bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rapid RP-HPLC method for the simultaneous estimation of Ivacaftor and Tezacaftor and in silico study of their metabolitic products
Authors: Donakonda Madhuri , Indrakanti Srija , Pasala Praveen Kumar , Desari Malleswari , Kammari Shireesha 
Published: June 2021

AbstractBackgroundThis study was designed to develop a reliable method for estimation of Ivacaftor and Tezacaftor in pure and its pharmaceutical dosage form by RP-HPLC in human plasma. Molecular docking studies were carried out and the results were visualized using PyMol and Discovery studio visualizer (Discovery studio visualizer ver. 2.5). The pharmacokinetic properties such as Swiss ADME and pKCSM of the Ivacaftor and its metabolites Ivacaftor M1, M6 and Tezacaftor and metabolites Tezacaftor M1, M2 were predicted. In admetSAR, web-based query tools incorporating a molecular built-in interface enable the database to be queried by SMILES.ResultsA simple, linear, precise, and accurate RP-HPLC method was developed and validated for the determination of Ivacaftor (IVA) and Tezacaftor (TEZ) in human plasma. Chromatographic separation was achieved isocratically on Inspire C18, (4.6 × 250 mm, 5 μm) column at 30°C. Mobile phase consisting of methanol and 0.05% formic acid in ratio of 95:5 with flow rate of 1 mL/min with injection volume 20 μl detector used is PDA at 235 nm. The developed method was validated according to ICH guidelines and found to be linearity range was found to be for TEZ (10–50 μg/mL) and IVA (15–75 μg/mL). IVA and TEZ drugs and its metabolites were retrieved from the PubChem database and the 2D chemical structures were generated from SMILES notation by using the Chemsketch Software. The structure was viewed using Swiss-PDB Viewer to form a better understanding of the molecule for toxicity and biological activity prediction.ConclusionThe results obtained by the proposed method from validation parameters and from assay confirmed that the determination of Tezacaftor (TEZ) and Ivacaftor (IVA) in their combined dosage form in human plasma was sensitive and selective method. In silico study has revealed that IVA and its metabolites IVA M1, IVA M6 are according to Lipinski rule. The oral bioactivity of IVA was found to be more when compared to its metabolites (Molinspiration) and TEZ and its metabolites TEZ M1, TEZ M2 even though they have the molecular weight > 500, but all other parameters from Molinspiration revealed better oral bioactivity of TEZ M2. Validation of the developed isocratic RP-HPLC procedure revealed that, regardless of how the sample was purified, the method was characterized by good linearity, sensitivity, reproducibility, specificity, and low values of LOD (0.090 μg/mL) and LOQ (0.275 μg/mL). From the in silico docking results, it is quite evident that metabolites of TEZ and IVA have the great potential against cystic fibrosis.
Rethinking methane from animal agriculture
Authors: Liu Shule , Proudman Joe , Mitloehner Frank M. 
Published: June 2021

Abstract
Background
As the global community actively works to keep temperatures from rising beyond 1.5 °C, predicting greenhouse gases (GHGs) by how they warm the planet—and not their carbon dioxide (CO2) equivalence—provides information critical to developing short- and long-term climate solutions. Livestock, and in particular cattle, have been broadly branded as major emitters of methane (CH4) and significant drivers of climate change. Livestock production has been growing to meet the global food demand, however, increasing demand for production does not necessarily result in the proportional increase of CH4 production. The present paper intends to evaluate the actual effects of the CH4 emission from U.S. dairy and beef production on temperature and initiate a rethinking of CH4 associated with animal agriculture to clarify long-standing misunderstandings and uncover the potential role of animal agriculture in fighting climate change.

Methods
Two climate metrics, the standard 100-year Global Warming Potential (GWP100) and the recently proposed Global Warming Potential Star (GWP*), were applied to the CH4 emission from the U.S. cattle industry to assess and compare its climate contribution.

Results
Using GWP*, the projected climate impacts show that CH4 emissions from the U.S. cattle industry have not contributed additional warming since 1986. Calculations show that the California dairy industry will approach climate neutrality in the next ten years if CH4 emissions can be reduced by 1% per year, with the possibility to induce cooling if there are further reductions of emissions.

Conclusions
GWP* should be used in combination with GWP to provide feasible strategies on fighting climate change induced by short-lived climate pollutants (SLCPs). By continuously improving production efficiency and management practices, animal agriculture can be a short-term solution to fight climate warming that the global community can leverage while developing long-term solutions for fossil fuel carbon emissions.
Planar liquid crystal polarization optics for augmented reality and virtual reality: from fundamentals to applications
Authors: Xiong Jianghao , Wu Shin-Tson 
Published: June 2021

AbstractPlanar and ultrathin liquid crystal (LC) polarization optical elements have found promising applications in augmented reality (AR), virtual reality (VR), and photonic devices. In this paper, we give a comprehensive review on the operation principles, device fabrication, and performance of these optical elements. Optical simulations methods for optimizing the device performance are discussed in detail. Finally, some potential applications of these devices in AR and VR systems are illustrated and analyzed.
Implication of Heterozygous Variants in Genes of the Leptin–Melanocortin Pathway in Severe Obesity
Authors: Courbage Sophie , Poitou Christine , Le Beyec-Le Bihan Johanne , Karsenty Alexandra , Lemale Julie , Pelloux Véronique , Lacorte Jean-Marc , Carel Jean-Claude , Lecomte Nathalie , Storey Caroline , De Filippo Gianpaolo , Coupaye Muriel , Oppert Jean-Michel , Tounian Patrick , Clément Karine , Dubern Béatrice 
Published: June 2021

Abstract

Context
Unlike homozygous variants, the implication of heterozygous variants on the leptin–melanocortin pathway in severe obesity has not been established.

Objective
To describe the frequency, the phenotype, and the genotype–phenotype relationship for heterozygous variants in LEP, LEPR, POMC, and PCSK1 in severe obesity.

Methods
In this retrospective study, genotyping was performed on at least 1 of the LEP, LEPR, POMC, and PCSK1 genes in 1486 probands with severe obesity (600 children, 886 adults). The phenotype was collected in 60 subjects with heterozygous variants and 16 with homozygous variants. We analyzed variant frequency, body mass index (BMI), age of obesity onset, food impulsivity, and endocrine abnormalities.

Results
The frequency of subjects with homozygous variants was 1.7% (n = 26), and 6.7% (n = 100) with heterozygous variants. Adults with homozygous variants had a higher BMI (66 vs 53 kg/m2, P = .015), an earlier onset of obesity (0.4 vs 5.4 years, P &lt; .001), more often food impulsivity (83% vs 42%, P = .04), and endocrine abnormalities (75% vs 26%, P &lt; .01). The BMI was higher for subjects with high-impact heterozygous variants (61 vs 50 kg/m², P = .045) and those with a second heterozygous variant on the pathway (65 vs 49 kg/m², P &lt; .01). In children, no significant differences were found for the age of obesity onset and BMI.

Conclusion
Heterozygous variants in LEP, LEPR, POMC, and PCSK1 are frequent in severe obesity and sometimes associated with a phenotype close to that of homozygotes. These data suggest a systematic search for variants in severe early-onset obesity, to discuss therapy that targets this key pathway.
Transcranial direct current stimulation with functional magnetic resonance imaging: a detailed validation and operational guide
Authors: Nardo Davide , Creasey Megan , Negus Clive , Pappa Katerina , Reid Alphonso , Josephs Oliver , Callaghan Martina F. , Crinion Jenny T. 
Published: June 2021

Introduction: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used to modulate human brain and behavioural function in both research and clinical interventions. The combination of functional magnetic resonance imaging (fMRI) with tDCS enables researchers to directly test causal contributions of stimulated brain regions, answering questions about the physiology and neural mechanisms underlying behaviour. Despite the promise of the technique, advances have been hampered by technical challenges and methodological variability between studies, confounding comparability/replicability. Methods: Here tDCS-fMRI at 3T was developed for a series of experiments investigating language recovery after stroke. To validate the method, one healthy volunteer completed an fMRI paradigm with three conditions: (i) No-tDCS, (ii) Sham-tDCS, (iii) 2mA Anodal-tDCS. MR data were analysed in SPM12 with region-of-interest (ROI) analyses of the two electrodes and reference sites. Results: Quality assessment indicated no visible signal dropouts or distortions introduced by the tDCS equipment. After modelling scanner drift, motion-related variance, and temporal autocorrelation, we found no field inhomogeneity in functional sensitivity metrics across conditions in grey matter and in the three ROIs. Discussion: Key safety factors and risk mitigation strategies that must be taken into consideration when integrating tDCS into an fMRI environment are outlined. To obtain reliable results, we provide practical solutions to technical challenges and complications of the method. It is hoped that sharing these data and SOP will promote methodological replication in future studies, enhancing the quality of tDCS-fMRI application, and improve the reliability of scientific results in this field. Conclusions: The method and data provided here provide a technically safe, reliable tDCS-fMRI procedure to obtain high quality MR data. The detailed framework of the Standard Operation Procedure SOP (https://doi.org/10.5281/zenodo.4606564) systematically reports the technical and procedural elements of our tDCS-fMRI approach, which we hope can be adopted and prove useful in future studies.
Ultraplex: A rapid, flexible, all-in-one fastq demultiplexer
Authors: Wilkins Oscar G , Capitanchik Charlotte , Luscombe Nicholas M. , Ule Jernej 
Published: June 2021

Background: The first step of virtually all next generation sequencing analysis involves the splitting of the raw sequencing data into separate files using sample-specific barcodes, a process known as “demultiplexing”. However, we found that existing software for this purpose was either too inflexible or too computationally intensive for fast, streamlined processing of raw, single end fastq files containing combinatorial barcodes. Results: Here, we introduce a fast and uniquely flexible demultiplexer, named Ultraplex, which splits a raw FASTQ file containing barcodes either at a single end or at both 5’ and 3’ ends of reads, trims the sequencing adaptors and low-quality bases, and moves unique molecular identifiers (UMIs) into the read header, allowing subsequent removal of PCR duplicates. Ultraplex is able to perform such single or combinatorial demultiplexing on both single- and paired-end sequencing data, and can process an entire Illumina HiSeq lane, consisting of nearly 500 million reads, in less than 20 minutes. Conclusions: Ultraplex greatly reduces computational burden and pipeline complexity for the demultiplexing of complex sequencing libraries, such as those produced by various CLIP and ribosome profiling protocols, and is also very user friendly, enabling streamlined, robust data processing. Ultraplex is available on PyPi and Conda and via Github.
Designing the marketing activities of a modern higher education institution
Authors: Pelekh Yuriy , Galatyuk Mikhail 
Published: June 2021

In the article, a technological simplex of designing the marketing activity of an modern institution of higher education. The content of the main components of the proposed technological simplex is revealed.
The author found that marketing activities should be carried out in compliance with the social and value principle withdrawal of profit. Adherence to this principle is the key to the success of a higher education institution.
The organization of marketing activities is carried out by the marketing service. This service involves the administration and all staff of the higher education institution, which can be useful in the process of developing individual components of a marketing plan.
In the context of the study, it was found technological simplex of designing marketing activity of a higher education institution is a structural and functional scheme, a simple prescription, a generalized and accessible action plan, which is an indicative basis for the activities of marketing services of higher education institutions.
The technological simplex of designing the marketing activities of a modern higher education institution consists of nine components. The implementation of each component is accompanied by reflection, control and correction, which are carried out in the process of managing the concept of marketing.
During the development of the technological simplex, the marketing management model of the organization, the main components of the marketing activity plan, as well as the process of implementing strategic marketing planning are taken into account.
The revealed content of the technological simplex of designing marketing activity of higher education institutions is a theoretically substantiated indicative basis to realize opportunities to improve the marketing culture of educational institutions of all levels of accreditation.
Climate change through the eyes of a chemist, energy, technologist
Authors: Zhukov Anatoliy , Gushcha Sergey , Bobro Elena 
Published: June 2021

In this article, the author made an attempt to present and analyze issues related to global environmental problems, and in particular, the role of carbon dioxide in global warming. Well-known facts and unexpected findings are intended to awaken in the reader a critical attitude towards the prevailing beliefs in these matters.
From the point of view of a chemist, the reality of extracting CO2 from air and converting it back into fuel is assessed. Simple energy calculations make it possible to assess the ability of "green" energy to replace carbon and influence the climate warming process. And finally, the key proposals are presented from the point of view of a technologist, since it is technologists who make real and implement the most daring discoveries and projects of scientists and inventors.
Sexual dimorphism of the frequency of significant correlations between the characteristics of body trunk and feet in children aged 4 to 6 years
Authors: Mrozkowiak Mirosław 
Published: June 2021

Introduction. Relatively few publications have concerned characteristics of body trunk and feet. It is generally suggested that correlations exist between the characteristics of the developing foot and the spinal column.
Materials and methods. The examinations conducted in a group of children aged 4 to 6 years allowed for recording 2988 observations, including 1482 girls and 1506 boys, and values of 87 characteristics that described body trunk and feet. The test stand for the measurement of the selected parameters using the photogrammetric method consisted of a personal computer, software, screen and printer, and a projection-reception device with a camera.
Conclusion
1. The general number of body trunk characteristics having significant correlations with feet parameters in females was slightly higher. The number of relationships in sagittal and frontal planes was the same in both sexes. The characteristics that differentiated males from females were found mainly in transverse and frontal planes.
2. The number of feet characteristics that most often showed significant correlations with body trunk parameters was higher in girls than in boys. These were mainly characteristics concerning width and length, longitudinal arch and disorders in the position of the feet. The characteristics that differentiated boys described only the longitudinal arch of the feet.
Sexual and environmental dimorphism, the frequency of significant relationships between body weight and height and foot features among 14-18-year-old adolescents
Authors: Mrozkowiak Mirosław 
Published: June 2021

Introduction: The objective of this study was to show the frequency of significant correlations between body weight and height and the selected parameters of body posture within trunk in 14-18-year-old adolescents.
Material and methods. The study conducted among randomly selected teenagers aged 14-18 years was carried out during the period of 3 years, in 6 half-year editions and enabled the author to record 2445 observations with regard to the measurement of 48 parameters describing trunk, body weight and height. The subjects involved in the study were enrolled from the Warminsko-Mazurski region. The photogrammetric method with the phenomenon of mora projection was used to measure the selected parameters.
Findings. The frequency of significant correlations between body height and the features of body posture was 21.42% and with regard to body weight it was 14.28%. The frequency of significant correlations between body height within sex was 14.28%, and concerning body weight it was 4.76%, whereas among girls the figures were 7.14% and 9.52% respectively.
Conclusions
1. Among adolescents aged 14-18 years, body height revealed significantly more frequent correlations with the parameters of feet than body weight.
2. Body height was reported to reveal more frequent significant correlations with the parameters of feet than body weight among boys. As regards girls involved in the study, the frequency of these significant relationships was similar and revealed lower values. Body weight and height showed more frequent correlations with the parameters of feet in children living in towns and cities than in their counterparts from the rural environment.
3. Among boys, more frequent significant correlations between body height and the parameters of feet were observed in subjects living in the urban environment, and the correlations concerning body weight significantly differed from the percentage of the relationships regarding body height. Among girls living in the rural environment, the correlations between body height and the parameters of feet were more frequent than in the subjects living in towns, and regarding weight, these correlations were reported to be bigger in towns than in villages. The percentage of significant relationships was very low in the rural environment.
Nursing level knowledge of strokes from the study of demographic and social factors
Authors: Gazdowicz Lucyna , Cipora Elżbieta , Niemiec Mateusz , Krowicka Edyta 
Published: June 2021

Introduction. Strokes often have very serious medical, social and economic consequences. Knowledge about strokes is the basis for effective prophylaxis and makes it possible to quickly notice the symptoms and initiate appropriate therapeutic treatment in a short time.
The aim of the research was to assess the level of knowledge of nursing students about strokes, taking into account selected demographic and social factors.
Material and methods. The research covered a group of 120 students of nursing at the State University of Jan Grodek in Sanok. The diagnostic survey method was used. The research tool was a proprietary questionnaire containing questions about the demographic and social situation and a stroke knowledge test. The IBM SPSS v 25.0 package was used in the statistical analysis. The value of p≤0.05 was adopted as statistically significant.
Results. The mean age of the respondents in the years was 33.82 (SD 9.75). The vast majority of the respondents (94.2%) were women. The average level of knowledge about stroke was highest in the 31-40 age group (83.3%). A statistically significant relationship was found between the level of education of the respondents and the level of their knowledge about strokes (p = 0.029). On the other hand, the age, marital status, place of residence and social and living conditions of students did not significantly affect the level of their knowledge about stroke.
Conclusions. The overall level of knowledge about strokes among nursing students was average. Most of the subjects studied were familiar with pre-hospital management procedures in the event of a stroke, but had significant gaps in knowledge regarding the time of thrombolytic treatment initiation after the onset of stroke. In the education of nursing students, particular attention should be paid to issues related to the prevention and management of strokes.
An attempt to identify significant correlations between parameters of body trunk and parameters of feet and their frequency in adolescents aged 14-18 years
Authors: Mrozkowiak Mirosław 
Published: June 2021

Introduction. All disorders are temporary as a natural consequence of ontogenetic processes usually disappearing after puberty. Therefore, it is important to provide incentives in this period in order to maintain physical activity at a previously achieved level and try to shape the parameters of feet through exerting a conscious influence on body trunk parameters.
Material and method. The study conducted with the group of adolescents aged 14 to 18 years enabled to record 2,343 observations with regard to the measurement of 90 parameters describing trunk and feet. The station for an assessment of body posture and feet using the photogrammetric method consisted of a computer, a card, software, a display monitor, a printer and a projection-reception device with a camera to measure the selected parameters.
Conclusions
1.The values of frontal and sagittal body trunk parameters revealed a significant correlation
with the parameters of feet. An increased frequency of these correlations was observed between the sagittal parameters of body trunk and feet. The relationship between transverse parameters was much less significant.
2.Feet parameters most often significantly correlated with: trunk flexion angle in the sagittal plane, height of thoracic kyphosis, angle of the projection line of lower scapula angles with the right or the left angle being more convex, lumbar lordosis length, asymmetry in the height of scapula triangles with the right scapula up, inclination of the thoracic and lumbar spine, shoulders line angle with the left one up and the angle of pelvic flexion to the right in the transverse plane.
3.Feet parameters with which trunk parameters most frequently correlated included:
width of longitudinal arch 1, length of longitudinal arch 2 in the right foot, varus angle of the fifth toe and width of the right foot and length of the first arch in the left foot and length of the right and left foot.