bluuebunny/crossref_metadata_2025 huggingface dataset:
The risk of SARS-CoV-2 outbreaks in low prevalence settings following the removal of travel restrictions
Authors: Sachak-Patwa Rahil , Byrne Helen , Dyson Louise , Thompson Robin
Published: June 2021

Countries around the world have introduced travel restrictions to reduce SARS-CoV-2 transmission. As vaccines are gradually rolled out, attention has turned to when travel restrictions and other non-pharmaceutical interventions (NPIs) can be relaxed. Here, using SARS-CoV-2 as a case study, we develop a mathematical branching process model to assess the risk that, following the removal of NPIs, cases introduced into new locations initiate a local outbreak. Our model accounts for changes in background population immunity due to vaccination. We consider two locations in which the vaccine rollout has progressed quickly – specifically, the Isle of Man (a British crown dependency in the Irish Sea) and the country of Israel. We show that the outbreak risk is unlikely to be eliminated completely when travel restrictions and other NPIs are removed, even once the vaccine programmes in these locations are complete. Specifically, the risk that an imported case initiates an outbreak following the vaccine rollout and removal of NPIs is projected to be 0.373 (0.223,0.477) for the Isle of Man and 0.506 (0.387,0.588) for Israel. Key factors underlying these risks are the potential for transmission even following vaccination, incomplete vaccine uptake, and the recent emergence of SARS-CoV-2 variants with increased transmissibility. Combined, these factors suggest that when travel restrictions are relaxed, it will still be necessary to implement surveillance of incoming passengers to identify infected individuals quickly. This measure, as well as tracing and isolating contacts of detected infected passengers, should remain in place to suppress potential outbreaks until case numbers globally are reduced.
Increased Nodular P Level Induced by Intercropping Stimulated Nodulation in Soybean Under Phosphorus Deficiency
Authors: Qin Xiao Min , Pan Hao Nan , Xiao Jing Xiu , Tang Li , Zheng Yi
Published: June 2021

Low P availability is a vital constraint for nodulation and efficient N2 fixation of legume, including soybean. To elucidate the mechanisms involved in nodule adaption to low P availability under legume/cereal intercropping systems, two experiments consisting of three cropping patterns (monocropped soybean, monocropped maize, soybean/maize intercropping) were studied under both sufficient-and deficient-P levels. Our results demonstrated that intercropped soybean with maize showed a higher nodulation and N2 fixation efficiency under low P availability than monocropped soybean as evidenced by improvement in the number, dry weight and nitrogenase activity of nodules. These differences might be attributed to increase in P level in intercropping-induced nodules under low P supply, which was caused by the elevated activities of phytase and acid phosphatases in intercropping-induced nodules. Additionally, the enhanced expression of phytase gene in nodules supplied with deficient P level coincided with an increase in phytase and acid phosphatase activities. Our results revealed a mechanism for how intercropped maize stimulated nodulation and N2 fixation of soybean under P deficient environments, where enhanced synthesis of phytase and acid phosphatases in intercropping-induced nodules, and stimulated nodulation and N2 fixation.
Epidemiology of Measles in West Arsi Zone, Oromia Region, Ethiopia: 2011-2015
Authors: Solomon Tesfaye , Nigatu Mamo , Areda Birhanu
Published: June 2021

Background

Measles is a leading vaccine-preventable childhood disease, which has been designated for elimination. Despite the success of measles control, measles is still responsible for 145,700 deaths worldwide each year, with many of the outbreaks in developing countries including Ethiopia. We analyzed to characterize the epidemiology of measles and recommend better prevention and control strategies in West Arsi Zone, Ethiopia.
Methods

Data from 2011–2015 from the Public Health Emergency and Management Unit of the West Arsi Zone Health Department database were obtained using a semi-standard checklist. We analyzed and described the data by person, place, and time.
Results

We identified 1735 cases of measles between 2011–2015. The annual average measles incidence rate during 2011–2014 was 3.4/100,000 while the incidence rate in 2015 was 14/100,000. During 2011–2015, most of the cases occurred in children age less than 15 years old (87%), and 33 % were under five. Measles cases were reported every month, and March had the highest number of cases (24%). The districts with the highest incidence rates of measles had high routine measles vaccination coverage’s. The proportion of districts with an annual detection rate for non-measles febrile rash was 67% both in 2014 and 2015 which was below the national target (> 80%).
Conclusions

Measles outbreaks in children in 2015 in an area with high routine vaccination coverage were identified. We recommended improving vaccine management and supplementary vaccination for children less than 15 years. It needs further study to identify contributing factors for measles outbreaks and evaluating the effectiveness of measles control and prevention strategies.
Discovery of succinate dehydrogenase candidate fungicides via lead optimization for effective resistance management of Fusarium oxysporum f. sp. capsici
Authors: Iftikhar Sehrish , Bengyella Louis , Shahid Ahmad Ali , Nawaz Kiran , Anwar Waheed , Ali Sajid
Published: June 2021

Fusarium wilt of chili caused by the fungus Fusarium oxysporum f. sp. capsici (FCO) severely reduces the production of chili worldwide. There is growing evidence of resistance to commercial fungicides targeting succinate dehydrogenase (Sdh) of FCO soliciting the development of new Sdh inhibitors (SdhIs). In the current work, optimize docking and virtual screening were used to mine twelve SdhIs from the ZINC database, followed by in vitro antifungal evaluation on spore and radial mycelium development. Four new promising SdhIs exhibiting a mean mycelium inhibition rate greater than 85.6% (F = 155.8, P = 0.001, P < 0.05) were observed on ten strains of virulent resistant FCO. Importantly, three of the discovered molecules exhibited potent spore germination inhibition (≥ 80%, P = 00.1, P < 0.05) compared to the commonly used fungicide penthiopyrad. A significant positive correlation (r* ≥ 0.67, P < 0.05) between the activities of the newly discovered SdhIs compared to penthiopyrad against all tested FCO strains indicated a broad-spectrum fungicidal activity. The current findings indicate that the four SdhI’s discovered could judiciously replace certain commercial SdhIs displaying resistance against F. oxysporum f. sp. capsici.
Metabolic Profiling, ADME Pharmacokinetics, Molecular Docking Studies and Antibacterial Potential of Phyllanthus muellerianus Leaves
Authors: Obuotor Tolulope , AMOS KOLAWOLE , apalowo oladayo , AKANMO Adio
Published: June 2021

Global increase in the level of antimicrobial resistance among bacterial pathogens has prompted the search for alternative treatment from medicinal plants. Phyllanthus muellerianus (PM) leaves has been used traditionally against microorganisms of medical importance, hence the need to evaluate the pharmacological pathways and mode of actions using in vitro and in silico approaches. Clinical isolates of eight (8) microorganisms associated with urinary tract infections (UTIs) were obtained and identified using morphological and biochemical methods. Phyllanthus muellerianus (PM) leaves were extracted and purified by solvent partitioning. Ethyl acetate fraction of PM had the highest yield and zone diameter range from 13.5±1.00mm to 28±1.53mm. The rate of protein leakage per time interval of Staphylococcus aureus increased from 9.29 μg/ml at 0 minute to 17.43 μg/ml at 120 minutes while leakage in Candida albicans also increased from 8.57 μg/ml at 0 minute to 70.43 μg/ml at 120 minutes. GCMS fingerprints, pharmacodynamics and pharmacokinetic studies revealed the active agent as quindoline, an azaindole and isotere of indoles having a binding energy of -9.1 kcal/mol. Analyses of the structural and atomic orientations of quindoline, and superimposition on ciprofloxacin, a common antibiotic revealed an interesting comparison, effecting a stronger binding affinity of Quindoline-HMG-CoA complex.
Basal Ganglia Infarction a Rare Neurological Manifestation of COVID-19 in an Elderly Patient: A Case Report
Authors: Kamal Manar Ahmed
Published: June 2021

Background: Coronavirus disease 2019 (COVID-19) is spreading rapidly worldwide since the first cases were observed in Wuhan, China. Patients with COVID-19 develop multiple neurological symptoms, including headache, disturbed consciousness, and paresthesia, in addition to systemic and respiratory symptoms. Case presentation: We presented a 57-years-old woman admitted to the emergency department (ED) - in December 2020 - with complaints of slurred speech, confusion, and left upper limb weakness after one week of positive nasopharyngeal swab sample for SARS-CoV-2. Conclusion: This case report concludes that unilateral acute basal ganglia infarction may be a unique neurological manifestation after COVID-19 infection in an elderly patient.
The Antitumor Activity of Pseudoginsengenin DQ Against Hypopharyngeal Cancer Cells via Targeting HIF-1α-GLUT1 Pathway
Authors: Wang Sanchun , Cai Yu , Feng Qingjie , Gao Jing , Teng Bo
Published: June 2021

Background
The ginsenosides have been reported to possess a variety of biological activities. Synthesized from the ginsenoside Protopanaxadiol (PPD), the octanone Pseudoginsengenin DQ (PDQ) may have stronger pharmacological effects as a secondary ginsenoside. Nevertheless, its antitumor activity and molecular mechanism against hypopharyngeal cancer cells remains unclear.
Methods
Cell Counting Kit-8, cell cycle assay and cell apoptosis assay were conducted to detect FADU cells proliferation, cell phase and apoptosis. The interactions between PDQ and HIF-1α were investigated by a molecular docking study. The expression of HIF-1α, GLUT1, apoptosis related proteins was tested by western blotting, direct stochastic optical reconstruction microscopy (dSTORM) and qRT-PCR. Glucose uptake assay was used to assess the glucose uptake capacity of FADU cells.
Results
PDQ was found to suppress the proliferation, reduce glucose uptake, induce the cell cycle arrest and apoptosis of FaDu cells. Molecular docking study demonstrated that PDQ could interact with the active site of HIF-1α. PDQ decreased the expression and mRNA levels of HIF-1α and its downstream factor GLUT1. Moreover, dSTORM results showed that PDQ reduced GLUT1 expression on the cell membrane but also inhibited its clustering.
Conclusion
Our work elucidated that the antitumor effect of PDQ is related to its downregulation of HIF-1α-GLUT1 pathway, suggesting that PDQ could be a potential therapeutic agent for hypopharyngeal cancer treatment.
USF1 Promotes Lung Adenocarcinoma Progression by Regulating Neurotrophin Signaling Pathway
Authors: Wang Yu , Zhao Yunxia , Zhang Xiangwei , Jiang Yuanzhu , Ma Wei , Zhang Lin , dong wei
Published: June 2021

Background: We aimed at investigation of the effect and the underlying neurotrophin signaling pathway of the upstream transcription factor 1 (USF1) in lung adenocarcinoma (LUAD).Methods: The Cancer Genome Atlas (TCGA) database was used to analyze USF1 expression data and to extract patients’ clinical records. Immunohistochemical assay and Western blotting (WB) were used to determine the expression levels of USF1 in LUAD. The neurotrophin signaling pathway was analyzed by bioinformatic analysis while the expression of all related proteins was determined by WB. In addition cellular viability, proliferation, migration and invasion potential were investigated by the CCK-8, colony formation, wound healing and transwell. Meanwhile, the effect of USF1 in LUAD progression was investigated in a mouse model. The link between USF1 and UGT1A3 (UDP Glucuronosyltransferase Family 1 Member A3) was studied by the dual-luciferase reporter assay. Results: We have detected a high expression level of USF1 in LUAD, which was associated with advanced tumor stage, nodal metastasis, and poor patient’s survival rate. The knockdown of USF1 inhibited cellular viability, proliferation, migration and invasion. Meanwhile, USF1 knockdown inhibited tumor growth in a mouse model. Besides, USF1 targeted UGT1A3, which was proven by the fact that the USF1 knockdown decreased the expression level of UGT1A3, whereas the upregulated expression of UGT1A3 increased cellular viability and proliferation. We have proved that the neurotrophin signaling pathway in LUAD was activated by USF1 and UGT1A3. The expression of the related proteins was also inhibited by the USF1 knockdown, while the overexpression of IRAK increased cancer cells’ migration and invasion potential.Conclusion: USF1 was highly expressed in LUAD and promoted LUAD progression by regulating the neurotrophin signaling pathway. These findings provide a new theoretical data that could serve as a good foundation for the treatment of LUAD.
Construction of Intelligent Integrated Model Framework for the Workshop Manufacturing System Via Digital Twin
Authors: Zhang Zhongyu , Zhu Zhenjie , Zhang Jinsheng , Wang Jingkun
Published: June 2021

With the drastic development of the globally advanced manufacturing industry, transition of the original production pattern from traditional industries to advanced intelligence is completed with the least delay possible, which are still facing new challenges. Because the timeliness, stability and reliability of them is significantly restricted due to lack of the real-time communication. Therefore, an intelligent workshop manufacturing system model framework based on digital twin is proposed in this paper, driving the deep inform integration among the physical entity, data collection, and information decision-making. The conceptual and obscure of the traditional digital twin is refined, optimized, and upgraded on the basis of the four-dimension collaborative model thinking. A refined nine-layer intelligent digital twin model framework is established. Firstly, the physical evaluation is refined into entity layer, auxiliary layer and interface layer, scientifically managing the physical resources as well as the operation and maintenance of the instrument, and coordinating the overall system. Secondly, dividing the data evaluation into the data layer and the processing layer can greatly improve the flexible response-ability and ensure the synchronization of the real-time data. Finally, the system evaluation is subdivided into information layer, algorithm layer, scheduling layer, and functional layer, developing flexible manufacturing plan more reasonably, shortening production cycle, and reducing logistics cost. Simultaneously, combining SLP and artificial bee colony are applied to investigate the production system optimization of the textile workshop. The results indicate that the production efficiency of the optimized production system is increased by 34.46%.
Association of Sequential Organ Failure Assessment (SOFA) components with mortality
Authors: Pölkki Anssi , Pekkarinen Pirkka T , Takala Jukka , Selander Tuomas , Reinikainen Matti
Published: June 2021

BackgroundSequential Organ Failure Assessment (SOFA) is a practical and widely used method to describe and quantify the presence and severity of organ system dysfunctions and failures. Some proposals suggest that SOFA could be employed as an endpoint in interventional trials. To justify this, all SOFA components should have comparable weights as organ dysfunction measures. In this study we aimed to investigate whether the associations of different SOFA components with in-hospital mortality are comparable.MethodsWe performed a study based on nationwide register data on adult patients admitted to 26 Finnish intensive care units (ICUs) during 2012−2015. We determined the SOFA score as the maximum score in the first 24 hours after ICU admission. We defined organ failure as an organ-specific SOFA score of three or higher. We evaluated the association of different SOFA component scores with mortality using multivariable logistic regression analysis. ResultsOur study population comprised 63,756 ICU patients. Overall hospital mortality was 10.7%. In-hospital mortality was 22.5% for patients with respiratory failure, 34.8% for those with coagulation failure, 40.1% for those with hepatic failure, 14.9% for those with cardiovascular failure, 26.9% for those with neurologic failure and 34.6% for the patients with renal failure. The age-adjusted odds ratio for in-hospital death was 2.41 [95% confidence interval (CI) 2.27-2.56] for respiratory failure, 4.04 (95% CI 3.57-4.57) for coagulation failure, 4.24 (95% CI 3.47-5.17), for hepatic failure, 1.57 (95% CI 1.47-1.67) for cardiovascular failure, 5.00 (95% CI 4.71-5.30) for neurologic failure, and 4.93 (95% CI 4.58-5.32) for renal failure. Organ failure combinations including cardiovascular failure were associated with lower mortality than other organ failure combinations.ConclusionsAll SOFA components are associated with mortality, but their weights are not comparable. High cardiovascular SOFA scores do not imply an equally high risk as high scores of other components.
Sustaining the Oil and Gas Multinationals’ Operations Through Corporate Social Responsibility Practices
Authors: Gyane Ama Twumwaa , Nunoo Edward Kweku , Suleman Shafic , Essandoh-Yeddu Joseph
Published: June 2021

The objective of this study is to provide empirical evidence from the perspective of prudent corporate social responsibility practices by oil and gas multinationals in emerging economies on how investments in and disclosure of the practices can enhance financial sustainability. Accounting-based measures on investments, financial performance, disclosures of activities and panel data set on company size (total assets) over a 10-year period (t) were analysed. Findings show that multinationals with interests in emerging economies take key aspects of their corporate social responsibility practices seriously. There was a significant positive relationship (p=0.0035<0.05) between investments in corporate social responsibility practices and sustainability of financial performance. No significant relationship (p=0.4409 > 0.05) was established between disclosure and financial performance. The paper concludes, by supporting the preposition with scientific data, that functional corporate social responsibility practices yield sustained dividend by presenting a stronger financial outlook for multinational oil and gas companies who engage in it. This is prudent for poverty alleviation initiatives and key to achieving the sustainable development goals and targets in emerging economies where they operate.
Two-Dimensional Simulation of Frost Formation on the NACA0012 Airfoil under Strong Convection by Using the P-VOF Method
Authors: Xia Bin , Xu Xianghua , Liang Xingang
Published: June 2021

A newly developed frosting simulation method, pseudo-VOF (p-VOF) method, has applied to simulate the dynamic frost formation on the NACA0012 airfoil under strong convection. The p-VOF method is a pseudo volume of fraction simulation method of the multiphase flow with phase change. By solving a simplified mass conservation equation explicitly instead of the original volume fraction equations in CFD software, the efficiency and robustness of calculation are greatly improved. This progress makes it possible to predict a long-time frost formation. The p-VOF method was successfully applied to the simulation of dynamic frosting on the two-dimensional NACA0012 airfoil under strong convection conditions with constant frost physical properties. The simulation result shows that the average thickness of the frost layer increases, and the frost bulges and flow separation appear earlier, when the airfoil surface temperature decreases or the air humidity increases. The frost bulges and flow separation appear earlier, when the air velocity is faster, the growth rate of the frost layer at the early stage is greater, but the final frost layer is thinner.
Comprehensive Analysis of Tumor Immune Microenvironment and Prognosis of m6A-Related lncRNAs in Gastric Cancer
Authors: Wang Yi , Zhu Gui-Qi , Tian Di , Zhou Chang-Wu , Li Na , Feng Ying , Zeng Meng-Su
Published: June 2021

Background N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play pivotal role in gastric cancer (GC) progression. The emergence of immunotherapy in GC has created a paradigm shift in the approach of treatment, whereas there is significant heterogeneity with regard to degree of treatment responses, which results from the variability of tumor immune microenvironment (TIME). How the interplay between them enrolled in the shaping of TIME remains unclear. Methods The RNA sequencing and clinical data of GC patients were collected from TCGA database. Pearson correlation test and univariate Cox analysis were used to screen out m6A-related lncRNAs. Consensus clustering was implemented to classify GC patients into 2 subtypes. Survival analysis, the infiltration of immune cells, Gene set enrichment analysis (GSEA) and the mutation profiles were analyzed and compared between two clusters. Then least absolute shrinkage and selection operator (LASSO) COX regression was implemented to select pivotal genes and risk score model was constructed accordingly. The prognosis value of the risk model was explored. In addition, the discrepancies of response to immune checkpoints inhibitor (ICIs) therapy were compared between different risk groups. Finally, we performed qRT-PCR to detect the expression pattern in 35 tumor tissues and paired adjacent normal tissue, and validated the prognostic value of risk model in the our cohort (N=35). Results The expression profiles of 23 lncRNAs were included to cluster patients into different subtypes. Cluster1 with worse prognosis harbored higher immune score, stromal score, ESTIMATE score and mutation rate of genes. Different immune cell infiltration pattern were also displayed between different clusters. GSEA showed that cluster1 was preferentially enriched with tumor hallmarks and tumor correlated biological pathways. Next, 9 lncRNAs were selected by LASSO regression model to construct risk model. Patients in the high risk group had poor prognosis. The prognosis value of this model was also validated in our cohort. As for predicting responses to the ICIs therapy, we found that patients from high risk group had lower TMB score and lower proportion of MSI-H subtype. Moreover, patients had distinct immunophenoscores in different risk groups. Conclusion Our study revealed that the potential interplay between m6A modification and lncRNAs might have critical role in predicting GC prognosis, sculpting TIME landscape and predicting the responses to immune checkpoints inhibitors therapy.
How Equitable Are the Distributions of the Physical Activity and Accessibility Benefits of Bicycle Infrastructure?
Authors: Standen Christopher , Crane Melanie , Greaves Stephen , Collins Andrew , Rissel Chris
Published: June 2021

BackgroundCycling for transport provides many health and social benefits – including physical activity and independent access to jobs, education, social opportunities, health care and other services (accessibility). However, inequalities exist for some population groups in the opportunity to reach everyday destinations, and public transport stops, by bicycle – owing in part to their greater aversion to riding in amongst motor vehicle traffic. Health equity can therefore be improved by providing separated cycleway networks that give people the opportunity to access places by bicycle using traffic-free routes. The aim of this study was to assess the health equity benefits of two bicycle infrastructure development scenarios – a single cycleway, and a complete network of cycleways – by examining the distribution of physical activity and accessibility benefits across gender, age and income groups.MethodsTravel survey data collected from residents in Sydney (Australia) were used to train a predictive transport mode choice model, which was then used to forecast the impact of the two scenarios on transport mode choice, physical activity and accessibility. Accessibility was measured using a utility-based accessibility measure derived from the mode choice model. The distribution of forecast physical activity and accessibility benefits was then calculated across gender, age and income groups.ResultsThe modelled physical activity and accessibility measures improve in both intervention scenarios. However, in the single cycleway scenario, the benefits are greatest for the male, high-income and older age groups. In the complete network scenario, the benefits are more equally distributed. Forecast increases in cycling time are largely offset by decreases in walking time – though the latter is typically low-intensity physical activity, which confers a lesser health benefit than moderate-intensity cycling.ConclusionsSeparated cycleway infrastructure can be used to improve health equity by providing greater opportunities for transport cycling in population groups more averse to riding amongst motor vehicle traffic. Disparities in the opportunity to access services and economic/social activities by bicycle – and incorporate more physical activity into everyday travel – could be addressed with connected, traffic-free cycleway networks that cater to people of all genders, ages and incomes.
Associations Between Elemental Constituents of Fine Particulate Matter and Subclinical Atherosclerosis in Adolescents and Young Adults
Authors: Chen Szu-Ying , Wu Charlene , Wu Chang-Fu , Chan Chang-Chuan , Hwang Jing-Shiang , Su Ta-Chen
Published: June 2021

BackgroundExisting studies have demonstrated the relationships between particulate matter (PM) exposure and subclinical atherosclerosis; however, whether PM and its elemental constituents predispose to atherosclerosis remains unclear in adolescents and young adults. This cross-sectional study included 789 subjects between the ages of 12 to 30 years who lived in Taipei metropolis since childhood. Health examination and carotid intima-media thickness (CIMT) measurements were performed between 2006 and 2008. Land use regression (LUR) model was used to estimate participants’ one-year exposure to fine particulate matter (PM2.5) and eight elemental constituents, i.e., silicon (Si), sulfur (S), titanium (Ti), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), and zinc (Zn). The associations between percent differences in CIMT at common carotid artery (CCA) segments and air pollutants were analyzed.ResultsAn interquartile range increment of PM2.5 (4.5 μg/m3), Fe (34.7 ng/m3), and Zn (20.7 ng/m3) are associated with 0.77% (95% confidence interval; 95%CI: 0.05 to 1.50), 0.83% (0.01 to 1.65), and 1.22% (0.35 to 2.10) higher for combined CIMT, respectively; while Mn (2.0 ng/m3) exposure is associated with 0.31% (0.01 to 0.60) higher for right CIMT. Stratified analyses show PM2.5 and elemental constituents, especially Zn, are associated with CIMT among subjects who are 18 years or older, females, lower household income, non-smokers, normal weight, non-hypertensive, non-hyperglycemic, or non-hypercholesterolemic. ConclusionsLong-term exposures to PM2.5 and elemental constituents mainly originating from traffic and industry operations are associated with subclinical atherosclerosis in young population. Individual characteristics, health behaviors, and biometric measures, may modify air pollution-related subclinical atherosclerosis.
Novel Drawing System Approach To Manufacture Performant Commercially Pure Aluminium Fine Wires
Authors: Caruso Serafino , Ambrogio Giuseppina
Published: June 2021

Due to its electro-mechanical properties, commercially pure aluminium wires have attracted the interest of automotive industry representing a functional and efficient economic solution to reduce vehicle’s weight leading to the diminishing of energy consumption and emissions in today’s society. However, to consolidate its use in this sector and in new market realities, it is necessary to increase the flexibility of the aluminium conductor wires, consenting their installation in very small spaces and with high curvatures, avoiding any failure and electrical conductivity decrease. Thus, the evolution of microstructure and service performance need to be investigated and controlled to improve the service safety. The present research shows a new approach to efficiently continuously manufacture long wires with smaller diameters and fine grains at room temperature. It is studied the strengthening effects (yield and tensile strength, plasticity, hardness), the electrical conductivity and the microstructural changes of commercial 1370 pure aluminium (99.7% Al) when traditional wire drawing process is combined with equal channel angular drawing (ECAD) technique. The results of this proposed procedure of deformation “drawing-ECAD-drawing” show an evident benefit, compared to the classic technology of production of aluminium wire, obtaining fine grain structure product with superior mechanical strength and not influenced electrical conductivity. The proposed manufacturing approach leads to fine wires enhancing the material mechanical properties by microstructural evolution (i.e. grain size reduction) avoiding the traditional post manufacturing thermal treatments requiring a high amount of energy and time and careful steps.
ANRIL Regulates Multiple Molecules of Pathogenetic Significance in Diabetic Nephropathy
Authors: Sooshtari Parisa , Feng Biao , Biswas Saumik , Levy Michael , Lin Hanxin , Su Zhaoliang , Chakrabarti Subrata
Published: June 2021

Background: Hyperglycemia-induced transcriptional alterations lead to aberrant synthesis of a large number of pathogenetic molecules leading to functional and structural damage to multiple end organs including the kidneys. Diabetic nephropathy (DN) remains a major cause of end stage renal disease. Multiple epigenetic mechanisms, including alteration of long non-coding RNAs (lncRNAs) may play a significant role mediating the cellular transcriptional activities. We have previously shown that lncRNA ANRIL may mediate diabetes associated molecular, functional and structural abnormalities in DN. Here we explored downstream mechanisms of ANRIL alteration in DN.Methods: We used renal cortical tissues from ANRIL knockout (KO) mice and wild type (WT) B6 mice, with or without streptozotocin (STZ) induced diabetes for RNA sequencing. The differentially expressed genes were identified using edgeR and DESeq2 computational methods. KEGG and Reactome pathway analyses and network analysesusing STRING and IPA were subsequently performed. Results: Diabetic animals showed hyperglycemia, reduced body weight gain, polyuria and increased urinary albumin. Both albuminuria and polyuria were corrected in the KO diabetic mice. RNA analyses showed Diabetes induced alterations of a large number of transcripts in the wild type (WT) animals. ANRIL knockout (KO) prevented a large number of such alterations. The altered transcripts include metabolic pathways, apoptosis, extracellular matrix protein synthesis and degradation, NFKB related pathways, AGERAGE interaction pathways etc. ANRIL KO prevented majority of these pathways. Conclusion: These findings suggest that as ANRIL regulates a large number of molecules of pathogenetic significance, it may potentially be a drug target for DN and other chronic diabetic complications.
Classification of RA Into Active or Inactive With a Modified DAS, for Future Use as a Treat-to-target Tool, With a HandScan Score Replacing Joint Counts
Authors: Verhoeven Maxime , Westgeest Anton , Tekstra Janneke , Laar Jacob van , Lafeber Floris , Welsing Paco , Jacobs Johannes
Published: June 2021

ObjectivesTo establish the value of a modified DAS (DAS-OST) without joint counts but with a HandScan score (OST), versus that of DAS28, to classify RA as active versus inactive, with as reference standard the rheumatologist's clinical classification.MethodsRA patients with at least one HandScan and DAS28 measurement performed at the same visit were included. Data was extracted from medical records, as was the clinical interpretation as active or inactive RA by the rheumatologist. Logistic regression analyses were performed to calculate areas under the receiver operating characteristics (AU-ROC) curves. The clinical interpretation was used as reference standard in all analyses, and disease activity measures were used as predictor variables. The performance of predictor variables (AU-ROCs) was compared.ResultsData of 1505 unique RA patients were used for analyses. The highest AU-ROC of 0.88 (95%CI 0.85 – 0.90) was shown for DAS28; AU-ROC of DAS-OST was 0.78 (95%CI 0.75 – 0.81), difference 0.10, p<0.01.ConclusionsCompared to DAS28, DAS-OST classified RA statistically significantly less well as active versus inactive, when using the clinical classification as reference standard. However, a DAS-modification without joint scores might have a place in strategies limiting routine outpatients’ visits to the rheumatologist.
Deaggregation of Probabilistic Seismic Hazard and Construction of Pseudo-Exact Conditional Spectrum for China
Authors: Ji Kun , Wen Ruizhi , Ren Yefei , Wang Weiyi , Chen Lansheng
Published: June 2021

For mainland China, the primary obstacle in conditional spectrum (CS) based ground motion selection work is that the corresponding seismic hazard deaggregation results were not released for the China national standard GB 18306- 2015 “Seismic Ground Motion Parameter Zonation Map”, which refers to the fifth-generation seismic hazard map. Therefore, this study firstly constructed a probabilistic seismic hazard map for mainland China using the three level seismicity source models as applied to produce the fifth-generation seismic hazard map. The derived peak ground acceleration (PGA) values in our seismic hazard map were basically consistent with the fifth-generation seismic hazard map for most of the 34 principal Chinese cities considered. Then, three-dimensional deaggregation scheme was performed for PGA and 5%-damped spectral acceleration (Sa) corresponding to mean return periods of 475 and 2475 years. Based on the magnitude-longitude-latitude deaggregation results of three example cities: Xichang, Kunming, and Xi’an, approximate and pseudo-exact conditional spectrum were established with/without considering multiple casual earthquakes and possible strike directions of the potential source areas. The mean pseudo-exact CS lies between the results of approximate CS using long and short axis GMMs. The conditional standard deviation of pseudo-exact CS is approximately 1.1 to 1.5 times larger than the approximate CS for the periods away from the conditional period. For three example cities, hazard consistency of the spectral accelerations of the ground motion realizations matching target distribution of pseudo-exact CS and geometric mean approximate CS were evaluated and validated. Moreover, for the 34 studied cities, we tabulated the uniform hazard curve and deaggregation results for PGA and Sa values (0.2, 0.3, 0.5, 0.7, 1.0, 1.5, and 2.0s) at MRPs of 475 and 2475 years. (https://github.com/JIKUN1990/China-Seismic-Hazard-Deaggregation-34cities)
Impact of Operational Conditions on Methane Yield and Microbial Community Composition during Biological Methanation in a Hybrid Reactor System
Authors: Wahid Radziah , Horn Svein Jarle
Published: June 2021

Background: Biogas can be upgraded to methane biologically by adding hydrogen to biogas reactors. The process is called biological methanation (BM) and can be done in-situ in a regular biogas reactor or the biogas can be transferred to a separate ex-situ upgrading reactor. The hybrid BM concept, a combination of in-situ and ex-situ BM, has received little attention, and only a few studies have been reported. The hybrid BM has the advantage of resolving the issue of pH increment during in-situ BM, while the size of the ex-situ BM reactor could be reduced.Results: In this study, the efficiency of in-situ and hybrid biological methanation (BM) for upgrading raw biogas was investigated. The hybrid BM system achieved a CH4 yield of 257 mL gVS-1 when degrading a feedstock blend of manure and cheese waste. This represented an increase in methane yield of 76% when compared to the control reactor with no H2 addition. A 2:1 H2:CO2 ratio resulted in stable reactor performance, while a 4:1 ratio resulted in a high accumulation of volatile fatty acids. H2 consumption rate was improved when a low manure-cheese waste ratio (90%:10%) was applied. Furthermore, feeding less frequently (every 48 hours) resulted in a higher CH4 production from CO2 and H2. Methanothermobacter was found to dominate the archaeal community in the in-situ BM reactor, and its relative abundance increased over the experimental time. Methanosarcina abundance was negatively affected by H2 addition and was nearly non-existent at the end of the experiment. Conclusions: Our results show that hybrid BM outperforms in-situ BM in terms of total CH4 production and content of CH4 in the biogas. The application of hybrid BM increased CH4 yield up to 42%. Furthermore, addition of H2 at 2:1 H2:CO2 ratio in in-situ BM resulted in stable reactor operation.
Construction of the Metabolomics-Based Prognosis-Prediction Models for ICU Septic Patients
Authors: Ding Xianfei , Tong Ran , Song Heng , Sun Guiying , Wang Dong , Liang Huoyan , Sun Junyi , Cui Yuqing , Zhang Xiaojuan , Liu Shaohua , Cheng Ming , Sun Tongwen
Published: June 2021

Background: Global mortality related to sepsis remains unacceptably high in intensive care units (ICUs). Accurate prognostic evaluation of sepsis could effectively reduce the mortality of septic patients. Our goal is to present an effective and rapid method to assess the prognosis of sepsis.Methods: We included 96 septic patients according to the sepsis 3.0 in ICU, who were grouped into survival and death groups according to 28-day, hospital, and 90-day prognosis. Liquid chromatography/mass spectrometry was performed to detect the metabolite changes in plasma. Multivariate logistic regression models, using differential metabolites and clinical indicators within 24 h after diagnosis of sepsis, were used to construct the prediction models for 28-day, hospital, and 90-day prognosis in sepsis.Results: Metabolic profiles related to 28-day, hospital, and 90-day prognosis were significantly different between the survival and the death group. Specifically, 13, 4, and 29 primary differential metabolites related to amino acid metabolism and fatty acid metabolism were identified between the survival and death group at 28-day, hospital, and 90-day prognosis, respectively. Further, we found that model 1 including indoleacetic acid, 3-methylene-indolenine, heart rate, respiratory support, and application of pressure drugs; model 2 including lymphocyte count, alkaline phosphatase, SOFA, and L-alpha-amino-1H-pyrrole-1-hexanoic acid; model 3 including pyrrolidine, dopamine, heart rate, respiratory support, and application of pressure drugs, could predict 28-day, hospital, and 90-day prognosis of sepsis with a sensitivity of 75.51%, 73.58%, and 83.33%, specificity of 78.72%, 72.09%, and 76.19%, the area under the receiver operating characteristics curve of 0.881, 0.830, 0.892, respectively.Conclusions: This research could be used to predict the 28-day, hospital, and 90-day prognosis of septic patients based on differential metabolites and clinical parameters, and could also be used to develop novel sepsis-treatment methods.
Evaluating Performance of Multiplex Real Time PCR for the Diagnosis of Malaria at Elimination Targeted Low Transmission Settings of Ethiopia.
Authors: Belachew Mahlet , Wolde Mistire , Nega Desalegn , Gidey Bokretsion , Negash Legessie , Assefa Ashenafi , Tasew Geremew , Woyessa Adugna , Hirpa Adugna Abera
Published: June 2021

Background: Malaria incidence has declined in Ethiopia in the past ten years. Current malaria diagnostic tests, including light microscopy and antigen-detecting rapid tests (RDTs) cannot reliably detect low-density infections. Studies have shown that nucleic acid amplification tests are highly sensitive and specific in detecting malaria infection. Thus, this study took place with the aim of evaluating the performance of multiplex real time PCR for the diagnosis of malaria using patient samples collected from health facilities located at malaria elimination targeted low transmission settings in Ethiopia. Methods: A health facility based cross sectional survey was conducted in selected malaria sentinel sites. Malaria suspected febrile outpatients referred to laboratory for malaria testing between December 2019 and March 2020 were enrolled into this study. Socio demographic information and capillary blood samples were collected from the study participants and tested at spot with RDTs. Additionally, five circles of dry blood sample (DBS) samples on Whatman filter paper and thick and thin smear were prepared for molecular testing and microscopic examination, respectively. Multiplex real time PCR assay was performed at EPHI malaria laboratory. The performance of multiplex real time PCR assay, microscopy and RDT for the diagnosis of malaria was compared and evaluated against each other.Results: Out of 271 blood samples, multiplex real time PCR identified 69 malaria cases as P. falciparum infection, 16 as P. vivax and 3 as mixed infections. Of the total samples, light microscopy detected 33 as Pf, 18 as PV and RDT detected 43 as Pf, 17 as PV, and one mixed infection. Using light microscopy as reference test, the sensitivity and specificity of multiplex real time PCR were 100% (95% CI [93-100]) and 83.2% (95% CI [77.6-87.9]), respectively. Using multiplex real time PCR as a reference, light microscopy and RDT had sensitivity of 58% (95% CI [46.9-68.4] and 67% (95% CI [56.2-76.7]); and 100% (95% CI [98-100] and 98.9 (95% CI (96-99.9), respectively. Substantial level of agreement was reported between microscopy and multiplex real time PCR results with kappa value of 0.65. Conclusions: Multiplex real time PCR had an advanced performance in parasite detection and species identification on febrile patients’ samples than did microscopy and RDT in low malaria transmission settings. It is highly sensitive malaria diagnostic method that can be used in malaria elimination program, particularly for community based epidemiological samples. Although microscopy and RDT had reduced performance when compared to multiplex real time PCR, still had an acceptable performance in diagnosis of malaria cases on patient samples at clinical facilities.
Global Impact of Non-essential Heavy Metal Contaminants in Industrial Cannabis Bioeconomy
Authors: Bengyella Louis , Ali Mohammed Q.O. , Mukherjee Piyali , Fonmboh Dobgima J. , Kaminski John E.
Published: June 2021

The intrinsic signatures of Cannabis species to bioaccumulate non-essential harmful heavy metals (HMs) are substantially determined by their high tolerance, weedy propensities, phenotypic plasticity attributes, and pedoclimatic stress adaptation in an ecological niche. The detection trends of HMs contaminants in cannabis products have reshaped the 2027 forecast and beyond for global cannabis trade valued at $57 billion. Consumer base awareness for the cohort of HMs contaminants viz., lead (Pb), mercury (Hg), arsenic (As), chromium (Cr), cadmium (Cd), and radioactive elements, and the associative dissuading effects significantly impact cannabis bioeconomy. On the premise that fiber hemp (Cannabis sativa L.) could be repurposed to diverse non-consumable products, concerns over HMs contamination would not significantly decrease fiber trade, a trend that could impact globally by 2025. The economic trend will depend on acceptable consumer risk, regulatory instruments, and grower's due diligence to implement agronomic best practices to mitigate HMs contamination in marketable cannabis-related products. In this unstructured meta-analysis study based on published literature, the application of Cannabis species in HMs phytoremediation, new insights into transportation, distribution, homeostasis of HMs, the impact of HMs on medical cannabis, and cannabis bioeconomic are discussed. Furthermore, a blueprint of agronomic strategies to alleviate HMs uptake by plant is proposed. Considering that one-third of the global arable lands are contaminated with HMs, revamping global production of domesticated cannabis requires a rethinking of agronomic best practices and post-harvest technologies to remove HMs contaminants.
Structure of the human RNA Polymerase I Elongation Complex
Authors: Xu Yanhui , Zhao Dan , Liu Weida , Chen Ke , Wu Zihan , Yang Huirong
Published: June 2021

Eukaryotic RNA polymerase I (Pol I) transcribes ribosomal DNA and generates RNA for ribosome synthesis. Pol I accounts for the majority of cellular transcription activity and dysregulation of Pol I transcription leads to cancers and ribosomopathies. Despite extensive structural studies of yeast Pol I, structure of human Pol I remains unsolved. Here, we determined the structures of the human Pol I in the pre-translocation, post-translocation, and backtracked states at near-atomic resolution. The single-subunit peripheral stalk lacks contacts with the DNA-binding clamp and is more flexible than the two-subunit stalk in yeast Pol I. Compared to yeast Pol I, human Pol I possesses a more closed clamp, which makes more contacts with DNA and may support more efficient transcription in human cells. The Pol I structure in the post-cleavage backtracked state shows that the C-terminal zinc ribbon of RPA12 inserts into an open funnel and facilitates “dinucleotide cleavage” on mismatched DNA-RNA hybrid. Critical disease-associated mutations are mapped on Pol I regions that are involved in catalysis and complex organization. In summary, the structures provide new sights into human Pol I complex organization and efficient proofreading, consistent with requirement of efficient transcription of ribosomal DNA in human cells.
An Ultrafast One-Step qRT-PCR Assay for Detection of SARS-CoV-2
Authors: Milosevic Jadranka , Lu Mengrou , Greene Wallace , He Hong-Zhang , Zheng Si-Yang
Published: June 2021

We developed an ultrafast one-step RT-qPCR assay for SARS-CoV-2 detection, which can be completed in only 30 mins on benchtop Bio-Rad CFX96. The assay significantly reduces the running time of conventional RT-qPCR: reduced RT step from 10 to 1 min, and reduced PCR cycle of denaturation from 10 to 1 s and extension from 30 to 1 s. A cohort of 60 nasopharyngeal swab samples testing showed that the assay had a clinical sensitivity of 100% and a clinical specificity of 100%.