bluuebunny/crossref_metadata_2025 huggingface dataset:
Social-Emotional Learning Competencies and Problematic Internet Use among Chinese Adolescents: A Structural Equation Modeling Analysis
Authors: Chen Chun , Yang Chunyan , Nie Qian
Published: March 2021

To advance the understanding about social-cognitive factors related to Chinese adolescents’ experience with problematic Internet use (PIU), we examined the associations between social-emotional learning (SEL) competencies (i.e., responsible decision-making, social awareness, self-management, self-awareness, and social relationship) and problematic Internet use (PIU) among 1141 11th grade high school students from Southwest China. Through comparing the latent means of PIU across students with different demographic background (i.e., gender, social-economic status, left-behind status), the study found that male students endorsed higher levels of overall PIU and more problematic time management with Internet use than female students. No latent PIU mean differences were observed across family income and students’ left-behind status. Using structural equation modeling (SEM) while controlling for demographic factors, overall SEL competencies were found to have a significantly negative association with PIU. Meanwhile, all five SEL domains were also negatively associated with students’ PIU. The findings imply the importance of fostering SEL competencies in preventing PIU among Chinese adolescents. The study provides important practical implications for informing school-based SEL competencies programs for PIU prevention among Chinese youths.
Effects of COVID-19 Lockdown on Physical Activity, Sedentary Behavior, and Satisfaction with Life in Qatar: A Preliminary Study
Authors: Hermassi Souhail , Sellami Maha , Salman Ahmad , Al-Mohannadi Abdulla S. , Bouhafs El Ghali , Hayes Lawrence D. , Schwesig René
Published: March 2021

This study examined the effects of home confinement on physical activity (PA) and life satisfaction during the COVID-19 outbreak in Qatar. A total of 1144 subjects participated (male: n = 588; female: n = 556; age: 33.1 ± 11.1 years; mass: 76.1 ± 16.4 kg; height: 1.70 ± 0.11 m; body mass index (BMI): 26.1 ± 4.44  kg/m2). Online survey questions considered “before” and “during” confinement. Confinement reduced all PA intensities (ηp2 = 0.27–0.67, p < 0.001) and increased daily sitting time from 3.57 ± 1.47 to 6.32 ± 1.33 h per weekday (ηp2 = 0.67, p < 0.001). The largest reduction was detected for the sum parameter all physical activity (minutes per week, ηp2 = 0.67, p < 0.001; MET (metabolic equivalent of task)-minutes/week, ηp2 = 0.69, p < 0.001). Life satisfaction decreased, with the score for “I am satisfied with my life” (ηp2 = 0.76, p < 0.001) decreasing from 28.1 ± 4.81 to 14.2 ± 6.41 arbitrary units (AU). Concerning life satisfaction, the largest change was detected for the statement “the conditions of my life are excellent” (dmale = 7.93). For all parameters, time effects were indicative of large negative effects in both genders. In terms of magnitude, the difference between gender was greatest for the parameter “the conditions of my life are excellent” (difference between groups, d = 4.84). In conclusion, COVID-19 confinement decreased PA, increased sitting time, and decreased life satisfaction in Qatar. These precautionary findings explicate the risk of psychosocial impairment and the potential physical harm of reducing physical activity during early COVID-19 confinement in 2020.
Different Curve Shapes of Fasting Glucose and Various Obesity-Related Indices by Diabetes and Sex
Authors: Wen Wei-Lun , Wu Pei-Yu , Huang Jiun-Chi , Tu Hung-Pin , Chen Szu-Chia
Published: March 2021

Fasting plasma glucose (FPG) and obesity-related indices are prognostic factors for adverse outcomes in both subjects with and without diabetes. A few studies have investigated sex differences in obesity indices related to the risk of diabetes, however no studies have compared the relationship between FPG and obesity-related indices by diabetes and sex. Therefore, in this study, we compared the curve shapes of FPG and various obesity-related indices by diabetes, and further explored sex differences in these associations. Data were derived from the Taiwan Biobank database, which included 5000 registered individuals. We used an adjusted generalized linear regression model and calculated the difference of least square means (Lsmean; standard error, SE) for males and females with and without diabetes. Associations between obesity-related indices and fasting glucose level by diabetes and sex groups were estimated, and the ORTHOREG procedure was used to construct B-splines. The post-fitting for linear models procedure was used to determine the range at which the trends separated significantly. The diabetes/sex/FPG interaction term was significant for all obesity-related indices, including body mass index, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, lipid accumulation product, body roundness index, conicity index, body adiposity index and abdominal volume index. B-spline comparisons between males and females did not reach significance. However, FPG affected the trend towards obesity-related indices. As the fasting glucose level increased, the values of obesity-related indices varied more obviously in the participants without diabetes than in those with diabetes mellitus. The current study revealed that there was a different relationship between FPG and obesity-related indices by diabetes and sex. FPG affected the trend towards obesity-related indices more obviously in participants without diabetes than in those with diabetes. Further studies with a longitudinal design would provide a better understanding of the underlying mechanisms for the relationships.
Community Health Workers as a Strategy to Tackle Psychosocial Suffering Due to Physical Distancing: A Randomized Controlled Trial
Authors: Vanden Bossche Dorien , Lagaert Susan , Willems Sara , Decat Peter
Published: March 2021

Background: During the COVID-19 pandemic, many primary care professionals were overburdened and experienced difficulties reaching vulnerable patients and meeting the increased need for psychosocial support. This randomized controlled trial (RCT) tested whether a primary healthcare (PHC) based community health worker (CHW) intervention could tackle psychosocial suffering due to physical distancing measures in patients with limited social networks. Methods: CHWs provided 8 weeks of tailored psychosocial support to the intervention group. Control group patients received ‘care as usual’. The impact on feelings of emotional support, social isolation, social participation, anxiety and fear of COVID-19 were measured longitudinally using a face-to-face survey to determine their mean change from baseline. Self-rated change in psychosocial health at 8 weeks was determined. Results: We failed to find a significant effect of the intervention on the prespecified psychosocial health measures. However, the intervention did lead to significant improvement in self-rated change in psychosocial health. Conclusions: This study confirms partially the existing evidence on the effectiveness of CHW interventions as a strategy to address mental health in PHC in a COVID context. Further research is needed to elaborate the implementation of CHWs in PHC to reach vulnerable populations during and after health crises.
Landscape Visual Sensitivity Assessment of Historic Districts—A Case Study of Wudadao Historic District in Tianjin, China
Authors: Fang Ya-Nan , Zeng Jian , Namaiti Aihemaiti
Published: March 2021

Against the backdrop of urban stock renewal, as the core area of a city rich in culture, aesthetics, and tourism resources, the assessment of landscape visual sensitivity of historic districts can provide an accurate, objective, and intuitive decision-making basis for the multi-purpose planning of districts. The main purpose of this study was to develop an assessment method based on the geographic information system (GIS) in order to make a visual sensitivity index map on a district scale. To this end, this study uses the multi-criteria evaluation (MCE) method, selects the visibility (VSv), the number of potential users (VSu), and remarkableness (VSe) as the main criteria, and constructs a comprehensive assessment model of the visual sensitivity of the historic landscape. The most well-protected Wudadao Historic District in Tianjin (Wudadao) was selected as the study area, and its visual sensitivity was assessed. The assessment results are divided into four levels: areas of high sensitivity, moderate sensitivity, low sensitivity, and very low sensitivity. Results indicate that after the optimization and improvement of the evaluation index for visual sensitivity of a large-scale forest landscape, it is feasible to evaluate the small-scale visual sensitivity of historic districts; the higher the sensitivity level, the more important it is to be protected, and the more cautious it should be in the renewal of districts; the higher the number of potential users, the higher the visual sensitivity level, and so on. Further attention needs to be paid to planning and design to improve visual quality.
Could Small Heat Shock Protein HSP27 Be a First-Line Target for Preventing Protein Aggregation in Parkinson’s Disease?
Authors: Navarro-Zaragoza Javier , Cuenca-Bermejo Lorena , Almela Pilar , Laorden María-Luisa , Herrero María-Trinidad
Published: March 2021

Small heat shock proteins (HSPs), such as HSP27, are ubiquitously expressed molecular chaperones and are essential for cellular homeostasis. The major functions of HSP27 include chaperoning misfolded or unfolded polypeptides and protecting cells from toxic stress. Dysregulation of stress proteins is associated with many human diseases including neurodegenerative diseases, such as Parkinson’s disease (PD). PD is characterized by the presence of aggregates of α-synuclein in the central and peripheral nervous system, which induces the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and in the autonomic nervous system. Autonomic dysfunction is an important non-motor phenotype of PD, which includes cardiovascular dysregulation, among others. Nowadays, the therapies for PD focus on dopamine (DA) replacement. However, certain non-motor symptoms with a great impact on quality of life do not respond to dopaminergic drugs; therefore, the development and testing of new treatments for non-motor symptoms of PD remain a priority. Since small HSP27 was shown to prevent α-synuclein aggregation and cytotoxicity, this protein might constitute a suitable target to prevent or delay the motor and non-motor symptoms of PD. In the first part of our review, we focus on the cardiovascular dysregulation observed in PD patients. In the second part, we present data on the possible role of HSP27 in preventing the accumulation of amyloid fibrils and aggregated forms of α-synuclein. We also include our own studies, highlighting the possible protective cardiac effects induced by L-DOPA treatment through the enhancement of HSP27 levels and activity.
Chromatin Regulator SRG3 Overexpression Protects against LPS/D-GalN-Induced Sepsis by Increasing IL10-Producing Macrophages and Decreasing IFNγ-Producing NK Cells in the Liver
Authors: Lee Sung Won , Park Hyun Jung , Jeon Jungmin , Park Yun Hoo , Kim Tae-Cheol , Jeon Sung Ho , Seong Rho Hyun , Van Kaer Luc , Hong Seokmann
Published: March 2021

We previously showed that ubiquitous overexpression of the chromatin remodeling factor SWItch3-related gene (SRG3) promotes M2 macrophage differentiation, resulting in anti-inflammatory responses in the experimental autoimmune encephalomyelitis model of multiple sclerosis. Since hepatic macrophages are responsible for sepsis-induced liver injury, we investigated herein the capacity of transgenic SRG3 overexpression (SRG3β-actin mice) to modulate sepsis in mice exposed to lipopolysaccharide (LPS) plus d-galactosamine (d-GalN). Our results demonstrated that ubiquitous SRG3 overexpression significantly protects mice from LPS/d-GalN-induced lethality mediated by hepatic M1 macrophages. These protective effects of SRG3 overexpression correlated with the phenotypic conversion of hepatic macrophages from an M1 toward an M2 phenotype. Furthermore, SRG3β-actin mice had decreased numbers and activation of natural killer (NK) cells but not natural killer T (NKT) cells in the liver during sepsis, indicating that SRG3 overexpression might contribute to cross-talk between NK cells and macrophages in the liver. Finally, we demonstrated that NKT cell-deficient CD1d KO/SRG3β-actin mice are protected from LPS/d-GalN-induced sepsis, indicating that NKT cells are dispensable for SRG3-mediated sepsis suppression. Taken together, our findings provide strong evidence that SRG3 overexpression may serve as a therapeutic approach to control overwhelming inflammatory diseases such as sepsis.
Diosmin Mitigates Cyclophosphamide Induced Premature Ovarian Insufficiency in Rat Model
Authors: Abogresha Noha M. , Mohammed Sally S. , Hosny Marwa M. , Abdallah Hoda Y. , Gadallah Ahmed M. , Greish Sahar M.
Published: March 2021

The current study was designed to investigate the protective role of diosmin against cyclophosphamide-induced premature ovarian insufficiency (POI). Female Swiss albino rats received a single intraperitoneal dose of cyclophosphamide (200 mg/kg) followed by 8 mg/kg/day for the next 15 consecutive days either alone or in combination with oral diosmin at 50 or 100 mg/kg. Histopathological examination of ovarian tissues, hormonal assays for follicle stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH), assessment of the oxidative stress status, as well as measurement of the relative expression of miRNA-145 and its target genes [vascular endothelial growth factor B (VEGF-B) and regulator of cell cycle (RGC32)] were performed. Diosmin treatment ameliorated the levels of E2, AMH, and oxidative stress markers. Additionally, both low and high diosmin doses significantly reduced the histopathological alterations and nearly preserved the normal ovarian reserve. MiRNA-145 expression was upregulated after treatment with diosmin high dose. miRNA-145 target genes were over-expressed after both low and high diosmin administration. Based on our findings, diosmin has a dose-dependent protective effect against cyclophosphamide-induced ovarian toxicity in rats.
Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression
Authors: Lai Trang Huyen , Ahmed Mahmoud , Hwang Jin Seok , Zada Sahib , Pham Trang Minh , Elashkar Omar , Kim Deok Ryong
Published: March 2021

Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, including ERK and NF-κκB. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The transcription regulation of RKIP gene in human cancers is not well understood. In this study, we suggested a possible transcription mechanism for the regulation of RKIP in human cancer cells. We found that Metadherin (MTDH) significantly repressed the transcriptional activity of RKIP gene. An analysis of publicly available datasets showed that the knockdown of MTDH in breast and endometrial cancer cell lines induced the expression RKIP. In addition, the results obtained from qRT-PCR and ChIP analyses showed that MTDH considerably inhibited RKIP expression. In addition, the RKIP transcript levels in MTDH-knockdown or MTDH-overexpressing MCF-7 cells were likely correlated to the protein levels, suggesting that MTDH regulates RKIP expression. In conclusion, we suggest that MTDH is a novel factor that controls the RKIP transcription, which is essential for cancer progression.
Factor XIII-A: An Indispensable “Factor” in Haemostasis and Wound Healing
Authors: Alshehri Fahad S. M. , Whyte Claire S. , Mutch Nicola J.
Published: March 2021

Factor XIII (FXIII) is a transglutaminase enzyme that catalyses the formation of ε-(γ-glutamyl)lysyl isopeptide bonds into protein substrates. The plasma form, FXIIIA2B2, has an established function in haemostasis, with fibrin being its principal substrate. A deficiency in FXIII manifests as a severe bleeding diathesis emphasising its crucial role in this pathway. The FXIII-A gene (F13A1) is expressed in cells of bone marrow and mesenchymal lineage. The cellular form, a homodimer of the A subunits denoted FXIII-A, was perceived to remain intracellular, due to the lack of a classical signal peptide for its release. It is now apparent that FXIII-A can be externalised from cells, by an as yet unknown mechanism. Thus, three pools of FXIII-A exist within the circulation: plasma where it circulates in complex with the inhibitory FXIII-B subunits, and the cellular form encased within platelets and monocytes/macrophages. The abundance of this transglutaminase in different forms and locations in the vasculature reflect the complex and crucial roles of this enzyme in physiological processes. Herein, we examine the significance of these pools of FXIII-A in different settings and the evidence to date to support their function in haemostasis and wound healing.
Effects of Low Dose Space Radiation Exposures on the Splenic Metabolome
Authors: Laiakis Evagelia C. , Shuryak Igor , Deziel Annabella , Wang Yi-Wen , Barnette Brooke L. , Yu Yongjia , Ullrich Robert L. , Fornace Albert J. , Emmett Mark R.
Published: March 2021

Future space missions will include a return to the Moon and long duration deep space roundtrip missions to Mars. Leaving the protection that Low Earth Orbit provides will unavoidably expose astronauts to higher cumulative doses of space radiation, in addition to other stressors, e.g., microgravity. Immune regulation is known to be impacted by both radiation and spaceflight and it remains to be seen whether prolonged effects that will be encountered in deep space can have an adverse impact on health. In this study, we investigated the effects in the overall metabolism of three different low dose radiation exposures (γ-rays, 16O, and 56Fe) in spleens from male C57BL/6 mice at 1, 2, and 4 months after exposure. Forty metabolites were identified with significant enrichment in purine metabolism, tricarboxylic acid cycle, fatty acids, acylcarnitines, and amino acids. Early perturbations were more prominent in the γ irradiated samples, while later responses shifted towards more prominent responses in groups with high energy particle irradiations. Regression analysis showed a positive correlation of the abundance of identified fatty acids with time and a negative association with γ-rays, while the degradation pathway of purines was positively associated with time. Taken together, there is a strong suggestion of mitochondrial implication and the possibility of long-term effects on DNA repair and nucleotide pools following radiation exposure.
Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl
Authors: Lorke Dietrich E. , Nurulain Syed M. , Hasan Mohamed Y. , Kuča Kamil , Petroianu Georg A.
Published: March 2021

Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD01, are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly (p ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use.
Expression and Localization of Thrombospondins, Plastin 3, and STIM1 in Different Cartilage Compartments of the Osteoarthritic Varus Knee
Authors: Mählich Daniela , Glasmacher Anne , Müller Ilka , Oppermann Johannes , Grevenstein David , Eysel Peer , Heilig Juliane , Wirth Brunhilde , Zaucke Frank , Niehoff Anja
Published: March 2021

Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca2+-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.
Adenosine Receptor Agonist HE-NECA Enhances Antithrombotic Activities of Cangrelor and Prasugrel in vivo by Decreasing of Fibrinogen Density in Thrombus
Authors: Polak Dawid , Talar Marcin , Wolska Nina , Wojkowska Dagmara W. , Karolczak Kamil , Kramkowski Karol , Bonda Tomasz A. , Watala Cezary , Przygodzki Tomasz
Published: March 2021

Blood platelets’ adenosine receptors (AR) are considered to be a new target for the anti-platelet therapy. This idea is based on in vitro studies which show that signaling mediated by these receptors leads to a decreased platelet response to activating stimuli. In vivo evidence for the antithrombotic activity of AR agonists published to date were limited, however, to the usage of relatively high doses given in bolus. The present study was aimed at verifying if these substances used in lower doses in combination with inhibitors of P2Y12 could serve as components of dual anti-platelet therapy. We have found that a selective A2A agonist 2-hexynyl-5’-N-ethylcarboxamidoadenosine (HE-NECA) improved the anti-thrombotic properties of either cangrelor or prasugrel in the model of ferric chloride-induced experimental thrombosis in mice. Importantly, HE-NECA was effective not only when applied in bolus as other AR agonists in the up-to-date published studies, but also when given chronically. In vitro thrombus formation under flow conditions revealed that HE-NECA enhanced the ability of P2Y12 inhibitors to decrease fibrinogen content in thrombi, possibly resulting in their lower stability. Adenosine receptor agonists possess a certain hypotensive effect and an ability to increase the blood–brain barrier permeability. Therefore, the effects of anti-thrombotic doses of HE-NECA on blood pressure and the blood–brain barrier permeability in mice were tested. HE-NECA applied in bolus caused a significant hypotension in mice, but the effect was much lower when the substance was given in doses corresponding to that obtained by chronic administration. At the same time, no significant effect of HE-NECA was observed on the blood–brain barrier. We conclude that chronic administration of the A2A agonist can be considered a potential component of a dual antithrombotic therapy. However, due to the hypotensive effect of the substances, dosage and administration must be elaborated to minimize the side-effects. The total number of animals used in the experiments was 146.
The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation
Authors: Rosik Jakub , Szostak Bartosz , Machaj Filip , Pawlik Andrzej
Published: March 2021

HLA matching, transplantation technique, or underlying disease greatly influences the probability of long-term transplantation success. It has been hypothesised that genetic variation affecting antigen presentation also contributes to the outcomes of both solid organ transplantation and allogeneic haematopoietic stem cell transplantation (AHSCT). Those genes, along with those responsible for innate and adaptive immunity, have become targets of investigation. In this review, we focus on the role of CTLA4 in the process of acute graft rejection and summarise the progress in our understanding of its role in predicting the outcome. We present the results of the latest studies investigating the link between CTLA4 gene variability and AHSCT, as well as organ transplantation outcomes. While some studies found a link between +49 A/G and −318 C/T and transplantation outcomes, comprehensive meta-analyses have failed to present any association. The most recent field reviews suggest that the −1772 T/C (rs733618) CC genotype is weakly associated with a lower risk of acute graft rejection, while +49 A/G might be clinically meaningful when investigated in the context of combinations with other polymorphisms. Studies verifying associations between 12 CTLA4 gene SNPs and AHSCT outcomes present inexplicit results. Some of the most commonly studied polymorphisms in this context include +49 A/G (rs231775) and CT60 A/G (rs3087243). The results signify that, in order to understand the role of CTLA4 and its gene polymorphisms in transplantology, further studies must be conducted.
Dopant-Dependent Toxicity of CeO2 Nanoparticles Is Associated with Dynamic Changes in H3K4me3 and H3K27me3 and Transcriptional Activation of NRF2 Gene in HaCaT Human Keratinocytes
Authors: Choi Jang Hyun , Lee Haram , Lee Hangil , Lee Hansol
Published: March 2021

Despite advances in the preparation of metal oxide (MO) nanoparticles (NPs) as catalysts for various applications, concerns about the biosafety of these particles remain. In this study, we prepared transition metal-doped cerium oxide (TM@CeO2; TM = Cr, Mn, Fe, Co, or Ni) nanoparticles and investigated the mechanism underlying dopant-dependent toxicity in HaCaT human keratinocytes. We show that doping with Cr or Co but not Fe, Mn, or Ni increased the toxicity of CeO2 NPs in dose- and time-dependent manners and led to apoptotic cell death. Interestingly, while both undoped and transition metal-doped NPs increased intracellular reactive oxygen species (ROS), toxic Cr@CeO2 and Co@CeO2 NPs failed to induce the expression of NRF2 (nuclear factor erythroid 2-related factor 2) as well as its downstream target genes involved in the antioxidant defense system. Moreover, activation of NRF2 transcription was correlated with dynamic changes in H3K4me3 and H3K27me3 at the promoter of NRF2, which was not observed in cells exposed to Cr@CeO2 NPs. Furthermore, exposure to relatively non-toxic Fe@CeO2 NPs, but not the toxic Cr@CeO2 NPs, resulted in increased binding of MLL1 complex, a major histone lysine methylase mediating trimethylation of histone H3 lysine 4, at the NRF2 promoter. Taken together, our findings strongly suggest that failure of cells to respond to oxidative stress is critical for dopant-dependent toxicity of CeO2 NPs and emphasize that careful evaluation of newly developed NPs should be preceded before industrial or biomedical applications.
Medical Versus Surgical Treatment for the Management of Diabetic Foot Osteomyelitis: A Systematic Review
Authors: Tardáguila-García Aroa , Sanz-Corbalán Irene , García-Alamino Josep M. , Ahluwalia Raju , Uccioli Luigi , Lázaro-Martínez José Luis
Published: March 2021

A systematic review and quality assessment was performed to assess the management of diabetic foot osteomyelitis by medical or surgical treatment. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was used. All selected studies were evaluated using the Cochrane Risk of Bias Tool to assess the risk of bias for randomized controlled trials. The literature was revised using PubMed (Medline) and Embase (Elsevier) up to September 2020 to identify clinical trials assessing medical or surgical treatment to manage diabetic foot osteomyelitis. A total of six clinical trials that met our inclusion criteria, with a total of 308 participants. Healing rate, complete closure of the wound, and type of complications were the outcomes evaluated. Risk of bias assessment showed that only two of the six clinical trials included in the systematic review had a low risk of bias. Based on our findings, we believe that the management of diabetic foot osteomyelitis remains challenging. There are few high-quality clinical trials that both stratify clinical presentations and compare these treatments. We conclude that the available evidence is insufficient to identify the best option to cure diabetic foot osteomyelitis.
Clinical Evidence behind Stereotactic Radiotherapy for the Treatment of Ventricular Tachycardia (STAR)—A Comprehensive Review
Authors: Miszczyk Marcin , Jadczyk Tomasz , Gołba Krzysztof , Wojakowski Wojciech , Wita Krystian , Bednarek Jacek , Blamek Sławomir
Published: March 2021

The electrophysiology-guided noninvasive cardiac radioablation, also known as STAR (stereotactic arrhythmia radioablation) is an emerging treatment method for persistent ventricular tachycardia. Since its first application in 2012 in Stanford Cancer Institute, and a year later in University Hospital Ostrava, Czech Republic, the authors from all around the world have published case reports and case series, and several prospective trials were established. In this article, we would like to discuss the available clinical evidence, analyze the potentially clinically relevant differences in methodology, and address some of the unique challenges that come with this treatment method.
Update on TDM (Therapeutic Drug Monitoring) with Ustekinumab, Vedolizumab and Tofacitinib in Inflammatory Bowel Disease
Authors: Restellini Sophie , Afif Waqqas
Published: March 2021

The goal of therapeutic drug monitoring (TDM) is to optimize anti-TNF (tumor necrosis factor) biologic treatment in patients with inflammatory bowel disease (IBD). Although commercial assays are readily available for both ustekinumab and vedolizumab, the use of TDM with these newer biologic medications is at its infancy. The clinical utility of TDM with non-anti-TNF mechanisms of action is not clear. This review summarizes the latest available data on the pharmacokinetics of newer biologic and oral small molecules and highlights the threshold concentrations that have been associated with improved outcomes in IBD patients.
Comparing Intensive Trauma-Focused Treatment Outcome on PTSD Symptom Severity in Older and Younger Adults
Authors: Gielkens Ellen M. J. , de Jongh Ad , Sobczak Sjacko , Rossi Gina , van Minnen Agnes , Voorendonk Eline M. , Rozendaal Linda , van Alphen Sebastiaan P. J.
Published: March 2021

Objective: To examine the treatment outcome of an intensive trauma-focused treatment program for post-traumatic stress disorder (PTSD) in older and younger adults. Methods: A non-randomized outcome study was conducted with 62 consecutively admitted older PTSD patients (60–78 years) and 62 younger PTSD patients (19–58 years), matched on gender and availability of follow-up data. Patients participated in an intensive eight-day trauma-focused treatment program consisting of eye movement desensitization and reprocessing (EMDR), prolonged exposure (PE), physical activity, and group psycho-education. PTSD symptom severity (Clinician-Administered PTSD Scale-5 (CAPS-5)) was assessed, at pre- and post-treatment, and for a subsample (n = 31 older; n = 31 younger patients) at six-month follow-up. Results: A repeated-measures ANCOVA (centered CAPS pre-treatment score as covariate) indicated a significant decrease in CAPS-5-scores from pre- to post-treatment for the total sample (partial η2 = 0.808). The treatment outcome was not significantly different across age groups (partial η2 = 0.002). There were no significant differences in treatment response across age groups for the follow-up subsample (pre- to post-treatment partial η2 < 0.001; post-treatment to follow-up partial η2 = 0.006), and the large decrease in CAPS-5 scores from pre- to post-treatment (partial η2 = 0.76) was maintained at follow-up (partial η2 = 0.003). Conclusion: The results suggest that intensive trauma-focused treatment is applicable for older adults with PTSD with a large within-effect size comparable to younger participants. Further research on age-related features is needed to examine whether these results can be replicated in the oldest-old (>80).
Cyber-Physical Production Systems (CPPS): Introduction
Authors: Thiede Sebastian
Published: March 2021

Digitalization is a major change driver in manufacturing and is nowadays typically linked to terms like Industry 4 [...]
Visible Fidelity Collector of a Zooplankton Sample from the Near-Bottom of the Deep Sea
Authors: Xiao Jing , Chen Jiawang , Tian Zhenwei , Zhu Hai , Wang Chunsheng , Yang Junyi , Sheng Qinghua , Zhang Dahai , Fang Jiasong
Published: March 2021

The multi-net visible fidelity zooplankton collector is designed to obtain near-bottom fidelity zooplankton. The collector is sent to the designated sampling location based on the information provided by the camera and altimeter. The host computer sends instructions to control the opening of the net port for sample collection and closing of the sampling cylinder cover after sampling. The collector contains three trawls so that three samples can be collected for each test, and environmental parameters can be collected simultaneously. After sampling, The sample maintains its fidelity, that is, maintaining the temperature and pressure of the seabed sample after sampling. Two experiments were carried out in the Western Pacific, and six bottles of zooplankton samples were successfully obtained. The development of a multi-net visible zooplankton collector is of great significance for the collection of near-bottom zooplankton.
Numerical Simulation of a Multi-Body System Mimicking Coupled Active and Passive Movements of Fish Swimming
Authors: Hu Jianxin , Xiao Qing , Li Ruoxin
Published: March 2021

A multi-body system model is proposed for the mimicking of swimming fish with coupled active and passive movements. The relevant algorithms of the kinematics and dynamics of the multi-body system and coupled fluid solver are developed and fully validated. A simplified three-body model is applied for the investigation of the hydrodynamic performance of both an active pitch motion and passive movement. In general, there is an optimal stiffness, under which the model swims with the fastest velocity. The effect of the damper can be drawn only when the stiffness is small. Comparing with the rigid tail, the flexible tail leads to a faster speed when the stiffness and damping coefficients are in a suitable range.
Holmium-Containing Bioactive Glasses Dispersed in Poloxamer 407 Hydrogel as a Theragenerative Composite for Bone Cancer Treatment
Authors: Zambanini Telma , Borges Roger , de Souza Ana C. S. , Justo Giselle Z. , Machado Joel , de Araujo Daniele R. , Marchi Juliana
Published: March 2021

Holmium-containing bioactive glasses can be applied in bone cancer treatment because the holmium content can be neutron activated, having suitable properties for brachytherapy applications, while the bioactive glass matrix can regenerate the bone alterations induced by the tumor. To facilitate the application of these glasses in clinical practice, we proposed a composite based on Poloxamer 407 thermoresponsive hydrogel, with suitable properties for applications as injectable systems. Therefore, in this work, we evaluated the influence of holmium-containing glass particles on the properties of Poloxamer 407 hydrogel (20 w/w.%), including self-assembly ability and biological properties. 58S bioactive glasses (58SiO2-33CaO-9P2O5) containing different Ho2O3 amounts (1.25, 2.5, 3.75, and 5 wt.%) were incorporated into the hydrogel. The formulations were characterized by scanning electron microscopy, differential scanning calorimetry, rheological tests, and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT cell viability against pre-osteoblastic and osteosarcoma cells. The results evidenced that neither the glass particles dispersed in the hydrogel nor the holmium content in the glasses significantly influenced the hydrogel self-assembly ability (Tmic ~13.8 °C and Tgel ~20 °C). Although, the glass particles considerably diminished the hydrogel viscosity in one order of magnitude at body temperature (37 °C). The cytotoxicity results evidenced that the formulations selectively favored pre-osteoblastic cell proliferation and osteosarcoma cell death. In conclusion, the formulation containing glass with the highest fraction of holmium content (5 wt.%) had the best biological results outcomes aiming its application as theragenerative materials for bone cancer treatment.
Control of Dynamics in Weak PMA Magnets
Authors: Álvarez-Prado Luis M.
Published: March 2021

We have recently shown that a hybrid magnetic thin film with orthogonal anisotropies presenting weak stripe domains can achieve a high degree of controllability of its ferromagnetic resonance. This work explores the origin of the reconfigurability through micromagnetic simulations. The static domain structures which control the thin film resonance can be found under a deterministic applied field protocol. In contrast to similar systems reported, our effect can be obtained under low magnetic fields. We have also found through simulations that the spin wave propagation in the hybrid is nonreciprocal: two adjacent regions emit antiparallel spin waves along the stripe domains. Both properties convert the hybrid in a candidate for future magnonic devices at the nanoscale.
Expression and Characterization of a Cold-Adapted Alginate Lyase with Exo/Endo-Type Activity from a Novel Marine Bacterium Alteromonas portus HB161718T
Authors: Huang Huiqin , Li Shuang , Bao Shixiang , Mo Kunlian , Sun Dongmei , Hu Yonghua
Published: March 2021

The alginate lyases have unique advantages in the preparation of alginate oligosaccharides and processing of brown algae. Herein, a gene alg2951 encoding a PL7 family alginate lyase with exo/endo-type activity was cloned from a novel marine bacterium Alteromonas portus HB161718T and then expressed in Escherichia coli. The recombinant Alg2951 in the culture supernatant reached the activity of 63.6 U/mL, with a molecular weight of approximate 60 kDa. Alg2951 exhibited the maximum activity at 25 °C and pH 8.0, was relatively stable at temperatures lower than 30 °C, and showed a special preference to poly-guluronic acid (polyG) as well. Both NaCl and KCl had the most promotion effect on the enzyme activity of Alg2951 at 0.2 M, increasing by 21.6 and 19.1 times, respectively. The TCL (Thin Layer Chromatography) and ESI-MS (Electrospray Ionization Mass Spectrometry) analyses suggested that Alg2951 could catalyze the hydrolysis of sodium alginate to produce monosaccharides and trisaccharides. Furthermore, the enzymatic hydrolysates displayed good antioxidant activity by assays of the scavenging abilities towards radicals (hydroxyl and ABTS+) and the reducing power. Due to its cold-adapted and dual exo/endo-type properties, Alg2951 can be a potential enzymatic tool for industrial production.
The Inhibition Effect of the Seaweed Polyphenol, 7-Phloro-Eckol from Ecklonia Cava on Alcohol-Induced Oxidative Stress in HepG2/CYP2E1 Cells
Authors: Lin Liyuan , Yang Shengtao , Xiao Zhenbang , Hong Pengzhi , Sun Shengli , Zhou Chunxia , Qian Zhong-Ji
Published: March 2021

The liver is vulnerable to oxidative stress-induced damage, which leads to many diseases, including alcoholic liver disease (ALD). Liver disease endanger people’s health, and the incidence of ALD is increasing; therefore, prevention is very important. 7-phloro-eckol (7PE) is a seaweed polyphenol, which was isolated from Ecklonia cava in a previous study. In this study, the antioxidative stress effect of 7PE on HepG2/CYP2E1 cells was evaluated by alcohol-induced cytotoxicity, DNA damage, and expression of related inflammation and apoptosis proteins. The results showed that 7PE caused alcohol-induced cytotoxicity to abate, reduced the amount of reactive oxygen species (ROS) and nitric oxide (NO), and effectively inhibited DNA damage in HepG2/CYP2E1 cells. Additionally, the expression levels of glutathione (GSH), superoxide dismutase (SOD), B cell lymphoma 2 (Bcl-2), and Akt increased, while γ-glutamyltransferase (GGT), Bcl-2 related x (Bax), cleaved caspase-3, cleaved caspase-9, nuclear factor-κB (NF-κB), and JNK decreased. Finally, molecular docking proved that 7PE could bind to BCL-2 and GSH protein. These results indicate that 7PE can alleviate the alcohol-induced oxidative stress injury of HepG2 cells and that 7PE may have a potential application prospect in the future development of antioxidants.
The Important Role of the Radiologist in Determining the Indications for the Surgical Treatment of Neuroblastoma with Vascular Image-Defined Risk Factors: A Case Report
Authors: Sosnowska-Sienkiewicz Patrycja , Mańkowski Przemysław , Wojas Anna , Jończyk-Potoczna Katarzyna , Januszkiewicz-Lewandowska Danuta
Published: March 2021

The International Neuroblastoma Risk Group Staging System (INRGSS) is based on the age of patients and preoperative imaging, with attention paid to whether the primary tumor is affected by one or more of specific image-defined risk factors (IDRFs). This publication presents a 2.5-year-old boy with neuroblastoma who had an accidental ligation of the celiac trunk during tumor resection. The consequences of this complication were pancreatic and spleen ischemia and necrosis, ischemia, and perforation of the common bile duct, gallbladder, stomach, and duodenum. The aim of this publication was to highlight the great role of the radiologist in determining the indications for neuroblastoma tumor removal, especially with current vascular IDRFs, and to show how the radiologist’s insightful approach can save the patient from irreversible complications.
The Process Design and Rapid Superplastic Forming of Industrial AA5083 for a Fender with a Negative Angle in a Small Batch
Authors: Du Zhihao , Wang Guofeng , Wang Hailun
Published: March 2021

A front automobile fender with a negative angle was trial produced via rapid superplastic forming (SPF) technology. The tensile test of industrial AA5083 was carried out at elevated temperatures, and the results showed that the maximum elongation was 242% at 480 °C/0.001 s−1. A rigid-plastic constitutive model of the SPF process was established. Initial dies of preforming and final forming were designed. The finite element method (FEM) was used to simulate the forming process and predict the thickness distribution of different areas. Furthermore, the dies were optimized to make the thickness distribution uniform. In the final structure, the maximum thinning ratio decreased from 83.2% to 63% due to the optimized design of the forming dies. The front automobile fender was then successfully fabricated by the preforming process and final forming process at 480 °C. A thickness measurement was carried out, and the minimum thickness of the preforming structure was 2.17 mm at the transverse tank, while that of the final structure was 2.49 mm near the edge of the lamp orifice. The average grain size grew from 20 to 35 μm. The grain growth led to the reduction of mechanical properties. Compared with the mechanical properties of the initial material, the maximum decrease in tensile strength for the material after superplastic forming was 5.78%, and that of elongation was 18.5%.
Microbiological Sulfide Removal—From Microorganism Isolation to Treatment of Industrial Effluent
Authors: Yang Zhendong , Liu Zhenghua , Sklodowska Aleksandra , Musialowski Marcin , Bajda Tomasz , Yin Huaqun , Drewniak Lukasz
Published: March 2021

Management of excessive aqueous sulfide is one of the most significant challenges of treating effluent after biological sulfate reduction for metal recovery from hydrometallurgical leachate. The main objective of this study was to characterize and verify the effectiveness of a sulfide-oxidizing bacterial (SOB) consortium isolated from post-mining wastes for sulfide removal from industrial leachate through elemental sulfur production. The isolated SOB has a complete sulfur-oxidizing metabolic system encoded by sox genes and is dominated by the Arcobacter genus. XRD analysis confirmed the presence of elemental sulfur in the collected sediment during cultivation of the SOB in synthetic medium under controlled physicochemical conditions. The growth yield after three days of cultivation reached ~2.34 gprotein/molsulfid, while approximately 84% of sulfide was transformed into elemental sulfur after 5 days of incubation. Verification of isolated SOB on the industrial effluent confirmed that it can be used for effective sulfide concentration reduction (~100% reduced from the initial 75.3 mg/L), but for complete leachate treatment (acceptable for discharged limits), bioaugmentation with other bacteria is required to ensure adequate reduction of chemical oxygen demand (COD).
Rapid Testing and Interventions to Control Legionella Proliferation following a Legionnaires’ Disease Outbreak Associated with Cooling Towers
Authors: Young Charlotte , Smith Duncan , Wafer Tim , Crook Brian
Published: March 2021

Most literature to date on the use of rapid Legionella tests have compared different sampling and analytical techniques, with few studies on real-world experiences using such methods. Rapid tests offer a significantly shorter feedback loop on the effectiveness of the controls. This study involved a complex of five factories, three of which had a history of Legionella contamination in their cooling water distribution system. Multiple sampling locations were utilised to take monthly water samples over 39 months to analyse for Legionella by both culture and quantitative polymerase chain reaction (qPCR). Routine monitoring gave no positive Legionella results by culture (n = 330); however, samples were frequently (68%) positive by qPCR for Legionella spp. (n = 1564). Legionella spp. qPCR assay was thus found to be a good indicator of cooling tower system health and suitable as a routine monitoring tool. An in-house qPCR limit of 5000 genomic units (GU)/L Legionella spp. was established to trigger investigation and remedial action. This approach facilitated swift remedial action to prevent Legionella proliferation to levels that may represent a public health risk. Cooling tower operators may have to set their own action levels for their own systems; however, in this study, 5000 GU/L was deemed appropriate and pragmatic.