong to this class of dual-target MOPr/DOPr ligands. In the present manuscript, the structure–activity relationships and the pharmacological fingerprint of LP1 and LP2 compounds as suitable drug candidates for persistent pain relief is described.
Anxiolytic Effect of Two Tobacco Essential Oils (Nicotiana tabacum Linn.) on Mice
Authors: Xie Danqing , Yao Lei , Huang Yan , Wu Shuaifan , Ma Li , Li Yuhong , Wang Wencui
Published: July 2021

Tobacco (Nicotiana tabacum Linn.) is a famous traditional herb used in folk medicine. The essential oils of tobacco have been demonstrated in modern studies to possess antioxidant, anti-inflammatory, and neuroprotective properties, while its anxiolytic effect has not been reported. The purpose of this study was to evaluate the anxiolytic effect of Yunnan tobacco essential oil (YTO) and Zimbabwe tobacco essential oil (ZTO) on mice. The constituents of YTO and ZTO were analyzed by GC/MS. The anxiolytic effect of YTO and ZTO (0.1%, 1%, and 10%, v/v) on male ICR mice was evaluated in the light–dark box test (LDB) and the elevated plus maze test (EPM) test via inhalation and transdermal administration. After the behavioral tests, salivary corticosterone levels in mice were measured. The behavioral analysis showed that the administration of both YTO and ZTO elevated the time that the mice spent in the light chamber in the LDB test compared to the untreated control. In the EPM test, YTO and ZTO increased the time spent in open arms and the number of entries into the open arms. In addition, both YTO and ZTO significantly decreased salivary corticosterone levels in mice (p ≤ 0.001). In summary, our results demonstrated that inhalation and transdermal administration of both YTO and ZTO showed anxiolytic effect on male ICR mice.
Validation of a Simple HPLC-Based Method for Lysine Quantification for Ruminant Nutrition
Authors: Albuquerque João , Casal Susana , Cruz Rebeca , Van Dorpe Ingrid , Maia Margarida Rosa Garcez , Fonseca António José Mira , Cabrita Ana Rita Jordão , Neves Ana Rute , Reis Salette
Published: July 2021

Robust and selective quantification methods are required to better analyze feed supplementation effectiveness with specific amino acids. In this work, a reversed-phase high-performance liquid chromatography method with fluorescence detection is proposed and validated for lysine quantification, one of the most limiting amino acids in ruminant nutrition and essential towards milk production. To assess and widen method applicability, different matrices were considered: namely Li2CO3 buffer (the chosen standard reaction buffer), phosphate buffer solution (to mimic media in cellular studies), and rumen inoculum. The method was validated for all three matrices and found to be selective, accurate (92% ± 2%), and precise at both the inter- and intra-day levels in concentrations up to 225 µM, with detection and quantification limits lower than 1.24 and 4.14 µM, respectively. Sample stability was evaluated when stored at room temperature, 4 °C, and −20 °C, showing consistency for up to 48 h regardless of the matrix. Finally, the developed method was applied in the quantification of lysine on real samples. The results presented indicate that the proposed method can be applied towards free lysine quantification in ruminant feeding studies and potentially be of great benefit to dairy cow nutrition supplementation and optimization.
Oleogel Formulations for the Topical Delivery of Betulin and Lupeol in Skin Injuries—Preparation, Physicochemical Characterization, and Pharmaco-Toxicological Evaluation
Authors: Pârvănescu (Pană) Ramona Daniela , Watz Claudia-Geanina , Moacă Elena-Alina , Vlaia Lavinia , Marcovici Iasmina , Macașoi Ioana Gabriela , Borcan Florin , Olariu Ioana , Coneac Georgeta , Drăghici George-Andrei , Crăiniceanu Zorin , Flondor (Ionescu) Daniela , Enache Alexandra , Dehelean Cristina Adriana
Published: July 2021

The skin integrity is essential due to its pivotal role as a biological barrier against external noxious factors. Pentacyclic triterpenes stand as valuable plant-derived natural compounds in the treatment of skin injuries due to their anti-inflammatory, antioxidant, antimicrobial, and healing properties. Consequently, the primary aim of the current investigation was the development as well as the physicochemical and pharmaco-toxicological characterization of betulin- and lupeol-based oleogels (Bet OG and Lup OG) for topical application in skin injuries. The results revealed suitable pH as well as organoleptic, rheological, and textural properties. The penetration and permeation of Bet and Lup oleogels through porcine ear skin as well as the retention of both oleogels in the skin were demonstrated through ex vivo studies. In vitro, Bet OG and Lup OG showed good biocompatibility on HaCaT human immortalized cells. Moreover, Bet OG exerted a potent wound-healing property by stimulating the migration of the HaCaT cells. The in ovo results demonstrated the non-irritative potential of the developed formulations. Additionally, the undertaken in vivo investigation indicated a positive effect of oleogels treatment on skin parameters by increasing skin hydration and decreasing erythema. In conclusion, oleogel formulations are ideal for the local delivery of betulin and lupeol in skin disorders.
Study on the Joint Toxicity of BPZ, BPS, BPC and BPF to Zebrafish
Authors: Han Ying , Fei Yumeng , Wang Mingxin , Xue Yingang , Chen Hui , Liu Yuxuan
Published: July 2021

Bisphenol Z (BPZ), bisphenol S (BPS), bisphenol C (BPC), and bisphenol F (BPF) had been widely used as alternatives to bisphenol A (BPA), but the toxicity data of these bisphenol analogues were very limited. In this study, the joint toxicity of BPZ, BPS, BPC, and BPF to zebrafish (Danio rerio) was investigated. The median half lethal concentrations (LC50) of BPZ, BPS, BPC, and BPF to zebrafish for 96 h were 6.9 × 105 µM, 3.9 × 107 µM, 7.1 × 105 µM, and1.6 × 106 µM, respectively. The joint toxicity effect of BPF–BPC (7.7 × 105–3.4 × 105µM) and BPZ–BPC (3.4 × 105–3.5 × 105µM) with the same toxic ratio showed a synergistic effect, which may be attributed to enzyme inhibition or induction theory. While the toxicity effect of the other two bisphenol analogue combined groups and multi-joint pairs showed an antagonistic effect due to the competition site, other causes need to be further explored. Meanwhile, the expression levels of the estrogen receptor genes (ERα, ERβ1) and antioxidant enzyme genes (SOD, CAT, GPX) were analyzed using a quantitative real-time polymerase chain reaction in zebrafish exposure to LC50 of BPZ, BPS, BPC, and BPF collected at 24, 48, 72, and 96 h. Relative expression of CAT, GPX, and ERβ1 mRNA declined significantly compared to the blank control, which might be a major cause of oxidant injury of antioxidant systems and the disruption of the endocrine systems in zebrafish.
Rational Design and Application of Covalent Organic Frameworks for Solar Fuel Production
Authors: Verma Priyanka , Le Brocq Joshua J.M. , Raja Robert
Published: July 2021

Harnessing solar energy and converting it into renewable fuels by chemical processes, such as water splitting and carbon dioxide (CO2) reduction, is a highly promising yet challenging strategy to mitigate the effects arising from the global energy crisis and serious environmental concerns. In recent years, covalent organic framework (COF)-based materials have gained substantial research interest because of their diversified architecture, tunable composition, large surface area, and high thermal and chemical stability. Their tunable band structure and significant light absorption with higher charge separation efficiency of photoinduced carriers make them suitable candidates for photocatalytic applications in hydrogen (H2) generation, CO2 conversion, and various organic transformation reactions. In this article, we describe the recent progress in the topology design and synthesis method of COF-based nanomaterials by elucidating the structure-property correlations for photocatalytic hydrogen generation and CO2 reduction applications. The effect of using various kinds of 2D and 3D COFs and strategies to control the morphology and enhance the photocatalytic activity is also summarized. Finally, the key challenges and perspectives in the field are highlighted for the future development of highly efficient COF-based photocatalysts.
Nanostructured Hybrid Metal Mesh as Transparent Conducting Electrodes: Selection Criteria Verification in Perovskite Solar Cells
Authors: Mohanraj John , Singh Chetan R. , Gujar Tanaji P. , Heinrich C. David , Thelakkat Mukundan
Published: July 2021

Nanostructured metal mesh structures demonstrating excellent conductivity and high transparency are one of the promising transparent conducting electrode (TCE) alternatives for indium tin oxide (ITO). Often, these metal nanostructures are to be employed as hybrids along with a conducting filler layer to collect charge carriers from the network voids and to minimize current and voltage losses. The influence of filler layers on dictating the extent of such ohmic loss is complex. Here, we used a general numerical model to correlate the sheet resistance of the filler, lateral charge transport distance in network voids, metal mesh line width and ohmic losses in optoelectronic devices. To verify this correlation, we prepared gold or copper network electrodes with different line widths and different filler layers, and applied them as TCEs in perovskite solar cells. We show that the photovoltaic parameters scale with the hybrid metal network TCE properties and an Au-network or Cu-network with aluminum-doped zinc oxide (AZO) filler can replace ITO very well, validating our theoretical predictions. Thus, the proposed model could be employed to select an appropriate filler layer for a specific metal mesh electrode geometry and dimensions to overcome the possible ohmic losses in optoelectronic devices.
Assessing the Toxicological Relevance of Nanomaterial Agglomerates and Aggregates Using Realistic Exposure In Vitro
Authors: Murugadoss Sivakumar , Godderis Lode , Ghosh Manosij , Hoet Peter H.
Published: July 2021

Low dose repeated exposures are considered more relevant/realistic in assessing the health risks of nanomaterials (NM), as human exposure such as in workplace occurs in low doses and in a repeated manner. Thus, in a three-week study, we assessed the biological effects (cell viability, cell proliferation, oxidative stress, pro-inflammatory response, and DNA damage) of titanium-di-oxide nanoparticle (TiO2 NP) agglomerates and synthetic amorphous silica (SAS) aggregates of different sizes in human bronchial epithelial (HBE), colon epithelial (Caco2), and human monocytic (THP-1) cell lines repeatedly exposed to a non-cytotoxic dose (0.76 µg/cm2). We noticed that neither of the two TiO2 NPs nor their agglomeration states induced any effects (compared to control) in any of the cell lines tested while SAS aggregates induced some significant effects only in HBE cell cultures. In a second set of experiments, HBE cell cultures were exposed repeatedly to different SAS suspensions for two weeks (first and second exposure cycle) and allowed to recover (without SAS exposure, recovery period) for a week. We observed that SAS aggregates of larger sizes (size ~2.5 µm) significantly affected the cell proliferation, IL-6, IL-8, and total glutathione at the end of both exposure cycle while their nanosized counterparts (size less than 100 nm) induced more pronounced effects only at the end of the first exposure cycle. As noticed in our previous short-term (24 h) exposure study, large aggregates of SAS did appear to be similarly potent as nano sized aggregates. This study also suggests that aggregates of SAS of size greater than 100 nm are toxicologically relevant and should be considered in risk assessment.
The Potential of Calorie Restriction and Calorie Restriction Mimetics in Delaying Aging: Focus on Experimental Models
Authors: Giacomello Emiliana , Toniolo Luana
Published: July 2021

Aging is a biological process determined by multiple cellular mechanisms, such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication, that ultimately concur in the functional decline of the individual. The evidence that the old population is steadily increasing and will triplicate in the next 50 years, together with the fact the elderlies are more prone to develop pathologies such as cancer, diabetes, and degenerative disorders, stimulates an important effort in finding specific countermeasures. Calorie restriction (CR) has been demonstrated to modulate nutrient sensing mechanisms, inducing a better metabolic profile, enhanced stress resistance, reduced oxidative stress, and improved inflammatory response. Therefore, CR and CR-mimetics have been suggested as powerful means to slow aging and extend healthy life-span in experimental models and humans. Taking into consideration the difficulties and ethical issues in performing aging research and testing anti-aging interventions in humans, researchers initially need to work with experimental models. The present review reports the major experimental models utilized in the study of CR and CR-mimetics, highlighting their application in the laboratory routine, and their translation to human research.
A Method to Estimate the Efficacy vs. Effectiveness in Meta-Analysis of Clinical Trials with Different Adherence Scenarios: A Monte Carlo Simulation Study in Nutrition
Authors: López-Espinoza Miguel Ángel , Lozano-Lozano José Antonio , Prieto-Merino David
Published: July 2021

Randomized clinical trials (RCTs) evaluating the effectiveness of interventions to promote fruit and vegetable (FV) consumption usually report intention-to-treat (ITT) analysis as the main outcome. These analyses compare the randomly assigned groups and accept that some individuals may not follow the recommendations received in their group. The ITT analysis is useful to quantify the global effect of promoting the consumption of FV in a population (effectiveness) but, if non-adherence is significant in the RCT, they cannot estimate the specific effect in the individuals that increased their FV consumption (efficacy). To calculate the efficacy of FV consumption, a per protocol analysis (PP) would have to be carried out, in which groups of individuals are compared according to their actual adherence to FV consumption, regardless of the group to which they were assigned; unfortunately, many RCTs do not report the PP analysis. The objective of this article is to apply a new method to estimate the efficacy of Meta-analysis (MA) PP which include RCTs of effectiveness by ITT, without estimates of adherence. The method is based on generating Monte Carlo simulations of percentages of adherence in each allocation group from prior distributions informed by expert knowledge. We illustrate the method reanalyzing a Cochrane Systematic Review (SR) of RCTs on increased FV consumption reported with ITT, simulating 1000 times the estimation of a PP meta-analyses, and obtaining means and ranges of the potential PP effects. In some cases, the range of estimated PP effects was clearly more favourable than the effect calculated with the original ITT assumption, and therefore this corrected analysis must be considered when estimating the true effect of the consumption of a certain food.
Living with Food Hypersensitivity as an Adolescent Impairs Health Related Quality of Life Irrespective of Disease Severity: Results from a Population-Based Birth Cohort
Authors: Jonsson Marina , Ekström Sandra , Protudjer Jennifer L. P. , Bergström Anna , Kull Inger
Published: July 2021

Food hypersensitivity (FHS) refers to food-related symptoms, with or without concurrent Immunoglobulin E (IgE) antibodies related to food(s). It remains unclear how different FHS phenotypes affect health-related quality of life (HRQoL). We examined self-reported HRQoL (with the generic instrument EQ-5D (dimensions and a Visual Analogue Scale (VAS), range 0–100) in association with phenotypes of FHS, and food-specific symptoms among adolescents (n = 2990) from a population-based birth cohort. Overall, 22% of the adolescents had FHS. Compared to adolescents without FHS, those with FHS reported more problems in the dimensions of pain/discomfort (p < 0.001), and anxiety/depression (p = 0.007). Females with FHS reported more problems than males in these dimensions (p < 0.001). Different FHS phenotypes (IgE-sensitization, allergic co-morbidity, and severity of symptoms) were not associated with differences in HRQoL. EQ-VAS scores were lowest for adolescents with symptoms for wheat vs. no wheat, median 80 vs. 89, p = 0.04) and milk vs. no milk (median 85 vs. 90, p = 0.03). Physician-diagnosed lactose intolerance median EQ-VAS was 80 vs. 90, p = 0.03 and also associated with more problems in the dimension of anxious/depression. In conclusion, FHS is associated with lower HRQoL in adolescence, irrespective of phenotypes, but differentially affects females vs. males, and those with vs. without symptoms for milk or wheat.
Insights into an Immunotherapeutic Approach to Combat Multidrug Resistance in Hepatocellular Carcinoma
Authors: Devan Aswathy R. , Kumar Ayana R. , Nair Bhagyalakshmi , Anto Nikhil Ponnoor , Muraleedharan Amitha , Mathew Bijo , Kim Hoon , Nath Lekshmi R.
Published: July 2021

Hepatocellular carcinoma (HCC) has emerged as one of the most lethal cancers worldwide because of its high refractoriness and multi-drug resistance to existing chemotherapies, which leads to poor patient survival. Novel pharmacological strategies to tackle HCC are based on oral multi-kinase inhibitors like sorafenib; however, the clinical use of the drug is restricted due to the limited survival rate and significant side effects, suggesting the existence of a primary or/and acquired drug-resistance mechanism. Because of this hurdle, HCC patients are forced through incomplete therapy. Although multiple approaches have been employed in parallel to overcome multidrug resistance (MDR), the results are varying with insignificant outcomes. In the past decade, cancer immunotherapy has emerged as a breakthrough approach and has played a critical role in HCC treatment. The liver is the main immune organ of the lymphatic system. Researchers utilize immunotherapy because immune evasion is considered a major reason for rapid HCC progression. Moreover, the immune response can be augmented and sustained, thus preventing cancer relapse over the post-treatment period. In this review, we provide detailed insights into the immunotherapeutic approaches to combat MDR by focusing on HCC, together with challenges in clinical translation.
Experimental Design Based Optimization and Ex Vivo Permeation of Desmopressin Acetate Loaded Elastic Liposomes Using Rat Skin
Authors: Altamimi Mohammad A. , Hussain Afzal , Alshehri Sultan , Imam Syed Sarim
Published: July 2021

The study aimed to develop elastic-liposome-based transdermal delivery of desmopressin acetate for enhanced permeation to control enuresis, central diabetes insipidus, and traumatic injury. Elastic liposomes (ELs)-loaded desmopressin acetate was prepared, optimized, and evaluated for improved transdermal permeation profiles using rat skin. Full factorial design with independent factors (X1 for lipid and X2 for surfactant) at three levels was used against four responses (Y1, Y2, Y3, and Y4) (dependent variables). Formulations were characterized for vesicle size, polydispersity index (PDI), zeta potential, % entrapment efficiency (% EE), in vitro drug release, in vitro hemolysis potential, ex vivo drug permeation and drug deposition (DD), and ex vivo vesicle–skin interaction using scanning electron microscopy studies. The optimized formulation ODEL1 based on desirability function was found to have vesicle size, % EE, % DR, and permeation flux values of 118.7 nm, 78.9%, 75.1%, and 5.3 µg/h·cm2, respectively, which were close to predicted values. In vitro release profiles indicated slow and sustained delivery. Permeation flux values of ODEL1 and ODEL2 were 5.3 and 3.1 µg/h·cm2, respectively, which are 7.5- and 4.4-fold higher as compared to DS (0.71 µg/h·cm2). The obtained flux was relatively higher than the clinical target value of the drug for therapeutic efficacy. Moreover, the DD value of ODEL1 was significantly higher than ODEL2 and DS. Hemocompatibility study confirmed safety concerns. Finally, vesicle–skin interaction corroborated mechanistic views of permeation through rat skin. Conclusively, the transdermal delivery may be a suitable alternative to oral and nasal delivery to treat nocturnal enuresis, central diabetes insipidus, hemophilia A and von Willebrand’s disease, and any traumatic injuries.
To Be or to Have Been Lucky, That Is the Question
Authors: Lesage Antony , Victor Jean-Marc
Published: July 2021

Is it possible to measure the dispersion of ex ante chances (i.e., chances “before the event”) among people, be it gambling, health, or social opportunities? We explore this question and provide some tools, including a statistical test, to evidence the actual dispersion of ex ante chances in various areas, with a focus on chronic diseases. Using the principle of maximum entropy, we derive the distribution of the risk of becoming ill in the global population as well as in the population of affected people. We find that affected people are either at very low risk, like the overwhelming majority of the population, but still were unlucky to become ill, or are at extremely high risk and were bound to become ill.
An Improved Large-Field Microscopic Speckle Interferometry System for Dynamic Displacement Measurement of MEMS
Authors: Gao Chenjia , Gao Zhan , Niu Yuhao , Wang Xu , Zhao Jieming , Deng Lin
Published: July 2021

The traditional microscopic speckle interferometer has limited applications in engineering due to its small field of view. In this paper, we propose a large-field microscopic speckle interferometer which embeds two doublet lens groups in the improved Mach–Zehnder optical path structure to expand its field of view. At the same time, the new system can reduce the coherent noise of reflected light in the optical path. We use this new system to measure the dynamic displacement process of the entire surface of the microchips. The experimental results show that our improved measurement system can achieve large-field, real-time and high-precision dynamic measurement of micro-electromechanical systems (MEMS).
Enhanced Performance of Nanotextured Silicon Solar Cells with Excellent Light-Trapping Properties
Authors: Dou Bingfei , Jia Rui , Xing Zhao , Yao Xiaojiang , Xiao Dongping , Jin Zhi , Liu Xinyu
Published: July 2021

Light-trapping nanostructures have been widely used for improving solar cells’ performance, but the higher surface recombination and poor electrode contact introduced need to be addressed. In this work, silicon nanostructures were synthesized via silver-catalyzed etching to texturize solar cells. Atomic-layer-deposited Al2O3 passivated the nanotextured cells. A surface recombination velocity of 126 cm/s was obtained, much lower than the 228 cm/s of the SiNX-passivated one. Additionally, the open-circuit voltage (VOC) of the nanotextured cells improved significantly from 582 to 610 mV, as did the short-circuit current (JSC) from 25.5 to 31 mA/cm2. Furthermore, the electrode contact property was enhanced by light-induced plating. A best efficiency of 13.3% for nano-textured cells was obtained, which is higher than the planar cell’s 12%.
Automated In Situ Seed Variety Identification via Deep Learning: A Case Study in Chickpea
Authors: Taheri-Garavand Amin , Nasiri Amin , Fanourakis Dimitrios , Fatahi Soodabeh , Omid Mahmoud , Nikoloudakis Nikolaos
Published: July 2021

On-time seed variety recognition is critical to limit qualitative and quantitative yield loss and asynchronous crop production. The conventional method is a subjective and error-prone process, since it relies on human experts and usually requires accredited seed material. This paper presents a convolutional neural network (CNN) framework for automatic identification of chickpea varieties by using seed images in the visible spectrum (400–700 nm). Two low-cost devices were employed for image acquisition. Lighting and imaging (background, focus, angle, and camera-to-sample distance) conditions were variable. The VGG16 architecture was modified by a global average pooling layer, dense layers, a batch normalization layer, and a dropout layer. Distinguishing the intricate visual features of the diverse chickpea varieties and recognizing them according to these features was conceivable by the obtained model. A five-fold cross-validation was performed to evaluate the uncertainty and predictive efficiency of the CNN model. The modified deep learning model was able to recognize different chickpea seed varieties with an average classification accuracy of over 94%. In addition, the proposed vision-based model was very robust in seed variety identification, and independent of image acquisition device, light environment, and imaging settings. This opens the avenue for the extension into novel applications using mobile phones to acquire and process information in situ. The proposed procedure derives possibilities for deployment in the seed industry and mobile applications for fast and robust automated seed identification practices.
Effect of Composite Core Materials on Fracture Resistance of Endodontically Treated Teeth: A Systematic Review and Meta-Analysis of In Vitro Studies
Authors: Zarow Maciej , Dominiak Marzena , Szczeklik Katarzyna , Hardan Louis , Bourgi Rim , Cuevas-Suárez Carlos Enrique , Zamarripa-Calderón Juan Eliezer , Kharouf Naji , Filtchev Dimitar
Published: July 2021

Various material properties are involved in the success of endodontically treated restorations. At present, restorative composites are commonly employed as core build-up materials. This study aimed to systematically review the literature to assess the effect of using composite core materials on the in vitro fracture of endodontically treated teeth. Two different reviewers screened the literature, up to June 2021, in five distinct electronic databases: PubMed (MedLine), Scopus, Scielo, ISI Web of Science, and EMBASE. Only in vitro studies reporting the effect of the use of composite core materials on the fracture resistance of endodontically treated teeth were included. A meta-analysis was carried out using a software program (Review Manager v5.4.1; The Cochrane Collaboration, Copenhagen, Denmark). The risk of bias in each study was assessed following the parameters of another systematic review. A total of 5016 relevant papers were retrieved from all databases. After assessing the title and abstract, five publications remained for qualitative analysis. From these, only three studies remained for meta-analysis. The fracture strength of endodontically treated teeth where a core build-up composite was used was statistically significantly higher than the control (p = 0.04). Most of the analyses showed a high heterogenicity. The in vitro evidence suggests that the composite core build-up with higher filler content tended to improve the fracture resistance of the endodontically treated teeth, in comparison with conventional composite resins. This research received no external funding. Considering that this systematic review was only carried out on in vitro papers, registration was not performed. Furthermore, there were no identified clinical studies assessing core build-up materials; therefore, more well-designed research on these materials is needed.