bluuebunny/crossref_metadata_2025 huggingface dataset:
The Sesquiterpene Lactone Cynaropicrin Manifests Strong Cytotoxicity in Glioblastoma Cells U-87 MG by Induction of Oxidative Stress
Authors: Rotondo Rossella , Oliva Maria Antonietta , Arcella Antonietta
Published: July 2022

Cynaropicrin has shown a wide range of pharmacological properties, such as antitumor action. Here, we showed the inhibitory effect of Cyn on human glioblastoma cell U-87 MG growth. According to the IC50 values, Cyn 4, 8 and 10 µM displayed a significant cytotoxicity, as confirmed by the cell count and MTT assay. Furthermore, Cyn completely abolished the ability of U-87 MG to form colonies and induced drastic morphological changes. Interestingly, pretreatment with ROS scavenger N-acetylcysteine 3 mM reversed the cytotoxicity induced by Cyn 25 µM and preserved the cells by morphological changes. Therefore, oxidative stress induction was evaluated at low 8- and high 25-µM concentrations in U-87 MG, as demonstrated by the quantitative and qualitative analysis of ROS. A prolonged increase in ROS generation under Cyn 25 µM exposure was followed by the loss of the mitochondrial membrane potential in treated U-87 MG cells. An acute treatment with Cyn 25 µM induced Cyt c release, as revealed by immunofluorescence staining and the activation of cell death pathways, apoptosis and autophagy. On the other hand, chronic treatment with Cyn 8 µM induced senescence, as revealed by the increase in SA-β-Gal activity. Moreover, at this concentration, Cyn led to ERK dephosphorylation accompanied by a relevant reduction of the NF-κB p65 subunit. Finally, the combined effect of TMZ and Cyn resulted in synergistic cytotoxicity, as evaluated by the Bliss additivity model. The strong cytotoxicity of Cyn was also confirmed on IDH1 mutant U-87 MG cells and patient-derived IDH wild-type glioblastoma cell lines NULU and ZAR. In conclusion, given the high toxicity at minimal concentrations, the high inhibition of tumor cell growth and synergy with the standard drug for glioblastoma TMZ, Cyn could be proposed as a potential adjuvant for the treatment of glioblastoma.
The Role of the Extracellular Matrix (ECM) in Wound Healing: A Review
Authors: Diller Robert B. , Tabor Aaron J.
Published: July 2022

The extracellular matrix (ECM) is a 3-dimensional structure and an essential component in all human tissues. It is comprised of varying proteins, including collagens, elastin, and smaller quantities of structural proteins. Studies have demonstrated the ECM aids in cellular adherence, tissue anchoring, cellular signaling, and recruitment of cells. During times of integumentary injury or damage, either acute or chronic, the ECM is damaged. Through a series of overlapping events called the wound healing phases—hemostasis, inflammation, proliferation, and remodeling—the ECM is synthesized and ideally returned to its native state. This article synthesizes current and historical literature to demonstrate the involvement of the ECM in the varying phases of the wound healing cascade.
Multifrequency Investigation of Single- and Double-Stranded DNA with Scalable Metamaterial-Based THz Biosensors
Authors: Weisenstein Christian , Richter Merle , Wigger Anna Katharina , Bosserhoff Anja K. , Haring Bolívar Peter
Published: July 2022

Due to the occurrence of THz-excited vibrational modes in biomacromolecules, the THz frequency range has been identified as particularly suitable for developing and applying new bioanalytical methods. We present a scalable THz metamaterial-based biosensor being utilized for the multifrequency investigation of single- and double-stranded DNA (ssDNA and dsDNA) samples. It is demonstrated that the metamaterial resonance frequency shift by the DNA’s presence depends on frequency. Our experiments with the scalable THz biosensors demonstrate a major change in the degree of the power function for dsDNA by 1.53 ± 0.06 and, in comparison, 0.34 ± 0.11 for ssDNA as a function of metamaterial resonance frequency. Thus, there is a significant advantage for dsDNA detection that can be used for increased sensitivity of biomolecular detection at higher frequencies. This work represents a first step for application-specific biosensors with potential advantages in sensitivity, specificity, and robustness.
Escalation of Tau Accumulation after a Traumatic Brain Injury: Findings from Positron Emission Tomography
Authors: Mohamed Abdalla Z. , Cumming Paul , Nasrallah Fatima A. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: July 2022

Traumatic brain injury (TBI) has come to be recognized as a risk factor for Alzheimer’s disease (AD), with poorly understood underlying mechanisms. We hypothesized that a history of TBI would be associated with greater tau deposition in elders with high-risk for dementia. A Groups of 20 participants with self-reported history of TBI and 100 without any such history were scanned using [18F]-AV1451 positron emission tomography as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Scans were stratified into four groups according to TBI history, and by clinical dementia rating scores into cognitively normal (CDR = 0) and those showing cognitive decline (CDR ≥ 0.5). We pursued voxel-based group comparison of [18F]-AV1451 uptake to identify the effect of TBI history on brain tau deposition, and for voxel-wise correlation analyses between [18F]-AV1451 uptake and different neuropsychological measures and cerebrospinal fluid (CSF) biomarkers. Compared to the TBI-/CDR ≥ 0.5 group, the TBI+/CDR ≥ 0.5 group showed increased tau deposition in the temporal pole, hippocampus, fusiform gyrus, and inferior and middle temporal gyri. Furthermore, the extent of tau deposition in the brain of those with TBI history positively correlated with the extent of cognitive decline, CSF-tau, and CSF-amyloid. This might suggest TBI to increase the risk for tauopathies and Alzheimer’s disease later in life.
Lipocalin-2 Deficiency Reduces Hepatic and Hippocampal Triggering Receptor Expressed on Myeloid Cells-2 Expressions in High-Fat Diet/Streptozotocin-Induced Diabetic Mice
Authors: Shin Hyun Joo , Jin Zhen , An Hyeong Seok , Park Gyeongah , Lee Jong Youl , Lee So Jeong , Jang Hye Min , Jeong Eun Ae , Kim Kyung Eun , Lee Jaewoong , Yoo Dae Young , Roh Gu Seob
Published: July 2022

Background: Lipocalin-2 (LCN2) is an acute-phase protein that has been linked to insulin resistance, diabetes, and neuroinflammatory diseases. Triggering receptor expressed on myeloid cells-2 (TREM2) has been also implicated in microglia-mediated neuroinflammation. However, the potential role of LCN2 on TREM2 in diabetic mouse models is not fully understood. Methods: We investigated hepatic and hippocampal TREM2 expressions in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic LCN2 knockout (KO) mice. Results: In addition to increased serum LCN2 level, diabetic wild-type (WT) mice had insulin resistance and hepatic steatosis. However, LCN2 deletion attenuated these metabolic parameters in diabetic mice. We also found that LCN2 deletion reduced hepatic inflammation and microglial activation in diabetic mice. In particular, diabetic LCN2 KO mice had a reduction in hepatic and hippocampal TREM2 expressions compared with diabetic WT mice. Furthermore, we found that many TREM2-positive Kupffer cells and microglia in diabetic WT mice were reduced through LCN2 deletion. Conclusions: These findings indicate that LCN2 may promote hepatic inflammation and microglial activation via upregulation of TREM2 in diabetic mice.
Automated Rule Checking for MEP Systems Based on BIM and KBMS
Authors: Xie Xuanfeng , Zhou Jianliang , Fu Xuehai , Zhang Ruoyi , Zhu Hui , Bao Quanxi
Published: July 2022

Due to the growing complexity of mechanical, electrical, and plumbing (MEP) designs and the rules that govern them, performing rule checks manually has become expensive. However, MEP-based rule checking has not received adequate attention compared to automated rule checking in other domains. Based on Knowledge Management and Building Information Modeling (BIM), an automated rule checking system integrated knowledge base management system (KBMS) for model information expansion, information extraction, system integrity checking, and element spacing checking was developed. MEP rules for automated rule checking were collected, optimized, and stored in the MEP knowledge base. The KBMS facilitates the management of MEP rules in the knowledge base. A Revit plug-in of MEP rule checking system was developed including functions of KBMS, Model Integrity Checking, Elements Space Checking, and Locating the non-compliant element in model view. This study integrated both KBMS and BIM technologies to achieve automated rule checking for MEP. This simplifies the process of rule checking of MEP systems in an automated manner.
Outdoor Cold Stress and Cold Risk for Children during Winter: A Study in China’s Severe Cold Regions
Authors: Shao Long , He Xiaoyun , Tang Yuexing , Wu Shenglong
Published: July 2022

This study uses the universal thermal climate index (UTCI) and whole-body and local cooling assessment to determine the thermal benchmarks and cold risk for children in China’s severe cold regions. The relevant measurements and survey were conducted in four open spaces at a children’s park in Harbin, China. The findings of the study are as follows: (1) In winter, solar radiation and global temperature affects winter thermal sensation in male and female children the most. (2) Female children have a lower neutral UTCI (6.0 °C) than male children (7.3 °C), and female children have lower upper and lower thresholds of the neutral UTCI range (−1.3–13.4 °C) than male children (0.6–14.1 °C). (3) Children who engaged in light-intensity activities, were exposed to cold winds, and touched cold surfaces with their bare fingers are at risk of whole-body and local cooling. (4) Children prefer exercising (PFemale = 35.5%, PMale = 48.3%) and moving to sunshine for thermal adaptation (PFemale = 31.1%, PMale = 26.4%). (5) Winter travel guidelines, cold-risk-prevention measures, and safety guidelines for winter outdoor activities are proposed. The results provide references for the design of open spaces in urban parks in China’s severe cold regions.
Computational Aerodynamic Optimization of Wind-Sensitive Irregular Tall Buildings
Authors: Alkhatib Fadi , Kasim Narimah , Goh Wan Inn , Shafiq Nasir , Amran Mugahed , Kotov Evgenii Vladimirovich , Albaom Mohammed Abdo
Published: July 2022

Wind-induced loads and motions play a critical role in designing tall buildings and their lateral structural systems. Building configuration represented by its outer shape is a key parameter in determining these loads and structural responses. However, contemporary architecture trends towards creating taller buildings with more complex geometrical shapes to offer unique designs that become a signature on the map of the world. As a result, evaluating wind-induced motions on such structures becomes more challenging to be evaluated and predicted. This paper presents a computational performance-based aerodynamic optimization with minor imposed modifications that have little to no impact on architectural and structural design intent. The developed tool aims to assist both architects and engineers to seek a sustainable optimal design decision at the early stage of design by employing different computational technological tools in an automated manner. A computational optimization methodology consisting of a computational fluid dynamic coupled with finite element analysis and embedded within a radial basis function surrogate model is proposed to mitigate wind-induced loads on tall buildings. In addition, a numerical example implementing the proposed methodology on selected case study is presented and discussed. The proposed approach was able to achieve a minimization of 13.83% and 23.12% for along-wind and across-wind loads, respectively, which is translated to a reduction in structural response by 12.95% and 14.31% in maximum deflection for along-wind and across-wind directions, respectively.
Supplier Selection through Multicriteria Decision-Making Algorithmic Approach Based on Rough Approximation of Fuzzy Hypersoft Sets for Construction Project
Authors: Rahman Atiqe Ur , Saeed Muhammad , Mohammed Mazin Abed , Majumdar Arnab , Thinnukool Orawit
Published: July 2022

The suppliers play a significant role in supply chain management. In supplier selection, factors like market-based exposure, community-based reputation, trust-based status, etc., must be considered, along with the opinions of hired experts. These factors are usually termed as rough information. Most of the literature has disregarded such factors, which may lead to a biased selection. In this study, linguistic variables in terms of triangular fuzzy numbers (TrFn) are used to manage such kind of rough information, then the rough approximations of the fuzzy hypersoft set (FHS-set) are characterized which are capable of handling such informational uncertainties. The FHS-set is more flexible as well as consistent as it tackles the limitation of fuzzy soft sets regarding categorizing parameters into their related sub-classes having their sub-parametric values. Based on these rough approximations, an algorithm is proposed for the optimal selection of suppliers by managing experts’ opinions and rough information collectively in the form of TrFn-based linguistic variables. To have a discrete decision, a signed distance method is employed to transform the TrFn-based opinions of experts into fuzzy grades. The proposed algorithm is corroborated with the help of a multi-criteria decision-making application to choose the best supplier for real estate builders. The beneficial facets of the put forward study are appraised through its structural comparison with few existing related approaches. The presented approach is consistent as it is capable to manage rough information and expert’s opinions about suppliers collectively by using rough approximations of FHS-set.
Improvement Strategies for Microclimate and Thermal Comfort for Urban Squares: A Case of a Cold Climate Area in China
Authors: Yu Haiming , Fukuda Hiroatsu , Zhou Mengyuan , Ma Xuan
Published: July 2022

Urban squares are an important part of a city’s overall spatial environment. However, many urban squares lack rational designs, causing the thermal environment to deteriorate. To ensure sustainable urban development, urban square microclimates should be improved. Given that, this study investigates the effects of three coverages of three landscape elements of urban squares through modeling and simulation using the ENVI-met model validated by field measurements. The correlation between physiological equivalent temperature (PET) and different amounts of landscape elements is investigated using Spearman analysis. This study presents a case study of a typical urban square in a cold climate area. Design strategies in the area are proposed. The results show that the microclimate and thermal comfort of the urban square can be improved by expanding water bodies, modest increasing buildings and optimizing vegetation. Vegetation is the most important landscape element affecting thermal comfort in the urban square. The PET can be reduced by about 1.5 °C by increasing the vegetation cover from 40% to 70%. However, the degree of microclimate regulation by vegetation is disturbed by water bodies and buildings (|ρ| ≥ 0.5). Therefore, to achieve a more comfortable thermal environment, a combination of landscape elements should be considered.
Research on the Evaluation of Resilience and Influencing Factors of the Urban Network Structure in the Three Provinces of Northeast China Based on Multiple Flows
Authors: Liu He , Li Xueming , Tian Shenzhen , Guan Yingying
Published: July 2022

An important indicator for measuring the resilience and ability of urban networks to recover under external environmental shock, which is essential for the healthy development of the region, is urban network structure resilience. Herein we analyzed the resilience of the urban network structure and explored the influencing factors of resilience in the three provinces of Northeast China. We accomplished this by utilizing the Gephi profiling social network analysis tools based on the Baidu Index, road mileage, statistical data, other multi-source data, construction information, and the transportation, innovation, and economic multiple linkage network. This analysis enabled us to propose relevant suggestions and strategies to optimize urban network structure resilience. Our results indicate that (1) in 2019, the multi-city network structure in the three provinces of Northeast China contains both commonalities and characteristics. Overall, each network demonstrates a spatial distribution pattern of “dense in the north and sparse in the south.” (2) There exist evident hierarchical differences in the resilience characteristics of the multi-city network structure in the three provinces; each provincial capital city and sub-provincial city possesses greater advantages, the innovation network exhibits the most evident hierarchy, the mismatch of the information network is the highest, and the transmission and agglomeration of the economic network are the most prominent. (3) The resilience of the urban network structure of the three provinces is the result of the interaction of several factors. Political and economic factors such as government capacity, economic status, and urban vitality are the main factors affecting the resilience of the network structure.
Surgical Management of Inherited Breast Cancer: Role of Breast-Conserving Surgery
Authors: Magnoni Francesca , Sacchini Virgilio , Veronesi Paolo , Bianchi Beatrice , Bottazzoli Elisa , Tagliaferri Valentina , Mazzotta Erica , Castelnovo Giulia , Deguidi Giulia , Rossi Elisabetta Maria Cristina , Corso Giovanni
Published: July 2022

Recent studies have demonstrated that hereditary breast cancer (BC) has a prevalence of 5–10% among all BC diagnoses. Nowadays, significant technological advances in the identification of an increasingly broad spectrum of genetic mutations allow for the discovery of an ever-growing number of inherited pathogenic (P) or likely pathogenic (LP) variants of breast cancer susceptibility genes. As the management of BC patients carrying mutations in the BRCA1/2 genes or other high-penetrance genes is currently a challenge, extensive research is being carried out and a lively scientific debate has been taking place on what the most appropriate local therapy, especially surgical treatment, of patients with inherited BC should be. In many studies, BC outcomes in BRCA carriers and non-carriers have been compared. A number of them showed that, when compared with mastectomy, breast-conserving surgery in BRCA patients is oncologically safe in terms of overall survival, although an increased risk of ipsilateral recurrence was reported. In these patients, devising a specific therapeutic strategy is an inevitably complex process, as it must take into consideration a series of factors, require a multimodal approach, guarantee personalization, strictly adhere to scientific international guidelines, and consider all available evidence. The present narrative review purposes to identify and illustrate evidence from significant selected studies that discussed those issues, as well as to suggest useful tools to clinicians managing this specific clinical condition in daily clinical practice.
An Overview on Radiation Sensitivity in Hereditary Breast and Ovarian Cancer Syndrome
Authors: Gonçalves Diana , Pires Ana Salomé , Marques Inês A. , Gomes Inês , Sousa Gabriela , Botelho Maria Filomena , Abrantes Ana Margarida
Published: July 2022

Hereditary breast and ovarian cancer (HBOC) syndrome is a condition in which individuals have an increased risk of developing different types of cancer when compared to the general population. BRCA1 repair associated (BRCA1) and BRCA2 repair associated (BRCA2) genes are tumor suppressor genes that play a crucial role in cell, by repairing DNA damage. Mutations in these genes are responsible for 25% of HBOC cases. Individuals with this syndrome are often subjected to diagnostic imaging techniques, as well as therapeutic options, that use ionizing radiation, so it is crucial to understand whether these individuals may present higher radiosensitivity and, therefore, its consequences. Several studies have been carried out to understand if the exposure to different ionizing radiation doses can induce cancer in individuals with HBOC. Some of these studies have shown that individuals with HBOC are hypersensitive to the ionizing radiation and, therefore, have neoplasms resulting from mutations in genes that are important in maintaining genomic stability. When mutated, genes no longer guarantee this stability and promote the induction of carcinogenesis. Oppositely, other studies show that there is no association between exposure to ionizing radiation and an increased risk of developing cancer. Thus, the results are inconsistent, and there is a great need to clarify this relationship. In this review, we present the characteristics of HBOC syndrome and the effects that ionizing radiation can induce in individuals who have it. In addition, we review the studies that have already been carried out on this subject.
A Novel Role of SMG1 in Cholesterol Homeostasis That Depends Partially on p53 Alternative Splicing
Authors: Li Muyang , Philantrope Fredrick , Diot Alexandra , Bourdon Jean-Christophe , Thompson Patricia
Published: July 2022

SMG1, a phosphatidylinositol 3-kinase-related kinase (PIKK), essential in nonsense-mediated RNA decay (NMD), also regulates p53, including the alternative splicing of p53 isoforms reported to retain p53 functions. We confirm that SMG1 inhibition in MCF7 tumor cells induces p53β and show p53γ increase. Inhibiting SMG1, but not UPF1 (a core factor in NMD), upregulated several cholesterol pathway genes. SMG1 knockdown significantly increased ABCA1, a cholesterol efflux pump shown to be positively regulated by full-length p53 (p53α). An investigation of RASSF1C, an NMD target, increased following SMG1 inhibition and reported to inhibit miR-33a-5p, a canonical ABCA1-inhibiting miRNA, did not explain the ABCA1 results. ABCA1 upregulation following SMG1 knockdown was inhibited by p53β siRNA with greatest inhibition when p53α and p53β were jointly suppressed, while p53γ siRNA had no effect. In contrast, increased expression of MVD, a cholesterol synthesis gene upregulated in p53 deficient backgrounds, was sensitive to combined targeting of p53α and p53γ. Phenotypically, we observed increased intracellular cholesterol and enhanced sensitivity of MCF7 to growth inhibitory effects of cholesterol-lowering Fatostatin following SMG1 inhibition. Our results suggest deregulation of cholesterol pathway genes following SMG1 knockdown may involve alternative p53 programming, possibly resulting from differential effects of p53 isoforms on cholesterol gene expression.
A Genome-First Approach to Estimate Prevalence of Germline Pathogenic Variants and Risk of Pancreatic Cancer in Select Cancer Susceptibility Genes
Authors: Astiazaran-Symonds Esteban , Kim Jung , Haley Jeremy S. , Kim Sun Young , Rao H. Shanker , Genetics Center Regeneron , Carey David J. , Stewart Douglas R. , Goldstein Alisa M.
Published: July 2022

Patients with germline pathogenic variants (GPV) in cancer predisposition genes are at increased risk of pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. The genes most frequently found to harbor GPV in unselected PDAC cases are ATM, BRCA1, BRCA2, CDKN2A, CHEK2, and PALB2. However, GPV prevalence and gene-specific associations have not been extensively studied in the general population. To further explore these associations, we analyzed genomic and phenotypic data obtained from the UK Biobank (UKB) and Geisinger MyCode Community Health Initiative (GHS) cohorts comprising 200,600 and 175,449 participants, respectively. We estimated the frequency and calculated relative risks (RRs) of heterozygotes in both cohorts and a subset of individuals with PDAC. The combined frequency of heterozygous carriers of GPV in the general population ranged from 1.22% for CHEK2 to 0.05% for CDKN2A. The frequency of GPV in PDAC cases varied from 2.38% (ATM) to 0.19% (BRCA1 and CDKN2A). The RRs of PDAC were elevated for all genes except for BRCA1 and varied widely by gene from high (ATM) to low (CHEK2, BRCA2). This work expands our understanding of the frequencies of GPV heterozygous carriers and associations between PDAC and GPV in several important PDAC susceptibility genes.
Poisoning and Reuse of Supported Precious Metal Catalysts in the Hydrogenation of N-Heterocycles, Part II: Hydrogenation of 1-Methylpyrrole over Rhodium
Authors: Hegedűs László , Nguyen Tien Thuy Thanh , Lévay Krisztina , László Krisztina , Sáfrán György , Beck Andrea
Published: July 2022

Poisoning effect of nitrogen on heterogeneous, supported precious metal catalysts, along with their recycling, was further examined in the liquid-phase hydrogenation of 1-methylpyrrole (MP) to 1-methylpyrrolidine (MPD) over rhodium on carbon or γ-alumina, in methanol, under non-acidic conditions, at 25–50 °C and 10 bar. Reusing a spent, unregenerated 5% Rh/C or 5% Rh/γ-Al2O3 catalyst, it was found that the conversion of this model substrate and the activity of the catalyst were strongly dependent on the amount of catalyst, the type of support, the catalyst pre- or after-treatment, the temperature, and the number of recycling, respectively. An unexpected catalytic behaviour of rhodium was observed when it was used in a prehydrogenated form, because no complete conversion of MP was achieved over even the fresh Rh/C or Rh/γ-Al2O3, contrary to the untreated one. In addition, there was a significant difference in the reusability and activity of these rhodium catalysts, depending on their supports (activated carbon, γ-alumina). These diversions were elucidated by applying dispersion (O2- and H2-titration), temperature-programmed desorption of ammonia (NH3-TPD), and transmission electron microscopy (TEM) measurements.
Abatement of Naphthalene by Persulfate Activated by Goethite and Visible LED Light at Neutral pH: Effect of Common Ions and Organic Matter
Authors: Sánchez-Yepes Andrés , Lorenzo David , Sáez Patricia , Romero Arturo , Santos Aurora
Published: July 2022

Naphthalene (NAP) has received particular attention due to its impact on the environment and human health, mandating its removal from water systems. In this work, the abatement of NAP in the aqueous phase was achieved using persulfate (PS) activated by Fe (III) and monochromatic LED light at a natural pH. The reaction was carried out in a slurry batch reactor using goethite as the Fe (III) source. The influence of the PS concentration, goethite concentration, irradiance, temperature and presence of organic matter, chloride, and bicarbonate on the abatement of NAP was studied. These variables were shown to have a different effect on NAP removal. The irradiance showed a maximum at 0.18 W·cm−2 where the photonic efficiency was the highest. As for the concentration of goethite and PS, the influence of the first one was negligible, whereas for PS, the best results were reached at 1.2 mM due to a self-inhibitory effect at higher concentrations. The temperature effect was also negative in the PS consumption. Regarding the effect of ions, chloride had no influence on NAP conversion but carbonates and humic acids were affected. Lastly, this treatment to remove NAP has proved to be an effective technique since minimum conversions of 0.92 at 180 min of reaction time were reached. Additionally, the toxicity of the final samples was decreased.
The Role of the Fibronectin Synergy Site for Skin Wound Healing
Authors: Gimeno-LLuch Irene , Benito-Jardón María , Guerrero-Barberà Gemma , Burday Natalia , Costell Mercedes
Published: July 2022

Skin is constantly exposed to injuries that are repaired with different outcomes, either regeneration or scarring. Scars result from fibrotic processes modulated by cellular physical forces transmitted by integrins. Fibronectin (FN) is a major component in the provisional matrix assembled to repair skin wounds. FN enables cell adhesion binding of α5β1/αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5/αIIb is the synergy site located in close proximity to the RGD motif. The mutation to impair the FN synergy region (Fn1syn/syn) demonstrated that its absence permits complete development. However, only with the additional engagement to the FN synergy site do cells efficiently resist physical forces. To test how the synergy site-mediated adhesion affects the course of wound healing fibrosis, we used a mouse model of skin injury and in-vitro migration studies with keratinocytes and fibroblasts on FNsyn. The loss of FN synergy site led to normal re-epithelialization caused by two opposing migratory defects of activated keratinocytes and, in the dermis, induced reduced fibrotic responses, with lower contents of myofibroblasts and FN deposition and diminished TGF-β1-mediated cell signalling. We demonstrate that weakened α5β1-mediated traction forces on FNsyn cause reduced TGF-β1 release from its latent complex.
mTOR-Dependent Autophagy Regulates Slit Diaphragm Density in Podocyte-like Drosophila Nephrocytes
Authors: Spitz Dominik , Comas Maria , Gerstner Lea , Kayser Séverine , Helmstädter Martin , Walz Gerd , Hermle Tobias
Published: July 2022

Both mTOR signaling and autophagy are important modulators of podocyte homeostasis, regeneration, and aging and have been implicated in glomerular diseases. However, the mechanistic role of these pathways for the glomerular filtration barrier remains poorly understood. We used Drosophila nephrocytes as an established podocyte model and found that inhibition of mTOR signaling resulted in increased spacing between slit diaphragms. Gain-of-function of mTOR signaling did not affect spacing, suggesting that additional cues limit the maximal slit diaphragm density. Interestingly, both activation and inhibition of mTOR signaling led to decreased nephrocyte function, indicating that a fine balance of signaling activity is needed for proper function. Furthermore, mTOR positively controlled cell size, survival, and the extent of the subcortical actin network. We also showed that basal autophagy in nephrocytes is required for survival and limits the expression of the sns (nephrin) but does not directly affect slit diaphragm formation or endocytic activity. However, using a genetic rescue approach, we demonstrated that excessive, mTOR-dependent autophagy is primarily responsible for slit diaphragm misspacing. In conclusion, we established this invertebrate podocyte model for mechanistic studies on the role of mTOR signaling and autophagy, and we discovered a direct mTOR/autophagy-dependent regulation of the slit diaphragm architecture.
Review of the Application of Hydrotalcite as CO2 Sinks for Climate Change Mitigation
Authors: Suescum-Morales David , Jiménez José Ramón , Fernández-Rodríguez José María
Published: July 2022

In recent decades, the environmental impact caused by greenhouse gases, especially CO2, has driven many countries to reduce the concentration of these gases. The study and development of new designs that maximise the efficiency of CO2 capture continue to be topical. This paper presents a review of the application of hydrotalcites as CO2 sinks. There are several parameters that can make hydrotalcites suitable for use as CO2 sinks. The first question is the use of calcined or uncalcined hydrotalcite as well as the temperature at which it is calcined, since the calcination conditions (temperature, rate and duration) are important parameters determining structure recovery. Other aspects were also analysed: (i) the influence of the pH of the synthesis; (ii) the molar ratio of its main elements; (iii) ways to increase the specific area of hydrotalcites; (iv) pressure, temperature, humidity and time in CO2 absorption; and (v) combined use of hydrotalcites and cement-based materials. A summary of the results obtained so far in terms of CO2 capture with the parameters described above is presented. This work can be used as a guide to address CO2 capture with hydrotalcites by showing where the information gaps are and where researchers should apply their efforts.
Recovery of Citric Acid from Citrus Peels: Ultrasound-Assisted Extraction Optimized by Response Surface Methodology
Authors: Fernandes Filipa A. , Heleno Sandrina A. , Pinela José , Carocho Márcio , Prieto Miguel A. , Ferreira Isabel C. F. R. , Barros Lillian
Published: July 2022

The production of citrus juice generates a large quantity of by-products, which are often discarded or used for animal feed. However, several studies have shown its richness in valuable compounds, namely organic acids. Thus, this work intended to valorize orange and lime peels as renewable sources of citric acid. An experimental design combining five levels of the independent variables time (2–45 min), ultrasonic power (50–500 W), and ethanol proportion (0–100%) was implemented and response surface methodology (RSM) was applied to optimize the extraction process. The UPLC-PDA analysis showed that orange peel presented a higher citric acid content than lime. For lime and orange peels, the extraction yield was maximized by sonicating at low power for 5.8 or 35.5 min, using a low ethanol proportion or only water as a solvent, respectively. Overall, optimal UAE conditions were defined for the sustainable extraction of citric acid from citrus by-products, thus contributing to its valorization and upcycling into natural food ingredients.
Neural Marker of Habituation at 5 Months of Age Associated with Deferred Imitation Performance at 12 Months: A Longitudinal Study in the UK and The Gambia
Authors: Katus Laura , Milosavljevic Bosiljka , Rozhko Maria , McCann Samantha , Mason Luke , Mbye Ebrima , Touray Ebou , Moore Sophie E. , Elwell Clare E. , Lloyd-Fox Sarah , de Haan Michelle ,   The BRIGHT Study Team
Published: July 2022

Across cultures, imitation provides a crucial route to learning during infancy. However, neural predictors which would enable early identification of infants at risk of suboptimal developmental outcomes are still rare. In this paper, we examine associations between ERP markers of habituation and novelty detection measured at 1 and 5 months of infant age in the UK (n = 61) and rural Gambia (n = 214) and infants’ responses on a deferred imitation task at 8 and 12 months. In both cohorts, habituation responses at 5 months significantly predicted deferred imitation responses at 12 months of age in both cohorts. Furthermore, ERP habituation responses explained a unique proportion of variance in deferred imitation scores which could not be accounted for by a neurobehavioural measure (Mullen Scales of Early Learning) conducted at 5 months of age. Our findings highlight the potential for ERP markers of habituation and novelty detection measured before 6 months of age to provide insight into later imitation abilities and memory development across diverse settings.
Adenomesenteritis following SARS-CoV-2 Vaccination in Children: A Case Report and Review of The Literature
Authors: Bloise Silvia , Marcellino Alessia , Martucci Vanessa , Sanseviero Mariateresa , Testa Alessia , Del Giudice Emanuela , Spatuzzo Mattia , Sermoneta Daniel , Ventriglia Flavia , Lubrano Riccardo
Published: July 2022

At present, the vaccine authorized in children aged 5 years and older is the BNT162b2 messenger RNA COVID-19 vaccine. Unlike adults, there is limited data available in the pediatric age describing adverse events after vaccine. We report a case of adenomesenteritis in a young girl following the first dose of vaccine.
Traditional and Modern Diagnostic Approaches in Diagnosing Pediatric Helicobacter pylori Infection
Authors: Mărginean Cristina Oana , Meliț Lorena Elena , Săsăran Maria Oana
Published: July 2022

Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, is usually acquired during childhood and is related to gastric carcinogenesis during adulthood. Therefore, its early proper diagnosis and subsequent successful eradication represent the cornerstones of gastric cancer prevention. The aim of this narrative review was to assess traditional and modern diagnostic methods in terms of H. pylori diagnosis. Several invasive and non-invasive methods were described, each with its pros and cons. The invasive diagnostic methods comprise endoscopy with biopsy, rapid urease tests, histopathological exams, cultures and biopsy-based molecular tests. Among these, probably the most available, accurate and cost-effective test remains histology, albeit molecular tests definitely remain the most accurate despite their high costs. The non-invasive tests consist of urea breath tests, serology, stool antigens and non-invasive molecular tests. Urea breath tests and stool antigens are the most useful in clinical practice both for the diagnosis of H. pylori infection and for monitoring the eradication of this infection after therapy. The challenges related to accurate diagnosis lead to a choice that must be based on H. pylori virulence, environmental factors and host peculiarities.
Effects of Strength Training on Body Fat in Children and Adolescents with Overweight and Obesity: A Systematic Review with Meta-Analysis
Authors: Méndez-Hernández Luis Diego , Ramírez-Moreno Esther , Barrera-Gálvez Rosario , Cabrera-Morales María del Consuelo , Reynoso-Vázquez Josefina , Flores-Chávez Olga Rocío , Morales-Castillejos Lizbeth , Cruz-Cansino Nelly del Socorro , Jiménez-Sánchez Reyna Cristina , Arias-Rico José
Published: July 2022

Childhood overweight and obesity represent a growing public health problem worldwide. Since the 1980s, the global prevalence of overweight and obesity in childhood and adolescence has increased by 47%. The promotion of exercise is an important intervention to reduce the physical damage of obesity. The meta-analysis was conducted in accordance with the general guidelines for the reporting of systematic reviews and meta-analyses (PRISMA). The PubMed, SciELO, ScienceDirect and Google Scholar databases were searched from August to December 2021. The search yielded 722 titles published between 2000 and 2021. After screening the titles and abstracts, 64 duplicate articles were detected, and 27 articles were ultimately included in the systematic review, including 26 articles published in English and one published in Spanish. There was a statistically significant effect of the strength training interventions on the percentage of body fat, Test of 0 i = (p = 0.00, z = 6.92), Test of 0 = (p = 0.00, Q (9) = 42.63). The findings reveal that strength training has a positive impact on the treatment of body fat in children and adolescents with overweight and obesity.
Total Esophagogastric and Cologastric Dissociation in Neurologically Normal Children: Systematic Review
Authors: Negri Elisa , Coletta Riccardo , Bici Kejd , Bianchi Adrian , Morabito Antonino
Published: July 2022

Total esophagogastric dissociation (TEGD) was first described by Bianchi as a definitive procedure for gastroesophageal reflux disease (GERD) in neurologically impaired children. In the last 20 years, different centers extended the indication to neurologically normal (NN) patients with GERD associated with congenital or acquired esophageal anomalies. The aim of this paper is to analyze the role of TEGD in this cluster of patients. A PubMed and Google Scholar search was conducted. All cases of NN children who underwent TEGD for GERD were collected. Patient characteristics and outcomes were analyzed. Complications were classified according to Clavien–Dindo classification. Forty-eight children were identified. In 56.25%, TEGD was the first anti-reflux procedure, while in 43.75% it was performed after failed fundoplications. Mean follow-up was 5.5 years. Mortality related to surgery was 2.08%. All of the survivors improved their condition, with resolution of GERD and weight gain. In addition, 50% of children weaned off enteral nutrition, with 14.6% having their gastrostomy removed, while 41.67% maintained partial enteral supplementation. Respiratory symptoms almost disappeared in 54.17% of patients. This review suggests that TEGD can also be considered for NN children where conventional methods seem insufficient to control reflux and preserve pulmonary function. Nevertheless, long-term follow-up is still required.
Using AI-Based Evolutionary Algorithms to Elucidate Adult Brain Tumor (Glioma) Etiology Associated with IDH1 for Therapeutic Target Identification
Authors: McInerney Caitríona E. , Lynn Joanna A. , Gilmore Alan R. , Flannery Tom , Prise Kevin M.
Published: July 2022

Adult brain tumors (glioma) represent a cancer of unmet need where standard-of-care is non-curative; thus, new therapies are urgently needed. It is unclear whether isocitrate dehydrogenases (IDH1/2) when not mutated have any role in gliomagenesis or tumor growth. Nevertheless, IDH1 is overexpressed in glioblastoma (GBM), which could impact upon cellular metabolism and epigenetic reprogramming. This study characterizes IDH1 expression and associated genes and pathways. A novel biomarker discovery pipeline using artificial intelligence (evolutionary algorithms) was employed to analyze IDH-wildtype adult gliomas from the TCGA LGG-GBM cohort. Ninety genes whose expression correlated with IDH1 expression were identified from: (1) All gliomas, (2) primary GBM, and (3) recurrent GBM tumors. Genes were overrepresented in ubiquitin-mediated proteolysis, focal adhesion, mTOR signaling, and pyruvate metabolism pathways. Other non-enriched pathways included O-glycan biosynthesis, notch signaling, and signaling regulating stem cell pluripotency (PCGF3). Potential prognostic (TSPYL2, JAKMIP1, CIT, TMTC1) and two diagnostic (MINK1, PLEKHM3) biomarkers were downregulated in GBM. Their gene expression and methylation were negatively and positively correlated with IDH1 expression, respectively. Two diagnostic biomarkers (BZW1, RCF2) showed the opposite trend. Prognostic genes were not impacted by high frequencies of molecular alterations and only one (TMTC1) could be validated in another cohort. Genes with mechanistic links to IDH1 were involved in brain neuronal development, cell proliferation, cytokinesis, and O-mannosylation as well as tumor suppression and anaplerosis. Results highlight metabolic vulnerabilities and therapeutic targets for use in future clinical trials.
Defect Properties of Li2NiGe3O8
Authors: Kuganathan Navaratnarajah , Sukumar Raveena , Iyngaran Poobalasuntharam
Published: July 2022

There is a growing interest in finding a suitable electrolyte material for the construction of rechargeable Li-ion batteries. Li2NiGe3O8 is a material of interest with modest Li-ionic conductivity. The atomistic simulation technique was applied to understand the defect processes and Li-ion diffusion pathways, together with the activation energies and promising dopants on the Li, Ni, and Ge sites. The Li-Ni anti-site defect cluster was found to be the dominant defect in this material, showing the presence of cation mixing, which can influence the properties of this material. Li-ion diffusion pathways were constructed, and it was found that the activation energy for a three-dimensional Li-ion migration pathway is 0.57 eV, which is in good agreement with the values reported in the experiment. The low activation energy indicated that Li-ion conductivity in Li2NiGe3O8 is fast. The isovalent doping of Na, Fe and Si on the Li, Ni and Ge sites is energetically favorable. Both Al and Ga are candidate dopants for the formation of Li-interstitials and oxygen vacancies on the Ge site. While Li-interstitials can improve the capacity of batteries, oxygen vacancies can promote Li-ion diffusion.
Influence of Plasma Torch Power on the Plasma Jet Properties and Microstructure of Alumina Coatings
Authors: Šuopys Airingas , Grigaitienė Viktorija , Marcinauskas Liutauras , Kėželis Romualdas , Uscila Rolandas , Aikas Mindaugas
Published: July 2022

In this study, alumina coatings were formed using atmospheric plasma spraying, increasing the torch power from 29.4 to 45.1 kW. The surface morphology of the coatings was determined using scanning electron microscopy; the elemental composition was examined using energy-dispersive X-ray spectroscopy (EDS); phase composition was investigated using X-ray diffraction; and surface roughness was determined using a profilometer. The steel surface temperature was measured using a type-K thermocouple, and the plasma jet temperature, at a distance of 70 mm, using a type-B thermocouple. Alumina particle velocity was calculated by analyzing high-speed camera footage using ImageJ software. The results indicate that plasma jet temperature, speed, and in-flight particle velocity increased with plasma torch power. Furthermore, the amount of γ-Al2O3 phase in the coating increased, and the α-Al2O3 decreased with increasing plasma power. The surface roughness (Rq) of the Al2O3 coatings decreased from 7.13 to 5.54 μm, with an increase in torch power. The EDS measurements indicate that the increase in torch power did not affect the elemental composition of as-sprayed coatings. The results provide a wider understanding of an atmospheric plasma spray technique, optimizing and controlling the parameters using air as a primary gas.
The Impact of Bias and Nitrogen Pressure on TiNbN Coatings in Arc-PVD Processes—A Multifactorial Study
Authors: Dempwolf Henry , Proft Matthias , Baumann Axel , Malz Sinah , Keßler Olaf
Published: July 2022

Titanium-based nitride physical vapour deposition (PVD) coatings, such as titanium nitride (TiN), are state-of-the-art solutions for surface modifications of CoCrMo-based implants for patients who are hypersensitive to metallic ions such as cobalt, chromium and nickel. Variations of the process parameters during the cathodic arc evaporation are known to exhibit an impact on the surface properties of coatings. The aim of this study was to characterise the effect of the substrate bias and the nitrogen pressure on the surface properties of TiNbN coatings deposited on CoCrMo alloys in a limited parameter set. Eighteen parameter sets were coated with TiNbN. The substrate bias (−100 to −200 V) and the nitrogen pressure (0.3–3.0 Pa) were selected following a randomised, multifactorial response surface test design. The coating thickness, roughness, hardness and scratch resistance were measured following standardised procedures. The structure of the coating was analysed by SEM and XRD. The substrate bias and the pressure exhibited a significant impact on the coating thickness and the surface roughness. The grain growth was predominantly impacted by the bias. The parameter variation did not show any significant impact on the XRD, hardness or scratch test results.
The Effect of Corrosion Conditions on Aging of Artificial Patina on Three Bronzes
Authors: Kapitanović Angela , Ćurković Helena Otmačić
Published: July 2022

The new bronze objects of art are almost always patinated before their exposure outdoors or indoors. Among the many patination methods used by practitioners, sulphide patination is one of the most common techniques. The aim of this work is to examine the corrosion behaviour of sulphide patinated bronzes under various aging conditions, including continuous immersion in simulated urban rain, alternating wet/dry cycles, and exposure to corrosion chamber with NO2 gas. The study was conducted on three types of bronzes with varying tin content. Corrosion characterisation of patinated bronze samples was performed by the means of electrochemical impedance spectroscopy and polarization measurements. Chemical composition and morphology of sulphide patinated bronze surface was examined by infrared spectroscopy and scanning electron microscopy. Obtained results show that freshly patinated bronze surfaces exhibit low corrosion resistance that gradually improves over time. An increase in corrosion resistance strongly depends on aging conditions, and it appears to be the highest under continuous immersion conditions.