bluuebunny/crossref_metadata_2025 huggingface dataset:
The “Yin and Yang” of Immunomodulatory Magnesium‐Enriched Graphene Oxide Nanoscrolls Decorated Biomimetic Scaffolds in Promoting Bone Regeneration
Authors: Zheng Zhiwei , Chen Yahong , Hong Hao , Shen Yi , Wang Yun , Sun Jian , Wang Xiansong
Published: November 2020

Tissue regeneration driven by immunomodulatory agents has emerged as a potential solution for repairing bone defects. However, the therapeutic benefits are compromised by disturbances in the pro‐ and anti‐inflammatory balance. Here, using magnesium nanoparticles (MgNPs) as a template, magnesium‐enriched graphene oxide nanoscrolls (MgNPs@GNSs) designed for combinational modulation of the inflammatory response are reported. First, the different effects of graphene oxide (GO) and magnesium ions (Mg2+) on Raw264.7 macrophage phenotype transformation are screened. The results reveal that GO activates inflammatory M1 macrophages, and that Mg2+ facilitates repolarization of M1 macrophages to the pro‐healing M2 phenotype. With sustained release of Mg2+, the MgNPs@GNS nanoplatform can orchestrate harmonious type 1 and type 2 inflammatory responses. Mg2+ decrease the internalization of GO and downregulate the nuclear factor kappa‐B pathway, which is profoundly involved in the inflammatory process. A series of experiments show that the ordered inflammatory response induced by MgNPs@GNSs stimulates in vitro angiogenesis and osteogenesis through chemotactic, mitogenic, and morphogenic actions. Obvious vascularized bone regeneration is achieved in a rat cranial bone defect model via MgNPs@GNS deposited decellularized bone matrix scaffold. Therefore, the potential of using inherently therapeutic nanomedicine to modulate biomaterial‐induced immune responses and thus enhance bone regeneration is demonstrated.
Neuromorphic Engineering: From Biological to Spike‐Based Hardware Nervous Systems
Authors: Yang Jia‐Qin , Wang Ruopeng , Ren Yi , Mao Jing‐Yu , Wang Zhan‐Peng , Zhou Ye , Han Su‐Ting
Published: November 2020

The human brain is a sophisticated, high‐performance biocomputer that processes multiple complex tasks in parallel with high efficiency and remarkably low power consumption. Scientists have long been pursuing an artificial intelligence (AI) that can rival the human brain. Spiking neural networks based on neuromorphic computing platforms simulate the architecture and information processing of the intelligent brain, providing new insights for building AIs. The rapid development of materials engineering, device physics, chip integration, and neuroscience has led to exciting progress in neuromorphic computing with the goal of overcoming the von Neumann bottleneck. Herein, fundamental knowledge related to the structures and working principles of neurons and synapses of the biological nervous system is reviewed. An overview is then provided on the development of neuromorphic hardware systems, from artificial synapses and neurons to spike‐based neuromorphic computing platforms. It is hoped that this review will shed new light on the evolution of brain‐like computing.
Recent Advances in the Application of Structural‐Phase Engineering Strategies in Electrochemical Nitrogen Reduction Reaction
Authors: Li Haonan , Huang Chengde
Published: November 2020

Ammonia (NH3) exists as an important chemical raw material in the chemical industry and national economy of all countries in the world. The widely used Haber–Bosch ammonia synthesis process not only requires a large amount of highly purified hydrogen, but also is inseparable from high‐temperature and high‐pressure reaction conditions, resulting in numerous problems that cannot be fundamentally solved in terms of safety, efficiency, cost, etc. It is considered to be an alternative technology with great potential to achieve the synthesis of ammonia under normal temperature and pressure making use of electrochemical nitrogen reduction reaction (NRR), which utilizes water in aqueous solution systems in replacement of hydrogen as hydrogen source. This paper succinctly explains the basic mechanism for electrocatalytic ammonia synthesis from the reduction of nitrogen in aqueous solution systems. Based on the research progress in the past year, the principles and related researches of constructing electrocatalysts of NRR using five structural‐phase strategies including defect engineering, interface engineering, strain engineering, atomic ordering engineering, and single‐atom engineering are reviewed. Finally, this paper provides an outlook to the future research and application.
Laser‐Induced Graphene Piezoresistive Sensors Synthesized Directly on Cork Insoles for Gait Analysis
Authors: Carvalho Alexandre F. , Fernandes António J. S. , Martins Rodrigo , Fortunato Elvira , Costa Florinda M.
Published: November 2020

Monitorization of gait‐related parameters is of the utmost importance to prevent complications in several diseases, ensuring affordable healthcare for the growing amount of chronic, lifestyle‐related diseases and also for improving motion performance. Sensorized insoles allow to both pressure data and gait timings to be extracted non‐intrusively in a point of care paradigm. Laser‐induced graphene (LIG) offers a path to the integration of sensors in different kinds of materials, including cork, a common insole material. In this work, piezoresistive sensors are developed by providing conductivity to natural cork and agglomerate cork through the direct synthesis of LIG by UV irradiation. Highly isotropic conductive LIG regions with less than 100 Ω sq−1 are patterned and their piezoresistive response for up to 1132 kPa is assessed with sensitivities up to 0.02 kPa−1. A low‐cost prototype insole is devised and tested, proving the potential of this kind of functional cork as a green alternative for gait analysis platforms.
Accurate Efficiency Measurements of Organic Light‐Emitting Diodes via Angle‐Resolved Spectroscopy
Authors: Archer Emily , Hillebrandt Sabina , Keum Changmin , Murawski Caroline , Murawski Jan , Tenopala‐Carmona Francisco , Gather Malte C.
Published: November 2020

The accurate characterization of thin‐film light emitting diodes (LEDs)—including organic light emitting diodes (OLEDs), perovskite LEDs, and quantum dot LEDs—is crucial to the understanding of the factors that influence their efficiency and thus to the fabrication of LEDs with improved performance and stability. In addition, detailed information about the angular characteristics of LED emission is useful to assess the suitability of individual architectures, e.g., for display applications. Here, the implementation of a goniometer‐based measurement system and corresponding protocol are described that allow to accurately determine the current–voltage–luminance characteristics, external quantum efficiency, and luminous efficacy of OLEDs and other emerging thin‐film LEDs. The system allows recording of angle‐resolved electroluminescence spectra and accurate efficiency measurements for devices with both Lambertian and non‐Lambertian emission characteristics. A detailed description of the setup and a protocol for assembling and aligning the required hardware are provided. Drawings of all custom parts and the open‐source Python software required to perform the measurement and to analyze the data are included.
A Ho3+‐Based Luminescent Thermometer for Sensitive Sensing over a Wide Temperature Range
Authors: van Swieten Thomas P. , Yu Dechao , Yu Ting , Vonk Sander J. W. , Suta Markus , Zhang Qinyuan , Meijerink Andries , Rabouw Freddy T.
Published: November 2020

Luminescence thermometry is used in a variety of research fields for noninvasive temperature sensing. Lanthanide‐doped micro‐/nanocrystals are exceptionally suitable for this. The popular concept of luminescence‐intensity‐ratio thermometry is based on emission from thermally coupled levels in a single lanthanide ion, following Boltzmann's law. These thermometers can measure temperature with low uncertainty, but only in a limited temperature range. In this work, a Ho3+‐based thermometer is presented and quantitatively modeled with sustained low temperature uncertainty from room temperature up to 873 K. The thermometer shows bright green and red luminescence with a strong and opposite dependence on temperature and Ho3+concentration. This is the result of temperature‐dependent competition between multi‐phonon relaxation and energy transfer, feeding the green‐ and red‐emitting levels, respectively, following excitation with blue light. This simple and quantitative model of this competition predicts the output spectrum over a wide range of temperatures (300–873 K) and Ho3+concentrations (0.1–30%). The optimum Ho3+concentration can thus be determined for reliable measurements over any temperature range of interest. Quantitative modeling as presented here is crucial to optimally benefit from the potential of energy‐transfer thermometers to achieve low measurement uncertainties over a wide temperature range.
Fully Printed Flexible Heat Flow Sensors and their Utilization toward Heat Generation Monitoring for People and Machineries
Authors: Suemori Kouji , Nobeshima Taiki , Uemura Sei
Published: November 2020

A flexible and highly sensitive heat flow sensor, which can be attached to the human body and to various types of machinery for measuring their heat generation, is an ideal device for monitoring human health and the operational conditions of machinery. These sensors may be of great value for the implementation of sophisticated cyber physical systems. However, the fabrication of flexible and highly sensitive heat flow sensors is challenging because it is difficult to fabricate efficient heat–voltage conversion materials on flexible film substrates. In this study, a fully printed flexible heat flow sensor with high sensitivity is examined, which allows the detection of minute quantities of heat flow with the magnitude of several tens of milliwatts. The sensor features a device structure, wherein thermoelectric layers comprising carbon nanotube and polymethyl methacrylate coating are placed on the top and bottom surfaces of the flexible substrate and are connected by through‐holes. Due to the resultant flexibility and high sensitivity, the sensor can be attached to a human arm and detect the heat emanating from it. Additionally, it is demonstrated that changes in the load of a machine under operation can be monitored by attaching the flexible heat flow sensor to the machine.
Metal Grid Structures for Enhancing the Stability and Performance of Solution‐Processed Organic Light‐Emitting Diodes
Authors: Burwell Gregory , Burridge Nicholas , Sandberg Oskar J. , Bond Eloise , Li Wei , Meredith Paul , Armin Ardalan
Published: November 2020

Transparent conducting electrodes (TCEs) are key components of optoelectronic devices where input or output light coupling are central functions—for example, solar cells, light‐emitting diodes, or displays. Indium tin oxide (ITO) has been the TCE of choice for over three decades, and there are few alternatives. The characteristic size of devices made with ITO is often limited to a few centimeters because of the intrinsic sheet resistance. This is an obstacle for scaling thin film photovoltaics and lighting platforms to technologically‐relevant large areas. In this article, the use of metallic micro‐grids is investigated to improve sheet resistance–visible transparency balance of TCEs, resulting in improved performance and stability of organic light‐emitting diodes (OLEDs). Finite element models are used to simulate OLEDs pixels on ITO with metal grids, and these simulations are supported by experimental performance analysis. The reduced potential drop from the presence of grids is shown to lower the Joule heating at the TCE resulting in higher power conversion efficiency and luminosity, as well as improved device stability. Such a strategy could be a very effective way of not only reducing indium usage but also opening new higher resistance TCEs to technological viability.
An Electronic Synapse Based on 2D Ferroelectric CuInP2S6
Authors: Li Bochang , Li Sifan , Wang Han , Chen Li , Liu Liang , Feng Xuewei , Li Yesheng , Chen Jingsheng , Gong X. , Ang Kah‐Wee
Published: November 2020

Memristors with biological synaptic behaviors and functions have been intensively studied as an important component for neuromorphic computing system, which hold promise to address the power consumption issue in modern computers based on von Neumann architecture. However, the resistive switching mechanism that relies on the stochastic formation of conductive filaments leads to poor cycle‐to‐cycle (temporal) and cell‐to‐cell (spatial) variations for filamentary memristors. The emergence of memristors based on 2D ferroelectric materials can potentially avoid these issues. Here, a vertical Au/CuInP2S6 (CIPS)/Ti diode is demonstrated using exfoliated ferroelectric CIPS flake. Through ferroelectric switching, the CIPS diode realizes resistive switching with a ratio larger than 6 × 103. The endurance measurement shows a small set and reset voltage variation of 5.3% and 9.1%, respectively. Key synaptic behaviors including spike‐time‐dependent plasticity, paired‐pulse‐facilitation, and paired‐pulse‐depression are successfully mimicked, manifesting the potential application of CIPS diode in a neuromorphic computing system. Moreover, pattern learning and memory behaviors are emulated using a 3 × 3 CIPS crossbar array.
The First Step towards a R2R Printing Foundry via a Complementary Design Rule in Physical Dimension for Fabricating Flexible 4‐Bit Code Generator
Authors: Park Hyejin , Sun Junfeng , Jung Younsu , Park Jinhwa , Maskey Bijendra Bishow , Shrestha Kiran , Koirala Gyan Raj , Parajuli Sajjan , Shrestha Sagar , Chung Ahnjung , Cho Gyoujin
Published: November 2020

Roll‐to‐roll (R2R) printed electronics have been considered as the holy grail for the low‐cost manufacturing of expendable and compliant electronic devices. However, a lapse exists in unlocking the full potential of R2R printed electronics in that there has yet to be a R2R foundry able to integrate complementary metal‐oxide‐semiconductor (CMOS) logic gates into such devices. Herein, a R2R printing foundry based on a complementary design rule of physical dimension in which the rheology of electronic inks, R2R printing speed, overlay printing registration accuracy and device design are complementary to one another is proposed. As a proof of concept of the complementary design rule, 44 single walled carbon nanotube‐based p‐type and n‐type thin film transistors are printed to integrate a CMOS ring oscillator, six CMOS NAND gates, and a CMOS OR gate for 4‐bit code generation through a R2R gravure printer. This low‐bit code generator fabricated via R2R printing illustrates is the first step in establishing R2R printing foundry for manufacturing logic gate‐based flexible devices.
Cold Sintered Metal–Ceramic Nanocomposites for High‐Frequency Inductors
Authors: Zhou Tingchuan , Liu Ying , Cao Peng , Du Jiao , Lin Zifeng , Wang Renquan , Jin Lichuan , Lian Lixian , Harris Vincent G.
Published: November 2020

Power electronics, including those inspired by 5G and 6G revolutions, have escalated the demand for miniaturized energy‐efficient inductor components with higher power density, higher operating frequencies, and smaller device sizes. Recently, cold sintering has proved to be a powerful tool for fabricating ceramics. Here, novel metal–ceramic nanocomposites are prepared by cold sintering for the first time. As a model system, Fe‐based nanocrytalline alloys with NiZn ferrites and α‐Fe2O3 ceramics are cold sintered at 150 °C under a uniaxial pressure of 320 MPa. These nanocomposites illustrate dense microstructures, fine grains, and high electrical resistivities, allowing remarkable high‐frequency performance, such as permeability values of ≈11.5 at frequencies up to ≈1 GHz with corresponding quality factors reaching over 100 at tens of megahertz. The power inductors using the developed composite materials demonstrate low DC resistance (18.35 mΩ), high efficiency (≈98.2%), and high current rating with small form factors far superior to those available as commercial products. The results presented here indicate a dramatic advance in the materials science and development of inductor composite materials for power electronics applications. This synthesis route of metal–ceramic composites shows great potential in fabrication of new composite materials that are targeted for functional components.
Field Effect versus Driving Force: Charge Generation in Small‐Molecule Organic Solar Cells
Authors: Nikolis Vasileios C. , Dong Yifan , Kublitski Jonas , Benduhn Johannes , Zheng Xijia , Huang Chengye , Yüzer A. Celil , Ince Mine , Spoltore Donato , Durrant James R. , Bakulin Artem A. , Vandewal Koen
Published: November 2020

Efficient charge generation in organic semiconductors usually requires an interface with an energetic gradient between an electron donor and an electron acceptor in order to dissociate the photogenerated excitons. However, single‐component organic solar cells based on chloroboron subnaphthalocyanine (SubNc) have been reported to provide considerable photocurrents despite the absence of an energy gradient at the interface with an acceptor. In this work, it is shown that this is not due to direct free carrier generation upon illumination of SubNc, but due to a field‐assisted exciton dissociation mechanism specific to the device configuration. Subsequently, the implications of this effect in bilayer organic solar cells with SubNc as the donor are demonstrated, showing that the external and internal quantum efficiencies in such cells are independent of the donor‐acceptor interface energetics. This previously unexplored mechanism results in efficient photocurrent generation even though the driving force is minimized and the open‐circuit voltage is maximized.
Atomically Dispersed Cobalt Trifunctional Electrocatalysts with Tailored Coordination Environment for Flexible Rechargeable Zn–Air Battery and Self‐Driven Water Splitting
Authors: Zhang Zheye , Zhao Xiaoxu , Xi Shibo , Zhang Lili , Chen Zhongxin , Zeng Zhiping , Huang Ming , Yang Hongbin , Liu Bin , Pennycook Stephen J. , Chen Peng
Published: November 2020

Designing multifunctional catalysts with high activity, stability, and low‐cost for energy storage and conversion is a significant challenge. Herein, a trifunctional electrocatalyst is synthesized by anchoring individually dispersed Co atoms on N and S codoped hollow carbon spheres (CoSA/N,S‐HCS), which exhibits outstanding catalytic activity and stability for the oxygen reduction reaction, oxygen evolution reaction, and hydrogen evolution reaction. When equipped in liquid or flexible solid‐state rechargeable Zn–air batteries, CoSA/N,S‐HCS endows them with high power and energy density as well as excellent long‐term cycling stability, outperforming benchmark batteries based on a commercial Pt/C + RuO2 dual catalyst system. Furthermore, a self‐driven water splitting system powered by flexible Zn–air batteries is demonstrated using CoSA/N,S‐HCS as the sole catalyst, giving a high H2 evolution rate of 184 mmol h−1. The state‐of‐art experimental characterizations and theoretical calculations reveal synergistic cooperation between atomically dispersed CoN4 active sites, nearby electron‐donating S dopants, and the unique carbon support to single‐atom catalysts (SACs). This work demonstrates a general strategy to design various multifunctional SAC systems with a tailored coordination environment.
The Underutilization of Community‐based Participatory Research in Psychology: A Systematic Review
Authors: Rodriguez Espinosa Patricia , Verney Steven P.
Published: November 2020

Traditional non‐participatory research methodologies have struggled to address the needs of multicultural populations in the United States (U.S.). Community‐based participatory research (CBPR) is a research paradigm offering a unique opportunity for culturally appropriate research and improving health equity. CBPR is an equitable, strength‐based approach involving all stakeholders throughout the research process. We investigate the field of psychology’s utilization of CBPR as an approach for working with multicultural populations to collaboratively address relevant and impactful research questions. A total of 1912 CBPR‐related articles, from 2004 to 2014, were identified using PsycINFO, PubMed, and CINAHL Complete databases. Of these, approximately 16% (n = 311) met our criteria for psychology‐related CBPR articles accounting for a negligible amount (<1%) of peer‐reviewed publications in mainstream psychological journals during the same time period. Among U.S. psychology‐related CBPR articles, 86% focused on multicultural and marginalized populations. Prominent topics of investigation included physical health, mental and behavioral health, and theoretical or methodological articles. Features of publications, including authors’ training, types of journals, study populations, and topics under investigation, were explored for all 1912 publications. Findings highlight an opportunity for further utilization of CBPR within psychology, with key implications for health equity. Recommendations for increasing CBPR uptake within the discipline are also offered.
Brazil's Craniofacial Project: Different approaches on orofacial clefts and 22q11.2 deletion syndrome
Authors: Gil‐da‐Silva‐Lopes Vera Lúcia , Tacla Milena Atique , Sgardioli Ilária Cristina , Vieira Társis Paiva , Monlleó Isabella Lopes
Published: November 2020

This article reports the present situation of Brazilian health care in genetics for Orofacial Cleft (OFC) and 22q11.2 Deletions Syndrome (22q11.2 DS) based on research conducted by Brazil's Craniofacial Project (BCFP). Established in 2003, BCFP is a voluntary and cooperative network aiming to investigate the health care of people with these diseases and other craniofacial anomalies. The initiatives and research results are presented in four sections: (a) a comprehensive report of the Brazilian public health system in craniofacial genetics; (b) multicentric studies developed on OFC and 22q11.2 DS; (c) education strategies focused on addressing these conditions for both population and health‐care professionals; and (d) the nosology through the Brazilian Database on Craniofacial Anomalies (BDCA). Since 2006, BDCA uses a standardized method with detailed clinical data collection, which allows for conducting studies on nosology, genotype–phenotype correlations, and natural history; data can also contribute to public policies. Currently, the BDCA stores data on 1,724 individuals, including 1,351 (78.36%) who were primarily admitted due to OFC and 373 (21.63%) with clinical suspicion of 22q11.2 DS. Chromosomal abnormalities/genomic imbalances were represented by 92/213 (43.19%) individuals with syndromic OFC, including 43 with 22q11.2 DS, which indicates the need for chromosomal microarray analysis in this group. The nosologic diversity reinforces that monitoring clinical is the best strategy for etiological investigation. BCFP's methodology has introduced the possibility of increasing scientific knowledge and genetic diagnosis of OFC and 22q11.2 DS to in turn improve health care and policies for this group of diseases.
A Stable [4,3]Peri‐acene Diradicaloid: Synthesis, Structure, and Electronic Properties
Authors: Shen Jun‐Jian , Han Yi , Dong Shaoqiang , Phan Hoa , Herng Tun Seng , Xu Tingting , Ding Jun , Chi Chunyan
Published: November 2020

The synthesis of peri‐fused acenes (peri‐acenes) with two or more rows is challenging due to their intrinsic open‐shell diradical character. Herein, we report the isolation of a derivative (4) of [4,3]peri‐acene in crystalline form. The parent [4,3]peri‐acene, containing three rows of tetracene, has a large diradical character (y0=94.8 %) originating from aromatic stabilization. Due to kinetic blocking, 4 showed a reasonable stability with a half‐life time of ≈157 h under ambient conditions. Its structure was determined by X‐ray crystallographic analysis, and bond‐length analysis revealed eight localized Clar's sextets. 4 exhibited an open‐shell singlet ground state with a narrow electrochemical energy gap (1.13 eV) and a small singlet–triplet energy gap (−0.57 kcal mol−1 from SQUID measurements). Its electronic properties are compared with previously reported peri‐tetracene and teranthene derivatives.
Quantification of Redox Sites during Catalytic Propane Oxychlorination by Operando EPR Spectroscopy
Authors: Zichittella Guido , Polyhach Yevhen , Tschaggelar René , Jeschke Gunnar , Pérez‐Ramírez Javier
Published: November 2020

Identification and quantification of redox‐active centers at relevant conditions for catalysis is pivotal to understand reaction mechanisms and requires development of advanced operando methods. Herein, we demonstrate operando EPR spectroscopy as an important technique to quantify the oxidation state of representative CrPO4 and EuOCl catalysts during propane oxychlorination, an attractive route for propylene production. In particular, we show that the space‐time‐yield of C3H6 correlates with the amount of Cr2+ and Eu2+ ions generated over the catalysts during reaction. These results provide a powerful strategy to gather quantitative understanding of selective alkane oxidation, which could potentially be extrapolated to other functionalization approaches and operating conditions.
Transparent and flame retardant vinylidene chloride‐methyl acrylate hybrid films with enhanced water vapor barrier, thermostability, and anti‐glare properties
Authors: Zhang Dongqiao , Yi Jiemin , Zhao Fei , Yin Ye , Jin Zhijun , Ma Wenshi , Peng Xiaohong , Yang Dongjie
Published: November 2020

Flexible organic light emitting diodes (FOLEDSs) require a barrier layer with transparency, thermal stability, and flame retardance to prevent water from inducing the corrosion of electrode and ultimately deterioration. Herein, HPS spheres were incorporated into the vinylidene chloride‐methyl acrylate (VDC‐MA) matrix to enhance the water vapor barrier property, thermostability, and anti‐glare effect. Scanning electron microscopy showed that HPS spheres were more compatible with VM (89.86‐10.14) by presenting better water vapor barrier property rather than with VM (92.38‐7.62). The anti‐glare effect of composite film was improved with HPS spheres, while the transparency still maintained over 80%. Thermogravimetric analysis showed that the weight loss still maintained over 50% with the incorporation of HPS spheres, indicating significant improvement compared with control VDC‐MA films. Our research supplies an effective approach to prepare transparent and flame retardant hybrid films with enhanced water vapor barrier, thermostability, and anti‐glare properties, which is promising in the encapsulation of FOLEDSs and other electronics areas.
GC‐content biases in protein‐coding genes act as an “mRNA identity” feature for nuclear export
Authors: Palazzo Alexander F. , Kang Yoon Mo
Published: November 2020

It has long been observed that human protein‐coding genes have a particular distribution of GC‐content: the 5′ end of these genes has high GC‐content while the 3′ end has low GC‐content. In 2012, it was proposed that this pattern of GC‐content could act as an mRNA identity feature that would lead to it being better recognized by the cellular machinery to promote its nuclear export. In contrast, junk RNA, which largely lacks this feature, would be retained in the nucleus and targeted for decay. Now two recent papers have provided evidence that GC‐content does promote the nuclear export of many mRNAs in human cells.
Why PGD2 has different functions from PGE2
Authors: Fujino Hiromichi
Published: November 2020

Prostaglandin (PG) D2 and PGE2 are positional isomers; however, they sometimes exhibit opposite physiological functions, such as in cancer development. Because DP receptors are considered to be a duplicated copy of EP2 receptors, PGD2 and PGE2 cross‐react with both receptors. These prostanoids may act as biased agonists for each receptor. In reviewing this field, a hypothesis was proposed to explain the opposed effects of these prostanoids from the viewpoints of the evolution of, mutations in, and biased activities of their receptors. Previous findings showing more mutations/variations in DP receptors than EP2 receptors among individuals worldwide indicate that DP receptors are still in a rapid evolutionary stage. The opposing effects of these prostanoids on cancer development may be attributed to the biased activity of PGE2 for DP receptors, which may incidentally develop during the process of the old ligand, PGE2 gaining selectivity to newly diverged DP receptors.
Comparison of normal distribution–based and nonparametric decision limits on the GH‐2000 score for detecting growth hormone misuse (doping) in sport
Authors: Liu Wei , Bretz Frank , Böhning Dankmar , Holt Richard , Böhning W. , Guha Nishan , Sönksen Peter , Cowan David
Published: November 2020

This paper is motivated by the GH‐2000 biomarker test, though the discussion is applicable to other diagnostic tests. The GH‐2000 biomarker test has been developed as a powerful technique to detect growth hormone misuse by athletes, based on the GH‐2000 score. Decision limits on the GH‐2000 score have been developed and incorporated into the guidelines of the World Anti‐Doping Agency (WADA). These decision limits are constructed, however, under the assumption that the GH‐2000 score follows a normal distribution. As it is difficult to affirm the normality of a distribution based on a finite sample, nonparametric decision limits, readily available in the statistical literature, are viable alternatives. In this paper, we compare the normal distribution–based and nonparametric decision limits. We show that the decision limit based on the normal distribution may deviate significantly from the nominal confidence level or nominal FPR when the distribution of the GH‐2000 score departs only slightly from the normal distribution. While a nonparametric decision limit does not assume any specific distribution of the GH‐2000 score and always guarantees the nominal confidence level and FPR, it requires a much larger sample size than the normal distribution–based decision limit. Due to the stringent FPR of the GH‐2000 biomarker test used by WADA, the sample sizes currently available are much too small, and it will take many years of testing to have the minimum sample size required, in order to use the nonparametric decision limits. Large sample theory about the normal distribution–based and nonparametric decision limits is also developed in this paper to help understanding their behaviours when the sample size is large.
Correspondence of categorical and feature‐based representations of music in the human brain
Authors: Nakai Tomoya , Koide‐Majima Naoko , Nishimoto Shinji
Published: November 2020

Introduction

Humans tend to categorize auditory stimuli into discrete classes, such as animal species, language, musical instrument, and music genre. Of these, music genre is a frequently used dimension of human music preference and is determined based on the categorization of complex auditory stimuli. Neuroimaging studies have reported that the superior temporal gyrus (STG) is involved in response to general music‐related features. However, there is considerable uncertainty over how discrete music categories are represented in the brain and which acoustic features are more suited for explaining such representations.

Methods

We used a total of 540 music clips to examine comprehensive cortical representations and the functional organization of music genre categories. For this purpose, we applied a voxel‐wise modeling approach to music‐evoked brain activity measured using functional magnetic resonance imaging. In addition, we introduced a novel technique for feature‐brain similarity analysis and assessed how discrete music categories are represented based on the cortical response pattern to acoustic features.

Results

Our findings indicated distinct cortical organizations for different music genres in the bilateral STG, and they revealed representational relationships between different music genres. On comparing different acoustic feature models, we found that these representations of music genres could be explained largely by a biologically plausible spectro‐temporal modulation‐transfer function model.

Conclusion

Our findings have elucidated the quantitative representation of music genres in the human cortex, indicating the possibility of modeling this categorization of complex auditory stimuli based on brain activity.
Adiponectin antagonises LPS‐regulated secretion of inflammatory factors in airway epithelial cells, and its expression is regulated by many factors
Authors: Liu Hu , Tang Huo‐yan , Wang Rui‐ying , Xu Jian‐ying
Published: November 2020

Many studies have shown that adiponectin is closely related to chronic obstructive pulmonary disease (COPD), but the specific role of adiponectin in COPD is still not well understood. Adiponectin and IL‐6 expression in patients with acute exacerbation of COPD (AECOPD) was detected by ELISA. Human bronchial epithelial cells (HBECs) were stimulated with TNF‐α, IL‐6, apoptotic cells or LPS. Then, the expression of adiponectin was detected by qRT‐PCR and western blotting, and pro‐ and anti‐inflammatory factors were detected by ELISA. Adiponectin expression in AECOPD patients increased after treatment. TNF‐α and apoptotic cells promoted adiponectin expression in HBECs in a dose‐dependent manner, and apoptotic cells significantly promoted adiponectin secretion. IL‐6 also promoted adiponectin expression, but it inhibited adiponectin expression at high doses and with long treatment times. LPS inhibited adiponectin expression, but when HBECs were pretreated with anti‐TNF‐α and then treated with LPS, the expression and secretion of adiponectin increased significantly with increasing anti‐TNF‐α concentrations. Adiponectin stimulated the secretion of pro‐inflammatory factors in HBECs, but this effect was not concentration dependent. Adiponectin promoted the secretion of anti‐inflammatory factors in a dose‐dependent manner. Although LPS also stimulated HBECs to secrete pro‐inflammatory and anti‐inflammatory factors, adiponectin inhibited LPS‐induced pro‐inflammatory factor secretion and enhanced anti‐inflammatory factor secretion. Many factors regulate the expression and secretion of adiponectin, and adiponectin regulates the balance of the inflammatory response and inhibits further expansion of inflammation.

Significance of the study

Many studies have shown that adiponectin is closely related to chronic obstructive pulmonary disease (COPD), but the specific role of adiponectin in COPD is still not well understood. Adiponectin expression in AECOPD patients increased after treatment. TNF‐α, IL‐6 and apoptotic cells promoted adiponectin expression in HBECs. Adiponectin stimulated the secretion of pro‐inflammatory factors in HBECs, but this effect was not concentration dependent. Adiponectin promoted the secretion of anti‐inflammatory factors in a dose‐dependent manner. Adiponectin inhibited LPS‐induced pro‐inflammatory factor secretion and enhanced anti‐inflammatory factor secretion. Therefore, many factors regulate the expression and secretion of adiponectin, and adiponectin regulates the balance of the inflammatory response and inhibits further expansion of inflammation.
The cardiovascular outcomes, heart failure and kidney disease trials tell that the time to use Sodium Glucose Cotransporter 2 inhibitors is now
Authors: Johansen Michael E. , Argyropoulos Christos
Published: November 2020

Sodium glucose contrasporter 2 inhibitors (SGLT2i) were initially introduced as a novel class of modestly effective antiglycemics. Over the last 5 years, multiple members of this class have been examined for their cardiovascular safety, effects on heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) in diverse populations with or without diabetes type 2. The plethora of studies and outcomes examined make it difficult for the practitioner to track the entirety of the evidence. SGLT2i improve cardiorenal outcomes and have a beneficial risk benefit ratio across populations with cardiovascular disease, HFrEF and kidney disease. In this quantitative review, we synthesize the data from the large outcomes trials about the benefits and risks of SGLT2i. SGLT2i reduce all cause, cardiovascular mortality, heart failure hospitalizations, need for dialysis and acute kidney injury as a class effect across a broad range of populations with diabetes Type 2 at risk for cardiovascular disease, patients with HFrEF or CKD with or without diabetes. While certain adverse events for example, diabetic ketoacidosis and genital mycotic infections are reproducibly increased by SGLT2i, the absolute increase in the risk of these complications is smaller than the absolute risk reductions conferred by SGLT2i. Other complications such as amputations, fractures and urinary tract infections are increased to a lesser degree, or not at all (e.g., hypoglycemia). Overall, SGLT2is appear to have a favorable safety profile and thus should be used by cardiologists, nephrologists, endocrinologists, primary care physicians when managing the cardiorenal risk of their patients.
Highly Phototoxic Transplatin‐Modified Distyryl‐BODIPY Photosensitizers for Photodynamic Therapy
Authors: Padrutt Roxane , Babu Vipin , Klingler Simon , Kalt Martina , Schumer Frank , Anania Maria I. , Schneider Lukas , Spingler Bernhard
Published: November 2020

We report the synthesis of the first transplatin‐BODIPY conjugates for application in photodynamic therapy (PDT). The distyryl BODIPYs containing two iodine atoms were designed to absorb in the red region, easily undergo intersystem crossing for efficient singlet oxygen generation, and additionally offer the possibility for coordination with mono‐activated transplatin. We were able to demonstrate that coordination of the BODIPYs with a mono‐activated transplatin increases the phototoxic index of the photosensitizers significantly, giving rise to highly phototoxic distyryl BODIPY derivatives, of which one was shown to have the highest ever reported phototoxic index against any cell line. Furthermore, the photophysical mechanism of singlet oxygen generation in distyryl BODIPYs undergoing intramolecular charge transfer was studied experimentally and using time‐dependent density functional theory.
Co‐Culture System of Human Enteroids/Colonoids with Innate Immune Cells
Authors: Staab Janet F. , Lemme‐Dumit Jose M. , Latanich Rachel , Pasetti Marcella F. , Zachos Nicholas C.
Published: November 2020

Human intestinal enteroids derived from adult stem cells offer a relevant ex vivo system to study biological processes of the human gut. They recreate cellular and functional features of the intestinal epithelium of the small intestine (enteroids) or colon (colonoids) albeit limited by the lack of associated cell types that help maintain tissue homeostasis and respond to external challenges. In the gut, innate immune cells interact with the epithelium, support barrier function, and deploy effector functions. We have established a co‐culture system of enteroid/colonoid monolayers and underlying macrophages and polymorphonuclear neutrophils to recapitulate the cellular framework of the human intestinal epithelial niche. Enteroids are generated from biopsies or resected tissue from any segment of the human gut and maintained in long‐term cultures as three‐dimensional structures through supplementation of stem cell growth factors. Immune cells are isolated from fresh human whole blood or frozen peripheral blood mononuclear cells (PBMC). Monocytes from PBMC are differentiated into macrophages by cytokine stimulation prior to co‐culture. The methods are divided into the two main components of the model: (1) generating enteroid/colonoid monolayers and isolating immune cells and (2) assembly of enteroid/colonoid‐immune cell co‐cultures with separate apical and basolateral compartments. Co‐cultures containing macrophages can be maintained for 48 hr while those involving neutrophils, due to their shorter life span, remain viable for 4 hr. Enteroid‐immune co‐cultures enable multiple outcome measures, including transepithelial resistance, production of cytokines/chemokines, phenotypic analysis of immune cells, tissue immunofluorescence imaging, protein or mRNA expression, antigen or microbe uptake, and other cellular functions. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Seeding enteroid fragments onto Transwells for monolayer formation

Alternate Protocol: Seeding enteroid fragments for monolayer formation using trituration

Basic Protocol 2: Isolation of monocytes and derivation of immune cells from human peripheral blood

Basic Protocol 3: Isolation of neutrophils from human peripheral blood

Basic Protocol 4: Assembly of enteroid/macrophage or enteroid/neutrophil co‐culture
Introduction of family‐based treatment to Japan with adaptations to optimize the cultural acceptability and advance current traditional treatments of adolescent anorexia nervosa
Authors: Iguchi Toshiyuki , Miyawaki Dai , Harada Tomoko , Ogiwara Kaori
Published: November 2020

Given the lack of clear consensus on effective treatment models for adolescent anorexia nervosa in Japan, treatment programs offered to this population vary widely between treatment facilities with limited testing of outcomes. Importantly, families have traditionally been left out of the core treatment process, as they are commonly viewed as being powerless in renourishing their child. The purpose of this commentary was to report the authors' preliminary efforts to introduce and implement family‐based treatment (FBT) in Japan so that, on par with international standards of practice, FBT may become the first‐line treatment option for Japanese families. This commentary will describe the systemic and cultural barriers which posed as challenges in introducing FBT to Japan in its manualized standard format and how these were addressed by introducing FBT during the patient's hospital admission and by assigning the father with a role which resembles the traditional gender role within the Japanese family culture. Authors have thus far observed that these adaptations led to increased accessibility of FBT and improved outcomes such as reduced number of hospitalizations and shorter time taken to reach 85–90% EBW. Further considerations for the broad dissemination and implementation of FBT in Japan are also presented.
The genetic differentiation of a cricket (Velarifictorus micado) with two modes of life cycle in East Asia after the middle Pleistocene and the invasion origin of the United States of America
Authors: Wang Baiqiu , Li Kai , He Zhu‐Qing , Takeda Makio
Published: November 2020

The cricket Velarifictorus micado is widely distributed in East Asia and colonized the United States of America (the USA) in 1959. It has two life cycles: one having egg diapause and the other having nymphal diapause. We aimed to investigate the biogeographic boundary between them and determine when and why V. micado diverged. Mitochondrial fragments including COI and CytB were used for haplotype network, demographic analysis, and divergence time estimation in individuals of East Asia. We selected several samples from the USA to find out the colonization origin. The haplotype network indicated there were three lineages based on COI, NE lineage (having egg diapause and mainly distributed in the northern regions), SE lineage (having egg diapause and mainly distributed in the south central regions), and SN lineage (the nymph diapause and mainly distributed in the deep south regions). The molecular chronograms indicated that the first divergence of V. micado into two main lineages, NE and southern lineages (SE and SN), was essentially bounded by the Yangtze River. It occurred around ~0.79 Ma (95% HPD: 1.13–0.46 Ma) in the Middle Pleistocene Transition. This was followed by the divergence of the southern lineage into two sublineages, SE and SN lineage, occurred around ~0.50 Ma (95% HPD: 0.71–0.25 Ma), corresponding to the time of development of glaciers in various parts of the Qinghai–Tibet Plateau (QTP) (0.73–0.46 Ma). SE lineage might originate from southwestern China based on the comparison between the haplotype network based on COI and CytB. Our study suggested that divergences of lineages have twice co‐occurred with the tendency of cooling climate in Asia after the Mid‐Pleistocene, and the life‐history strategy may play an important role in lineage diversification. The results suggest that US populations are originally established twice by independent colonization from the SE and NE.

[Correction added on 02 June 2021 after first publication: the sixth sentence has been updated to clarify the distributions of the SE and SN lineages, which were originally described as being in the “southern regions”; the last sentence of the abstract has been rewritten for clarity.]
A closer look at invasiveness and relatedness: life histories, temperature, and establishment success of four congeners
Authors: Rehage J. S. , Maurer E. F. , Lopez L. K. , Sih A.
Published: November 2020

Successful invasive species are often closely related to other invasive species, suggesting that shared traits contribute to their invasion success. Alternatively, related species can differ in invasiveness, where some are highly invasive yet congeners seem unable to invade. Here, we compared the traits and establishment abilities of two highly successful invasive species, Gambusia affinis and G. holbrooki, to those of two close relatives, G. geiseri and G. hispaniolae. Using laboratory experiments, we compared low‐temperature tolerances and life histories of the four species. In a semi‐natural mesocosm experiment, we simulated the invasion of standardized, simple pond communities and examined the effects of these traits on each species’ ability to become established. The invasive species, G. affinis and G. holbrooki, were more tolerant of low‐temperature stress, had greater fecundities, higher growth rates, and reached maturity sooner than G. geiseri and G. hispaniolae. In mesocosms, the invasive Gambusia exhibited higher intrinsic growth rates and carrying capacities and thus achieved and maintained larger populations than the two congeners. Only G. affinis and G. holbrooki successfully established long‐term populations in these experimental communities. G. geiseri and G. hispaniolae failed to establish as a result of 100% overwintering mortality. These results support the notion that the ability of invaders to cope with the abiotic conditions of target communities has a major effect on whether establishment occurs, while life histories play an important secondary role. Our results showed that invasiveness is likely not a trait of the entire genus Gambusia.
Deep learning support for intelligent transportation systems
Authors: Guerrero‐Ibañez J. , Contreras‐Castillo J. , Zeadally S.
Published: November 2020

Intelligent Transportation Systems (ITS) help improve the ever‐increasing vehicular flow and traffic efficiency in urban traffic to reduce the number of accidents. The generation of massive amounts of data generated by all the digital devices connected to the transportation network enables the creation of datasets to perform an in‐depth analysis of the data using deep learning methods. Such methods can help predict traffic performance, automated traffic light management, lane detection, and identifying objects near vehicles to increase the safety and efficiency of ITS. We discuss some of the challenges that need to be solved to achieve seamless integration between ITS and deep learning methods to address issues such as (1) improving traffic flow/transportation logistics, (2) predicting best routes for the transportation of goods, (3) optimal fuel consumption, (4) intelligent environmental conditions perception, (5) traffic speed management, and accident prevention.