bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Personal Exposure to Fine Particulate Matter (PM2.5) during the Spring 2020 COVID-19 Lockdown in the UK: Results of a Simulation Model
Authors: Dobson Ruaraidh , Eadie Douglas , O’Donnell Rachel , Stead Martine , Cherrie John W. , Semple Sean
Published: February 2022

Objectives: Policy responses to the COVID-19 pandemic in 2020 led to behaviour changes in the UK’s population, including a sudden shift towards working from home. These changes may have affected overall exposure to fine particulate matter (PM2.5), an air pollutant and source of health harm. We report the results of a simulation model of a representative sample of the UK’s population, including workers and non-workers, to estimate PM2.5 exposure before and during the pandemic. Methods: PM2.5 exposure was simulated in April and August 2017–2020 for 10,000 individuals across the UK drawn from the 2011 nationwide census. These data were combined with data from the UK’s ambient PM2.5 monitoring network, time use data and data on relevant personal behaviour before and during the first stage of the pandemic (such as changes in smoking and cooking). Results: The simulated exposures were significantly different between each year. Changes in ambient PM2.5 resulted in regional and temporal variation. People living in homes where someone smoked experienced higher exposure than those in smoke-free homes, with an increase of 4 µg/m3 in PM2.5 exposure in 2020. Conclusions: Changes in PM2.5 exposure were minimal for most individuals despite the simulated increases in cooking activity. Those living in smoking homes (estimated to be around 11% of the UK population) experienced increased exposure to PM2.5 during COVID lockdown measures and this is likely to have increased mortality and morbidity among this group. Government policy should address the risk of increased exposure to second-hand smoke in the event of future COVID-19-related restrictions.
Model Study of the Effects of Climate Change on the Methane Emissions on the Arctic Shelves
Authors: Malakhova Valentina , Golubeva Elena
Published: February 2022

Based on a regional ice-ocean model, we simulated the state of the water masses of the Arctic Ocean to analyze the transport of dissolved methane on the Arctic shelves. From 1970 to 2019, we obtained estimates of methane emissions at the Arctic seas due to the degradation of submarine permafrost and gas release at the ocean–bottom interface. The calculated annual methane flux from the Arctic shelf seas into the atmosphere did not exceed 2 Tg CH4 year−1. We have shown that the East Siberian shelf seas make the main contribution to the total methane emissions of the region. The spatial variability of the methane fluxes into the atmosphere is primarily due to the peculiarities of the water circulation and ice conditions. Only 7% of the dissolved methane originating from sediment enters the atmosphere within the study area. Most of it appears to be transported below the surface and oxidized by microbial activity. We found that increasing periods and areas of ice-free water and decreasing ice concentration have contributed to a steady increase in methane emissions since the middle of the first decade of the current century.
Use of Deferasirox Film-Coated Tablets in Pediatric Patients with Transfusion Dependent Thalassemia: A Single Center Experience
Authors: Adramerina Alkistis , Printza Nikoleta , Hatzipantelis Emmanouel , Symeonidis Symeon , Tarazi Labib , Teli Aikaterini , Economou Marina
Published: February 2022

Thalassemic syndromes are characterized by clinical heterogenicity. For severe disease forms, lifelong blood transfusions remain the mainstay of therapy, while iron overload monitoring and adequate chelation treatment are required in order to ensure effective disease management. Compared to previous chelators, the new deferasirox film-coated tablet (DFX FCT) is considered to offer a more convenient and well-tolerated treatment scheme, aiming at better treatment-related and patient-related outcomes. The present study’s objective was to prospectively evaluate the safety and efficacy of DFX FCT in children and adolescents with transfusion-dependent thalassemia. Data collected included patient demographics, hematology and biochemistry laboratory work up, magnetic resonance imaging of heart and liver for iron load, as well as ophthalmological and audiological examination prior to and a year following drug administration. Study results confirmed DFX FCT safety in older children in a manner similar to adults, but demonstrated increased frequency of adverse events in younger patients, mainly, involving liver function. With regards to efficacy, study results confirmed the preventive role of DFX FCT in iron loading of liver and heart, however, higher doses than generally recommended were required in order to ensure adequate chelation.
Relevance of miR-223 as Potential Diagnostic and Prognostic Markers in Cancer
Authors: Aziz Faisal , Chakraborty Abhijit , Khan Imran , Monts Josh
Published: February 2022

In 1993, the discovery of microRNAs in Caenorhabditis elegans (C. elegans) altered the paradigmatic view of RNA biology and post-transcriptional gene regulation. Further study revealed the role of microRNAs in disease development and progression. In particular, this review highlights microRNA-223 (miR-223 or miRNA-223) expression in malignant neoplastic disorders. miR-223 expression controls aspects of hematopoiesis and apoptosis, and cell proliferation, migration, and invasion. miR-223 regulates a number of gene targets, including cytoplasmic activation/proliferation-associated protein-1 (Caprin-1), insulin-like growth factor-1 receptor (IGF-1R), and other cell proliferation- and cell cycle-associated genes. Several studies have proposed miR-223 as a novel biomarker for early cancer diagnosis. Here, we emphasize miR-223′s role in the development and progression of cancer.
Sex-Specific and Long-Term Impacts of Early-Life Venlafaxine Exposure in Zebrafish
Authors: Thompson William Andrew , Shvartsburd Zachary , Vijayan Mathilakath M.
Published: February 2022

Venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is a widely prescribed antidepressant that is detected in municipal wastewater effluents at µg/L concentrations. It has been shown to impact the early life stages of fish, including neurodevelopment and behaviour in larvae, but whether such early exposures have longer-term consequences are far from clear. Here, we sought to determine whether zygotic deposition of venlafaxine, mimicking a maternal transfer scenario, disturbs the metabolic rate and behavioural performance using zebrafish (Danio rerio). This was tested using freshly fertilized embryos (1–4 cell stage) microinjected with either 0, 1 or 10 ng of venlafaxine and raised to either juvenile (60 days post-fertilization) or adult (10–12 months post-fertilization). Zygotic venlafaxine exposure led to a reduction in the active metabolic rate and aerobic scope, but this was only observed in female fish. On the other hand, the total distance travelled in an open field assessment was greater at the highest concentration of venlafaxine only in the adult males. At the juvenile stage, behavioural assessments demonstrated that venlafaxine exposure may increase boldness—including hyperactivity, lower thigmotaxis, and a reduction in the distance to a novel object. Taken together, these results demonstrate that zygotic venlafaxine exposure may impact developmental programming in a sex-specific manner in fish.
Phosphate Solubilizing Microorganism Bacillus sp. MVY-004 and Its Significance for Biomineral Fertilizers’ Development in Agrobiotechnology
Authors: Mažylytė Raimonda , Kaziūnienė Justina , Orola Liana , Valkovska Valda , Lastauskienė Eglė , Gegeckas Audrius
Published: February 2022

In this study, a phosphate solubilizing microorganism was isolated from the soil of an agricultural field in Lithuania. Based on 16S rRNA gene sequence analysis, the strain was identified as Bacillus sp. and submitted to the NCBI database, Sector of Applied Bio-catalysis, University Institute of Biotechnology, Vilnius, Lithuania and allocated the accession number KY882273. The Bacillus sp. was assigned with the number MVY-004. The culture nutrient medium and growth conditions were optimized: molasses was used as a carbon source; yeast extract powder was used as an organic source; NH4H2PO4 was used as a nitrogen source; the culture growth temperature was 30 ± 0.5 °C; the initial value of pH was 7.0 ± 0.5; the partial pressure of oxygen (pO2) was 60 ± 2.0; the mixer revolutions per minute (RPM) were 25–850, and the incubation and the fermentation time was 48–50 h. Analysis using Liquid Chromatography Time-of-Flight Mass Spectrometry (LC-TOF/MS) results showed that Bacillus sp. MVY-004 produced organic acids such as citric, succinic, 2-ketogluconic, gluconic, malic, lactic, and oxalic acids. Furthermore, the experiment showed that Bacillus sp. MVY-004 can also produce the following phytohormones: indole-3-acetic (IAA), jasmonic (JA), and gibberellic (GA3) acids. In the climate chamber, the experiment was performed using mineral fertilizer (NPS-12:40:10 80 Kg ha−1) and mineral fertilizers in combination with Bacillus sp. MVY-004 cells (NPS-12:40:10 80 Kg ha−1 + Bacillus sp. MVY-004) in loamy soil. Analysis was performed in three climate conditions: normal (T = 20 °C; relative humidity 60%); hot and dry (T = 30 °C; relative humidity 30%); hot and humid (T = 30 °C; relative humidity 80%).
Procollagen C-Endopeptidase Enhancer 2 Secreted by Tonsil-Derived Mesenchymal Stem Cells Increases the Oxidative Burst of Promyelocytic HL-60 Cells
Authors: Yoon Hee-Soo , Kim Hee-Yeon , Cho Kyung-Ah , Kim Yu-Hee , Woo So-Youn , Kim Han-Su , Kang Jihee-Lee , Ryu Kyung-Ha , Park Joo-Won
Published: February 2022

Reactive oxygen species (ROS) generated by neutrophils provide a frontline defence against invading pathogens. We investigated the supportive effect of tonsil-derived mesenchymal stem cells (TMSCs) on ROS generation from neutrophils using promyelocytic HL-60 cells. Methods: Differentiated HL-60 (dHL-60) cells were cocultured with TMSCs isolated from 25 independent donors, and ROS generation in dHL-60 cells was measured using luminescence. RNA sequencing and real-time PCR were performed to identify the candidate genes of TMSCs involved in augmenting the oxidative burst of dHL-60 cells. Transcriptome analysis of TMSCs derived from 25 independent donors revealed high levels of procollagen C-endopeptidase enhancer 2 (PCOLCE2) in TMSCs, which were highly effective in potentiating ROS generation in dHL-60 cells. In addition, PCOLCE2 knockdown in TMSCs abrogated TMSC-induced enhancement of ROS production in dHL-60 cells, indicating that TMSCs increased the oxidative burst in dHL-60 cells via PCOLCE2. Furthermore, the direct addition of recombinant PCOLCE2 protein increased ROS production in dHL-60 cells. These results suggest that PCOLCE2 secreted by TMSCs may be used as a therapeutic candidate to enhance host defences by increasing neutrophil oxidative bursts. PCOLCE2 levels in TMSCs could be used as a marker to select TMSCs exhibiting high efficacy for enhancing neutrophil oxidative bursts.
Correlation of Occupational Exposure to Carcinogenic Polycyclic Aromatic Hydrocarbons (cPAHs) and Blood Levels of p53 and p21 Proteins
Authors: Saleh Saleh A. K. , Adly Heba M. , Aljahdali Imad A. , Khafagy Abdullah A.
Published: February 2022

Carcinogenic polycyclic aromatic hydrocarbons (cPAHs) are considered the most serious cancer risk. This study was conducted to assess the effect of acute exposure to cPAHs on cancer biomarker proteins p53 and p21 in occupational workers during the hajj season in Makkah. One hundred five participants were recruited, including occupational workers and apparently healthy individuals; air samples were collected using personal sample monitors to identify the subjects’ exposure to cPAHs. Quantitative analyses of benzo(a)anthracene (BaA), benzo(b)fluoranthene (BbF), benzo(a)pyrene (BaP), dibenzo(a,h)fluronathene (DBA), indeno(1,2,3-c,d)pyrene (IND) and chyresene (CRY) were carried out using the GC/Mass technique. Serum p53 and p21 proteins were analyzed using ELISA. The ambient air samples collected by the occupationally exposed group were more highly polluted by cPAHs, (90.25 ± 14.1) ng/m3, than those of the unexposed control groups, (30.12 ± 5.56) ng/m3. The concentration of distributive cPAHs was markedly more elevated in the air samples of the exposed group than in those taken from the non-exposed group. The study results demonstrated significant links between short-term exposure to cPAHs and serum p53 and p21 levels. Serum p53 and p21 proteins potentially influence biomarkers when exposed to ambient air cPAHs.
Apparent Absence of BMAL1-Dependent Skeletal Muscle–Kidney Cross Talk in Mice
Authors: Crislip Gene Ryan , Wohlgemuth Stephanie E. , Wolff Christopher A. , Gutierrez-Monreal Miguel A. , Douglas Collin M. , Ebrahimi Elnaz , Cheng Kit-Yan , Masten Sarah H. , Barral Dominique , Bryant Andrew J. , Esser Karyn A. , Gumz Michelle L.
Published: February 2022

BMAL1 is a core mammalian circadian clock transcription factor responsible for the regulation of the expression of thousands of genes. Previously, male skeletal-muscle-specific BMAL1-inducible-knockout (iMS-BMAL1 KO) mice have been described as a model that exhibits an aging-like phenotype with an altered gait, reduced mobility, muscle weakness, and impaired glucose uptake. Given this aging phenotype and that chronic kidney disease is a disease of aging, the goal of this study was to determine if iMS-BMAL1 KO mice exhibit a renal phenotype. Male iMS-BMAL1 KO and control mice were challenged with a low potassium diet for five days. Both genotypes responded appropriately by conserving urinary potassium. The iMS-BMAL1 KO mice excreted less potassium during the rest phase during the normal diet but there was no genotype difference during the active phase. Next, iMS-BMAL1 KO and control mice were used to compare markers of kidney injury and assess renal function before and after a phase advance protocol. Following phase advance, no differences were detected in renal mitochondrial function in iMS-BMAL1 KO mice compared to control mice. Additionally, the glomerular filtration rate and renal morphology were similar between groups in response to phase advance. Disruption of the clock in skeletal muscle tissue activates inflammatory pathways within the kidney of male mice, and there is evidence of this affecting other organs, such as the lungs. However, there were no signs of renal injury or altered function following clock disruption of skeletal muscle under the conditions tested.
Protein Binding of Benzofuran Derivatives: A CD Spectroscopic and In Silico Comparative Study of the Effects of 4-Nitrophenyl Functionalized Benzofurans and Benzodifurans on BSA Protein Structure
Authors: Scognamiglio Pasqualina Liana , Vicidomini Caterina , Fontanella Francesco , De Stefano Claudio , Palumbo Rosanna , Roviello Giovanni N.
Published: February 2022

Benzofuran derivatives are synthetic compounds that are finding an increasing interest in the scientific community not only as building blocks for the realization of new materials, but also as potential drugs thanks to their ability to interact with nucleic acids, interfere with the amyloid peptide aggregation and cancer cell cycle. However, their ability to interact with proteins is a theme still in need of investigation for the therapeutic importance that benzofurans could have in the modulation of protein-driven processes and for the possibility of making use of serum albumins as benzofurans delivery systems. To this scope, we investigated the protein binding ability of two 4-nitrophenyl-functionalized benzofurans previously synthesized in our laboratory and herein indicated as BF1 and BDF1, which differed for the number of furan rings (a single moiety in BF1, two in BDF1), using bovine serum albumin (BSA) as a model protein. By circular dichroism (CD) spectroscopy we demonstrated the ability of the two heteroaromatic compounds to alter the secondary structure of the serum albumin leading to different consequences in terms of BSA thermal stability with respect to the unbound protein (ΔTm > 3 °C for BF1, −0.8 °C for BDF1 with respect to unbound BSA, in PBS buffer, pH 7.5) as revealed in our CD melting studies. Moreover, a molecular docking study allowed us to compare the possible ligand binding modes of the mono and difuranic derivatives showing that while BF1 is preferentially housed in the interior of protein structure, BDF1 is predicted to bind the albumin surface with a lower affinity than BF1. Interestingly, the different affinity for the protein target predicted computationally was confirmed also experimentally by fluorescence spectroscopy (kD = 142.4 ± 64.6 nM for BDF1 vs. 28.4 ± 10.1 nM for BF1). Overall, the above findings suggest the ability of benzofurans to bind serum albumins that could act as their carriers in drug delivery applications.
Channelopathy Genes in Pulmonary Arterial Hypertension
Authors: Welch Carrie L. , Chung Wendy K.
Published: February 2022

Pulmonary arterial hypertension (PAH) is a rare, progressive vasculopathy with significant cardiopulmonary morbidity and mortality. The underlying pathogenetic mechanisms are heterogeneous and current therapies aim to decrease pulmonary vascular resistance but no curative treatments are available. Causal genetic variants can be identified in ~13% of adults and 43% of children with PAH. Knowledge of genetic diagnoses can inform clinical management of PAH, including multimodal medical treatment, surgical intervention and transplantation decisions, and screening for associated conditions, as well as risk stratification for family members. Roles for rare variants in three channelopathy genes—ABCC8, ATP13A3, and KCNK3—have been validated in multiple PAH cohorts, and in aggregate explain ~2.7% of PAH cases. Complete or partial loss of function has been demonstrated for PAH-associated variants in ABCC8 and KCNK3. Channels can be excellent targets for drugs, and knowledge of mechanisms for channel mutations may provide an opportunity for the development of PAH biomarkers and novel therapeutics for patients with hereditary PAH but also potentially more broadly for all patients with PAH.
SWATH-Based Comprehensive Determination of the Localization of Apical and Basolateral Membrane Proteins Using Mouse Liver as a Model Tissue
Authors: Hirano Satoshi , Goto Ryohei , Uchida Yasuo
Published: February 2022

The purpose of this study was to develop a method to comprehensively determine the localization of apical and basolateral membrane proteins, using a combination of apical/basolateral membrane separation and accurate SWATH (Sequential Window Acquisition of all THeoretical fragment ion spectra) proteomics. The SWATH analysis of basolateral and apical plasma membrane fractions in mouse liver quantified the protein expression of 1373 proteins. The basolateral/apical ratios of the protein expression levels were compared with the reported immunohistochemical localization for 41 model proteins (23 basolateral, 11 apical and 7 both membrane-localized proteins). Three groups were perfectly distinguished. Border lines to distinguish the apical-, both- and basolateral localizations were determined to be 0.766 and 1.42 based on probability density. The method that was established was then applied to the comprehensive determination of the proteins in mouse liver. The findings indicated that 154 and 125 proteins were localized in the apical and basolateral membranes, respectively. The levels of receptors, CD antigens and integrins, enzymes and Ras-related molecules were much higher in apical membranes than in basolateral membranes. In contrast, the levels of adhesion molecules, scaffold proteins and transporters in basolateral membranes were much higher than in apical membranes.
Epstein-Barr Virus Load Correlates with Multiple Sclerosis-Associated Retrovirus Envelope Expression
Authors: Pérez-Pérez Silvia , Domínguez-Mozo María Inmaculada , García-Martínez María Ángel , Ballester-González Rubén , Nieto-Gañán Israel , Arroyo Rafael , Alvarez-Lafuente Roberto
Published: February 2022

pHERV-W ENV and syncytin-1, the envelope proteins of the human endogenous retrovirus W family (HERV-W), have been proposed as etiological factors for MS development. In addition, herpesviruses, such as the Epstein-Barr virus (EBV) and the human herpesvirus 6A/B (HHV-6A/B), have been also strongly associated with the disease. This work aims to study the possible link between viral loads and antibody titers against EBV and HHV-6A/B and the pHERV-W ENV/syncytin-1 protein/gene expression. For this purpose, we conducted a 12-month longitudinal study involving 98 RRMS patients. Peripheral blood samples were obtained from each patient. Serum antibody titers against EBV and HHV-6A/B were determined by ELISA, while viral loads were analyzed using qPCR. HLA MS-related alleles were also genotyped. pHERV-W ENV/syncytin-1 protein and gene expression levels in immune cells were assessed by flow cytometry and qPCR, respectively. We found that the 12-month variation of the pHERV-W ENV gene expression levels positively correlated with the variation of the EBV viral load, especially in those patients with high baseline EBV loads. Therefore, these results could support previous studies pointing to the transactivation of pHERV-W ENV by EBV. However, further studies are needed to better understand this possible relationship.
Bioluminescence Resonance Energy Transfer (BRET) Allows Monitoring the Barnase-Barstar Complex In Vivo
Authors: Marchenkov Victor , Ivashina Tanya , Marchenko Natalia , Ksenzenko Vladimir , Semisotnov Gennady
Published: February 2022

Bioluminescence resonance energy transfer (BRET) seems to be a promising biophysical technique to study protein–protein interactions within living cells due to a very specific reaction of bioluminescence that essentially decreases the background of other cellular components and light-induced destruction of biomacromolecules. An important direction of the development of this technique is the study of known strong protein–protein complexes in vivo and the estimation of an average distance between chromophores of the donor and acceptor. Here, we demonstrate an in vivo interaction between barnase fused with luciferase (from Renilla reniformis, RLuc) and barstar fused with EGFP (enhanced green fluorescent protein of Aequorea victoria) monitored by BRET. The distance between the luciferase and EGFP chromophores within the complex has been evaluated as equal to (56 ± 2) Å.
Rapid Multiplex Strip Test for the Detection of Circulating Tumor DNA Mutations for Liquid Biopsy Applications
Authors: Kalligosfyri Panagiota M. , Nikou Sofia , Karteri Sofia , Kalofonos Haralabos P. , Bravou Vasiliki , Kalogianni Despina P.
Published: February 2022

In the era of personalized medicine, molecular profiling of patient tumors has become the standard practice, especially for patients with advanced disease. Activating point mutations of the KRAS proto-oncogene are clinically relevant for many types of cancer, including colorectal cancer (CRC). While several approaches have been developed for tumor genotyping, liquid biopsy has been gaining much attention in the clinical setting. Analysis of circulating tumor DNA for genetic alterations has been challenging, and many methodologies with both advantages and disadvantages have been developed. We here developed a gold nanoparticle-based rapid strip test that has been applied for the first time for the multiplex detection of KRAS mutations in circulating tumor DNA (ctDNA) of CRC patients. The method involved ctDNA isolation, PCR-amplification of the KRAS gene, multiplex primer extension (PEXT) reaction, and detection with a multiplex strip test. We have optimized the efficiency and specificity of the multiplex strip test in synthetic DNA targets, in colorectal cancer cell lines, in tissue samples, and in blood-derived ctDNA from patients with advanced colorectal cancer. The proposed strip test achieved rapid and easy multiplex detection (normal allele and three major single-point mutations) of the clinically relevant KRAS mutations in ctDNA in blood samples of CRC patients with high specificity and repeatability. This multiplex strip test represents a minimally invasive, rapid, low-cost, and promising diagnostic tool for the detection of clinically relevant mutations in cancer patients.
Detection of a Double-Stranded MGMT Gene Using Electrochemically Reduced Graphene Oxide (ErGO) Electrodes Decorated with AuNPs and Peptide Nucleic Acids (PNA)
Authors: Safarzadeh Mina , Pan Genhua
Published: February 2022

The ability to detect double-stranded DNA (dsDNA) as a biomarker without denaturing it to single-stranded DNA (ss-DNA) continues to be a major challenge. In this work, we report a sandwich biosensor for the detection of the ds-methylated MGMT gene, a potential biomarker for brain tumors and breast cancer. The purpose of this biosensor is to achieve simultaneous recognition of the gene sequence, as well as the presence of methylation. The biosensor is based on reduced graphene oxide (rGO) electrodes decorated with gold nanoparticles (AuNPs) and uses Peptide Nucleic Acid (PNA) that binds to the ds-MGMT gene. The reduction of GO was performed in two ways: electrochemically (ErGO) and thermally (TrGO). XPS and Raman spectroscopy, as well as voltammetry techniques, showed that the ErGO was more efficiently reduced, had a higher C/O ratio, showed a smaller crystallite size of the sp2 lattice, and was more stable during measurement. It was also revealed that the electro-deposition of the AuNPs was more successful on the ErGO surface due to the higher At% of Au on the ErGO electrode. Therefore, the ErGO/AuNPs electrode was used to develop biosensors to detect the ds-MGMT gene. PNA, which acts as a bio-recognition element, was used to form a self-assembled monolayer (SAM) on the ErGO/AuNPs surface via the amine-AuNPs interaction, recognizing the ds-MGMT gene sequence by its invasion of the double-stranded DNA and the formation of a triple helix. The methylation was then detected using biotinylated-anti-5mC, which was then measured using the amperometric technique. The selectivity study showed that the proposed biosensor was able to distinguish between blank, non-methylated, non-complementary, and target dsDNA spiked in mouse plasma. The LOD was calculated to be 0.86 pM with a wide linear range of 1 pM to 50 µM. To the best of our knowledge, this is the first report on using PNA to detect ds-methylated DNA. This sandwich design can be modified to detect other methylated genes, making it a promising platform to detect ds-methylated biomarkers.
Ion Interference Therapy of Tumors Based on Inorganic Nanoparticles
Authors: Chi Yongjie , Sun Peng , Gao Yuan , Zhang Jing , Wang Lianyan
Published: February 2022

As an essential substance for cell life activities, ions play an important role in controlling cell osmotic pressure balance, intracellular acid–base balance, signal transmission, biocatalysis and so on. The imbalance of ion homeostasis in cells will seriously affect the activities of cells, cause irreversible damage to cells or induce cell death. Therefore, artificially interfering with the ion homeostasis in tumor cells has become a new means to inhibit the proliferation of tumor cells. This treatment is called ion interference therapy (IIT). Although some molecular carriers of ions have been developed for intracellular ion delivery, inorganic nanoparticles are widely used in ion interference therapy because of their higher ion delivery ability and higher biocompatibility compared with molecular carriers. This article reviewed the recent development of IIT based on inorganic nanoparticles and summarized the advantages and disadvantages of this treatment and the challenges of future development, hoping to provide a reference for future research.
Age-Related Alterations in EEG Network Connectivity in Healthy Aging
Authors: Javaid Hamad , Kumarnsit Ekkasit , Chatpun Surapong
Published: February 2022

Emerging studies have reported that functional brain networks change with increasing age. Graph theory is applied to understand the age-related differences in brain behavior and function, and functional connectivity between the regions is examined using electroencephalography (EEG). The effect of normal aging on functional networks and inter-regional synchronization during the working memory (WM) state is not well known. In this study, we applied graph theory to investigate the effect of aging on network topology in a resting state and during performing a visual WM task to classify aging EEG signals. We recorded EEGs from 20 healthy middle-aged and 20 healthy elderly subjects with their eyes open, eyes closed, and during a visual WM task. EEG signals were used to construct the functional network; nodes are represented by EEG electrodes; and edges denote the functional connectivity. Graph theory matrices including global efficiency, local efficiency, clustering coefficient, characteristic path length, node strength, node betweenness centrality, and assortativity were calculated to analyze the networks. We applied the three classifiers of K-nearest neighbor (KNN), a support vector machine (SVM), and random forest (RF) to classify both groups. The analyses showed the significantly reduced network topology features in the elderly group. Local efficiency, global efficiency, and clustering coefficient were significantly lower in the elderly group with the eyes-open, eyes-closed, and visual WM task states. KNN achieved its highest accuracy of 98.89% during the visual WM task and depicted better classification performance than other classifiers. Our analysis of functional network connectivity and topological characteristics can be used as an appropriate technique to explore normal age-related changes in the human brain.
Increased Monocyte Production of IL-6 after Toll-like Receptor Activation in Children with Autism Spectrum Disorder (ASD) Is Associated with Repetitive and Restricted Behaviors
Authors: Hughes Heather K. , Onore Charity E. , Careaga Milo , Rogers Sally J. , Ashwood Paul
Published: February 2022

The prevalence of autism spectrum disorder (ASD) has starkly increased, instigating research into risk factors for ASD. This research has identified immune risk factors for ASD, along with evidence of immune dysfunction and excess inflammation frequently experienced by autistic individuals. Increased innate inflammatory cytokines, including interleukin (IL)-6, are seen repeatedly in ASD; however, the origin of excess IL-6 in ASD has not been identified. Here we explore specific responses of circulating monocytes from autistic children. We isolated CD14+ monocytes from whole blood and stimulated them for 24 h under three conditions: media alone, lipoteichoic acid to activate TLR2, and lipopolysaccharide to activate TLR4. We then measured secreted cytokine concentrations in cellular supernatant using a human multiplex bead immunoassay. We found that after TLR4 activation, CD14+ monocytes from autistic children produce increased IL-6 compared to monocytes from children with typical development. IL-6 concentration also correlated with worsening restrictive and repetitive behaviors. These findings suggest dysfunctional activation of myeloid cells, and may indicate that other cells of this lineage, including macrophages, and microglia in the brain, might have a similar dysfunction. Further research on myeloid cells in ASD is warranted.
Stochasticity, Entropy and Neurodegeneration
Authors: Panegyres Peter K.
Published: February 2022

We previously suggested that stochastic processes are fundamental in the development of sporadic adult onset neurodegenerative disorders. In this study, we develop a theoretical framework to explain stochastic processes at the protein, DNA and RNA levels. We propose that probability determines random sequencing changes, some of which favor neurodegeneration in particular anatomical spaces, and that more than one protein may be affected simultaneously. The stochastic protein changes happen in three-dimensional space and can be considered to be vectors in a space-time continuum, their trajectories and kinetics modified by physiological variables in the manifold of intra- and extra-cellular space. The molecular velocity of these degenerative proteins must obey the second law of thermodynamics, in which entropy is the driver of the inexorable progression of neurodegeneration in the context of the N-body problem of interacting proteins, time-space manifold of protein-protein interactions in phase space, and compounded by the intrinsic disorder of protein-protein networks. This model helps to elucidate the existence of multiple misfolded proteinopathies in adult sporadic neurodegenerative disorders.
Effects of Transcranial Direct Current Stimulation on Brain Electrical Activity, Heart Rate Variability, and Dual-Task Performance in Healthy and Fibromyalgia Women: A Study Protocol
Authors: Gomez-Alvaro Mari Carmen , Villafaina Santos , Leon-Llamas Juan Luis , Murillo-Garcia Alvaro , Melo-Alonso María , Sánchez-Gómez Jesús , Molero Pablo , Cano-Plasencia Ricardo , Gusi Narcis
Published: February 2022

People with fibromyalgia could experience physical and cognitive impairments. Furthermore, when performing two tasks at the same time, people with fibromyalgia showed a higher dual-task cost compared to a single task than healthy people. This may result in poorer performance of activities of daily living that are commonly presented as a combination of two or more tasks. Transcranial direct current stimulation (tDCS) is a promising nonpharmacological therapy. However, there is controversy regarding the intensities and the effectiveness of this therapy. Thus, the present study will aim: (1) to compare the effectiveness and the impact of two tDCS intensities (1 mA and 2 mA) on cognitive, motor, brain functions, and cardiac autonomic modulation; (2) to study the impact of tDCS on the dual-task performance and creativity after applying tDCS in dorsolateral prefrontal cortex. In this study, 26 women will participate and will be divided into two groups: women with fibromyalgia (n = 13), and healthy controls (n = 13). A reduction in cognitive-motor interference in dual-task performance is expected, as well as a modification in neurophysiological parameters and an improvement in cardiac autonomic modulation. Lastly, no different effects are expected depending on the stimulation intensity applied. The obtained results will help to determine if tDCS in the dorsolateral prefrontal cortex could improve the occupational performance of women with fibromyalgia.
Procrastination during the COVID-19 Pandemic: A Scoping Review
Authors: Unda-López Alejandro , Osejo-Taco Gabriel , Vinueza-Cabezas Andrea , Paz Clara , Hidalgo-Andrade Paula
Published: February 2022

Procrastination involves voluntarily or habitually delaying unpleasant tasks for later. It is characterized by short-term benefits and long-term costs. The COVID-19 pandemic set specific circumstances that may have influenced procrastination behavior. This scoping review identified the existing peer-reviewed literature in English or Spanish about procrastination during the COVID-19 pandemic (January 2020 to April 2021) in six electronic databases. To conduct the review, a five-step methodological framework, as well as established PRISMA guidelines, was followed. A total of 101 articles were found. After removing duplicates and reviewing the articles, only 13 were included in the review. Findings indicate that procrastination was studied mostly in academic contexts in various parts of the globe. Procrastination behavior was related to anxiety, distress, time management, self-control, and other variables. There is limited information about interventions to prevent or decrease procrastinating behaviors in the context of confinement or in the living conditions generated by the pandemic. Future research should consider how procrastination evolved during the pandemic using longitudinal methodologies. Individual differences related to procrastination also should be identified, and the evaluation of the efficacy of existing interventions is still needed. This information might help in the creation of appropriate interventions that target detrimental procrastination behaviors.
Ventilation Strategies for Mitigation of Infection Disease Transmission in an Indoor Environment: A Case Study in Office
Authors: Ren Chen , Zhu Hao-Cheng , Cao Shi-Jie
Published: February 2022

During the normalization phase of the COVID-19 epidemic, society has gradually reverted to using building space, especially for public buildings, e.g., offices. Prevention of airborne pollutants has emerged as a major challenge. Ventilation strategies can contribute to mitigating the spread of airborne disease in an indoor environment, including increasing supply air rate, modifying ventilation mode, etc. The larger ventilation rate can inevitably lead to high energy consumption, which may be also ineffective in reducing infection risk. As a critical factor affecting the spread of viral contaminant, the potential of ventilation modes for control of COVID-19 should be explored. This study compared several ventilation strategies in the office, including mixing ventilation (MV), zone ventilation (ZV), stratum ventilation (SV) and displacement ventilation (DV), through analyzing ventilation performance and infection risk for the optimal one. By using ANSYS Fluent, the distributions of airflow and pollutant were simulated under various ventilation modes and infected occupants. The SV showed greater performance in mitigating infection disease spread than MV, ZV and DV, with an air distribution performance index (ADPI) of 90.5% and minimum infection risk of 13%. This work can provide a reference for development of ventilation strategies in public space oriented the prevention of COVID-19.
Sustainability Assessment of a Low-Income Building: A BIM-LCSA-FAHP-Based Analysis
Authors: Filho Marcus V. A. P. M. , da Costa Bruno B. F. , Najjar Mohammad , Figueiredo Karoline V. , de Mendonça Marcos Barreto , Haddad Assed N.
Published: February 2022

The construction industry is one of the most significant consumers of environmental resources worldwide. Faced with the need to produce new buildings, but without further burdening the environment, attempts to improve social, economic, and environmental indicators have turned attention to building construction in recent decades. The objective of this research is to develop a novel framework to assess the most sustainable choice of materials applied to the construction of low-income buildings, according to the three pillars of the Triple Bottom Line (TBL). A BIM-LCSA-FAHP-based model was proposed with the creation of nine different scenarios, where the materials of the structure (precast concrete, cast-in-place concrete, and structural masonry), painting (PVA water-based and acrylic), and roofing (ceramic and fiber cement tiles) varied. The proposed procedure consists of the elaboration of a 3D Building Information Modeling (BIM) model, for which the parameters described above were evaluated according to the Life Cycle Sustainability Assessment (LCSA)-TBL-based criteria, divided into ten sub-criteria, that includes: (1) environmental (acidification, eutrophication, global warming, ozone depletion, smog formation, primary energy, non-renewable energy, and mass total), (2) economic (construction cost) and (3) socio-political issues (community impact). Finally, the Fuzzy Analytical Hierarchy Process (AHP) was used as a multi-criteria decision-making technique that helps in aggregating and classifying the impacts of each scenario in a sustainability index (SI). Regarding the best option for low-income construction, the results indicated that precast concrete when combined with acrylic paint and fiber cement tiles (scenario 3) proved to be the most advantageous and achieved first place in the sustainability index (SI) developed in this work. This methodology is replicable for different construction typologies and several categories of materials, making it a robust decision-aiding tool for engineers, architects, and decision makers.
Serious Damage Localization of Continuous Girder Bridge by Support Reaction Influence Lines
Authors: Cheng Qifeng , Ruan Xuzhi , Wang Yize , Chen Zhiwei
Published: February 2022

A novel damage detection approach is proposed in this study for a continuous girder bridge in which support reaction influence lines (ILs) are adopted. First, the relationship between the local damage of a continuous girder bridge and a damage index, based on support reaction ILs, is established through analytical derivation. Subsequently, the sensitivity of a support reaction IL-based damage index is analyzed using Dempster-Shafer (D-S) evidence theory, and it shows that the support reaction IL-based damage index is more noise-resistant if more support reaction ILs from a variety of locations are used. Three case studies (a simple numerical study of a two-span continuous beam, a laboratory experimental study of a two-span aluminum beam, and a complicated numerical study of a continuous girder bridge in Xiamen) have been conducted to validate the effectiveness of the proposed method in different damage scenarios, including single damage and multiple damages. Satisfactory damage identification results can be obtained even in high-level measurement noise conditions, showing that the proposed approach offers a promising field detection technique for identifying local structural damages in continuous girder bridges.
Quantifying the Effects of Projected Climate Change on the Durability and Service Life of Housing in Wales, UK
Authors: Hayles Carolyn , Huddleston Matt , Chinowsky Paul , Helman Jacob
Published: February 2022

This research aimed to provide the Welsh Government with measured and quantified climate vulnerabilities associated with housing building-fabric, including the potential financial cost of not planning for climate change. Wales’s climate is projected to become warmer but wetter and it is known that hygrothermal impacts can accelerate deterioration, leading to damp and, subsequently, a loss of thermal performance. A stressor-response methodology was applied, which assumes that the exogenous stressors of solar flux, precipitation, and humidity have a direct effect on building-fabric performance. The resultant stressor-response values equate to the quantitative impact that a specific stressor has on individual specific building elements, presented as an adjusted service life and associated costs. Results show a modest reduction in the service life of building materials due to increases in and changing patterns of precipitation and subsequent moisture ingress. Although modest, with 1.5 million dwellings in Wales, the impact is significant. Advocating regular maintenance and repair will not only reduce the risks associated with changing weather patterns, but also encourage energy efficiency by improving the thermal performance of the building envelope. This will reduce the risk of adverse climate related outcomes, increased vulnerability to climate change, now or in the future.
Moderating Effects of Internationalization between Corporate Social Responsibility and Financial Performance: The Case of Construction Firms
Authors: Sang Meiyue , Zhang Yuqing , Ye Kunhui , Jiang Weiyan
Published: February 2022

The relationship between corporate social responsibility (CSR) and corporate financial performance (CFP) has been crucial in academia and business circles. Numerous construction firms have continued to internationalize construction business over time despite the influence of the COVID-19. The internationalization of construction business makes the CSR–CFP relationship more complicated than usual. Construction firms’ CSR fulfillment serves to engage in reliable relationships with stakeholders and consequently improve CFP. It can bring both benefits and costs to the firm, which suggests that the CSR–CFP relationship is non-linear. This study examines the impacts of CSR on the financial performance of construction firms. We took Chinese-listed construction companies as an example, and an inverted U-shaped curve relationship between CSR and CFP was eventually revealed. Further, the significant moderating role of the degree of corporate internationalization (DOI) in the CSR–CFP relationship is disclosed. The results show that matching a high DOI-high CSR and a low DOI-low CSR is more conducive to CFP promotion. Thus, this research makes contributions to the academic perception of the impacts of CSR and DOI on CFP and provides insights for CSR fulfillment in the international arena.
Energy Citizenship in Positive Energy Districts—Towards a Transdisciplinary Approach to Impact Assessment
Authors: van Wees Mark , Revilla Beatriz Pineda , Fitzgerald Helena , Ahlers Dirk , Romero Natalia , Alpagut Beril , Kort Joke , Tjahja Cyril , Kaiser Gabi , Blessing Viktoria , Patricio Lia , Smit Sander
Published: February 2022

It is commonly assumed by the projects demonstrating concepts for positive energy districts in cities across Europe that citizens want and need to be involved in the development of these concepts as an essential condition for positive energy districts to be deployed successfully and to achieve the expected societal goals. Six different research and innovation projects are investigating the different forms of energy citizenship in positive energy districts and their impacts. They aim to apply a transdisciplinary approach to collaborative research and to impact assessment. The interim results are described, and preliminary conclusions on impact are drawn. The projects each used different approaches to engaging citizens, while differentiating between different groups. Progress is monitored but only fragmentary evidence on the impact has been gathered. Transdisciplinary approaches are being developed but are still immature.
Private Renting vs. Mortgage Home Buying: Case of British Housing Market—A Bayesian Network and Directed Acyclic Graphs Approach
Authors: Sobieraj Janusz , Metelski Dominik
Published: February 2022

The worsening of housing problems in many countries has become a topic of global interest. Researchers point to a variety of factors that influence individual housing tenure decisions. Our study is based on longitudinal English Housing Survey (EHS) data (2008–2009 to 2019–2020, with survey years matching financial years, i.e., running April–March) and identifies flows between different forms of housing tenure in the U.K. and analyses conditional dependencies of a range of EHS variables using a directed acyclic graph (DAG). More specifically, we take into account variables such as first-time buyers (FTB), mortgage payments, rent payments, share of mortgage/rent in household income, and receipt of housing benefit (HB), with some variables also reflecting a regional breakdown (captured separately for London and England excluding London) to illustrate the complex nature of regional differences in explaining changes in housing tenure. We address some of the problems and challenges of the housing market in the U.K. today, and, in particular, examine what influences private renters and those buying with a mortgage. A key conclusion from this study is that housing benefit does not necessarily ease the way for private renters into their own housing. The study is quantitative in nature and uses the English Housing Survey and Bayesian network (BN) analysis. Unlike traditional methods, such as multiple regression or panel regression, where the researcher somehow suggests the type of a relationship between certain variables, BN’s learning algorithm analyses different iterations between variables and finds the most appropriate relationships between them.