bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and immune microenvironment characterization of HER2‐positive gastric cancer: Their association with response to trastuzumab‐based treatment
Authors: Kwon Hyun Jung , Park Yujun , Nam Soo Kyung , Kang Enoch , Kim Ka‐Kyung , Jeong Inhae , Kwak Yoonjin , Yoon Jeesun , Kim Tae‐Yong , Lee Keun‐Wook , Oh Do‐Youn , Im Seock‐Ah , Kong Seong‐Ho , Park Do Joong , Lee Hyuk‐Joon , Kim Hyung‐Ho , Yang Han‐Kwang , Lee Hye Seung
Published: March 2023

Background

We aimed to determine the molecular and immune microenvironment characteristics of HER2‐positive gastric cancer (GC) related to the patient's response to first‐line trastuzumab‐based treatment.

Methods

Eighty‐three cases of HER2‐positive advanced gastric adenocarcinoma patients treated with trastuzumab were enrolled. Targeted deep sequencing and transcriptome analysis were performed on selected 21 cases (exploration cohort) along with two post‐treatment samples. The results were compared between patients progressed before 6 months (Group 2) and others (Group 1), and were validated by FISH and immunohistochemistry in total cohort. Tumor‐infiltrating immune cells were evaluated using RNA sequencing data and multiplex immunohistochemistry. Progression‐free survival (PFS) analysis was performed.

Results

Group 1 showed frequent amplification of G1/S cell cycle checkpoint‐related genes and upregulated KEGG pathways related to cell proliferation. In contrast, Group 2 had more frequent EGFR, HER3, and MET amplification and higher RNA expression in immune‐related KEGG pathways than Group 1. In total cohort, significant predictors of better PFS were cell cycle‐related including CCNE1 amplification, Cyclin A and PLK1 overexpression, and decreased Cyclin D3 and HER3 expression (p < 0.05), or immune‐related including high density of CD3−CD57+ NK cells and PD‐L1 combined positive score ≥5 (p < 0.05). The best prognostic predictors were a combination of Cyclin A, Cyclin E, p21, and HER3 (p < 0.001).

Conclusion

HER2‐positive GC with favorable response to trastuzumab were characterized by cell cycle‐related gene alterations and increased CD3−CD57+ NK cell infiltration. These findings would be helpful to the fine modulation of therapeutic strategies for patients with HER2‐positive GC.
Discovery of New D‐Ring Modified Isosteviol Derivatives as Potent Cardioprotective Agents against Oxidative Stress‐Trigged Damage
Authors: Chen Zhenyu , Xu Ruilong , Jia Qi , Xu Xiaojia , Li Dehuai , Li Zhiyin , Luo Liping , Zhao Yu
Published: March 2023

Cardiovascular diseases (CVDs) are a major global health concern, and oxidative stress is known to play a central role in their pathogenesis. The identification of new agents capable of inhibiting oxidative stress presents a promising strategy for preventing and treating CVDs. Natural products and their derivatives offer a valuable source for drug discovery, and isosteviol, a readily available natural product, is known to exhibit cardioprotective effects. In this study, 22 new D‐ring modified isosteviol derivatives were synthesized and evaluated for their cardioprotective effect in vivo using the zebrafish cardiomyopathy model. The findings revealed that derivative 4e exhibited the most potent cardioprotective effect, surpassing its parent compound isosteviol and the positive drug levosimendan. At 1 μM, derivative 4e significantly protected the cardiomyocytes from injury, while at 10 μM it effectively maintained normal heart phenotypes, preventing cardiac dysfunction in zebrafish. Further investigation demonstrated that 4e protected cardiomyocytes from oxidative stress‐induced damage by inhibiting reactive oxygen species overaccumulation, activating superoxide dismutase 2 expression, and enhancing the endogenous antioxidant defense system. These results suggest that isosteviol derivatives, particularly 4e, have the potential to serve as a novel class of cardioprotective agents for the prevention and treatment of CVDs.
Characterization of commercial cricket protein powder and impact of cricket protein powder replacement on wheat dough protein composition
Authors: Perez‐Fajardo Mayra , Bean Scott R. , Ioerger Brian , Tilley Michael , Dogan Hulya
Published: March 2023

Background and Objectives

Supplementation of foods with insect flours has been shown to be promising for improving the nutritional profile of food products. The objective of this study was to characterize two commercially available cricket protein powders and investigate their impact on molecular weight distribution when incorporated into wheat dough.

Findings

Characterization of commercial cricket protein powders, GrioPro® (G) and Entomo Farms (E) was carried out by size exclusion high‐performance liquid chromatography (SEC‐HPLC), and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE). The functionality of the cricket protein powders was examined by measuring water holding capacity (WHC) and protein solubility across a range of pH. To see the interactions between the cricket proteins in a food‐based system wheat dough samples containing 10% or 20% replacement levels of the cricket powders were collected at peak torque development and analyzed to SEC‐HPLC to quantify the change in soluble polymeric proteins (SPP) and insoluble polymeric proteins (IPP) and provide information on changes to protein molecular weight distribution. SDS‐PAGE analysis showed bands ranging from 40 kDa to 160 kDa for sample E while sample G had no visible bands either due to poor solubility in SDS‐PAGE sample buffer and/or the presence of very high molecular proteins that did not enter the gel. Sample E absorbed approximately 2.5 times its weight in water, which was significantly lower than G (~3.0 times its weight) while sample G was significantly lower in solubility than E across all pH levels.

Conclusions

Both cricket protein powders increased in WHC and solubility as the pH increased. Wheat dough samples containing sample E had lower peak areas of IPP and no significant difference in SPP peak areas compared to the control. On the other hand, doughs containing sample G had a significant increase in IPP peak areas at the 20% replacement level.

Significance and Novelty

This study shows how the difference in processing changed the functionality of G and E which impacted their interactions when added to a wheat dough‐based system.
Stereoselective Synthesis and Characterization of Indenone Azine‐Based Electron‐Accepting π‐Conjugated Systems
Authors: Takagi Shu I. , Hayakawa Masahiro , Fukazawa Aiko
Published: March 2023

Indenone azines, in which the exocyclic C=C bond in dibenzopentafulvalene is replaced by an azine moiety (C=N−N=C), have been synthesized as novel electron‐accepting π‐conjugated scaffolds. Structural modulation at the 7,7′‐positions of indenone azines enabled stereoselective syntheses of diastereomers in which the configurations of the two C=N bonds are E,E or Z,Z. X‐ray crystallographic analyses revealed that all the indenone azines exhibit high coplanarity in contrast to the twisted frameworks of dibenzopentafulvalene derivatives, resulting in the formation of densely π‐stacked structures. Electrochemical measurements and quantum chemical calculations revealed the electron‐accepting character of indenone azines comparable to isoindigo dyes. In particular, the intramolecular hydrogen bonds of 7,7′‐dihydroxy‐substituted derivatives impart enhanced electron‐accepting character and significantly red‐shifted photoabsorption. This study demonstrates that indenone azines represent a promising candidate as electron‐accepting building blocks for optoelectronic materials.
Oxidation State Tuning of Room Temperature Phosphorescence and Delayed Fluorescence in Phenothiazine and Phenothiazine‐5,5‐dioxide Dimers
Authors: Wright Iain A. , Etherington Marc K. , Batsanov Andrei S. , Monkman Andrew P. , Bryce Martin R.
Published: March 2023

Heterocyclic dimers consisting of combinations of butterfly‐shaped phenothiazine (PTZ) and its chemically oxidized form phenothiazine‐5,5‐dioxide (PTZ(SO2)) have been synthesized. A twist is imposed across the dimers by ortho‐substituents including methyl ethers, sulfides and sulfones. X‐ray crystallography, cyclic voltammetry and optical spectroscopy, underpinned by computational studies, have been employed to study the interplay between the oxidation state, conformational restriction, and emission mechanisms including thermally activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP). While the PTZ(SO2) dimers are simple fluorophores, the presence of PTZ induces triplet‐mediated emission with a mixed PTZ‐PTZ(SO2) dimer displaying concentration dependent hallmarks of both TADF and RTP.
Triboelectric Nanogenerators Assembled by Cobalt(II) Coordination Polymer Incorporated Composite Films and their Application for Self‐Powered Anticorrosion
Authors: Huang Chao , Zhang Sheng , Liu Saiwei , Zhang Qiang , Zhang Ying‐Ying , Mi Liwei
Published: March 2023

A friction layer with stability and durability is important to promote the practical application of triboelectric nanogenerators (TENGs). In this work, a two‐dimensional cobalt coordination polymer (Co‐CP) was successfully synthesized using cobalt nitrate, 4,4′,4′′‐tricarboxyltriphenylamine and 2,2′‐bipyridine. To clearly clarify the effect of the doping proportions of Co‐CP and the types of composite polymers on the output performance of the TENG, Co‐CP was combined with two organic polymers having different polarities (polyvinylidene fluoride (PVDF) and ethyl cellulose (EC)) to form a series of composite films, which were used as the friction electrode materials to fabricate TENGs. Electrical characterizations indicated that a high output current and voltage were obtained from the TENG based on 15 wt.% Co‐CP incorporated in PVDF (Co‐CP@PVDF), which could be further improved by the Co‐CP@EC composite film at the same doping ratio. Furthermore, the optimally fabricated TENG was demonstrated to prevent electrochemical corrosion of carbon steel.
Nickel‐Catalyzed Regio‐ and Enantioselective Ring Opening of 3,4‐Epoxy Amides and Esters with Aromatic Amines
Authors: Liu Jiawei , Tang Wei , Wang Chuan
Published: March 2023

Herein we present a nickel‐catalyzed regio‐ and enantioselective ring opening reaction of 3,4‐epoxy amides and esters with aromatic amines as nucleophiles. This method features high regiocontrol, diastereospecific SN2 reaction pathway, broad substrate scope, and mild reaction conditions, furnishing a wide range of γ‐amino acid derivatives in a highly enantioselective manner. Notably, the selective nucleophilic attack to the C‐4 position of epoxides is controlled by the directing effect of the pendant carbonyl group.
Electrically Heated Oxide Ceramic Tubes for High Temperature Reactions
Authors: Matthies Jörn , Schall Thomas , Pritzkow Walter , Tuttlies Ute , Nieken Ulrich
Published: March 2023

Endothermic high temperature reactions are usually carried out in metal tubes heated by gas burners. Electrical heating allows substantial reduction of CO2 emissions. We propose the usage of a composite tube, where a thin metallic layer is embedded between an inner and outer ceramic layer. While monolithic ceramics suffer from brittleness and low tolerance to thermal stress, only the inner layer is made from monolithic ceramics, while the outer layer is made of fiber reinforced oxide ceramics. In first tests the hybrid ceramic tube was electrically heated to 1250 °C with a maximum heat release of 85 kW m−2.
Born global in 1847: International entrepreneurship at Siemens
Authors: Schmidt Heiko M. , Santamaria‐Alvarez Sandra Milena
Published: March 2023

The early internationalization of new ventures has been described as a contemporary phenomenon enabled by globalization and digital technologies. However, today's multinational enterprise Siemens, founded in 1847, fits extant definitions of born globals. Based on this historical case, this study seeks to answer the question: What are enduring and contextually invariant aspects of early internationalization processes? An abductive analysis of the company's first 3 decades finds six relevant and emergent themes. We contribute to international entrepreneurship research by presenting evidence that early internationalization is not a new phenomenon, showing support for multiple extant findings, and providing new insights for otherwise underexplored themes. We also provide future research directions regarding personal‐level processes in international new ventures based on the analyzed 30 years.
Impact of turbulence modeling on the simulation of blood flow in aortic coarctation
Authors: Katz Sarah , Caiazzo Alfonso , Moreau Baptiste , Wilbrandt Ulrich , Brüning Jan , Goubergrits Leonid , John Volker
Published: March 2023

Numerical simulations of pulsatile blood flow in an aortic coarctation require the use of turbulence modeling. This paper considers three models from the class of large eddy simulation (LES) models (Smagorinsky, Vreman, ‐model) and one model from the class of variational multiscale models (residual‐based) within a finite element framework. The influence of these models on the estimation of clinically relevant biomarkers used to assess the degree of severity of the pathological condition (pressure difference, secondary flow degree, normalized flow displacement, wall shear stress) is investigated in detail. The simulations show that most methods are consistent in terms of severity indicators such as pressure difference and stenotic velocity. Moreover, using second‐order velocity finite elements, different turbulence models might lead to considerably different results concerning other clinically relevant quantities such as wall shear stresses. These differences may be attributed to differences in numerical dissipation introduced by the turbulence models.
Cluster based energy efficient routing protocol for heterogeneous wireless sensor networks
Authors: Prashanth G. S. , Manjunatha P.
Published: March 2023

With the advancement in recent technologies, wireless sensor networks (WSNs) have emerged to become one of the key research areas. Sensor nodes in WSN are deployed randomly to sense the events that occur in an area. Clustering of sensor nodes in a wireless sensor network will result in better energy efficiency and topology management. In many scenarios, wireless sensor networks are deployed in remote areas and in hostile environments where batteries cannot be recharged or replaceable. In real world applications, heterogeneous sensor nodes with different initial energies in a WSN are more preferable to prolong stability period, network lifetime, and throughput. The main objective of this article is to design and develop a cluster‐based energy efficient routing protocol for heterogeneous wireless sensor networks (CEER). The proposed CEER routing protocol is based on the residual energy of all the sensor nodes in each round, distance of each sensor node from the base station, weighted election probabilities and reliability of a sensor node and the network. It is found from the results that, the proposed CEER routing protocol provides better stability, network lifetime, and throughput as compared with the existing routing protocols of heterogeneous wireless sensor networks.
Acetylene‐Mediated Borophosphene Dirac Materials as Efficient Anode Materials for Lithium‐Ion Batteries
Authors: Esackraj Karthikraja , Nulakani Naga Venkateswara Rao , Choutipalli Venkata Surya Kumar , Chowdhury Chandra , Murugan Palanichamy , Vaidyanathan V. G. , Subramanian Venkatesan
Published: March 2023

Generally, graphynes have been generated by the insertion of acetylenic content (−C≡C−) in the graphene network in different ratios. Also, several aesthetically pleasing architectures of two‐dimensional (2D) flatlands have been reported with the incorporation of acetylenic linkers between the heteroatomic constituents. Prompted by the experimental realization of boron phosphide, which has provided new insights on the boron‐pnictogen family, we have modelled novel forms of acetylene‐mediated borophosphene nanosheets by joining the orthorhombic borophosphene stripes with different widths and with different atomic constituents using acetylenic linkers. Structural stabilities and properties of these novel forms have been assessed using first‐principles calculations. Investigation of electronic band structure elucidates that all the novel forms show the linear band crossing closer to the Fermi level at Dirac point with distorted Dirac cones. The linearity in the hole and electronic bands impose the high Fermi velocity to the charge carriers close to that of graphene. Finally, we have also unravelled the propitious features of acetylene‐mediated borophosphene nanosheets as anodes in Li‐ion batteries.
A Second‐Order Nonlinear Optical Material Consisting of Two π‐Conjugated Groups
Authors: Li Minjuan , Wang Ziyi , Ahmed Belal , Li Yanqiang , Wang Han , Song Yipeng , Song Xianyu , Kuang Xiaojun , Luo Junhua , Zhao Sangen
Published: March 2023

This work reports a new second‐order nonlinear optical (NLO) material [C(NH2)3]3C3N3S3 (GU3TMT), consisting of π‐conjugated planar (C3N3S3)3− and triangular [C(NH2)3]+ groups. Interestingly, GU3TMT exhibits a large NLO response (2.0×KH2PO4) and moderate birefringence 0.067 at wavelength 550 nm, even though (C3N3S3)3− and [C(NH2)3]+ do not exhibit the most favorable arrangement in the structure of GU3TMT. First‐principles calculations suggest that NLO properties mainly originate from the highly π‐conjugated (C3N3S3)3− rings, and the π‐conjugated [C(NH2)3]+ triangles contribute much less to the overall NLO response. This work will inspire new thoughts with in‐depth on the role of π‐conjugated groups in NLO crystals.
Corporate environmental responsibility in polluting firms: Does digital transformation matter?
Authors: Lin Boqiang , Zhang Qianxiang
Published: March 2023

The motivations for firms to undertake corporate environmental responsibility (CER) have been a hot topic in academia. However, with the rise of the digital economy, it is still been determined whether digital transformation will become a driving force for firms to assume CER. Based on panel data of Chinese listed firms in polluting industries, this article empirically tests whether and how digital transformation affects CER. The results show that digital transformation significantly motivates firms to assume more CER, especially for state‐owned and large‐scale firms and those located in the western region and ordinary‐level cities. The influence mechanism behind the relationship reveals that digital transformation improves financing ability and further encourages firms to assume CER. However, the effect is only short‐term and has no significant influence on the long‐term financing ability. Further research shows that regional differences in environmental governance pressure can strengthen the effect of digital transformation on CER. Our empirical findings provide policy implications for firms' digital transformation and sustainable development.
An efficient wideband cascode class FF−1 Doherty power amplifier with control harmonic impedance inverter for X‐band applications
Authors: Kumar Rajesh , Kumar Sachin , Kanaujia Binod Kumar
Published: March 2023

This paper presents an efficient Doherty power amplifier (DPA) with optimized harmonic impedance inverter. The proposed design consists of carrier and peaking power amplifiers designed for class F‐ and class F−1‐based operations. Also, multiharmonic non‐uniform stepped‐impedance transmission line‐based input–output matching network is designed for the proposed circuit. The new design maximizes the operating bandwidth by optimizing the control harmonic impedance inverter. The DPA circuit is implemented using the advanced design system simulator, and the chip is made of GaAs 0.25‐μm PHEMT on silicon nitride monolithic microwave integrated circuit die. The fabricated chip exhibits drain efficiency (DE) of 41%–51.5%, power added efficiency of 36.4%–41%, gain of 10.9 dB, and adjacent power leakage ratio of −34.6‐dBc at 30‐dBm peak power. The size of the chip is 2.8 × 1.9 mm2, and it occupies less die area as compared to the existing DPAs.
Electrolytic capacitor‐less reduced power processing single‐phase LED driver with power decoupling using split capacitor
Authors: Pallapati Ramesh Babu , Chinthamalla Ramulu
Published: March 2023

Light emitting diode (LED) driver systems are now moving toward reduced processing power to improve conversion efficiency in indoor and outdoor applications. LED drivers connected to a single‐phase supply must meet the requirements for power factor correction with lower input current harmonics to maintain the alternating current (AC) power grid's quality and maintain a constant current through the LED load to eliminate the flickering effect in the light output. An LED driver is required to fulfill these requirements. In this paper, a new reduced processing power LED driver is proposed. By splitting the output capacitor into two capacitors and with the help of hardware design, the processing power can be reduced by using fewer semiconductors than in earlier designs. The proposed driver employs a simple ripple cancellation control approach to eliminate the 100 Hz ripple in the LED load current. Using this principle, an LED driver was designed and tested. The experimental results demonstrated that the proposed LED driver achieved an input power factor close to unity with lower input current harmonics and 92.5% of peak efficiency when operating at full power.
A metamaterial‐incorporated wireless power transmission system for efficiency enhancement
Authors: Wang Meng , Guo Jingjing , Shi Yanyan , Wang Mengmeng , Song Guangcheng , Yin Renliang
Published: March 2023

In this paper, an efficient wireless power transmission (WPT) system that incorporates a new negative permeability metamaterial is presented. The operating principle of the metamaterial with negative permeability is first analyzed. To improve transmission efficiency of the WPT system at the operating frequency of 13.56 MHz, a new metamaterial with three open rings is designed. By respectively placing a single metamaterial slab and double metamaterial slabs at different positions between transmitting coil and receiving coil, the performance of the proposed WPT system is evaluated by simulation work. The corresponding magnetic field distribution is also analyzed. Besides, comparison is made with the conventional WPT system without metamaterial. It is found that transmission efficiency of the proposed WPT system is obviously improved when incorporating the metamaterial since the designed metamaterial effectively focuses magnetic field towards the receiving coil. Comparing with the conventional system, the results also show that the proposed WPT system is more robust to lateral and angular misalignment of the receiving coil. With the designed metamaterial, it is found that the proposed system with double metamaterial slabs performs better than that with a single metamaterial slab.
Extensive flow cytometric immunophenotyping of human PBMC incorporating detection of chemokine receptors, cytokines and tetramers
Authors: van Wolfswinkel Marjolein , van Meijgaarden Krista E. , Ottenhoff Tom H. M. , Niewold Paula , Joosten Simone A.
Published: March 2023

Characterization of immune cells is essential to advance our understanding of immunology and flow cytometry is an important tool in this context. Addressing both cellular phenotype and antigen‐specific functional responses of the same cells is valuable to achieve a more integrated understanding of immune cell behavior and maximizes information obtained from precious samples. Until recently, panel size was limiting, resulting in panels generally focused on either deep immunophenotyping or functional readouts. Ongoing developments in the field of (spectral) flow cytometry have made panels of 30+ markers more accessible, opening up possibilities for advanced integrated analyses. Here, we optimized immune phenotyping by co‐detection of markers covering chemokine receptors, cytokines and specific T cell/peptide tetramer interaction using a 32‐color panel. Such panels enable integrated analysis of cellular phenotypes and markers assessing the quality of immune responses and will contribute to our understanding of the immune system.
Immunocytochemical detection by a fully automated immunostainer for assisting subclassification of pulmonary tumors on ThinPrep slides in real‐life clinical samples: A single‐institution experience
Authors: Zhao LinLin , Ma HaiYue , Sun Yue , Wang Cong , Chang XinXiang , Guo HuiQin , Zhao Huan , Zhang ZhiHui
Published: March 2023

Introduction

This study aims to investigate the feasibility and reliability of ThinPrep slides in detecting the subclassification of lung cancer and develop a process for immunocytochemistry (ICC) with optimized staining steps of an automated immunostainer.

Methods

Cytomorphology and ancillary ICC by automated immunostainer on ThinPrep slides were performed to subclassify 271 cytology cases of pulmonary tumor, which were stained with 2 or more of the following antibodies: p40, p63, thyroid transcription factor‐1 (TTF‐1), Napsin A, synaptophysin (Syn), and CD56.

Results

The accuracy of cytological subtyping was improved from 67.2% to 92.7% (p < .0001) after ICC. The accuracy of cytomorphology combined with ICC results for lung squamous‐cell carcinoma (LUSC), lung adenocarcinomas (LUAD), and small cell carcinoma (SCLC) was 89.5% (51 of 57), 97.8% (90 of 92), and 98.8% (85 of 86), respectively. The sensitivity and specificity of 6 antibodies were as follows: p63 (91.2%, 90.4%) and p40 (84.2%, 95.1%) for LUSC, TTF‐1(95.6%, 64.6%) and Napsin A (89.7%, 96.7%) for LUAD and Syn (90.7%, 60.0%) and CD56 (97.7%, 50.0%) for SCLC, respectively. P40 expression on ThinPrep slides had the highest agreement (κ = 0.881) with immunohistochemistry (IHC) results, followed by p63 (κ = 0.873), Napsin A (κ = 0.795), TTF‐1 (κ = 0.713), CD56 (κ = 0.576), and Syn (κ = 0.491).

Conclusion

The result of ancillary ICC on ThinPrep slides by fully automated immunostainer was in good agreement with the gold standard in pulmonary tumors subtype and immunoreactivity, objectively achieving accurate subtyping in cytology.
Canopy height, rather than neighborhood effects, shapes leaf herbivory in a tropical rainforest
Authors: Zhang Shuang , Xu Guo‐Rui , Zhang Yu‐Xin , Zhang Wen‐Fu , Cao Min
Published: March 2023

Factors shaping the interspecific variations in herbivory have puzzled ecologists for decades and several hypotheses have been proposed to explain interspecific variation in leaf herbivory. In a tropical rainforest in Yunnan Province, China, we collected 6732 leaves from 129 species with canopy heights ranging from 1.6 to 65.0 m above the ground. We tested the role of canopy height, the diversity, composition and structural heterogeneity of neighbors and leaf traits in shaping the interspecific variations in herbivory. Results show that leaf herbivory decreased with canopy height and specific leaf area (SLA) and increased with leaf size. However, neighboring species' diversity, composition, and structural heterogeneity showed no association with herbivory. Therefore, neither the visual apparency effect nor the associational resistance effect was detected in this hyperdiverse tropical rainforest. These findings highlight the importance of vertical structure in shaping herbivory patterns in natural communities.
Insights into B‐cell ontogeny inferred from human immunology
Authors: Dirks Johannes , Viemann Dorothee , Beyersdorf Niklas , Härtel Christoph , Morbach Henner
Published: March 2023

Due to ontogenetic changes in B‐cell developmental lineages, the mature B‐cell compartment constitutes by functionally different B‐cell subsets that emerged from prenatal, early postnatal or adult precursors. While negative selection processes operate primarily within the framework of B‐cell tolerance checkpoints during B‐cell development, further differentiation into distinct B‐cell subsets is additionally induced by positive selection. In addition to endogenous antigens, contact with microbial antigens is also involved in this selection process, with intestinal commensals having a significant influence on the development of a large layer within the B‐cell compartment. The decisive threshold that triggers negative selection seems to be relaxed during fetal B‐cell development, thereby allowing recruitment of polyreactive and also autoreactive B‐cell clones into the mature naïve B‐cell compartment. Almost all of the concepts on B‐cell ontogeny are based on observations in laboratory mice that not only differ from humans in their developmental timeline but also in their composition of commensal microorganisms or rather a lack of exposure to these. In this review, we summarize conceptual findings on B‐cell ontogeny and particularly describe key insights into the developing human B‐cell compartment and immunoglobulin repertoire formation.
A Straightforward Access to Cyclic (Alkyl)(amino)carbene Copper (I) Complexes
Authors: Lorkowski Jan , Serrato Melinda R. , Gembicki Milan , Mauduit Marc , Bertrand Guy , Jazzar Rodolphe
Published: March 2023

The synthesis and characterization of cyclic (alkyl)(amino)carbene, bicyclic (alkyl)(amino)carbene and cyclic (amino)(barrelene)carbene copper (I) complexes is reported. These complexes are obtained via a scalable, versatile, green, and cost/user‐friendly strategy.
Self‐Promoted N‐Glycosylation: Extended Substrate Scope and Substituent Effects
Authors: Rønne Kristensen Benedicte , Pedersen Christian Marcus
Published: March 2023

A self‐promoted glycosylation method for the stereoselective formation of β‐glucosides from a substrate library of glycosyl trichloroacetimidate glycosyl donors and glycosyl acceptors is presented. The simple two‐component reaction takes place at elevated temperatures, without the addition of any additives or catalysts. After a simple basic workup, N‐glycosides were obtained in good yields and with high β‐selectivity and hence this method allows for easy access to glycoconjugates under very mild conditions. The influences of neighboring group participation and substituents, in both the glycosyl donor and acceptor, were studied. Kinetic data were obtained from in situ IR and these were used for a Hammett study. A connection between the pKa of the acceptor and reaction rate was found and new mechanistic insight in self‐promoted glycosylations gained.
Clinical utility of a mHealth assisted intervention for activity modulation in chronic pain: The pilot implementation of pain ROADMAP
Authors: Andrews Nicole Emma , Ireland David , Deen Michael , Varnfield Marlien
Published: March 2023

Background

Being able to successfully self‐regulate one's activity levels is a key adaptation strategy for many people with chronic pain. This study aimed to explore the clinical utility of a mobile health platform (Pain ROADMAP) for assisting with the delivery of a tailored activity modulation intervention for people with persistent pain.

Methods

Twenty adults with chronic pain undertook 1‐week monitoring intervals which involved wearing an Actigraph activity monitor and entering pain, opioid use, and activity participation data into a custom‐made phone app. The Pain ROADMAP online portal integrated and analysed the data to detect activities that caused a severe pain exacerbation and provided summary statistics pertaining the data collected. As part of a 15‐week treatment protocol, participants received feedback from three dispersed Pain ROADMAP monitoring periods. Treatment focused on adapting pain‐provoking activities, gradually increase goal‐related activity and optimizing routine.

Results

Results revealed good participant acceptability of monitoring procedures and reasonable adherence to both monitoring procedures and clinical follow‐up appointments. Preliminary efficacy was established through clinically meaningful decreases in overactivity behaviour, pain variation, opioid use, depression, activity avoidance, and increases in productivity. No adverse outcomes were observed.

Conclusion

The results of this study provide initial support for the clinical utility of mHealth assisted activity modulation interventions that involve remote monitoring.

Significance

This is the first study to demonstrate how mHealth innovations that utilise ecological momentary assessment can be successfully integrated with wearable technologies to provide a tailored activity modulation intervention that is both highly valued by people with chronic pain and assists individuals to make constructive behavioural changes. Adaptions such as low costs sensors, increased customisability and gamification may be important for enhanced uptake, adherence and scalability.
β‐Cyclodextrin and folic acid host–guest interaction binding parameters determined by Taylor dispersion analysis and affinity capillary electrophoresis
Authors: Dai Yuanli , Sun Chang , Yang Yunhe , Wang Shuanghao , Li Huihui , Chen David Da Yong
Published: March 2023

The thermodynamic properties of molecular recognition in host–guest inclusion complexes can be studied by Taylor dispersion analysis (TDA). Host–guest inclusion complexes have modest size, and it is possible to get convergent results fast, achieving greater certainty for the obtained thermodynamic properties. Cyclodextrins (CDs) and their derivatives can be used as drug carriers that can boost stability, solubility, and bioavailability of physiologically active substances. A simple and effective approach for assessing the binding properties of CD complexes that are critical in the early stages of drug and formulation development is needed to fully understand the process of CD and guest molecules’ complex formation. In this work, TDA was successfully used to rapidly determine interaction parameters, including binding constant and stoichiometry, between β‐CD and folic acid (FA) along with the diffusivities of the free FA and its complex with β‐CD. Additionally, the FA diffusion coefficient obtained by TDA was compared to the results previously obtained by nuclear magnetic resonance. Affinity capillary electrophoresis (ACE) was also used to compare the binding constants obtained by different methods. The results showed that the binding constants obtained by ACE were somewhat lower than those obtained by the two TDA procedures.
Effects of simmering time, salt and sugar addition on the flavour and nutrient release of Morchella soup
Authors: Fu Ruiqing , Wang Juan , Guo Yanyin , Wang Yujiang , Zhang Haijuan
Published: March 2023

This study aimed to investigate the effect of different simmering times, salt and sugar addition on the quality of the Morchella soup. The change in the released contents of nutrients and flavour compounds in the Morchella soup within 120 min was studied. The automatic amino acid analyser, solid‐phase microextraction–gas chromatography–mass spectrometry, phenosulphuric acid method, acid–base neutralization principle and 1,1‐dipheny2‐picrylhydrazyl scavenging activity were used to determine the changes in free amino acids, volatile flavour compounds, total sugar, titratable acids and antioxidant activities in the Morchella soup respectively. The results showed that the amount of amino acids, volatile flavour compounds, titratable acid, antioxidant capacity and total sugar in the Morchella soup were significantly higher at 40‐min simmering time than at other simmering times. At 40‐min simmering time, the salt and sugar addition increased the amounts of umami amino acids (54.33%, 23.48%) and total amino acids (40.83%, 20.02%), organic acids (211.6%, 127.74%), sulphur‐containing compounds (130.40%, 237.20%), titratable acids (43.3%, 16.7%), and total sugar (23.8%, 16.7%) and antioxidant activity (87.5%, 23.8%) in the Morchella soup respectively. This study revealed the influence mechanism of simmering time, salt and sugar addition on the Morchella soup and provided a basis for further processing the Morchella soup.
Prevalence of food thermometers usage and temperature control in restaurants in Dammam, Saudi Arabia
Authors: Javed Nargis Begum , AL‐Mohaithef Mohammed
Published: March 2023

The Saudi Ministry of Municipal and Rural Affairs is planning to initiate a hazard analysis critical control point (HACCP) system in restaurants and cafeterias to manage issues of food safety in Saudi Arabia. One of the most important elements in the HACCP system is the monitoring temperature of cooked and stored food. The present study aimed to investigate the prevalence and use of refrigerators/freezers and food thermometers among food handlers in local and international restaurants in Dammam, Saudi Arabia. A cross‐sectional study was conducted in municipality‐licensed restaurants. The temperatures of refrigerator and freezer were checked, and the survey form was completed by the researcher according to logbook entries. We then checked for the presence of a food thermometer, and if a functional thermometer was present, the chef was asked to complete an online questionnaire using Survey Monkey website on a tablet. The response rate of the survey was 68% (238/350 restaurants). We found that 88.1% of restaurants used a thermometer to check the temperature of their refrigerators and freezers. Thirty‐one restaurants (13.0%) had a regular temperature‐monitoring record available for both the refrigerator and freezer. International restaurants had significantly greater temperature‐monitoring data than local restaurants (88.1% vs 63.3%; p = .0001). The prevalence of food thermometers in restaurants was 53.4% (127/238 restaurants), with significantly higher prevalence in international restaurants than in local restaurants (96.6% vs 10.8%; p = .0001). The practice of using food thermometer “always” when meat turned brown was significantly associated with the chef's age and education level. The study results showed poor monitoring and documentation of refrigerator and freezer temperatures along with a low prevalence of food thermometer use. The study result provides an insight into one of the barriers to the implementation of the HACCP system in Dammam.
Contemporaneous and noncontemporaneous idiosyncratic risk spillovers in commodity futures markets: A novel network topology approach
Authors: Zhang Xu , Yang Xian , Li Jianping , Hao Jun
Published: March 2023

This paper proposes a new network topology approach to identify the contemporaneous and noncontemporaneous idiosyncratic spillovers of lower‐moment and higher‐moment risks in commodity futures markets using high‐frequency data. Our results show that contemporaneous information has more explanatory power in constructing a network than noncontemporaneous information, especially for higher‐moment risk spillover networks. In contemporaneous spillover networks, the role of one commodity future and the structure of the networks vary across different realized estimators. Specifically, gold, silver, and wheat are the main volatility and kurtosis risk transmitters, while corn and silver are the main skewness spillover transmitters. Agricultural futures markets are relatively closed in the volatility and kurtosis risk spillover networks, while in the skewness network, they become closer to precious metal futures. Furthermore, crisis events can enlarge the idiosyncratic volatility spillovers in commodity markets. The total spillover effects of higher‐moment risk are stronger than those of lower‐moment risk.
Predicting hospital emergency department visits accurately: A systematic review
Authors: Silva Eduardo , Pereira Margarida F. , Vieira Joana T. , Ferreira‐Coimbra João , Henriques Mariana , Rodrigues Nuno F.
Published: March 2023

Objectives

The emergency department (ED) is a very important healthcare entrance point, known for its challenging organisation and management due to demand unpredictability. An accurate forecast system of ED visits is crucial to the implementation of better management strategies that optimise resources utilization, reduce costs and improve public confidence. The aim of this review is to investigate the different factors that affect the ED visits forecasting outcomes, in particular the predictive variables and type of models applied.

Methods

A systematic search was conducted in PubMed, Web of Science and Scopus. The review methodology followed the PRISMA statement guidelines.

Results

Seven studies were selected, all exploring predictive models to forecast ED daily visits for general care. MAPE and RMAE were used to measure models' accuracy. All models displayed good accuracy, with errors below 10%.

Conclusions

Model selection and accuracy was found to be particularly sensitive to the ED dimension. While ARIMA‐based and other linear models have good performance for short‐time forecast, some machine learning methods proved to be more stable when forecasting multiple horizons. The inclusion of exogenous variables was found to be advantageous only in bigger EDs.
Implementation of probe rheology simulation technique in atomistically detailed molecular dynamics simulations
Authors: Nourian Pouria , Peters Andrew J.
Published: March 2023

The probe rheology simulation technique is a technique for measuring the viscosity of a fluid by measuring the motion of an inserted probe particle. This approach has the benefit of greater potential accuracy at a lower computational cost than other conventional simulation techniques used for the calculation of mechanical properties, such as the Green–Kubo approach and nonequilibrium molecular dynamics simulations, and the potential to allow for sampling local variations of properties. This approach is implemented and demonstrated for atomistically detailed models. The viscosity of four different simple Newtonian liquids is calculated from both the Brownian motion (passive mode) and the forced motion (active mode) of an embedded probe particle. The probe particle is loosely modeled as a nano‐sized diamond particle: a rough sphere cut out of an FCC lattice made of carbon atoms. The viscosities obtained from the motion of the probe particle are compared with those obtained from the periodic perturbation method, and good agreement between the two sets of values is observed once the probe‐fluid interaction strength (i.e., in the pair‐wise Lennard–Jones interaction) is two times higher than their original values, and the artificial hydrodynamic interactions between the probe particle and its periodic images are accounted for. The success of the proposed model opens new opportunities for applying such a technique in the rheological characterization of local mechanical properties in atomistically detailed molecular dynamics simulations, which can be directly compared with or help guide experiments of similar nature.
Temporal dynamics of interoceptive attention and positive and negative affect in adults engaging in disordered eating and nonsuicidal self‐injury
Authors: Velkoff Elizabeth A. , Smith April. R.
Published: March 2023

Objective

Interoception (the sense of the body's state) is associated with eating disorders and nonsuicidal self‐injury, potentially through relationships with affect. We examined the relationship between interoceptive attention and both positive and negative affect.

Methods

Participants (N = 128) who reported recent self‐harm (i.e., disordered eating and/or non‐suicidal self‐injury) completed ecological momentary assessment for 16 days. Participants completed multiple daily assessments of affect and interoceptive attention. We then tested the temporal dynamic relationship between interoceptive attention and affect.

Results

There was a relationship between positive affect and interoceptive attention such that people with higher average positive affect, and times when people were above their typical positive affect, were associated with higher interoceptive attention. There was a negative relationship between negative affect and interoceptive attention, such that people with higher average negative affect, and times when people were above their own typical negative affect, were associated with lower interoceptive attention.

Conclusions

Better mood may associate with greater willingness to attend to body sensations. Our findings support active inference models of interoception and highlight the importance of refining our understanding of the dynamic nature of interoception and its relationship with affect.
Use of Clinical Trial Simulations to Compare the Performance of Different Approaches for Population Analyses of Pediatric Pharmacokinetic Data
Authors: Temrikar Zaid , Muensterman Elena , Engelhardt Benjamin , Mohamed Mohamed‐Eslam F.
Published: March 2023

The adequate characterization of the pharmacokinetics of a drug used in pediatrics is a mainstay of pediatric development programs and is critical for accurate dose selection in pediatrics. Analysis approaches can impact the estimation and characterization of pediatric pharmacokinetic parameters. Simulations were conducted to compare the performance of different approaches for analyzing pediatric pharmacokinetic data in the presence of extensive data from adult studies. Simulated clinical trial datasets were generated encompassing different scenarios that might be encountered in pediatric drug development. For each scenario, 250 clinical trials were simulated and analyzed using each of the following approaches: (1) estimating pediatric parameters using only pediatric data; (2) fixing specific parameters to adult estimates and estimating the remaining pediatric parameters using only pediatric data; (3) estimating pediatric parameters using adult parameters as informative Bayesian priors; (4) estimating pediatric parameters using combined adult and pediatric datasets with exponents for body weight effects estimated using adult and pediatric data; and (5) estimating pediatric parameters using combined adult and pediatric datasets with exponents for body weight effects estimated using pediatric data only. Each analysis approach was evaluated for its success in the estimation of true pediatric pharmacokinetic parameter values. Results demonstrated that analyzing pediatric data using a Bayesian approach generally performed best and had the lowest probability of significant bias in the estimated pediatric pharmacokinetic parameters among different scenarios evaluated. This clinical trial simulation framework can be used to inform the optimal approach for analyses of pediatric data for other pediatric drug development program scenarios beyond the cases evaluated in these analyses.