bluuebunny/crossref_metadata_2025 huggingface dataset:
Valproic Acid Accelerates Bone Repair via Activating Notch Signaling Pathway in Ovariectomized Rats
Authors: Tao Zhoushan , Li Tian-Lin , Xu Hong-Guang , Yang Min
Published: July 2021

The purpose was to observe whether Valproic acid (VPA) has a positive effect on bone defect repair via activating Notch signaling pathway in an OVX rat model. The MC3T3-E1 cells were co-cultured with VPA and induced to osteogenesis, and the osteogenic activity was observed by Alkaline phosphatase (ALP) staining, Alizarin Red(RES) staining and Western blotting(WB). Then the hydrogel containing VPA was implanted into the femoral epiphysis bone defect model of ovariectomized(OVX) rats for 12 weeks. Micro-CT, Biomechanical testing, histology, Immunofluorescence, RT-qPCR, WB analysis were used to observe the therapeutic effect and explore the possible mechanism. ALP and ARS staining and WB results show that the cell mineralization, osteogenic activity and protein expression of ALP, OPN, RUNX-2, OC, Notch 1, HES1, HEY1, JAG1 of VPA group is significantly higher than the Control group. Micro-CT, Biomechanical testing, histology, Immunofluorescence and RT-qPCR evaluation show that, group VPA presented the stronger effect on bone strength, bone regeneration, bone mineralization, higher expression of VEGFA, BMP-2, ALP, OPN, RUNX-2, OC, Notch 1, HES1, HEY1, JAG1 of VPA when compared with OVX group. Our current study demonstrated that local treatment with VPA could stimulate repair of femoral condyle defects, and these effects may be achieved by activating Notch signaling pathway and acceleration blood vessel and bone formation.
Contribution of Genetic and Environmental Risk Factors in a Juvenile Idiopathic Arthritis Large Family With SERPINA1 Gene Mutations
Authors: Popescu Cyprian
Published: July 2021

Objectives

Although the underlying mechanisms and mediators of arthritis in juvenile idiopathic arthritis (JIA) are not well understood, accumulated evidence supports the mixt role of genetic and environmental factors. Few reports of multiplex families with JIA were published until now. The aim of this study was to identify new genetic or environmental associations concerning the patients of a kindred with juvenile idiopathic arthritis and psoriatic features (JIAPs).
Methods

Here, we characterized an extended multiplex family of 5 patients with juvenile idiopathic arthritis and psoriatic features (PsA) at the clinical and genetic level, using whole exome sequencing.
Results

We did not confirm in our family the linkage with the genetic factors already described that might be associated with increase susceptibility to JIA. We found a carrier status of siblings who inherited a pathogenic allele of the SERPINA1 gene from their mother who herself has two heterozygous pathogenic variants in the SERPINA1 gene.
Conclusions

Our data showed that JIA results from pleiotropic effects of environmental background with an only minor monogenic contribution. Even that a monogenetic factor could not be proved, some genetic factor as SERPINA1 mutations which can sensitize for psoriatic arthritis development seems to be involved. Further investigation must be done to prove whether SERPINA1 mutations may have a potential JIA causality.
Pharmaceutical R&D Portfolio Optimization with Minimum Borrowed Capital Based on Fuzzy Set Theory
Authors: Zhang Ming-Yu , Liu Yong-Jun
Published: July 2021

Due to long lead times, uncertain outcomes and lack of enough historical data, pharmaceutical research and development (R$\&$D) portfolio selection is a often very complex decision issue.

The aim of this paper is to investigate pharmaceutical R$\&$D portfolio selection with unavailable and unreliable project information, where the borrowed capital is allowed.

Based on fuzzy set theory, we propose two pharmaceutical R$\&$D portfolio optimization models with minimum borrowed capital by taking into account corporate strategy in developing new products, scarcity of resources, lack of investment budget and cardinality constraint. In the two proposed models, the pharmaceutical R$\&$D company is assumed to achieve the objectives of maximizing terminal wealth and minimizing the cumulative borrowed capital over the whole investment horizon.

Then, we transform the two proposed bi-objective models into the corresponding single-objective models by using the weighted sum approach and employ the modified artificial bee colony (ABC) algorithm to solve the transformed models. Finally, we provide a numerical example to illustrate the application of the proposed models.
Synthesis of the SWCNTS/TiO2 Nanostructure and Its Effect on the Thermal, Optical, and Conductivity Properties of the CMC/PEO as Application of Low Energy Density Devices
Authors: alsulami qana A. , Rajeh A. .
Published: July 2021

The TiO2 NPs synthesized by sol-gel method and the SWCNTs/TiO2 nanostructure fabricated by a simple mixing technique. By a solution casting process, pure CMC/PEO and SWCNTs/TiO2 nanohybrid doped CMC/PEO polymer blend films are prepared. It discussed the influence of polymer blend and MWCNTs/TiO2 nanohybrid loading on the properties of physical of the polymer blend. The XRD pattern shows that the average crystallite size of the nanoparticles for TiO2 and SWCNTs/TiO2 is 20 nm and 15 nm, respectively, and an increase in amorphicity was observed with an increase in doping. The interaction of CMC/PEO chains and SWCNTs/TiO2 nanohybrid is confirmed by FTIR spectra. The optical absorption spectrum shows that the energy gap reduces with the dopant increase. The miscibility between the CMC and PEO is demonstrated by DSC thermograms. An Enhancement in the thermal stability of the prepared samples with an increase in content of dopant is seen in the TGA analysis. The maximum value of the blend's AC conductivity is 4.77 10-5 S/m, and by increasing the loading of SWCNTs/TiO2 to 4.8 (wt.%) increased to 8.07 10-4 S/m. The conduction mechanism changed with SWCNTs/TiO2 loading from the correlated barrier hopping, in the blend, to the large Polaron tunneling. Usage of these nanocomposite films in the semiconductor industry is encouraged by the observed improvements in optical, thermal, and AC conductivity.
Family factors related to executive functioning in children with ADHD: a systematic review protocol
Authors: Reder Martyna , Lipowska Małgorzata , Izydorczyk Bernadetta , Sitnik-Warchulska Katarzyna
Published: July 2021

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder diagnosed among children and adolescents. The axial symptom is a deficit in cognitive functioning, including executive functioning. Some studies have shown that the quality of executive functioning in children and adolescents with ADHD is modified by some characteristics of the family environment.MethodsThe authors plan to conduct a systematic review in accordance with the PRISMA guidelines. Searches will be carried out in electronic databases (PsycINFO, PsycARTICLES, and PubMed) and in the bibliography of identified publications. Relevant studies will be selected by using keywords and taking into account the inclusion and exclusion criteria. The analysis will be performed using a specially design data spreadsheet. These activities will be carried out under appropriate methodological rigor to minimize the risk of bias.DiscussionConducting a systematic review will provide an opportunity to describe the current research on the topic. This action will allow us to summarize the knowledge from the published results. Possible gaps will be identified, and future directions for research projects in this field will be proposed.Systematic review registrationPROSPERO CRD42021246496
Softmax Function Based Neutrosophic Aggregation Operators and Application in Multi-Attribute Decision Making Problem
Authors: Garai Totan , Dalapati Shyamal , Smarandache Florentin
Published: July 2021

Softmax function is a well-known generalization of the logistic function. It has been extensively used in various probabilistic classification methods such as softmax regression, linear discriminant analysis, naive bayes classifiers, and artificial neural networks. Inspired by the advantages of softmax function, we focused on this paper is to develop the softmax function based single valued neutrosophic aggregation operators. Then we have established some essential properties of aggregation operators based on softmax function with neutrosophic set. Additionally, we have defined a multi-attribute decision making method based on the proposed aggregation operators. Using this MADM method we exercised a realistic MADM problem with neutrosophic informations. Finally, we checked the validity and reliability of the proposed methods considering by one numerical illustration.
Dietary Approach to Stop Hypertension and Obesity Among Iranian Adults: Yazd Health Study-TAMYZ and Shahedieh Cohort
Authors: Sarkhosh-Khorasani Sahar , Mozaffari-Khosravi Hassan , Mirzaei Masoud , Nadjarzadeh Azadeh , Hosseinzadeh Mahdieh
Published: July 2021

PurposeEstablished data revealed a relationship between obesity and increasing the risk of mortality and morbidity of chronic diseases. There are conflicting data regarding the association between adherence of Dietary Approach to Stop Hypertension (DASH) and obesity. Therefore, this study intends to investigate this relationship among a large sample of Iranian adults.MethodsThis cross-sectional study was performed by 10693 individuals; in the urban population: Yazd Health Study (n=6750), and in the suburb region: Shahedieh cohort study (n=3943). Dietary intake was evaluated by using a validated Food Frequency Questionnaire (FFQ). In all participants, anthropometric indices including body mass index were measured. The DASH score was considered utilizing gender-specific quintiles of DASH items. To evaluate the relationship of DASH diet and obesity, multivariate logistic regression analysis was used.ResultsBy adjusting confounders, participants in highest quintiles of DASH diet compared to the lowest have lower odds of obesity in suburb area (OR: 0.78; 95% CI: 0.63, 0.96), in urban (OR: 0.71; 95% CI: 0.52, 0.99), and in whole population of both studies (OR: 0.75; 95% CI: 0.63, 0.90). Besides, more compliance of women to this diet in urban (OR: 0.64; 95% CI: 0.48, 0.85) and population of both studies (OR: 0.77; 95% CI: 0.62, 0.96) were associated with reduced odds of central obesity. ConclusionsDASH dietary pattern could decrease odds of obesity in both urban and suburb area, and central obesity in urban area only. Further prospective studies are needed for causal conclusion.
Biodegradation of P-Nitrophenol by Engineered Strain
Authors: Xu Jing , Wang Bo , Zhang Wen-Hui , Zhang Fu-Jian , Deng Yong-Dong , Wang Yu , Gao Jian-Jie , tian yongsheng , Peng Ri-He , Yao Quan-Hong
Published: July 2021

p-Nitrophenol (PNP) is an important environmental pollutant and can causes significant environmental and health risks. Compared with the traditional methods, biodegradation is a useful one to completely remove the harmful pollutants from the environment. Here, an engineered strain was first constructed by introducing PNP biodegradation pathway via the hydroquinone (HQ) pathway into Escherichia coli. In the engineered strain BL-PNP, PNP was completely degraded to β-ketoadipate and subsequently enter the metabolites of multiple anabolic pathways. The high tolerance and rapid degradation ability to PNP enable the engineered strain to have the potential to degrade toxic substances. The engineered strain created in this study can be used as a functional strain for bioremediation of PNP and potential toxic intermediates, and the method of assembling aromatic hydrocarbons metabolic pathway can be used to eradicate nitroaromatic pollutants in the environment.
Multivariate Analysis of Spider Diversity in Agricultural, Horticultural and Silvicultural Ecosystems and their Relation to Subtropical Climatic Conditions
Authors: Gogoi Jyotim , Ningthoujam Kennedy
Published: July 2021

Spiders are the Arthropod and belong to the Phylum: Arthropoda, Class: Arachnida, Order: Araneae. Spiders totally depend on predation of small insects and other animals and have important role in the structure of communities and food webs both as an individual numbers and as an energy consumer.. Hence, documentation of spiders gives information about biodiversity of ecosystem in a particular geographical area. Totally arthropods belonged to 14 orders and 85 Nos. of different families. To study the similarity between two groups in species, family and ordinal level is used Agglomerative Hierarchical Clustering (AHC). Principal Component Analysis (PCA) and Correspondence Analysis (CA) were evaluated to understand the arthropod population dynamics and habitat specific occurrence of spiders in different ecosystem Viz., Silvicultural, Horticultural and Agricultural ecosystem. To correlate the weather parameters with spider population we used Pearson correlation, regression line, Redundancy Analysis (RDA) and Canonical Coefficient Analysis (CCA). Correlation analysis showed arthropod population positively correlated to maximum and minimum temperature and evening relative humidity and negatively correlated to morning relative humidity and rainfall. The eigenvectors at generic level was found maximum in horticultural ecosystem (0.591) followed by silvicultural (0.581), maize (0.407), rice (0.329) and potato ecosystem (0.183) in factor (F1). The asymmetric CA row and column plot in generic level suggested that the genus Tylorida,, potato and horticultural ecosystems respectively. In case of weather perimeter with relation to arthropod population RDA showed that Arachnids families viz., Lycosidae, Thomisidae, Theridiidae, Tetraganthidae etc are closely associated with maximum temperature in silvicultural and horticultural ecosystems.
Effects of Room Temperature and Cold Storage on The Metabolic and Hemostatic Properties of Whole Blood for Acute Normovolemic Hemodilution
Authors: Ichikawa Junko , Kouta Masaki , Oogushi Masako , Komori Makiko
Published: July 2021

Background: Acute normovolemic hemodilution (ANH), as a blood-conservation technique, avoids the need for allogeneic blood transfusions. The historic practice of cold-storing type-O whole blood (WB) in military fields popularized the transfusion of refrigerated WB to treat acute bleeding in surgical/trauma patients. In this study, we compared the effects of room temperature (RT) and refrigeration up to 24 hours on the coagulation properties of WB for ANH.Methods: Each WB sample, collected from 12 male volunteers, in citrate-phosphate-dextrose adenine solution was divided into two parts, which were stored at RT (20-24℃) and refrigerated (1-6℃) for 24 hours, respectively.Complete blood counts (CBC), mean platelet volume, and blood gas and fibrinogen levels were measured, and rotational thromboelastometry (ROTEM) measurements, including aggregation response, were performed at the initial collection time point (baseline) and at 6, 12, and 24 hours after initial collection.Results: The preservation of platelet aggregation response induced by arachidonic acid and adenosine diphosphate was better in cold-stored WB compared to that in RT-stored WB, which significantly decreased after 12 hours of storage when compared with baseline. The platelet aggregation response induced by thrombin receptor-activating peptide 6 was significantly decreased in all samples after 24 hours of storage when compared with that at baseline. Although pH levels were within acceptable limits for all samples, the glycolytic metabolism of WB stored at RT was accelerated, leading to a significant increase in lactate levels after 6 hours of storage compared to that of cold-stored samples. There were no significant differences in CBC, coagulation profiles, mean platelet volume, and ROTEM variables between the cold-stored and RT-stored WB samples.Conclusions: WB for ANH stored in the refrigerator showed better metabolic characteristics after 6 hours of storage and better aggregation response after 12 hours of storage than WB stored at RT. Considering the safety of refrigerated products in terms of reducing bacterial growth, these data suggest that cold-stored WB may improve outcomes in patients with acute bleeding.
Foci Classification in Malaria Elimination Setting: A Conceptual Framework
Authors: Ranjbar Mansour
Published: July 2021

The concept of malaria elimination is becoming more and more important. Among countries with malaria transmission in 2015, eliminating malaria from 35 countries including those in the Great Mekong has been targeted by 2030. In the journey to elimination through the foci classification procedure, a limited number of “hotspots” among a large number of foci should be precisely defined to be covered by effective controlling measures. There is a common consensus that foci and case classification are fundamental principles of malaria elimination and prevention of reintroduction. However, there are numerous ambiguities and controversies in almost all aspects of foci classifications. These uncertainties result in misclassification that, in turn, wastes lives, time, and money thereby violating value for money principles. New progress in the literature such as ignoring “new potential” foci and using the class of “active foci” instead of the two classes of “new active” and “residual active” is in opposition to the philosophy of foci classification. In this paper, we seek to elaborate the controversies and ambiguities around the concept of foci classification and ultimately suggest some solutions. Some of the ways forward include: (a) foci classification should be done by parasite type; (b) a set of foci classes includes “cleared up”, “new potential”, “new active”, “residual active”, and “residual nonactive”; (c) The number and population of various foci classes should be regularly updated and monitored as the basis for measuring progress toward elimination and it can be considered as the basis for needs assessment and planning response; (d) The coverage and completeness of the controlling interventions by foci classes should be regularly monitored; and (e) The criteria for early detection of outbreaks should be defined. Furthermore, two applicable models for foci classification by parasite have been proposed.
SPC212 Human Mesothelioma Cell Underwent Apoptosis, Oxidative Stress, Morhological Deformation Following Astaxanthin Treatment
Authors: Kacar Sedat , Sevimli Tuğba S. , Sahinturk Varol
Published: July 2021

Although astaxanthin (ASX) is one type of carotenoid, it is a more bioactive compound than other carotenoids. Despite its utilization against different cancer types, the effect of ASX on mesothelioma has yet to be well-studied. In this study, our goal is to ascertain how ASX will affect SPC212 human mesothelioma cells. First, the effective doses of ASX against SPC212 cells were uncovered by the MTT test. Thereafter, with flow cytometry analysis, Annexin-V and caspase 3/7 assay were implemented for the evaluation of apoptotic cell death and an oxidative stress test was carried out to determine how the free radicals changed. Ultimately, the cells’ morphology was examined under a light microscope. The effective doses of ASX were found as 50,100 and 200 µM. In Annexin V assay, the total apoptosis increased to around 12%, 30%, and %45 with increasing doses of ASX. In the caspase 3/7 assay, the total apoptosis was around %25 and %38 at 100 and 200 µM. In oxidative stress analysis, ROS-positive cells rose from 4.54 at the lowest dose to 86.95 at the highest dose. In morphological analysis, cellular shrinkage, decrease in cell density, swelling and vacuolations in some cells, membrane blebbing and apoptotic bodies are observed in ASX-treated cells. To conclude, the current study provided insights into the efficacy and effects of ASX against SPC212 mesothelioma cells regarding morphology, proliferation and cell death for future studies.
The Effect of Different Concentration of Aqueous Extracts of Labisia pumila in Preventing Osteoporosis and Improvement of Dermal Elasticity in Polycystic Ovary Syndrome Rats
Authors: Zakaria Alif Aiman , Latip Mohd Qayyum Ab , Azizan Tengku Rinalfi Putra Tengku , Ahmad Hafandi , Mazlan Mazlina , Hassim Hasliza Abu , Noor Mohd Hezmee Mohd
Published: July 2021

Background: Labisia pumila (LP) a Malaysian herb thought to have phytoestrogenic effects in rats with PCOS. In this study we investigate the effects of LP aqueous extracts on bone composition, bone biomarkers and metabolic disorder in female rats fed continuously with high fat diet to induce PCOS. Hypothesis: The administration of Labisia pumila treatment in PCOS rats for 90 days will ameliorate the adverse effect of osteoporosis by reducing the inflammatory cytokine and improving the dermal elasticity of PCOS rats. Study design: On the 90th day of the development of PCOS model rats fed with high fat diet and after the vaginal smear analysis indicating a prolonged estrus cycle of more than 2 weeks, all PCOS rats were divided into 4 groups which consisted of control, placebo (water), LP25 (LP 25mg/kg) and LP50 (LP 50 mg/kg) respectively. All PCOS continue to received the formulated high fat diet and control animals continued to received normal chow and water ad libitum. Method: Vehicle and treatments, which were given orally by using stomach gavaging needle size 16 gauge straight and curve retrolingual administration. The rats were sacrificed at the end of the trial phase and organs, tissues and blood samples were harvested for multiple assays and analysis listed below.Results: The level of estradiol was significantly increased in LP25 and LP50 as compared with placebo. The inflammatory cytokine of C-reactive protein and TNF-ɑ were significantly decreased in LP25 and LP50.Conclusion: Treatment of LP extract might reduce the inflammatory cytokine related to the formation of osteoporosis and loss of bone mass, increase the insulin sensitivity and reduce of osteoporosis in PCOS patients. The phytoestrogenic of LP all of the above significant positive results are proven in lowering osteoporosis and metabolic disorder in PCOS rats.
Tumor Histology is an Independent Prognostic Factor in Locally Advanced Cervical Carcinoma. A Retrospective Study
Authors: Gallardo-Alvarado Lenny , León David Cantú-de , Ramirez-Morales Rebeca , Santiago-Concha Gabriel , Barquet-Muñoz Salim , Salcedo-Hernandez Rosa , Reyes Cinthya , Perez-Alvarez Sandra , Perez-Montiel Delia , Perez-Plasencia Carlos , Trejo-Duran Elizabeth , Galicia Juan Pablo , León David Cantú
Published: July 2021

Background: Even with different histologic origins, squamous cell carcinoma (SCC) and adenocarcinoma (AC) are considered a single entity, and the first-line treatment is the same. Locally advanced disease at the diagnosis of cervical cancer is the most important prognostic factor, the recurrence rate is high, making it necessary to evaluate prognostic factors other than clinical or radiological staging; histology could be one of them but continues to be controversial. The aim of this study was to evaluate tumor histology as a prognostic factor in terms of treatment outcomes, disease-free survival (DFS) and overall survival (OS) in a retrospective cohort of patients with Locally Advanced Cervical Carcinoma (LACC). Methods: The records of 1291patients with LACC were reviewed, all of them were treated with 45-50 Gy of external bean radiotherapy with concurrent chemotherapy and brachytherapy. A descriptive and comparative analysis was conducted. Treatment response was analyzed by the chi-square test; DFS and OS were calculated for each histology with the Kaplan-Meier method and compared with the log-rank test; and the Cox model was applied for the multivariate analysis. Results: We included 1291 patients with LACC treated from 2005 to 2014, of which 1154 (89·4%) had SCC and 137 (10·6%) had AC. Complete response to treatment was achieved in 933 (80·8%) patients with SCC and 113 (82·5%) patients with AC. Recurrence of the disease was reported in 29·9% of SCC patients and 31·9% of AC patients. Five-year DFS was 70% for SCC and 62·2% for AC. The five-year OS rates were 74·3% and 60% for SCC and AC, respectively. The mean DFS was 48·8 months for SCC vs 46·10 for AC (p=0·043), the mean OS was 50·8 for SCC and 47·0 for AC (p=0·002).Conclusion: Our findings support the hypothesis that SCC and AC are different clinical entities. Trial Registration: NCT04537273
Perimeter Confinements of Basic Health Zones and COVID-19 Incidence in Madrid, Spain
Authors: David García-García , Rafael Herranz-Hernandez , Ayelén Rojas-Benedicto , Inmaculada León-Gomez , Amparo Larrauri , Marina Peñuelas , Maria Guerrero-Vadillo , Rebeca Ramis , Diana Gomez-Barroso
Published: July 2021

Background: A unique policy of perimeter closures of Basic Health Zones (small administrative health units) was implemented in the Autonomous Region of Madrid from September 21st 2020 to May 23rd 2021 to face the COVID-19 pandemic.Aim: To assess the impact of local perimeter confinements on the 14-days cumulative incidence of SARS-CoV-2 during the second wave of the pandemic in Madrid, Spain.Methods: We compare the errors in estimation of two families of mathematical models: ones that include the perimeter closures as explanatory covariables and ones that do not, in search of a significant improvement in estimation of one family over the other. We incorporate leave-one-out cross-validation and the choice of the best over 15 models at each step in our analysis for statistical signification.Results: The two families of models provided very similar estimations (correlation of the errors > 0.95 (±10-3 95% CI), difference in means of the errors < 1.2 (±0.7 95% CI) 14-days cumulative incidence), both for a 2 weeks and 3 weeks delay in observed cumulative incidence and also when restricting the analysis to only those Basic Health Zones that were subject to at least one closure during the time under study.Conclusion: Our analysis suggests that the perimeter closures by Basic Health Zone did not have a significant effect on the epidemic curve in Madrid, either 2 or 3 weeks after their activation.
Evaluation of a Large-Scale School Wellness Intervention Through the Consolidated Framework for Implementation Research (CFIR): Implications for Dissemination and Sustainability
Authors: McLoughlin Gabriella M , Sweeney Rachel , Liechty Laura , Lee Joey A , Rosenkranz Richard R , Welk Gregory J
Published: July 2021

BackgroundThe need for sustainable and scalable comprehensive school wellness interventions is evident, and the lack of attention toward capacity-building models warrants investigation. Furthermore, there is a dearth of understanding regarding implementation determinants grounded in dissemination and implementation (D&I) frameworks. This study sought to address: 1) implementation determinants of adoption, fidelity, and penetration for school-wide wellness programming; and 2) nuanced determinants between schools with prior experience and those new to the program, to enhance tailored implementation support and sustainability.MethodsThe School Wellness Integration Targeting Child Health (SWITCH®) capacity-building intervention was adopted in 52 elementary and middle (22 new; 30 experienced) schools across Iowa, United States in the 2019–2020 academic year. Mixed methods data collection and analysis procedures followed the Consolidated Framework for Implementation Research (CFIR) protocols, adapted to school settings. Implementation outcomes included: 1) fidelity/compliance to established quality elements; 2) adoption of best practices in multiple settings; and 3) penetration of behavior change practices across classrooms and grade levels. Assessed determinants comprised organizational readiness/capacity and CFIR constructs via interviews and surveys. Interview data were scored using a systematic process; each CFIR domain was assigned a score (ranging between -2 and +2) to denote either a positive or negative influence on implementation. Independent t-tests were conducted to capture potential differences between new and experienced schools, followed by Pearson bivariate correlation analyses to determine relationships between CFIR determinants and implementation outcomes. ResultsExperienced schools reported insignificantly higher fidelity (t=-1.86 p=.07) and higher rates of adoption (t=-2.03 p=.04) compared to new schools. Correlation analyses revealed positive relationships between implementation outcomes and CFIR determinants including innovation source, culture and relative priority, and leadership engagement. Negative relationships were observed in tension for change and networks and communications. Specific negative relationships for new schools between determinants and outcomes included relative advantage, engaging key stakeholders, and reflecting/evaluating, among others. ConclusionsFindings highlight the specific relationships between implementation outcomes and determinants; nuanced challenges for new schools highlight the need for a more tailored approach to implementation support and offer insights for sustainability. Adapted CFIR protocols provide opportunities for replication in other school-and community-based projects.
Air Pollution and Outpatient Visits for Cardiovascular and Cerebrovascular Diseases: A Time-Series Analysis in Luoyang, China
Authors: Guo Hengliang , Wang Mengfei , Wei Haitao , Gong Xiyun , Yang Hong
Published: July 2021

Background: Previous studies have shown that air pollution has a great impact on cardiovascular and cerebrovascular diseases (CCD), but there is a lack of research on low and medium pollution areas. This study was the first time to explore the effects of air pollutants on the outpatient visits of CCD in Luoyang, which is located in low and medium pollution areas.Methods: In this study, the Generalized Additive Model (GAM) was used to establish a single pollutant model, a multi-pollutant model and stratified modes of age, sex and season to evaluate the effects of PM2.5, PM10, SO2, NO2, CO and O3 on the outpatient visits of CCD within a week.Results: The results of single pollutant model showed that PM2.5, PM10, SO2, NO2, CO and O3 all had significant effects on the outpatient visits of CCD with a lag effect, interquartile range (IQR) increased in their concentration, the outpatient visits with CCD increased by 2.8%(95%CI:1.7%-4.0%), 3.0%(95%CI:1.8%-4.1%), -4.2% (95%CI: -5.5%- -2.9%), 20.5%(95%CI:18.2%-22.7%), 10.4%(95%CI:8.8%-12.1%), 2.3%(95%CI:0.8%-3.9%). The multi-pollutant model showed that there may be complex interactions among pollutants. The results of stratified model showed that there was no significant difference in the effects of different pollutants on different genders and ages, and the results of seasonal stratification showed that PM2.5, PM10, SO2 and CO had a greater influence on the outpatient visits of CCD in spring and summer, while NO2 and O3 had a greater influence on the outpatient visits of CCD in autumn and winter.Conclusion: The results showed that air pollutants significantly affected the outpatient visits of CCD, among which NO2 had the greatest influence, and seasonal effects and the combined effects of various pollutants should be considered in the prevention of CCD.
A Novel Intelligent Manufacturing Mode With Human-cyber-physical Collaboration and Fusion in the Non-Ferrous Metal Industry
Authors: Liu Qing , Liu Min , Wang Zichun , Yan Feng , Ma Yingyi , Shen Weiming
Published: July 2021

The non-ferrous metal industry is one of the most important part in China’s process industry, and has an extremely important strategic position in national economy. However, in the smelting process of non-ferrous metal, there still exists many problems: 1) the production process of non-ferrous is long, the utilization rate of resource and energy is low; 2) the large amount of waste discharge in the production process has caused prominent environmental protection issue; 3) product homogeneity is serious and the added value is low. To solve these problems, we constructed a novel intelligent manufacturing mode with human-cyber-physical (HCP) collaboration and fusion from three aspects: 1) intelligent manufacturing system with HCP collaboration and fusion, 2) product service system based on ecosystem platform, and 3) sustainable business model, to realize the safe, efficient and green production for the non-ferrous metal smelting process. In the case study on the largest copper smelting enterprise in the world, the digital twin based manufacturing system collaborative platform architecture, product &service system framework, and sustainable business model canvas are built by the proposed intelligent manufacturing mode with HCP collaboration and fusion.
Effects of A Nurse-Led Transitional Burns Rehabilitation Programme (4Cs-TBuRP) For Adult Burn Survivors: Protocol for a Randomised Control Trial
Authors: BAYUO JONATHAN , Wong Frances Kam Yuet Yuet , Chung Loretta Yuet Foon
Published: July 2021

Background: Transitioning from the burn unit to the home/ community can be chaotic with limited professional support. Some adult burn survivors may face varied concerns leading to poor outcomes in the early post-discharge period with limited access to professional help. Based on these, a nurse-led transitional burns rehabilitation programme has been developed and the current trial aims to ascertain its effects as well as explore the implementation process. Methods: A single-centre, double-arm randomised controlled trial with a process evaluation phase will be utilised for this study. All adult burn survivors aged ≥18 years with burn size ≥10% total burn surface area at the site during the study period will be screened for eligibility at least 72hours to discharge. A sample size of 150 will be block randomised to treatment (receiving the nurse-led transitional care programme and routine post-discharge service) and control groups (receiving routine post-discharge service). The nurse-led transitional care programme comprises of predischarge and follow-up phases with the delivery of bundle of holistic interventions lasting for 8 weeks. There are three timelines for data collection: baseline, immediate post-intervention, 4 weeks post-intervention. Discussion: The findings from this study can potentially inform the development and organisation of post-discharge care and affirm the need for ongoing comprehensive home-based care for burn survivors and their families. Trial registration: ClinicalTrials.gov Trial Registry approved the prospective registration on 20 th August 2020. Registration details can be viewed on https://clinicaltrials.gov/ct2/show/record/NCT04517721 .
Long Non-Coding RNA NEAT1 Accelerates Lung Cancer Development Via MicroRNA-107/FOXK1 Axis
Authors: Cao Peng , Hu Shan , Kong Kangle , Han Peng , Deng Yu , Li fan , Zhao Bo
Published: July 2021

Objective: Studies have abstracted the partial mechanism of long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) in lung cancer, but its reciprocal with microRNA-107/Forkhead box k1 (miR-107/FOXK1) is not disclosed clearly. Hence, the mechanism of NEAT1/miR-107/FOXK1 was delved out in lung cancer.Methods: NEAT1, miR-107 and FOXK1 expression in clinical cancer tissues were determined, along with their interactions. The relation between the survival of lung cancer patients and NEAT1 expression was determined. NEAT1 and/or miR-107-related lentivirus or plasmid were transfected into A549 cells, after which cell biological functions were tested. Tumors were xenografted in mice to observe tumor formation and cell apoptosis.Results: High NEAT1 and FOXK1 and low miR-107 levels were tested in lung cancer tissues. High NEAT1 was connected with low overall survival of lung cancer patients. Depleting NEAT1 or augmenting miR-107 inhibited the biological functions of lung cancer cells. Depleted NEAT1 suppressed tumor-forming ability of A549 cells in vivo. Inhibited miR-107 antagonized depleted NEAT1-mediated effects on A549 cells. NEAT1 regulated FOXK1 by competitively binding miR-107.Conclusion: Silenced NEAT1 suppresses lung cancer development through elevating miR-107 and reducing FOXK1 expression, which supplies a plan to treat lung cancer.
Self-Organization of Water Molecules Over 11-Year Solar Cycle
Authors: Shevchenko Igor
Published: July 2021

The variations of solar activity and distribution of solar energy due to the rotation of the Earth around its axis and around the Sun exert a strong influence on the self-organization of water molecules. As a result, the rate of hydrolytic processes with the participation of water clusters displays diurnal, very large annual variations, and is also modulated by the 11-year cycles of solar activity. It also depends on the geographic latitude and can be different at the same time in the Northern and Southern Hemispheres.
This phenomenon is well accounted for by the influence of muons on the self-organization of water molecules. Muons are constantly generated in the upper atmosphere by the solar wind. They reach the surface of the Earth and can penetrate to some depth underground. Buildings also absorb muons. For this reason, the rate of hydrolysis outside and inside buildings, as well as underground, can differ significantly from each other.
Changes in NfL Plasma Levels and Association with Cognitive and Imaging Markers of Alzheimer’s Disease
Authors: Bajaj Sumali , Hadjichrysanthou Christoforos , McRae-McKee Kevin , De Wolf Frank , Anderson Roy M.
Published: July 2021

INTRODUCTION: We assessed the association of plasma neurofilament light chain (pNfL) with cognitive decline and neuroimaging markers, and investigated its potential relationship with the clinical progression to dementia due to Alzheimer’s disease (AD).METHODS: Individuals had evidence of amyloid beta accumulation. Linear and beta-regression models were developed to consider: i) the association between pNfL and cognition, ii) the association between the rate of change (ROC) of pNfL and that of imaging markers, iii) the temporal dynamics of pNfL before and after cognitive impairment as assessed by the Clinical Dementia Rating.RESULTS: Higher levels of pNfL were associated with declining cognition. The ROC of pNfL was associated with the ROC of ventricular, hippocampal and whole brain volumes, but not with PET amyloid. pNfL levels did not reflect the clinical progression of AD.DISCUSSION: pNfL is associated with cognitive decline and brain imaging markers. However, it is not specific to AD clinical diagnosis.
Targeting Autophagy Peptidase ATG4B With A Novel Natural Product Inhibitor Azalomycin F4a For Advanced Gastric Cancer
Authors: Zhong Lin , Yang Bin , zhang Zhenhua , Wang Xiaojuan , Guo Yinfeng , Huang Weifeng , Wang Qianqian , Cai Guodi , Xia Fan , Zhou Shengning , Ma Shuai , Nie Yichu , Lei Jinping , Li Min , Liu Peiqing , Deng Wenbin , Liu Yonghong , Wang Junfeng , Han Fanghai , Wang Junjian
Published: July 2021

Background: Advanced gastric cancer (GCa) remains highly lethal due to the lack of effective therapies. Identifying promising therapeutic targets and developing effective treatment against GCa are urgently needed. Here, we investigated whether Autophagy-related gene 4B (ATG4B) could be a potential therapeutic target against GCa and identified marine natural product Azalomycin F4a (Am-F4a) as a potent ATG4B inhibitor and a potential anticancer agent. Methods: The expression of ATG4B in clinical GCa tumor specimens were examined by immunoblotting and interrogation of public databases. The association between ATG4B expression and patient’s survival was assessed. FRET, surface plasmon resonance, transmission electron microscopy analysis, enzyme activity assay and compute docking were used to assess the binding and inhibition of ATG4B by Am-F4a. RNA interference, inhibitors, CCK-8 cell viability assay, colony formation, apoptosis assay, wound-healing, transwell invasion assay, western blotting and Patient-derived organoids were used to assess the role of ATG4B in GCa cells. GCa cell-derived xenograft models, patient-derived xenografts and orthotopic metastasis xenografts were used to evaluate the anti-tumor growth and anti-metastasis effects of Am-F4a alone or in combination with 5-FU in vivo.Results: ATG4B was highly upregulated in GCa tumors. Its high expression was associated with patient’s poor prognosis. knockdown of ATG4B significantly inhibited GCa cell survival and tumor growth. Am-F4a was identified as a novel and potent ATG4B inhibitor. Am-F4a effectively inhibited GCa cell autophagy and growth via targeting ATG4B both in vitro and in vivo. Besides, both pharmacological inhibition and knockdown of ATG4B significantly suppressed GCa cell migration and invasion. Am-F4a potently blocked the metastasis of primary GCa tumors and effectively sensitized tumors to chemotherapy.Conclusion: These findings indicate that ATG4B is a potential novel therapeutic target against GCa and that the natural product Am-F4a is a novel ATG4B inhibitor that can be further developed for treatment of GCa.
Research on Magnetic Bead Motion Characteristics based on Magnetic Beads Preset Technology
Authors: Li Zhao , Zu Xiangyang , Du Zhe , Hu Zhigang
Published: July 2021

In order to improve the detection efficiency and accuracy of microfluidic chip, a magnetic beads preset technology were designed by using double permanent magnets as external magnetic field and the motion characteristics of preset magnetic beads were studied. The control principle of magnetic beads preset technology was introduced in detail, and the control structure was designed. The coupled field characteristics for magnetic beads in microchannels were analyzed, and the motion models of magnetic beads were established based on the bead preset technology, including capture motion and mixing motion. The relationship between the magnetic field force and the flow velocity for capturing magnetic bead, and the mixing time under the influence of flow field and magnetic field were derived. The magnetic beads capture effect of magnetic beads preset technology was verified by experiments. The study showed the magnetic beads preset technology can better realize the accuracy and efficiency of the magnetic bead control in the microchannel. The derivation of the magnetic bead motion model can understand the motion characteristics of the magnetic bead more clearly, facilitate accurate control of the magnetic bead, and improve the success rate of the microfluidic detection.
Incidence of and Risk Factors for Missing Events Due to Wandering in Community-dwelling Older People with Dementia and Mild Cognitive Impairment
Authors: Jeong seungwon , Suzuki Takao , Miura Kiyoko , Sakurai Takashi
Published: July 2021

BackgroundThe burden of missing incidents is not only on the person with dementia, but also on their family, neighbors, and community. The extent to which dementia-related wandering and missing incidents occur in the community has not been evaluated thoroughly in the published literature. Therefore, we evaluated the incidence of and risk factors for missing events due to wandering.MethodsWe conducted a non-randomized prospective one-year follow-up cohort study based on symptom registration with missing events due to wandering as the endpoint. In the first consultation, 374 patients with dementia or mild cognitive impairment (MCI) and their caregivers who visited the National Center for Geriatrics and Gerontology in Japan were included. The incidence and recurrence rate of missing events were calculated. Participants were divided into (those with) dementia and (those with) MCI. Patients' basic and medical information was documented at baseline and after one year of follow-up. Furthermore, analysis of variance and logistic regression analysis were performed to clarify the risk factors associated with the missing event.ResultsAmong the 236 patients with dementia enrolled, 65 (27·5%) had a previous missing event at baseline, and 28 had a missing event during the one-year follow-up period (recurrence rate of 43·1%). Of the 171 who did not have a previous missing event at baseline, 23 had a missing event during the one-year follow-up period (incidence rate of 13·5%). The scores of Mini-Mental State Examination (MMSE), Dementia Behavior Disturbance Scale (DBD), and Alzheimer's Disease Assessment Scale (ADAS) were statistically significant as the risk factors for the incidence of wandering leading to a missing event (p<0·05).ConclusionsPrevention of missing event due to wandering requires focused attention on changes in the MMSE, DBD, ADAS scores, and the development of a social environment to support family caregivers.
Armington elasticity estimation with or without instruments
Authors: Kim Jiyoung , Nakano Satoshi , Nishimura Kazuhiko
Published: July 2021

This paper discusses measurement of the elasticity of substitution between goods from different countries. To remedy potential endogeneity problems in regression estimations, we use the instrumental variables (IV) approach, and the Feenstra method that does not require the use of instruments. The commodities that we study here and for which we were able to find relevant instruments are bovine, swine, and poultry meat imports by Japan. We find that the two approaches yield very similar results for these commodities. Further, upon extracting the implicit IVs of the Feenstra method, we find them as useful as the external IVs for measuring the aggregate of foreign commodities with a fixed effects regression and for estimating the foreign-domestic substitution elasticity possibly for each commodity.
A Newcastle disease virus-vector expressing a prefusion-stabilized spike protein of SARS-CoV-2 induces protective immune responses against prototype virus and variants of concern in mice and hamsters
Authors: Sun Weina , Liu Yonghong , Amanat Fatima , González-Domínguez Irene , McCroskery Stephen , Slamanig Stefan , Coughlan Lynda , Rosado Victoria , Lemus Nicholas , Jangra Sonia , Rathnasinghe Raveen , Schotsaert Michael , Martinez Jose , Sano Kaori , Mena Ignacio , Innis Bruce , Wirachwong Ponthip , Thai Duong Huu , Oliveira Ricardo , Scharf Rami , Hjorth Richard , Raghunandan Rama , Krammer Florian , Garcia-Sastre Adolfo , Palese Peter
Published: July 2021

Rapid development of coronavirus disease 2019 (COVID-19) vaccines and expedited authorization for use and approval has been proven beneficial to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and given hope in this desperate situation. It is believed that sufficient supplies and equitable allocations of vaccines are necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here we provide evidence that the NDV vector expressing an optimized spike antigen (NDV-HXP-S), upgraded from our previous construct, is a versatile vaccine that can be used live or inactivated to induce strong antibody responses and to also cross-neutralize variants of concern. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters. It is noteworthy that vaccine lots produced by existing egg-based influenza virus vaccine manufacturers in Vietnam, Thailand and Brazil exhibited excellent immunogenicity and efficacy in hamsters, demonstrating that NDV-HXP-S vaccines can be quickly produced at large-scale to meet global demands.