bluuebunny/crossref_metadata_2025_split huggingface dataset:
APPLICATION OF MULTIVARIATE ANOVA AND GENERALIZED DESIRABILITY TO OPTIMIZE THE COMPOSITION AND TECHNOLOGY OF TABLETS CONTAINING N-BENZYL-N-METHYL-1-PHENYLPYRROLO [1,2-A] PYRAZINE-3-CARBOXAMIDE
Authors: Tishkov S. V. , Blynskaya E. V. , Alekseev K. V. , Alekseev V. K. , Gavrilov D. I. 
Published: March 2022

The creation of drugs with an anxiolytic activity, which do not have the main side effects characteristic of drugs of this group, is an important and socially significant task. For its implementation, within the framework of the development of an original drug with an anxiolytic activity, the composition and manufacturing of GML-1 tablets (N-benzyl-N-methyl-1-phenylpyrrolo [1,2-a] pyrazine-3-carboxamide) are being developed.The aim of this article is to study, using a four-factor analysis of variance, the influence of composition factors on the manufacturing properties of GML-1 tablets and the selection of the type, the amount, stage of the disintegrant addition and the type of lubricating excipients used in the technology of wet granulation of GML-1 tablets.Materials and methods. The materials used are: the substance – GML-1 (N-benzyl-N-methyl-1-phenylpyrrolo [1,2-a] pyrazine-3-carboxamide). Excipients: microcrystalline cellulose 101 (MCC 101); polyvinylpyrrolidone (PVP); crospovidone, croscarmellose sodium (CCS), sodium starch glycolate (SSG); magnesium stearate (MS), sodium stearyl fumarate (SSF). To obtain tablet mixtures, wet granulation and tableting with the study of their main pharmaceutical and technological properties was used.Results. Model compositions were developed and their pharmaceutical and technological properties were studied. These results have been analyzed, the degree of these factors’ influence and their interactions have been determined. In most of the cases considered, the interactions of the factors did not cause a significant change in the optimization criteria. With an increase in the amount of a disintegrant, the disintegration time decreased unevenly, so an increase in the amount of these excipients from 4 to 6 mg had a stronger effect than from 2 to 4 mg. Factor B affected the release degree non-linearly. Factor A influenced all the optimization criteria considered, especially a PS release. The best release and disintegration were observed with crospovidone, which was of a particular importance when processing the test results using a generalized desirability method.Conclusion. In view of the conflicting variance analysis results, for particular factors, the resulting values were additionally analyzed using the generalized desirability function. The use of this method made it possible to reduce the conflicting variance analysis results to the most optimal composition.
PHARMACOTHERAPY POSSIBILITIES OF CARDIOVASCULAR AUTONOMOUS NEUROPATHY IN CHILDREN WITH TYPE 1 DIABETES MELLITUS AT THE PRECLINICAL STAGE
Authors: Malyuzhinskaya N. V. , Shishimorov I. N. , Magnitskaya O. V. , Stepanenko K. V. , Polyakova O. V. , Klitochenko G. V. , Petrova I. V. , Emelyanova S. A. , Skiba A. P. 
Published: March 2022

The aim of the article is to evaluate the effectiveness of the thioctic acid preparation in the complex therapy of type 1 diabetes mellitus (T1DM) in children with cardiovascular autonomic neuropathy at the preclinical stage.Materials and methods. A design is a prospective randomized study. A clinical and instrumental examination of 64 children with preclinical stage signs of diabetic cardiovascular autonomic neuropathy (DCAN) was carried out. The cohort was divided into 2 groups: in the main and control groups, glycemic control was normalized by adjusting a dose of insulin therapy; in the main group, the children additionally received thioctic acid at the dose of 600 mg/day for 3 months. To control the effectiveness of the therapy, the technique of laser Doppler flowmetry was used.Results. After the pharmacological intervention, there was an improvement in the disease course, normalization of carbohydrate and lipid metabolism, increased vasomotor mechanisms of the regulation of the tissue blood flow due to an increase in endothelial and neurogenic kinds of activity in combination with a decrease in the intravascular tone and an increase in the effective perfusion in tissues. An increase in the heart rate variability was detected, positive dynamics of cardiovascular tests indicators according to D. Ewing, temporal (pNN50%, SDNN) and spectral indicators (VLF) were diagnosed. Achievement and maintenance of the target values of glycemic control indicators, as well as the absence of glycemic variability, turned out to be clinically significant for reducing the manifestations of neuropathy. The non-invasive technique of laser Doppler flowmetry is informative for the early diagnosis of DCAN in T1DM children.Conclusion. The carried out studies have demonstrated the effectiveness of the lipoic acid use at the dose of 600 mg/day for 3 months in the children with DCAN signs at the preclinical stage. The method of laser Doppler flowmetry for determining indications and monitoring the effectiveness of therapy makes it possible to implement a personalized approach to prescribing preventive treatment in T1DM children.
Effects of grape phylloxera leaf infestation on grapevine growth and yield parameters in commercial vineyards: a pilot study
Authors: Wilmink Jurrian , Breuer Michael , Forneck Astrid 
Published: March 2022

Grape phylloxera (Daktulosphaira vitifoliae) can infest both roots and leaves of Vitis species. In commercial vineyards planted with Vitis vinifera scions grafted on rootstocks, grape phylloxera infestation is generally limited to root feeding. Vineyards are, however, increasingly subjected to vineyard-wide foliar infestations that last throughout the growing season. While some vineyards are affected by the infestation pressure of external leaf-feeding populations, other annually affected V. vinifera vineyards do not have these in their vicinity. Much is known about the damage potential of grape phylloxera root feeding; however, data on how phylloxera leaf infestation affects V. vinifera grapevines in commercial vineyards are lacking. This study, therefore, aimed to assess whether grapevine growth and yield are affected due to leaf infestation as it occurred in three commercial vineyards in the study area. Treatments were based on phylloxera leaf infestation and additional defoliation. Single-leaf carbon acquisition was measured with gas exchange analyses on healthy and galled leaves. Pruning weight and internode length were measured to assess the effect of leaf infestation and the effect of plant growth and vigour on leaf gall outbreaks. Yield quantity and quality were measured, and grapes were vinified for sensory analyses. Furthermore, using enzymatic analyses, non-structural carbohydrates were analysed in perennial wood. A significant decrease in sugar content in grapes (10 %) and starch reserves in perennial wood (11 %) was found in the most heavily infested vineyard. Grape must of infested plants in another vineyard furthermore showed a significantly higher level of titratable acid (7.5 %). Significant infestation effects seen in one vineyard were not significant in the other two vineyards. No significant differences were seen for carbon acquisition, harvest quantity, wine sensory analysis, pruning weight or internode length. The overall effect of phylloxera leaf infestation in the studied vineyards was, therefore, marginal. Grapevine vigour did not differ between infested vines, insecticide-sprayed vines, and vines on which no leaf infestation outbreaks took place. By analysing phylloxera leaf infestation under field conditions, these preliminary results form a basis for future long-term field studies about phylloxera leaf feeding on Vitis vinifera within the context of other biotic and abiotic plant stresses.
Analysis and Research on Borehole Shrinkage Mechanisms and Their Control in Directional Wells in Deep Composite Salt Formations
Authors: Li Shiyuan , Fang Chao , Chen Chaowei , Xiang Degui , Li Fuyao , Huang Hao 
Published: March 2022

Abstract
The composite salt formations in West China are characterized by the deep burial, complex tectonic stress, and alternating development of salt rock and mudstone, and salt rock creep during drilling poses great challenges to the safety of drilling. This research is aimed at the serious blockage and sticking in build-up sections in deep composite salt formations. A 2D mechanical model for inclined wells penetrating multiple vertical layers was established by combining the analysis of creep mechanisms of composite salt formations with the high-temperature creep experiment results so as to investigate the wellbore stability of directional wells in composite salt formations in a certain block from the perspective of rock mechanics and probe the influence of inclination angles on borehole shrinkage under different in situ stress and interlayer conditions. Moreover, a directional well in the block was taken as an example to analyze the creep and borehole shrinkage in composite salt formations. The method for wellbore stability control was proposed, and the drilling fluid density chart was established. This research reveals the relationship among the wellbore trajectory, the degree of borehole shrinkage, and drilling fluid density in build-up sections of directional wells in composite salt formations and provides a theoretical reference for the establishment of the method for controlling blockage and sticking accidents in directional wells.
Three Step Plan to Put Canada at the Front of the Petroleum Sector's Race to Net-Zero
Authors: Malik Humera , Askari Forogh 
Published: March 2022

Abstract
Globally, the oil and gas industry, directly and indirectly, accounts for 42% of global emissions, according to a Mckinsey study. In Canada, the oil and gas industry is the single biggest source of Greenhouse Gas (GHG) emissions, contributing 10% to the country's total gas emissions. At the same time, the sector is crucial for Canada's growth, accounting for 5% of its GDP and generating employment for several thousands. It is then no surprise that the industry is under tremendous pressure to produce energy with reduced emissions.
AI plays a pivotal role in helping the oil and gas industry to reduce their emissions. In fact, the WEF estimates that with AI the oil and gas industry can reduce 350 million tonnes of CO2 emissions and 800 million gallons of water consumed by 2025. When it comes to process and asset optimization, oil and gas companies can reduce greenhouse gas emissions by 20% with minimal capital investment.
However, deploying AI is not without challenges. If not implemented properly, it can prevent the company from realizing the benefits of the deployment. In fact, Gartner says that 85% of the AI projects will continue to fail by 2022. World Economic Forum states that 36% of oil and gas companies have already invested in big data and analytics. However, only 13% use the insights from this technology to drive their approach towards the market and their competitors. Both of these point to companies applying the technology in a piecemeal manner and how a lack of lack of effective strategy can make it challenging to accomplish the desired goals.
In this presentation, Humera Malik and Forogh Askari will outline the three-step plan for oil and gas companies to effectively deploy AI across their operations that augments their workforce with AI insights to accelerate their sustainability efforts in the race to net zero.
Characterizing a Complex Induced Fracture Network: A Case Study of a Diagnostic Fracture Injection Test in the Heterogeneous Overpressured Montney Formation
Authors: Sarvaramini Erfan , Dusseault Maurice 
Published: March 2022

Abstract
This study provides new insights into hydraulic fracture growth during a Diagnostic Fracture Injection Test (DFIT) in the presence of mechanical heterogeneity in the overpressured Montney Formation in British Columbia. A novel continuum non-local poro-elastic-plastic model of a Stimulated Rock Volume (SRV) developed in the context of the Finite Element Method is used for analysis. It is shown that DFITs in the Montney Formation can generate substantial fracture network complexity. We provide insights on potential complex fracturing patterns and distributions at the well spacing scale. Additionally, the SRV tends to span and extend several meters away on each side of the induced fracture plane. We quantify the fracture tortuosity factor which appears to deviate significantly from unity, as in the cubic law. It is further demonstrated that the aperture within the SRV can significantly drop after shut-in before it reverts and begin to heal mechanically. We show that the onset of the aperture self-healing coincides with the time when the pressure during the fall-off period becomes equal to the final effective ISIP.
Effect of Natural Fracture Characteristics on Proppant Transport and Placement in an Irregular, Nonplanar Fracture
Authors: Qu Hai , Liu Ying , Zeng Shunpeng , Xiao Hui , Lu Yu , Liu Zhonghua 
Published: March 2022

Summary
Hydraulic fracturing is recognized as the primary stimulating technique to enhance recovery in unconventional reservoirs. Connecting natural fractures and filling proppant are crucial elements to achieve the effective development of the reservoirs. Many studies have investigated the interaction characteristics between hydraulic fracture and natural fracture and proppant transport in complex fracture systems. However, few studies show how natural fracture affects proppant migration and placement. In this work, we experimentally explore proppant transport in an irregular, nonplanar fracture containing hydraulic fractures and a natural fracture. The objective is to identify the influence of natural fractures on proppant transport and placement.
In this paper, proppant transport in a nonplanar fracture with bends is studied experimentally by a laboratory size slot, and the bending section represents a natural fracture. A high-resolution particle image velocimetry (PIV) system is used to detect the instantaneous velocity field in the complex pathway to understand particle transport behaviors. Proppant placement is quantitatively evaluated by the proppant coverage area as the proppant bed reaches the equilibrium state. Also, the effects of natural fracture width and height, intersection angle with hydraulic fracture, and relative location with the inlet on proppant placement are investigated.
The results identify that the natural fracture would significantly increase the complexity of proppant transport and lead to a discontinuous and irregular proppant bed in the complex fracture. The vorticity flow appears around the bend and resuspends deposited proppants through the bending section. The small natural fracture width and height increase flow erosion and are not conducive to proppant settlement, resulting in no proppant. The more the bending angle, the lower the coverage area and bed height. When the natural fracture is close to the inlet, a depleted region without proppants would be formed around the wellbore. The multiple linear regression method developed two reliable models expressed by four normalized parameters to predict the bed coverage areas. The experimental results and laws provide ways to quantitatively analyze natural fracture characteristics' effect on proppant transport and placement in unconventional reservoirs and fissured formations.
taxaTarget: Fast, sensitive, and precise classification of microeukaryotes in metagenomic data
Authors: Commichaux Seth , Javkar Kiran , Muralidharan Harihara Subrahmaniam , Ramachandran Padmini , Ottesen Andrea , Rand Hugh , Pop Mihai 
Published: March 2022

Abstract
BackgroundMicrobial eukaryotes are nearly ubiquitous in microbiomes on Earth and contribute to many integral ecological functions. Metagenomics is a proven tool for studying the microbial diversity, functions, and ecology of microbiomes, but has been underutilized for microeukaryotes due to the computational challenges they present. For taxonomic classification, the use of a eukaryotic marker gene database can improve the computational efficiency, precision and sensitivity. However, tools which use marker gene databases often implement universal thresholds for classification rather than dynamically learning the thresholds from the database structure, impacting the accuracy of the classification process.ResultsHere we introduce taxaTarget, a method for the taxonomic classification of microeukaryotes in metagenomic data. Using a database of eukaryotic marker genes and a supervised learning approach for training, we learned the discriminatory power and classification thresholds for each 20 amino acid region of each marker gene in our database. This approach provided improved sensitivity and precision compared to other approaches, with rapid runtimes and low memory usage. Additionally, taxaTarget was better able to detect the presence of multiple closely related species as well as species with no representative sequences in the database. Several algorithms were implemented, including threshold padding, which effectively handled the scarce training data available and reduced classification errors. Using taxaTarget on metagenomes from human fecal microbiomes, a broader range of genera were detected, including multiple parasites that the other tested tools missed.ConclusionData-driven methods for learning classification thresholds from the structure of an input database can provide granular information about the discriminatory power of the sequences and improve the sensitivity and precision of classification. These methods will help facilitate a more comprehensive analysis of metagenomic data and expand our knowledge about the diverse eukaryotes in microbial communities.
Research on the Economic Impact of Environmental Tax under the Background of State-Owned Enterprise Shareholding Reform in an Open Economic System
Authors: Wang Zongxian , Wang Hui , Wang Yi 
Published: March 2022

Abstract
In this paper, we construct a Stackelberg-Cournot tripartite game model and discuss the impact of tariff policy on the privatization of the state-owned enterprise, environmental tax, pollutant emission and social welfare in an open economic system. We find that with the increase in tariff, the proportion of privatization of the state-owned enterprise increases, environmental tax falls, and environmental pollution alleviates. The relationship between social welfare and tariff is inverted U-shaped. A closed trade environment is most conducive to environmental protection, but the environmental tax at this time is very detrimental to social welfare. When social welfare is optimal, environmental damage is not the smallest.
Analysis of the molecular mechanism of Evodia rutaecarpa fruit in the treatment of nasopharyngeal carcinoma using network pharmacology and molecular docking
Authors: He Yingchun , Xu Runshi , Yang Ximing , Tao Yangyang , Luo Wang , Xiong Yu , He Lan , Zhou FangLiang 
Published: March 2022

Abstract
Background: Nasopharyngeal carcinoma (NPC), a neoplasm of the head and neck, has high incidence and mortality rates in East and Southeast Asia. Evodia rutaecarpa is a tree that is native to Korea and China, and its fruit (hereafter referred to as Evodia) exhibits remarkable antitumor properties. However, little is known about its mechanism of action in NPC. In this study, we employed network pharmacology to identify targets of active Evodia compounds in nasopharyngeal carcinoma and generate an interaction network.Methods: The active ingredients of Evodia and targets in NPC were obtained from multiple databases, and an interaction network was constructed via the Cytoscape and STRING databases. The key biological processes and signaling pathways were predicted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Molecular docking technology was used to identify the affinity and activity of target genes, and The Cancer Genome Atlas and Human Protein Atlas databases were used to analyze differential expression. Cell Counting Kit (CCK)-8 and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) dual-fluorescence staining were used for experimental verification.Results: Active Evodia compounds included quercetin, isorhamnetin, and evodiamine, and important NPC targets included MAPK14, AKT1, RELA, MAPK1, JUN, and p53, which were enriched in lipid and atherosclerosis signaling pathways. Additionally, we verified the high affinity and activity of the active compounds through molecular docking, and the target proteins were verified using immunohistochemistry and differential expression analyses. Furthermore, CCK-8 assays and Annexin V-FITC/PI dual-fluorescence staining showed that isorhamnetin inhibited the proliferation of NPC cells and induced apoptosis.Conclusion: Our results identified the molecular mechanisms of Evodia and demonstrated its ability to alter the proliferation and apoptosis of NPC cells through multiple targets and pathways, thereby providing evidence for clinical application of Evodia.
A Novel Easy-to-use Index to Predict Institutionalization and Death in Older Population – a 10-year Population-based Follow-up Study
Authors: Heikkilä Elisa , Salminen Marika , Viljanen Anna , Katajamäki Taina , Koivula Marja-Kaisa , Pulkki Kari , Isoaho Raimo , Kivelä Sirkka-Liisa , Viitanen Matti , Löppönen Minna , Vahlberg Tero , Venäläinen Mikko S , Elo Laura L , Viikari Laura , Irjala Kerttu 
Published: March 2022

Abstract
Background: Various indexes have been developed to estimate the risk for mortality, institutionalization, and other adverse outcomes for older people. Most indexes are based on a large number of clinical or laboratory parameters. An index based on only a few parameters would be more practical to use in every-day clinical practice.Methods: A prospective study with a 10-year follow-up period. Thirty-six clinical and fourteen laboratory parameters were combined to form an index. Cox regression model was used to analyze the association of the index with institutionalization and mortality. A backward statistical method was used to reduce the number of parameters to form an easy-to-use index for predicting institutionalization and mortality.Results: The mean age of the participants (n=1172) was 73.1 (SD 6.6, range 64‒97) years. Altogether, 149 (14%) subjects were institutionalized, and 413 (35%) subjects deceased during the follow-up. Institutionalization and mortality rates increased as index scores increased both for the large 50-parameter combined index and for the reduced indexes. After a backward variable selection in the Cox regression model, three clinical parameters remained in the index to predict institutionalization and six clinical and three laboratory parameters in the index to predict mortality. The reduced indexes showed a slightly better predictive value for both institutionalization and mortality compared to the full index.Conclusions: A large index with fifty parameters included many unimportant parameters that did not increase its predictive value, and therefore could be replaced with a reduced index with only a few carefully chosen parameters, that were individually associated with institutionalization or death.