bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultralight and Resilient Bicontinuous Si3N4/SiC Nanowire Network for Tunable and Highly Efficient Electromagnetic Wave Absorption in Extreme Conditions
Authors: Cai Zhixin , Su Lei , Niu Min , Wang Lei , Ni Zhentao , Wang Hongjie , Peng Kang , Zhuang Lei
Published: October 2022

Developing tunable and highly efficient electromagnetic wave (EMW) absorbers with low density is crucial for the development of wireless telecommunications devices in extreme conditions. SiC ceramic has received much attention because of its dielectric tenability, low density, and chemical stability. However, the present SiC‐based materials usually show limited EMW absorbing performance than they are expected. Herein, an ultralight and resilient bicontinuous Si3N4/SiC network (8 mg cm−3) composed of EMW‐transparent Si3N4 microbelts and EMW‐absorption SiC nanowires is designed and prepared to achieve improved impedance matching and EMW attenuation capacity. The optimized bicontinuous network exhibits a broad effective absorption bandwidth of 8.62 GHz and a strong RLmin of −52.31 dB. Furthermore, the resulting bicontinuous Si3N4/SiC network, with thickness of 6 mm, shows a tunable absorption bandwidth ranging from 5.36 to 18 GHz by resilient action. It also exhibits excellent thermal stability (up to 1000 °C), thermal shock resistance (from −196 to 900 °C), and thermal insulation performance (32 Mw m−1 K−1), enabling it to be an ideal candidate for EMW absorption in extreme environments.
Triarylborane‐Functionalized Au8Ag8(CCR)16 Nanocluster with Enhanced Lewis Acidity
Authors: Lu Hui , Fan Jinsong , Ran Guangliu , Li Jiang , Wang Lihua , Zhu Ying , Shen Jianlei , Zhang Wenkai , Chen Jing , Fan Chunhai
Published: October 2022

Functionalization of ligated metal nanoclusters with versatile ligands is highly desired for wide applications. Lewis acids have shown promise in multiple realms such as self‐assembly and catalysis, which may endow nanoclusters with diverse functions. However, metal nanoclusters with Lewis acid surface have not been reported. Here, the functionalization of a bimetallic nanocluster Au8Ag8(CCR)16 with triarylborane (TAB) is reported, which exhibits enhanced Lewis acidity. By using single‐crystal X‐ray crystallography, the structure of the nanocluster with 16 boron receptor sites is confirmed, which presents ≈15‐fold enhancement of quenching efficiency in sensing fluoride compared to that of free triarylborane ligand. By the combined analysis using ultrafast transient absorption and photoluminescent (PL) decay measurements, the quenching mechanism of Au8Ag8 to fluoride is elucidated. The PL quenching is realized via two pathways with enhanced non‐radiation energy dissipation, i.e., prolonged electron–phonon coupling and reverse intersystem crossing (RISC). This work may open a new route to diverse applications of metal nanoclusters.
Switching Behavior of Dip‐Coated Organic Ferroelectric Trialkylbenzene‐1,3,5‐tricarboxamide (BTA)
Authors: Butkevich Andrey A. , Kemerink Martijn
Published: October 2022

Supramolecular organic ferroelectrics have unique properties related to plasticity and freedom of design but the extensive post‐deposition treatments that are typically required to achieve saturation polarization limit their applicability. A possible solution is to pre‐align the molecules. Here, the effect of dip‐coating on the pre‐alignment of the prototypical supramolecular ferroelectric trialkylbenzene‐1,3,5‐tricarboxamide (BTA) and the resulting changes in the ferroelectric switching behavior of the resulting thin films are analyzed. Dip‐coated films are characterized by different BTA concentrations and dip‐coating velocities. Landau–Levich and evaporation regimes are identified. The corresponding ferroelectric switching behavior is investigated and reveals that dip‐coating in general enhances the ferroelectric switching of pristine films. Dip‐coating perpendicular to the electrodes (parallel to the electric field direction) has the most significant effect, and without further alignment steps, leads to equal switching behavior as films that are aligned by post‐deposition treatment, that is, field annealing. The results are expected to be transferable to other small molecular ferroelectrics.
Monitoring of Drug Release via Intra Body Communication with an Edible Pill
Authors: Lamanna Leonardo , Cataldi Pietro , Friuli Marco , Demitri Christian , Caironi Mario
Published: October 2022

Oral drug administration provides a convenient and patient‐compliant way for drug delivery, especially for chronic diseases and prolonged pharmacological treatments. However, due to the repetitiveness of such therapeutic approach, the patients are led to neglect/forget the therapy affecting the healthcare delivery. Indeed, the non‐adherence to pharmacological prescriptions and the unknown amount of real‐time drug release result in a non‐compliant therapeutic drug level over the protracted therapies. The proposed technology will enable the monitoring of both pharmacological adherence and real‐time drug release. The approach exploits a passive intrabody communication (IBC) activation in order to enable an edible pill, realized starting from food additives and food‐grade materials, to monitor pharmacological adherence. Following activation, the signal is modulated by IBC coupling switching triggered by pill degradation in a gastrointestinal tract, resulting in a monitored drug release. The proof‐of‐concept is designed for a targeted release and monitoring of Metformin in the intestine. The system shows an in vitro limit of cumulative drug release detection of 18 µg mL−1 and a limit of real‐time drug release detection of 2 µg mL−1 min−1. This platform represents the first solution to monitor passive drug release in real‐time, from intake to complete absorption, enabling unique and long‐sought healthcare therapy and treatment opportunity.
Printable Coffee‐Ring Structures for Highly Uniform All‐Oxide Optoelectronic Synaptic Transistors
Authors: Liang Kun , Wang Rui , Ren Huihui , Li Dingwei , Tang Yingjie , Wang Yan , Chen Yitong , Song Chunyan , Li Fanfan , Liu Guolei , Wang Hong , Leow Wan Ru , Zhu Bowen
Published: October 2022

Printable oxide transistors have emerged as important optoelectronic synaptic devices to emulate the human visual cognitive system by integrating both photo‐sensing and visual perception functions. However, the inferior electrical performance and low pixel density of printed oxide synaptic transistors impede their implementation of complex neuromorphic computing. Herein, a printable all‐oxide optoelectronic synaptic transistor array based on a modified coffee‐ring structure of indium tin oxide (ITO) is reported. The extraordinary structural design endows the printed ITO transistors with high device uniformity, outstanding electrical performance, and superior process efficiency. Furthermore, a 10 × 12 coffee‐ring structure optoelectronic synaptic transistor array with a high spatial resolution (142 dpi) exhibits durable visual detection and memory behaviors. Meanwhile, an artificial neural network based on the coffee‐ring structure synaptic transistors exhibits high accuracy in the recognition rate. These results promise the efficiency of the exceptional printing strategy in developing advanced optoelectronic synaptic transistors for artificial visual systems.
Broadband NIR Phosphor Ca2LuScAl2Si2O12:Cr3+ for NIR LED Applications
Authors: Jin Ye , Zhou Zhen , Ran Rongxia , Tan Shuang , Liu Yongfu , Zheng Jinju , Xiang Guotao , Ma Li , Wang Xiao‐jun
Published: October 2022

Near‐infrared phosphor‐converted light‐emitting diodes (NIR pc‐LEDs) have promising applications in food analysis, night vision imaging, and biological probes. Developing NIR phosphors with broadband emission and high efficiency has attracted immense interest. Herein, a novel NIR phosphor Ca2LuScAl2Si2O12:Cr3+ (CLSAS:Cr3+) is reported for the first time. Under the excitation of 442 nm light, CLSAS:Cr3+ shows broadband emission from 600 to 900 nm with a full width at half maximum (FWHM) of 142 nm, benefiting from the emissions of two Cr3+ centers in CLSAS, which is proved by the spectra and the decay curves. The internal quantum efficiency (IQE) of 73.7% is achieved and, at 423 K, the emission intensity maintains 76% of the value at room temperature. Combining the CLSAS:Cr3+ phosphor and the 450 nm blue chip, the NIR pc‐LED is fabricated and demonstrated for fast imaging of veins in human palm and fist, as well as night vision for objects.
Thermoelectric Silver‐Based Chalcogenides
Authors: Tee Si Yin , Ponsford Daniel , Lay Chee Leng , Wang Xiaobai , Wang Xizu , Neo Darren Chi Jin , Wu Tianze , Thitsartarn Warintorn , Yeo Jayven Chee Chuan , Guan Guijian , Lee Tung‐Chun , Han Ming‐Yong
Published: October 2022

Heat is abundantly available from various sources including solar irradiation, geothermal energy, industrial processes, automobile exhausts, and from the human body and other living beings. However, these heat sources are often overlooked despite their abundance, and their potential applications remain underdeveloped. In recent years, important progress has been made in the development of high‐performance thermoelectric materials, which have been extensively studied at medium and high temperatures, but less so at near room temperature. Silver‐based chalcogenides have gained much attention as near room temperature thermoelectric materials, and they are anticipated to catalyze tremendous growth in energy harvesting for advancing internet of things appliances, self‐powered wearable medical systems, and self‐powered wearable intelligent devices. This review encompasses the recent advancements of thermoelectric silver‐based chalcogenides including binary and multinary compounds, as well as their hybrids and composites. Emphasis is placed on strategic approaches which improve the value of the figure of merit for better thermoelectric performance at near room temperature via engineering material size, shape, composition, bandgap, etc. This review also describes the potential of thermoelectric materials for applications including self‐powering wearable devices created by different approaches. Lastly, the underlying challenges and perspectives on the future development of thermoelectric materials are discussed.
Atomically Interfacial Engineering on Molybdenum Nitride Quantum Dots Decorated N‐doped Graphene for High‐Rate and Stable Alkaline Hydrogen Production
Authors: Huang Yichao , Zhou Wenbo , Kong Weichao , Chen Lulu , Lu Xiaolong , Cai Hanqing , Yuan Yongrui , Zhao Lianming , Jiang Yangyang , Li Haitao , Wang Limin , Wang Lin , Wang Hang , Zhang Jiangwei , Gu Jing , Fan Zhuangjun
Published: October 2022

The development of low‐cost, high‐efficiency, and stable electrocatalysts for hydrogen evolution reaction (HER) under alkaline conditions is a key challenge in water electrolysis. Here, an interfacial engineering strategy that is capable of simultaneously regulating nanoscale structure, electronic structure, and interfacial structure of Mo2N quantum dots decorated on conductive N‐doped graphene via codoping single‐atom Al and O (denoted as AlO@Mo2N‐NrGO) is reported. The conversion of Anderson polyoxometalates anion cluster ([AlMo6O24H6]3−, denoted as AlMo6) to Mo2N quantum dots not only result in the generation of more exposed active sites but also in situ codoping atomically dispersed Al and O, that can fine‐tune the electronic structure of Mo2N. It is also identified that the surface reconstruction of AlOH hydrates in AlO@Mo2N quantum dots plays an essential role in enhancing hydrophilicity and lowering the energy barriers for water dissociation and hydrogen desorption, resulting in a remarkable alkaline HER performance, even better than the commercial 20% Pt/C. Moreover, the strong interfacial interaction (MoN bonds) between AlO@Mo2N and N‐doped graphene can significantly improve electron transfer efficiency and interfacial stability. As a result, outstanding stability over 300 h at a current density higher than 100 mA cm−2 is achieved, demonstrating great potential for the practical application of this catalyst.
Farmers' risk preferences in 11 European farming systems: A multi‐country replication of Bocquého et al. (2014)
Authors: Rommel Jens , Sagebiel Julian , Baaken Marieke Cornelia , Barreiro‐Hurlé Jesús , Bougherara Douadia , Cembalo Luigi , Cerjak Marija , Čop Tajana , Czajkowski Mikołaj , Espinosa‐Goded María , Höhler Julia , Kuhfuss Laure , Lagerkvist Carl‐Johan , Lapierre Margaux , Lefebvre Marianne , Matzdorf Bettina , Ott Edward , Paparella Antonio , Quendler Erika , Rodriguez‐Entrena Macario , Schulze Christoph , Šumrada Tanja , Tensi Annika , Thoyer Sophie , Maksan Marina Tomić , Vecchio Riccardo , Willinger Marc , Zagórska Katarzyna
Published: October 2022

We replicate Bocquého et al. (2014), who used multiple price lists to investigate the risk preferences of 107 French farmers. We collected new data from 1430 participants in 11 European farming systems. In agreement with the original study, farmers' risk preferences are best described by Cumulative Prospect Theory. Structural model estimates show that farmers in the new samples are, on average, less loss averse and more susceptible to probability distortion than in the original study. Explorative analyses indicate differences between estimation approaches, as well as heterogeneity between and within samples. We discuss challenges in replications of economic experiments with farmers across farming contexts.
Teaching perspectives on the communication of difficult news of genetic conditions to medical students
Authors: Vanasse Ashley M. , Weiler Tracey , Roth Elizabeth A. , Upadhya Sharmila , Toriello Helga V. , VanLeuven Ariel J. , Norris John R. , Carey John C. , Sobering Andrew K.
Published: October 2022

Informing parents that their child has a diagnosis of Down syndrome (DS) is a common example of the delivery of unexpected or difficult news. Expectations and life planning will change, and if detected prenatally, discussions might include the option of pregnancy termination. Medical school curricula currently include training in breaking unexpected news; however, it is difficult to teach and assess. We use the perspectives of clinicians, educators, and a medical student who is the parent of a child with DS to frame a discussion on teaching, practicing, and assessing communication of difficult news in human genetics during medical school.
Cost‐effectiveness models for Alzheimer's disease and related dementias: IPECAD modeling workshop cross‐comparison challenge
Authors: Handels Ron L.H. , Green Colin , Gustavsson Anders , Herring William L. , Winblad Bengt , Wimo Anders , Sköldunger Anders , Karlsson Andreas , Anderson Robert , Belger Mark , Brück Chiara , Espinosa Robert , Hlávka Jakub P. , Jutkowitz Eric , Lin Pei‐Jung , Mendez Mauricio Lopez , Mar Javier , Shewmaker Peter , Spackman Eldon , Tafazzoli Ali , Tysinger Bryan , Jönsson Linus ,   IPECAD modeling workshop 2020 participants
Published: October 2022

Introduction

The credibility of model‐based economic evaluations of Alzheimer's disease (AD) interventions is central to appropriate decision‐making in a policy context. We report on the International PharmacoEconomic Collaboration on Alzheimer's Disease (IPECAD) Modeling Workshop Challenge.

Methods

Two common benchmark scenarios, for the hypothetical treatment of AD mild cognitive impairment (MCI) and mild dementia, were developed jointly by 29 participants. Model outcomes were summarized, and cross‐comparisons were discussed during a structured workshop.

Results

A broad concordance was established among participants. Mean 10‐year restricted survival and time in MCI in the control group ranged across 10 MCI models from 6.7 to 9.5 years and 3.4 to 5.6 years, respectively; and across 4 mild dementia models from 5.4 to 7.9 years (survival) and 1.5 to 4.2 years (mild dementia).

Discussion

The model comparison increased our understanding of methods, data used, and disease progression. We established a collaboration framework to assess cost‐effectiveness outcomes, an important step toward transparent and credible AD models.
Oxygen‐Sensing Chemiluminescent Iridium(III) 1,2‐Dioxetanes: Unusual Coordination and Activity
Authors: Kagalwala Husain N. , Bueno Lorena , Wanniarachchi Hashini , Unruh Daniel K. , Hamal Khagendra B. , Pavlich Cyprian I. , Carlson Graham J. , Pinney Kevin G. , Mason Ralph P. , Lippert Alexander R.
Published: October 2022

Next generation chemiluminescent iridium 1,2‐dioxetane complexes have been developed which consist of the Schaap's 1,2‐dioxetane scaffold directly attached to the metal center. This was achieved by synthetically modifying the scaffold precursor with a phenylpyridine moiety, which can act as a ligand. Reaction of this scaffold ligand with the iridium dimer [Ir(BTP)2(μ‐Cl)]2(BTP=2‐(benzo[b]thiophen‐2‐yl)pyridine) yielded isomers which depict ligation through either the cyclometalating carbon or, interestingly, the sulfur atom of one BTP ligand. Their corresponding 1,2‐dioxetanes display chemiluminescent responses in buffered solutions, exhibiting a single, red‐shifted peak at 600 nm. This triplet emission was effectively quenched by oxygen, yielding in vitro Stern‐Volmer constants of 0.1 and 0.009 mbar−1for the carbon‐bound and sulfur compound, respectively. Lastly, the sulfur‐bound dioxetane was further utilized for oxygen sensing in muscle tissue of living mice and xenograft models of tumor hypoxia, depicting the ability of the probe chemiluminescence to penetrate biological tissue (total flux ∼106 p/s).
Trogbrücke mit Versprung
Authors: Jacob‐Freitag Susanne , Miebach Frank
Published: October 2022

Vor der Küste der holländischen Gemeinde Delfzijl werden im Rahmen eines Stadtentwicklungsprogramms Salzwiesen mit Sand und Schlick angelegt und der Seedeich in eine Rad‐ und Wanderpromenade umgewandelt. Seit Herbst 2020 verbindet nun auch eine neue Fußgänger‐ und Radwegbrücke das Stadtzentrum von Delfzijl mit dem Boulevard am Wattenmeer. Beauftragt hat sie die gleichnamige Gemeinde, verknüpft mit dem Wunsch nach einem nachhaltigen Bauwerk. So stand von vornherein fest, dass Holz zum Zug kommen sollte. Entsprechend nutzten die Planer Brettschichtholz (BSH) für das Haupttragwerk, kombinierten es mit Stahl jedoch so, dass ein auf geschickte Weise variierter Typus der Trogbrücke entstanden ist. Die daraus hervorgegangene Z‐Form gibt der Brücke ihren eigenen Charakter und sorgt für ein markantes Erscheinungsbild, das auch aus der Ferne zu erkennen ist.
Analyzing recurrent and nonrecurrent terminal events data in discrete time
Authors: Wen Chi‐Chung , Chen Yi‐Hau
Published: October 2022

Joint analysis of recurrent and nonrecurrent terminal events has attracted substantial attention in literature. However, there lacks formal methodology for such analysis when the event time data are on discrete scales, even though some modeling and inference strategies have been developed for discrete‐time survival analysis. We propose a discrete‐time joint modeling approach for the analysis of recurrent and terminal events where the two types of events may be correlated with each other. The proposed joint modeling assumes a shared frailty to account for the dependence among recurrent events and between the recurrent and the terminal terminal events. Also, the joint modeling allows for time‐dependent covariates and rich families of transformation models for the recurrent and terminal events. A major advantage of our approach is that it does not assume a distribution for the frailty, nor does it assume a Poisson process for the analysis of the recurrent event. The utility of the proposed analysis is illustrated by simulation studies and two real applications, where the application to the biochemists' rank promotion data jointly analyzes the biochemists' citation numbers and times to rank promotion, and the application to the scleroderma lung study data jointly analyzes the adverse events and off‐drug time among patients with the symptomatic scleroderma‐related interstitial lung disease.
Motivation, self‐efficacy, perception, curiosity, and barriers toward medical research among undergraduates in China
Authors: Chen Huiyu , Teng Teng , Chen Hongyu , Liu Xiaoying , Liu Zhaohong , Li Xuemei , Jie Wang , Wu Xiang , Cao Lu , Hongyan Wu , Zhu Dan , Zhou Xinyu
Published: October 2022

Medical research is important to scientific progress and medical education. Institutions worldwide have sought to increase student involvement in research such as clinician–scientists training programs, while little is known about how medical undergraduates perceive research. A cross‐sectional study was conducted in Chongqing Medical University, Chongqing, China, with first–fourth year undergraduates. An online, anonymous, and self‐rating 5‐point Likert questionnaire was conducted to investigate medical undergraduates' demographic characteristics and assess motivation, self‐efficacy, perception, curiosity, and barriers regarding medical research. Content validity was checked with experts and face validity was checked for clarity and understanding of the questionnaire. The Cronbach's alpha coefficient of the questions ranged from 0.813 to 0.879. A total of 3273 medical undergraduates were surveyed, and 86.62% (2835) participants (male 962, female 1873) were identified as effective. Males scored higher than females on self‐efficacy (p < 0.001), perception (p = 0.017), and curiosity (p < 0.001), and lower on barriers (p < 0.001). The second year students are at the peak of their perception (p = 0.006) and lowest barrier scores (p = 0.003). Students with scientific research experience scored higher in motivation (p = 0.002), self‐efficacy (p < 0.001), perception (p < 0.001), and curiosity (p < 0.001). Lack of proper mentoring opportunity (86.2%) and knowledge (84.5%) were the main barriers in conducting research. Even though they have a positive perspective, only a few undergraduates enrolled in research. Medical universities should encourage faculties to supervise and guide undergraduates' projects, and provide feasible solutions for students to learn scientific knowledge and skills. It is vital to build a research‐oriented environment and academic atmosphere.
Metabolomics study based on GC–MS reveals a protective function of luteolin against glutamate‐induced PC12 cell injury
Authors: Gao Ying , Zhu Jinfeng , Sun Mengyao , Wang Shaomin , Liu Hongmin
Published: October 2022

Oxidative stress response is closely related to neurodegenerative diseases. This study aimed to investigate the cytoprotective effects of luteolin on glutamate‐induced oxidative stress injury in PC12 cells. GC–MS combined with multivariate statistical approaches was used to perform metabolomics studies to assess the possible mechanisms. Our results identified 23 metabolites as differential expressed metabolites in the glutamate group, including cysteine content in cells that decreased drastically. This suggests that glutathione synthesis, which balances the redox state of cells, was affected. Luteolin inhibits the reduction in viability in glutamate‐induced PC12 cells and regulates 13 differential expressed metabolites in glutamate‐induced cell damage. These metabolites associated with luteolin included glycine, serine, and threonine metabolism; glyoxylate and dicarboxylate metabolism; aminoacyl‐tRNA biosynthesis; cysteine and methionine metabolism; inositol phosphate metabolism; and starch and sucrose metabolism. In summary, the systemic antioxidant capacity of luteolin in PC12 cells is related to its regulation of amino acid, glucose, and nucleotide metabolism pathways.
Why do young people engage in some civic actions and not others? Exploring the roles of individual and collective civic efficacy
Authors: Gee Matthew N. , Johnson Sara K.
Published: October 2022

Civic actions are behaviours intended to improve conditions for others or help shape a community's future. Such actions vary widely from voting to voluntary helping, from canvassing to community organizing, and attempts have been made to categorize the array of civic actions. However, the question of why young adults engage in some types of civic actions versus others is not well understood. Using data from 598 White, cisgender, heterosexual young adults in the United States, we examined the relations between individual civic efficacy, collective civic efficacy, and seven actions: writing social media posts, voting, buycotting, volunteering, participating in an organization, supporting political candidates, and protesting. We hypothesized that individual efficacy would be positively related to all seven actions, but collective efficacy would be more strongly related to collective or political actions, compared to the individual or civil ones. Logistic regression analyses showed that individual efficacy positively predicted engagement in all seven civic actions. Individual and collective efficacy had a complex curvilinear relation with buycotting and supporting political candidates. Implications for future research and applications aimed at promoting civic engagement amongst young adults are discussed. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.
Gold(III) Catalyzed Overman Rearrangements: Controlling Steric Interactions using Pincer‐Type Ligands
Authors: Engbers Silène , Trifonova Evgeniya A. , van der Geest Kirsten M. , Nauta Wietske J. , Hess Kristopher M. , Klein Johannes E. M. N.
Published: October 2022

Spatial control of reactivity is intrinsically difficult in gold catalysis due to the linear coordination mode of Au(I) and the commonly flat ligands employed for Au(III) complexes. Our recent report of a novel and sterically encumbered (NNN)diiPrAu−OH complex (Eur. J. Inorg. Chem. 2021, 3561–3564.) suggested that the (NNN) ligand framework is capable of sterically interacting with substrates through its conveniently oriented aryl groups. We have now examined these steric properties in more detail by varying the ortho‐substituent of the aryl group in (NNN)xAu−Cl complexes. With just small modifications we were able to vary the buried volume around the Cl atom and correlate this to yields obtained in a Au‐catalyzed Overman rearrangement. Computationally we further elucidate that the stark difference in yields obtained originates from a shift in binding mode of the substrate to the Au catalyst in the rate limiting step of the reaction. We thus conclude that delicate spatial control can be exercised in gold catalysis and propose the (NNN) ligand framework to be an attractive platform for the efficient design of Au(III) complexes for stereoselective catalysis.
Gene expression pattern of adenosine receptors in lung tumors
Authors: Asgharkhah Elnaz , Saghaeian Jazi Marie , Asadi Jahanbakhsh , Jafari Seyyed Mehdi
Published: October 2022

Background

Adenosine, a purine nucleoside, plays an important function in the pathogenesis of cancer through interaction with the cell surface G protein‐coupled adenosine receptors. It is important to determine the expression pattern of these receptors in different cancers. Previously in our lab, we found up‐regulation of A1 adenosine receptor (AR) in lung tumors playing as a putative target for cancer cell inhibition, and here we aimed to investigate the significance of other adenosine receptor isoforms (A2aAR, A2bAR, and A3AR).

Methods

In this study, first of all, we evaluated the adenosine receptors gene expression in the bioinformatics database (GENT2). Then the genes expression was measured experimentally in the 20 lung cancer tumor tissues in comparison to the matched tumor‐adjacent normal tissue (as control). The mRNA expression of receptors was evaluated by real‐time PCR. The tumors were categorized by the tumor size and the gene expression change was evaluated.

Results

The experimental results indicated a significant increase in A2aAR (p value = .021) and A3AR (p value = .01) expression in lung tumor tissues compared to the adjacent tumor margins which were in accordant to bioinformatics analysis. We found a non‐significant increase in A2bAR expression; however, when comparing the patients according to the tumor size, our data showed that the expression of A2bAR adenosine receptor in patients with smaller lung tumor sizes was higher than the other group (p = .011).

Conclusion

The results of this study showed that adenosine receptors A3AR, and A2aAR are highly expressed in lung tumors relative to tumor‐adjacent normal tissue. We suggest that overexpression of adenosine receptors in lung cancer is due to their regulatory role in various aspects of lung cancer.
Population Pharmacokinetic Analysis of Valsartan in Healthy Chinese Subjects
Authors: Yang Haiyun , Gao Ruomei , Ji Xingfang , Wang Zhipeng , Qiu Wen
Published: October 2022

The study was conducted to establish a population pharmacokinetic (PPK) model of valsartan in Chinese healthy subjects and investigate potential covariate impacts on the pharmacokinetics (PK) parameters. Data from a bioequivalence study with 78 Chinese healthy subjects were retrospectively analyzed to develop a PPK model of valsartan. Phoenix NLME 8.1 was used to build a PPK model and quantify the effects of covariates, such as demographic data and biochemical, on the PK parameters of valsartan. For the healthy Chinese population, valsartan conformed to the two‐compartment model with an absorption lag time. In the final PPK model, food affected the absorption rate constant, while aspartate aminotransferase, alanine aminotransferase, and creatinine affected the clearance of the central compartment. The final PPK model was verified to be reproducible, and it can be used to evaluate the PK parameters. This is the first research describing the PPK profile of valsartan in healthy Chinese subjects, and it is expected to provide relevant PK parameters for further study of valsartan.
Effect of Severe Renal Impairment on Pharmacokinetics, Safety, and Tolerability of ACT‐1014‐6470, a Novel Oral Complement Factor 5a Receptor 1 Antagonist
Authors: Hammann‐Hänni Anya , Kaufmann Priska , Klein Gernot , Schmid Karin , Dingemanse Jasper
Published: October 2022

The aim of this study was to examine the safety and the effect of severe renal impairment (RI) on the pharmacokinetics of ACT‐1014‐6470, a novel oral complement factor 5a receptor 1 antagonist. A phase 1 single‐center, open‐label, single‐dose, parallel‐group study was conducted in subjects with severe RI (n = 8) compared to demographically pairwise matched subjects with normal renal function (n = 8). Plasma levels of ACT‐1014‐6470 were measured up to 120 hours following an oral 40‐mg dose. Safety evaluations included adverse events (AEs), vital signs, hematology, coagulation, clinical chemistry tests, and electrocardiograms. All 16 subjects completed the study. Relative to subjects with normal renal function, ACT‐1014‐6470 time to maximum plasma concentration was delayed with a median of differences of 3 hours. The maximum plasma concentration and the area under the plasma concentration–time profile from time zero to infinity were comparable indicated by geometric mean ratios (90%CI) of 0.85 (0.53–1.37) and 1.17 (0.73–1.85), respectively. Four transient and mild AEs in three subjects with severe RI were reported; three AEs were considered not related to ACT‐1014‐6470. These results support the use of ACT‐1014‐6470 in subjects with mild to severe RI without the need of dose adjustment.
Prevalence of diabetic retinopathy in patients with newly diagnosed type 2 diabetes: A systematic review and meta‐analysis
Authors: Cai Ke , Liu Yi‐Ping , Wang Dan
Published: October 2022

Aims

Type 2 diabetes mellitus (T2DM) can remain undiagnosed for many years, during which micro‐ and macro‐vascular complications may develop. This study aimed to assess the worldwide prevalence of diabetic retinopathy (DR) in patients with newly diagnosed T2DM.

Materials and Methods

We systematically searched electronic databases for relevant studies published from inception to 01 January 2022. Selected studies reported the prevalence of DR among patients with newly diagnosed T2DM, specifying the case definition used. Random‐effects meta‐analysis was used to derive the pooled prevalence. Subgroup and meta‐regression analyses were used to investigate variations in the prevalence estimates in terms of available variables.

Results

Data from 77 studies including 99,847 patients with newly diagnosed T2DM were included from 26 countries. The pooled prevalence of DR among patients with newly diagnosed T2DM was 13.1% (95% CI, 11.1%–15.1%; I2 = 97.0%). DR was higher in clinic‐based samples compared with community‐based samples (15.0%, 95% CI = 12.4%–17.8% vs. 11.5%, 95% CI = 8.9%–14.5%; p = 0.05; I2 = 97.0%) and was higher in countries in the WHO African 19.2% (95% CI, 14.6%–24.3%; I2 = 76.0%), South‐East Asia 15.4% (95% CI, 10.0%–21.6%; I2 = 79.1%), and European 15.0% (95% CI, 11.2%–19.2%; I2 = 82.0%) regions. A higher proportion of female patients was significantly associated with a lower prevalence of DR in patients with newly diagnosed T2DM. We observed that the prevalence of DR in patients with newly diagnosed T2DM has remained unchanged over time.

Conclusions

Globally, DR is a prevalent complication among patients with newly diagnosed T2DM indicating the importance of establishing effective strategies to promote regular screening for the early diagnosis of T2DM alongside routine ophthalmic assessment at the time of T2DM diagnosis to reduce the burden of vision‐threatening retinopathy.
Determination of the microbial community of traditional Mongolian cheese by using culture‐dependent and independent methods
Authors: Guo Liang , Xu Wei‐Liang , Li Chun‐Dong , Wang Fu‐Chao , Guo Yuan‐Sheng , Ya Mei
Published: October 2022

Mongolian cheese is not only a requisite source of food for the nomadic Mongolian but also follows a unique Mongolian dairy artisanal method of production, possessing high nutritional value and long shelf‐life. In this study, the ancient technique for the production of Mongolian cheese was investigated. The nutritional value of Mongolian cheese was characterized by its high‐protein content (30.13 ± 2.99%) and low‐fat content (9.66 ± 3.36%). Lactobacillus, Lactococcus, and Dipodascus were the predominant bacterial and fungal genera, and Lactobacillus helveticus, Lactococcus piscium, and Dipodascus geotrichum were the predominant species in the Mongolian cheese. The microbiota of products from different cheese factories varies significantly. The high‐temperature (85°C–90°C) kneading of coagulated curds could eliminate most of the thermosensitive microorganisms for extending the shelf‐life of cheese. The indigenous spore‐forming microbes, which included yeasts, belonging to Pichia and Candida genera, and molds, belonging to Mucor and Penicillium genera, which originated from the surroundings during the process of cooling, drying, demolding, and vacuum packaging could survive and cause the package to swell and the cheese to grow mold. The investigation of production technology, nutrition, microbiota, and viable microbes related to shelf‐life contributes to the protection of traditional technologies, extraction of highlights (nutritional profiles and curd scalding) for merchandise marketing, and standardization of Mongolian cheese production, including culture starters and aseptic technique.
Attitudes and practices of health care providers towards improving adherence to smoking cessation medications in Australia: A descriptive study
Authors: Mersha Amanual Getnet , Eftekhari Parivash , Kennedy Michelle , Gould Gillian Sandra
Published: October 2022

Issue Addressed

Adherence to smoking cessation medications is low and predicts the success of quit attempts. Health care providers (HCPs) role in delivering smoking cessation support is crucial. HCPs support to improve adherence to smoking cessation medication has not been evaluated in Australia. This study describes the attitudes and practices of HCPs in Australia towards adherence to smoking cessation medications (nicotine replacement therapies, varenicline and bupropion) and intervention options.

Methods

A descriptive cross‐sectional study was conducted using a convenience sample of 70 HCPs in Australia. Participants were recruited through the social media platforms of professional societies in Australia. Data was collected in the periods between November 2020 and September 2021. Descriptive statistics were performed using SPSS statistical software version 27.0 and data was presented using proportions and percentages.

Results

The majority of participants were doctors, nurses and midwives (82.8%). Almost two‐thirds of the participants (68.6%) self‐reported that they provided adequate adherence support to individuals taking smoking cessation medications. The majority of participants (87.1%) identified adherence support service as part of their professional role. Only 11.1% of the participants who did not believe supporting medication adherence to be their role reported providing adherence support. The main perceived barriers to adherence support are lack of skill, knowledge, time and resources. HCPs believed that providing additional counselling and monitoring of adherence can improve adherence rates.

Conclusions

In an online survey conducted in Australia, HCPs indicated multiple barriers to providing adherence support and intervention strategies that should be considered for smoking cessation programs. A higher proportion of participants who perceived adherence support as their professional role reported supporting adherence to smoking cessation medications.

So What?

Considerations should be given to improve HCPs attitudes and practices towards smoking cessation medications adherence support. Smoking cessation programs should consider the issue of adherence support. Further studies with a larger sample size across a broader range of HCPs are needed to extensively understand adherence service provision among HCPs in Australia.
Downregulated formyl peptide receptor 2 expression in the epileptogenic foci of patients with focal cortical dysplasia type IIb and tuberous sclerosis complex
Authors: Huang Kaixuan , Wang Zhongke , He Zeng , Li Yang , Li Shujing , Shen Kaifeng , Zhu Gang , Liu Zhonghong , Lv Shengqing , Zhang Chunqing , Yang Hui , Yang Xiaolin , Liu Shiyong
Published: October 2022

Background

Focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) show persistent neuroinflammation, which promotes epileptogenesis and epilepsy progression, suggesting that endogenous resolution of inflammation is inadequate to relieve neuronal network hyperexcitability. To explore the potential roles of formyl peptide receptor 2 (FPR2), which is a key regulator of inflammation resolution, in epilepsy caused by FCDIIb and TSC, we examined the expression and cellular distribution of FPR2.

Method

The expression of FPR2 and nuclear factor‐κB (NF‐κB) signaling pathway was examined by real‐time PCR, western blots, and analyzed via one‐way analysis of variance. The distribution of FPR2 was detected using immunostaining. The expression of resolvin D1 (RvD1, the endogenous ligand of FPR2) was observed via enzyme‐linked immunosorbent assay. Pearson's correlation test was used to evaluate the correlation between the expression levels of FPR2 and RvD1 and the clinical variants.

Results

The expression of FPR2 was significantly lower in FCDIIb (p = .0146) and TSC (p = .0006) cortical lesions than in controls, as was the expression of RvD1 (FCDIIb: p = .00431; TSC: p = .0439). Weak FPR2 immunoreactivity was observed in dysmorphic neurons (DNs), balloon cells (BCs), and giant cells (GCs) in FCDIIb and TSC tissues. Moreover, FPR2 was mainly distributed in dysplastic neurons; it was sparse in microglia and nearly absent in astrocytes. The NF‐κB pathway was significantly activated in patients with FCDIIb and TSC, and the protein level of NF‐κB was negatively correlated with the protein level of FPR2 (FCDIIb: p = .00395; TSC: p = .0399). In addition, the protein level of FPR2 was negatively correlated with seizure frequency in FCDIIb (p = .0434) and TSC (p = .0351) patients.

Conclusion

In summary, these results showed that the expression and specific distribution of FPR2 may be involved in epilepsy caused by FCDIIb and TSC, indicating that downregulation of FPR2 mediated the dysfunction of neuroinflammation resolution in FCDIIb and TSC.
Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL‐6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro
Authors: Liu Jie , Xie Xiaolan , Qin Kai , Xu Le , Peng Juxiang , Li Xiangyu , Li Xiongjuan , Liu Zhiheng
Published: October 2022

Background

Dexamethasone (Dexa) and potassium canrenoate (Cane) modulate nociceptive behavior via glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) by two mechanisms (genomic and nongenomic pathways). This study was designed to investigate the Dexa‐ or Cane‐mediated nongenomic and genomic effects on mechanical nociception and inflammation‐induced changes in interleukin‐6 (IL‐6) mediated signaling pathway in rats.

Methods

Freund's complete adjuvant (FCA) was used to trigger an inflammation of the right hind paw in male Sprague–Dawley rats. First, the mechanical nociceptive behavioral changes were examined following intraplantar administration of GR agonist Dexa and/or MR antagonist Cane in vivo. Subsequently, the protein levels of IL‐6, IL‐6Rα, JAK2, pJAK2, STAT3, pSTAT3Ser727, migration inhibitory factor, and cyclooxygenase‐2 were assessed by Western blot following intraplantar injection of Dexa or Cane or the combination. Moreover, the molecular docking studies determined the interaction between Dexa, Cane, and IL‐6. The competition binding assay was carried out using enzyme‐linked immunosorbent assays (ELISA).

Results

Administration of Dexa and Cane dose‐dependently attenuated FCA‐induced inflammatory pain. The sub‐additive effect of Dexa/Cane combination was elucidated by isobologram analysis, accompanied by decrease in the spinal levels of IL‐6, pJAK2, and pSTAT3Ser727. The molecular docking study demonstrated that both Dexa and Cane displayed a firm interaction with THR138 binding site of IL‐6 via a strong hydrogen bond. ELISA revealed that Dexa has a higher affinity to IL‐6 than Cane.

Conclusions

There was no additive or negative effect of Dexa and Cane, and they modulate the IL‐6/JAK2/STAT3 signaling pathway through competitive binding with IL‐6 and relieves hypersensitivity during inflammatory pain.
DOS strategy, crystal structure, and in silico evaluation of the anti‐inflammatory activity of hydroxysulfanylazole derivatives
Authors: Akhmadiev Nail , Mescheryakova Ekaterina , Khayrullina Veronica , Khalilov Leonard , Akhmetova Vnira
Published: October 2022

We developed a DOS approach to the synthesis of hydroxysulfanylazole derivatives (12 examples) using diversification with various N,N‐ and N,O‐binucleophilic reagents of the carbonyl groups of hydroxysulfanyl diketones (6 examples) obtained by the piperidine‐catalyzed thiomethylation reaction involving the С(α)‐Н position of 2,4‐pentanedione with aromatic aldehydes and 2‐mercaptoethanol. X‐ray diffraction analysis was used to determine the structures and crystal packing for three hydroxysulfanylpyrazoles. The calculation of the intermolecular interactions in the crystals (analysis of Hirshfeld surfaces) demonstrated the influence of the substituent nature on the contribution of the H…O/O…H contacts. Using molecular docking studies, justified assumptions were made about the complementarity of the obtained series of compounds to the active sites of COX isoforms.
Plasma SNORD42B and SNORD111 as potential biomarkers for early diagnosis of non‐small cell lung cancer
Authors: Wang Kangyu , Song Xingguo , Wang Shiwen , Li Xinyi , Zhang Zhijun , Xie Li , Song Xianrang
Published: October 2022

Background

Non‐small‐cell lung cancer (NSCLC) still occupied the leading reason of cancer death due to lack of availability of early detection. This study aimed to identify the effective biomarkers for the early‐stage NSCLC diagnostics based on plasma snoRNAs.

Materials and Methods

The differential snoRNAs between lung cancer patients and healthy donors were analyzed using the SNORic and TCGA databases. SNORD42B and SNORD111 were screened out and further verified in 48 FFPE NSCLC and adjacent normal tissues, as well as in plasma from 165 NSCLC patients and 118 health donors using qRT‐PCR. Next, their diagnostic efficiency, as well as combined with carcinoembryonic antigen (CEA), was obtained by the analysis of receiver operating characteristic (ROC).

Results

We first screened out 47 top differential snoRNAs, among which the top 10 upregulated snoRNAs in LUAD were U44, U75, U78, U77, SNORD72, SNORD13, SNORD12B, SCARNA5, U80, SNORD41, and in LUSC were U44, U75, U78, SNORD41, SNORD111, SNORA56, U17a, SNORD35A, SNORD32A, SNORA71D. SNORD42B and SNORD111 was significantly increased not only in tumor tissues but also in plasma from NSCLC and early‐stage NSCLC patients. They were capable to act as promising biomarkers for NSCLC and early‐stage NSCLC diagnosis. Moreover, CEA diagnostic efficiency for early‐stage NSCLC was significantly improved when combined with these two plasma snoRNAs.

Conclusion

SNORD42B and SNORD111 could act as the potential and non‐invasive diagnostic biomarkers for NSCLC and early‐stage NSCLC.
Diagnostic performance of gray‐scale ultrasound and shear wave elastography in assessing salivary gland involvement in patients with primary Sjögren's syndrome
Authors: Özer Halil , Tezcan Dilek , Hakbilen Selda , Gülcemal Semral , Topaloğlu Ömer Faruk , Yazol Merve , Yılmaz Sema
Published: October 2022

Purpose

To investigate the diagnostic performance of gray‐scale ultrasound (US) and shear wave elastography (SWE) for determining salivary gland involvement primary Sjögren's syndrome (pSS).

Methods

In this prospective study, the salivary glands of 72 healthy volunteers and 74 participants with pSS were examined by two blinded radiologists with consensus using gray‐scale US and SWE. SWE parameters were compared between groups. The area under the curve (AUC), sensitivity, and specificity of gray‐scale US and SWE was analyzed. The correlation between SWE and clinical findings was investigated.

Result

The SWE parameters of the parotid and submandibular glands were significantly higher in the pSS group, but did not differ significantly based on serologic assays, Schirmer test, minor salivary gland biopsy, and comorbidities. The AUC values for gray‐scale US of the salivary glands were significantly lower than the AUC values for SWE. The elasticity modulus (kPa) of parotid gland had the highest AUC value (0.937; 95% CI, 0.901–0.973), with a sensitivity of 93.2% and a specificity of 83.3%. SWE had no correlation with age, disease duration, laboratory values, or disease activity.

Conclusion

SWE provides excellent diagnostic performance for submandibular and parotid gland involvement in pSS and can be used to complement gray‐scale US.
Development of electrostatic‐induced charge detector for multiturn time‐of‐flight mass spectrometer
Authors: Bajo Ken‐ichi , Aoki Jun , Ishihara Morio , Furuya Shizuho , Nishimura Masahiro , Yoshitake Miwa , Yurimoto Hisayoshi
Published: October 2022

We developed an autocorrelation function to resolve the overtaking problem in a multiturn time‐of‐flight mass spectrometer (TOF–MS). The function analyzes the characteristic period for one lap of each ion packet and derives a mass spectrum from a signal pulse train composed of multiturn ion packets. To detect the ion pulse train, a new nondestructive ion detector was developed and installed in the multiturn orbit of MULTUM‐S II. This detector is composed of an electrostatically induced charge detector, a preamplifier, and a digitizer. The electrostatic noises are smaller than the single‐ion signals owing to the accumulation of the multiturn TOF spectrum. The conventional ion detector of TOF–MS is operated after collecting the signal pulse train. The multiturn TOF spectrum was convolved with an autocorrelation function to derive the mass spectrum. The convolved mass spectrum performed a mass resolving power (MRP) of 28,200 at m/z 69 and mass accuracy of 28 ppm for the perfluorotributylamine (PFTBA) gas sample.