bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel MYT1 variants expose the complexity of oculo‐auriculo‐vertebral spectrum genetic mechanisms
Authors: Zamariolli Malú , Burssed Bruna , Moysés‐Oliveira Mariana , Colovati Mileny , Bellucco Fernanda Teixeira da Silva , dos Santos Leonardo Caires , Alvarez Perez Ana Beatriz , Bragagnolo Silvia , Melaragno Maria Isabel
Published: April 2021

Oculo‐auriculo‐vertebral spectrum (OAVS) is a developmental disorder characterized by anomalies mainly involving the structures derived from the first and second pharyngeal arches. The spectrum presents with heterogeneous clinical features and complex etiology with genetic factors not yet completely understood. To date, MYT1 is the most important gene unambiguously associated with the spectrum and with functional data confirmation. In this work, we aimed to identify new single nucleotide variants (SNVs) affecting MYT1 in a cohort of 73 Brazilian patients diagnosed with OAVS. In addition, we investigated copy number variations (CNVs) encompassing this gene or its cis‐regulatory elements and compared the frequency of these events in patients versus a cohort of 455 Brazilian control individuals. A new SNV, predicted as likely deleterious, was identified in five unrelated patients with OAVS. All five patients presented hearing impairment and orbital asymmetry suggesting an association with the variant. CNVs near MYT1, located in its neighboring topologically associating domain (TAD), were found to be enriched in patients when compared to controls, indicating a possible involvement of this region with OAVS pathogenicity. Our findings highlight the genetic complexity of the spectrum that seems to involve more than one variant type and inheritance patterns.
Operator Transpose within Normal Ordering and its Applications for Quantifying Entanglement
Authors: Hu Liyun , Zhang Luping , Chen Xiaoting , Ye Wei , Guo Qin , Fan Hongyi
Published: April 2021

Partial transpose is an important operation for quantifying entanglement. In this study, the (partial) transpose of any single (two‐mode) operator is investigated. Using the Fock basis expansion, it is found that the transposed operator of an arbitrary operator can be obtained by replacing with , rather than the c‐number within the normal ordering form. The transpose of the displacement and Wigner operators is also investigated, from which the relation of the Wigner function, characteristics function, and average values such as covariance matrix is constructed between the density operator and transposed density operator. These observations can be further extended to multi‐mode cases. As for the application, partial transpose of the two‐mode squeezed operator and the entanglement of the two‐mode squeezed vacuum through a laser channel is considered.
A Supramolecular Complex of C60–S with High‐Density Active Sites as a Cathode for Lithium–Sulfur Batteries
Authors: Xiang Jingwei , Shen Wangqiang , Guo Zezhou , Meng Jintao , Yuan Lixia , Zhang Yi , Cheng Zexiao , Shen Yue , Lu Xing , Huang Yunhui
Published: April 2021

The well‐known “shuttle effect” of the intermediate lithium polysulfides (LiPSs) and low sulfur utilization hinder the practical application of lithium–sulfur (Li–S) batteries. Herein, we describe a novel C60–S supramolecular complex with high‐density active sites for LiPS adsorption that was formed by a simple one‐step process as a cathode material for Li–S batteries. Benefiting from the cocrystal structure, 100 % of the C60 molecules in the complex can offer active sites to adsorb LiPSs and catalyze their conversion. Furthermore, the lithiated C60 cores promote internal ion transport inside the composite cathode. At a low electrolyte/sulfur ratio of 5 μL mg−1, the C60–S cathode with a sulfur loading of 4 mg cm−2 exhibited a high capacity of 809 mAh g−1 (3.2 mAh cm−2). The development of the C60–S supramolecular complex will inspire the invention of a new family of S/fullerenes as cathodes for high‐performance Li–S batteries and extend the application of fullerenes.
Acridinium Salts and Cyanoarenes as Powerful Photocatalysts: Opportunities in Organic Synthesis
Authors: Tlili Anis , Lakhdar Sami
Published: April 2021

The use of organic photocatalysts has revolutionized the field of photoredox catalysis, as it allows access to reactivities that were traditionally restricted to transition‐metal photocatalysts. This Minireview reports recent developments in the use of acridinium ions and cyanoarene derivatives in organic synthesis. The activation of inert chemical bonds as well as the late‐stage functionalization of biorelevant molecules are discussed, with a special focus on their mechanistic aspects.
An Ultralow Temperature Aqueous Battery with Proton Chemistry
Authors: Yue Fang , Tie Zhiwei , Deng Shenzhen , Wang Shuai , Yang Min , Niu Zhiqiang
Published: April 2021

Conventional aqueous batteries usually suffer from serious capacity loss under subzero conditions owing to the freeze of electrolytes. To realize the utilization of aqueous batteries in extremely cold climates, low‐temperature aqueous battery systems have to be developed. Herein, an aqueous Pb‐quinone battery based on p‐chloranil/reduced graphene oxide (PCHL‐rGO) in H2SO4 electrolyte is developed. Such aqueous Pb/PCHL‐rGO batteries display H+ insertion chemistry, which endows the batteries with fast reaction kinetics and high rate capability. In addition, the hydrogen bonds between water molecules can be significantly damaged in electrolyte by modulating the interaction between SO42− and water molecules, lowering the freezing point of electrolyte. As a result, the Pb/PCHL‐rGO batteries deliver extraordinary electrochemical performance even at −70 °C. This work will broaden the horizons of aqueous batteries and open up new opportunities to construct low‐temperature aqueous batteries.
Stable Acidic Water Oxidation with a Cobalt–Iron–Lead Oxide Catalyst Operating via a Cobalt‐Selective Self‐Healing Mechanism
Authors: Simondson Darcy , Chatti Manjunath , Bonke Shannon A. , Tesch Marc F. , Golnak Ronny , Xiao Jie , Hoogeveen Dijon A. , Cherepanov Pavel V. , Gardiner James L. , Tricoli Antonio , MacFarlane Douglas R. , Simonov Alexandr N.
Published: April 2021

The instability and expense of anodes for water electrolyzers with acidic electrolytes can be overcome through the implementation of a cobalt‐iron‐lead oxide electrocatalyst, [Co–Fe–Pb]Ox, that is self‐healing in the presence of dissolved metal precursors. However, the latter requirement is pernicious for the membrane and especially the cathode half‐reaction since Pb2+ and Fe3+ precursors poison the state‐of‐the‐art platinum H2 evolving catalyst. To address this, we demonstrate the invariably stable operation of [Co–Fe–Pb]Ox in acidic solutions through a cobalt‐selective self‐healing mechanism without the addition of Pb2+ and Fe3+ and investigate the kinetics of the process. Soft X‐ray absorption spectroscopy reveals that low concentrations of Co2+ in the solution stabilize the catalytically active Co(Fe) sites. The highly promising performance of this system is showcased by steady water electrooxidation at 80±1 °C and 10 mA cm−2, using a flat electrode, at an overpotential of 0.56±0.01 V on a one‐week timescale.
Investigation of rheological, mechanical, and thermal properties of nanocomposites based on nitrile rubber‐phenolic resin reinforced with nanographene
Authors: Bazli Leila , Barghamadi Mohammad , Shafiee Sara , Karrabi Mohammad , Ghoreishy Mir Hamid Reza
Published: April 2021

In this study, nanocomposites of acrylonitrile butadiene rubber (NBR)/phenolic resin/graphene nanoparticles (GNPs) were prepared using a two‐roll mill. According to the results, the addition of GNPs increased the scorch time, vulcanization time, and viscosity of the blends. By adding phenolic resin and in the presence of a higher percentage of acrylonitrile, the modulus and tensile strength increased and the elongation at break decreased. The mechanical properties of the nanocomposites improved with increasing the amount of nanoparticles. The addition of 1.5 phr GNP to the blends containing NBR with 33% and 45% acrylonitrile increased the tensile modulus by 56% and 49%, respectively. The tensile properties of the nanocomposites were also investigated at 50, 25, and 75°C. It was observed that with increasing the amount of nanoparticles, the deterioration of the mechanical properties at elevated temperatures was reduced. Also, thermal stability increased with increasing the amount of nanoparticles in all the samples.
Prediction and analyses of HLA‐II restricted Mycobacterium tuberculosis CD4+ T cell epitopes in the Chinese population
Authors: Jia Zaixing , Gong Wenping , Liang Yan , Wu Xueqiong , Zhao Weiguo
Published: April 2021

The Bacillus Calmette‐Guérin (BCG) vaccine has been used to prevent tuberculosis (TB), but it cannot prevent adults against TB. The Mycobacterium tuberculosis Beijing strain is the most popular strain in China, but no vaccine is designed for the Beijing strain. It is vital to design a multiepitopes‐based vaccine against the Beijing strain for the Chinese population. The bioinformatics tools were used to predict CD4+ T‐cell epitopes in five protective antigens based on the Chinese population‐specific alleles. The antigenicity, allergenicity, toxicity, IFN‐γ level, population coverage, and three‐dimensional structure were predicted using Vaxijen, AllerTOP, ToxinPred, IFN‐γ epitope server, IEDB, and I‐TASSER, respectively. One‐hundred one promiscuous epitopes were obtained from Rv1813c, Rv2608, Rv3131, and Rv3628 proteins. After screening with antigenicity, allergenicity, toxicity, and IFN‐γ level, seven epitopes from Rv2608 and Rv3131 proteins were selected to be vaccine candidates. Further study determined their three‐dimensional structure and the coverage in the Chinese population as high as 99%. Our study predicted seven CD4+ T‐cell dominant epitopes from the proteins Rv2608 and Rv3131 of M. tuberculosis Beijing strain for the first time, which may provide a basis for improving the design of multiepitopes‐based vaccines for TB.
Tannin: a new insight into a key product for the bioeconomy in forest regions
Authors: Pagliaro Mario , Albanese Lorenzo , Scurria Antonino , Zabini Federica , Meneguzzo Francesco , Ciriminna Rosaria
Published: April 2021

Produced by extraction from certain woods and barks with boiling water, tannin is the name given to a mixture of high molecular weight biophenols increasingly used in a number of industries. This study offers a new bioeconomy insight into an old natural product that, we argue in this study, will likely play a crucial role in the development of the bioeconomy of forest regions. After providing an updated picture of selected key economic and production aspects, we show how flourishing research on tannin's biological activity and technological applications has revealed many new properties that are likely to drive significant growth in demand in the near and mid‐term future. The study concludes with two lessons learned and one forecast that will hopefully accelerate progress in the bioeconomy of forest areas based on the circular economy of tannin enabled by new extraction and purification technologies. © 2021 Society of Industrial Chemistry and John Wiley & Sons Ltd.
Sensitive LC–MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies
Authors: de Oliveira Alexandre Cavenatti , Davanço Marcelo Gomes , de Campos Daniel Rossi , Sanches Pedro Henrique Godoy , Cirino João Pedro Gonçalves , Carvalho Patricia de Oliveira , Antônio Márcia Aparecida , Coelho Edvaldo Capobiango , Porcari Andreia M.
Published: April 2021

Rivaroxaban is an anticoagulant (orally active direct Xa inhibitor) considered to reduce the risk of stroke and systemic embolism and treat deep vein thrombosis, pulmonary embolism, and other cardiovascular complications. Bioanalytical methods for rivaroxaban quantification in plasma are necessary for application in pharmacokinetic studies, as well as in drug therapeutic monitoring. In this work, we developed and validated a sensitive bioanalytical method using LC–MS/MS for rivaroxaban quantification in human plasma using an one‐step liquid–liquid extraction. The linear concentration range was 1–600 ng/mL. The bioanalytical method was also applied to pharmacokinetic studies in healthy volunteers under fasting and fed conditions. The results demonstrated that the method is rapid, sensitive, and adequate for application in pharmacokinetic studies.
β‐Amyloid Targeting with Two‐Dimensional Covalent Organic Frameworks: Multi‐Scale In‐Silico Dissection of Nano‐Biointerface
Authors: Maleki Reza , Khedri Mohammad , Rezvantalab Sima , Afsharchi Fatemeh , Musaie Kiyan , Shafiee Sepehr , Shahbazi Mohammad‐Ali
Published: April 2021

Cytotoxic aggregation of misfolded β‐amyloid (Aβ) proteins is the main culprit suspected to be behind the development of Alzheimer's disease (AD). In this study, Aβ interactions with the novel two‐dimensional (2D) covalent organic frameworks (COFs) as therapeutic options for avoiding β‐amyloid aggregation have been investigated. The results from multi‐scale atomistic simulations suggest that amine‐functionalized COFs with a large surface area (more than 1000 m2/gr) have the potential to prevent Aβ aggregation. Gibb's free energy analysis confirmed that COFs could prevent protofibril self‐assembly in addition to inhibiting β‐amyloid aggregation. Additionally, it was observed that the amine functional group and high contact area could improve the inhibitory effect of COFs on Aβ aggregation and enhance the diffusivity of COFs through the blood‐brain barrier (BBB). In addition, microsecond coarse‐grained (CG) simulations with three hundred amyloids reveal that the presence of COFs creates instability in the structure of amyloids and consequently prevents the fibrillation. These results suggest promising applications of engineered COFs in the treatment of AD and provide a new perspective on future experimental research.
Pressure loss recovery in aortic valve stenosis: Contemporary relevance
Authors: Herrmann Howard C. , Laskey Warren K.
Published: April 2021

Pressure loss recovery (PLR) is a hydrodynamic phenomenon that occurs when blood flow encounters a narrowing typified by aortic valve stenosis (AS). Multiple factors contribute to the magnitude of PLR including the volumetric rate of flow, the geometry of the entrance to the vena contracta (VC) or point of minimum dimension, including that of the left ventricular outflow tract and valve orifice, and the geometry of the proximal aorta. In the majority of clinical circumstances, PLR results in echocardiographic Doppler gradient estimates that are modestly, but generally not clinically important, greater than those derived from rigorously performed catheter measurements. The contribution of PLR to the echocardiographically‐measured gradient may not differ significantly between currently available valve prostheses and is likely to be small in patients with mild AS following TAVR.
Effects of alternate wetting and drying irrigation management and air temperature during grainfill on rice grain physicochemical and functionality traits of US inbred varieties
Authors: Chen Ming‐Hsuan , McClung Anna M. , Rohila Jai S. , Barnaby Jinyoung Y.
Published: April 2021

Background and objectives

Declining irrigation resources and warming cropping seasons present challenges to rice production. The alternate wetting and drying (AWD) management system conserve water, but its impact on rice grain quality is not well understood. To determine the effects of AWD irrigation management and varying seasonal temperatures on rice grain quality, a field experiment with two AWD irrigation methods and continuous flood (CF), as a control, was conducted in one year. Two environmental temperatures were observed as a result of two plating dates, one month apart.

Findings

Results revealed that AWD relative to CF, at either planting date, had minimum effect on grain quality traits of seven US varieties having diverse physicochemical and functional properties. On the other hand, mild warmer air temperatures that occurred during the grainfill period of the first planting were associated with lower head rice yield and higher chalkiness in brown and milled rice of some US varieties. The functional traits of apparent amylose content of low amylose varieties, Tp of a high gelatinization temperature variety, and total carbon were sensitive to air temperature changes during grain development.

Conclusions

AWD had no significant impact on rice grain quality, while some US varieties were more resilient to warmer temperature during grainfill on milling yield, chalk, and functional traits.

Significance and novelty

This study demonstrated that rice varieties can withstand moderate soil moisture stress from AWD management with minimum negative effects on grain appearance traits and functional properties.
One‐Pot Synthesis of 11C‐Labelled Primary Benzamides via Intermediate [11C]Aroyl Dimethylaminopyridinium Salts
Authors: Ferrat Mélodie , Dahl Kenneth , Schou Magnus
Published: April 2021

Electrophilic 11C‐labelled aroyl dimethylaminopyridinium salts, obtained by carbonylative cross‐coupling of aryl halides with [11C]carbon monoxide, were prepared for the first time and shown to be valuable intermediates in the synthesis of primary [11C]benzamides. The methodology furnished a set of benzamide model compounds, including the two poly (ADP‐ribose) polymerase (PARP) inhibitors niraparib and veliparib, in moderate to excellent radiochemical yields. In addition to providing a convenient and practical route to primary [11C]benzamides, the current method paves the way for future application of [11C]aroyl dimethylaminopyridinium halide salts in positron emission tomography (PET) tracer synthesis.
Validation of Ab‐Initio‐Predicted Magnetic Anisotropies and Magneto‐structural Correlations in Linear Hetero‐trinuclear DyIII‐NiII2 Compounds
Authors: Comba Peter , Enders Markus , Großhauser Michael , Hiller Markus , Klingeler Rüdiger , Koo Changhyun , Müller Dennis , Rajaraman Gopalan , Swain Abinash , Tavhelidse Msia , Wadepohl Hubert
Published: April 2021

Reported are single crystal SQUID and single crystal high‐frequency/high‐field EPR data of a trinuclear complex with a rare six‐coordinate coordination sphere of a DyIII center coupled to two terminal six‐coordinate NiII ions. The analysis of the single crystal spectroscopic parameters allows for an accurate description of the ground state wavefunction. The experimental analysis is supplemented by the analysis of the paramagnetic NMR spectra, allowing for a thorough description of the DyIII center. The experimental data are interpreted on the basis of an ab initio ligand field analysis, and the computed parameters are in good agreement with the experimental observations. This supports the quality of the theoretical approach based on a pseudo‐spin Hamiltonian for the electronic ground state. Further support emerges from the ab initio ligand field theory based analysis of a structurally very similar system that, in contrast to the complex reported here, shows single molecule magnetic properties, and this is in agreement with the quantum‐chemical prediction and analysis.
Solvent Effects in Halogen and Hydrogen Bonding Mediated Electrochemical Anion Sensing in Aqueous Solution and at Interfaces
Authors: Patrick Sophie C. , Hein Robert , Docker Andrew , Beer Paul D. , Davis Jason J.
Published: April 2021

Sensing anionic species in competitive aqueous media is a well‐recognised challenge to long‐term applications across a multitude of fields. Herein, we report a comprehensive investigation of the electrochemical anion sensing performance of novel halogen bonding (XB) and hydrogen bonding (HB) bis‐ferrocene‐(iodo)triazole receptors in solution and at self‐assembled monolayers (SAMs), in a range of increasingly competitive aqueous organic solvent media (ACN/H2O). In solution, the XB sensor notably outperforms the HB sensor, with substantial anion recognition induced cathodic voltammetric responses of the ferrocene/ferrocenium redox couple persisting even in highly competitive aqueous solvent media of 20 % water content. The response to halides, in particular, shows a markedly lower sensitivity to increasing water content associated with a unique halide selectivity at unprecedented levels of solvent polarity. The HB sensor, in contrast, generally displayed a preference towards oxoanions. A significant surface‐enhancement effect was observed for both XB/HB receptive films in all solvent systems, whereby the HB sensor generally displayed larger responses towards oxoanions than its halogen bonding analogue.
Fluorescent Indolo[3,2‐a]phenazines against Toxoplasma gondii: Concise Synthesis by Gold‐Catalyzed Cycloisomerization with 1,2‐Silyl Migration and ipso‐Iodination Suzuki Sequence
Authors: Merkt Franziska K. , Mazzone Flaminia , Sazzadeh Shabnam Shaneh , Bonda Lorand , Hinz Larissa K. E. , Gruber Irina , Buchholz Karin , Janiak Christoph , Pfeffer Klaus , Müller Thomas J. J.
Published: April 2021

A gold‐catalyzed cycloisomerization of 2‐indolyl‐3‐[(trimethylsilyl)ethynyl)]quinoxalines with concomitant 1,2‐silyl shift forms 6‐(trimethylsilyl)indolo[3,2‐a]phenazines in moderate to excellent yield. These silylated heterocycles are readily transformed into 6‐aryl‐indolo[3,2‐a]phenazines in moderate to good yield by one‐pot ipso‐iodination Suzuki coupling. The title compounds represent a novel type of tunable luminophore. Structure‐property relationships for 6‐aryl‐indolo[3,2‐a]phenazines obtained from Hammett correlations with σp+ substituent parameters indicate that emission maxima, Stokes shifts, and fluorescence quantum yields can be fine‐tuned by the remote para‐aryl substituent. Furthermore, indolo[3,2‐a]phenazines were found to exhibit interesting activities against medically relevant pathogens such as the Apicomplexa parasite Toxoplasma gondii with an IC50 of up to 0.67±0.13 μM. Thus, these compounds are promising candidates for novel anti‐parasitic therapies.
A phase II basket trial of Dual Anti–CTLA–4 and Anti–PD–1 Blockade in Rare Tumors (DART) SWOG S1609: High‐grade neuroendocrine neoplasm cohort
Authors: Patel Sandip Pravin , Mayerson Edward , Chae Young Kwang , Strosberg Jonathan , Wang Jue , Konda Bhavana , Hayward Jourdain , McLeod Christine M. , Chen Helen X. , Sharon Elad , Othus Megan , Ryan Christopher W. , Plets Melissa , Blanke Charles D. , Kurzrock Razelle
Published: April 2021

Background

The authors previously reported the results of the nonpancreatic neuroendocrine neoplasm cohort of the SWOG S1609 DART (Dual Anti–CTLA‐4 and Anti–PD‐1 Blockade in Rare Tumors) trial, which permitted all histologic grades and had a 44% overall response rate (ORR) among patients with high‐grade disease. Here they sought to validate their findings in a dedicated prospective cohort of high‐grade neuroendocrine neoplasms within S1609.

Methods

A prospective, open‐label, multicenter, phase 2 clinical trial of ipilimumab plus nivolumab was conducted across multiple rare tumor cohorts. The dedicated, high‐grade neuroendocrine neoplasm cohort was examined here. The primary end point was the ORR according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Secondary end points included progression‐free survival (PFS), overall survival (OS), and toxicity.

Results

Nineteen patients with high‐grade neuroendocrine neoplasms (defined by local pathology review) were enrolled in this cohort of S1609. The most common primary sites were unknown primaries (21%), which were followed by the rectum, gastroesophageal junction, cervix, and pancreas (11%). The median number of lines of prior therapy was 1 (range, 0‐3). All patients were microsatellite‐stable. The median Ki‐67 value was 80%. The ORR was 26% (95% confidence interval [CI], 11%‐45%), and the clinical benefit rate (stable disease for ≥6 months plus partial responses plus complete responses) was 32% (95% CI, 13%‐57%). The 6‐month PFS rate was 32% (95% CI, 16%‐61%) with a median PFS of 2.0 months (95% CI, 1.8 months to ∞) and a median OS of 8.7 months (95% CI, 6.1 months to ∞). The most common toxicities were fatigue (32%) and rash (26%), and the most common grade 3/4 immune‐related adverse event was rash (15%); there were no events that required treatment discontinuation and no grade 5 events.

Conclusions

Ipilimumab plus nivolumab demonstrated a 26% ORR in patients with high‐grade neuroendocrine neoplasms, with durable responses seen in patients with refractory disease.
Extended finite element method for fluid‐structure interaction in wave membrane blood pump
Authors: Martinolli Marco , Biasetti Jacopo , Zonca Stefano , Polverelli Luc , Vergara Christian
Published: April 2021

Numerical simulations of cardiac blood pump systems are integral to the optimization of device design, hydraulic performance and hemocompatibility. In wave membrane blood pumps, blood propulsion arises from the wave propagation along an oscillating immersed membrane, which generates small pockets of fluid that are pushed towards the outlet against an adverse pressure gradient. We studied the Fluid–Structure Interaction between the oscillating membrane and the blood flow via three‐dimensional simulations using the Extended Finite Element Method (XFEM), an unfitted numerical technique that avoids remeshing by using a fluid fixed mesh. Our three‐dimensional numerical simulations in a realistic pump geometry highlighted, for the first time in this field of application, that XFEM is a reliable strategy to handle complex industrial problems. Moreover, they showed the role of the membrane deformation in promoting a blood flow towards the outlet despite an adverse pressure gradient. We also simulated the pump system at different pressure conditions and we validated the numerical results against in‐vitro experimental data.
High‐Throughput Screening of Compound Neurotoxicity Using 3D‐Cultured Neural Stem Cells on a 384‐Pillar Plate
Authors: Kang Soo‐Yeon , Joshi Pranav , Lee Moo‐Yeal
Published: April 2021

Assessing the neurotoxicity of test chemicals has typically been performed using two‐dimensionally (2D)‐cultured neuronal cell monolayers and animal models. The in vitro 2D cell models are simple and straightforward compared to animal models, which have the disadvantage of being relatively low throughput, expensive, and time consuming. Despite their extensive use in this area of neurotoxicology research, both models often do not accurately recapitulate human outcomes. To bridge this gap and attempt to better replicate what happens in vivo, three‐dimensionally (3D) cultured neural stem cells (NSCs) encapsulated in hydrogels on a 384‐pillar plate have been developed via miniature 3D bioprinting. This technology allows users to print NSCs on a pillar plate for rapid 3D cell culture as well as high‐throughput compound screening. For this, the 384‐pillar plate with bioprinted NSCs is sandwiched with a standard 384‐well plate with growth medium for 3D culture, allowing researchers to expose the cells to test compounds and stain them with various fluorescent dyes for a suite of high‐content imaging assays, including assays for DNA damage, mitochondrial impairment, cell membrane integrity, intracellular glutathione levels, and apoptosis. After acquiring cell images from an automated fluorescence microscope and extracting fluorescence intensities, researchers can obtain the IC50 value of each compound to evaluate critical parameters in neurotoxicity. Here, we provide a detailed description of protocols for cell printing on a 384‐pillar plate, 3D NSC culture, compound testing, 3D cell staining, and image acquisition and analysis, which altogether will allow researchers to investigate mechanisms of compound neurotoxicity with 3D‐cultured NSCs in a high‐throughput manner. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Three‐dimensional neural stem cell culture on a 384‐pillar plate

Basic Protocol 2: Compound treatment and cell staining

Basic Protocol 3: Image acquisition, processing, and data analysis
CyTOF: An Emerging Technology for Single‐Cell Proteomics in the Mouse
Authors: Tracey Lauren J. , An Yeji , Justice Monica J.
Published: April 2021

The ability to analyze the proteome of single cells is critical for the advancement of studies of steady‐state and pathological processes. Mass cytometry, or CyTOF, combines principles of mass spectrometry and flow cytometry to enable single‐cell analysis of protein expression. CyTOF can simultaneously assess DNA content and proteins and has the capacity to measure 40 to 100 parameters in each cell. Applying this technology to tissues or cells on slides, termed imaging mass cytometry (IMC), allows for visualization of normal and diseased tissues in situ. The high‐dimensional proteomic analysis that can be undertaken with CyTOF and IMC has the potential to enhance our understanding of complex and heterogeneous developmental and disease pathways. This article will describe the CyTOF experimental workflow, including reagent selection, sample preparation, and data analysis. CyTOF is compared to flow cytometry, focusing on the strengths and weaknesses of these powerful techniques. Importantly, we review key studies in mouse models of human disease that highlight the strength of CyTOF and IMC to drive discovery research and therapeutic advancement. © 2021 Wiley Periodicals LLC.
Mechanoenzymology: State of the Art and Challenges towards Highly Sustainable Biocatalysis
Authors: Pérez‐Venegas Mario , Juaristi Eusebio
Published: April 2021

Global awareness of the importance of developing environmentally friendlier and more sustainable methods for the synthesis of valuable chemical compounds has led to the design of novel synthetic strategies, involving bio‐ and organocatalysis as well as the application of novel efficient and ground‐breaking technologies such as present‐day solvent‐free mechanochemistry. In this regard, the evaluation of biocatalytic protocols mediated by the combination of mechanical activation and enzymatic catalysis has recently attracted the attention of the chemical community. Such mechanoenzymatic strategy represents an innovative and promising “green” approach in chemical synthesis that poses nevertheless new paradigms regarding the relative resilience of biomolecules to the mechanochemical stress and to the apparent high energy, at least in so‐called hot‐spots, during the milling process. Herein, relevant comments on the conceptualization of such mechanoenzymatic approach as a sustainable option in chemical synthesis, recent progress in the area, and associated challenges are discussed.
A fourth‐order bidirectional DC–DC converter for interfacing battery in a solar ‐photovoltaic‐fed low‐voltage residential DC nano‐grid: Design and analysis
Authors: Saxena Anmol Ratna , Kulshreshtha Ashima
Published: April 2021

In this paper, a non‐isolated fourth‐order bidirectional DC–DC converter (FoBiDC) which exhibits continuous input and output current together with minimum‐phase response, both during buck and boost modes, is proposed and analyzed. It is then used to interface a battery in a solar photovoltaic (SPV) fed low‐voltage low‐power residential DC nano‐grid (LVRDNG). The design equations for the converter are derived by performing steady‐state and time‐domain analysis. The small‐signal models are developed and used for designing voltage‐mode controller to regulate the DC bus voltage of LVRDNG and perform stability analysis. The small‐signal analysis reveals the possibility of right‐half plane (RHP) zero and formation of an up–down glitch in the frequency response of converter transfer functions which results in slower dynamic response and increased sub‐system interactions. Therefore, an optimized power stage design methodology, using particle swarm optimization (PSO), is adopted for optimal parameter selection with the aim to shift RHP zero to left‐half plane (LHP) and to mitigate the effect of up–down glitch. The effect of sub‐system interactions, arising due to interfacing of FoBiDC, on other coherently operating converter in the LVRDNG is also analyzed by formulating an integrated small‐signal model of LVRDNG. The scaled down laboratory prototype of FoBiDC and LVRDNG is developed to experimentally validate the steady‐state and dynamic performance. The theoretical and experimental results are found to be in close correlation with each other.
Adaptive multiple access assists multiple users over multiple‐input‐multiple‐output non‐orthogonal multiple access wireless networks
Authors: Tran Thanh‐Nam , Voznak Miroslav
Published: April 2021

The works in this study examine three scenarios. The scenario (I) as a common scenario with the base station (BS) and users are equipped with multiple antennae over Nakagami‐m fading channels. To improve system performance, the transmit antenna selection (TAS) and maximization of successive interference cancellation (max‐SIC) framework are deployed. A novel cumulative distribute function (CDF) for the scenario (I) is proposed, and the outage probability (OP) in novel closed form can be obtained. It is challenging due to scenario (I) consists of massive users equipped with multiple antennae over Nakagami‐m fading channels. Therefore, this study proposes scenario (II) with a maximum of SIC and minimum of instantaneous bit rate (max‐SIC‐min‐rate) framework for aiding multiple access to reduce the algorithm complexity of the scenario (I). Some adaptive multiple access strategies are proposed as adaptive PA factors, adaptive min–max bit rate threshold, and adaptive Nakagami‐m coefficient are proposed. Finally, the scenario (III) is examined by also applying the max‐SIC‐min‐rate framework as the scenario (II), however, comparing to the adaptive min–max bit rate threshold to investigate the OP, system throughput, and energy‐efficient (EE) performances. The obtained results as shown in the numerical results section confirm that, on one hand, the system performance of the scenario (II) is approximate or better than the scenario (I) at the same transmit power; on another hand, the scenario (III) reaches the system throughput and EE performances better than the other scenarios at the high transmit power. The analysis results are proved and verified by Monte Carlo simulation results.
The natural history of sporadic non‐ampullary duodenal epithelial tumors: Can we wait and see?
Authors: Sakaguchi Yoshiki , Tsuji Yosuke , Ushiku Tetsuo , Kubota Dai , Sato Junichi , Obata Miho , Cho Rina , Nagao Sayaka , Sakuma Nobuyuki , Tamura Naoki , Miura Yuko , Fukagawa Kazushi , Ohki Daisuke , Mizutani Hiroya , Takeuchi Chihiro , Takahashi Yu , Minatsuki Chihiro , Niimi Keiko , Yamamichi Nobutake , Koike Kazuhiko
Published: April 2021

Objectives

The natural history of sporadic non‐ampullary duodenal epithelial tumors (SNADETs) is poorly documented. The aim of this study was to evaluate the history of SNADETs in patients where immediate resection could not be performed.

Methods

This is a single‐center retrospective study of 86 consecutive cases of SNADETs who did not undergo immediate resection and were followed‐up with upper gastrointestinal endoscopy for more than 6 months.

Results

During a follow‐up period of 36.8 (6.0–613.0) months, macroscopic progression was admitted in eight (9.3%). Of these, the final histology in four was adenocarcinoma, and three cases demonstrated submucosal invasion. Rates of macroscopic progression at 150 months after detection were 11.1%, 16.7%, and 30.0% for SNADETs <5 mm, <10 mm, and ≥10 mm, respectively.

Conclusion

The overall risk of SNADETs progressing to invasive cancer is low. However, changes in macroscopic size or shape of SNADETs signify a high risk of progression to invasive cancer.
Validation of the nine itemARFIDscreen (NIAS) subscales for distinguishingARFIDpresentations and screening forARFID
Authors: Burton Murray Helen , Dreier Melissa J. , Zickgraf Hana F. , Becker Kendra R. , Breithaupt Lauren , Eddy Kamryn T. , Thomas Jennifer J.
Published: April 2021

Objective

The Nine Item Avoidant/Restrictive Food Intake Disorder (ARFID) Screen (NIAS) has three subscales aligned with ARFID presentations but clinically validated cutoff scores have not been identified. We aimed to examine NIAS subscale (picky eating, appetite, fear) validity to: (1) capture clinically‐diagnosed ARFID presentations; (2) differentiate ARFID from other eating disorders (other‐ED); and (3) capture ARFID symptoms among individuals with ARFID, individuals with other‐ED, and nonclinical participants.

Method

Participants included outpatients (ages 10–76 years; 75% female) diagnosed with ARFID (n = 49) or other‐ED (n = 77), and nonclinical participants (ages 22–68 years; 38% female,n = 40). We evaluated criterion‐related concurrent validity by conducting receiver operating curve (ROC) analyses to identify potential subscale cutoffs and by testing if cutoffs could capture ARFID with and without use of the Eating Disorder Examination‐Questionnaire (EDE‐Q).

Results

Each NIAS subscale had high AUC for capturing those who fit versus do not fit each ARFID presentation, resulting in proposed cutoffs of ≥10 (sensitivity = .97, specificity = .63), ≥9 (sensitivity = .86, specificity = .70), and ≥ 10 (sensitivity = .68, specificity = .89) on the NIAS‐picky eating, NIAS‐appetite, and NIAS‐fear subscales, respectively. ARFID versus other‐ED had high AUC on the NIAS‐picky eating (≥10 proposed cutoff), but not NIAS‐appetite or NIAS‐fear subscales. NIAS subscale cutoffs had a high association with ARFID diagnosis, but only correctly classified other‐ED in combination with EDE‐Q Global <2.3.

Discussion

To screen for ARFID, we recommend using a screening tool for other‐ED (e.g., EDE‐Q) in combination with a positive score on any NIAS subscale (i.e., ≥10, ≥9, and/or ≥10 on the NIAS‐picky eating, NIAS‐appetite, and NIAS‐fear subscales, respectively).
Splanchnic nerve modulation in heart failure: mechanistic overview, initial clinical experience, and safety considerations
Authors: Fudim Marat , Ponikowski Piotr P. , Burkhoff Daniel , Dunlap Mark E. , Sobotka Paul A. , Molinger Jeroen , Patel Manesh R. , Felker G. Michael , Hernandez Adrian F. , Litwin Sheldon E. , Borlaug Barry A. , Bapna Anisha , Sievert Horst , Reddy Vivek Y. , Engelman Zoar J. , Shah Sanjiv J.
Published: April 2021

Volume recruitment from the splanchnic compartment is an important physiological response to stressors such as physical activity and blood loss. In the setting of heart failure (HF), excess fluid redistribution from this compartment leads to increased cardiac filling pressures with limitation in exercise capacity. Recent evidence suggests that blocking neural activity of the greater splanchnic nerve (GSN) could have significant benefits in some patients with HF by reducing cardiac filling pressures and improving exercise capacity. However, to date the long‐term safety of splanchnic nerve modulation (SNM) in the setting of HF is unknown. SNM is currently used in clinical practice to alleviate some forms of chronic abdominal pain. A systematic review of the series where permanent SNM was used as a treatment for chronic abdominal pain indicates that permanent SNM is well tolerated, with side‐effects limited to transient diarrhoea or abdominal colic and transient hypotension. The pathophysiological role of the GSN in volume redistribution, the encouraging findings of acute and chronic pilot SNM studies and the safety profile from permanent SNM for pain provides a strong basis for continued efforts to study this therapeutic target in HF.
Metal‐free Photocatalytic Intermolecular anti‐Markovnikov Hydroamination of Unactivated Alkenes
Authors: Zhao Gaoyuan , Li Juncheng , Wang Ting
Published: April 2021

The development of photocatalytic intermolecular hydroamination reaction between N‐aminated dihydropyridines and unactivated alkenes is reported. Metal‐free co‐catalysts, rhodamine 6G and thiophenol, in presence of visible light are used to initiate the process. The transformation shows a broad substrate scope, both alkenes and amidyl radical can act as coupling partners. The radical strategy provides excellent anti‐Markovnikov selectivity and regioselectivity in diene substrates.
Electrochemical Synthesis of Imino‐C‐Nucleosides by “Reactivity Switching” Methodology for in situ Generated Glycoside Donors
Authors: Okamoto Kazuhiro , Tsutsui Mizuki , Morizumi Haruka , Kitano Yoshikazu , Chiba Kazuhiro
Published: April 2021

Redox‐induced regioselective C(sp3)‐H C‐glycosidation for unactivated prolinols was achieved by controlling the anomeric reactivity of electrochemically generated iminium cations. A mechanistic study revealed that the intermediate was pooled as covalent azaribose or iminium cation species in situ, and the electrophilicity of intermediates can be adjusted by changing coexisting acids. We found that the armed/disarmed analogy concept of traditional glycochemistry can be adapted to our C‐glycosidation reaction. Finally, we invented a logical synthetic methodology, named “reactivity switching” concept, and synthesized a series of imino‐C‐nucleosides (C‐azanucleosides) based on this methodology.
Study of Rhodamine‐Based Fluorescent Probes for Organic Radical Intermediates
Authors: He Jiaxin , Yan Boyu , Meng Jiangtao , Ran Maogang , Zhou Yutong , Deng Jinfei , Li Chao‐Jun , Yao Qiuli
Published: April 2021

Rhodamine‐based amide derivatives for the detection of radical intermediates in organic reactions were synthesized and used as fluorescent probes over a wide range of solvents. The mechanistic studies confirm a reversible opening and closing of the spirolactam ring. Compound 21 can be used to support the radical mechanism or in the real‐time monitoring of radical intermediates.
Catalytic degradation of methyl red using PZnW11/m‐Go as a high‐performance photocatalyst
Authors: Aghbolagh Zahra Shokri , Rahmatyan Mohammad Saim , Khorrami Mohammad Reza Khanmohammadi
Published: April 2021

In this research, zinc (II)‐substituted Keggin‐type polyoxometalate [(C4H9)4N] PZnW11O39 (PZnW11) was prepared and stabilized on the modified graphene oxide (m‐GO) for removal of methyl red (MR) dye from aqueous solution. The maximum dye degradation and significance of variables on the decolorization system in static conditions were determined using response surface methodology (RSM). The main variables affecting the decolorization performance on dye decolorization, including system temperature (25–40°C), catalyst amount (0.001–0.005 g), and irradiation time (5–25 min), were evaluated. The optimum temperature, catalyst applying amount, and irradiation time were identified as 35°C, 0.003 g, and 20 min, respectively, and the experimental dye removal value was 96.8%. The high regression coefficient between the response and the variables (R2 = 0.9335) showed a good investigation of the experimental results by regression‐based polynomial model. In comparison with the previously reported photocatalytic decolorization systems, the dye removal system suggested in this work is quick, easy and involves a small amount of catalyst. Polyoxometalate‐based photocatalyst (PZnW11/m‐GO) shows potent visible‐light photocatalytic activity for the decolorization of methyl red dye, due to the generates the strong oxidants hydroxyl radical (OH) and superoxide anion radical (O2−) via photoelectrochemical decomposition of H2O and O2 in the presence of visible light irradiation. Efficient decolorization and degradation of organic contaminants by synthesized catalyst PZnW11/m‐GO suggest its potential for real industrial applications in removal of synthetic dye wastewater.
Emerging trends in sustainable treatment and valorisation technologies for plastic wastes in Nigeria: A concise review
Authors: Nyakuma Bemgba B. , Ivase Tertsegha J.‐P.
Published: April 2021

The article presents an overview of the status, challenges, and prospects of current and emerging trends for the sustainable treatment and valorisation technologies of plastic wastes. The proliferation is ascribed to the growing population, living standards, and use of low cost, unbiodegradable, and chemically resistant plastic wastes in Nigeria. This scenario is exacerbated by the lack of comprehensive strategies for the collection, transport, segregation, and management of plastic wastes. Currently, plastic wastes treatment is accomplished by open‐air burning, dumping, and landfilling. More advanced technologies, such as thermal (incineration, gasification), chemical (catalytic cracking and selective dissolution), and biological (microbial degradation) methods, are also utilized for treatment and valorisation. However, these high‐cost, obsolete, and inefficient technologies result in GHG emissions, toxic fumes, toxins and leachates. Hence, novel technologies for the reuse, recycling, reduction, and valorisation of plastic wastes must emphasize energy, materials, and resource recovery. The article proposes the upcycling of plastic wastes into carbon nanomaterials (carbon microspheres, carbon nanofibers (CNFs), graphene flakes, carbon nanotubes), polymeric composite materials (wood‐polyethylene composites, wood‐fiber‐reinforced plastics), biocrude/bio‐oil, fuels, chemicals, and char through solvent/solvothermal treatment and plasma conversion. Solvent/solvothermal treatment can effectively treat and upcycle plastic wastes along with the removal of toxic, recalcitrant and bio‐accumulative pollutants such as brominated flame retardants and organophosphorus flame retardants. However, the study identified numerous challenges that currently hamper plastic wastes disposal, management, and valorisation. Hence, sustainable and socially friendly approaches for plastic waste management and valorisation are required to address their short‐ and long‐term impacts on human health, safety and the environment in Nigeria.
Landscape archaeology—The value of context to archaeological interpretation: A case study from Waitore, New Zealand
Authors: Goff James , McFadgen Bruce , Marriner Nick
Published: April 2021

Landscape archaeology is a relatively young subdiscipline that has grown in a multitude of directions, particularly in recent decades. It is strongly multidisciplinary and has borrowed tools from an array of fields, including the archaeological sciences, geology, geography, palaeoecology and geochronology; many landscape archaeologists have backgrounds beyond traditional archaeology sensu stricto. Landscape archaeology has become an important facet of most archaeological excavations and has shifted the focus of archaeological interpretation well beyond existing paradigms. In this paper, we report on a landscape reinterpretation of a single archaeological site in New Zealand. Waitore comprises an assemblage of artefacts, including wooden pieces (e.g., broken canoe fragments), oven stones, stone sinkers and fish bones but is not associated with an occupation site. The assemblage was originally studied in the 1970s—at a time when there was little understanding of tectonic processes in the region—and attributed to permanent ritual interment or temporary burial based largely on ethnographic analogies with contemporary Māori practices. By bringing together the physical and cultural components of landscape archaeology, we reinterpret these artefacts as being the scattered remnants of a reworked occupation site, possibly associated with a tsunami inundation dating to around the 15th century. We conclude that re‐examination of past archaeological work is as relevant now as undertaking new research. We also insist upon the importance of multidisciplinary dialogue, particularly between the social and physical sciences, in helping to move beyond current paradigms.