bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual Communication of Data: It Is Not a Programming Problem, It Is Viewer Perception
Authors: Mulrow Edward , du Toit Nola
Published: November 2021

Creating effective data graphics can become very technical, and some visualizations require complicated programs and techniques. Often, the graphic developer gets too engrossed in the method without considering how users will perceive the visual. Sometimes, the wrong method can obscure the data story. At worst, the developer could create a visual lie. We discuss how a commonly used performance feedback process can be used as a tool to help graphic developers create functional, useful, and effective graphics that correctly depict the data. Using two fictitious cases studies, we illustrate common problems in selecting a graphical format, along with alternative solutions. In addition, we outline leading resources and strategies that will assist graphic developers in producing successful visualizations. Our goal is to help developers stop and think about the data, and how graphics are perceived, before moving onto the technical parts of creating the visual.
Finite Horizon Process Monitoring
Authors: Chakraborti Subhabrata , Celano Giovanni , Castagliola Philippe , Nenes George
Published: November 2021

In some industrial environments
flexibility
is a key for the manufacturer, that is, the ability to switch frequently from the production of one product code to another and produce batches of different items during consecutive short production time intervals, called finite production horizons; such a setting is called a finite horizon process (FHP). The frequent process changeovers may require new setup activities and machine reconfigurations every time before the beginning of a new production run. An erroneous setup or a process failure can negatively impact the quality of the manufactured products. In order to perform statistical quality control for these types of processes, practitioners have to deal with the challenging issues of designing, scheduling, and performing only a limited number of inspections. This is typically not the case in traditional quality control and monitoring applications. In this article, we highlight various aspects of statistical process monitoring (SPM) implemented in an FHP setting that need to be considered by quality practitioners. We describe available statistical process monitoring tools, such as the control charts, properly designed to monitor quality characteristics in the FHP setting. Finally, we discuss some of the still open challenges in the area of FHP monitoring.
Wettability and Droplet Directional Spread Investigation of Crescent Array Surface Inspired by Slippery Zone of Nepenthes
Authors: Jing Xian , Si Wenfang , Sun Jie , Zhou Jiakang , Lin Jieqiong , Yu Baojun , Lu Mingming
Published: November 2021

In this report, the surface topography of crescent array in the Nepenthes slippery zone is measured and bionic fabricated by two‐photon polymerization (TPP) technology. A subregion outside‐in scanning method (SOSM) is proposed to solve the photoresist converge and large area surface positioning problem existing in bionic crescent array surface (BCAS) fabrication. The geometric parameters of BCAS, including area fraction, height, offset, and outer–inner radius ratio, are systematically investigated to reveal their effects on the hydrophobic performance. Perfluorinated polyether oil and fluorocarbon solvent were used to increase the hydrophobicity and homogeneity of bionic surface. The contact angles of BCASs coated with and without the solution are measured. The maximum contact angle can reach to 152.1°. What's more, considering the anisotropy of BCAS, anisotropic wetting research is conducted. Offset and outer–inner radius ratio are found to have obvious effects on the contact angle differences between convexity and concavity directions. The maximum contact angle difference can reach to 5.1°. Spreading and pinning phenomenon caused by droplet anisotropic wetting are observed and explained. This work is expected to provide references for the BCAS to be applied in super‐hydrophobic and droplets motion fields.
Deep Convolutional Neural Networks to Predict Mutual Coupling Effects in Metasurfaces
Authors: An Sensong , Zheng Bowen , Shalaginov Mikhail Y. , Tang Hong , Li Hang , Zhou Li , Dong Yunxi , Haerinia Mohammad , Agarwal Anuradha Murthy , Rivero‐Baleine Clara , Kang Myungkoo , Richardson Kathleen A. , Gu Tian , Hu Juejun , Fowler Clayton , Zhang Hualiang
Published: November 2021

Metasurfaces have provided a novel and promising platform for realizing compact and high‐performance optical devices. The conventional metasurface design approach assumes periodic boundary conditions for each element, which is inaccurate in most cases since near‐field coupling effects between elements will change when the element is surrounded by nonidentical structures. In this paper, a deep learning approach is proposed to predict the actual electromagnetic (EM) responses of each target meta‐atom placed in a large array with near‐field coupling effects taken into account. The predicting neural network takes the physical specifications of the target meta‐atom and its neighbors as input, and calculates its actual phase and amplitude in milliseconds. This approach can be used to optimize metasurfaces’ efficiencies when combined with optimization algorithms. To demonstrate the efficacy of this methodology, large improvements in efficiency for a beam deflector and a metalens over the conventional design approach are obtained. Moreover, it is shown that the correlations between a metasurface's performance and its design errors caused by mutual coupling are not bound to certain specifications (materials, shapes, etc.). As such, it is envisioned that this approach can be readily applied to explore the mutual coupling effects and improve the performance of various metasurface designs.
Efficient Helium and Helium Isotopes Separation by Phosphorus Carbide P2C3 Membrane
Authors: Li Min , Wang Lu , Lei Huixia , Yang Yanmei , Li Yong‐Qiang , Zhao Mingwen , Guan Jing , Li Weifeng , Qu Yuanyuan
Published: November 2021

The problem of ever‐increasing industrial demand versus the supply shortage of helium (He) is inevitably encountered by scientists worldwide. Membrane‐based separation technology provides an economical method to alleviate the current He scarcity. In this study, using a combination of first‐principles calculations and molecular dynamics simulations, it is theoretically demonstrated that the phosphorus carbide membrane P2C3 possesses high efficiency in He separation from the natural gas (H2, N2, CO, H2O, CO2, and CH4) and other noble gas atoms (Ne and Ar). In addition, the He permeance exceeds 10–4 mol m–2 s–1 Pa–1 over a wide range of temperatures (200–500 K), which is far beyond the industrially acceptable value. Combining the zero‐point‐energy and quantum tunneling effects, the quantum analysis shows that the P2C3 membrane has great potential for 3He/4He isotope separation, thus providing a combined means for both He and 3He isotope separation. The results uncover a new solution of utilizing P2C3 nanomaterial as a novel medium for gas treatment and the findings of this study will promote experimental efforts in the future.
Tunable and Reconfigurable Higher‐Order Topological Insulators in Photonic Crystals with Phase Change Materials
Authors: Zhang Yuexin , Li Zhongfu , Xu Shixiang , Xiang Yuanjiang
Published: November 2021

Higher‐order topological insulators (HOTIs) have attracted great interest due to the unconventional bulk‐boundary correspondence. However, the realization of HOTIs usually requires a geometrical transformation of the photonic crystals (PhCs), setting high demands on the manufacturing process. Here a scheme is reported of tunable and reconfigurable HOTIs with phase change materials (PCMs) by controlling the temperature. The temperature change can transform the amorphous states to crystalline states, leading to the reconfigurable edge states and corner states. It is proven that both Sb2S3 and Sb2Se3 can support the reconfigurable HOTIs at the phase change temperature 270 °C at different wavelengths. This work discovers a new platform for the practical implementation of high‐order topological phase transition optical apparatus in the foreseeable future, such as nanocavities, waveguides, and metasurfaces.
HFIP Mediates a Direct C−C Coupling between Michael Acceptors and Eschenmoser's salt
Authors: Lemmerer Miran , Riomet Margaux , Meyrelles Ricardo , Maryasin Boris , González Leticia , Maulide Nuno
Published: November 2021

A direct C−C coupling process that merges Michael acceptors and Eschenmoser's salt is presented. Although reminiscent of the Morita–Baylis–Hillman reaction, this process requires no Lewis base catalyst. The underlying mechanism was unveiled by a combination of kinetic, isotopic labelling experiments as well as computational investigations, which showcased the critical role of HFIP as a superior mediator for proton‐transfer events as well as the decisive role of the halide counterion.
Studies on slow radio transients
Authors: Wołowska Aleksandra , Kunert‐Bajraszewska Magdalena , Mooley Kunal , Siemiginowska Aneta , Kharb Preeti , Ishwara‐Chandra C. H. , Hallinan Gregg , Gromadzki Mariusz , Kozieł‐Wierzbowska Dorota
Published: November 2021

We present a brief overview of a very extensive study of the group of active galactic nuclei (AGNs) that transitioned to the radio‐loud state over the past few decades. The sample consists of 12 sources, both quasars and galaxies, showing the characteristics of the gigahertz‐peaked spectrum objects undergoing relatively rapid changes, due to the evolution of their newly born radio jets. Discussed objects also show a wide range of physical parameters such as bolometric luminosity, black hole mass, and jet power, suggesting a great diversity among young AGNs and their hosts. Furthermore, we introduce a new observational project, the aim of which will be to investigate and gain a more in‐depth understanding of the phenomenon of slow radio transients.
Authority Claims Situating Socialist Science Studies in the GDR**
Authors: Cain Friedrich
Published: November 2021

This essay studies the narrative self‐positioning of Science Studies in the German Democratic Republic during the 1980s. Drawing on archival material on the foundation of the Council for Marxist‐Leninist Science Studies at the Academy of Sciences in East Berlin in March 1988, it analyses how boundaries between Science Studies as a lone standing discipline and several other fields were construed and crossed at the same time and how (scientific) authority was claimed from the intermediate position of anexternal insider. Not only did Science Studies engage with their subject – the sciences –, but also with the politics of the Socialist Party, with the institution of the Academy, and with (industrial) production. After a formative institutional phase that spanned across the 1970s, Science Studies made efforts to centralize their work during the 1980s, to bind themselves closer to the state and scientific institutions, and to distinguish themselves from them at the same time.
Tick bite induced α‐gal syndrome highlights anticancer effect of allergy
Authors: Apari Péter , Földvári Gábor
Published: November 2021

Tick bite induced α‐gal syndrome (AGS) following consumption of mammalian meat is a recently described intriguing disease occurring worldwide. Here we argue that AGS and delayed allergy in general is an adaptive defence method against cancer. Our hypothesis synthesizes two lines of supporting evidence. First, allergy has been shown to have direct anti‐cancer effects with unknown mechanism. Second, eating processed meat was shown to be linked to developing cancer. Humans lost their genes encoding molecules α‐gal 30 MYA and Neu5Gc 2 MYA, the latter co‐occurring with the start of using fire. These molecules are acquired from external sources, as tick bite for α‐gal and mammalian meat for Neu5Gc, the latter accumulating in tumors. The resulting specific delayed allergic response is a molecular adaptation to fight cancer. By further testing and applying our hypothesis, new avenues in cancer research and therapy will open that might save lives and decrease human suffering.
Computational Prediction of the Potential Target of SARS‐CoV‐2 Inhibitor Plitidepsin via Molecular Docking, Dynamic Simulations and MM‐PBSA Calculations
Authors: El Hassab Mahmoud A. , Hemeda Loah R. , Elsayed Zainab M. , Al‐Rashood Sara T. , Abdel‐Hamid Amin Mohammed K. , Abdel‐Aziz Hatem A. , Eldehna Wagdy M.
Published: November 2021

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) replication depends on the interaction between the viral proteins and the human translation machinery. The cytotoxic peptide plitidepsin was found to inhibit CoV‐2 up to 90 % at a concentration of 0.88 nM. In vitro studies suggest that this activity may be attributed to the inhibition of the eukaryotic translation elongation factor 1A (eEF1A). However, recent reports raised the potential for other cellular targets which plitidepsin may use to exert its potent antiviral activity. The lack of data about these potential targets represents a major limitation for its structural optimization. This work describes the use of a molecular modeling approach to rationalize the in vitro antiviral activity of plitidepsin and to identify potential cellular targets. The developed protocol involves an initial molecular docking step followed by molecular dynamics and binding free energy calculations. The results reveal the potential for plitidepsin to bind to the active site of the key enzyme SARS‐CoV‐2 RdRp. The results also highlight the importance of van der Waals interactions for proper binding with the enzyme. We believe that the results presented in this study could provide the grounds for the optimization of plitidepsin analogs as SARS‐CoV‐2 inhibitors.
Delafossite Ag2CuMnO4 is a Novel Catalytic Material for Low‐Temperature Oxidation of CO and NH3
Authors: Svintsitskiy Dmitry A. , Sokovikov Nikolai A. , Slavinskaya Elena M. , Fedorova Elizaveta A. , Boronin Andrei I.
Published: November 2021

Ternary oxide of silver, copper, and manganese (Ag2CuMnO4) was prepared by hydrothermal synthesis in an alkaline solution. The prepared sample was characterized by a delafossite crystal structure without any other crystallized phases. The catalytic properties of Ag2CuMnO4 in oxidation reactions using molecular oxygen were investigated. High catalytic activity was found for Ag2CuMnO4 in the CO oxidation at room temperature, while ammonia oxidation occurred above 100 °C. Ammonia oxidation resulted in the formation of N2O/N2 or NO/NO2 products depending on the reaction temperature. As a result of the reaction exposure on Ag2CuMnO4 during heating up to 400 °C, a modification of surface composition with preservation of the delafossite structure was found. Oxide Ag2CuMnO4 was shown to be operating in wet CO oxidation under ambient conditions. Obtained data emphasize that Ag2CuMnO4 can be considered as a novel and prospective catalytic material with a high potential of application for oxidation processes at low temperatures including ambient conditions.
Selection of Formal Baseline Correction Methods in Thermal Analysis
Authors: Gibson Rebecca L. , Simmons Mark J. H. , Stitt E. Hugh , Horsburgh Lockhart , Gallen Robert W.
Published: November 2021

Baseline correction is a key step in processing of thermal analysis data. Whilst this is a common step, techniques range from linear baselines to use of high‐order polynomials. When considering a formal baseline correction (those without physical or experimental justification), only linear correction methods should be used: linear with time, linear with temperature, and linear with extent of reaction. The absence of baseline correction should also be considered. An in silico study shows that the wrong baseline correction can significantly impact the parameters obtained from kinetic modeling. The four baseline correction methods are demonstrated with a mass spectrometry dataset. It is recommended that the selection of correction method should be based on comparison of Akaike weights.
Monitoring the Thiol/Thiophenol Molecule‐Modulated Plasmon‐Mediated Silver Oxidation with Dark‐Field Optical Microscopy
Authors: Wang Yaoli , Liang Yan , Sheng Huixiang , Wang Jin , Wang Junjie , He Shunhao , Guan Mengdan , Chen Yaqi , Lu Gang
Published: November 2021

Surface plasmon can trigger or accelerate many photochemical reactions, especially useful in energy and environmental industries. Recently, molecular adsorption has proven effective in modulating plasmon‐mediated photochemistry, however the realized chemical reactions are limited and the underlying mechanism is still unclear. Herein, by using in situ dark‐field optical microscopy, the plasmon‐mediated oxidative etching of silver nanoparticles (Ag NPs), a typical hot‐hole‐driven reaction, is monitored continuously and quantitatively. The presence of thiol or thiophenol molecules is found essential in the silver oxidation. In addition, the rate of silver oxidation is modulated by the choice of different thiol or thiophenol molecules. Compared with the molecules having electron donating groups, the ones having electron accepting groups accelerate the silver oxidation dramatically. The thiol/thiophenol modulation is attributed to the modulation of the charge separation between the Ag NPs and the adsorbed thiol or thiophenol molecules. This work demonstrates the great potential of molecular adsorption in modulating the plasmon‐mediated photochemistry, which will pave a new way for developing highly efficient plasmonic photocatalysts.
What type of carrier bag has the lowest environmental impact? Introduction to plastics in an everyday context
Authors: Kirschner Marlena , Heimann Rebekka
Published: November 2021

In diesem Beitrag wird ein Konzept vorgestellt, das der Einführung der Kunststoffe in der Sekundarstufe I dienen soll. Eigenschaften, Herstellung und Recycling von Kunststoffen werden im Rahmen eines Stationenlernens erarbeitet. Am Ende soll deutlich werden, dass die Frage nach dem umweltfreundlichsten Einkaufsbeutel nicht eindeutig zu beantworten ist, sondern auch unser konkretes Nutzungsverhalten entscheidend ist.
Thin Loewner Carpets and Their Quasisymmetric Embeddings in S2
Authors: Cheeger Jeff , Eriksson‐Bique Sylvester
Published: November 2021

A carpet is a metric space that is homeomorphic to the standard Sierpiński carpet in , or equivalently, in S2. A carpet is called thin if its Hausdorff dimension is . A metric space is called Q‐Loewner if its Q‐dimensional Hausdorff measure is Q‐Ahlfors regular and if it satisfies a ‐Poincaré inequality. As we will show, Q‐Loewner planar metric spaces are always carpets, and admit quasisymmetric embeddings into the plane.

In this paper, for every pair , with , we construct infinitely many pairwise quasisymmetrically distinct Q‐Loewner carpets X that admit explicit snowflake embeddings, , for which the image f(X) admits an explicit description and is ‐Ahlfors regular. In particular, these f are quasisymmetric embeddings. By a result of Tyson, the Hausdorff dimension of a Loewner space cannot be lowered by a quasisymmetric homeomorphism. By definition, this means that the carpets X and f(X) realize their conformal dimension. Each of images f(X) can be further uniformized via post composition with a quasisymmetric homeomorphism of S2, so as to yield a circle carpet and also a square carpet.

Our Loewner carpets X are constructed via what we call an admissible quotiented inverse system. This mechanism extends the inverse limit construction for PI spaces given in [25], which, however, does not yield carpets. Loewner spaces are a particular subclass of PI spaces. They have strong rigidity properties that do not hold for PI spaces in general.

In many cases the construction of the carpets and their snowflake embeddings, f, can also be described in terms of substitution rules. The statement above concerning is already a consequence of these examples. The images of these snowflake embeddings can be de‐snowflaked using a deformation by a strong weight, which multiplies the metric infinitesimally by a conformal factor of the form . Consequently, our examples also yield new examples of strong ‐weights for which the associated metrics admit no bi‐Lipschitz embeddings into Banach spaces with the Radon‐Nikodym property such as , for and . © 2021 Wiley Periodicals LLC.
The Effect of Oral Letermovir Administration on the Pharmacokinetics of a Single Oral Dose of P‐Glycoprotein Substrate Digoxin in Healthy Volunteers
Authors: Scheuenpflug Jürgen , Kropeit Dirk , Erb‐Zohar Katharina , Theis Jochen G.W. , Stobernack Hans‐Peter , McCormick David , Zimmermann Holger , Rübsamen‐Schaeff Helga
Published: November 2021

Letermovir is a human cytomegalovirus (CMV) terminase inhibitor approved in the United States, Canada, Japan, and the European Union for prophylaxis of CMV infection and disease in CMV‐seropositive, allogeneic, hematopoietic stem‐cell transplant recipients. In vitro, letermovir is a substrate and potential modulator of P‐glycoprotein. The potential of letermovir to alter the pharmacokinetics of digoxin (a P‐glycoprotein substrate) upon coadministration in healthy subjects was therefore investigated in a phase 1 trial (EudraCT: 2011‐004516‐39). Oral letermovir 240 mg was administered twice daily for 12 days with a single oral digoxin 0.5‐mg dose on day 7; after a washout period, oral digoxin 0.5 mg was administered on day 35 (sequence 1). The period order was reversed after a 28‐day washout for sequence 2. Pharmacokinetics and safety were evaluated. The presence of steady‐state letermovir reduced digoxin area under the plasma concentration–time curve from administration until last quantifiable measurement by 12% and maximum plasma concentration by 22% compared with digoxin alone; digoxin half‐life and elimination rate remained similar in both conditions. The between‐subject variability of digoxin maximum plasma concentration was higher with letermovir than without (42% vs 31%) and similar for digoxin area under the plasma concentration–time curve in both periods. No specific safety or tolerability concerns were identified. Overall, letermovir had no clinically relevant effect on concomitant administration with digoxin.
Software to Visualize Proteins and Perform Structural Alignments
Authors: Barber Robert D.
Published: November 2021

Availability of protein structural data is accelerating at an astounding rate, facilitating in silico biochemical and biophysical analyses that require visualization methods. In particular, increased accessibility of representatives within respective protein families is empowering investigators to perform structural model comparisons that provide both functional and evolutionary insights at much more refined levels than previously possible. Numerous software platforms, including several free and open source versions, are available for users to interrogate protein structural models. In this article, three structural alignment protocols are described using freely available software to investigate aspects of protein structure evolution at quaternary, tertiary, and domain levels, respectively. Mapping distinct subunit interfaces and active site positioning within the PfpI/DJ‐1 protein superfamily reveals quaternary structure that can have a prominent role in determination of distinct enzyme activities. In contrast, cytochrome c proteins are under strong evolutionary constraints due to their critical role in energy generation, and as a result, structural conservation is observed. However, substitutions within these conserved folds occur in distinct species, presumably to influence interactions with protein complexes involved in electron transport. Lastly, evolution of distinct allosteric mechanisms within winged helix‐turn‐helix transcriptional regulators, as well as protein dynamics, are revealed through visualization of metal‐ and redox‐responsive DNA‐binding proteins. The software platforms used in these protocols are Swiss‐PDBViewer and PyMOL. Swiss‐PDBViewer is an easy to implement, end‐user software that is excellent for entry into protein visualization methods. PyMOL is also easy to implement, but offers greater depth for advanced investigations and visualizations, as well as the ability to capture protein structure conformational changes. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Exploring quaternary structure evolution with Swiss‐PDBViewer

Alternate Protocol: Exploring tertiary structure evolution with Swiss‐PDBViewer

Basic Protocol 2: Visualizing allostery using PyMOL
The influence of corporate social responsibility on students' emotional appeal in the HEIs: The mediating effect of reputation and corporate image
Authors: Aledo‐Ruiz María Dolores , Martínez‐Caro Eva , Santos‐Jaén José Manuel
Published: November 2021

The purpose of this paper is to study the influence of corporate social responsibility (CSR) over higher education institutions' (HEIs) students' emotional appeal and the effect of two mediating variables, corporate image, and reputation. A sample of 211 students surveyed was obtained, and the study was conducted using partial least squares path modeling (PLS‐SEM) technique. The results showed that emotional appeal is influenced by corporate reputation, corporate image, and CSR practices. These effects are not only direct and positive but significant indirect effects are also obtained, which allow the positive effects of CSR to be heightened. This paper contributes to the literature on CSR considering mediating effects of corporative image and reputation in the relationship between CSR and emotional appeal. The findings provide important implications for theory and practice, indicating consistent strategies for competitive advantage in HEIs by achieving stakeholder engagement and new lines of research in terms of emotional marketing.
Monitoring Molecular Weight Changes during Technical Lignin Depolymerization by Operando Attenuated Total Reflectance Infrared Spectroscopy and Chemometrics
Authors: Khalili Khaled N. M. , de Peinder Peter , Donkers Jacqueline , Gosselink Richard J. A. , Bruijnincx Pieter C. A. , Weckhuysen Bert M.
Published: November 2021

Technical lignins are increasingly available at industrial scale, offering opportunities for valorization, such as by (partial) depolymerization. Any downstream lignin application requires careful tailoring of structural properties, such as molecular weight or functional group density, properties that are difficult to control or predict given the structure variability and recalcitrance of technical lignins. Online insight into changes in molecular weight (Mw), to gauge the extent of lignin depolymerization and repolymerization, would be highly desired to improve such control, but cannot be readily provided by the standard ex‐situ techniques, such as size exclusion chromatography (SEC). Herein, operando attenuated total reflectance infrared (ATR‐IR) spectroscopy combined with chemometrics provided temporal changes in Mw during lignin depolymerization with high resolution. More specifically, ex‐situ SEC‐derived Mw and polydispersity data of kraft lignin subjected to aqueous phase reforming conditions could be well correlated with ATR‐IR spectra of the reaction mixture as a function of time. The developed method showed excellent regression results and relative error, comparable to the standard SEC method. The method developed has the potential to be translated to other lignin depolymerization processes.
COVID‐19: Using high‐throughput flow cytometry to dissect clinical heterogeneity
Authors: del Molino del Barrio Irene , Hayday Thomas S. , Laing Adam G. , Hayday Adrian C. , Di Rosa Francesca
Published: November 2021

Here we consider how high‐content flow cytometric methodology at appropriate scale and throughput rapidly provided meaningful biological data in our recent studies of COVID‐19, which we discuss in the context of other similar investigations. In our work, high‐throughput flow cytometry was instrumental to identify a consensus immune signature in COVID‐19 patients, and to investigate the impact of SARS‐CoV‐2 exposure on patients with either solid or hematological cancers. We provide here some examples of our ‘holistic’ approach, in which flow cytometry data generated by lymphocyte and myelomonocyte panels were integrated with other analytical metrics, including SARS‐CoV‐2‐specific serum antibody titers, plasma cytokine/chemokine levels, and in‐depth clinical annotation. We report how selective differences between T cell subsets were revealed by a newly described flow cytometric TDS assay to distinguish actively cycling T cells in the peripheral blood. By such approaches, our and others' high‐content flow cytometry studies collectively identified overt abnormalities and subtle but critical changes that discriminate the immuno‐signature of COVID‐19 patients from those of healthy donors and patients with non‐COVID respiratory infections. Thereby, these studies offered several meaningful biomarkers of COVID‐19 severity that have the potential to improve the management of patients and of hospital resources. In sum, flow cytometry provides an important means for rapidly obtaining data that can guide clinical decision‐making without requiring highly expensive, sophisticated equipment, and/or “‐omics” capabilities. We consider how this approach might be further developed.
Detection of testosterone microdosing in healthy females
Authors: Savkovic Sasha , Ly Lam P. , Desai Reena , Howa John , Nair Vinod , Eichner Daniel , Handelsman David J.
Published: November 2021

The ready detectability of synthetic androgens by mass spectrometry (MS)‐based antidoping tests has reoriented androgen doping to using testosterone (T), which must be distinguished from its endogenous counterpart making detection of exogenous T harder. We investigated urine and serum steroid and hematological profiling individually and combined to determine the optimal detection model for T administration in women. Twelve healthy females provided six paired blood and urine samples over 2 weeks prior to treatment consisting of 12.5‐mg T in a topical transdermal gel applied daily for 7 days. Paired blood and urine samples were then obtained at the end of treatment and Days 1, 2, 4, 7, and 14 days later. Compliance with treatment and sampling was high, and no adverse effects were reported. T treatment significantly increased serum and urine T, serum dihydrotestosterone (DHT), urine 5α‐androstane‐3α,17β‐diol (5α‐diol) epitestosterone (E), and urine T/E ratio with a brief window of detection (2–4 days) as well as total and immature (medium and high fluorescence) reticulocytes that remained elevated over the full 14 posttreatment days. Carbon isotope ratio MS and the OFF score and Abnormal Blood Profile score (ABPS) were not discriminatory. The optimal multivariate model to identify T exposure combined serum T, urine T/E ratio with three hematological variables (% high fluorescence reticulocytes, mean corpuscular hemoglobin, and volume) with the five variables providing 93% correct classification (4% false positive, 10% false negatives). Hence, combining select serum and urine steroid MS variables with reticulocyte measures can achieve a high but imperfect detection of T administration to healthy females.
Eligibility of patients with heart failure with preserved ejection fraction for sacubitril/valsartan according to the PARAGON‐HF trial
Authors: Lund Lars H. , Savarese Gianluigi , Venkateshvaran Ashwin , Benson Lina , Lundberg Anna , Donal Erwan , Daubert Jean‐Claude , Oger Emmanuel , Linde Cecilia , Hage Camilla
Published: November 2021

Aims

In the heart failure (HF) with preserved ejection fraction (HFpEF) PARAGON‐HF trial, sacubitril/valsartan vs. valsartan improved mortality/morbidity in patients with left ventricular ejection fraction (LVEF) below median (57%). We assessed eligibility for sacubitril/valsartan based on four scenarios.

Methods and results

Eligibility was assessed in the Karolinska‐Rennes study (acute HFpEF, LVEF ≥ 45%, and N‐terminal pro‐B‐type natriuretic peptide ≥300 pg/mL subsequently assessed as outpatients including echocardiography) in (i) a trial scenario (all trial criteria); (ii) a pragmatic scenario (selected trial criteria); (iii) LVEF below lower limit of normal range (<54% in women and <52% in men); and (iv) LVEF below mean of normal range (<64% in women and <62% in men). Among 425 patients [age 78 (72–83) years, 57% women, 28% LVEF ≤ 57% (median in PARAGON‐HF), the trial scenario, identified 34% as eligible. Left atrial enlargement and/or left ventricular hypertrophy were present in 99%. Inclusion criteria not met were diuretic treatment and New York Heart Association class. Important exclusion criteria were estimated glomerular filtration rate <30 mL/min/1.73 m2, haemoglobin <10 g/day, and cancer. In the pragmatic scenario, 63% were eligible. In LVEF below lower limit of normal range, 5.4% were eligible, and in LVEF below mean of normal range, 41% were eligible. In patients with LVEF ≤ 57%, eligibility was 42%, 69%, 21%, and 91% according to the trial scenario, pragmatic scenario, LVEF below lower limit of normal range, and LVEF below mean of normal range, respectively.

Conclusions

In real‐world HFpEF (LVEF ≥ 45%) with N‐terminal pro‐B‐type natriuretic peptide and cardiac structure/function assessed, eligibility for sacubitril/valsartan was according to PARAGON‐HF complete criteria 34%, pragmatic criteria 63%, LVEF below lower limit of normal range 5.4%, and LVEF below mean of normal range 41%. Cardiac structural impairment was almost ubiquitous. Ineligibility was more due to exclusion criteria than failing to meet inclusion criteria.
Long‐term impact of β‐blocker in elderly patients without myocardial infarction after percutaneous coronary intervention
Authors: Fukase Tatsuya , Dohi Tomotaka , Koike Takuma , Yasuda Hidetoshi , Takeuchi Mitsuhiro , Takahashi Norihito , Chikata Yuichi , Endo Hirohisa , Doi Shinichiro , Nishiyama Hiroki , Okai Iwao , Iwata Hiroshi , Okazaki Shinya , Miyauchi Katsumi , Daida Hiroyuki , Minamino Tohru
Published: November 2021

Aims

Little is known about the long‐term outcomes of β‐blockers use in patients with coronary artery disease (CAD) without myocardial infarction (MI) and reduced ejection fraction (rEF). However, more attention should be paid to the oral administration of β‐blockers in elderly patients who are susceptible to heart failure (HF), sinus node dysfunction, or rate response insufficiency. We aimed to evaluate the long‐term impact of β‐blockers in elderly patients with CAD without MI or systolic HF who have undergone percutaneous coronary intervention.

Methods and results

A total of 1018 consecutive elderly patients with CAD (mean age, 72 ± 7 years; 77% men) who underwent their first intervention between 2010 and 2018 were included in this study. According to the presence or absence of the use of β‐blockers, 514 patients (50.5%) were allocated to the β‐blocker group, and 504 (49.5%) to the non‐β‐blocker group. We evaluated the incidence of 4‐point major adverse cardiovascular events (4P‐MACE), including cardiovascular death, non‐fatal MI, non‐fatal stroke, admission for HF, target vessel revascularization (TVR), and all‐cause death. We focused on the association between chronotropic incompetence of β‐blockers and incidence of a new HF and analysed the results using an exercise electrocardiogram regularly performed in the outpatient department after percutaneous coronary intervention. During a median follow‐up duration of 5.1 years, 83 patients (8.3%) developed 4P‐MACE, including cardiovascular death in 17, non‐fatal MI in 13, non‐fatal stroke in 25, and admission for HF in 39 patients. Additionally, 124 patients (12.2%) had a TVR and 104 (10.2%) died of other causes. Kaplan–Meier analysis showed that the cumulative incidence rate of 4P‐MACE in the β‐blocker group was significantly higher than that in the non‐β‐blocker group (15.4% vs. 10.0%, log‐rank test, P = 0.015). Above all, the cumulative incidence rate of admission for HF in the β‐blocker group was significantly higher (8.8% vs. 3.2%, log‐rank test, P < 0.001). The β‐blocker group had significantly lower resting heart rate, stress heart rate, and stress‐rest Δ heart rate on exercise electrocardiogram. Multivariate Cox hazard analysis revealed that EF, β‐blocker use, stress‐rest Δ heart rate, and CKD were strong independent predictors of admission for HF.

Conclusions

Long‐term β‐blocker use was significantly associated with an increased risk of adverse cardiovascular events in elderly patients with CAD without MI or systolic HF. In particular, the chronotropic incompetence action of β‐blockers could increase the risk of admission for HF in elderly patients with CAD without MI and systolic HF, and the present findings warrant further investigation.
Copper‐Catalyzed Cascade N‐Dealkylation/N‐Methyl Oxidation of Aromatic Amines by Using TEMPO and Oxygen as Oxidants
Authors: Wang Shihaozhi , Yang Jiale , Li Dianjun , Yang Jinhui
Published: November 2021

A novel tandem N‐dealkylation and N‐methyl aerobic oxidation of tertiary aromatic amines to N‐arylformamides using copper and TEMPO has been developed. This methodology suggested an alternative synthetic route from N‐methylarylamines to N‐arylformamides.
Shared functional connections within and between cortical networks predict cognitive abilities in adult males and females
Authors: Dhamala Elvisha , Jamison Keith W. , Jaywant Abhishek , Kuceyeski Amy
Published: November 2021

A thorough understanding of sex‐independent and sex‐specific neurobiological features that underlie cognitive abilities in healthy individuals is essential for the study of neurological illnesses in which males and females differentially experience and exhibit cognitive impairment. Here, we evaluate sex‐independent and sex‐specific relationships between functional connectivity and individual cognitive abilities in 392 healthy young adults (196 males) from the Human Connectome Project. First, we establish that sex‐independent models comparably predict crystallised abilities in males and females, but only successfully predict fluid abilities in males. Second, we demonstrate sex‐specific models comparably predict crystallised abilities within and between sexes, and generally fail to predict fluid abilities in either sex. Third, we reveal that largely overlapping connections between visual, dorsal attention, ventral attention, and temporal parietal networks are associated with better performance on crystallised and fluid cognitive tests in males and females, while connections within visual, somatomotor, and temporal parietal networks are associated with poorer performance. Together, our findings suggest that shared neurobiological features of the functional connectome underlie crystallised and fluid abilities across the sexes.
The expression pattern of β‐carotene ketolase gene restricts the accumulation of astaxanthin in Dunaliella under salt stress
Authors: Chen Hao‐Hong , He Yu‐Jing , Liang Ming‐Hua , Yan Bing , Jiang Jian‐Guo
Published: November 2021

Dunaliella salina can accumulate a large amount of β‐carotene which is generally considered to be its terminal product of carotenoid metabolism. In this study, it was proved that D. salina has the ketolase (DsBKT) of catalyzing the synthesis of astaxanthin, the downstream products of β‐carotene. Therefore, the reason why D. salina does not synthesize astaxanthin is the purpose of this study. The enzymatic activity of DsBKT was detected by functional complementation assays in Escherichia coli, results showed that DsBKT had efficient ketolase activity toward β‐carotene and zeaxanthin to produce astaxanthin, indicating that there were complete astaxanthin‐producing genes in Dunaliella. Unlike the induced expression of Lycopene cyclase (catalyzing β‐carotene synthesis) under salt stress, the expression of DsBKT was very low under both normal and stress conditions, which may be the main reason why D. salina cannot accumulate astaxanthin. On the contrary, with the astaxanthin‐rich Haematococcus pluvialis as a control, its BKT gene was significantly upregulated under salt stress. Further study showed that DsBKT promoter had strong promoter ability and could stably drive the expression of ble‐egfp in D. salina. Obviously, DsBKT promoter is not the reason of DsBKT not being expressed which may be caused by Noncoding RNA.
MyD88 deficiency ameliorates weight loss caused by intestinal oxidative injury in an autophagy‐dependent mechanism
Authors: Qi Ming , Liao Simeng , Wang Jing , Deng Yuankun , Zha Andong , Shao Yirui , Cui Zhijuan , Song Tongxing , Tang Yulong , Tan Bie , Yin Yulong
Published: November 2021

Background

Gut health plays a vital role in the overall health and disease control of human and animals. Intestinal oxidative stress is a critical player in the induction and progression of cachexia which is conventionally diagnosed and classified by weight loss. Therefore, reduction of intestinal oxidative injury is a common and highly effective strategy for the maintenance of human and animal health. Here we identify intestinal myeloid differentiation primary response gene 88 (MyD88) as a novel target for intestinal oxidative stress using canonical oxidative stress model induced by paraquat (PQ) in vitro and in vivo.

Methods

Intestinal oxidative stress was induced by administration of PQ in intestinal epithelial cells (IECs) and mouse model. Cell proliferation, apoptosis, DNA damage, mitochondrial function, oxidative status, and autophagy process were measured in wild‐type and MyD88‐deficient IECs during PQ exposure. Autophagy inhibitor (3‐methyladenine) and activator (rapamycin) were employed to assess the role of autophagy in MyD88‐deficient IECs during PQ exposure. MyD88 specific inhibitor, ST2825, was used to verify function of MyD88 during PQ exposure in mouse model.

Results

MyD88 protein levels and apoptotic rate of IECs are increased in response to PQ exposure (P < 0.001). Intestinal deletion of MyD88 blocks PQ‐induced apoptosis (~42% reduction) and DNA damage (~86% reduction), and improves mitochondrial fission (~37% reduction) and function including mitochondrial membrane potential (~23% increment) and respiratory metabolism capacity (~26% increment) (P < 0.01). Notably, there is a marked decrease in reactive oxygen species in MyD88‐deficient IECs during PQ exposure (~70% reduction), which are consistent with high activity of antioxidative enzymes (~83% increment) (P < 0.001). Intestinal ablation of MyD88 inhibits mTOR signalling, and further phosphorylates p53 proteins during PQ exposure, which eventually promotes intestinal autophagy (~74% increment) (P < 0.01). Activation of autophagy (rapamycin) promotes IECs growth as compared with 3‐methyladenine‐treatment during PQ exposure (~173% increment), while inhibition of autophagy (3‐methyladenine) exacerbates oxidative stress in MyD88‐deficient IECs (P < 0.001). In mouse model, inhibition of MyD88 using specific inhibitor ST2825 followed by PQ treatment effectively ameliorates weight loss (~4% increment), decreased food intake (~92% increment), gastrocnemius and soleus loss (~24% and ~20% increment, respectively), and intestinal oxidative stress in an autophagy dependent manner (P < 0.01).

Conclusions

MyD88 modulates intestinal oxidative stress in an autophagy‐dependent mechanism, which suggests that reducing MyD88 level may constitute a putative therapeutic target for intestinal oxidative injury‐induced weight loss.
circRNAome profiling reveals circFgfr2 regulates myogenesis and muscle regeneration via a feedback loop
Authors: Yan Junyu , Yang Yalan , Fan Xinhao , Liang Guoming , Wang Zishuai , Li Jiju , Wang Liyuan , Chen Yun , Adetula Adeyinka Abiola , Tang Yijie , Li Kui , Wang Dazhi , Tang Zhonglin
Published: November 2021

Background

Circular RNAs (circRNAs) represent a novel class of non‐coding RNAs formed by a covalently closed loop and play crucial roles in many biological processes. Several circRNAs associated with myogenesis have been reported. However, the dynamic expression, function, and mechanism of circRNAs during myogenesis and skeletal muscle development are largely unknown.

Methods

Strand‐specific RNA‐sequencing (RNA‐seq) and microarray datasets were used to profile the dynamic circRNAome landscape during skeletal muscle development and myogenic differentiation. Bioinformatics analyses were used to characterize the circRNAome and identify candidate circRNAs associated with myogenesis. Bulk and single‐cell RNA‐seq were performed to identify the downstream genes and pathways of circFgfr2. The primary myoblast cells, C2C12 cells, and animal model were used to assess the function and mechanism of circFgfr2 in myogenesis and muscle regeneration in vitro or in vivo by RT‐qPCR, western blotting, dual‐luciferase activity assay, RNA immunoprecipitation, RNA fluorescence in situ hybridization, and chromatin immunoprecipitation.

Results

We profiled the dynamic circRNAome in pig skeletal muscle across 27 developmental stages and detected 52 918 high‐confidence circRNAs. A total of 2916 of these circRNAs are conserved across human, mouse, and pig, including four circRNAs (circFgfr2, circQrich1, circMettl9, and circCamta1) that were differentially expressed (|log2 fold change| > 1 and adjusted P value < 0.05) in various myogenesis systems. We further focused on a conserved circRNA produced from the fibroblast growth factor receptor 2 (Fgfr2) gene, termed circFgfr2, which was found to inhibit myoblast proliferation and promote differentiation and skeletal muscle regeneration. Mechanistically, circFgfr2 acted as a sponge for miR‐133 to regulate the mitogen‐activated protein kinase kinase kinase 20 (Map3k20) gene and JNK/MAPK pathway. Importantly, transcription factor Kruppel like factor 4 (Klf4), the downstream target of the JNK/MAPK pathway, directly bound to the promoter of circFgfr2 and affected its expression via an miR‐133/Map3k20/JNK/Klf4 auto‐regulatory feedback loop. RNA binding protein G3BP stress granule assembly factor 1 (G3bp1) inhibited the biogenesis of circFgfr2.

Conclusions

The present study provides a comprehensive circRNA resource for skeletal muscle study. The functional and mechanistic analysis of circFgfr2 uncovered a circRNA‐mediated auto‐regulatory feedback loop regulating myogenesis and muscle regeneration, which provides new insight to further understand the regulatory mechanism of circRNAs.
Do universal adhesives provide the benefits from double‐application or an extra bonding layer in composite repair?
Authors: Karadas Muhammet
Published: November 2021

This study aimed to determine whether the application of extra hydrophobic resin (EHR) or double layer (DL) improves microtensile bond strength (μTBS) of two universal adhesives to composite resin. Composite blocks were fabricated and exposed to thermal cycles. The specimens were horizontally sectioned into two halves. Scotch Bond Universal (SBU) and Clearfil S3 Bond Universal (CSBU) were applied to the ground composite surface according to the manufacturers' instructions, or with DL application or EHR application. The repair composite was incrementally placed to bonded planes. Composite sticks were achieved and tensed with a universal testing machine, followed by examining the fracture surfaces by a scanning electron microscope. Data were evaluated by Weibull analysis (shape and scale [σθ and σ0.10] parameters) using the maximum likelihood method. The σθ and σ0.10, respectively, estimate strength at 63.2 and 10% probability of failure. Shape parameter values showed significant differences among treatments. DL application of CSBU did not affect μTBS values at σθ of failure but caused to decrease μTBS values at σ0.10 of failure. DL application of SBU reduced μTBS values at σθ of failure. DL or EHR coating did not improve μTBS of SBU. EHR application increased μTBS of CSBU, whereas DL application did not benefit.