bluuebunny/crossref_metadata_2025 huggingface dataset:
Doğal Reklamların Marka Farkındalığı Oluşturma Rollerinin Takip Edilme Motivasyonlarına Etkisi Üzerine Bir Araştırma
Authors: ARKLAN Ümit , TUZCU Nilgün
Published: October 2021

Dijital ortamların reklamcılık alanına sunduğu imkanların etkisiyle ortaya çıkmış yeni nesil uygulamalardan birisi de doğal reklamlardır. Sağladığı olanaklar nedeniyle, kurumsal yapılar marka farkındalığı oluşturabilmek ve tüketici motivasyonlarına hitap edebilmek adına doğal reklamlardan son zamanlarda sıklıkla yararlanmaya başlamıştır. Bu durum doğal reklamların marka farkındalığı oluşturma rollerini, takip edilme motivasyonlarını ve bunlar arasındaki etkileşimi önemli hale getirmiştir. Çalışmanın temel amacını oluşturan bu önemli konuya ışık tutmak maksadıyla Süleyman Demirel Üniversitesi öğrencileri üzerinde bir alan araştırması gerçekleştirilmiştir. Araştırma sonucunda; doğal reklamların marka farkındalığı oluşturma rollerinin, kişiselleştirme, bilgilendirme, etkileşim kurma ve güven verme olmak üzere birbirleriyle etkileşim halindeki dört alt boyuttan meydana geldiği; takip edilme motivasyonlarının ise, bireysel tatmin, farkındalık, işlevsellik ve ilgi çekicilik şeklinde dört alt boyuttan oluştuğu ve bireylerin etkileşimsel bir şekilde bu motivasyonların tesiriyle doğal reklamları takip ettiği anlaşılmıştır. Doğal reklamların marka farkındalığı oluşturma rollerinin takip edilme motivasyonlarına etkisine bakıldığında ise, kişiselleştirme, bilgilendirme, etkileşim kurma ve güven verme rollerinin tümü farkındalık motivasyonu üzerinde etkiliyken; kişiselleştirme ve güven verme rolünün bireysel tatmin ve işlevsellik motivasyonunu artırıcı bir etkiye sahip olduğu; kişiselleştirme ve etkileşim kurma rolünün ise ilgi çekicilik motivasyonu üzerinde anlamlı ve olumlu bir etkisinin bulunduğu ortaya çıkmıştır.
Perceived Stress Scale, a tool to explore psychological stress in Mexican women
Authors: Flores-Torres Mario H , Tran Alvin , Familiar Itziar , López-Ridaura Ruy , Ortiz-Panozo Eduardo
Published: October 2021

Objective. To examine the factor structure of the 4- and 10-item Perceived Stress Scale (PSS) among 1 310 Mexican women participating in a prospective cancer cohort study. Materials and methods. We performed exploratory and confirmatory factor analyses in two sub-samples of the Mexican Teachers’ Cohort. We evaluated internal consistency, estimated the correlation between PSS-4 and PSS-10, and assessed their correlation with a depressive symptoms scale. Results. Two-factor models were the solutions with the best fit to the data for both PSS-4 and -10, exhibiting strong factor loadings (0.39 to 0.75) and high internal consistency (Cronbach’s alpha 0.72 and 0.83). The correlation between PSS-4 and PSS-10 was r=0.91 and the correlations of these two scales with a depressive symptoms scale were r=0.41 and r=0.46, respectively. Conclusions. PSS might be an adequate scale to assess perceived stress in this prospective cancer cohort study. PSS-4 may be advantageous due to its simplicity, low cost, and short application time in multicountry studies on stress and cancer.
Synthesis of ZnWO4/Cu2O Composites and Efficient Catalytic Properties for 4-nitrophenol Removal
Authors: Wang Ziwei , Fu Fengping , He Qian , Zhu Ting , Liao Fang
Published: October 2021

Preparation of ZnWO4/Cu2O composite materials by environmental protection experimental method. ZnWO4 nanorods were prepared by a simple hydrothermal method, and then ZnWO4/Cu2O composites were prepared by chemical precipitation method. The experimental method is simple and clean. Due to the unique structural characteristics of Cu2O, the wide band gap of ZnWO4 was improved and the ZnWO4/Cu2O composite with better catalytic performance was generated. Various tests show that the catalytic performance and stability of ZnWO4/Cu2O is not lower than that of ZnWO4. Among them, ZnWO4/Cu2O-5 has the best catalytic degradation effect. The Cu-H generated during the degradation of 4-nitrophenol (4-NP) prevents the oxidation of Cu+, and the neutral product 4-aminophenol (4-AP) is easier to fall off, which improves its recycling efficiency. These encouraging results show that the ZnWO4/Cu2O composites have great potential to degrade 4-NP.
Accumulation of As and Pb in vegetables grown in agricultural soils contaminated by historical mining in Zacatecas, Mexico
Authors: Muñoz Silvia Salas , Valdez Elvia Valdez , Castillo Jorge Armando Mauricio , Badillo Fátima Berenice Salazar , Carrillo Héctor René Vega , Salas-Luevano Miguel Angel
Published: October 2021

Historical mining activities are a source of environmental pollution that affects the food chain and the health of human beings. This study aimed to assess the accumulation of arsenic (As) and lead (Pb) in vegetables grown in agricultural soils contaminated by historical mining in Zacatecas, Mexico. The concentration of As and Pb in agricultural soil and edible parts of carrot (Daucus carota L.), garlic (Allium sativum L.), and pepper (Capsicum annum L.) was analyzed by atomic absorption spectrometry. The Pb pollution index and soil-vegetable bioconcentration factor were determined. The pH values of the farmland were moderately alkaline. The concentration of As in agricultural soil exceeds the permissible limit of Mexican and international standards representing public and environmental health risks. The Pb content in most soil samples they were low, only two soil sample exceeds the permissible limit of Mexican and international standards. The As and Pb content in edible parts of vegetables exceeded the national standards from various countries and values established by Codex Alimentarius (FAO-WHO). The highest As concentration was found in C. annum (111 mg/kg− 1) and A. sativum (100 mg/kg− 1). The highest concentration of Pb was in pepper fruits. The pollution index indicates that the soil sample is classified as polluted, and its quality is not suitable for agricultural use; thus, the vegetables cannot safely be consumed. Among vegetables, the higher BCF value was for As, ranging from 2.33 to 0.64, and the average for all vegetable samples was 1.01. According to the findings, the state and national agricultural and health authorities should not recommend cultivating vegetables in agricultural soil located in this region. Likewise, preventive measures must be taken to avoid consuming contaminated vegetables and certifying their safety grade.
Dietary Supplement of Anoectochilus Roxburghii (Wall.) Lindl Polysaccharides Ameliorates Cognitive Dysfunction induced by high fat diet via “Gut-Brain” axis
Authors: Fu Liya , Zhu Wanlong , Tian Dongmei , Tang Yong , Ye Yun , Wei Qiming , Zhang Chengbin , Qiu Wenqiao , Qin Dalian , Yang Xuping , Huang Yilan
Published: October 2021

Purpose Anoectochilus roxburghii (Wall.) Lindl polysaccharides (ARPs) has been reported to exhibit multiple pharmacological activities including anti-inflammatory and anti-hyperglycemia. The study tried to investigate the effect of ARPs on cognitive dysfunction induced by high fat diet (HFD).Methods C57BL/6J mice were given ARPs by dietary supplementation for 14-week. The effect of ARPs on cognitive function was determined by assessing the changes in spatial learning and memory ability, neurotrophic factors in hippocampus, inflammatory parameters, intestinal barrier integrity, and fecal microbiota. Results ARPs supplementation can effectively ameliorate cognitive dysfunction, decrease the expressions of Tau protein in hippocampus. Meanwhile, increased body weight, plasma glucose and lipids levels induced by HFD were abolished by ARPs treatment. It was revealed that the levels inflammatory cytokines and the LPS were remarkably higher in the HFD group than those in the chow diet group, but ARPs treatment reversed these detrimental effects. Furthermore, ARPs treatment restored the intestinal epithelial barrier as evidenced by upregulation of intestinal tight junction proteins (ZO-1 and occluding). Additionally, ARPs supplementation significantly decreased the relative abundance of eight bacteria genus such as Parabacteroides, which was negatively correlated with cognitive function.Conclusions These results suggest that ARPs might be a promising strategy for the treatment of cognitive dysfunction induced by HFD. Mechanistically, alleviation of cognitive dysfunction by ARPs was at least partially through regulating the “gut-brain” axis.
Assessing Variability in Segmentation Algorithms for 3D Printing at the Point of Care
Authors: Fogarasi Magdalene , Coburn James , Ripley Beth
Published: October 2021

Background: 3D printing (3DP) has enabled medical professionals to create patient-specific medical devices to assist in surgical planning. Anatomical models can be generated from patient scans using a wide array of software, but there are limited studies on the geometric variance that is introduced during the digital conversion of images to models. The final accuracy of the 3D printed model is a function of manufacturing hardware quality control and the variability introduced during the multiple digital steps that convert patient scans to a printable format. This study provides a brief summary of common algorithms used for segmentation and their principal features. We also identify critical parameters and steps in the workflow where geometric variation may be introduced. We then provide suggested methods to measure or reduce the variation and mitigate these risks.Methods: Using a clinical head CT scan of a mandible containing a tumor, we performed segmentations in four separate programs using workflows optimized for each. Differences in segmentation were calculated using several techniques.Results: Visual inspection of print-ready models showed distinct differences in the thickness of the medial wall of the mandible adjacent to the tumor. Residual volumes were calculated to generate pairwise agreement and disagreement percentages between each as the program’s model. For the relevant ROIs, statistically significant differences were found globally in the volume and surface area comparisons between final bone and tumor models, as well locally between nerve centroid measurements – major variance introduced due to workflow is highlighted in difference heat maps. As with all clinical use cases, statistically significant results must be weighed against the clinical significance of any deviations found.Conclusions: Statistically significant geometric variations can be introduced to patient-specific models from differences in software applications. The global and local variations should be evaluated for a full understanding of geometric variations. The clinical implications of these variations vary by anatomical location and should be evaluated on a case-by-case basis by certified clinicians. Understanding the basic functions of segmentation and 3D print preparation software is essential for users intending to adopt the use of patient-specific models for clinical intervention or decision making.
Evaluation of the Genotoxicity in Fish Erythrocytes to Diagnose the Water Quality of Two Amazonian Estuaries Using the Micronucleus Test and Comet Assay
Authors: DE OLIVEIRA CLAUDIA ANTONIA CAMPOS RODRIGUES , Souto Paulo Sergio dos Santos , Palheta Dulcideia da Conceição , Bahia Marcelo de Oliveira , Cunha Lorena Araújo da , Santos Maria de Lourdes Souza , Rodrigues Tatiane do Nascimento Medeiros , Bentes Bianca
Published: October 2021

Genotoxicity studies in coastal ecosystems have been a priority in Environmental Risk Assessment (ERA). This research aimed to study the genotoxicity by the micronucleus test and comet assay in two Brazilian Amazon estuaries (anthropized and control) using Plagioscion squamosissimus as a bioindicator. Blood samples were collected from 54 specimens. No significant genotoxic effects were detected in the cells analyzed, although the highest occurrence was observed in anthropized site. The percentage of genomic damage differed between the sites studied, being always higher in anthropizes site as well. Of the nucleoids analyzed in this site, on average 28±14.42% of the cells were classified in the highest damage class (4). The fish analyzed in the present study are direct influence of xenobiont agents capable of producing damage to the genetic material of aquatic organisms in both sites and, consequently, may bring consequences still little reported in studies of morphophysiological alterations in humans.
The Neuropeptide Y Single-nucleotide Polymorphism rs16147 Moderates the Effect of Alcohol Dependence on Depression
Authors: Wang Fan , Zhou Siyao , Chen Li , Shen Guanghui , Yang Fan , Sun Huankun , Hong Liuzhi , Zou Yang , Li Hui , Chen Yu-Hsin , Liu Yanlong , Wang Wei
Published: October 2021

Background: Previous studies suggest that alcohol dependence is associated with depression, however, the effect of alcohol dependence varies from individual to individual, which may be due to different genetic backgrounds. The interactions between alcohol dependence and different gene polymorphisms may finally shape the onset of depression. Neuropeptide Y (NPY), which can maintain homeostasis from high-stress stimulation, may protect individuals from the onset of depression. Here, we explored whether the NPY rs16147 regulates depression in individuals with alcohol dependence during the period of alcohol dependence withdrawal.Methods: A total of 455 males with alcohol dependence were recruited. The scale of MAST and SDS were respectively used to analyze the condition of alcohol dependence and depression. Genomic DNA was extracted from each blood sample and NPY polymorphisms were genotyped. The interaction between NPY rs16147 and alcohol dependence on depression was first analyzed. Then, region of significance analysis was used to confirm which model provided the best fit for the interaction (diathesis-stress or differential susceptibility). Finally, by using internal replication analyses, the accuracy and robustness of the interaction results were improved.Results: Alcohol dependence was positively correlated with depression. CC homozygotes of NPYrs16147 exhibited less depression when exposed to low alcohol dependence, but more depression when exposed to high alcohol dependence. Individuals with the T allele showed the opposite result.Conclusions: NPY rs16147 might be correlated with susceptibility for depression in males during alcohol dependence withdrawal. The findings support the differential susceptibility model.
Uncertainty Prediction of Mining Safety Production Situation
Authors: WU Menglong , YE Yicheng , HU Nanyan , WANG Qihu , TAN Wenkan
Published: October 2021

In order to explore the occurrence and development law of mining safety production accidents, analyze its future change trends, and aim at the ambiguity, non-stationarity, and randomness of mining safety production accidents, an uncertainty prediction model for mining safety production situation is proposed. Firstly, the time series effect evaluation function is introduced to determine the optimal time granularity, which is used as the window width of fuzzy information granulation (FIG), and the time series of mining safety production situation is mapped to Low, R and Up three granular parameter sequences, according to the triangular fuzzy number; Then, the mean value of the intrinsic mode function (IMF) is maintained in the normal dynamic filtering range. After the ensemble empirical mode decomposition (EEMD), the three non-stationary granulation parameter sequences of Low, R and Up are decomposed into the intrinsic mode function components representing the detail information and the trend components representing the overall change, and then the sub-sequences are reconstructed according to the sample entropy to highlight the correlation among the sub-sequences; Finally, the cloud model language rules of mining safety production situation prediction are created. Through time series discretization, cloud transformation, concept jump, time series set division, association rule mining and uncertain reasoning, the reconstructed component sequence is modeled and predicted by uncertainty information extraction. The accuracy of the uncertainty prediction model was verified by 21 sets of test samples. The average relative errors of Low, R and Up sequences were 9.472 %, 16.671 % and 3.625 %, respectively. The research shows that the uncertainty prediction model of mining safety production situation overcomes the fuzziness, non-stationarity and uncertainty of safety production accidents, and provides theoretical reference and practical guidance for mining safety management and decision-making.
Predictive Factors of Crucial Nutrition Impact Symptom Clusters in Patients With Head and Neck Cancer Undergoing Radiotherapy
Authors: Wang Yujie , Zhang Lichuan , Zhuang Bing , Zhang Tong , Jin Sanli , Huang Zhou , Zhao Dan , Zheng Baomin , Xiao Shaowen , Gong Liqing , Sun Yan , Lu Qian
Published: October 2021

Purpose: To identify crucial nutrition impact symptom (NIS) clusters related to both weight loss rate (WLR) and quality of life (QoL) in patients with head and neck cancer (HNC) receiving RT, and analyze their predictive factors.Methods: This prospective study enrolled 334 patients. At baseline (T1), we collected the demographics, clinical information, nutritional risk (Nutritional risk screening 2002, NRS 2002), nutritional status (Global Leadership Initiative on Malnutrition, GLIM), weight, and QoL before RT. At the third week (T2) and the end of RT (T3), we evaluated the severity and interference of NIS using the head and neck patient symptom checklist (HNSC), weight, and QoL. Exploratory factor analysis was used to extract the symptom clusters. Generalized estimating equations were used to analyze NIS clusters’ relationship with WLR and QoL, and cluster’s predictive factors.Results: Four NIS clusters were identified: RT-specific symptom cluster, upper gastrointestinal symptom cluster, psychological status cluster, and eating experience cluster. The former two NIS clusters had a negative impact on both WLR and QoL, so they were defined as crucial NIS clusters. Patients who were female, with older age, oral cavity cancer, had nutritional risk or were malnutrition at baseline were more likely to get severe RT-specific symptom cluster. Patients who were female, accepted intensive therapy were more likely to get severe upper gastrointestinal symptom cluster.Conclusions: Healthcare professionals should recognize patients at risk and intervene early, and give early nutritional management before RT to improve HNC patients’ NIS severity, nutritional status and QoL during treatment.
Discovery of Novel Inhibitors Targeting HDM2: Virtual Screening, Molecular Dynamics Simulation and Binding affinity predication
Authors: Cao Feng , Chen Liang , Xiong Feng , Liu Xingyong , Zhang Li
Published: October 2021

HDM2(human double-minute 2 protein) is an important drug target for tumor treatment. The main physiological function of HDM2 is to negatively regulate the tumor suppressor protein p53 and inhibit the normal biological function of p53, which leads to the occurrence and development of tumors. Therefore, the discovery of small molecules that can inhibit the activity of HDM2 is a promising cancer therapy. In this study, we reported a virtual screening as an effective strategy to discover potential HDM2 inhibitors from the Specs database. Then 100 ns all-atom molecular dynamics (MD) simulation and binding free energies calculated were carried out on the selected compounds. In conclusion, we reported seven prospective candidates with novel skeletons among them Hit4 is a potential HDM2 inhibitor and provided an insight into the mechanism of interaction of the compounds to HDM2 target.
Mortality Risk from COVID-19 among Unvaccinated Subjects with Autoimmune Phenotypes of Interstitial Lung Disease
Authors: Strykowski Rachel , Poonawalla Maria , Tyker Albina , Ventura Iazsmin Bauer , Lee Cathryn , Garcia Nicole , Guzy Robert , Jablonski Renea , Vij Rekha , Chung Jonathan , Strek Mary , Adegunsoye Ayodeji
Published: October 2021

Background: The impact of the SARS-CoV-2 virus on patients with interstitial lung disease (ILD) remains poorly understood. As patients with ILD often have severe underlying lung parenchymal involvement, and immunosuppressive therapy is common in this population, they are presumed to be at high risk for severe COVID-19 pneumonitis. We investigated differences between those with ILD who tested positive for the SARS-CoV-2 virus compared to those with ILD who did not, and explored the relationship with use of immunosuppressive therapy.Methods: In this retrospective cohort study, we identified patients evaluated at the University of Chicago in 2020 with a multidisciplinary diagnosis of ILD, and stratified by detection of the SARS-CoV-2 virus presence or absence on PCR. Demographic data, laboratory values, and pulmonary function testing values were obtained at time of ILD diagnosis. Immunosuppressive therapies received since ILD diagnosis were assessed, as was mortality. Variable comparisons were determined by two-sided t-tests, or chi-square tests as appropriate, and logistic regression models were fitted to assess the odds of death from COVID-19 using generalized linear models with maximum-likelihood estimation.Results: Of the 309 individuals with ILD in our cohort, 6.8% (n=21) tested positive for SARS-CoV-2. Those that were SARS-CoV-2 positive were younger (57 yrs vs 66 yrs; P=0.002), had baseline higher TLC (81% vs 73%, P=0.045), similar FVC (71% vs. 67%, P=0.37), and similar DLCO (71% vs. 62%, P=0.10) at baseline. Among patients with ILD and COVID-19, 67% had received immunosuppressive therapies compared to 74% of those with ILD without COVID-19. Those with ILD and COVID-19 were also more likely to have had a diagnosis of autoimmune related-ILD (CTD-ILD or IPAF) (62% vs 38%, P=0.029), and were more frequently hypoxemic (SpO2 ≤ 92%; 4% vs 19%; P=0.012) at ILD diagnosis than those without COVID-19. The majority of patients (62%) with COVID-19 had received lymphocyte-depleting immunosuppressive therapy prior to infection. Overall, the mortality hazard was highest amongst unvaccinated subjects with autoimmune related-ILD who had COVID-19 (OR=9.6, 95%CI=1.7-54.0; P=0.01).Conclusion: SARS-CoV-2 is prevalent in ILD, and may put those who are younger, with autoimmune ILD, and on immunosuppressive therapy at higher risk. Larger studies are needed to fully explore the relationship between ILD and immunosuppressive therapy in COVID-19.
Stability Analysis and Control Measures of Tunnel Face in Water-Rich Sandy Dolomite Stratum
Authors: Jiang Yifan , Zhou Ping , Zhou Feicong , Lin Jiayong , Li Jinyi , Lin Ming , Yongli Qi , Wang Zhijie
Published: October 2021

Revealing the conditions for the occurrence of sand gushing accidents in tunnels with water-rich sandy dolomite strata can help the tunnels to be constructed safely. In this paper, we found that sandy dolomite and the water environment are the key factors causing sand surges through geophysical prospecting at the tunnel face where 12,000 m 3 sand surge occurred. Through the flow-solid coupling model, the extrusion deformation at the tunnel face is the main deformation form in the tunnel of water-rich sandy dolomite strata. The influence of different factors on the deformation value of the tunnel face is from strong to weak: sandification degree, head height, and tunnel depth. Combined with the study of pressure arch characteristics of the model, the limit equilibrium theory considering seepage effects and pressure arch characteristics is proposed. We get that sand surges will occur in the tunnel in the intensively sandy dolomite strata where the head exceeds 80m. For the intensively sandy dolomite strata with head below 80m, the stability of the tunnel face is controlled by the degree of seepage damage. According to the reason of sand gushing, the comprehensive control measures consisting of risk identification by over-detection, double-layer close-packed pipe shed, grouting sealing technology and dewatering technology, and Milling and blasting combined construction method are proposed, and the effective control of tunnel working face is realized in practical application.
Cluster Evolution in Thermal Decomposition of CL-20/TNT Co-Crystal in Compressed State:A ReaxFF Reactive Molecular Dynamics Simulation Study
Authors: Li Yan , Yu Wen-li , Huang Huang , Zhu Min
Published: October 2021

The thermal decomposition process of CL-20/TNT co-crystal in different compression states is simulated by ReaxFF reactive molecular dynamics method. Co-crystals models with different degrees of compression are obtained under four pressures of atmospheric pressure, 4.6GPa, 9.2GPa and 18.4GPa. The potential energy evolution, product formation and cluster evolution in the process are analyzed. We find that the formation of clusters is the key to the decomposition process. When the system is compressed, there will be more clusters which can bind the free atoms, resulting in the reaction to be inhibited. Other evolution information conforms this.
Five Genes as Diagnostic Markers of Ischemic Stroke and Their Correlation with Immune Infiltration
Authors: Wang Meng , Zhang Ruijie , Guan Qiongfeng , Yao Yindan , Han Liyuan
Published: October 2021

Background: This study aimed to identify potential diagnostic markers of ischemic stroke (IS) and discuss the function of immune cell infiltration during the pathological process. Methods: We used IS datasets from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified, and functional correlation analysis was performed. We then screened and verified the diagnostic markers of IS. We evaluated the infiltration of immune cells in infarcts using CIBERSORT and analyzed the correlation between diagnostic markers and infiltrating immune cells. Results: A total of 366 DEGs were screened in this study. Genes encoding CTSG, F13A1, PABPC1, ECHDC2, BIRC2 and infiltrating monocytes, M0 macrophages, activated dendritic cells, and neutrophils (area under the curve [AUC] = 0.945) were identified as diagnostic markers of IS. Immune cell infiltration analysis suggested that memory B cells, regulatory T cells, M0 macrophages, CD8 + T cells, γδT cells, activated natural killer cells, monocytes, activated mast cells, and neutrophils were involved in the IS process. Analysis of correlations between expressed genes and infiltrating immune cells found that CTSG was positively associated with M0 macrophages, F13A1 was positively associated with monocytes, PABPC1 was positively associated with activated dendritic cells, eosinophils were negatively associated with neutrophils, ECHDC2 was negatively associated with monocytes, and BIRC2 was positively associated with eosinophils. Conclusion: five genes and four types of immune cells were identified as diagnostic markers of IS, and immune cell infiltration may play an important role in the progression of IS.
The PCSK9 Involves in the Dyslipidemia of Ovariectomized Mice and Its Mechanism
Authors: Zhao Dan , Zhang Xue-qin , Guo Wen-jing , Cui Zhi-hui , Wang Yi-cheng , Ma Yong-dan , Zhang Li-xue , Zhang Jin-hu , Nie Li , Yue Limin
Published: October 2021

Ovarian failure in postmenopausal female leads E2 to dramatic decrease which is an important reason of menopausal dyslipidemia. PCSK9 as a secretory lipid metabolic regulator plays a critical role in the cholesterol metabolism by negatively regulating LDLR in hepatocytes. Clinical data showed PCSK9 was elevated and positively correlated with LDL-C in the blood of postmenopausal women. However, the relationship between E2 and PCSK9 and the role of PCSK9 in postmenopausal dyslipidemia are still unclear. In this research, 10-week-old ovariectomized mice were fed for 4 weeks with normal diet or high-fat diet, then tested the lipid metabolism profiles and PCSK9 in the blood and the expression of LDLR and PCSK9 in the liver. On this basis, PCSK9-/- ovariectomized mice were used to further verify the effect of PCSK9 in dyslipidemia of ovariectomized mice. Finally, the ovariectomized mice with high-fat diet were subcutaneous injected respectively with E2 or PCSK9 inhibitor alone or both together for 2 weeks and were tested as previous experiment. The results showed PCSK9, TC and LDL-c all increased in the blood of in WT ovariectomized mice and their PCSK9 is positively correlated with LDL-c, while there were on obvious lipid metabolism disorder in the PCSK9−/− ovariectomized mice. PCSK9 inhibitor increased the LDLR on the liver and ameliorated the dyslipidemia in WT ovariectomized mice. It suggests that PCSK9 plays an important role in the dyslipidemia of ovariectomized mice, which provides a new strategy for clinical diagnosis and treatment of the dyslipidemia in post-menopause.
Oxidative Stimuli Induce Antioxidant Responses by Affecting Nrf2/are Signal Pathway in Common Carp (Cyprinus Carpio)
Authors: Liu Yi , Li Xueting , Yu Lidong , He Mingyue , Gu Ning , Li Bingsheng , LI LI , Cheng Lei
Published: October 2021

The Nrf2/ARE signal pathway is a key pathway for antioxidant stress responses and resistance to external stimuli in most organisms. It plays an important role in anti-inflammatory, immune and antioxidant responses. In this paper, the expression of Nrf2/ARE signal pathway related genes in the larval and adult zebrafish were analyzed, including the degree of conservation of the key sites of Nrf2 and Keap1 in carp. And the stress status of the Nrf2/ARE signal pathway was investigated in response to external environment change. The result showed that nrf2 and keap1 binding sites were highly conserved in carp. The expression of nrf2a and keap1a was highest at 48 hpf, keap1b at 8 hpf and varied in adults, suggesting that these genes play different functional roles in different stages of zebrafish. Stimulation by oxidant can induce upregulation of genes related to the Nrf2/ARE signalling pathway, playing an important role in the protection of the organism. This paper not only lays the foundation for studying the role of Nrf2/ARE signaling pathway in the embryonic and adult stages of carp, but also provides a direction for the development of antioxidant drugs and feeds for carp.
Vaccinations or Non-Pharmaceutical Interventions: Safe Reopening of Schools in England
Authors: Cuesta-Lazaro Carolina , Quera-Bofarull Arnau , Aylett-Bullock Joseph , Lawrence Bryan N. , Fong Kevin , Icaza-Lizaola Miguel , Sedgewick Aidan , Truong Henry , Vernon Ian , Williams Julian , Pagel Christina , Krauss Frank
Published: October 2021

With high levels of the Delta variant of COVID-19 circulating in England during September 2021, schools are set to reopen with few school-based non-pharmaceutical interventions (NPIs). In this paper, we present simulation results obtained from the individual-based model, JUNE, for English school opening after a prior vaccination campaign using an optimistic set of assumptions about vaccine efficacy and the likelihood of prior-reinfection. We take a scenario-based approach to modelling potential interventions to assess relative changes rather than real-world forecasts. Specifically, we assess the effects of vaccinating those aged 16-17, those aged 12-17, and not vaccinating children at all relative to only vaccinating the adult population, addressing what might have happened had the UK began teenage vaccinations earlier. Vaccinating children in the 12-15 age group would have had a significant impact on the course of the epidemic, saving thousands of lives overall in these simulations. In the absence of such a vaccination campaign our simulations show there could still be a significant positive impact on the epidemic (fewer cases, fewer deaths) by continuing NPI strategies in schools. Our analysis suggests that the best results in terms of lives saved are likely derived from a combination of the now planned vaccination campaign and NPIs in schools.
Commensal Bacillus From Cow Milk Inhibits Staphylococcus Aureus Biofilm Formation and Mastitis in Mice
Authors: Qiu Min , Zhao Caijun , Feng Lianjun , Gao Siyuan , Hu Xiaoyu , Fu Yunhe , Zhang Naisheng
Published: October 2021

Background: Mastitis, one of the most serious diseases in dairy industry, could cause tremendous economic losses worldwide and is commonly trigged by pathogen invasion. Staphylococcus aureus (S. aureus) -induced mastitis has been reported to play an important role in mastitis etiology characterized by high morbidity, recurrence, and increased antibiotic resistance, which may attribute to the formation of biofilm formation, a form of bacterial aggregation for better growth and resistance to adverse conditions. Probiotics Bacillus has been reported to disrupt bacteria quorum-sensing (QS) system, a central regulator for biofilm formation. However, whether commensal Bacillus affects S. aureus biofilm formation and consequent colonization during mastitis is still unknown. Results：Here, we identified that the Bacillus is associated with reduced colonization of S. aureus in the mammary gland of cows. Interestingly, Bacillus did not affect S. aureus growth but inhibited the biofilm formation of S. aureus by interfering with S. aureus QS signaling. The most obvious anti-biofilm effect was found in Bacillus subtilis H28, so it was selected for further study. We found that bacillus subtilis H28 treatment alleviated S. aureus-induced mastitis in mice, as showed by limiting pro-inflammatory cytokines production, enhancing barrier integrity, and reducing S. aureus burden. Consistently, Bacillus subtilis with the capacity to interfere S. aureus QS ameliorated S. aureus-induced NF-κB activation in mice mammary epithelial cells（MMECs）. Conclusions: Collectively, our results indicate that commensal Bacillus inhibits S. aureus colonization and alleviates S. aureus-induced mastitis by influencing biofilm formation, which suggests a potential strategy for the decolonization of S. aureus and acts as a basis for the prevention and treatment of S. aureus-related disease.
From compartments to gene loops: Functions of the 3D genome in the human brain
Authors: Roussos Panos , Rahman Samir , Dong Pengfei , Apontes Pasha , Fernando Michael , Townsley Kayla , Girdhar Kiran , Bendl Jaroslav , Shao Zhiping , Misir Ruth , Tsankova Nadejda , Kleopoulos Steven , Brennand Kristen , Fullard John
Published: October 2021

The 3D genome plays a key role in the regulation of gene expression. However, little is known about the spatiotemporal organization of chromatin during human brain development. We investigated the 3D genome in human fetal cortical plate and in adult prefrontal cortical neurons and glia. We found that neurons have weaker compartments than glia that emerge during fetal development. Furthermore, neurons form loop domains whereas glia form compartment domains. We show through CRISPRi on CNTNAP2 that transcription is coupled to loop domain insulation. Gene regulation during neural development involves increased use of enhancer-promoter and repressor-promoter loops. Finally, transcription is associated with gene loops. Altogether, we provide novel insights into the relationship between gene expression and different scales of chromatin organization in the human brain.
The Effect of Phosphate Binders in Patients With End Stage Kidney Disease Undergoing Hemodialysis: a Prospective Cohort Study
Authors: Ge Jie , Mali Niroj , Fan WenXing , Ma JingYuan
Published: October 2021

The authors have requested that this preprint be removed from Research Square.
Formation and function of bacterial outer membrane proteins- incorporated liposomes using an in vitro translation system
Authors: Kamiya Koki
Published: October 2021

Outer membrane proteins (OMPs), located on the outer membrane of gram-negative bacteria, have a β-strand structure and form nanopores, which allow passage of ions, sugars, and small molecules. Recently, OMPs have been used as sensing elements to detect biological molecules. OMPs are normally expressed and purified from E. coli.. Although the cell-free synthesis of OMPs, such as OmpA and OmpG, is achieved in the presence of liposomes and periplasmic chaperones, the amount of OmpA and OmpG incorporated into the nano-sized liposomes is not clear. In this study, after in vitro translation, the incorporation of OmpG into purified nano-sized liposomes, with various lipid compositions, was investigated. Liposomes containing the synthesized OmpG were purified using a stepwise sucrose density gradient. We report that liposomes prepared with the E. coli lipid extract (PE/PG) had the highest amount of OmpG incorporated compared to liposomes with other lipid compositions, as detected by recording the current across the OmpG containing liposomes using the patch clamp technique. This study reveals some of the requirements for the insertion and refolding of OMPs synthesized by the in vitro translation system into lipid membranes, which plays a role in the biological sensing of various molecules.
WITHDRAWN: Evaluation of the Efficacy of Lactogenic Immunity of Sow Induced by Porcine Epidemic Diarrhea Virus (PEDV) Vaccine By Intranasal Immunization
Authors: Deng Shengchao , Wang Juan , Mohiuddin Mudassar , Zhu Lisai , Wang Guiping , Jia Aiqing
Published: October 2021

Background: Porcine epidemic diarrhea virus belongs to family of coronaviruses which are notorious for rapid spread of severe diarrhea among suckling piglets. The virus mainly replicates in the epithelial cells of duodenum, jejunum, ileum and colon and is a life threatening condition in pigs. A highly virulent strain “CHYJ130330” having high mortality rate was isolated from a field outbreak, identified as a new virulent genotype II/G2-b strain and adapted successfully to vero cells was used to prepare inactivated vaccine against PEDV. This newly prepared vaccine was given through intranasal route and is compared with the commercially available bi-combined (PEDV and TGEV) vaccine given by intramuscular injection. In this study milk or mucosal IgA and IgG antibody levels have been used to predict vaccine efficacy and the level of protective immunity against PED virus. Antibody titers in the milk of sows and intestines of suckling piglets were compared by enzyme-linked immunosorbent assay (ELISA). Results: It was shown that CHYJ vaccine induced significantly higher levels of PEDV IgA antibody in milk of sows and intestines of piglets as compared to commercial bi-combined vaccine. Both CHYJ and commercial vaccines were not able to induce detectable IgG levels in the intestines of piglets; the later however induced higher IgG levels when detected in the sow’s milk. Protective efficacy of vaccines was determined against a highly virulent PEDV strain. CHYJ intranasal vaccine gives a better protection 80% (4/5) rate as compared to commercial i.m. vaccine conferring 60% (3/5) immunity in suckling piglets. Conclusions: It is therefore concluded that PEDV inactivated CHYJ vaccine confer better lactogenic immunity and gives more protection to suckling piglets than available bi-combined TGEV and PEDV vaccine through passive immunization.
Tuberculosis Poor Treatment Outcomes and its determinants in Kilifi County, Kenya: A Retrospective Cohort Study
Authors: Katana Geoffrey G. , Ngari Moses , Maina Teresia Wamuyu , Sanga Deche , Abdullahi Osman A
Published: October 2021

Background:Tuberculosis (TB) is one of the leading causes of deaths in Africa, monitoring its treatment outcome is essential to evaluate treatment effectiveness. In this study, we aimed to evaluate proportion of poor TB treatment outcome (PTO) and its determinants during six-months of treatment in Kilifi County, Kenya. Methods:This study was a retrospective analysis of data from the TB surveillance system (TIBU) in Kilifi County, Kenya from 2012 to 2019. The outcome of interest was PTO (lost-to-follow-up (LTFU), death, transferred out, treatment failure, drug resistance) or successful (cured or completed treatment) treatment. We performed time-stratified (at three months follow-up) survival regression analyses accounting for sub-county heterogeneity to determine factors associated with PTO.Results:We included 14706 TB patients, median (IQR) age 37 (28–50) years old and 8791 (60%) males. A total of 13389 (91%) were on first line anti-TB treatment (2RHZE/4RH), 4242 (29%) were HIV infected and 192 (1.3%) had other underlying medical conditions. During 6586 person-years of follow-up, 2408 (16%) patients had PTO: 1074 (45%) deaths, 776 (32%) LTFU, 415 (17%) transferred out, 103 (4.3%) treatment failure and 30 (1.3%) multidrug resistance. The proportion of poor outcome increased from 7.9% in 2012 peaking at 2018 (22.8%) and slightly declining to 20% in 2019 (trend test P=0.03). Over two-thirds 1734(72%), poor outcomes occurred within first three months of follow-up. In the first three months of starting TB treatment, HIV infection (aHR 1.72 (95% CI 1.28–2.30)) and year of starting treatment were positively associated with PTO. However, in the last three months of treatment, elderly age ≥50 years, a retreatment patient, HIV infection, other underlying medical conditions (aHR 2.24 (95%CI 1.41–3.54)) and year of starting treatment were positively associated with PTO while being a female (aHR 0.83 (95%CI 0.70–0.97)) was negatively associated with PTO.ConclusionsOver two-thirds of poor outcomes occur in the first three months of TB treatment, therefore greater efforts are needed during this phase. Intervention targeting the HIV infected and other underlying medical conditions, the elderly and retreated patients provide an opportunity to improve TB treatment outcome.
Monitoring Geological Storage of CO2 – A New Rock Physics Model to Estimate Saturation
Authors: Fawad Manzar , Mondol Nazmul Haque
Published: October 2021

To mitigate the global warming crisis, one of the effective ways is to capture CO2 at an emitting source and inject it underground in saline aquifers, depleted oil and gas reservoirs, or in coal beds. This process is known as carbon capture and storage (CCS). With CCS, CO2 is considered a waste product that has to be disposed of properly, like sewage and other pollutants. While and after CO2 injection, monitoring of the CO2 storage site is necessary to observe CO2 plume movement and detect potential leakage. For CO2 monitoring, various physical property changes are employed to delineate the plume area and migration pathways with their pros and cons. We introduce a new rock physics model to facilitate the time-lapse estimation of CO2 saturation and possible pressure changes within a CO2 storage reservoir based on physical properties obtained from the prestack seismic inversion. We demonstrate that the CO2 plume delineation, saturation, and pressure changes estimation are possible using a combination of Acoustic Impedance (AI) and P- to S-wave velocity ratio (Vp/Vs) inverted from time-lapse or four-dimensional (4D) seismic. We assumed a scenario over a period of 40 years comprising an initial 25 year injection period. Our results show that monitoring the CO2 plume in terms of extent and saturation can be carried out using our rock physics-derived method. The suggested method without going into the elastic moduli level handles the elastic property cubes which are commonly obtained from the prestack seismic inversion. Pressure changes quantification is also possible within un-cemented sands; however, the stress/cementation coefficient in our proposed model needs further study to relate that with effective stress in various types of sandstones. The three-dimensional (3D) seismic usually covers the area from the reservoir's base to the surface makes it possible to detect the CO2 plume's lateral and vertical migration. However, the comparatively low resolution of seismic, the inversion uncertainties, lateral mineral, and shale property variations are some limitations, which warrant consideration. This method can also be applied for the exploration and monitoring of hydrocarbon production.
Predicting the Metro Scenario-based Spatiotemporal Evolution of Land Use Using CA-Kalman Filter Model: a Case Study of Nanjing City, China
Authors: Dai Jialing , Li Xiaozhao , Zhang Wei , Liao Ke , Liu Tao , Zhao Peng , Xu Wentao
Published: October 2021

The expansion of metro system can bring varying degrees of impact to the surrounding environment. To study this complex system problem, this paper discusses the temporal and spatial impact by metro system from the perspective of land use change simulation and scenario analysis. The traditional cellular automata (CA) model can realize the simulation of land use change under various scenarios through system dynamics or Markov chain to control the long-term demand forecasting. However, this type of model ignores the filtering of noise data from imageries and increases uncertainty of the system. Therefore, based on the Future Land Use Simulation (FLUS) model, this paper integrates Kalman filter to control the stochastic process of the state-space system, and predicts the spatio-temporal evolution of land use change impacted by metro system in Nanjing from 2019 to 2035. The results show that: (1) The proposed CA-Kalman filter model can realize the optimized simulation of land use change with good accuracy; (2) Urban patches impacted by metro system will emerge from the existing urban boundaries at the cost of occupation of cultivated land, although there is still significant expansion of urban land and construction land, it will reach the upper limit in 2050.
Separator-less Amino Acid-powered Biofuel Cell Through an Artificial Multi-enzyme Cascade Reaction
Authors: Satomura T , Horinaga Kousaku , Takamura Eiichiro , Sakamoto Hiroaki , Sakuraba Haruhiko , Ohshima Toshihisa , Suye Shin-ichiro
Published: October 2021

Objective This study was aimed at constructing a highly stable one-compartment enzymatic biofuel cell (EFC) without a separator through a multi-enzyme cascade reaction pathway. Results A separator-less EFC composed of a multi-enzyme cascade anode containing four dehydrogenases from a thermophile and a cathode devised using a multi-copper oxidase mutant with enhanced enzyme activity from a hyperthermophile was developed. To fabricate an EFC without a separator, redox mediators utilized in the enzymatic cascade reaction were also immobilized on the anode. In the presence of the fuel 100 mM L -proline, the separator-less EFC with four thermophilic dehydrogenase-modified anode achieved a maximum power density of 11.3 υW/cm 2 at 37°C, which was 1.6-fold higher than that of a similar EFC fabricated with a one enzyme-modified anode. The separator-less EFC composed of a multi-enzyme modified anode maintained approximately 57% of the load current at 0.3 V measured on the first day of EFC fabrication, even after 4 days.Conclusion Efficient L-proline electric generation utilizing a separator-less EFC composed of a multi-enzyme modified anode through a multi-step fuel oxidation reaction and a highly stable multi-copper oxidase mutant-modified cathode was successfully achieved over a long period. The long-term stability of the separator-less EFC can facilitate its application as an efficient power source for implantable medical devices requiring continuous operation.