bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal burn‐in policy based on a set of cutoff points using mixture inverse Gaussian degradation process and copulas
Authors: Morita Lia H. M. , Tomazella Vera L. , Ferreira Paulo H. , Ramos Pedro L. , Balakrishnan Narayanaswamy , Louzada Francisco
Published: January 2021

Burn‐in tests have been discussed extensively in the reliability literature, wherein we operate items until high degradation values are observed, which could separate the weak units from the normal ones before they get to the market. This concept is often referred to as a screening procedure, and it involves misclassification errors. Commonly, the underlying degradation process is assumed to be a Wiener or a gamma process, based on which several optimal burn‐in policies have been developed in the literature. In this article, we consider the mixture inverse Gaussian process, which possesses monotone degradation paths and some interesting properties. Under this process, we present a decision rule for classifying a unit under test as normal or weak based on burn‐in time and a set of cutoff points. Then, an economic cost model is used to find the optimal burn‐in time and the optimal cutoff points, when the estimation of model parameters is based on an analytical method or an approximate method involving copula theory. Finally, an example of a real dataset on light amplification by stimulated emission of radiations, well known in the reliability literature, is used to illustrate the model and the inferential approach proposed here.
The Relationship Between Developmental Coordination Disorder and Concurrent Deficits in Social Communication and Repetitive Behaviors Among Children with Autism Spectrum Disorder
Authors: Ketcheson Leah R. , Pitchford E. Andrew , Wentz Chandler F.
Published: January 2021

Children with Autism Spectrum Disorder (ASD), characterized by core deficits in social communication and restrictive behaviors, can exhibit concurrent motor incoordination and/or intellectual disability (ID). While pervasive delays in motor behavior are common, formal diagnosis of Development Coordination Disorder (DCD) is uncommon. It is not clear how DCD and ID impact core deficits in ASD. This study utilized the Simons Foundation SPARK cohort to describe the scope of motor incoordination among children with ASD and examine the interrelationships between DCD risk, ID, and ASD core deficits. 10,234 children with ASD, between the ages of 5 and 15 years, were included in the analysis. Parents completed online versions of the DCD Questionnaire (DCD‐Q), Social Communication Questionnaire (SCQ) and Restrictive Behavior Scale (RBS‐R). 85% of children with ASD had DCD‐Q scores consistent with being at‐risk for DCD, but only 14% reported a formal diagnosis. Children with ID exhibited significantly greater motor incoordination compared to children without ID (P < 0.001). Significantly, greater core deficits were identified in both children at‐risk for DCD (P < 0.001) and with ID (P < 0.001). However, the effects of DCD risk were independent of ID and exhibited a medium effect size for SCQ (η2p = 0.063) and a small effect size for RBS‐R (η2p = 0.04) scores. Collectively, study outcomes reinforce the pervasiveness of motor incoordination among children with ASD, both with and without concurrent ID, and provide further justification for the inclusion of motor behavior in the early intervention and prescription for children with ASD.

Lay Summary

This secondary data analysis of the Simons Foundation SPARK cohort found high rates (85%) of DCD risk among children with ASD. Deficits in motor coordination were greater among children with ASD with concurrent ID diagnoses. Meaningful differences in ASD core deficits (social communication and repetitive behaviors) were independently found in children at risk for DCD, both with and without ID. Autism Res 2021, 14: 804–816. © 2021 International Society for Autism Research and Wiley Periodicals LLC
Parent‐reported Autism Diagnostic Stability and Trajectories in the Longitudinal Study of Australian Children
Authors: May Tamara , Brignell Amanda , Williams Katrina
Published: January 2021

This study aimed to explore the stability of parent‐reported diagnosis of Autism Spectrum Disorder (ASD) and factors influencing the trajectories in two cohorts from the prospective Longitudinal Study of Australian Children (LSAC). Parent‐reported ASD diagnosis was collected for children from 6 years of age in a Birth cohort and 10 years of age in a Kinder cohort; allowing for exploration of diagnostic stability at age 6, 8, 10, and 12 years (Birth cohort) and 10, 12, 14, 16 years (Kinder cohort). Children were grouped based on persisting, desisting, inconsistent and late (diagnosis after 6 years—Birth cohort; after 10 years—Kinder) subgroups over four timepoints. Multinomial logistic regression explored predictors of diagnostic trajectories; generalized estimating equations examined trajectories of emotional and behavioral problems. Of 66 Birth cohort children parent‐reported to have ASD at age 6, with data at all four time points, 14% did not at 12 years; of 73 Kinder cohort children at age 10 years, 26% no longer had parent‐reported ASD at 16 years. Children with late diagnoses showed increasing trajectories of emotional and behavioral problems, while children with persisting or desisting diagnoses showed decreasing trajectories. Between 86% and 74% had a reported ASD diagnosis after 6 years. Findings indicate that children with ASD need services and supports that can adapt to their changing needs, which may be increasing, decreasing or different. This has implications for the provision of services and funding.

Lay Summary

This study explored how consistent parent‐reported ASD diagnosis is over time in two groups of children from the Longitudinal Study of Australian Children (LSAC). Although up to 26% of children no longer had parent‐reported ASD after 6‐years follow up, persisting or late trajectories were more common. The outcome of late onset trajectories requires ongoing review. Autism Res 2021, 14: 773–786. © 2021 International Society for Autism Research and Wiley Periodicals LLC
Trends in lipase engineering for enhanced biocatalysis
Authors: Soni Surabhi
Published: January 2021

Lipases, also known as triacylglycerol hydrolases (E.C.No. 3.1.1.3), are considered as leading biocatalysts in the lipid modification business. With properties like ease of availability, capability to work in heterogeneous media, stability in organic solvents, property of catalyzing at the lipid–water interface and even in nonaqueous conditions, have made them a versatile choice for applications in the food, flavor, detergent, pharmaceutical, leather, textile, cosmetic, and paper industries [1]. The increasing alertness toward sustainable technologies, lesser waste generation and solvent usage and minimization of energy input has brought light toward the production and usage of recombinant/improved lipases. For example, Novozym 435, a broadly used recombinant lipase isolated from Candida antarctica, dominates the lipase industry and has even created a supplier bias in the market. This shows that there is a desperate need for novel, low‐cost lipases with better properties. For this, mining of existing extremophilic genomes seems more rewarding. But considering the diversity of industrial requirements such as types of solvents used or carrier systems employed for enzyme immobilization, tailor‐designed enzymes are an unrealized pressing priority. Therefore, protein engineering strategies in collaboration with the discovery of new lipases can serve as a vital tool to obtain tailor‐made enzymes with specific characteristics.
The effect of brimonidine and proparacaine on metabolic enzymes: Glucose‐6‐phosphate dehydrogenase, 6‐phosphogluconate dehydrogenase, and glutathione reductase
Authors: Çalışkan Büşra , Öztürk Kesebir Arzu , Demir Yeliz , Akyol Salman İlknur
Published: January 2021

Oxidative stress is to upregulate the pentose phosphate pathway (PPP). The PPP consists of two functional branches, glucose‐6‐phosphate dehydrogenase (G6PD) and 6‐phosphogluconaste dehydrogenase (6PGD). Glutathione reductase (GR) has a significant role in catalyzing an oxidized glutathione form into a reduced form. The purpose of this study is to investigate the effects of brimonidine and proparacaine on the activity of 6PGD, G6PD, and GR enzymes purified from human erythrocytes. Brimonidine displayed considerable inhibition profile against G6PD with IC50 value and KI constant of 29.93 ± 3.56 and 48.46 ± 0.66 μM, respectively. On the other hand, proparacaine had no inhibitory effect against G6PD. KI values were found to be 66.06 ± 0.78 and 811.50 ± 11.13 μM for brimonidine and proparacaine, respectively, for 6PGD. KI values were found to be 144.10 ± 2.01 and 1,654.00 ± 26.29 μM for brimonidine and proparacaine, respectively, for GR. Herein, also in silico molecular docking studies were performed between drugs and enzymes.
TRR 277: Additive Fertigung im Bauwesen
Authors: Kloft Harald , Gehlen Christoph , Dörfler Kathrin , Hack Norman , Henke Klaudius , Lowke Dirk , Mainka Jeldrik , Raatz Annika
Published: January 2021

Die Bauwirtschaft stellt eine der bislang am wenigsten digitalisierten Branche dar. Im Unterschied zu anderen Produktionsbereichen ist die Herstellung von Gebäuden durch individualisierte Bauprozesse gekennzeichnet. Digitale Fertigungstechniken anderer Wirtschaftszweige haben sich im Bauwesen nicht durchgesetzt, da sie nicht die notwendige Individualisierung ermöglichen oder unwirtschaftlich sind. Die Vorteile additiver Fertigungstechnologien bestehen darin, dass Automatisierung und Individualisierung nicht im Widerspruch zueinanderstehen und dass beim 3‐D‐Drucken nur dort Material aufgebaut wird, wo es strukturell oder funktionell erforderlich ist. Die additive Fertigung ist insofern wirtschaftlich und ressourceneffizient zugleich. Der DFG‐Sonderforschungsbereich/Transregio TRR 277 der beiden Universitäten TU Braunschweig und TU München will die Technologie der additiven Fertigung grundlegend für das Bauwesen erforschen und zur Digitalisierung der Bauwirtschaft beitragen. Der vorliegende Beitrag gibt einen Überblick zu den Zielen, der Struktur und den Methodiken des TRR 277 sowie zu den drei Projektbereichen mit seinen insgesamt 18 wissenschaftlichen Teilprojekten.
Effects of 2600 MHz Radiofrequency Radiation in Brain Tissue of Male Wistar Rats and Neuroprotective Effects of Melatonin
Authors: Delen Kevser , Sırav Bahriye , Oruç Sinem , Seymen Cemile M. , Kuzay Dilek , Yeğin Korkut , Take Kaplanoğlu Gülnur
Published: January 2021

The debate on the biological effects of radiofrequency radiation (RFR) still continues due to differences in the design of studies (frequency, power density, specific absorption rate [SAR], exposure duration, cell, tissue, or animal type). The current study aimed to investigate the effects of 2,600 MHz RFR and melatonin on brain tissue biochemistry and histology of male rats. Thirty‐six rats were divided into six groups randomly: cage‐control, sham, RFR, melatonin, sham melatonin, and RFR melatonin. In RFR groups, animals were exposed to 2,600 MHz RFR for 30 days (30 min/day, 5 days/week) and the melatonin group animals were subcutaneously injected with melatonin (7 days/week, 10 mg/kg/day) for 30 days. SAR in brain gray matter was calculated as 0.44 and 0.295 W/kg for 1 and 10 g averaging, respectively. RFR exposure decreased the GSH, GSH‐Px, and SOD levels and increased the MPO, MDA, and NOx levels (P < 0.005) significantly. RFR exposure also led to an increase in structural deformation and apoptosis in the brain tissue. This study revealed that exogenous high‐dose melatonin could reduce these adverse effects of RFR. Limiting RFR exposure as much as possible is recommended, and taking daily melatonin supplements may be beneficial. Bioelectromagnetics. © 2021 Bioelectromagnetics Society
Dehnungsmessung bei mehraxialen Druckversuchen an Beton mittels faseroptischer Sensoren
Authors: Speck Kerstin , Vogdt Fritz , Curbach Manfred , Petryna Yuri , Marx Steffen
Published: January 2021

Für die Quantifizierung lastinduzierter anisotroper Schädigungen unter verschiedenen mehraxialen Spannungszuständen ist die Dehnungsmessung im Inneren kleinformatiger Probekörper erforderlich. Quasikontinuierlich messende faseroptische Sensoren ohne werksseitige Schutzummantelung können dafür neue Möglichkeiten eröffnen. Dieser Beitrag erläutert die Herausforderungen bei der Dehnungsmessung bei mehraxialen Versuchen und das Potenzial der quasikontinuierlichen Dehnungsmessung mit faseroptischen Sensoren. Es wird die Positionierung der Messfasern mittels eines Messingprofils in den unbewehrten Probekörpern erläutert und die Beeinflussung der Betoneigenschaften durch dieses Trägergestell. Die möglichen Messgenauigkeiten und messtechnischen Besonderheiten speziell hinsichtlich der querdruckempfindlichen und nicht alkaliresistenten Messfasern werden aufgezeigt. Ein Vergleich mit der häufig angewandten Dehnungsmessung über die Bürstenverformung zeigt, dass trotz aller bestehenden Herausforderungen die faseroptischen Sensoren eine Dehnungsmessung bei dreiaxialen Versuchen in bisher nicht erreichbarer Genauigkeit ermöglichen.
Preparation of graphene quantum dots with glycine as nitrogen source and its interaction with human serum albumin
Authors: Ke Yi , Liu Yong‐Chang , Ren Wen‐Wen , Bai Ai‐Min , Li Xiao‐Yun , Hu Yan‐Jun
Published: January 2021

Graphene quantum dots (GQDs) could be regarded as graphene with a lateral dimension less than 100 nm. Compared with graphene, GQDs not only possess the excellent properties of graphene but also have been proven to have low toxicity, high fluorescence stability, strong water solubility, as well as better biocompatibility. In this work, an amide bond‐based, N‐doped graphene quantum dot was synthesized using a simple hydrothermal method. When the reaction time was 4 h and the temperature was 180°C, fluorescence excitation and emission peaks of the product were 340 nm and 450 nm, respectively. Its interaction with human serum albumin (HSA) was investigated using spectroscopy, gel electrophoresis, and molecular simulation. Gel electrophoresis showed that the product did not cause complete scission of the peptide chain in HSA, indicating good biocompatibility. The results of molecular docking showed that the product tended to bind to site III of HSA. This paper provides a meaningful reference for design and development in nanomedicine.
Size Control of LaNbON2 Particles for Enhanced Photocatalytic Water Oxidation Under Visible Light Irradiation
Authors: Seo Jeongsuk
Published: January 2021

Perovskite‐type LaNbON2 has the longest wavelength onset of visible light absorption—up to approximately 740 nm—among (oxy)nitrides based on transition metals Ti, Ta, and Nb. Water oxidation using visible‐light‐responsive LaNbON2 is challenging because the synthesis of the oxynitride has rarely been studied. Herein, we report the synthesis of small LaNbON2 particles and their size effect on photocatalytic water oxidation under visible light illumination. The small scheelite‐type LaNbO4, prepared by a polymerized complex method, was transformed into less‐defective LaNbON2 during nitridation as compared with that nitrided from LaNbO4 via a solid‐state reaction method. The small LaNbON2 particles, capable of absorbing intense visible light 700 nm above, improved the O2 evolution during 5 h of water oxidation under 300 W Xe light irradiation (λ > 420 nm). This enhancement was attributed to the size reduction of LaNbON2 particles, leading to increased surface area and encouragement of mild nitridation.
Green bonds, sustainable development and environmental policy in the European Union carbon market
Authors: Leitao Joao , Ferreira Joaquim , Santibanez‐Gonzalez Ernesto
Published: January 2021

This study assesses the non‐linear effects of green bonds, conventional bonds and energy commodities on the behaviour of the cap‐and‐trade European Union carbon market (European Union Emissions Trading System [EU‐ETS]). By estimating four models, using Markov‐switching (MS) econometric methodology, non‐linearities are confirmed in dynamic behaviours, observing in the global calculation a positive effect of green bonds (S&P GreenandSol Green) on the carbon market, in regimes of both high and low volatility, whereas conventional bonds (S&P Agg) and energy commodities (DJCI En) contribute to a decrease in the carbon market in regimes of high volatility. The relevance of green bonds is underlined in determining the behaviour of the carbon market, besides observing greater persistence of the low volatility regime. These results allow both investors and fund managers to implement strategies in different volatility or economic activity contexts through a diversified portfolio and green/climate structure.
Spinal arachnoid sleeves and their possible causative role in cauda equina syndrome and transient radicular irritation syndrome
Authors: Riquelme Irene , Reina Miguel A. , Boezaart André P. , Tubbs R. Shane , Carrera Anna , Reina Francisco
Published: January 2021

Introduction

We have previously described arachnoid sleeves around cauda equina nerve roots, but at that time we did not determine whether injections could be performed within those sleeves. The purpose of this observational study was to establish whether the entire distal orifice of a spinal needle can be accommodated within an arachnoid sleeve.

Materials and methods

We carefully dissected the entire dural sacs off four fresh cadavers, opened them by longitudinal incision, and immersed them in saline. Under direct vision, we penetrated the cauda equina roots nerves traveling almost vertically downward at 30 locations each with a 27‐ and a 25‐G pencil‐point needle (60 punctures total). We captured the images with a stereoscopic camera.

Results

The nerve root offered no noticeable resistance to needle entry. Although the arachnoid sleeves could not be identified with the naked eye, they were translucent but visible under microscopy. In 21 of 30 attempts with a 27‐gauge needle, and in 20 of 30 attempts with a 25‐gauge needle, the distal orifice of the spinal needle was completely within the arachnoid sleeve.

Conclusion

It seems possible to accommodate the distal orifice of a 25‐ or a 27‐gauge pencil‐point spinal needle completely within the space of the arachnoid sleeve. An injection within this sleeve could potentially lead to a neurological syndrome, as we have previously proposed.
Universal fixed‐point digital controller for control theory studies
Authors: Sanchez Alberto , de Castro Angel , Benedicto Jorge , Martínez‐García María Sofía
Published: January 2021

The laboratories of control theory are often limited to simulations and a few or none experimental tests. As in other technical subjects, practical experiments really help to understand the theory but need much time and the experimental platforms are usually expensive. This paper describes a platform that implements a universal third‐order discrete controller based on field programmable gate array (FPGA). The controller is implemented using fixed‐point arithmetic, with 17‐bit coefficients, but students can reduce the number of bits to find the resolution problems that may arise. This low‐cost platform, based on a Xilinx Spartan FPGA, allows students to try controllers just by configuring the coefficients of the controller through a computer application and a USB port. It drastically reduces the implementation time, allowing more time for design and testing. Therefore, students can try many controllers in the same laboratory session so that they can check experimentally their behavior in real prototypes and see the differences between simulations and physical systems. This platform has been applied in a real course over two academic years. The student opinion survey shows that the survey respondents consider the platform useful for more deeply understanding the subject, with an average score of 4.47/5.00 on a Likert scale (with a margin of error of 15.56% with a 95% confidence level). Besides this, the platform records the usage statistics showing that there is a relationship between the application usage and the marks in both the theory and laboratory parts.
Surge arrester operation investigation in low‐ and high‐current regions using MATLAB GUI: Implementing an educational goal for undergraduate students
Authors: Seyyedbarzegar Seyyedmeysam , Khodsuz Masume
Published: January 2021

Metal oxide surge arresters (MOSAs) have been widely used as protective devices against switching and lightning overvoltages in power electrical systems. MOSAs have dynamic characteristics in low‐ and high‐current regions. The unique model of MOSA, which is able to evaluate all the possible operating conditions of power systems, would surely be so complicated. Therefore, by the selection of an operating condition, the appropriate model of MOSA has been created. Many parameters affect MOSA performance in low‐ and high‐current regions. As a result, MOSA's performance under different operating conditions has been investigated by using a MATLAB GUI environment. To make a software environment to simulate MOSA performance in a high voltage laboratory, temperature variations influence on leakage current and its harmonic components under power frequency applied voltages and also the efficacy of impulse parameters variations on MOSA's residual voltage have been investigated. The designed graphical environment has been used by 40 electrical engineering students. The results showed that the use of the graphical environment had a great impact on the concepts' understanding of MOSA's performance.
Melatonin alleviates d‐galactose‐decreased hyaluronic acid production in synovial membrane cells via Sirt1 signalling
Authors: Han Na , Wang Zhiqiang , Li Xianhui
Published: January 2021

Hyaluronic acid (HA) exerts a critical role in the lubricating and buffering properties of synovial fluid in joints. The production of HA is regulated by growth factors, hormones, inflammatory cytokines and mechanical load. The reduction of HA contributes to the progression of osteoarthritis. Herein, we found that d‐galactose (d‐gal) induced the senescence of rabbit synovial membrane cells, accompanied by decreased HA production. The mRNA level of HA synthase 2 (HAS2) was downregulated by d‐gal, as analysed by real‐time polymerase chain reaction. Melatonin, an endocrine hormone, can regulate the homeostasis of bone and cartilage. We found that melatonin treatment attenuated d‐gal‐induced cell senescence and decreased the expression of p21, p16 and pp65 proteins. Melatonin could reverse HA production and maintain HAS2 expression. Furthermore, we revealed that Sirt1 signalling was required for melatonin effects. Sirt1 inhibitor could counteract melatonin‐mediated HA production and HAS2 expression. Additionally, Sirt1 overexpression directly antagonized d‐gal‐induced cell aging and HA downregulation. Taken together, our results suggest that melatonin‐Sirt1 signal has a protective effect on synovial membrane cells, enhancing HA synthesis and interrupting cell senescence.
Inducible CRISPR‐dCas9 Transcriptional Systems for Sensing and Genome Regulation
Authors: Wu Han , Wang Fenglin , Jiang Jian‐Hui
Published: January 2021

The clustered, regularly interspaced short palindromic repeats‐associated protein 9 endonuclease (CRISPR‐Cas9) and the nuclease‐deactivated Cas9 (dCas9) systems have revolutionized our ability to precisely engineer and regulate genomes. Inducible CRISPR‐dCas9‐based transcriptional systems have been rapidly developed to conditionally control genetic manipulation. Current strategies mainly focus on conditional control of gRNA function and dCas9 protein using exogenous and endogenous triggers, including external light, small molecules, synthetic and intracellular oligonucleotides. These strategies have established novel platforms for the spatiotemporal regulation of genome activation and repression, epigenome editing, and so on. Herein, we summarize the recent progress in conditionally controlling CRISPR‐dCas9 transcriptional systems through gRNA modulation and dCas9 protein engineering.
Stable Hairpin Structures Formed by Xylose‐Based Nucleic Acids
Authors: Mattelaer Charles‐Alexandre , Maiti Mohitosh , Smets Laurent , Maiti Munmun , Schepers Guy , Mattelaer Henri‐Philippe , Rosemeyer Helmut , Herdewijn Piet , Lescrinier Eveline
Published: January 2021

Xenobiology explores synthetic nucleic acid polymers as alternative carriers of genetic information to expand the central dogma. The xylo‐ and deoxyxylo‐nucleic acids (XyNA and dXyNA), containing 3’ epimers of riboses and deoxyriboses, are considered to be potential candidates for an orthogonal system. In this study, thermal and spectroscopic analyses show that XyNA and dXyNA form stable hairpins. The dXyNA hairpin structure determined by NMR spectroscopy contains a flexible loop that locks the stem into a stable ladder‐like duplex with marginal right‐handed helicity. The reduced flexibility of the dXyNA duplex observed in the stem of the hairpin demonstrates that folding of dXyNA yields more stable structures described so far.
Tagged Benzoxazin‐4‐Ones as Novel Activity‐Based Probes for Serine Proteases
Authors: Yang Jian , Mendowicz Rafal J. , Verhelst Steven H. L.
Published: January 2021

Activity‐based probes (ABPs) are valuable chemical tools for profiling enzymes. They have been particularly useful in the study of proteases. ABPs rely on electrophilic scaffolds that covalently modify the target enzymes. Ideally, they can be made in a fast and uncomplicated manner. Here, we explore alkyne‐substituted benzoxazin‐4‐ones as ABPs for serine proteases, because they inhibitserine proteases covalently and their synthesis is very straightforward. We show that alkyne‐tagged benzoxazin‐4‐ones can be used in two‐step bioorthogonal tandem labeling procedures or pre‐functionalized with a biotin or fluorophore. We demonstrate that these reagents can be used to label and identify various serine proteases. Therefore, we expect that tagged benzoxazin‐4‐ones will offer easily synthesizable tools for profiling of serine proteases.
Distinct immunomodulatory properties of extracellular vesicles released by different strains of Acanthamoeba
Authors: Costa Adriana Oliveira , Chagas Isabela Aurora Rodrigues , de Menezes‐Neto Armando , Rêgo Felipe Dutra , Nogueira Paula Monalisa , Torrecilhas Ana Claudia , Furst Cinthia , Fux Blima , Soares Rodrigo Pedro
Published: January 2021

Free living amoeba of the genus Acanthamoeba are opportunist protozoan involved in corneal, systemic, and encephalic infections in humans. Most of the mechanisms underlying intraspecies variations and pathogenicity are still unknown. Recently, the release of extracellular vesicles (EVs) by Acanthamoeba was reported. However, comparative characterization of EVs from distinct strains is not available. The aim of this study was to evaluate EVs produced by Acanthamoeba from different genotypes, comparing their proteases profile and immunomodulatory properties. EVs from four environmental or clinical strains (genotypes T1, T2, T4, and T11) were obtained by ultracentrifugation, quantitated by nanoparticle tracking analysis and analyzed by scanning and transmission electron microscopy. Proteases profile was determined by zymography and functional properties of EVs (measure of nitrite and cytokine production) were determined after peritoneal macrophage stimulation. Despite their genotype, all strains released EVs and no differences in size and/or concentration were detected. EVs exhibited a predominant activity of serine proteases (pH 7.4 and 3.5), with higher intensity in T4 and T1 strains. EVs from the environmental, nonpathogenic T11 strain exhibited a more proinflammatory profile, inducing higher levels of Nitrite, tumor necrosis factor alpha and interleukin‐6 via TLR4/TLR2 than those strains with pathogenic traits (T4, T1, and T2). Preincubation with EVs treated with protease inhibitors or heating drastically decreased nitrite concentration production in macrophages. Those data suggest that immunomodulatory effects of EVs may reflect their pathogenic potential depending on the Acanthamoeba strains and are dependent on protease integrity.
Complete response of cutaneous SCC to topical treatment with ascorbic acid solution: A case report
Authors: Pernice Carmine , Murri Domenico , Valli Riccardo , Crocetta Francesco M. , Iori Michele , Asti Mattia , Ghidini Angelo , Capponi Pier C.
Published: January 2021

Clinical use of topical ascorbic acid solution could have both the role as an adjunct to consolidated therapies and as an alternative to them, for the treatment of BCC and SCC of the skin.
Utility of objective gait measures in levodopa‐unresponsive freezing in Parkinson's
Authors: Virmani Tuhin , Glover Aliyah , Pillai Lakshmi , Lotia Mitesh , Dhall Rohit
Published: January 2021

Levodopa‐unresponsive gait freezing in Parkinson disease is debilitating. Gait kinematics, while time‐consuming, can help optimize levodopa's benefit on gait stride length and stride velocity, and thereby improve freezing and falls in these patients.
High‐grade B‐cell lymphoma developed during the treatment of chronic myeloid leukemia with bosutinib
Authors: Takakuwa Teruhito , Sakai Ryota , Koh Shiro , Okamura Hiroshi , Nanno Satoru , Nakashima Yasuhiro , Nakane Takahiko , Koh Hideo , Hino Masayuki , Nakamae Hirohisa
Published: January 2021

Tyrosine kinase inhibitor (TKI) can help to increase the survival time in chronic myeloid leukemia (CML) patients; however, the risk of secondary malignancies due to TKIs is a growing concern. Only few reports showed clinical course of patients who developed lymphoma during TKI therapies. Herein, we report a case of high‐grade B‐cell lymphoma diagnosed in the course of CML treatment with bosutinib. The 75‐year‐old male patient had been diagnosed with CML 25 years ago. After receiving TKIs (imatinib, nilotinib, and bosutinib), he achieved a major molecular response. Over 3 years after starting bosutinib, he was diagnosed with a high‐grade B‐cell lymphoma. A total of six courses of DA‐EPOCH‐R therapy brought complete remission of the lymphoma. Moreover, BCR‐ABL1 transcript copies remained undetectable by RT‐PCR, 8 months after stopping bosutinib. The risk of secondary malignancy due to TKI has been controversial. It is reported that TKI induces irreversible chromosomal abnormalities or chromosome aberrations and inhibits the proliferation or function of T cells, B cells, and NK cells. These mechanisms of TKI may contribute to the development of secondary malignancy. There remains no consensus on the management of secondary lymphoma during TKI therapies. At present, the only alternative is to observe patients receiving TKI treatment cautiously and to treat secondary lymphoma in the same manner as de novo lymphoma.
In‐situ XAS Study of Catalytic N2O Decomposition Over CuO/CeO2 Catalysts
Authors: Zabilskiy Maxim , Arčon Iztok , Djinović Petar , Tchernychova Elena , Pintar Albin
Published: January 2021

We performed in‐situ XAS study of N2O decomposition over CuO/CeO2 catalysts. The Cu K‐edge and Ce L3‐edge XANES and EXAFS analyses revealed the dynamic and crucial role of Cu2+/Cu+ and Ce4+/Ce3+ ionic pairs during the catalytic reaction. We observed the initial formation of reduced Cu+ and Ce3+ species during activation in helium atmosphere at 400 °C, while concentration of these species decreased significantly during steady‐state nitrous oxide degradation reaction (2500 ppm N2O in He at 400 °C). In‐situ EXAFS analysis further revealed a crucial role of copper−ceria interface in this catalytic reaction. We observed dynamic changes in average number of Cu−Ce scatters under reaction conditions, indicating an enlarging of the interface between both copper and ceria phases, where electron and oxygen transfer occurs.
Green Synthesis of Zinc Oxide Nanoparticles by Justicia adhatoda Leaves and Their Antimicrobial Activity
Authors: Pachaiappan Rekha , Rajendran Saravanan , Ramalingam Gomathi , Vo Dai-Viet N. , Priya P. Mohana , Soto-Moscoso Matias
Published: January 2021

Zinc oxide is recognized as one of the best antimicrobial agents. Zinc oxide nanoparticles were fabricated through a green approach using zinc sulfate, zinc nitrate, and zinc acetate dihydrate as precursors and an extract of Justicia adhatoda leaves as a reducing agent. The synthesized zinc oxide nanoparticles were checked for their antimicrobial activity against the bacterial strains Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and the fungal strains Aspergillus niger, Aspergillus flavus, and Aspergillus fumigates. All three zinc oxide nanoparticles were found to inhibit the growth of microbes by the release of zinc ions and production of reactive oxygen species followed by destruction of microbes. Antimicrobial results of zinc oxide nanoparticles from the three different precursors were compared.
Photoinduced DNA Interstrand Cross‐Linking by 1,1′‐Biphenyl Analogues: Substituents and Leaving Groups Combine to Determine the Efficiency of Cross‐Linker
Authors: Fan Heli , Sun Huabing , Zhang Qi , Peng Xiaohua
Published: January 2021

Two series of 1,1′‐biphenyl analogues with various leaving groups (L=OAc, OCH3, OCHCH=CH2, OCH2Ph, SPh, SePh, and Ph3P+) were synthesized. Their reactivity towards DNA and the reaction mechanism were investigated by determining DNA interstrand cross‐link (ICL) efficiency, radical and carbocation formation, and the cross‐linking reaction sites. All compounds induced DNA ICL formation upon 350 nm irradiation via a carbocation that was generated from oxidation of the corresponding free radicals. The ICL efficiency and the reaction rate strongly depended on the combined effect of the leaving group and the substituent. Among all compounds tested, the high ICL efficiency (30–43 %) and fast reaction rate were observed with compounds carrying a nitrophenyl group and acetate (2 a), ether (2 b and 2 c), or triphenylphosphonium salt (2 g) as leaving groups. Most compounds with a 4‐methoxybenzene group showed similar DNA ICL efficiency (≈30 %) with a slow DNA cross‐linking reaction rate. Both cation trapping and free radical trapping adducts were detected in the photo activation process of these compounds, which provided direct evidence for the proposed mechanism. Heat stability study in combination with sequence study suggested that these photo‐generated benzyl cations alkylate DNA at dG, dA, and dC sites.
De Novo and Divergent Synthesis of Highly Functionalized Furans by Cascade Reactions of 2‐Hydroxy‐1,4‐diones with Nucleophiles
Authors: Liu Hai‐xuan , Ji Fei , Chen Yu , Gao Ya , Wang Jun‐ke , Zhang Ming‐zhi , Liu Fang , Sha Qiang
Published: January 2021

Herein, a divergent synthesis of a variety of 2α‐ and 5α‐substituted furan derivatives from 2‐hydroxy‐1,4‐diones is reported. By using appropriate substrates and an acid catalyst, the reactions occurred selectively through cyclization/1,6‐conjugate addition or cyclization/Friedel–Crafts‐type cascade reactions. A broad range of nucleophilic reagents (>10 types for the 1,6‐conjugate addition for 5α substitution and >20 types for the Friedel–Crafts‐type cascade reaction for 2α substitution), including alcohols, amides, furan, thiophene, pyrrole, indole, phenols, and many others, can successfully participate in the reactions, providing a universal strategy for a diversity‐oriented synthesis of α‐substituted furan derivatives. Deuteriation experiments and DFT calculations were carried out to support the proposed reaction mechanisms. Antifungal activity experiments revealed that products with an indole or 4‐hydroxycoumarin core substituted at the 2α position showed moderate activities against Rhizoctorzia solani and Botrytis cinerea, respectively.
Beyond the Isoprene Pattern: Bifunctional Polyene Cyclizations
Authors: Feilner Julian M. , Haut Franz‐Lucas , Magauer Thomas
Published: January 2021

Polyene cyclizations are capable of producing molecular complexity in a single step. While classical systems are limited to simple alkyl substitution patterns only, bifunctional polyenes take advantage of the unique reactivity of higher‐functionalized alkenes. Here, we highlight the potential of these variants for the synthesis of structurally complex polycycles involving unprecedented termination steps. We also want to provide a stimulus for the development of novel modes of cyclization that involve bifunctional units to enable efficient synthesis of yet inaccessible natural products.
Tuning the Regioselective Functionalization of Trifluoromethylated Dienes via Lanthanum‐Mediated Single C−F Bond Activation
Authors: Kumar Tarun , Yang Yan , Sghaier Sirine , Zaid Yassir , Le Goff Xavier F. , Rousset Elodie , Massicot Fabien , Harakat Dominique , Martinez Agathe , Taillefer Marc , Maron Laurent , Behr Jean‐Bernard , Jaroschik Florian
Published: January 2021

The development of new fluorine‐containing building blocks and their efficient synthetic access is currently a challenging research field. Herein, the highly regio‐ and stereoselective addition of a large range of aldehydes onto trifluoromethylated benzofulvenes was achieved using a simple La/I2/DIBAL‐Cl system via a selective C−F bond activation process. This versatile methodology provided homodienyl alcohols bearing a terminal CF2‐alkene with potential further applications, as shown by the dehydration to the first benzofulvenes carrying a difluorovinyl group. In addition, for certain electron‐poor aldehydes, unprecedented ipso substitution of the CF3 group in a diene was observed, which, according to DFT studies, is related to the presence of the large, Lewis‐acidic lanthanum metal.
Postsynthetic‐Modified PANI/MOF Composites with Tunable Thermoelectric and Photoelectric Properties
Authors: Xu Wenjuan , Zhao Yujie , Wang Huarui , Wang Hongfei , Pan Fangfang , Xu Ruixue , Hou Hongwei
Published: January 2021

A 3D Co‐based metal–organic framework (Co‐MOF) with two kinds of large pores filled by free Co2+ ions and ligands was synthesized and characterized. To expand the MOF structure and conductivity, the free Co2+ ions and ligands were exchanged by conductive ionic liquid EtpyBr and photosensitive AgNO3 through single crystal‐to‐single crystal transformation, which produced structure‐changed 3D MOFs Co‐MOF‐Br and Co‐Ag‐MOF, which were characterized by single‐crystal X‐ray diffraction. Incorporating small quantities of doped polyaniline (PANI) with redox activity into the pores could further tune the stability and conductivity of the three MOFs. The PANI/MOFs all show outstanding electrical conductivity (≈10−2 S cm−1), and PANI/Co‐MOF‐Br has the largest p‐type Seebeck coefficient of 66.6 μV K−1. PANI/Co‐MOF‐Br and PANI/Co‐Ag‐MOF have 4 and 15 times higher photocurrent density compared with PANI/Co‐MOF, respectively. This work sheds light on the design of advanced electrically conductive 3D MOFs.
Merging Pd0/PdII Redox and PdII/PdII Non‐redox Catalytic Cycles for the Allylarylation of Electron‐Deficient Alkenes
Authors: Semba Kazuhiko , Ohta Naoki , Paulus Fritz , Ohata Masaki , Nakao Yoshiaki
Published: January 2021

An allylarylation of electron‐deficient alkenes with aryl boronates and allylic carbonates has been developed. This method allows access to a wide variety of carbon skeletons from readily available starting materials. Mechanistic studies indicate that this reaction is enabled by a cooperative catalysis based on merging Pd0/PdII redox and PdII/PdII non‐redox catalytic cycles.
Intramolecular Pyridinium Oxide Cycloadditions: Systematic Study of Substitution, Diastereoselectivity, and Regioselectivity
Authors: Lu Yi , Dey Patrick N. , Beaudry Christopher M.
Published: January 2021

Intramolecular pyridinium oxide cycloadditions form complex polycyclic nitrogenous architectures. The diastereoselectivity and regioselectivity of pyridinium oxide cycloadditions was systematically investigated for the first time using complex substrates. Predictably high levels of diastereoselectivity and regioselectivity are observed, which can be attributed to minimization of steric (syn‐pentane) and torsional strain in the products. The reaction is reversible under the reaction conditions, and it is stereospecific with respect to the dipolarophile geometry.
Boosting the Capacitive Performance of Cobalt(II) Phthalocyanine by Non‐peripheral Octamethyl Substitution for Supercapacitors†
Authors: Li Minzhang , Ramachandran Rajendran , Wang Yu , Chen Qian , Xu Zong‐Xiang
Published: January 2021

Main observation and conclusion

In this paper, pristine cobalt(II) phthalocyanine (CoPc) and non‐peripheral octamethyl substituted CoPc (N‐CoMe2Pc) are the focus of electrochemical investigation. CoPc and N‐CoMe2Pc nanorods (NR) were synthesized by a facile precipitation process from sublimated bulk phthalocyanine powders and their electrochemical properties were explored. Due to the large specific surface area, the capacitance performance of the nanorods was significantly higher than that of the sublimated powder sample. N‐CoMe2Pc powder exhibited better pseudocapacity compared with CoPc powder and CoPc NR, which is attributed to enhanced charge transfer rate and improved redox activity after the introduction of octamethyl substituents on phthalocyanine ring. The maximum specific capacitance value was achieved by N‐CoMe2Pc NR based electrode, exhibiting 210.2 F g–1 capacitance at 5 mV s–1 scan rate and 156.1 F g–1 at 0.25 A g‐1 current density, and also showing high efficiency and satisfactory retention. These results indicate that according to proper molecular design, N‐CoMe2Pc NR could be applied as the potential candidate for electrode material in supercapacitors.
Advances in Nucleoside and Nucleotide Analogues in Tackling Human Immunodeficiency Virus and Hepatitis Virus Infections
Authors: Ramesh Deepthi , Vijayakumar Balaji Gowrivel , Kannan Tharanikkarasu
Published: January 2021

Nucleoside and nucleotide analogues are structurally similar antimetabolites and are promising small‐molecule chemotherapeutic agents against various infectious DNA and RNA viruses. To date, these analogues have not been documented in‐depth as anti‐human immunodeficiency virus (HIV) and anti‐hepatitis virus agents, these are at various stages of testing ranging from pre‐clinical, to those withdrawn from trials, or those that are approved as drugs. Hence, in this review, the importance of these analogues in tackling HIV and hepatitis virus infections is discussed with a focus on the viral genome and the mechanism of action of these analogues, both in a mutually exclusive manner and their role in HIV/hepatitis coinfection. This review encompasses nucleoside and nucleotide analogues from 1987 onwards, starting with the first nucleoside analogue, zidovudine, and going on to those in current clinical trials and even the drugs that have been withdrawn. This review also sheds light on the prospects of these nucleoside analogues in clinical trials as a treatment option for the COVID‐19 pandemic.
Timing, number, and type of sexual partners associated with risk of oropharyngeal cancer
Authors: Drake Virginia E. , Fakhry Carole , Windon Melina J. , Stewart C. Matthew , Akst Lee , Hillel Alexander , Chien Wade , Ha Patrick , Miles Brett , Gourin Christine G. , Mandal Rajarsi , Mydlarz Wojciech K. , Rooper Lisa , Troy Tanya , Yavvari Siddhartha , Waterboer Tim , Brenner Nicole , Eisele David W. , D’Souza Gypsyamber
Published: January 2021

Background

Case‐control studies from the early 2000s demonstrated that human papillomavirus–related oropharyngeal cancer (HPV‐OPC) is a distinct entity associated with number of oral sex partners. Using contemporary data, we investigated novel risk factors (sexual debut behaviors, exposure intensity, and relationship dynamics) and serological markers on odds of HPV‐OPC.

Methods

HPV‐OPC patients and frequency‐matched controls were enrolled in a multicenter study from 2013 to 2018. Participants completed a behavioral survey. Characteristics were compared using a chi‐square test for categorical variables and a t test for continuous variables. Adjusted odds ratios (aOR) were calculated using logistic regression.

Results

A total of 163 HPV‐OPC patients and 345 controls were included. Lifetime number of oral sex partners was associated with significantly increased odds of HPV‐OPC (>10 partners: odds ratio [OR], 4.3 [95% CI, 2.8‐6.7]). After adjustment for number of oral sex partners and smoking, younger age at first oral sex (<18 vs >20 years: aOR, 1.8 [95% CI, 1.1‐3.2]) and oral sex intensity (>5 sex‐years: aOR, 2.8 [95% CI, 1.1‐7.5]) remained associated with significantly increased odds of HPV‐OPC. Type of sexual partner such as older partners when a case was younger (OR, 1.7 [95% CI, 1.1‐2.6]) or having a partner who had extramarital sex (OR, 1.6 [95% CI, 1.1‐2.4]) was associated with HPV‐OPC. Seropositivity for antibodies to HPV16 E6 (OR, 286 [95% CI, 122‐670]) and any HPV16 E protein (E1, E2, E6, E7; OR, 163 [95% CI, 70‐378]) was associated with increased odds of HPV‐OPC.

Conclusion

Number of oral sex partners remains a strong risk factor for HPV‐OPC; however, timing and intensity of oral sex are novel independent risk factors. These behaviors suggest additional nuances of how and why some individuals develop HPV‐OPC.
A Control Variate Method Driven by Diffusion Approximation
Authors: Garnier Josselin , Mertz Laurent
Published: January 2021

In this paper we introduce a control variate estimator for a quantity of interest that can be expressed as the expectation of a function of a random process, that is itself the solution of a differential equation driven by fast mean‐reverting ergodic random forces. The control variate is built with the same function and with the limit diffusion process that approximates the original random process when the mean reversion time of the driving forces goes to 0. We propose a coupling of the original process and the limit diffusion process that gives a control variate estimator with small variance. We show that the correlation between the two processes indeed goes to 1 when the mean reversion time goes to 0 and we quantify the convergence rate, which allows us to characterize the variance reduction of the proposed control variate estimator. The efficiency of the method is illustrated on a few examples. © 2021 Wiley Periodicals LLC.
Safety, Pharmacokinetics, and Pharmacodynamics of a Dipeptidyl Peptidase‐4 Inhibitor: A Randomized, Double‐Blinded, Placebo‐Controlled Daily Administration of Fotagliptin Benzoate for 14 Days for Type 2 Diabetes Mellitus
Authors: Wu Min , Li Qian‐Qian , Zhang Hong , Zhu Xiao‐Xue , Li Xiao‐Jiao , Li Ying , Sun Hai‐Gang , Ding Yan‐Hua
Published: January 2021

This study investigated the pharmacokinetics, pharmacodynamics, and safety of fotagliptin benzoate (fotagliptin), a dipeptidyl peptidase‐4 (DPP‐4) inhibitor, in Chinese patients with type 2 diabetes mellitus (T2DM). In a randomized, double‐blinded, placebo‐controlled study, 10 and 4 patients with T2DM were randomized and received, respectively, once‐daily oral fotagliptin (24 mg) or placebo, for 14 days. The pharmacokinetics and pharmacodynamics were assessed throughout the study, including monitoring DPP‐4, glucagon‐like peptide‐1 (GLP‐1), glycosylated hemoglobin, and fasting blood glucose. Fotagliptin was rapidly absorbed, and the median time to maximum concentration value was ∼1.5 hours. Plasma fotagliptin levels were stable after 14 days of once‐daily dosage. The accumulation ratios for the area under the plasma concentration–time curve of fotagliptin, M1, and M2‐1, were 1.19 ± 0.10, 1.59 ± 0.27, and 1.39 ± 0.26, respectively. The durations for DPP‐4 inhibition >80% in the fotagliptin group on days 1 and 14 were 23.5 and 24.0 hours, respectively. The concentrations of GLP‐1 were higher on days 1 and 14 than at the baseline. No serious complications occurred. Fotagliptin showed favorable pharmacokinetics and pharmacodynamics and was well tolerated. Treatment with fotagliptin can achieve high DPP‐4 inhibition and increase plasma GLP‐1. A once‐per‐day dosing regimen may be recommended as clinically efficacious.