bluuebunny/crossref_metadata_2025 huggingface dataset:
Art-technologies as innovative approaches in the learning process
Authors:   Yerevan State University, Republic of Armenia, HAYRAPETYAN Lusine
Published: December 2021

Pedagogical art technologies and methods to increase the efficiency of the teaching process are considered as innovative approaches to the pedagogical process. Within the framework of the article, new approaches to make the pedagogical process more creative were revealed, due to which a number of problems of pedagogical nature can be solved, including the organization of the process of teaching, socialization, upbringing, etc. Aim of the article: The aim of the research conducted within the framework of the article is to identify the importance of involving art technologies and methods in increasing the efficiency of the learning process, to interpret their role in terms of improving the learning process. A number of scientific-pedagogical research methods were used for the research, such as analysis, comparison, abstract, generalization, coordination. As a result of the study, we came to the conclusion that pedagogical art methods and technologies are unique pedagogical alternatives that can solve not only the problem of making the teaching process more active, creative and effective. Those can also contribute to the development of a person's creative potential, self- discovery and self-perception, as well as be useful in organizing joint educational activities for biologically healthy children and children with special needs as unique mechanisms of mental regulation, making the learning process more inclusive, collaborative and constructive. Key words: Pedagogical art technologies, art methods, isotherapy, book therapy, music therapy, teaching process, pedagogical process.
Ways of motivation to learn foreign languages of future aviation specialists in remote learning conditions
Authors:   Flight Academy of National Aviation University, HERASYMENKO Liudmyla , MURAVSKA Svitlana ,   Flight Academy of National Aviation University, PIDLUBNA Olha ,   Flight Academy of National Aviation University
Published: December 2021

The problem of future aviation specialists� motivation to learn foreign languages in the conditions of remote learning has been analyzed in the given article. It has been defined that motivation is a critical component of students� learning and their achievements as their success in studying depends on the level of their motivation. It has been underlined that demotivation has a negative effect on educational process. The results of the observation and students� interviewing have helped to define the main problems which lead to students� demotivation. Among them we can distinguish the following ones: the students are not ready to perceive a big amount of information online; technical problems with the Internet; some personal problems caused by the fact that students stay at home; the absence of universal approach for teaching different subjects; the teachers� lack of knowledge in the sphere of IT; a big amount of tasks online which do not fully correspond to the learning tasks. A few practices have been developed to make online learning more effective. They are presented underneath: using the tasks in which students express their point of view on the learnt material and the aspects they haven�t covered yet; making the activities used in the classroom shorter and, therefore, more effective; using tests and other evaluation techniques to monitor the quality of the learning process; using the sessions in which students can ask questions and take part in the discussions; meetings in breakout rooms during online classes; personal messages to students encouraging them to be actively involved in the learning process; applying real life situations to demonstrate the content; using the project method and additional work with it. The process of modernization of the sphere of education nowadays in the terms of online classes in higher educational establishments is a real challenge today. To succeed in it, we need to create friendly and comfortable virtual environment which will help students to become successful and overcome language barriers. It has also been advised to use different methods to motivate the students to learn the languages by referring to group work and interactive methods and developing critical thinking skills. Key words: motivation to learn foreign languages, aviation specialists� training, remote learning, development of communicative competence, COVID-19 pandemic, interactive teaching methods.
Preparation of scientific and pedagogical workers for work in the conditions of distance learning
Authors:   Flight Academy of National Aviation University, LESHCHENKO Hennadii
Published: December 2021

The article deals with the problem of improving the quality of education on the basis of introduction into the educational process of distance learning. It is determined that distance education is a kind of educational system, which uses mainly remote learning technologies and educational process organization, or one of the forms of obtaining education, in which the mastery of one or another of its levels in one or another specialty is carried out in the process of distance learning. Factors that contributed to the emergence of forms of distance education are: globalization, increasing the dynamics of socio-economic development of society, the emergence of new needs of those who study, and the development of information and communication technologies, their full implementation in virtually all spheres of human life, the need for wide application in educational Practice as a means of learning and subject of study. It is established that the effectiveness of distance learning depends on the professional training of the teacher-tutor as a subject of the educational process. The process of training the tutors focuses on the development of their communicative, analytical, reflective skills and psychological readiness to work in the virtual space, the skills of facilitation, that is, the establishment and maintenance of information links and interaction between the listeners and other participants in the system of distance education, the regulation of various problems, conflict resolution, adaptation of listeners to a new form of learning. The author stresses that the main problems of the creation and implementation of distance learning systems are computer-technological, organizational-managerial, psychological and pedagogical, financial-economic and normative-legal. Along with the awareness of the need for an integrated and balanced solution to each of these problems, one should highlight the psychological and pedagogical as such, the theoretical and practical solution of which today is the task of the most complex, to the required boundary is not defined and therefore not properly resolved. The conceptual foundations of practical implementation of the model of training of teachers of higher education and designing the routes of their professional training for the implementation of distance learning are determined. Key words: distance learning, tutor, advanced training courses, educational process, professionally important qualities.
Presentations, portfolio and blog-folio as a variety of innovative educational technologies among methods of studying a foreign language in higher educational establishments
Authors:   Flight Academy of National Aviation University, CHALA Natalya , KOVALOVA Inna ,   Flight Academy of National Aviation University
Published: December 2021

The article presents an analysis of the most popular innovative educational technologies used in the modern educational process in Ukraine and abroad � presentations, portfolios and blog folios. The main methodological principles and criteria that can ensure the effectiveness of innovative educational technologies use and improve the quality of foreign language learning in higher educational establishments. Key words: educational process, innovative technologies, millennials, educational technologies, portfolio, portfolio presentation, checklist, blog folio, interactive online blog.
Features of providing english � language training of future aviation specialists for professional self-realization with the use of distance learning technologies
Authors:   Flight Academy of National Aviation University, RADUL Serhii
Published: December 2021

The article considers the peculiarities of providing English-language training of (future) aviation specialists for professional self-realization and performance of professional duties with the use of modern distance learning technologies. The specifics of distance learning are revealed. Terms and concepts, forms of learning are provided. Distance learning technologies, namely: psychological and pedagogical, information and communication, web-environment provide an opportunity to implement the process of distance learning in educational institutions. There are also two strategies for organizing distance learning: asynchronous distance learning and synchronous distance learning. During the planning and organization of distance learning a great role is given to the independent work of cadets. There are also IT elements that a lecturer and a cadet should be able to use in professional interaction. It is noted that Internet technologies, the ability to use Internet resources have a special place in the formation of professional self-realization of a future aviation specialist and providing innovative approaches to the educational environment. The main tasks of English language training in the educational language centers of the Flight Academy of NAU are: improving language skills and strengthening the communicative competence of the teacher / instructor to teach the professional disciplines in English, teaching professional English, preparation for the general English exam at level B2. The use of distance learning technologies in the English-language training of future aviation specialists requires a high level of knowledge, both theoretical and practical. It is necessary to interest and direct students to the use of innovative methods in order to build their professional capacity to use information and communication technologies in their further professional self-realization. Key words: distance learning, English language training of an aviation specialist, ICT, Internet resources, innovations, professional self-realization.
Comparative analysis of systems of higher education management in Greece and Italy
Authors:   Yerevan State University, AVETISYAN Meri
Published: December 2021

The article touches upon in details and presents the governing bodies of the higher education systems in Greece and Italy, emphasizes the similarities and differences in the education process in the universities of the above-mentioned countries. It mentions their management pecularities, as well as reveals the importance and role of higher education in the progressive development of each of these countries. At the same time, this article covers favorable conditions for the productive conduct of the education process in universities and the correct approach to solving various issues regarding higher education in Greece and Italy. Key words: University; higher education system; management; assessment system; admission; academic freedom; structure of higher education, educational degrees.
Naturaleza jurídica de las ¨sociedades civiles y mercantiles¨ y su relación con la práctica notarial
Authors: Arroba López David Alejandro
Published: December 2021

En el Ecuador, coexisten un sin número de sociedades de distinta naturaleza, entre las que conviene mencionar a las sociedades civiles, sociedades mercantiles, y aquellas sociedades llamadas ¨de hecho¨.  Pero además de las referidas, existe un tipo de sociedad que en la práctica se está constituyendo, me refiero con esto a las sociedades ¨civiles y mercantiles¨ mismas que conforme se analizará a lo largo de este artículo no pueden ser consideradas como si se tratase de un tipo societario, ya que las sociedades o bien son civiles o, bien mercantiles, y que la atribución contenida en el numeral 29, del artículo 18, de la ley notarial -que es el sustento legal en el que se está basando la creación de estas sociedades- lo que pretendía era eliminar el requisito de aprobación judicial existente para las compañías mercantiles en nombre colectivo y en comandita simple, transfiriendo esa facultad al servicio notarial, más no crear una figura jurídica inexistente como lo es la llamada ¨sociedad civil y mercantil¨. Objetivo.- el objetivo del presente trabajo es demostrar a través del análisis de varios casos, cómo mediante la interpretación del artículo 18, numeral 29, de la ley Notarial, se están constituyendo erróneamente sociedades ¨civiles y mercantiles¨ como si fuesen una especie de compañía. Metodología.- En el presente trabajo de investigación se ha aplicado los métodos: inductivo e histórico lógico. Aportes.- El presente trabajo busca aportar en el debate jurídico societario ecuatoriano, al criticar la interpretación que se está dando de una norma que equivocadamente ha permitido la constitución de las llamadas ¨sociedades civiles y mercantiles¨, que conforme se analizará no tiene un sustento legal.
Development of Learning Unit Book based on Insect Inventory Results of Amorphophallus titanum as an Effort to Foster Students’ Concern to the Environment
Authors: Harianto Harianto , Karyadi Bhakti , Wardana Rendy W.
Published: December 2021

Natural Science subject learning materials emphasize the observation of natural phenomena and their application in daily life. This research aims to foster students' concern for the environment through a learning unit book on the interaction of living things. The type of research was a "research and development method" with the design of 4-D model development research. The learning unit book was made based on the results of insect inventory on Amorphophallus titanum. The learning unit book was presented to the 8th-grade students of SMP Negeri Rejang Lebong, Bengkulu.  The subject in this study was class VIII B on a limited trial. The subject was selected using the purposive sampling method. The data from the study was obtained by providing a questionnaire on environmental concerns. Analysis used test-n-Gain, and small-scale test results of environmental concern found an average score of 77.24 that are well categorized.
The Implementation of Strain Liquefaction Learning Package to Cultivate the Critical Thinking of High School Students
Authors: Pirnandes Lubis , Karyadi Bhakti , Farid M.
Published: December 2021

This study aims to explain the potential of liquefaction in Padang Lekat Village and Pasar Ujung Village Kepahiang District, explaining the feasibility of developed learning packages, and explaining students' critical thinking skills after learning the wave material through the learning package "Strain Liquidity Learning". The type of study used was research and development which aims to develop digital-based physics learning packages that are integrated with disaster mitigation education on the basic competencies of waves in high school education units.  This research was conducted using ADDIE development research procedures.  The results of research on the analysis of liquefaction potential based on microtremor data using the Ground Shear Strain method, zoning indication of liquefaction potential due to geological conditions and seismic potential, generally Padang Lekat Village and Pasar Ujung Kepahiang Village are areas that have no potential to experience liquefaction.  However, there are a number of locations indicated by potential liquefaction, although not significantly.  Learning Package Book "Learning Liquid Strain" compiled based on the analysis of liquefaction potential based on expert validation is appropriate to be used as a learning medium for seismic and liquefaction waves.  In its application with distance learning, the compiled learning package book has been able to improve critical thinking skills in students even though the N-gain improvement obtained is still in the low and medium categories.
Optimasi Sintesis Ligan Diheksilditiofosfat (DHDTP) Menggunakan Response Surface Method (RSM)
Authors: Hendrati Diana , Mardhotillah Yulia , Anggraeni Anni , Firdaus M. Lutfi , Wyantuti Santhy
Published: December 2021

Dihexyldithiophosphate (DHDTP) ligand is one of the homologues of dialkyldithiophosphate which is potentially better as an extractant in solvent extraction. The longer the chain in the dialkyldithophosphate compound, ability to dissolve into the organic phase is increasing compared to the shorter chain. The purpose of this study is to synthesize DHDTP ligands and find out the optimum reaction conditions to produce DHDTP ligands with optimal purity using the BoxBehnken (BBD) response surface method (RSM). DHDTP ligands are synthesized from P2S5 by reflux after addition of n-hexanol under a nitrogen gas environment. Ammonium carbonate is added to the reflux to pH 7, then evaporated to remove the solvent. The synthesized DHDTP ligand was then purified by column chromatography with a mobile phase methanol : aquadest (2.5% gradient). DHDTP ligands were examined for purity using a reverse phase HPLC with a mobile phase methanol: aquadest 3: 2. The purity of the best DHDTP synthesis results obtained was 87.34%. The DHDTP ligand formed was characterized to confirm the structure of its ligand compound by using a UV spectrophotometer in which the synthesis product showed maximum absorption at a wavelength of 212 nm and mass spectroscopy ES- with m / z 297.1687.
Investigating avoidance and attraction responses in lesser black-backed gulls Larus fuscus to offshore wind farms
Authors: Johnston DT , Thaxter CB , Boersch-Supan PH , Humphreys EM , Bouten W , Clewley GD , Scragg ES , Masden EA , Barber L , Conway GJ , Clark NA , Burton NHK , Cook ASCP
Published: December 2021

Movements through or use of offshore wind farms by seabirds while commuting or foraging may increase the potential for collision with turbine blades. Collision risk models provide a method for estimating potential impacts of wind farms on seabird populations, but are sensitive to input parameters, including avoidance rates (ARs). Refining understanding of avoidance through the use of high-resolution empirical movement data has the potential to inform assessments of the collision impacts of offshore wind farms on seabird populations. We assessed the movements of GPS-tagged lesser black-backed gulls Larus fuscus from a breeding colony in northwest England to estimate the species’ AR and avoidance/attraction index (AAI) to nearby offshore wind farms. To investigate both macro- (0-4 km) and meso-scale (0-200 m) responses to wind turbines, we used calculations of AR and AAI based on simulated vs. observed tracks. We found that birds exhibited an AR of -0.15 (95% CI: -0.44 to 0.06), indicating a degree of attraction within 4 km of the wind farms. However, AAI values varied with distance from wind farm boundaries, with a degree of avoidance displayed between 3 and 4 km, which weakened as distance bands approach wind farm boundaries. Meso-scale avoidance/attraction was assessed with regard to the nearest individual turbine, and flight height relative to the rotor height range (RHR) of the nearest turbine. We found attraction increased below the RHR at distances <70 m, while avoidance increased within the RHR at distances approaching the turbine. We explore how high-resolution tracking data can be used to improve our knowledge of L. fuscus avoidance/attraction behaviour to established wind farms, and so inform assessments of collision impacts.
Effects of perceived competition and water temperature on the functional responses of invasive and native crabs
Authors: Howard BR , Wong DTS , Aguiar V , Desforges J , Oishi EM , Stewart J , Côté IM
Published: December 2021

As the frequency of species introductions increases globally, the need for predicting the ecological impacts of invaders becomes ever more urgent. Functional responses, i.e. how resource uptake by consumers changes as a function of resource density, describe the species-specific ability to deplete resources under standardized conditions, and their shape has been used as a tool to predict the impact of non-native species. However, functional responses are usually derived from individuals foraging alone, which overlooks the important roles of intra- and interspecific interactions in shaping per capita consumption rates. We tested the extent to which the functional responses of invasive European green crabCarcinus maenasand native graceful rock crabMetacarcinus gracilisare affected by the perceived presence of con- and heterospecific individuals. Overall, crabs did not consume significantly more prey in the perceived presence of either a conspecific or novel heterospecific, but did demonstrate significantly higher attack rates in warmer water in the presence of a conspecific. Regardless of competitor type, green crabs consumed, on average, 16% more prey than the native crabs. This was largely due to their higher attack rate and lower prey handling time in warmer water. Green crab prey consumption increased significantly with increasing water temperature while that of the native crab species was unaffected (12 vs. 3.5% per 1°C increase, respectively). Higher maximum feeding rates are congruent with green crab impacts throughout their invaded range and suggest that green crabs might be undeterred from feeding in the presence of this co-occurring native crab species.
The Rise of Telemedicine: Lessons from a Global Pandemic
Authors: Seivert Samantha , Badowski Melissa E.
Published: December 2021

Telemedicine has been available for healthcare systems to assist patient care for many years; however, it was not until recently that the field of telemedicine exploded. Inconsistent coverage of telemedicine services as well as a general level of unfamiliarity with the technology required to perform telemedicine services contributed to the lack of its widespread use. The coronavirus disease (COVID-19) pandemic drove the institution of telemedicine in all areas of healthcare. Healthcare institutions around the world adapted both inpatient and outpatient services in order to utilise telemedicine. The implementation of telemedicine can partly be attributed to the expansion of insurance coverage as well as the relaxation of technology requirements to avoid Health Insurance Portability and Accountability Act (HIPAA) violations. During the global pandemic, telemedicine helped to preserve personal protective equipment during a worldwide shortage, protect healthcare workers from being infected, and allowed the monitoring of patients’ chronic conditions without putting them at risk by attending medical settings. The COVID-19 outbreak has highlighted the advantages that telemedicine has to offer and has served as the push many health systems needed to implement telemedicine services more widely across these institutions. This article highlights the role of telemedicine during the ongoing COVID-19 global pandemic.
Dress and Dress Fasteners from the Pagan Norse Graves of Scotland: Origins and Identity
Authors: Paterson Caroline
Published: December 2021

The pagan Norse graves of Scotland provide a tantalising glimpse of what the interred were wearing at the time of burial. However, the survival of actual clothing, frequently in a mineralised state, is rare. Yet dress accessories—typically brooches, cloak pins and belt fittings—help to create a more comprehensive picture of the dress worn, and of contemporary fashion. The origins of these fittings can be identified by their form, ornament and metallic composition. Some, such as the paired oval brooches found in female burials, are typically Scandinavian and indicative of the wearing of a pinafore-like dress, corroborated on occasion by surviving textile loops mineralised within their shells. However, others, including penannular brooches, ringed pins and bossed belt fittings, are of Insular origin and illustrate an emerging Hiberno-Scandinavian identity. Such evidence for cultural interaction through dress provides a fascinating insight into contemporary perceptions of identity, just prior to the abandonment of the pagan ritual with the subsequent loss of this rich source of evidence.
Experience with stereotaxis in patient with local relapse of neuroblastoma in central nervous system in context of combination therapy
Authors: Mikhailova E. A. , Kulyova S. A. , Ivanova S. V. , Novikov S. N. , Senchurov E. M. , Gumbatova E. D. , Khabarova R. I. , Borokshinova K. M. , Gogun A. A.
Published: December 2021

Neuroblastoma is a complicated systemic malignant process that requires risk-adapted, multimodal therapy. Certainly, the dissemination of the tumor process is an extremely unfavorable prognosis for the patient’s life and health, however, local relapses can be cured successfully. The aim of the article is to demonstrate a rare clinical case of using SBRT in a patient with central nervous system neuroblastoma local relapse in the context of combined modality treatment.
ДУХОВНОЕ ВЛИЯНИЕ СОВЕТСКОГО СТРОЯ НА ИЕРАРХОВ И ДУХОВЕНСТВО В 1960-е - 1980-е ГОДЫ
Authors: Кириченко Олег Викторович
Published: December 2021

Статья посвящена малоизученному явлению – церковному инакомыслию, которое было порождено влиянием «советской духовности» не только на общество, но и на Церковь. Автор ставит проблему инакомыслия и диссидентства как явлений, выросших в недрах высшей советской номенклатуры и потом уже распространившихся на низшие слои, затронувшие и церковную среду. Апелляция к Западу, как к третейскому судье, была закономерным явлением советской действительности, что требует научной проработки и объяснения.
The article is devoted to a little-studied phenomenon - church dissent, which was generated by the influence of "Soviet spirituality" not only on society, but also on the Church. The author poses the problem of dissent and dissidentism as phenomena that grew up in the the higher Soviet nomenclature and then spread to the lower layers, affecting the church environment. An appeal to the West as an arbitrator was a natural phenomenon of Soviet reality, which requires scientific study and explanation.
NF-κB/p65 Competes With Peroxisome Proliferator-Activated Receptor Gamma for Transient Receptor Potential Channel 6 in Hypoxia-Induced Human Pulmonary Arterial Smooth Muscle Cells
Authors: Wang Yan , Li Naijian , Wang Yingfeng , Zheng Guobing , An Jing , Liu Chang , Wang Yajie , Liu Qicai
Published: December 2021

Objective: Peroxisome proliferator-activated receptor gamma (PPARγ) has an anti-proliferation effect on pulmonary arterial smooth muscle cells (PASMCs) via the transient receptor potential channel (TRPC) and protects against pulmonary artery hypertension (PAH), whereas nuclear factor-kappa B (NF-κB) has pro-proliferation and pro-inflammation effects, which contributes to PAH. However, the association between them in PAH pathology remains unclear. Therefore, this study aimed to investigate this association and the mechanisms underlying TRPC1/6 signaling-mediated PAH.

Methods: Human pulmonary arterial smooth muscle cells (hPASMCs) were transfected with p65 overexpressing (pcDNA-p65) and interfering plasmids (shp65) and incubated in normal and hypoxic conditions (4% O2 and 72 h). The effects of hypoxia and p65 expression on cell proliferation, invasion, apoptosis, [Ca2+]i, PPARγ, and TRPC1/6 expression were determined using Cell Counting Kit-8 (CCK-8), Transwell, Annexin V/PI, Fura-2/AM, and western blotting, respectively. In addition, the binding of p65 or PPARγ proteins to the TRPC6 promoter was validated using a dual-luciferase report assay, chromatin-immunoprecipitation-polymerase chain reaction (ChIP-PCR), and electrophoretic mobility shift assay (EMSA).

Results: Hypoxia inhibited hPASMC apoptosis and promoted cell proliferation and invasion. Furthermore, it increased [Ca2+]i and the expression of TRPC1/6, p65, and Bcl-2 proteins. Moreover, pcDNA-p65 had similar effects on hypoxia treatment by increasing TRPC1/6 expression, [Ca2+]i, hPASMC proliferation, and invasion. The dual-luciferase report and ChIP-PCR assays revealed three p65 binding sites and two PPARγ binding sites on the promoter region of TRPC6. In addition, hypoxia treatment and shPPARγ promoted the binding of p65 to the TRPC6 promoter, whereas shp65 promoted the binding of PPARγ to the TRPC6 promoter.

Conclusion: Competitive binding of NF-κB p65 and PPARγ to TRPC6 produced an anti-PAH effect.
Early Thalamic Injury After Resuscitation From Severe Asphyxial Cardiac Arrest in Developing Rats
Authors: Ton Hoai T. , Raffensperger Katherine , Shoykhet Michael
Published: December 2021

Children who survive cardiac arrest often develop debilitating sensorimotor and cognitive deficits. In animal models of cardiac arrest, delayed neuronal death in the hippocampal CA1 region has served as a fruitful paradigm for investigating mechanisms of injury and neuroprotection. Cardiac arrest in humans, however, is more prolonged than in most experimental models. Consequently, neurologic deficits in cardiac arrest survivors arise from injury not solely to CA1 but to multiple vulnerable brain structures. Here, we develop a rat model of prolonged pediatric asphyxial cardiac arrest and resuscitation, which better approximates arrest characteristics and injury severity in children. Using this model, we characterize features of microglial activation and neuronal degeneration in the thalamus 24 h after resuscitation from 11 and 12 min long cardiac arrest. In addition, we test the effect of mild hypothermia to 34°C for 8 h after 12.5 min of arrest. Microglial activation and neuronal degeneration are most prominent in the thalamic Reticular Nucleus (nRT). The severity of injury increases with increasing arrest duration, leading to frank loss of nRT neurons at longer arrest times. Hypothermia does not prevent nRT injury. Interestingly, injury occurs selectively in intermediate and posterior nRT segments while sparing the anterior segment. Since all nRT segments consist exclusively of GABA-ergic neurons, we asked if GABA-ergic neurons in general are more susceptible to hypoxic-ischemic injury. Surprisingly, cortical GABA-ergic neurons, like their counterparts in the anterior nRT segment, do not degenerate in this model. Hence, we propose that GABA-ergic identity alone is not sufficient to explain selective vulnerability of intermediate and posterior nRT neurons to hypoxic-ischemic injury after cardiac arrest and resuscitation. Our current findings align the animal model of pediatric cardiac arrest with human data and suggest novel mechanisms of selective vulnerability to hypoxic-ischemic injury among thalamic GABA-ergic neurons.
YKL-40 Aggravates Early-Stage Atherosclerosis by Inhibiting Macrophage Apoptosis in an Aven-dependent Way
Authors: Huan Wei , Yandong Liu , Chao Wang , Sili Zou , Jun Bai , Mingfang Liao , Yu Chen , Lefeng Qu
Published: December 2021

Objective: programmed cell removal in atherosclerotic plaques plays a crucial role in retarding lesion progression. Macrophage apoptosis has a critical role in PrCR, especially in early-stage lesions. YKL-40 has been shown to be elevated as lesions develop and is closely related to macrophages. This study aimed to determine the effect of YKL-40 on regulating macrophage apoptosis and early-stage atherosclerosis progression.

Research design and Methods: The correlations among the expression level of YKL-40, the area of early-stage plaque, and the macrophage apoptosis rate in plaques have been shown in human carotid atherosclerotic plaques through pathological and molecular biological detection. These results were successively confirmed in vivo (Ldlr−/- mice treated by YKL-40 recombinant protein/neutralizing antibody) and in vitro (macrophages that Ykl40 up-/down-expressed) experiments. The downstream targets were predicted by iTRAQ analysis.

Results: In early-stage human carotid plaques and murine plaques, the YKL-40 expression level had a significant positive correlation with the area of the lesion and a significant negative correlation with the macrophage apoptosis rate. In vivo, the plaque area of aortic roots was significantly larger in the recomb-YKL-40 group than that in IgG group (p = 0.0247) and was significantly smaller in the anti-YKL-40 group than in the IgG group (p = 0.0067); the macrophage apoptosis rate of the plaque in aortic roots was significantly lower in the recomb-YKL-40 group than that in IgG group (p = 0.0018) and was higher in anti-YKL-40 group than that in VC group. In vitro, the activation level of caspase-9 was significantly lower in RAW264.7 with Ykl40 overexpressed than that in controls (p = 0.0054), while the expression level of Aven was significantly higher than that in controls (p = 0.0031). The apoptosis rate of RAW264.7 treated by recomb-YKL40 was significantly higher in the Aven down-regulated group than that in the control group (p < 0.001). The apoptosis inhibitor Aven was confirmed as the target molecule of YKL-40. Mechanistically, YKL-40 could inhibit macrophage apoptosis by upregulating Aven to suppress the activation of caspase-9.

Conclusion: YKL-40 inhibits macrophage apoptosis by upregulating the apoptosis inhibitor Aven to suppress the activation of caspase-9, which may impede normal PrCR and promote substantial accumulation in early-stage plaques, thereby leading to the progression of atherosclerosis.
A Novel lncRNA Panel Related to Ferroptosis, Tumor Progression, and Microenvironment is a Robust Prognostic Indicator for Glioma Patients
Authors: He Yikang , Ye Yangfan , Tian Wei , Qiu Huaide
Published: December 2021

Objective: To establish a lncRNA panel related to ferroptosis, tumor progression, and microenvironment for prognostic estimation in patients with glioma.

Methods: LncRNAs associated with tumor progression and microenvironment were screened via the weighted gene co-expression network analysis (WGCNA). Overlapped lncRNAs highlighted in WGCNA, related to ferroptosis, and incorporated in Chinese Glioma Genome Atlas (CGGA) were identified as hub lncRNAs. With expression profiles of the hub lncRNA, we conducted the least absolute shrinkage and selection operator (LASSO) regression and built a ferroptosis-related lncRNA signature to separate glioma patients with distinct survival outcomes. The lncRNA signature was validated in TCGA, the CGGA_693, and CGGA_325 cohorts using Kaplan-Meier survival analysis and ROC curves. The ferroptosis-related lncRNA panel was validated with 15 glioma samples using quantitative real-time PCR (qRT-PCR). Multivariate Cox regression was performed, and a nomogram was mapped and validated. Immune infiltration correlated to the signature was explored using TIMER and CIBERSORT algorithms.

Results: The present study identified 30 hub lncRNAs related to ferroptosis, tumor progression, and microenvironment. With the 30 hub lncRNAs, we developed a lncRNA signature with distinct stratification of survival chance in patients with glioma in two independent cohorts (HRs>1, p < 0.05). The lncRNA signature revealed a panel of 14 lncRNAs, i.e., APCDD1L-AS1, H19, LINC00205, LINC00346, LINC00475, LINC00484, LINC00601, LINC00664, LINC00886, LUCAT1, MIR155HG, NEAT1, PVT1, and SNHG18. These lncRNA expressions were validated in clinical specimens using qRT-PCR. Robust predictive accuracies of the signature were present across different datasets at multiple timepoints. With univariate and multivariate regressions, we demonstrated that the risk score based on the lncRNA signature is an independent prognostic indicator after clinical factors were adjusted. A nomogram was constructed with these prognostic factors, and it has demonstrated decent classification and accuracy. Additionally, the signature-based classification was observed to be correlated with multiple clinical characteristics and molecular subtypes. Further, extensive immune cells were upregulated in the high-risk group, such as CD8+ T cell, neutrophil, macrophage, and myeloid dendritic cell, indicating increased immune infiltrations.

Conclusion: We established a novel ferroptosis-related lncRNA signature that could effectively stratify the prognosis of glioma patients with adequate predictive performance.
BBS7–SHH Signaling Activity Regulates Primary Cilia for Periodontal Homeostasis
Authors: Chang Pi En , Li Shujin , Kim Hyun-Yi , Lee Dong-Joon , Choi Yoon Jeong , Jung Han-Sung
Published: December 2021

Objectives: Mechanical stimuli are essential for the maintenance of periodontal ligament (PDL) homeostasis. Although there are several studies on atrophic changes in PDL due to occlusal hypofunction, the underlying mechanism is still unknown. Here, we aimed to explore the changes of gene expression in occlusal hypofunctional PDL and elucidate the related role in maintaining the PDL homeostasis.

Methods: To investigate the transcriptomic difference between control and hypofunctional PDL tissue from patients, RNA sequencing was performed on 34 human teeth. The atrophic changes in PDL were evaluated by histological analysis. The effect of the Bardet-Biedl syndrome 7 (BBS7) knockdown was evaluated by the RT-qPCR, Western blot, wound healing, and tubule formation assay.

Results: We detected that the expression of BBS7 was downregulated in occlusal hypofunctional PDL through RNA sequencing. Dynamic changes, including the number of periodontal ligament cells, alignment of collagen fibers, diameter of blood vessels, appearance of primary cilia, and torturous oxytalan fibers, were observed following occlusal hypofunction. Furthermore, Sonic hedgehog signaling (Shh) activity was closely associated with BBS7 expression in PDL cells. In addition, the cell migration and angiogenesis were also suppressed by BBS7 knockdown in vitro.

Conclusion: We suggest that BBS7 plays an essential role in maintaining Shh signaling activity for PDL homeostasis.
Periodontal Disease: The Good, The Bad, and The Unknown
Authors: Sedghi Lea M. , Bacino Margot , Kapila Yvonne Lorraine
Published: December 2021

Periodontal disease is classically characterized by progressive destruction of the soft and hard tissues of the periodontal complex, mediated by an interplay between dysbiotic microbial communities and aberrant immune responses within gingival and periodontal tissues. Putative periodontal pathogens are enriched as the resident oral microbiota becomes dysbiotic and inflammatory responses evoke tissue destruction, thus inducing an unremitting positive feedback loop of proteolysis, inflammation, and enrichment for periodontal pathogens. Keystone microbial pathogens and sustained gingival inflammation are critical to periodontal disease progression. However, recent studies have revealed the importance of previously unidentified microbes involved in disease progression, including various viruses, phages and bacterial species. Moreover, newly identified immunological and genetic mechanisms, as well as environmental host factors, including diet and lifestyle, have been discerned in recent years as further contributory factors in periodontitis. These factors have collectively expanded the established narrative of periodontal disease progression. In line with this, new ideologies related to maintaining periodontal health and treating existing disease have been explored, such as the application of oral probiotics, to limit and attenuate disease progression. The role of systemic host pathologies, such as autoimmune disorders and diabetes, in periodontal disease pathogenesis has been well noted. Recent studies have additionally identified the reciprocated importance of periodontal disease in potentiating systemic disease states at distal sites, such as in Alzheimer’s disease, inflammatory bowel diseases, and oral cancer, further highlighting the importance of the oral cavity in systemic health. Here we review long-standing knowledge of periodontal disease progression while integrating novel research concepts that have broadened our understanding of periodontal health and disease. Further, we delve into innovative hypotheses that may evolve to address significant gaps in the foundational knowledge of periodontal disease.
Building an Artificial Intelligence Laboratory Based on Real World Data: The Experience of Gemelli Generator
Authors: Damiani A. , Masciocchi C. , Lenkowicz J. , Capocchiano N. D. , Boldrini L. , Tagliaferri L. , Cesario A. , Sergi P. , Marchetti A. , Luraschi A. , Patarnello S. , Valentini V.
Published: December 2021

The problem of transforming Real World Data into Real World Evidence is becoming increasingly important in the frameworks of Digital Health and Personalized Medicine, especially with the availability of modern algorithms of Artificial Intelligence high computing power, and large storage facilities.Even where Real World Data are well maintained in a hospital data warehouse and are made available for research purposes, many aspects need to be addressed to build an effective architecture enabling researchers to extract knowledge from data.We describe the first year of activity at Gemelli Generator RWD, the challenges we faced and the solutions we put in place to build a Real World Data laboratory at the service of patients and health researchers. Three classes of services are available today: retrospective analysis of existing patient data for descriptive and clustering purposes; automation of knowledge extraction, ranging from text mining, patient selection for trials, to generation of new research hypotheses; and finally the creation of Decision Support Systems, with the integration of data from the hospital data warehouse, apps, and Internet of Things.
SGLT2is vs. GLP1RAs Reduce Cardiovascular and All-Cause Mortality
Authors: Qiu Mei , Wei Xu-Bin , Wei Wei
Published: December 2021

Lin et al. recently did a network meta-analysis based on cardiovascular (CV) outcome trials (CVOTs) of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and those of glucagon-like peptide-1 receptor agonists (GLP1RAs). Due to the absence of CVOTs directly comparing SGLT2is with GLP1RAs, Lin et al.'s network meta-analysis identified the indirect evidence that SGLT2is vs. GLP1RAs reduced hospitalization for heart failure (HHF) but did not reduce CV death and all-cause mortality (ACM) in patients with type 2 diabetes (T2D). We did another meta-analysis incorporating those CV outcome cohort studies directly comparing SGLT2is with GLP1RAs, and identified that SGLT2is vs. GLP1RAs were significantly associated with the lower risks of not only HHF but also CV death and ACM. These findings may suggest that SGLT2is should be considered over GLP1RAs in terms of preventing CV and all-cause death and HHF in T2D patients.
The Clinical Course of Alcohol Use Disorder Depicted by Digital Biomarkers
Authors: Zetterström Andreas , Hämäläinen Markku D. , Winkvist Maria , Söderquist Marcus , Öhagen Patrik , Andersson Karl , Nyberg Fred
Published: December 2021

Aims: This study introduces new digital biomarkers to be used as precise, objective tools to measure and describe the clinical course of patients with alcohol use disorder (AUD).

Methods: An algorithm is outlined for the calculation of a new digital biomarker, the recovery and exacerbation index (REI), which describes the current trend in a patient's clinical course of AUD. A threshold applied to the REI identifies the starting point and the length of an exacerbation event (EE). The disease patterns and periodicity are described by the number, length, and distance between EEs. The algorithms were tested on data from patients from previous clinical trials (n = 51) and clinical practice (n = 1,717).

Results: Our study indicates that the digital biomarker-based description of the clinical course of AUD might be superior to the traditional self-reported relapse/remission concept and conventional biomarkers due to higher data quality (alcohol measured) and time resolution. We found that EEs and the REI introduce distinct tools to identify qualitative and quantitative differences in drinking patterns (drinks per drinking day, phosphatidyl ethanol levels, weekday and holiday patterns) and effect of treatment time.

Conclusions: This study indicates that the disease state—level, trend and periodicity—can be mathematically described and visualized with digital biomarkers, thereby improving knowledge about the clinical course of AUD and enabling clinical decision-making and adaptive care. The algorithms provide a basis for machine-learning-driven research that might also be applied for other disorders where daily data are available from digital health systems.
Intensified Impact of Winter Arctic Oscillation on Simultaneous Precipitation Over the Mid–High Latitudes of Asia Since the Early 2000s
Authors: Zhou Haibo , Fan Ke
Published: December 2021

This study reveals an intensified impact of winter (November–February mean) Arctic Oscillation (AO) on simultaneous precipitation over the mid–high latitudes of Asia (MHA) since the early 2000s. The unstable relationship may be related to the changes in the tropospheric AO mode and the subtropical jet. Further analyses suggest that their changes may be attributable to the interdecadal changes in the stratospheric polar vortex. During 2002–2017, the anomalously weak stratospheric polar vortex is accompanied by intensified upward-propagating tropospheric planetary-scale waves anomalies. Subsequently, the stratospheric geopotential height anomalies over the North Atlantic high-latitudes propagate downward strongly, causing the changes in the tropospheric AO mode, that is, the positive height anomalies over the North Atlantic high-latitudes are stronger and extend southward, corresponding to the stronger and eastward extension of negative height anomalies over the North Atlantic mid-latitudes. Thus, the Rossby wave source anomalies over Baffin Bay and the Black Sea are strong, and correspondingly so too are their subsequently excited the Rossby waves anomalies. Meanwhile, the planetary-scale waves anomalies propagate weakly along the low-latitude waveguide, causing the intensified and southward shift of the subtropical jet. Therefore, the strong Rossby waves anomalies propagate eastward to the MHA. By contrast, during 1979–1999, the strong stratospheric polar vortex anomaly is accompanied by weak upward-propagating planetary-scale waves anomalies, resulting in weaker height anomalies over the North Atlantic mid–high latitudes. Consequently, the anomalous Rossby waves are weak. In addition, the subtropical jet weakens and shifts northward, which causes the Rossby waves anomalies to dominate over the North Atlantic, and thereby the impact of winter AO on simultaneous precipitation over the MHA is weak.
Educational Accommodations for Students With Disabilities: Two Equity-Related Concerns
Authors: Lovett Benjamin J.
Published: December 2021

Educational accommodations are frequently given to students with disabilities. For instance, students might be given a copy of class notes or provided additional time to complete a test. One purpose of accommodations is to improve educational equity, putting all students on equal footing. However, research on current accommodations practices raises two distinct equity-related concerns. First, students from privileged backgrounds are more likely to receive certain accommodations even without adequate evidence of need; this can provide an unfair boost in performance and widen gaps among students. Second, when students from less privileged backgrounds are given accommodations, the incentive for schools to provide academic remediation, compensatory strategies, and coping skills is lessened, leaving these students in a worse position when accommodations are not available outside of educational settings. Implications for practice are discussed.