bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiles of Sterigmatocystin and Its Metabolites during Traditional Chinese Rice Wine Processing
Authors: Zhang Jia , Xu Liwei , Xu Xinxin , Wu Xiaoling , Kuang Hua , Xu Chuanlai
Published: April 2022

Mycotoxin pollution is widespread in cereal, which greatly threatens food security and human health. In this study, the migration and transformation of sterigmatocystin (STG) mycotoxin during the contaminated rice wine processing was systematically assessed. QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) coupled with ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UPLC−MS/MS) method was firstly established for STG analysis in rice wine. It was found that high levels of rice leaven caused a significant reduction in STG in the fermented rice and wine, which was mainly due to the adsorption of yeast cells and Rhizopus biological degradation. However, compared with rice, the levels of STG in separated fermented wine was significantly decreased by 88.6%, possibly attributed to its high log Kow (3.81) and low water solubility (1.44 mg/L). The metabolites of STG (i.e., monohydroxy STG) were identified in rice wine fermentation for the first time. Moreover, STG disturbed the metabolic profile rice wine composition mainly by glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, purine metabolism pathway, particularly with regard to eight amino acids and sixteen lipids. This study elucidated the STG migration and transformation mechanism during the rice wine processing. The finding provided new analytical method for mycotoxin exposure and pollutant in food production, which may support agricultural production and food security.
Artificial Visual System for Orientation Detection Based on Hubel–Wiesel Model
Authors: Li Bin , Todo Yuki , Tang Zheng
Published: April 2022

The Hubel–Wiesel (HW) model is a classical neurobiological model for explaining the orientation selectivity of cortical cells. However, the HW model still has not been fully proved physiologically, and there are few concise but efficient systems to quantify and simulate the HW model and can be used for object orientation detection applications. To realize a straightforward and efficient quantitive method and validate the HW model’s reasonability and practicality, we use McCulloch-Pitts (MP) neuron model to simulate simple cells and complex cells and implement an artificial visual system (AVS) for two-dimensional object orientation detection. First, we realize four types of simple cells that are only responsible for detecting a specific orientation angle locally. Complex cells are realized with the sum function. Every local orientation information of an object is collected by simple cells and subsequently converged to the corresponding same type complex cells for computing global activation degree. Finally, the global orientation is obtained according to the activation degree of each type of complex cell. Based on this scheme, an AVS for global orientation detection is constructed. We conducted computer simulations to prove the feasibility and effectiveness of our scheme and the AVS. Computer simulations show that the mechanism-based AVS can make accurate orientation discrimination and shows striking biological similarities with the natural visual system, which indirectly proves the rationality of the Hubel–Wiesel model. Furthermore, compared with traditional CNN, we find that our AVS beats CNN on orientation detection tasks in identification accuracy, noise resistance, computation and learning cost, hardware implementation, and reasonability.
Qualitative Assessment of Collaborative Behavior Based on Self-Perception Personality Tests for BIM Staff
Authors: Biabani Fatemeh , Kim Ju-Hyung , Ham Namhyuk
Published: April 2022

Collaboration, such as communication and coordination, using BIM is the key to a successful BIM-based construction project. In spite of existing studies on BIM competency and the optimal arrangement of BIM staff, there have not been many studies on the tendencies of BIM staff in the humanities aspect. The purpose of this study is to qualitatively evaluate the collaborative behavior of BIM staff through a cognitive survey targeting BIM staff. For this, 13 tasks essential for collaboration were defined. The frequency of tasks performed by the BIM staff differed according to the role they are in charge of, and the frequency of tasks considered important to support the collaboration of project participants also appeared to be different. In addition, the personal behavior of the BIM staff, which is the core outcome of this study, was investigated by dividing it into two types: the importance level of personality traits and the required level of personality traits. A survey on the perception of BIM staff was conducted through three categories (leadership, communication, job performance) and a total of 17 personality traits. The research findings, visualized through a correspondence analysis, strongly suggest that it is necessary to consider the personality traits of the BIM staff to improve collaboration performance.
Preferences for Hotels with Biophilic Design Attributes in the Post-COVID-19 Era
Authors: Khozaei Fatemeh , Carbon Claus Christian , Hosseini Nia Mahdieh , Kim Mi Jeong
Published: April 2022

Since the COVID-19 crisis has caused the cancellation of a great number of travel plans in the last two years, this study examines the prospects of the post-COVID-19 era, during which we expect tourism will return strongly. The impact of the epidemic on people’s attitudes toward tourism, particularly their tourist choices, appears to be a major challenge for post-COVID-19 international tourism development. Very little is known about tourists’ accommodation preferences during the period emerging after the COVID-19 crisis. With a long and challenging experience of lockdowns, stress, and fear of disease, the current study attempts to examine peoples’ preferences for hotel attributes during the post-COVID-19 era. It examines factors contributing to peoples’ preferences for hotels with biophilic attributes. A total of 507 Iranian undergraduate and graduate students participated in the study. They answered questions on their perceived stress, level of depression, the specific burden of COVID-19, the perceived benefits of nature, and their preferences for biophilic design attributes in their accommodation. The online survey was conducted from August to October 2021. We found that the burden of COVID-19 increased the stress level of the respondents, which consequently increased the chance of depression. We further found that perceived stress and the benefits of nature significantly affect tourists’ preferences for exposure to nature and hotels with biophilic attributes. Based on the data, we suggest that the demand for biophilic buildings will be strongly increased during the post-COVID-19 era.
A Multidisciplinary Approach for the Vulnerability Assessment of a Venetian Historic Palace: High Water Phenomena and Climate Change Effects
Authors: Berto Luisa , Talledo Diego Alejandro , Bruschi Greta , Zamboni Isabella , Lazzarini Enrico , Zofrea Chiara , Faccio Paolo , Saetta Anna
Published: April 2022

This paper illustrates a multidisciplinary approach aimed at the vulnerability assessment of historic masonry heritage in Venice, focusing on questions of method and practice, which specifically involve the disciplines of restoration, building archaeology and structural engineering. Taking into account the existing standards for the management and assessment of cultural heritage, an integrated methodology is proposed for analyzing and interpreting historic constructions. Particular reference is made to Venetian scenery and its relationship with water, from the worldwide known high tide phenomena to the new perspectives offered by MOSE (i.e., Experimental Electromechanical Module, a system of a series of retractable mobile gates) and the new challenges due to climate change. Within such an approach, the different disciplines, including the building archeology, contribute to obtaining an interpretative model for historic buildings subjected to the high tide phenomena, with the aim of performing a vulnerability assessment and to design possible restoration interventions. The proposed methodology is applied to the case study of a Venetian historic palace facing the Grand Canal. For this palace, all the steps of the knowledge path have been carried out, from historical study to geometrical, Material-Constructive Survey, Crack Pattern and Degradation Analysis to stratigraphic analysis. The interpretative model obtained at the end of this path is enriched with the results of preliminary numerical analyses that investigate, in greater depth, the effects of high water phenomena on the rising damp front in masonry walls. Some previsions on the effects of MOSE activation and of climatic change, in particular in terms of sea-level rise, are presented.
Dynamic Network Analysis of the Risks of Mega Infrastructure Projects from a Sustainable Development Perspective
Authors: Li Yuanli , Xiang Pengcheng , You Kairui , Guo Jin
Published: April 2022

Mega infrastructure projects (MIPs) are exposed to numerous interdependent risks of various natures which pose difficulties in risk management. Thus far, the research on the risk interactions of MIPs has been focused on developing static risk networks within a single category of risks, at certain stages of the project. It is essential to understand the risk interactions at various stages of MIPs to identify the key risks and key risk relationships that jeopardise their success. This is especially relevant nowadays, as MIPs are expected to be delivered sustainably. Therefore, to analyse the dynamic risk interaction of MIPs, initially, through literature analysis and expert interviews, combined with the four dimensions of sustainable development and the four stages of MIPs, 98 risk factors of MIPs were identified. Subsequently, semi-structured interviews were conducted to determine risk relationships and weights. Risk networks were developed for each stage of MIPs, and improved social network analysis was applied to these risk networks. Finally, the key risks and key risk relationships in each stage of MIPs were identified by analysing the changes of multi-level network indicators. This aided in determining risk control strategies. The results demonstrate that the key risks and key risk relationships are different for each stage of MIPs. Furthermore, the risks of different dimensions of sustainable development have different relationships at different stages. This research is the first to identify the risk relationships involved in MIPs by taking into consideration the whole project life cycle and its sustainable development. This research provides theoretical support for the risk management of MIPs, and strategic suggestions for controlling the risks at each stage of the project.
Molecularly Targeted Therapy towards Genetic Alterations in Advanced Bladder Cancer
Authors: Thomas Jonathan , Sonpavde Guru
Published: April 2022

Despite the introduction of immune checkpoint inhibitors and antibody–drug conjugates to the management of advanced urothelial carcinoma, the disease is generally incurable. The increasing incorporation of next-generation sequencing of tumor tissue into the characterization of bladder cancer has led to a better understanding of the somatic genetic aberrations potentially involved in its pathogenesis. Genetic alterations have been observed in kinases, such as FGFRs, ErbBs, PI3K/Akt/mTOR, and Ras-MAPK, and genetic alterations in critical cellular processes, such as chromatin remodeling, cell cycle regulation, and DNA damage repair. However, activating mutations or fusions of FGFR2 and FGFR3 remains the only validated therapeutically actionable alteration, with erdafitinib as the only targeted agent currently approved for this group. Bladder cancer is characterized by genomic heterogeneity and a high tumor mutation burden. This review highlights the potential relevance of aberrations and discusses the current status of targeted therapies directed at them.
Formulation and Characterization of Poly (Ethylene Glycol)-Coated Core-Shell Methionine Magnetic Nanoparticles as a Carrier for Naproxen Delivery: Growth Inhibition of Cancer Cells
Authors: Yeganeh Faten Eshrati , Yeganeh Amir Eshrati , Yousefi Mohammad , Farasati Far Bahareh , Akbarzadeh Iman , Bokov Dmitry Olegovich , Raahemifar Kaamran , Soltani Madjid
Published: April 2022

An efficient and selective drug delivery vehicle for cancer cells can remarkably improve therapeutic approaches. In this study, we focused on the synthesis and characterization of magnetic Ni1−xCoxFe2O4 nanoparticles (NPs) coated with two layers of methionine and polyethylene glycol to increase the loading capacity and lower toxicity to serve as an efficient drug carrier. Ni1−xCoxFe2O4@Methionine@PEG NPs were synthesized by a reflux method then characterized by FTIR, XRD, FESEM, TEM, and VSM. Naproxen was used as a model drug and its loading and release in the vehicles were evaluated. The results for loading efficiency showed 1 mg of Ni1−xCoxFe2O4@Methionine@PEG NPs could load 0.51 mg of the naproxen. Interestingly, Ni1−xCoxFe2O4@Methionine@PEG showed a gradual release of the drug, achieving a time-release up to 5 days, and demonstrated that a pH 5 release of the drug was about 20% higher than Ni1−xCoxFe2O4@Methionine NPs, which could enhance the intracellular drug release following endocytosis. At pH 7.4, the release of the drug was slower than Ni1−xCoxFe2O4@Methionine NPs; demonstrating the potential to minimize the adverse effects of anticancer drugs on normal tissues. Moreover, naproxen loaded onto the Ni1−xCoxFe2O4@Methionine@PEG NPs for breast cancer cell lines MDA-MB-231 and MCF-7 showed more significant cell death than the free drug, which was measured by an MTT assay. When comparing both cancer cells, we demonstrated that naproxen loaded onto the Ni1−xCoxFe2O4@Methionine@PEG NPs exhibited greater cell death effects on the MCF-7 cells compared with the MDA-MB-231 cells. The results of the hemolysis test also showed good hemocompatibility. The results indicated that the prepared magnetic nanocarrier could be suitable for controlled anticancer drug delivery.
Role of mTOR through Autophagy in Esophageal Cancer Stemness
Authors: Du Liang , Wang Da , Nagle Peter W. , Groen Andries A. H. , Zhang Hao , Muijs Christina T. , Plukker John Th. M. , Coppes Robert P.
Published: April 2022

Esophageal cancer (EC) is a highly aggressive disease with a poor prognosis. Therapy resistance and early recurrences are major obstacles in reaching a better outcome. Esophageal cancer stem-like cells (CSCs) seem tightly related with chemoradiation resistance, initiating new tumors and metastases. Several oncogenic pathways seem to be involved in the regulation of esophageal CSCs and might harbor novel therapeutic targets to eliminate CSCs. Previously, we identified a subpopulation of EC cells that express high levels of CD44 and low levels of CD24 (CD44+/CD24−), show CSC characteristics and reside in hypoxic niches. Here, we aim to clarify the role of the hypoxia-responding mammalian target of the rapamycin (mTOR) pathway in esophageal CSCs. We showed that under a low-oxygen culture condition and nutrient deprivation, the CD44+/CD24− population is enriched. Since both low oxygen and nutrient deprivation may inhibit the mTOR pathway, we next chemically inhibited the mTOR pathway using Torin-1. Torin-1 upregulated SOX2 resulted in an enrichment of the CD44+/CD24− population and increased sphere formation potential. In contrast, stimulation of the mTOR pathway using MHY1485 induced the opposite effects. In addition, Torin-1 increased autophagic activity, while MHY1485 suppressed autophagy. Torin-1-mediated CSCs upregulation was significantly reduced in cells treated with autophagy inhibitor, hydroxychloroquine (HCQ). Finally, a clearly defined CD44+/CD24− CSC population was detected in EC patients-derived organoids (ec-PDOs) and here, MHY1485 also reduced this population. These data suggest that autophagy may play a crucial role in mTOR-mediated CSCs repression. Stimulation of the mTOR pathway might aid in the elimination of putative esophageal CSCs.
Combinations of ATR, Chk1 and Wee1 Inhibitors with Olaparib Are Active in Olaparib Resistant Brca1 Proficient and Deficient Murine Ovarian Cells
Authors: Chiappa Michela , Guffanti Federica , Anselmi Martina , Lupi Monica , Panini Nicolò , Wiesmüller Lisa , Damia Giovanna
Published: April 2022

Background. Poly(ADP-ribose) polymerases inhibitor (PARPi) have shown clinical efficacy in ovarian carcinoma, especially in those harboring defects in homologous recombination (HR) repair, including BRCA1 and BRCA2 mutated tumors. There is increasing evidence however that PARPi resistance is common and develops through multiple mechanisms. Methods. ID8 F3 (HR proficient) and ID8 Brca1-/- (HR deficient) murine ovarian cells resistant to olaparib, a PARPi, were generated through stepwise drug concentrations in vitro. Both sensitive and resistant cells lines were pharmacologically characterized and the molecular mechanisms underlying olaparib resistance. Results. In ID8, cells with a HR proficient background, olaparib resistance was mainly caused by overexpression of multidrug resistance 1 gene (MDR1), while multiple heterogeneous co-existing mechanisms were found in ID8 Brca1-/- HR-deficient cells resistant to olaparib, including overexpression of MDR1, a decrease in PARP1 protein level and partial reactivation of HR repair. Importantly, combinations of ATR, Chk1 and Wee1 inhibitors with olaparib were synergistic in sensitive and resistant sublines, regardless of the HR cell status. Conclusion. Olaparib-resistant cell lines were generated and displayed multiple mechanisms of resistance, which will be instrumental in selecting new possible therapeutic options for PARPi-resistant ovarian tumors.
Clinical Phenotypes of Cardiovascular and Heart Failure Diseases Can Be Reversed? The Holistic Principle of Systems Biology in Multifaceted Heart Diseases
Authors: Lourida Katerina , Louridas George
Published: April 2022

Recent advances in cardiology and biological sciences have improved quality of life in patients with complex cardiovascular diseases (CVDs) or heart failure (HF). Regardless of medical progress, complex cardiac diseases continue to have a prolonged clinical course with high morbidity and mortality. Interventional coronary techniques together with drug therapy improve quality and future prospects of life, but do not reverse the course of the atherosclerotic process that remains relentlessly progressive. The probability of CVDs and HF phenotypes to reverse can be supported by the advances made on the medical holistic principle of systems biology (SB) and on artificial intelligence (AI). Studies on clinical phenotypes reversal should be based on the research performed in large populations of patients following gathering and analyzing large amounts of relative data that embrace the concept of complexity. To decipher the complexity conundrum, a multiomics approach is needed with network analysis of the biological data. Only by understanding the complexity of chronic heart diseases and explaining the interrelationship between different interconnected biological networks can the probability for clinical phenotypes reversal be increased.
Dimethyl Ether Hydrolysis over WO3/γ-Al2O3 Supported Catalysts
Authors: Smyrnioti Maria , Ioannides Theophilos
Published: April 2022

Dimethyl ether (DME) is considered an alternative hydrogen carrier with potential use in fuel cells and automotive and domestic applications. Dimethyl ether hydrolysis to methanol is a thermodynamically limited reaction catalyzed by solid-acid catalysts, mainly Al2O3 and zeolites. Moreover, it is the rate-limiting step of the DME steam reforming reaction, which is employed for the production of hydrogen fuel for fuel cell feeding. In the present study, the performance of WO3/Al2O3 catalysts (0–44% wt. WO3) was tested in DME hydrolysis reaction. The catalysts were characterized by means of N2-physisorption, XRD, Raman spectroscopy, XPS, NH3-TPD and 2,6-di-tert-butylpyridine adsorption experiments. The reaction rate of DME hydrolysis exhibited a volcanic trend as a function of tungsten surface density, while the best-performing catalyst was 37WO3/Al2O3, with a tungsten surface density of 7.4 W/nm2, noting that the theoretical monolayer coverage for the specific system is 4–5 W/nm2. Brønsted acidity was directly associated with the catalytic activity, following the same volcanic trend as a function of tungsten surface density. Blocking of Brønsted acid sites with 2,6-di-tert-butylpyridine led to a dramatic decrease in hydrolysis rates by 40 times, proving that Brønsted acid sites are primarily responsible for the catalytic activity. Thus, the type and strength rather than the concentration of acid sites are the key factors influencing the catalytic activity.
Synthesis of (S)- and (R)-β-Tyrosine by Redesigned Phenylalanine Aminomutase
Authors: Peng Fei , Aliyu Habibu , Delavault André , Engel Ulrike , Rudat Jens
Published: April 2022

Phenylalanine aminomutase from Taxus chinensis (TchPAM) is employed in the biosynthesis of the widely used antitumor drug paclitaxel. TchPAM has received substantial attention due to its strict enantioselectivity towards (R)-β-phenylalanine, in contrast to the bacterial enzymes classified as EC 5.4.3.11 which are (S)-selective for this substrate. However, the understanding of the isomerization mechanism of the reorientation and rearrangement reactions in TchPAM might support and promote further research on expanding the scope of the substrate and thus the establishment of large-scale production of potential synthesis for drug development. Upon conservation analysis, computational simulation, and mutagenesis experiments, we report a mutant from TchPAM, which can catalyze the amination reaction of trans-p-hydroxycinnamic acid to (R)- and (S)-β-tyrosine. We propose a mechanism for the function of the highly conserved residues L179, N458, and Q459 in the active site of TchPAM. This work highlights the importance of the hydrophobic residues in the active site, including the residues L104, L108, and I431, for maintaining the strict enantioselectivity of TchPAM, and the importance of these residues for substrate specificity and activation by altering the substrate binding position or varying the location of neighboring residues. Furthermore, an explanation of (R)-selectivity in TchPAM is proposed based on the mutagenesis study of these hydrophobic residues. In summary, these studies support the future exploitation of the rational engineering of corresponding enzymes with MIO moiety (3,5-dihydro-5-methylidene-4H-imidazole-4-one) such as ammonia lyases and aminomutases of aromatic amino acids.
Neurotoxic Astrocytes Directly Converted from Sporadic and Familial ALS Patient Fibroblasts Reveal Signature Diversities and miR-146a Theragnostic Potential in Specific Subtypes
Authors: Gomes Cátia , Sequeira Catarina , Likhite Shibi , Dennys Cassandra N. , Kolb Stephen J. , Shaw Pamela J. , Vaz Ana R. , Kaspar Brian K. , Meyer Kathrin , Brites Dora
Published: April 2022

A lack of stratification methods in patients with amyotrophic lateral sclerosis (ALS) is likely implicated in therapeutic failures. Regional diversities and pathophysiological abnormalities in astrocytes from mice with SOD1 mutations (mSOD1-ALS) can now be explored in human patients using somatic cell reprogramming. Here, fibroblasts from four sporadic (sALS) and three mSOD1-ALS patients were transdifferentiated into induced astrocytes (iAstrocytes). ALS iAstrocytes were neurotoxic toward HB9-GFP mouse motor neurons (MNs) and exhibited subtype stratification through GFAP, CX43, Ki-67, miR-155 and miR-146a expression levels. Up- (two cases) and down-regulated (three cases) miR-146a values in iAstrocytes were recapitulated in their secretome, either free or as cargo in small extracellular vesicles (sEVs). We previously showed that the neuroprotective phenotype of depleted miR-146 mSOD1 cortical astrocytes was reverted by its mimic. Thus, we tested such modulation in the most miR-146a-depleted patient-iAstrocytes (one sALS and one mSOD1-ALS). The miR-146a mimic in ALS iAstrocytes counteracted their reactive/inflammatory profile and restored miR-146a levels in sEVs. A reduction in lysosomal activity and enhanced synaptic/axonal transport-related genes in NSC-34 MNs occurred after co-culture with miR-146a-modulated iAstrocytes. In summary, the regulation of miR-146a in depleted ALS astrocytes may be key in reestablishing their normal function and in restoring MN lysosomal/synaptic dynamic plasticity in disease sub-groups.
Mitotic Maturation Compensates for Premature Centrosome Splitting and PCM Loss in Human cep135 Knockout Cells
Authors: Chu Zhenzhen , Gruss Oliver J.
Published: April 2022

Centrosomes represent main microtubule organizing centers (MTOCs) in animal cells. Their duplication in S-phase enables the establishment of two MTOCs in M-phase that define the poles of the spindle and ensure equal distribution of chromosomes and centrosomes to the two daughter cells. While key functions of many centrosomal proteins have been addressed in RNAi experiments and chronic knockdown, knockout experiments with complete loss of function in all cells enable quantitative analysis of cellular phenotypes at all cell-cycle stages. Here, we show that the centriolar satellite proteins SSX2IP and WDR8 and the centriolar protein CEP135 form a complex before centrosome assembly in vertebrate oocytes and further functionally interact in somatic cells with established centrosomes. We present stable knockouts of SSX2IP, WDR8, and CEP135 in human cells. While loss of SSX2IP and WDR8 are compensated for, cep135 knockout cells display compromised PCM recruitment, reduced MTOC function, and premature centrosome splitting with imbalanced PCMs. Defective cep135 knockout centrosomes, however, manage to establish balanced spindle poles, allowing unperturbed mitosis and regular cell proliferation. Our data show essential functions of CEP135 in interphase MTOCs and demonstrate that loss of individual functions of SSX2IP, WDR8, and CEP135 are fully compensated for in mitosis.
Better Outcomes with Intranigral versus Intrastriatal Cell Transplantation: Relevance for Parkinson’s Disease
Authors: Droguerre Marine , Brot Sébastien , Vitrac Clément , Benoit-Marand Marianne , Belnoue Laure , Patrigeon Maelig , Lainé Anaïs , Béré Emile , Jaber Mohamed , Gaillard Afsaneh
Published: April 2022

Intrastriatal embryonic ventral mesencephalon grafts have been shown to integrate, survive, and reinnervate the host striatum in clinical settings and in animal models of Parkinson’s disease. However, this ectopic location does not restore the physiological loops of the nigrostriatal pathway and promotes only moderate behavioral benefits. Here, we performed a direct comparison of the potential benefits of intranigral versus intrastriatal grafts in animal models of Parkinson’s disease. We report that intranigral grafts promoted better survival of dopaminergic neurons and that only intranigral grafts induced recovery of fine motor skills and normalized cortico-striatal responses. The increase in the number of toxic activated glial cells in host tissue surrounding the intrastriatal graft, as well as within the graft, may be one of the causes of the increased cell death observed in the intrastriatal graft. Homotopic localization of the graft and the subsequent physiological cell rewiring of the basal ganglia may be a key factor in successful and beneficial cell transplantation procedures.
The Physiological Roles of the Exon Junction Complex in Development and Diseases
Authors: Asthana Shravan , Martin Hannah , Rupkey Julian , Patel Shray , Yoon Joy , Keegan Abiageal , Mao Yingwei
Published: April 2022

The exon junction complex (EJC) becomes an increasingly important regulator of early gene expression in the central nervous system (CNS) and other tissues. The EJC is comprised of three core proteins: RNA-binding motif 8A (RBM8A), Mago homolog (MAGOH), eukaryotic initiation factor 4A3 (EIF4A3), and a peripheral EJC factor, metastatic lymph node 51 (MLN51), together with various auxiliary factors. The EJC is assembled specifically at exon-exon junctions on mRNAs, hence the name of the complex. The EJC regulates multiple levels of gene expression, from splicing to translation and mRNA degradation. The functional roles of the EJC have been established as crucial to the normal progress of embryonic and neurological development, with wide ranging implications on molecular, cellular, and organism level function. Dysfunction of the EJC has been implicated in multiple developmental and neurological diseases. In this review, we discuss recent progress on the EJC’s physiological roles.
How Cargo Identity Alters the Uptake of Cell-Penetrating Peptide (CPP)/Cargo Complexes: A Study on the Effect of Net Cargo Charge and Length
Authors: Hymel Hannah C. , Rahnama Alireza , Sanchez Olivia M. , Liu Dong , Gauthier Ted J. , Melvin Adam T.
Published: April 2022

Cell-penetrating peptides (CPPs) have emerged as a powerful tool for the delivery of otherwise impermeable cargoes into intact cells. Recent efforts to improve the delivery capability of peptides have mainly focused on the identity of the CPP; however, there is evidence that the identity of the cargo itself affects the uptake. The goal of this work was to investigate how the characteristics of a peptide cargo, including net charge and length, either enhance or diminish the internalization efficiency of the CPP/cargo complex. A small library of CPP/cargo complexes were synthesized consisting of structured and unstructured CPPs with cargoes of net positive, negative, or neutral charge and lengths of 4 or 8 amino acids. Cargoes with a net positive charge were found to enhance the overall uptake of the complexes while net neutral and negatively charged cargoes diminished uptake. Conversely, the net length of the cargo had no significant effect on uptake of the CPP/cargo complexes. Microcopy images confirmed the increased uptake of the positively charged cargoes; however, an increase in punctate regions with the addition of a cargo was also observed. The effects of the net positively charged cargoes were confirmed with both structured and unstructured CPPs, which demonstrated similar trends of an increase in uptake with the addition of positively charged residues. These findings demonstrate that the net charge of cargoes impacts the uptake of the complex, which can be considered in the future when designing peptide-based reporters or therapeutics.
The Double-Sided Nature of Meaningful Work: Promoting and Challenging Factors within the Swedish Equine Sector
Authors: Bergman Bruhn Åsa
Published: April 2022

Meaningful work is related to a range of positive outcomes, but also negative effects. Research regarding meaningful work and lifestyle-oriented work; i.e., when making a livelihood based on a leisure interest and personal lifestyle, is deficient. The aim of this qualitative study is therefore to explore factors that promote and challenge meaningful work in a lifestyle-oriented setting. The study focuses on the perspective of employees within the Swedish equine sector, and is based on individual interviews. The results show that person–environment fit, task significance, and occupational culture seem to be important factors in the promotion of meaningful work. In addition, the analysis also illustrates how the nature of meaningful work has an inherent duality, constructed by a balancing act between doing good for oneself and for others. The tension is reinforced by the fact that the same factors can both promote meaningful work and challenge meaningfulness. This study shows that meaningful work not only comes with satisfaction, enjoyment, and fulfillment, but also an acceptance of challenging working conditions, which may lead to sacrifices and exhaustion. The double-sided nature of meaningful work can therefore affect the employees’ well-being, and challenge the willingness and ability to remain in the occupation.
Au-Decorated 1D SnO2 Nanowire/2D WS2 Nanosheet Composite for CO Gas Sensing at Room Temperature in Self-Heating Mode
Authors: Kim Jae-Hun , Sakaguchi Isao , Hishita Shunich , Suzuki Taku T. , Saito Noriko
Published: April 2022

We have designed a new ternary structure to enhance the sensing properties of WS2 nanosheet (NS)-based gas sensors at room temperature (RT) in self-heating mode. SnO2 nanowires (NWs, 10–30 wt%) were added to WS2 NSs and then Au nanoparticles (NPs) were deposited on the surface of the resulting composites by UV irradiation. The Au-decorated 10 wt% SnO2–WS2 composition showed the highest gas sensing properties. The presence of SnO2 NWs on the WS2 NSs effectively enhanced the diffusion and adsorption of gas species into deeper parts of the gas sensor. Furthermore, the chemical sensitization of Au (increase in oxygen ionosorption; spillover effect and catalytic effect towards CO) contributed to an enhanced response to CO gas. Gas sensing tests performed in the self-heating mode demonstrated the possibility of realizing a low-voltage, low-power-consumption CO gas sensor based on the Au-decorated 10 wt% SnO2–WS2. The sensor response under 60% relative humidity (RH) conditions was 84% of that under dry conditions, which shows that CO sensing is possible in wet environments at room temperature operation.
Excellent Cooperation between Carboxyl-Substituted Porphyrins, k-Carrageenan and AuNPs for Extended Application in CO2 Capture and Manganese Ion Detection
Authors: Epuran Camelia , Fratilescu Ion , Macsim Ana-Maria , Lascu Anca , Ianasi Catalin , Birdeanu Mihaela , Fagadar-Cosma Eugenia
Published: April 2022

Significant tasks of the presented research are the development of multifunctional materials capable both to detect/capture carbon dioxide and to monitor toxic metal ions from waters, thus contributing to maintaining a sustainable and clean environment. The purpose of this work was to synthesize, characterize (NMR, FT-IR, UV-Vis, Fluorescence, AFM) and exploit the optical and emission properties of a carboxyl-substituted A3B porphyrin, 5-(4-carboxy-phenyl)-10,15,20-tris-(4-methyl-phenyl)–porphyrin, and based on it, to develop novel composite material able to adsorb carbon dioxide. This porphyrin-k-carrageenan composite material can capture CO2 in ambient conditions with a performance of 6.97 mmol/1 g adsorbent. Another aim of our research was to extend this porphyrin- k-carrageenan material’s functionality toward Mn2+ detection from polluted waters and from medical samples, relying on its synergistic partnership with gold nanoparticles (AuNPs). The plasmonic porphyrin-k-carrageenan-AuNPs material detected Mn2+ in the range of concentration of 4.56 × 10−5 M to 9.39 × 10−5 M (5–11 mg/L), which can be useful for monitoring health of humans exposed to polluted water sources or those who ingested high dietary manganese.
Early Evidence of the Interplay between Separation Anxiety Symptoms and COVID-19-Related Worries in a Group of Children Diagnosed with Cancer and Their Mothers
Authors: Dotto Chiara , Montanaro Maria , Spaggiari Silvia , Cecinati Valerio , Brescia Letizia , Insogna Simona , Zuliani Livia , Grotto Paolo , Pizzato Cristina , Di Riso Daniela
Published: April 2022

Having cancer in childhood is a risk factor for separation anxiety symptoms, with negative effects on the disease and psychological wellbeing. The Covid-19-pandemic-related concerns could have a negative effect. The present study explores the interplay between separation anxiety symptoms and COVID-19-related worries in pediatric cancer patients and their mothers, compared to a group of healthy children and their mothers, during the pandemic. Thirty-three subjects with cancer, aged 7–15 years, and their mothers were compared to a control sample of 36 healthy children and caregivers. They were administered a pandemic-related psychological experience survey and standardized questionnaires assessing psychological wellbeing, anxiety, and separation anxiety symptoms. Children with cancer reported significantly higher prosocial behaviors, fear of being alone, and fear of abandonment. Their mothers had worse psychological wellbeing, higher COVID-19 concerns, anxiety, and separation anxiety symptoms. The multiple linear regression model showed that an increase in children’s separation anxiety symptoms was associated with younger age, more recent diagnosis, more mother-child time, lower mothers’ worry for children’s contagion, and higher mothers’ and children’s anxiety. COVID-19-related worries of clinical children’s mothers seem to be protective for children’s psychological wellbeing. Early psychosocial support interventions for mothers are essential in health services for cancer.
Could COVID-19′s Aftermath on Children’s Health Be Felt into the 22nd Century?
Authors: Mentis Alexios-Fotios A. , Paltoglou George , Demakakos Panayotes , Ahmed Faheem , Chrousos George P.
Published: April 2022

The COVID-19 pandemic has massively affected people’s health, societies, and the global economy. Our lives are no longer as they were before COVID-19, and, most likely, will never be the same again. We hypothesize that the effect of the COVID-19 pandemic on population health and the economy will last for a very long time and will still be felt in the 22nd century. Our hypothesis is based on evidence from the 1918–1919 influenza pandemic, the Dutch famine during the Second World War, and the 2007–2008 economic crisis, as well as from the rationally predicted impact of COVID-19 on human development. We expect that the COVID-19 pandemic, including the mitigation measures taken against it, will affect children’s development in multiple ways, including obesity, both while in utero and during critical and sensitive windows of development, including the early childhood years and those of puberty and adolescence. The psychosocial and biological impact of this effect will be considerable and unequally distributed. The implications will last at least a lifetime, and, through inter-generational transmission, will likely take us to future generations, into the 22nd century. We argue for the urgent need of designing and initiating comprehensive longitudinal cohort studies to closely monitor the long-term effects of COVID-19 on children conceived, born, and raised during the pandemic. Such an approach requires a close and effective collaboration between scientists, healthcare providers, policymakers, and the younger generations, and it will hopefully uncover evidence necessary to understand and mitigate the impact of the pandemic on people’s lives in the 21st and 22nd centuries.
The Effects of Ayres Sensory Integration and Related Sensory Based Interventions in Children with Cerebral Palsy: A Scoping Review
Authors: Kantor Jiří , Hlaváčková Lucie , Du Jian , Dvořáková Petra , Svobodová Zuzana , Karasová Kristýna , Kantorová Lucia
Published: April 2022

The theory of Ayres Sensory Integration® was formulated in the 1960s, and is also known as sensory integration (SI). It has been used in people with cerebral palsy (CP), though the research evidence for its effects in this population is contradictory and inconclusive. To fill in this knowledge gap, we conducted a scoping review of the body of literature on the topic, including any type of quantitative or qualitative research of SI in people with CP without any restrictions of age, language, geography, professionals involved, etc. In September 2020, we searched Scopus, ProQuest Central, MEDLINE (via PubMed), CINAHL Plus and the Academic Search Ultimate and Web of Science, as well as the grey literature sources OpenGrey and MedNar. Two reviewers independently screened the texts and the references lists of the included papers. We finally included seven relevant papers (four randomized controlled trials, two quasi-experimental studies and one case series), though not all fidelity measures required for Ayres SI were reported in the papers. The age of participants ranged from 3 months to 15 years; no studies were identified on adults. There is some evidence that SI or related sensory-based interventions (SBI) may be useful for movement development and other outcomes (attention span, therapy of sensory processing disorders, body perception and therapy of strabismus), but there is only scarce and low-quality evidence comparing interventions. We recommend to conduct well-designed randomized controlled trials (RCTs) with an optimal sample size on the effectiveness of formal Ayres SI for the motor development or other outcomes (as attention span or self-care abilities) using standardized measurement tools.
House Dust Mite Subcutaneous Immunotherapy and Lung Function Trajectory in Children and Adolescents with Asthma
Authors: Nogami Kazutaka , Nagao Mizuho , Takase Takafumi , Yasuda Yasuaki , Yamada Shingo , Matsunaga Mayumi , Hoshi Miyuki , Hamada Kana , Kuwabara Yu , Tsugawa Takeshi , Fujisawa Takao
Published: April 2022

Background: Allergen-specific immunotherapy is currently the only disease-modifying treatment for allergic asthma, and it has been shown to improve control of asthma while reducing both drug use and asthma exacerbations. However, its effects on lung function—especially its long-term effects—remain controversial. We aimed to identify factors associated with a possible beneficial effect of allergen-specific immunotherapy on lung function in asthma by retrospectively evaluating the long-term changes in lung function in children with asthma who received house dust mite subcutaneous immunotherapy (HDM-SCIT). Methods: We enrolled children with asthma who had undergone HDM-SCIT for more than 1 year. Clinical information and lung function measurements were retrieved from the electronic chart system. To characterize the trajectory of lung function change, we performed linear regression analysis to evaluate the maximal expiratory flow at 50% of the forced vital capacity during two periods: before and during HDM-SCIT. Slopes from a least-squares regression line for the two periods, i.e., S1 before HDM-SCIT and S2 during HDM-SCIT, were compared. The subjects were then classified into two groups: an improving group (Group I) defined as S2 − S1 > 0, and a declining group (Group D) defined as S2 − S1 < 0. The clinical factors at the start of HDM-SCIT were compared between the two groups. Results: A total of 16 patients were analyzed. Eight patients were classified into each of Group I and Group D. The mean ages were 10.5 and 11.8 years, and the mean treatment periods were 4.1 and 3.9 years. Group I had a significantly lower blood eosinophil count and a significantly higher HDM-specific IgE level than Group D. Logistic regression showed a strong relationship between those two markers and the lung function trajectory. Conclusion: Control of the blood eosinophil count in highly HDM-sensitized patients may increase the beneficial effect of HDM-SCIT on lung function.
Formulation Challenges and Strategies to Develop Pediatric Dosage Forms
Authors: Malkawi Wedad , AlRafayah Enas , AlHazabreh Mohammad , AbuLaila Salam , Al-Ghananeem Abeer
Published: April 2022

The development of pediatric-specific dose forms is particularly difficult due to a variety of factors relating to pediatric population differences from adult populations. The buccal dosage form is considered a good alternative to oral dosage form if the latter cannot be used in pediatric patients. Both oral and buccal dosage formulations uphold great application qualities for pediatric patients. This review sheds light on both oral and buccal, as they are the most convenient dosage forms for pediatrics. The use of adult drugs to treat children is a legislation concern, as it may result in incorrect dose, safety, and efficacy. The Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) are two key pieces of legislation that encourage and regulate pediatric medication research. Both contribute to a well-balanced approach to emphasizing critical safety and efficacy warnings for the of medications within pediatric populations. These contributions are what enable companies to continue making significant investments in pediatric drug developments. Despite the importance of investigating medicines for children, there is still a demand for pediatric-specific formulations and dosage forms. Many formulations and dosage forms can be designed, among which the buccal drug delivery seems a good modality for pediatric-friendly dosage forms. The main issues associated with these pediatric dosage forms development, particularly clinical and physiological factors, are discussed in this review. In addition, formulation developments and regulatory expectations are highlighted. In turn, suggestions are made to potentially improve future pediatric formulation development.
Epidemiology, Microbiology and Severity of Bronchiolitis in the First Post-Lockdown Cold Season in Three Different Geographical Areas in Italy: A Prospective, Observational Study
Authors: Camporesi Anna , Morello Rosa , Ferro Valentina , Pierantoni Luca , Rocca Alessandro , Lanari Marcello , Trobia Gian , Sciacca Tiziana , Bellinvia Agata , De Ferrari Alessandra , Valentini Piero , Roland Damian , Buonsenso Danilo
Published: April 2022

The aim of this study was to understand the epidemiology, disease severity, and microbiology of bronchiolitis in Italy during the 2021–2022 cold season, outside of lockdowns. Before COVID-19, the usual bronchiolitis season in Italy would begin in November and end in April, peaking in February. We performed a prospective observational study in four referral pediatric centers located in different geographical areas in Italy (two in the north, one in the center and one in the south). From 1 July 2021 to 31 January 2022, we collected all new clinical diagnoses of bronchiolitis in children younger than two years of age recording demographic, clinical and microbiological data. A total of 657 children with a clinical diagnosis of bronchiolitis were enrolled; 56% children were admitted and 5.9% required PICU admission. The first cases were detected during the summer, peaking in November 2021 and declining into December 2021 with only a few cases detected in January 2022. RSV was the commonest etiological agent, while SARS-CoV-2 was rarely detected and only since the end of December 2021. Disease severity was similar in children with RSV vs. non-RSV bronchiolitis, and in those with a single infectious agent detected compared with children with co-infections. The 2021–2022 bronchiolitis season in Italy started and peaked earlier than the usual pre-pandemic seasons, but had a shorter duration. Importantly, the current bronchiolitis season was not more severe when data were compared with Italian published data, and SARS-CoV-2 was rarely a cause of bronchiolitis in children younger than 24 months of age.
Discordance among Belief, Practice, and the Literature in Infection Prevention in the NICU
Authors: Alslaim Hossam S. , Chan Jonathan , Saleem-Rasheed Fozia , Ibrahim Yousef , Karabon Patrick , Novotny Nathan
Published: April 2022

This study evaluates practices of infection control in the NICU as compared with the available literature. We aimed to assess providers’ awareness of their institutional policies, how strongly they believed in those policies, the correlation between institution size and policies adopted, years of experience and belief in a policy’s efficacy, and methods employed in the existing literature. An IRB-approved survey was distributed to members of the AAP Neonatal Section. A systematic review of the literature provided the domains of the survey questions. Data was analyzed as appropriate. A total of 364 providers responded. While larger NICUs were more likely to have policies, their providers are less likely to know them. When a policy is in place and it is known, providers believe in the effectiveness of that policy suggesting consensus or, at its worst, groupthink. Ultimately, practice across the US is non-uniform and policies are not always consistent with best available literature. The strength of available literature is adequate enough to provide grade B recommendations in many aspects of infection prevention. A more standardized approach to infection prevention in the NICU would be beneficial and is needed.