bluuebunny/crossref_metadata_2025 huggingface dataset:
The Combination of Atorvastatin With Silymarin Enhances Hypolipidemic, Antioxidant and Anti-Inflammatory Effects in a Rat Model of Metabolic Syndrome
Authors: MARKOVÁ I , MALÍNSKÁ H , HÜTTL M , MIKLÁNKOVÁ D , OLIYARNYK O , PORUBA M , RÁCOVÁ Z , KAZDOVÁ L , VEČEŘA R
Published: March 2021

Hypolipidemic and cardioprotective effects of statins can be associated with the development of myopathies and new-onset type 2 diabetes. These adverse effects may be related to increased oxidative stress. The plant extract silymarin (SM) is known for its antioxidant and anti-inflammatory actions. We tested the hypothesis that the combination of atorvastatin (ATV) with SM could improve therapy efficacy and eliminate some negative effects of statin on hypertriglyceridemia-induced metabolic disorders. Hereditary hypertriglyceridemic rats were fed a standard diet for four weeks without supplementation; supplemented with ATV (5 mg/kg b. wt./day) or a combination of ATV with 1 % micronized SM (ATV+SM). ATV treatment elevated plasma levels of HDL-cholesterol (p<0.01), glucose and insulin and decreased triglycerides (p<0.001). The combination of ATV+SM led to a significant reduction in insulin, an improvement of glucose tolerance, and the hypolipidemic effect was enhanced compared to ATV alone. Furthermore, ATV supplementation increased skeletal muscle triglycerides but its combination with SM decreased triglycerides accumulation in the muscle (p<0.05) and the liver (p<0.01). In the liver, ATV+SM treatment increased the activities of antioxidant enzymes, glutathione and reduced lipid peroxidation (p<0.001). The combined administration of ATV with SM potentiated the hypolipidemic effect, reduced ectopic lipid accumulation, improved glucose metabolism, and increased antioxidant and anti-inflammatory actions. Our results show that SM increased the effectiveness of statin therapy in a hypertriglyceridemic rat model of metabolic syndrome.
CCR5Δ32 Deletion as a Protective Factor in Czech First-Wave COVID-19 Subjects
Authors: HUBACEK J , DUSEK L , MAJEK O , ADAMEK V , CERVINKOVA T , DLOUHA D , PAVEL J , ADAMKOVA V
Published: March 2021

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), has spread widely around the globe. Significant inter-individual differences have been observed during the course of the infection, which suggests that genetic susceptibility may be a contributing factor. CC chemokine receptor 5 (CCR5), which acts as a co-receptor for the entry of HIV-1 into cells, is promising candidate whose can have an influence on SARS-CoV-2 infection. A genetic mutation known as CCR5Δ32, consisting of a 32-nucleotide deletion, encodes a truncated protein that protects homozygous carriers of the deletion from HIV-1 infection. Similarly, inhibition of CCR5 seems to be protective against COVID-19. In our study, we successfully genotyped 416 first-wave SARS-CoV-2-positive infection survivors (164 asymptomatic and 252 symptomatic) for CCR5Δ32, comparing them with a population based sample of 2,404 subjects. We found the highest number (P=0.03) of CCR5Δ32 carriers in SARS-CoV-2-positive/COVID-19-asympto-matic subjects (23.8 %) and the lowest number in SARS-CoV-2-positive/COVID-19-symptomatic patients (16.7 %), with frequency in the control population in the middle (21.0 %). We conclude that the CCR5Δ32 I/D polymorphism may have the potential to predict the severity of SARS-CoV-2 infection.
THE CONCEPTS OF ‘METATEXTUALITY’ AND ‘METAFICTION’ IN LITERARY CRITICISM
Authors: Vatazhko Elvira
Published: March 2021

Undoubtedly, the second half of the 20th century and the early 21st century are notable for the extensive artistic experiment, including metatextual and metafictional phenomena. Such scholars as Gérard Genette, Anna Wierzbicka, Patricia Waugh, Linda Hutcheon, Robert Sholes, and many others focused on the mentioned issues in their research work. Therefore, this paper considers metatextuality and metafiction in the theoretical perspective tracing the origins of metatextuality and its connections with postmodern literature. The terms ‘metatext’ and ‘metafiction’ appeared as rather close in time. Notably, both of them are based on the discursive practices of the late 20th century. However, the term ‘metatext’ originated in the scholarly practice of structuralism. It is obvious that ‘metatext’ was constructed by analogy with the concept of ‘metalanguage’. Either of them does not exist without the initial text (or language). Metatextual elements are important for analyzing styles, genres, types of expression, discursive functions, and more. On the other hand, the term ‘metafiction’ has an obvious connection with genre studies. Metafiction qualifies as a special kind of literary text that became characteristic of the postmodern era. Such features as self-referentiality of artistic expression, introspection, and self-consciousness became essential for postmodern aesthetics. Metatextuality relates to the narrative theory and metacritiсism, while metafictionality is applicable within the intertextual analysis. Thus, the paper highlights an advance of metadiscourse in the cultural consciousness of the late 20th century.
RESTAURANTS AND TAVERNS IN SHEVCHENKO’S STORY “THE ARTIST” (FROM THE NEW COMMENTARIES)
Authors: Boron Oleksandr
Published: March 2021

Besides specifying or clarifying the current address of the restaurants and taverns mentioned in the story, it appeared necessary to give a minimum description of this or that eating-house as most of the relevant names and cases of comparing and contrasting some of them say little to a common reader and sometimes to a specialist as well. The study of these restaurants and taverns adds many new details to Shevchenko’s biography. Based on the information of the author’s contemporaries (mostly from the 1830s—1840s), descriptions in the fiction ot the time, as well as city guides and directories, the paper presents characteristics of St. Petersburg restaurants and confectioneries of Alexander, Delli, Dume, Klee, Saint Georges, the Roman cafes Lepri and Greco.

The paper proves that Madame Jurgens’ eating-house was located not on the sixth line of Vasilyevsky Island, but the third one, near the Great Avenue, not far from the wine cellar of Ja. Vochts on the second line. It refutes the erroneous localization by M. Morenets who believed that Jurgens canteen worked in a house at the modern address 6 Buzky Lane / 7 the 6th line. In fact, there was a tavern “The Golden Anchor”, which is also visited by the characters of the story. There is evidence that allows assuming that the tavern “Berlin” mentioned in the story as one in the corner of the 6th line and Academic Lane was located at the modern address 3 6th line / 10 Academic Lane, because since the early 19th century there was a wine shop in this particular building, and not in the one at the opposite corner.

When not lacking money to pay, Shevchenko and his Academy classmates had lunch mostly in Madame Jurgens’ eating-house. If they could afford it, getting paid for a portrait or something, they visited the restaurant Klee. K. Bryullov could sometimes invite them for dinner at Delli’s confectionery or Alexander’s restaurant. Shevchenko also knew some other aristocratic eating-houses and, of course, just heard of Roman cafes from others.
A POET ON THE OTHER BANK: POETICS OF AFFECT IN THE PROSE BY BOHDAN IHOR ANTONYCH
Authors: Haleta Olena
Published: March 2021

The is the second paper of the two-part study examining the ‘unwritten novel’ “On the Other Bank” by Bohdan Ihor Antonych, a notable Western Ukrainian writer of the interwar period. Known primarily for his poetry, Antonych did not finish this novel-in-progress, leaving behind only draft notes, that offer a glimpse into the very process of his writing. Analyzed from the perspective of genetic criticism, Antonych’s manuscripts are treated as an avant-text, demonstrating a ‘scenario of writing’ in the transition from the novel of action to the novel of state. In contrast to his image-based poetry Antonych’s prose rests on the technique of description. Depicting nature or the urban environment, the author conveys a certain emotional and psychological condition. Paying special attention to qualitative adjectives, he appeals to the sensory experience of the reader. Despite the fact that the plan of the novel indicates the main events of the plot, the author mainly captures the emotions of the characters. Dialogues also play an unusual role in the text, as their function is expressive rather than a communicative one. Since the dynamics of the text is based on emotional and psychological movement, and not on the sequence of events or judgments, it is considered to be an example of affective poetics in Ukrainian modern literature. Affect appears in Antonych’s text as force and tension. It shapes the human personality and at the same time challenges it. Affect goes beyond discursiveness and captures the body; its intensity is expressed through the voice and speed. Antonych’s characters share a common transpersonal experience in their childhood and a common object of desire after becoming adults. Moreover, the transfer of emotions into the sphere of interpersonal relations gives the affect not only a psychological but also an ethical dimension. Analyzing Antonych’s manuscript, the author of the paper focuses on the dynamics of writing, not on the one of the plot, and finds grounds for conclusions about the affective nature of Antonych’s prose. It is evident that in the ‘unwritten novel’ “On the Other Bank” Antonych depicts the modernist type of literary character as homo sentiens, who perceives the world in a subtle way and experiences it deeply.
IVAN HNATIUK’S POETIC TRILOGY IN THE EARLY 1990S: WHY DIDN’T UKRAINE HEAR THE PROPHET OF THE ‘NEW CHRONOLOGY’?
Authors: Koloshuk Nadiia
Published: March 2021

The poetry books by I. Hnatiuk, edited in independent Ukraine, are especially valuable due to the first publication of his poems written in prison. He appeared in front of the reader in his true poetic self, without distortion of censorship, only in the 1990s — in a kind of poetical trilogy beginning with the collection “New calculus of time” (Kyiv, 1990). Three poetry books from the early 1990s — “New calculus of time”, “Via Dolorosa” and “True Revenge” — contain the restored early lyrics and poems of the author prisoner. I. Hnatiuk introduced into Ukrainian poetry the topics and issues related to the crimes of Stalin’s tyranny, the national resistance movement, and the threats of imperial aggression from Moscow in the time of Ukrainian independence. Hnatiuk never announced any prophecies of the expected ‘happy future’ in the new Ukraine, although the collections had a distinct prophetic orientation. The poems of the 1980s and 1990s were also presented, including the cycles brought to life by the Chornobyl disaster. The poet perceived the man-made environmental catastrophe as the last ‘wrath of God’, ‘the deadly tornado’ of the atomic Apocalypse. The evident journalistic component of the three-volume collection requires deeper reading and study in the context of the post-Soviet literature. Based on the classical poetic means and great verse epic forms, the poet created a new expressive type of the lyrical character — the persistent and uncompromising martyr of the Soviet concentration camp. According to the author of the paper, the unsubstantiated evaluations of Hnatiuk’s works as graphomania can be easily refuted by examples of his unique mastery and free command of the word.
Теплозащитные и влажностные свойства наружных стен зданий из керамзитопенобетонных блоков
Authors: АНАНЬЕВ Алексей Иванович , РЫМАРОВ Андрей Георгиевич , ДЕНЩИКОВ Никита Александрович
Published: March 2021

Рассмотрены вопросы, связанные с энергосбережением в зданиях при теплопередаче через наружные стены. В качестве материала наружных стен приняты керамзитопенобетонные блоки с неравномерным распределением теплопроводности и плотности по толщине, что влияет на теплозащитные и влажностные свойства стен зданий. Приведены результаты комплексных теплотехнических исследований на крупноразмерном фрагменте стены. Кривые сорбции и десорбции показывают, что керамзитопенобетон пониженной плотности обладает меньшей способностью поглощать влагу из воздуха по сравнению с плотным керамзитопенобетоном. Анализ влажностного режима однородных фрагментов наружных стен из керамзитопенобетона различной плотности позволяет сделать вывод о значительно меньшей способности керамзитопенобетона пониженной плотности накапливать в себе влагу в сравнении с керамзитопенобетоном высокой плотности. Подтверждается целесообразность создания конструкции многослойного керамзитопенобетонного блока, состоящего из следующих слоев: слои низкой плотности, приближенные к наружной поверхности, плотный внутренний слой, препятствующий миграции влаги из воздуха помещения, и плотный наружный слой, предохраняющий стену от воздействия дождевой влаги. Предложена технология изготовления керамзитопенобетонных блоков с неравномерным распределением плотности по толщине.
Трансформация жилых зданий в современных условиях
Authors: ХАРИТОНОВ Андрей Анатольевич , ДУБЫНИН Николай Васильевич
Published: March 2021

Новые тенденции развития общества требуют трансформации представлений о жилище, особенно в виде многоквартирных жилых зданий. В этой связи возникает острая необходимость соответствия таким современным вызовам и требованиям, как санитарно-эпидемиологическая безопасность, дистанционная работа, бытовое обслуживание с соблюдением социальной дистанции и другие. Таким образом, существующее жилище по архитектурным и инженерно-техническим параметрам должно быть пересмотрено, а обоснованием новых требований должны служить результаты научно-исследовательских работ. При этом не менее важными остаются вопросы комфорта и доступности жилья при реализации государственных программ. Показано, что для успешного проектирования и строительства нового жилища требуется корректировка действующих норм и разработка соответствующих рекомендаций по проектированию. Сделан вывод о том, что концепция трансформации позволит проектировать, строить и эксплуатировать жилые здания максимально соответствующие современным запросам общества.
О пешеходной нагрузке на крыши с теплоизоляцией из минераловатных плит и водоизоляционным ковром из рулонных материалов
Authors: ПЕШКОВА Александра Викторовна , ВОРОНИН Алексей Михайлович
Published: March 2021

Изложены результаты проведенных исследований теплоизоляционных минераловатных плит в конструкциях крыши с водоизоляционным ковром из ПВХ-мембраны, битумно-полимерных рулонных материалов (БПРМ), уложенных на теплоизоляцию насухо с механическим креплением к несущему металлическому профилированному настилу, и из БПРМ, приклеенных к поверхности теплоизоляции. Получены зависимости предела упругости и модуля упругости минераловатных плит от исходных показателей прочности при сжатии в случае 10 %-ной линейной деформации. Установлено, что наибольшему разрушающему воздействию от пешеходной нагрузки подвергаются конструкции крыши с утеплителем из минераловатных плит и водоизоляционным ковром из ПВХ-мембраны, механически закрепленным к несущему настилу. Испытания показали, что увеличение толщины ПВХ-мембраны не влияет на остаточную прочность минераловатных плит. Более высокие качества крыше обеспечивают материалы водоизоляционного ковра клеевой системы с применением БПРМ с механическим креплением нижнего и приклейкой верхнего слоев или с приклейкой обоих слоев рулонного материала к минераловатным плитам.
Обратный численно-аналитический метод расчета легких стальных тонкостенных стержневых элементов
Authors: БЕЛЫЙ Григорий Иванович , СМИРНОВ Максим Олегович
Published: March 2021

Для совершенствования и развития практических методов расчета стержневых элементов легких стальных тонкостенных конструкций предложен обратный численно-аналитический метод, позволяющий сократить время расчета на несколько порядков по сравнению с существующими методами. По заданному предельному напряженному состоянию в нередуцированном сечении при совместном действии продольной силы и изгибающих моментов в двух плоскостях определяется редукция, позволяющая численно, с помощью алгоритма "сечение", установить фактически воспринимаемые этим сечением усилия - обратное решение задач прочности. В задачах пространственной устойчивости полученные таким образом усилия принимаются в наиболее нагруженном сечении за деформационные. При этом влияние редукции компенсируется догружением фиктивными усилиями. Затем, задаваясь гибкостью стержня, обратным аналитическим решением деформационной задачи вычисляют соответствующие условия загружения: концевые двухосные эксцентриситеты фактически действующей силы. Таким же образом решаются более простые задачи устойчивости по изгибной и изгибно-крутильной формам. С целью практического применения решения построены в безразмерных параметрах с использованием коэффициентов продольной силы, относительных эксцентриситетов и приведенных гибкостей. Сопоставления многочисленных результатов расчета по предложенному методу и методу конечных элементов по программе ANSYS показало их достаточно хорошую согласованность, а сопоставление с еврокодом выявило, что последний существенно занижает пространственную устойчивость. В примерах расчета иллюстрируется также влияние фактической редукции сечения на несущую способность, которая может быть учтена коэффициентом потери местной устойчивости и формы сечения, что позволяет сохранить традиционные проверки прочности и общей устойчивости.
A Multi-Methodological Analysis of a Non-Clinical Healthcare Executive and Servant Leader: Attributes and Behaviour’s and their Associations with Reporting Relationships and Business Structures
Authors: Ray Griffin* Dr. Harold , Foster Ms. Dana
Published: March 2021

A multi-methodological approach was used to examine the personal and professional life of a well-respected, nonclinical, healthcare executive for purposes of determining if “Don” was a servant leader and, if so, uncover the antecedents contributing to his leadership style. The results provided the backdrop for examining linkages between servant leadership, reporting relationships, and business structures. Content analysis and Spears’ 10 constructs of servant leaders were used as a priori themes to affirm that Don is a servant leader. Nonparametric testing revealed moderate to strong associations between the reporting relationships of the respondents (x1) and the types of business structures (x2) where the respondents and our servant leader forged their initial relationship and the perceived behaviors and attributes of Don (y). We discovered that relationships, spiritual centeredness, and desire for career advancement served as antecedents in shaping Don’s leadership style. Implications for practice and future research are also addressed.
Internal controls and human capital reengineering to improve financial performance in firm
Authors: Law Professor Philip
Published: March 2021

Financial and internal controls are important to the success of firms. ABC group is undergoing internal controls and knowledge reengineering in the company to improve the group’s operations and financial performance. Various measures are implemented and the results provide insights for firms to succeed in today’s competitive financial markets.
POTENTIALS AND PITFALLS OF THE IMPLEMENTATION OF HYBRID LEARNING IN STRUCTURE CLASS IN RELATION TO THE STUDENTS’ DIGITAL LITERACY AND LEARNING ACHIEVEMENT
Authors: Vonti Lungguh Halira , Grahadila Leora
Published: March 2021

The purpose of this study is to describe the potential and the pitfalls of the implementation of hybrid learning in structure class.  The sampling technique used was purposive sampling since there was only one class who experienced hybrid learning in grammar class. The samples were 20 students of class D from the third semester. The research instrument was a questionnaire and also Focus Group Interview. The research method used is mixed method. The quantitative data is taken from experimental research design and is processed by using SPSS (Statistical Package for Social Science) software version 25.0. the qualitative data is taken from the questionnaire and focus group interview.  The results showed the application of hybrid learning affected positively to the students’ score in structure class since there is significant increase of their posttest score. Based on the qualitative data, it is shown that the application of hybrid learning model has certain aspects that affect their improvement in structure class.  Yet, based on the FGI, the researcher also found out some disadvantages of pitfalls of the implementation of hybrid learning.
VILLAGE ELITE AND CEMENT COMPANY: POWER RELATION OF VILLAGE HEADS ASSOCIATION OF BAYAH AND CEMENT COMPANY IN LEBAK, BANTEN
Authors: Bangsawan Try Adhi , Paskarina Caroline , Bainus Arry
Published: March 2021

This research started from industrial construction in rural area, which is the construction of a cement company in Bayah that give the impact on the environment and social of society, this study used a qualitative descriptive method, the data of research were obtained through interview and documentation study, with the aim to describe how the power relation took place in the village between the head of village and the cement company. To describe this power relation, this research used Gaventa's Power Cube theory, that look at the power from three dimensions of the power cube. These dimensions are the form of power, power space, and power level. The three dimensions above are seen separately, but each other has relationship like rubik cube, which if one dimension is changed, it will have the impact on the others. From this study, there are several findings, that the power relation based on three dimensions of the power cube, the power relation between the village heads and the cement company is related each other when illustrated in a rubik cube.
Genomic architecture differences at the HTT locus associated with symptomatic and pre-symptomatic cases of Huntington’s disease in a pilot study
Authors: Salter Matthew , Powell Ryan , Back Jennifer , Grand Francis , Koutsothanasi Christina , Green Jayne , Hunter Ewan , Ramadass Aroul , Westra Jurjen , Akoulitchev Alexandre
Published: March 2021

Huntington’s Disease (HD) is a progressive neurodegenerative condition that causes degeneration of neurons in the brain, ultimately leading to death. The root cause of HD is an expanded trinucleotide Cytosine-Adenine-Guanine (CAG) repeat in the “huntingtin gene” (HTT). While there is a rough correlation between the number of CAG repeats and disease onset, the development of clinical symptoms can vary by decades within individuals and little is known about this presymptomatic phase. Using peripheral blood samples from HD patients and healthy controls we used EpiSwitch®, a validated high-resolution industrial platform for the detection of chromosome conformations, to assess chromatin architecture in the immediate vicinity of the HTT gene. We evaluated chromatin conformations at 20 sites across 225 kb of the HTT locus in a small cohort of healthy controls, verified symptomatic HD patients (CAG, n>39) and patients with CAG expansions who had not yet manifested clinical symptoms of HD. Discrete chromosome conformations were observed across the patient groups. We found two constitutive interactions (occurring in all patient groups) and seven conditional interactions which were present in HD, but not in healthy controls. Most important, we observed three conditional interactions that were present only in HD patients manifesting clinical symptoms (symptomatic cases), but not in presymptomatic cases. 85% (6 out of 7) of the patients in the symptomatic HD cohort demonstrated at least one of the specific chromosome conformations associated with symptomatic HD. Our results provide the first evidence that chromatin architecture at the HTT locus is systemically altered in patients with HD, with conditional differences between clinical stages. Given the high clinical need in having a molecular tool to assess disease progression in HD, these results strongly suggest that the non-invasive assessment of Chromosome Conformation Signatures (CCS) warrant further study as a prognostic tool in HD.
Hydrogen as a Co-electron Donor for Chain Elongation With Complex Communities
Authors: Baleeiro Flávio C. F. , Kleinsteuber Sabine , Sträuber Heike
Published: March 2021

Electron donor scarcity is seen as one of the major issues limiting economic production of medium-chain carboxylates from waste streams. Previous studies suggest that co-fermentation of hydrogen in microbial communities that realize chain elongation relieves this limitation. To better understand how hydrogen co-feeding can support chain elongation, we enriched three different microbial communities from anaerobic reactors (A, B, and C with ascending levels of diversity) for their ability to produce medium-chain carboxylates from conventional electron donors (lactate or ethanol) or from hydrogen. In the presence of abundant acetate and CO2, the effects of different abiotic parameters (pH values in acidic to neutral range, initial acetate concentration, and presence of chemical methanogenesis inhibitors) were tested along with the enrichment. The presence of hydrogen facilitated production of butyrate by all communities and improved production of i-butyrate and caproate by the two most diverse communities (B and C), accompanied by consumption of acetate, hydrogen, and lactate/ethanol (when available). Under optimal conditions, hydrogen increased the selectivity of conventional electron donors to caproate from 0.23 ± 0.01 mol e–/mol e– to 0.67 ± 0.15 mol e–/mol e– with a peak caproate concentration of 4.0 g L–1. As a trade-off, the best-performing communities also showed hydrogenotrophic methanogenesis activity by Methanobacterium even at high concentrations of undissociated acetic acid of 2.9 g L–1 and at low pH of 4.8. According to 16S rRNA amplicon sequencing, the suspected caproate producers were assigned to the family Anaerovoracaceae (Peptostreptococcales) and the genera Megasphaera (99.8% similarity to M. elsdenii), Caproiciproducens, and Clostridium sensu stricto 12 (97–100% similarity to C. luticellarii). Non-methanogenic hydrogen consumption correlated to the abundance of Clostridium sensu stricto 12 taxa (p < 0.01). If a robust methanogenesis inhibition strategy can be found, hydrogen co-feeding along with conventional electron donors can greatly improve selectivity to caproate in complex communities. The lessons learned can help design continuous hydrogen-aided chain elongation bioprocesses.
Cellulose Isolated From Waste Rubber Wood and Its Application in PLA Based Composite Films
Authors: Ou Zhiqiang , Zhou Qi , Rao Xin , Yang Haifeng , Huo Chunqing , Du Xueyu
Published: March 2021

Waste rubber wood (RW) is the castoff of rubber plantation with abundant reservation but without high-value utilization. In this study, cellulose with high purity has been efficiently isolated from waste RW and further processed into cellulose nanocrystals. By means of acetylation, more hydrophobic cellulose-based products, namely acetylated rubber wood cellulose (Ac–RWC) and acetylated rubber wood cellulose nanocrystals (Ac–RW–CNC) had been attempted as reinforcing fillers for fabricating two series of PLA-based composite films via spin coating instead of currently prevailing melt compounding technique. To ensure a uniformed dispersion of fillers in PLA matrix, the addition of reinforcing filler should be equal to or less than 5% based on the film dry weight. Compared with pure PLA film, the Ac–RWC reinforced PLA composite films are more thermally stable, while the Ac–RW–CNC reinforced PLA composite films on the other hand exhibit more enhanced performance in mechanical properties and the degree of crystallinity. The highest tensile strength (55.0 MPa) and Young’s modulus (3.9 GPa) were achieved for 5%Ac–RW–CNC/PLA composite film.
IRF6 Genetic Variation and Maternal Smoking During Pregnancy in Cleft Lip/Palate
Authors: Vieira Alexandre R. , Koruyucu Mine , Bekele Eyosiyas K. , Seymen Figen , Modesto Adriana
Published: March 2021

The goal of the present work was to revisit published data to test if genetic variation in interferon regulatory factor 6 (IRF6) is associated with children born with cleft lip with or without cleft palate (CL/P) for cases with positive history of maternal smoking. From the 573 individuals originally studied, this reanalysis focused on 57 who had a positive history of maternal smoking during pregnancy (39 born with CL/P and 18 born without CL/P). Seven IRF6 markers (rs4844880, rs2235371, rs2013162, ra861019, rs2073487, rs642961, and rs658860) were tested for over-transmission of alleles and an alpha of 0.05 was considered statistically significant. All individuals born with CL/P were homozygous for the wild type allele of rs2235371 in comparison to just two individuals born without clefts (p = 0.0000001). For rs861019, individuals born with CL/P were more likely to have the variant allele (p = 0.006). A similar trend was seen for rs642961 (p = 0.09). The results suggest that statistical evidence of over-representation of IRF6 alleles in individuals born with CL/P may be unveiled only when maternal smoking during pregnancy is used as the inclusion criterion in the analysis.
Geochemical and Isotopic Evidence for Provenance of the Western Sea of Japan Over the Last 30000 Years
Authors: Dou Ruxi , Zou Jianjun , Shi Xuefa , Zhu Aimei , Dong Zhi , Gorbarenko Sergey , He Lianhua , Gao Jingjing , Zhang Ying , Cui Jingjing
Published: March 2021

The Sea of Japan (JS) is a unique marginal sea in the western North Pacific that is characterized by four shallow straits. It can provide information about the paleoenvironment, for instance indicating variations in the East Asian Monsoon, Tsushima Warm Current, sea ice coverage, and Westerly Jet. Compared with other marginal seas in the western North Pacific, the JS is currently the only marginal sea without influx from large rivers. It is, therefore, of interest to determine the source of terrigenous sediments over time, particularly in the western JS, which has been less investigated in previous reports. In this study, a suite of multi-proxies including Sr and Nd isotopes and minor elements were measured for fine fractions (<63 μm) of core LV53-18-2 that were recovered from the western JS over the last 30 ka. Our results show that the sediments are rich in volcanic detritus and that the provenance of terrigenous sediments in the western JS is mainly derived from the arid region in northern China and coastal areas in the Far East. During the Last Glacial Maximum, the increased coverage of sea ice may have contributed to the accumulation of terrigenous debris. Meanwhile, the stronger East Asian Winter Monsoon and expansion of the Westerly Jet over northern China also carried more dust to the study area. However, the weakened atmospheric circulation and rise in sea level, induced by the ascending boreal insolation during the last deglaciation and early Holocene, remarkably reduced input of terrigenous debris, and the intense melting of sea ice delivered an amount of detritus from coastal areas to the research area. After 8 ka, the high stand sea level and opening of the Tatar Strait may have led to the development of the Liman Cold Current, which transports large quantities of volcanic materials to the study area continuously and produces more positive Eu anomalies, radiogenic εNd, and depleted ΣREE.
Broadband Q-Factor Imaging for Geofluid Detection in the Gulf of Trieste (Northern Adriatic Sea)
Authors: Vesnaver Aldo , Böhm Gualtiero , Busetti Martina , Dal Cin Michela , Zgur Fabrizio
Published: March 2021

Seismic surveys allow estimating lithological parameters, as P-wave velocity and anelastic absorption, which can detect the presence of fracture and fluids in the geological formations. Recently, a new method has been proposed for high-resolution imaging of anelastic absorption, which combines a macro-model from seismic tomography with a micro-model obtained by the pre-stack depth migration of a seismic attribute, i.e., the instantaneous frequency. As a result, we can get a broadband image that provides clues about the presence of saturating fluids. When the saturation changes sharply, as for gas reservoirs with an impermeable caprock, the acoustic impedance contrast produces “bright spots” because of the resulting high reflectivity at its top. When the fluid content changes smoothly, the anelastic absorption becomes a good detector, as fluid-filled formations absorb more seismic energy than hard rocks. We apply this method for imaging the anelastic absorption in a regional seismic survey acquired by OGS in the Gulf of Trieste (northern Adriatic Sea, Italy).
Application of the Educational Game to Enhance Student Learning
Authors: Cheung Siu Yin , Ng Kai Yin
Published: March 2021

The purpose of this study is to investigate the use of an educational game to enhance student learning effectiveness. This study consisted of 56 college students majoring in physical education and recreation management (32 men, 24 women, ageM= 21 years,SD= 1.72). Students used the educational computer game “PaGamO” to study the motor learning and development course. Students received rewards based on their individual and group “PaGamO” scores. Regression analysis indicated that “PaGamO” score was a significant (p< 0.01) predictor of multiple choice (MC) score in the final examination, there was a medium positive correlation (β = 0.354). TheR2suggests that 12.6% of MC score was explained by “PaGamO” score. Quantitative and qualitative mixed-method approach was used to gain insights into students’ perceptions and experiences of the educational game. The top three statements of a modified questionnaire fromRiemer and Schrader (2015)are: (1) “In my opinion, the use of ‘PaGamO’ enables me to better prepare for the final examination” (M=5.04, SD=1.41), (2) “In my opinion, the use of ‘PaGamO’ enables me to understand learning contents” (M=4.8, SD=1.19), (3) “In my opinion, the use of ‘PaGamO’ allows me to apply knowledge” (M=4.75, SD=1.08). The top three motives to play “PaGamO” were “fun,” “self-learning,” and “want to get a higher grade in the final examination.” By using gamification as a tool for learning and studying, students did find “PaGamO” effective for their learning experience. Both intrinsic and extrinsic participation motives are reasons why students play “PaGamO.” Furthermore, due to its convenience, using mobile devices to play “PaGamO” is more popular than using computers and tablet devices. In conclusion, the combination of gamification and traditional learning methods can enhance students’ learning outcomes.
Association Between 10-Year Fracture Probability and Nonalcoholic Fatty Liver Disease With or Without Sarcopenia in Korean Men: A Nationwide Population-Based Cross-Sectional Study
Authors: Lee Hye Jun , Lee Duk Chul , Kim Choon Ok
Published: March 2021

Objective

Nonalcoholic fatty liver disease (NAFLD) and sarcopenia, which are common in elderly men, are known as risk factors of fracture. However, few studies have examined the association with fracture in these patients. Therefore, we aimed to investigate the association between NAFLD with or without sarcopenia and 10-year fracture probability in Korean men aged ≥50 years.

Materials and Methods

Data of 2,525 individuals from the 2010–2011 Korea National Health and Nutrition Examination Survey were analyzed. NAFLD was defined using the fatty liver index (FLI) and comprehensive NAFLD score (CNS), and liver fibrosis using the fibrosis 4 calculator. Sarcopenia was defined as the lowest quintile for sex-specific sarcopenia index cutoff; values. The Fracture Risk Assessment (FRAX) tool was used to predict the 10-year probability of major osteoporotic and hip fractures.

Results

Compared to the no NAFLD group, the 10-year major osteoporotic fracture probability was significantly associated with the FLI-defined (β = 0.16, P = 0.002) and CNS-defined (β = 0.20, P < 0.001) NAFLD groups with liver fibrosis. Similarly, the 10-year hip fracture probability was significantly associated with the FLI- and CNS-defined NAFLD with liver fibrosis groups compared to the group without NAFLD (FLI-defined group, β = 0.04, P = 0.046; CNS-defined group, β = 0.05, P = 0.048). Furthermore, in the group with sarcopenia, the 10-year major osteoporotic fracture probability was significantly associated with the FLI- and CNS-defined NAFLD with liver fibrosis groups compared to the group without NAFLD (FLI-defined group, β = 0.29, P = 0.003; CNS-defined group, β = 0.38, P < 0.001).

Conclusions

NAFLD with liver fibrosis is significantly associated with a higher 10-year major osteoporotic and hip fracture probability in Korean men aged ≥50 years, and this positive association was more profound in patients with sarcopenia. Therefore, screening middle-aged to elderly men who have NAFLD combined with liver fibrosis and sarcopenia may help prevent fractures.
Type 2 Diabetes Mellitus and COVID-19: A Narrative Review
Authors: Corrao Salvatore , Pinelli Karen , Vacca Martina , Raspanti Massimo , Argano Christiano
Published: March 2021

The pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has involved more than one hundred million individuals, including more than two million deaths. Diabetes represents one of the most prevalent chronic conditions worldwide and significantly increases the risk of hospitalization and death in COVID-19 patients. In this review, we discuss the prevalence, the pathophysiological mechanisms, and the outcomes of COVID-19 infection in people with diabetes. We propose a rationale for using drugs prescribed in patients with diabetes and some pragmatic clinical recommendations to deal with COVID-19 in this kind of patient.
Resistance to Thyroid Hormone Beta: A Focused Review
Authors: Pappa Theodora , Refetoff Samuel
Published: March 2021

Resistance to thyroid hormone (RTH) is a clinical syndrome defined by impaired sensitivity to thyroid hormone (TH) and its more common form is caused by mutations in the thyroid hormone receptor beta (THRB) gene, termed RTHβ. The characteristic biochemical profile is that of elevated serum TH levels in absence of thyrotropin suppression. Although most individuals are considered clinically euthyroid, there is variability in phenotypic manifestation among individuals harboring different THRB mutations and among tissue types in the same individual due in part to differential expression of the mutant TRβ protein. As a result, management is tailored to the specific symptoms of TH excess or deprivation encountered in the affected individual as currently there is no available therapy to fully correct the TRβ defect. This focused review aims to provide a concise update on RTHβ, discuss less well recognized associations with other thyroid disorders, such as thyroid dysgenesis and autoimmune thyroid disease, and summarize existing evidence and controversies regarding the phenotypic variability of the syndrome. Review of management addresses goiter, attention deficit disorder and “foggy brain”. Lastly, this work covers emerging areas of interest, such as the relevance of variants of unknown significance and novel data on the epigenetic effect resulting from intrauterine exposure to high TH levels and its transgenerational inheritance.
Brain-Body Control of Glucose Homeostasis—Insights From Model Organisms
Authors: MacDonald Alastair J. , Yang Yu Hsuan Carol , Cruz Ana Miguel , Beall Craig , Ellacott Kate L. J.
Published: March 2021

Tight regulation of blood glucose is essential for long term health. Blood glucose levels are defended by the correct function of, and communication between, internal organs including the gastrointestinal tract, pancreas, liver, and brain. Critically, the brain is sensitive to acute changes in blood glucose level and can modulate peripheral processes to defend against these deviations. In this mini-review we highlight select key findings showcasing the utility, strengths, and limitations of model organisms to study brain-body interactions that sense and control blood glucose levels. First, we discuss the large platform of genetic tools available to investigators studying mice and how this field may yet reveal new modes of communication between peripheral organs and the brain. Second, we discuss how rats, by virtue of their size, have unique advantages for the study of CNS control of glucose homeostasis and note that they may more closely model some aspects of human (patho)physiology. Third, we discuss the nascent field of studying the CNS control of blood glucose in the zebrafish which permits ease of genetic modification, large-scale measurements of neural activity and live imaging in addition to high-throughput screening. Finally, we briefly discuss glucose homeostasis in drosophila, which have a distinct physiology and glucoregulatory systems to vertebrates.
Improving Genomic Prediction for Seed Quality Traits in Oat (Avena sativa L.) Using Trait-Specific Relationship Matrices
Authors: Campbell Malachy T. , Hu Haixiao , Yeats Trevor H. , Brzozowski Lauren J. , Caffe-Treml Melanie , Gutiérrez Lucía , Smith Kevin P. , Sorrells Mark E. , Gore Michael A. , Jannink Jean-Luc
Published: March 2021

The observable phenotype is the manifestation of information that is passed along different organization levels (transcriptional, translational, and metabolic) of a biological system. The widespread use of various omic technologies (RNA-sequencing, metabolomics, etc.) has provided plant genetics and breeders with a wealth of information on pertinent intermediate molecular processes that may help explain variation in conventional traits such as yield, seed quality, and fitness, among others. A major challenge is effectively using these data to help predict the genetic merit of new, unobserved individuals for conventional agronomic traits. Trait-specific genomic relationship matrices (TGRMs) model the relationships between individuals using genome-wide markers (SNPs) and place greater emphasis on markers that most relevant to the trait compared to conventional genomic relationship matrices. Given that these approaches define relationships based on putative causal loci, it is expected that these approaches should improve predictions for related traits. In this study we evaluated the use of TGRMs to accommodate information on intermediate molecular phenotypes (referred to as endophenotypes) and to predict an agronomic trait, total lipid content, in oat seed. Nine fatty acids were quantified in a panel of 336 oat lines. Marker effects were estimated for each endophenotype, and were used to construct TGRMs. A multikernel TRGM model (MK-TRGM-BLUP) was used to predict total seed lipid content in an independent panel of 210 oat lines. The MK-TRGM-BLUP approach significantly improved predictions for total lipid content when compared to a conventional genomic BLUP (gBLUP) approach. Given that the MK-TGRM-BLUP approach leverages information on the nine fatty acids to predict genetic values for total lipid content in unobserved individuals, we compared the MK-TGRM-BLUP approach to a multi-trait gBLUP (MT-gBLUP) approach that jointly fits phenotypes for fatty acids and total lipid content. The MK-TGRM-BLUP approach significantly outperformed MT-gBLUP. Collectively, these results highlight the utility of using TGRM to accommodate information on endophenotypes and improve genomic prediction for a conventional agronomic trait.
High Throughput Multi-Omics Approaches for Clinical Trial Evaluation and Drug Discovery
Authors: Zielinski Jessica M. , Luke Jason J. , Guglietta Silvia , Krieg Carsten
Published: March 2021

High throughput single cell multi-omics platforms, such as mass cytometry (cytometry by time-of-flight; CyTOF), high dimensional imaging (>6 marker; Hyperion, MIBIscope, CODEX, MACSima) and the recently evolved genomic cytometry (Citeseq or REAPseq) have enabled unprecedented insights into many biological and clinical questions, such as hematopoiesis, transplantation, cancer, and autoimmunity. In synergy with constantly adapting new single-cell analysis approaches and subsequent accumulating big data collections from these platforms, whole atlases of cell types and cellular and sub-cellular interaction networks are created. These atlases build an ideal scientific discovery environment for reference and data mining approaches, which often times reveals new cellular disease networks. In this review we will discuss how combinations and fusions of different -omic workflows on a single cell level can be used to examine cellular phenotypes, immune effector functions, and even dynamic changes, such as metabolomic state of different cells in a sample or even in a defined tissue location. We will touch on how pre-print platforms help in optimization and reproducibility of workflows, as well as community outreach. We will also shortly discuss how leveraging single cell multi-omic approaches can be used to accelerate cellular biomarker discovery during clinical trials to predict response to therapy, follow responsive cell types, and define novel druggable target pathways. Single cell proteome approaches already have changed how we explore cellular mechanism in disease and during therapy. Current challenges in the field are how we share these disruptive technologies to the scientific communities while still including new approaches, such as genomic cytometry and single cell metabolomics.
Single-Cell Sequencing Reveals the Transcriptome and TCR Characteristics of pTregs and in vitro Expanded iTregs
Authors: Hui Zhenzhen , Zhang Jiali , Zheng Yu , Yang Lili , Yu Wenwen , An Yang , Wei Feng , Ren Xiubao
Published: March 2021

Regulatory T cells (Tregs) play a critical role in the maintenance of immune tolerance and tumor evasion. However, the relative low proportion of these cells in peripheral blood and tissues has hindered many studies. We sought to establish a rapamycin-based in vitro Treg expansion procedure in patients diagnosed with colorectal cancer and perform single-cell sequencing to explore the characteristics of Treg cells. CD25+ cells enriched from peripheral blood mononuclear cells (PBMC) of colorectal tumor patients were cultured in X-VIVO15 medium, supplemented with 5% human AB serum, L-glutamine, rapamycin, interleukin-2 (IL-2), and Dynabeads human Treg expander for 21 days to expand Tregs. Treg cells with satisfactory phenotype and function were successfully expanded from CD4+CD25+ cells in patients with colorectal cancer. The median expansion fold was 75 (range, 20–105-fold), and >90.0% of the harvest cells were CD4+CD25+CD127dim/− cells. The ratio of CD4+CD25+Foxp3+ cells exceeded 60%. Functional assays showed that iTregs significantly inhibited CD8+T cell proliferation in vitro. Single-cell sequencing showed that the transcriptome of pTreg (CD4+CD25+CD127dim/− cells isolated from PBMC of colorectal cancer patients) and iTreg (CD4+CD25+CD127dim/− cells expanded in vitro according to the above regimen) cells were interlaced. pTregs exhibited enhanced suppressive function, whereas iTregs exhibited increased proliferative capacity. TCR repertoire analysis indicated minimal overlap between pTregs and iTregs. Pseudo-time trajectory analysis of Tregs revealed that pTregs were a continuum composed of three main branches: activated/effector, resting and proliferative Tregs. In contrast, in vitro expanded iTregs were a mixture of proliferating and activated/effector cells. The expression of trafficking receptors was also different in pTregs and iTregs. Various chemokine receptors were upregulated in pTregs. Activated effector pTregs overexpressed the chemokine receptor CCR10, which was not expressed in iTregs. The chemokine CCL28 was overexpressed in colorectal cancer and associated with poor prognosis. CCR10 interacted with CCL28 to mediate the recruitment of Treg into tumors and accelerated tumor progression. Depletion of CCR10+Treg cells from tumor microenvironment (TME) could be used as an effective treatment strategy for colorectal cancer patients. Our data distinguished the transcriptomic characteristics of different subsets of Treg cells and revealed the context-dependent functions of different populations of Treg cells, which was crucial to the development of alternative therapeutic strategies for Treg cells in autoimmune disease and cancer.