bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spoken language outcomes in limited language preschoolers with autism and global developmental delay: RCT of early intervention approaches
Authors: Kasari Connie , Shire Stephanie , Shih Wendy , Landa Rebecca , Levato Lynne , Smith Tristram 
Published: April 2023

AbstractPreschool autistic children with significant global developmental delays and very limited language skills are at high risk for remaining minimally verbal at entry into primary school. This study compared two early intervention models for improving social communication and spoken language outcomes in 164 children who received intervention in their community preschool program for 6 months, with a six‐month follow‐up. The primary outcome measure was a standardized language assessment, and secondary measures focused on social communication. Results indicated children on average made 6 months gain in language development in the active 6 months of intervention with no difference between intervention models. Children who initiated joint attention more frequently, or who had higher receptive language at baseline made more progress if assigned to receive JASPER, a naturalistic developmental behavioral intervention. Children who received Discrete Trial Training made greater spoken language progress from exit to follow‐up. These findings suggest that progress can be made in autistic children who have very little spoken language and who receive targeted early interventions. Individual trajectories vary and depend in part on initial abilities in social communication and receptive language. Future research might consider methods to systematically personalize approaches to fit child characteristics and family preference.Lay SummaryThis study compared two different early intervention approaches for teaching spoken language to minimally verbal, globally delayed autistic preschoolers. Children were given an hour of therapy daily for 6 months and then reassessed 6 months later. The majority of the 164 participants were from historically excluded populations (low income and minority), and therapy was delivered in school community settings by expert clinicians. Results indicated that the participants made significant progress regardless of intervention approach: 6 months gain in standardized language scores over 6 months, but slower progress during the period after therapy ended. Children who initiated joint attention more frequently, or who had higher language understanding at baseline made more progress if assigned to receive JASPER, a naturalistic developmental behavioral intervention. Children who received Discrete Trial Training made greater language progress during 6‐month period after therapy ended. These findings suggest that progress can be made in children with ASD who have very little spoken language and who receive targeted early interventions.
Evaluation of in vitro effect, molecular docking, and molecular dynamics simulations of some dihydropyridine‐class calcium channel blockers on human serum paraoxonase 1 (hPON1) enzyme activity
Authors: Gökçe Başak , Muhammed Muhammed Tilahun 
Published: April 2023

AbstractParaoxonase 1 (PON1) was purified 148.80‐fold in 37.92% yield by hydrophobic interaction chromatography technique. The purity of PON1 was checked by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) with a single band of 43 kDa. The in vitro effects of nine different calcium channel blockers on PON1 activity were evaluated. All drugs strongly decreased PON1 activity, and IC50 levels were between 13.987 ± 0.59 and 238.104 ± 2.14 μM, Ki values between 8.58 ± 0.36 and 111 ± 1.27 μM. The drugs with the strongest inhibitory effect were nisoldipine with 13.987 ± 0.59 μM and nicardipine with 20.158 ± 0.43 μM. The mechanism of action for the inhibition of the enzyme by nisoldipine and nicardipine was investigated through molecular docking. The stability of enzyme–ligand complexes obtained from the docking was explored through molecular dynamics simulation. The binding affinity of the ligands toward the enzyme was also investigated through MMPBSA (molecular mechanics Poisson–Boltzmann surface area method). The computational analysis demonstrated these compounds could inhibit the enzyme. Nisoldipine had the strongest binding, and its complex was the most stable one. Furthermore, nicardipine was found to have the highest affinity toward the enzyme.
Bipolar Isoindoline Nitroxide for Nonaqueous Symmetrical Redox Flow Battery
Authors: Loomans Benjamin I. , Bottle Steven E. , Blinco James P. 
Published: April 2023

AbstractCrossover in non‐aqueous redox flow batteries remains a critical challenge to the cycle stability of these devices. The use of bipolar redox‐active organic materials (ROM) is an emerging strategy for mitigating crossover. Herein we report the first example of a bipolar ROM derived from an isoindoline nitroxide, a ring class which gives a number of advantages over the more commonly employed piperidines, including greater stability and a 200 mV higher oxidation potential. Through facile synthetic transformation, the unsubstituted isoindoline nitroxide was nitrated to give a novel bipolar molecule, 5‐nitro‐1,1,3,3‐tetramethylisoindoline‐2‐yloxyl (NTMIO). This material was investigated electrochemically, revealing a reversible oxidation and quasi‐reversible reduction giving a cell potential of 2.07 V. NTMIO was then assessed as an active material in both a static and flow battery model, where cycling was observed for both oxidative and reductive redox couples for over 70 and 20 cycles respectively.
Stilbene ligand‐based metal–organic frameworks for efficient dye adsorption and nitrobenzene detection
Authors: Kim Jiyun , Na Chanju , Son Younghu , Prabu Mani , Yoon Minyoung 
Published: April 2023

AbstractThe technological developments of metal–organic framework (MOF) for selective adsorption and sensing have been achieved in recent years. Herein, we report two stilbene‐based MOFs, denoted as Zn3(SDC)3(bpy) (1) and Zn(SDC)(bpy)·2DMF (2). MOFs 1 and 2 were synthesized in pure form by controlling the organic linker ratio and were used for the adsorptive removal of dye molecules. Despite their low adsorption capacities, the MOFs were more selective toward cationic dye (methylene blue) than anionic dye (methyl orange). The unique fluorescent property of the MOFs was harnessed for the sensing of harmful organic molecules. Interestingly, the fluorescence of 1′ was quenched by aromatic analytes containing amine and nitro functional groups. However, 2′ only showed modest fluorescence quenching by nitrobenzene. The quenching efficiency of nitrobenzene had a low detection limit for 1′ and 2′ (14.28 and 25.42 μM, respectively). These MOFs can be used as adsorbents and highly sensitive chemical sensors.
A comparative metabolomics study on dried and processed Rehmannia Radix
Authors: Liu Tong , Zhou Ning , Bai Zhiyao , Cao Yumin , Zhang Jinying , Wang Yongxiang , Zheng Xiaoke , Feng Weisheng 
Published: April 2023

AbstractThe efficacy of Rehmannia Radix changes after processing. However, the precise effect of processing on the properties of Rehmannia Radix is an intricate topic, as this effect cannot be explained by traditional methods. The purpose of this study was to investigate how processing methods influence the properties of Rehmannia Radix, as well as the changes in body function after administering dried Rehmannia Radix (RR) and processed Rehmannia Radix (PR) using a metabolomics approach. In addition, principal component analysis and orthogonal partial least‐squares discriminant analysis models were generated using SIMCA‐P 14.0 to evaluate the properties of RR and PR. Potential biomarkers were identified, and associated metabolic networks were established to clarify differences in the properties and efficacies of RR and PR. The results showed that RR and PR have cold and hot properties, respectively. RR can exert a hypolipidaemic effect by regulating nicotinate and nicotinamide metabolism. PR exerts a tonic effect and regulates the body’s reproductive function through the regulation of alanine, aspartate and glutamate metabolism, arachidonic acid, pentose and glucuronate metabolism, respectively. Ultra‐high‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry‐based metabolomics is a promising approach to determine the cold/hot properties of traditional Chinese medicine formulations.
Immersive virtual reality in AECO/FM to enhance education: Systematic literature review and future directions
Authors: Tastan Hasan , Tong Togan 
Published: April 2023

AbstractImmersive virtual reality (IVR) is considered as an effective and efficient instructional tool for architecture, engineering, construction, operation, and facility management (AECO/FM) education. However, it is essential to systematically evaluate them to obtain consolidated evidence on the impact of IVR applications. Thus, the aim of this article is to present the state‐of‐the‐art on all AECO/FM use cases, including learning theories/models, all key factors, and experimental design, and to suggest future directions for IVR research. This review follows a systematic literature review methodology to analyze 79 papers between 2013 and 2022. The results show that learning theories/models are not sufficiently applied. There is consensus that IVR influences affective factors positively. It is necessary to consider task type, task complexity, virtual environment design, and ergonomics of IVR tools in terms of cognitive factors. Cognitive/affective factors associated with learning performance should be examined in depth to develop more effective learning methods. Future studies should design and conduct experimental procedures with more scientific rigor.
An educational tool for understanding MPEG‐2 video compression and coding techniques
Authors: Fernández‐Plazaola Unai , Gómez Gerardo , López‐Martínez F. Javier 
Published: April 2023

AbstractThe understanding of the video encoding/decoding processes is a key skill for students of computer science, engineering, or telecommunications, especially those specialized in multimedia. The special characteristics of the video signals, and how such features are leveraged to compress the video frames using coding theory, are hard to understand for engineering students. In this paper, we describe MPEG‐2 analyzer, an educational tool designed to provide a comprehensive and interactive way to understand MPEG‐2 video compression and encoding techniques. We have used our tool to evaluate its usefulness in reinforcing the knowledge about the MPEG‐2 video (de)coding process to Telecommunication Engineering students. Results show that the evaluation of the tool is very positive, and it has helped them to understand many of the complex concepts covered in the course.
Discovery of Potent Pyrazoline‐Based Covalent SARS‐CoV‐2 Main Protease Inhibitors**
Authors: Moon Patrick , Zammit Charlotte M. , Shao Qian , Dovala Dustin , Boike Lydia , Henning Nathaniel J. , Knapp Mark , Spradlin Jessica N. , Ward Carl C. , Wolleb Helene , Fuller Daniel , Blake Gabrielle , Murphy Jason P. , Wang Feng , Lu Yipin , Moquin Stephanie A. , Tandeske Laura , Hesse Matthew J. , McKenna Jeffrey M. , Tallarico John A. , Schirle Markus , Toste F. Dean , Nomura Daniel K. 
Published: April 2023

AbstractWhile vaccines and antivirals are now being deployed for the current SARS‐CoV‐2 pandemic, we require additional antiviral therapeutics to not only effectively combat SARS‐CoV‐2 and its variants, but also future coronaviruses. All coronaviruses have relatively similar genomes that provide a potential exploitable opening to develop antiviral therapies that will be effective against all coronaviruses. Among the various genes and proteins encoded by all coronaviruses, one particularly “druggable” or relatively easy‐to‐drug target is the coronavirus Main Protease (3CLpro or Mpro), an enzyme that is involved in cleaving a long peptide translated by the viral genome into its individual protein components that are then assembled into the virus to enable viral replication in the cell. Inhibiting Mpro with a small‐molecule antiviral would effectively stop the ability of the virus to replicate, providing therapeutic benefit. In this study, we have utilized activity‐based protein profiling (ABPP)‐based chemoproteomic approaches to discover and further optimize cysteine‐reactive pyrazoline‐based covalent inhibitors for the SARS‐CoV‐2 Mpro. Structure‐guided medicinal chemistry and modular synthesis of di‐ and tri‐substituted pyrazolines bearing either chloroacetamide or vinyl sulfonamide cysteine‐reactive warheads enabled the expedient exploration of structure‐activity relationships (SAR), yielding nanomolar potency inhibitors against Mpro from not only SARS‐CoV‐2, but across many other coronaviruses. Our studies highlight promising chemical scaffolds that may contribute to future pan‐coronavirus inhibitors.
Phospholipid‐Coated Boronic Oxide Nanoparticles as Boron Agents for Boron Neutron Capture Therapy
Authors: Kawasaki Riku , Hirano Hidetoshi , Yamana Keita , Oshige Ayano , Nishimura Kotaro , Kono Nanami , Sanada Yu , Bando Kaori , Tabata Anri , Yasukawa Naoki , Azuma Hideki , Takata Takushi , Sakurai Yoshinori , Tanaka Hiroki , Suzuki Minoru , Tarutani Naoki , Katagiri Kiyofumi , Nagasaki Takeshi , Ikeda Atsushi 
Published: April 2023

AbstractMinimally invasive boron neutron capture therapy (BNCT) is an elegant approach for cancer treatment. The highly selective and efficient deliverability of boron agents to cancer cells is the key to maximizing the therapeutic benefits of BNCT. In addition, enhancement of the frequencies to achieve boron neutron capture reaction is also significant in improving therapeutic efficacy by providing a highly concentrated boron agent in each boron nanoparticle. As the density of the thermal neutron beam remains low, it is unable to induce high‐efficiency cell destruction. Herein, we report phospholipid‐coated boronic oxide nanoparticles as agents for BNCT that can provide a highly concentrated boron atom in each nanoparticle. The current system exhibited in vitro BNCT activity seven times higher than that of commercial boron agents. Furthermore, the system could penetrate cancer spheroids deeply, efficiently suppressing thermal neutron irradiation‐induced growth.
Precise and Controlled Modification of Proteins using Multifunctional Chemical Constructs
Authors: Albada Bauke 
Published: April 2023

AbstractBioconjugation of chemical entities to biologically active proteins has increased our insight in the inner workings of a cell and resulted in novel therapeutic agents. A current challenge is the efficient generation of homogeneous conjugates of native proteins, not only when isolated, but also when still present in their native environment. To do this, various features of protein‐modifying enzymes have been combined in artificial constructs. In this concept, the current status of this approach is evaluated, and the interplay between designs and protein modification will be discussed. Particular focus is directed on the protein‐binding anchor, the chemistry that is used for the modification, and the linker that connects these two units. Suggestions how to include additional elements such as a trigger‐responsive switch that regulated protein modification are also presented.
Aldehyde‐Based Inhibitors of the Peptidoglycan O‐Acetylesterase Ape
Authors: Voskoboinyk Dmytro , Mahmoodi Niusha , Lin Chang Sheng‐Huei , Murphy Michael E. P. , Tanner Martin E. 
Published: April 2023

AbstractThe O‐acetylation of the muramic acid residues in peptidoglycan (PG) is a modification that protects the bacteria from lysis due to the action of lysozyme. In Gram‐negative bacteria, deacetylation is required to allow lytic transglycosylases to promote PG cleavage during cell growth and division. This deacetylation is catalyzed by O‐acetylpeptidoglycan esterase (Ape) which is a serine esterase and employs covalent catalysis via a serine‐linked acyl enzyme intermediate. Loss of Ape activity affects the size and shape of bacteria and dramatically reduces virulence. In this work, we report the first rationally designed aldehyde‐based inhibitors of Ape from Campylobacter jejuni. The most potent of these acts as a competitive inhibitor with a Ki value of 13 μM. We suspect that the inhibitors are forming adducts with the active site serine that closely mimic the tetrahedral intermediate of the normal catalytic cycle. Support for this notion is found in the observation that reduction of the aldehyde to an alcohol effectively abolishes the inhibition.
c‐Jun‐mediated JMJD6 restoration enhances resistance of liver cancer to radiotherapy through the IL‐4‐activated ERK pathway
Authors: Liu Yong , Sui Aixia , Sun Jirui , Wu Yifan , Liu Fuquan , Yang Yang 
Published: April 2023

AbstractRadiotherapy is widely used in the treatment of liver cancer, but the efficacy can be limited by radioresistance. In this study, we attempt to delineate the possible molecular mechanism of c‐Jun‐regulated Jumonji domain‐containing protein 6/interleukin 4/extracellular signal‐regulated kinase (JMJD6/IL‐4/ERK) axis in radioresistance of liver cancer. The expression of c‐Jun was quantified in liver cancer tissues and cell lines, and the results indicated that c‐Jun was upregulated in liver cancer tissues and cells. We further illustrated the role of c‐Jun following gain‐ and loss‐of‐function strategies in malignant phenotypes of liver cancer cells. It was established that c‐Jun elevated JMJD6 expression and augmented the malignancy and aggressiveness of liver cancer cells. The in vivo effects of c‐Jun on radioresistance in liver cancer were validated in nude mice, in response to IL‐4 knockdown or the ERK pathway inhibitor, PD98059. In the presence of JMJD6 upregulation, the expression of IL‐4 was elevated in mice with liver cancer, which enhanced the radiation resistance. Moreover, knockdown of IL‐4 inactivated the ERK pathway, thereby reversing the radiation resistance caused by overexpressed JMJD6 in tumor‐bearing mice. Taken together, c‐Jun augments the radiation resistance in liver cancer by activating the ERK pathway through JMJD6‐upregulated IL‐4 transcription.
Computed tomography‐derived membranous septum length as predictor of conduction abnormalities and permanent pacemaker implantation after TAVI: A meta‐analysis of observational studies
Authors: Sá Michel Pompeu , Van den Eynde Jef , Jacquemyn Xander , Erten Ozgun , Rodriguez Roberto , Goldman Scott , Coady Paul M. , Gnall Eric , Gray William A. , Jarrett Harish , Abramson Sandra V. , Clavel Marie‐Annick , Pibarot Philippe , Ramlawi Basel 
Published: April 2023

AbstractBackgroundPermanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) is associated with higher risk of mortality and rehospitalization for heart failure. Efforts to prevent conduction abnormalities (CA) requiring PPI after TAVI should be made. The membranous septum (MS) length and its interaction with implantation depth (ID–ΔMSID) could provide useful information about the risk of CA/PPI following TAVI.ObjectivesTo identify MS length and ΔMSID as predictors of CA/PPI following TAVI.MethodsStudy‐level meta‐analysis of studies published by September 30, 2022.ResultsEighteen studies met our eligibility including 5740 patients. Shorter MS length was associated with a significantly higher risk of CA/PPI (per 1 mm decrease: odds ratio [OR] 1.60, 95% confidence interval [CI] 1.28–1.99, p < 0.001). Similarly, lower ΔMSID was associated with a significantly higher risk of CA/PPI (per 1 mm decrease: OR 1.75, 95% CI 1.32–2.31, p < 0.001). Meta‐regression analyses revealed a statistically significant modulation of the effect of shorter MS length and lower ΔMSID on the outcome (CA/PPI) by balloon postdilatation (positive regression coefficients with p < 0.001); with increasing use of balloon postdilatation, the effect of shorter MS length and lower ΔMSID on the outcome increased. MS length and ΔMSID demonstrated excellent discriminative abilities, with diagnostic ORs equaling 9.49 (95% CI 4.73–19.06), and 7.19 (95% CI 3.31–15.60), respectively.ConclusionConsidering that short MS length and low ΔMSID are associated with higher risk of CA and PPI, we should include measurement of MS length in the pre‐TAVI planning with MDCT and try to establish optimal ID values before the procedure to avoid CA/PPI.
Optical Super‐Localisation of Single Nanoparticle Nucleation and Growth in Nanodroplets
Authors: Ciocci Paolo , Valavanis Dimitrios , Meloni Gabriel N. , Lemineur Jean‐François , Unwin Patrick R. , Kanoufi Frédéric 
Published: April 2023

AbstractInvited for this issue's Front Cover are the groups of Prof. Frédéric Kanoufi, Université Paris Cité‐CNRS (France), and Prof. Patrick Unwin, University of Warwick (United Kingdom), collaborating under the EU Horizon 2020 ‘Single‐entity Nanoelectrochemistry’ programme. The cover picture illustrates the use of their hybrid technique to investigate the dynamics of the electrodeposition of individual Ag nanoparticles within an ensemble. The particles are represented by band members whose individual performances can be monitored. Read the full text of the Research Article at 10.1002/celc.202201162.
A context‐specific conceptual framework of evidence synthesis to improve childhood cancer health outcomes and resource use in Egypt: Using real‐world data and addressing the implementation gaps
Authors: Soliman Ranin 
Published: April 2023

AbstractIntroductionGiven the large numbers of children with cancer in Egypt, the limited resources, and inferior survival outcomes, there is a need to better target resources to improve outcomes efficiently based on evidence. Nevertheless, there is a gap in knowledge about childhood cancer health outcomes and resource use in Egypt. This commentary presents a “context‐specific” conceptual framework of evidence synthesis to improve childhood cancer health outcomes and resource use in a resource‐limited setting in Egypt, using real‐world data and addressing the implementation gaps.MethodsReal‐world data is defined as data relating to health status and/or the delivery of health services routinely collected from various sources outside the contexts of randomized controlled trials that can be used to conduct prospective/retrospective observational research studies.ResultsTo better address this context‐specific clinical problem, the conceptual framework of evidence synthesis proposes to generate three types of evidence using hybrid research methods; (1) Real‐world evidence (obtained from observational studies based on routinely collected data from local context); (2) systematic evidence from the literature (systematic review); and (3) qualitative evidence based on experts' opinions in the local setting (interview study). Generating evidence from the three pillars altogether makes for a stronger approach to better research and tackle the local problem in this specific resource‐limited context, and address the implementation gaps.ConclusionsThis framework serves as a methodological roadmap to generate relevant evidence in similar resource‐limited contexts in low‐ and middle‐income countries, where there is a paucity of published studies in the literature about childhood cancer survival outcomes and resource use.
One‐Pot Synthesis of Diverse 1,4‐[60]Fullerephenols via Three‐Component Umpolung Cascade Coupling of Phenols, C60, and Nucleophiles
Authors: Zhang Jun‐Xiang , Wu Yuan‐Ze , Chen Dong‐Mei , Xuan Jun , Li Fei 
Published: April 2023

AbstractA three‐component umpolung cascade coupling reaction of phenols, C60, and different nucleophiles which includes H2O, alcohols, triphenylamines and carbazoles was developed. Furthermore, one‐pot 1,4‐bisphenol coupling on C60 has been realized by this method. This practical protocol features high chemo‐ and regioselectivity, wide substrate range, easy operation and low cost, thus providing a robust method for the one‐pot synthesis of various unsymmetrical 1,4‐[60]fullerephenols.