Search results for: genetic profiles

Authors: Harvey Sanchez-Restrepo, Jorge Louca

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Equity and education are major focus of government policies around the world due to its relevance for addressing the sustainable development goals launched by Unesco. In this research, we developed a primary analysis of a data set of more than one hundred educational and non-educational factors associated with learning, coming from a census-based large-scale assessment carried on in Ecuador for 1.038.328 students, their families, teachers, and school directors, throughout 2014-2018. Each participating student was assessed by a standardized computer-based test. Learning outcomes were calibrated through item response theory with two-parameters logistic model for getting raw scores that were re-scaled and synthetized by a learning index (LI). Our objective was to develop a network for modelling educational deprivation and analyze the structure of inequality gaps, as well as their relationship with socioeconomic status, school financing, and student's ethnicity. Results from the model show that 348 270 students did not develop the minimum skills (prevalence rate=0.215) and that Afro-Ecuadorian, Montuvios and Indigenous students exhibited the highest prevalence with 0.312, 0.278 and 0.226, respectively. Regarding the socioeconomic status of students (SES), modularity class shows clearly that the system is out of equilibrium: the first decile (the poorest) exhibits a prevalence rate of 0.386 while rate for decile ten (the richest) is 0.080, showing an intense negative relationship between learning and SES given by R= –0.58 (p < 0.001). Another interesting and unexpected result is the average-weighted degree (426.9) for both private and public schools attending Afro-Ecuadorian students, groups that got the highest PageRank (0.426) and pointing out that they suffer the highest educational deprivation due to discrimination, even belonging to the richest decile. The model also found the factors which explain deprivation through the highest PageRank and the greatest degree of connectivity for the first decile, they are: financial bonus for attending school, computer access, internet access, number of children, living with at least one parent, books access, read books, phone access, time for homework, teachers arriving late, paid work, positive expectations about schooling, and mother education. These results provide very accurate and clear knowledge about the variables affecting poorest students and the inequalities that it produces, from which it might be defined needs profiles, as well as actions on the factors in which it is possible to influence. Finally, these results confirm that network analysis is fundamental for educational policy, especially linking reliable microdata with social macro-parameters because it allows us to infer how gaps in educational achievements are driven by students’ context at the time of assigning resources.

Keywords: complex network, educational deprivation, evidence-based policy, large-scale assessments, policy informatics

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Authors: Maria V. Mishatkina

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The modelling of dialogical environment is an essential feature of modern education. The dialogue of cultures is a foundation and an important prerequisite for a formation of a human’s main moral qualities such as an ability to understand another person, which is manifested in such values as tolerance, respect, mutual assistance and mercy. A formation of a modern expert occurs in an educational environment that is significantly different from what we had several years ago. Nowadays university education has qualitatively new characteristics. They may be observed in Peoples’ Friendship University of Russia (RUDN University), a top Russian higher education institution which unites representatives of more than 150 countries. The content of its educational strategies is not an adapted cultural experience but material between science and innovation. Besides, RUDN University’s profiles and specialization are not equal to the professional structures. People study not a profession in a strict sense but a basic scientific foundation of an activity in different socio-cultural areas (science, business and education). RUDN University also provides a considerable unit of professional education components. They are foreign languages skills, economic, political, ethnic, communication and computer culture, theory of information and basic management skills. Moreover, there is a rich social life (festive multicultural events, theme parties, journeys) and prospects concerning the inclusive approach to education (for example, a special course ‘Social Pedagogy: Issues of Tolerance’). In our research, we use such methods as analysis of modern and contemporary scientific literature, opinion poll (involving students, teachers and research workers) and comparative data analysis. We came to the conclusion that knowledge transfer of RUDN student in the activity happens through making goals, problems, issues, tasks and situations which simulate future innovative ambiguous environment that potentially prepares him/her to dialogical way of life. However, all these factors may not take effect if there is no ‘personal inspiration’ of students by communicative and dialogic values, their participation in a system of meanings and tools of learning activity that is represented by cooperation within the framework of scientific and pedagogical schools dialogue. We also found out that dominating strategies of ensuring the quality of education are those that put students in the position of the subject of their own education. Today these strategies and approaches should involve such approaches and methods as task, contextual, modelling, specialized, game-imitating and dialogical approaches, the method of practical situations, etc. Therefore, University in the modern sense is not only an educational institution, but also a generator of innovation, cooperation among nations and cultural progress. RUDN University has been performing exactly this mission for many decades.

Keywords: dialogical developing situation, dialogue of cultures, readiness for dialogue, university graduate

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Authors: Atitallah Sofien, Bouyahia Olfa, Romdhani Meriam, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Spondylothoracic dysostosis, also known as Jarcho-Levin syndrome, is defined by a shortened neck and thorax, a protruding abdomen, inguinal and umbilical hernias, atypical spinal structure and rib fusion, leading to restricted chest movement or difficulty in breathing, along with urinary tract abnormalities and, potentially severe scoliosis. Aim: This is the case of a patient diagnosed with Jarcho-Levin syndrome, aiming to detail the range of abnormalities observed in this syndrome, the observed complications, and the therapeutic approaches employed. Results: A three-month-old male infant, born of a consanguineous marriage, delivered at full term by cesarean section, was admitted to the pediatric department for severe acute bronchiolitis. In his prenatal history, morphological ultrasound revealed macrosomia, a shortened spine, irregular vertebrae with thickened skin, normal fetal cardiac ultrasound, and the absence of the right kidney. His perinatal history included respiratory distress, requiring ventilatory support for five days. Upon physical examination, he had stunted growth, scoliosis, a short neck and trunk, longer upper limbs compared to lower limbs, varus equinus in the right foot, a neural tube defect, a low hairline, and low-set ears. Spondylothoracic dysostosis was suspected, leading to further investigations, including a normal transfontaneous ultrasound, a spinal cord ultrasound revealing a lipomyelocele-type closed dysraphism with a low-attached cord, an abdominal ultrasound indicating a single left kidney, and a cardiac ultrasound identifying Kommerell syndrome. Due to a lack of resources, genetic testing could not be performed, and the diagnosis was based on clinical criteria. Conclusion: Jarcho-Levin syndrome can result in a mortality rate of about 50%, primarily due to respiratory complications associated with thoracic insufficiency syndrome. Other complications, like heart and neural tube defects, can also lead to premature mortality. Therefore, early diagnosis and comprehensive treatment involving various specialists are essential.

Keywords: Jarcho-Levin syndrome, congenital disorder, scoliosis, spondylothoracic dysostosis, neural tube defect

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Authors: Cecilia Moreira, Rita Paiva, Daniela Macedo, Leonor Ribeiro, Isabel Fernandes, Luis Costa

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Background: Head and neck paragangliomas are a rare group of tumors with a large spectrum of clinical manifestations. The approach to evaluate and treat these lesions has evolved over the last years. Surgery was the standard for the approach of these patients, but nowadays new techniques of imaging and radiation therapy changed that paradigm. Despite advances in treating, the growth potential and clinical outcome of individual cases remain largely unpredictable. Objectives: Characterization of our institutional experience with clinical management of these tumors. Methods: This was a cross-sectional study of patients followed in our institution between 01 January and 31 December 2017 with paragangliomas of the head and neck and cranial base. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic workup, treatment modality, tumor control and recurrence, complications of treatment and hereditary status were collected and summarized. Results: A total of four female patients were followed between 01 January and 31 December 2017 in our institution. The mean age of our cohort was 53 (± 16.1) years. The primary locations were at the level of the tympanic jug (n=2, 50%) and carotid body (n=2, 50%), and only one of the tumors of the carotid body presented pulmonary metastasis at the time of diagnosis. None of the lesions were catecholamine-secreting. Two patients underwent genetic testing, with no mutations identified. The initial clinical presentation was variable highlighting the decrease of visual acuity and headache as symptoms present in all patients. In one of the cases, loss of all teeth of the lower jaw was the presenting symptomatology. Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were employed as treatment approaches according to anatomical location and resectability of lesions. As post-therapeutic sequels the persistence of tinnitus and disabling pain stands out, presenting one of the patients neuralgia of the glossopharyngeal. Currently, all patients are under regular surveillance with a median follow up of 10 months. Conclusion: Ultimately, clinical management of these tumors remains challenging owing to heterogeneity in clinical presentation, the existence of multiple treatment alternatives, and potential to cause serious detriment to critical functions and consequently interference with the quality of life of the patients.

Keywords: clinical outcomes, head and neck, management, paragangliomas

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Authors: A. M. Tarola, R. Preti, A. M. Girelli, P. Campana

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Safeguarding, studying and enhancing biodiversity play an important and indispensable role in re-launching agriculture. The ancient local varieties are therefore a precious resource for genetic and health improvement. In order to protect biodiversity through the recovery and valorization of autochthonous varieties, in this study we analyzed 12 samples of four ancient apple cultivars representative of Friuli Venezia Giulia, selected by local farmers who work on a project for the recovery of ancient apple cultivars. The aim of this study is to evaluate the polyphenolic profile and the antioxidant capacity that characterize the organoleptic and functional qualities of this fruit species, besides having beneficial properties for health. In particular, for each variety, the following compounds were analyzed, both in the skins and in the pulp: gallic acid, catechin, chlorogenic acid, epicatechin, caffeic acid, coumaric acid, ferulic acid, rutin, phlorizin, phloretin and quercetin to highlight any differences in the edible parts of the apple. The analysis of individual phenolic compounds was performed by High Performance Liquid Chromatography (HPLC) coupled with a diode array UV detector (DAD), the antioxidant capacity was estimated using an in vitro essay based on a Free Radical Scavenging Method and the total phenolic compounds was determined using the Folin-Ciocalteau method. From the results, it is evident that the catechins are the most present polyphenols, reaching a value of 140-200 μg/g in the pulp and of 400-500 μg/g in the skin, with the prevalence of epicatechin. Catechins and phlorizin, a dihydrohalcone typical of apples, are always contained in larger quantities in the peel. Total phenolic compounds content was positively correlated with antioxidant activity in apple pulp (r² = 0,850) and peel (r² = 0,820). Comparing the results, differences between the varieties analyzed and between the edible parts (pulp and peel) of the apple were highlighted. In particular, apple peel is richer in polyphenolic compounds than pulp and flavonols are exclusively present in the peel. In conclusion, polyphenols, being antioxidant substances, have confirmed the benefits of fruit in the diet, especially as a prevention and treatment for degenerative diseases. They demonstrated to be also a good marker for the characterization of different apple cultivars. The importance of protecting biodiversity in agriculture was also highlighted through the exploitation of native products and ancient varieties of apples now forgotten.

Keywords: apple, biodiversity, polyphenols, antioxidant activity, HPLC-DAD, characterization

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Authors: Justin Fu, Thomas Mazzuchi, Shahram Sarkani

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A key factor in technological immaturity in defense weapons acquisition is lack of understanding critical integrations at the subsystem and component level. To address this shortfall, recent research in integration readiness level (IRL) combines with technology readiness level (TRL) to form a system readiness level (SRL). SRL can be enriched with more robust quantitative methods to provide the program manager a useful tool prior to committing to major weapons acquisition programs. This research harnesses previous mathematical models based on graph theory, Petri nets, and tropical algebra and proposes a modification of the desirable SRL mathematical properties such that a tightly integrated (multitude of interfaces) subsystem can display a lower SRL than an inherently less coupled subsystem. The synthesis of these methods informs an improved decision tool for the program manager to commit to expensive technology development. This research ties the separately developed manufacturing readiness level (MRL) into the network representation of the system and addresses shortfalls in previous frameworks, including the lack of integration weighting and the over-importance of a single extremely immature component. Tropical algebra (based on the minimum of a set of TRLs or IRLs) allows one low IRL or TRL value to diminish the SRL of the entire system, which may not be reflective of actuality if that component is not critical or tightly coupled. Integration connections can be weighted according to importance and readiness levels are modified to be a cardinal scale (based on an analytic hierarchy process). Integration arcs’ importance are dependent on the connected nodes and the additional integrations arcs connected to those nodes. Lack of integration is not represented by zero, but by a perfect integration maturity value. Naturally, the importance (or weight) of such an arc would be zero. To further explore the impact of grouping subsystems, a multi-objective genetic algorithm is then used to find various clusters or communities that can be optimized for the most representative subsystem SRL. This novel calculation is then benchmarked through simulation and using past defense acquisition program data, focusing on the newly introduced Middle Tier of Acquisition (rapidly field prototypes). The model remains a relatively simple, accessible tool, but at higher fidelity and validated with past data for the program manager to decide major defense acquisition program milestones.

Keywords: readiness, maturity, system, integration

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Authors: Aleksandra Zieminska-Stolarska, Ireneusz Zbicinski

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Introduction: The objective of the present work was to develop and validate a 3D CFD numerical model for simulating flow through 17 kilometers long dam reservoir of a complex bathymetry. In contrast to flowing waters, dam reservoirs were not emphasized in the early years of water quality modeling, as this issue has never been the major focus of urban development. Starting in the 1970s, however, it was recognized that natural and man-made lakes are equal, if not more important than estuaries and rivers from a recreational standpoint. The Sulejow Reservoir (Central Poland) was selected as the study area as representative of many lowland dam reservoirs and due availability of a large database of the ecological, hydrological and morphological parameters of the lake. Method: 3D, 2-phase and 1-phase CFD models were analysed to determine hydrodynamics in the Sulejow Reservoir. Development of 3D, 2-phase CFD model of flow requires a construction of mesh with millions of elements and overcome serious convergence problems. As 1-phase CFD model of flow in relation to 2-phase CFD model excludes from the simulations the dynamics of waves only, which should not change significantly water flow pattern for the case of lowland, dam reservoirs. In 1-phase CFD model, the phases (water-air) are separated by a plate which allows calculations of one phase (water) flow only. As the wind affects velocity of flow, to take into account the effect of the wind on hydrodynamics in 1-phase CFD model, the plate must move with speed and direction equal to the speed and direction of the upper water layer. To determine the velocity at which the plate will move on the water surface and interacts with the underlying layers of water and apply this value in 1-phase CFD model, the 2D, 2-phase model was elaborated. Result: Model was verified on the basis of the extensive flow measurements (StreamPro ADCP, USA). Excellent agreement (an average error less than 10%) between computed and measured velocity profiles was found. As a result of work, the following main conclusions can be presented: •The results indicate that the flow field in the Sulejow Reservoir is transient in nature, with swirl flows in the lower part of the lake. Recirculating zones, with the size of even half kilometer, may increase water retention time in this region •The results of simulations confirm the pronounced effect of the wind on the development of the water circulation zones in the reservoir which might affect the accumulation of nutrients in the epilimnion layer and result e.g. in the algae bloom. Conclusion: The resulting model is accurate and the methodology develop in the frame of this work can be applied to all types of storage reservoir configurations, characteristics, and hydrodynamics conditions. Large recirculating zones in the lake which increase water retention time and might affect the accumulation of nutrients were detected. Accurate CFD model of hydrodynamics in large water body could help in the development of forecast of water quality, especially in terms of eutrophication and water management of the big water bodies.

Keywords: CFD, mathematical modelling, dam reservoirs, hydrodynamics

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Authors: Lei Zhou, Chao Li, Ruiqi Ren, Dan Li, Yali Wang, Daxin Ni, Zijian Feng, Qun Li

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Background: Since the first human infection with avian influenza A(H7N9) case was reported in China on 31 March 2013, five epidemics have been observed in China through February 2013 and September 2017. Though the overall mortality rate of H7N9 has remained as high as around 40% throughout the five epidemics, the specific mortality rate in Mainland China varied by provinces. We conducted a descriptive analysis of mortality rates of H7N9 cases to explore the various severity features of the disease and then to provide clues of further analyses of potential factors associated with the severity of the disease. Methods: The data for analysis originated from the National Notifiable Infectious Disease Report and Surveillance System (NNIDRSS). The surveillance system and identification procedure for H7N9 infection have not changed in China since 2013. The definition of a confirmed H7N9 case is as same as previous reports. Mortality rates of H7N9 cases are described and compared by time and location of reporting, age and sex, and genetic features of H7N9 virus strains. Results: The overall mortality rate, the male and female specific overall rates of H7N9 is 39.6% (608/1533), 40.3% (432/1072) and 38.2% (176/461), respectively. There was no significant difference between the mortality rates of male and female. The age-specific mortality rates are significantly varied by age groups (χ²=38.16, p < 0.001). The mortality of H7N9 cases in the age group between 20 and 60 (33.17%) and age group of over 60 (51.16%) is much higher than that in the age group of under 20 (5.00%). Considering the time of reporting, the mortality rates of cases which were reported in the first (40.57%) and fourth (42.51%) quarters of each year are significantly higher than the mortality of cases which were reported in the second (36.02%) and third (27.27%) quarters (χ²=75.18, p < 0.001). The geographic specific mortality rates vary too. The mortality rates of H7N9 cases reported from the Northeast China (66.67%) and Westeast China (56.52%) are significantly higher than that of H7N9 cases reported from the remained area of mainland China. The mortality rate of H7N9 cases reported from the Central China is the lowest (34.38%). The mortality rates of H7N9 cases reported from rural (37.76%) and urban (38.96%) areas are similar. The mortality rate of H7N9 cases infected with the highly pathogenic avian influenza A(H7N9) virus (48.15%) is higher than the rate of H7N9 cases infected with the low pathogenic avian influenza A(H7N9) virus (37.57%), but the difference is not statistically significant. Preliminary analyses showed that age and some clinical complications such as respiratory failure, heart failure, and septic shock could be potential risk factors associated with the death of H7N9 cases. Conclusions: The mortality rates of H7N9 cases varied by age, sex, time of reporting and geographical location in mainland China. Further in-depth analyses and field investigations of the factors associated with the severity of H7N9 cases need to be considered.

Keywords: H7N9 virus, Avian Influenza, mortality, China

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Authors: Khethiwe Mtshali, Zamantungwa T. H. Khumalo, Stanford Kwenda, Ismail Arshad, Oriel M. M. Thekisoe

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Ecologically, the gut, mammary glands and bloodstream consist of distinct microbial communities of commensals, mutualists and pathogens, forming a complex ecosystem of niches. The by-products derived from these body sites i.e. faeces, milk and blood, respectively, have many uses in rural communities where they aid in the facilitation of day-to-day household activities and occasional rituals. Thus, although livestock rearing plays a vital role in the sustenance of the livelihoods of rural communities, it may serve as a potent reservoir of different pathogenic organisms that could have devastating health and economic implications. This study aimed to simultaneously explore the microbial profiles of corresponding faecal, milk and blood samples from lactating cows using 16S rRNA metagenomic sequencing. Bacterial communities were inferred through the Divisive Amplicon Denoising Algorithm 2 (DADA2) pipeline coupled with SILVA database v138. All downstream analyses were performed in R v3.6.1. Alpha-diversity metrics showed significant differences between faeces and blood, faeces and milk, but did not vary significantly between blood and milk (Kruskal-Wallis, P < 0.05). Beta-diversity metrics on Principal Coordinate Analysis (PCoA) and Non-Metric Dimensional Scaling (NMDS) clustered samples by type, suggesting that microbial communities of the studied niches are significantly different (PERMANOVA, P < 0.05). A number of taxa were significantly differentially abundant (DA) between groups based on the Wald test implemented in the DESeq2 package (Padj < 0.01). The majority of the DA taxa were significantly enriched in faeces than in milk and blood, except for the genus Anaplasma, which was significantly enriched in blood and was, in turn, the most abundant taxon overall. A total of 30 phyla, 74 classes, 156 orders, 243 families and 408 genera were obtained from the overall analysis. The most abundant phyla obtained between the three body sites were Firmicutes, Bacteroidota, and Proteobacteria. A total of 58 genus-level taxa were simultaneously detected between the sample groups, while bacterial signatures of at least 8 of these occurred concurrently in corresponding faeces, milk and blood samples from the same group of animals constituting a pool. The important taxa identified in this study could be categorized into four potentially pathogenic clusters: i) arthropod-borne; ii) food-borne and zoonotic; iii) mastitogenic and; iv) metritic and abortigenic. This study provides insight into the microbial composition of bovine faeces, milk, and blood and its extent of overlapping. It further highlights the potential risk of disease occurrence and transmission between the animals and the inhabitants of the sampled rural community, pertaining to their unsanitary practices associated with the use of cattle by-products.

Keywords: microbial profiling, 16S rRNA, NGS, feces, milk, blood, lactating cows, small-scale farmers

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Authors: Ratneev Kaur, Tajinder Kaur, Anupam Kaur

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Introduction: Polycystic Ovary Syndrome (PCOS) is a heterogenous disorder of endocrine system among women of reproductive age. PCOS is characterized by hyperandrogenism, anovulation, polycystic ovaries, hirsutism, obesity, and hyperinsulinemia. Several pathways are implicated in its etiology including the metabolic pathway of steroid hormone synthesis regulatory pathways. PCOS is an androgen excess disorder, genes operating in steroidogenesis may alter pathogenesis of PCOS. The cytochrome P450scc is a cholesterol side chain cleavage enzyme coded by CYP11A1 gene and catalyzes conversion of cholesterol to pregnenolone, the initial and rate-limiting step in steroid hormone synthesis. It is postulated that polymorphisms in this gene may play an important role in the regulation of CYP11A1 expression and leading to increased or decreased androgen production. The present study will be the first study from north India to best of our knowledge, to analyse the association of CYP11A1 (rs11632698) polymorphism in women suffering from PCOS. Methodology: The present study was approved by ethical committee of Guru Nanak Dev University in consistent with declaration of Helsinki. A total of 300 samples (150 PCOS cases and 150 controls) were recruited from Hartej hospital, for the present study. Venous blood sample (3ml) was withdrawn from women diagnosed with PCOS by doctor, according to Rotterdam 2003 criteria and from healthy age matched controls only after informed consent and detailed filled proforma. For molecular genetics analysis, blood was stored in EDTA vials. After DNA isolation by organic method, PCR-RFLP approach was used for genotyping and association analysis of rs11632698 polymorphism. Statistical analysis was done to check for significance of selected polymorphism with PCOS. Results: In 150 PCOS cases, the frequency of AA, AG and GG genotype was found to be 48%, 35%, and 13% compared to 62%, 27% and 8% in 150 controls. The major allele (A) and minor allele (G) frequency was 68% and 32% in cases and 78% and 22% in controls. Minor allele frequency was higher in cases as compared to controls, as well as the distribution of genotype was observed to be statistically significant (ᵡ²=6.525, p=0.038). Odds ratio in dominant, co-dominant and recessive models observed was 1.81 (p=0.013), 1.54 (p=0.012) and 1.77 (p=0.132) respectively. Conclusion: The present study showed statistically significant association of rs11632698 with PCOS (p=0.038) in North Indian women.

Keywords: polycystic ovary syndrome, CYP11A1, rs11632698, hyperandrogenism

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Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Hyeon-Seung Kim, Sang-Mi Park, Sun-Ju Han, Leen-Seok Kang

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As BIM (Building Information Modeling) application continually expands, the visual simulation techniques used for facility design and construction process information are becoming increasingly advanced and diverse. For building structures, BIM application is design - oriented to utilize 3D objects for conflict management, whereas for civil engineering structures, the usability of nD object - oriented construction stage simulation is important in construction management. Simulations of 5D and 6D objects, for which cost and resources are linked along with process simulation in 4D objects, are commonly used, but they do not provide a decision - making function for process management problems that occur on site because they mostly focus on the visual representation of current status for process information. In this study, an nD CAD system is constructed that facilitates an optimized schedule simulation that minimizes process conflict, a construction duration reduction simulation according to execution progress status, optimized process plan simulation according to project cost change by year, and optimized resource simulation for field resource mobilization capability. Through this system, the usability of conventional simple simulation objects is expanded to the usability of active simulation objects with which decision - making is possible. Furthermore, to close the gap between field process situations and planned 4D process objects, a technique is developed to facilitate a comparative simulation through the coordinated synchronization of an actual video object acquired by an on - site web camera and VR concept 4D object. This synchronization and simulation technique can also be applied to smartphone video objects captured in the field in order to increase the usability of the 4D object. Because yearly project costs change frequently for civil engineering construction, an annual process plan should be recomposed appropriately according to project cost decreases/increases compared with the plan. In the 5D CAD system provided in this study, an active 5D object utilization concept is introduced to perform a simulation in an optimized process planning state by finding a process optimized for the changed project cost without changing the construction duration through a technique such as genetic algorithm. Furthermore, in resource management, an active 6D object utilization function is introduced that can analyze and simulate an optimized process plan within a possible scope of moving resources by considering those resources that can be moved under a given field condition, instead of using a simple resource change simulation by schedule. The introduction of an active BIM function is expected to increase the field utilization of conventional nD objects.

Keywords: 4D, 5D, 6D, active BIM

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Authors: Aurélie Michaud, Émilie Gaudet, Mónika Koós, Léna Nagy, Zsolt Demetrovics, Shane W. Kraus, Marc N. Potenza, Beáta Bőthe

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Pornography use is prevalent among adults worldwide. Prior studies have assessed the associations between pornography use frequency and sexual satisfaction, in cisgender and heterosexual individuals, with mixed results. However, measuring pornography use solely by pornography use frequency is problematic, as it can lead to disregarding important contextual factors that may be related to pornography use’s potential effects. Pornography use motivations (PUMs) represent key predictors of sexual behaviors. Yet, their associations with different indicators of sexual wellbeing have yet to be extensively studied. This cross-cultural study examined the links between the eight PUMs most often reported in the general population (i.e. sexual pleasure, sexual curiosity, emotional distraction or suppression, fantasy, stress reduction, boredom avoidance, lack of sexual satisfaction, and self-exploration) and sexual satisfaction in gender diverse and cisgender individuals. Given the lack of scientific data on associations between individuals’ PUMs and sexual satisfaction, these links were examined in an exploratory manner. A total of 43 countries from five continents were included in the International Sex Survey (ISS). A secure online platform was used to collect self-report, anonymous data from 82,243 participants (39.6% men, 57% women, 3.4% gender diverse individuals; M = 32.4 years, SD = 12.5). Gender-based differences in levels of sexual pleasure, sexual curiosity, emotional distraction, fantasy, stress reduction, boredom avoidance, lack of sexual satisfaction, and self-exploration PUMs were examined using one-way ANOVAs. Then, for each gender group, the associations between each PUM and sexual satisfaction were examined using multiple linear regression, controlling for frequency of masturbation. One-way ANOVAs indicated significant differences between men, women, and gender diverse individuals on all PUMs. For sexual pleasure, sexual curiosity, fantasy, boredom avoidance, lack of sexual satisfaction, emotional distraction, and stress reduction PUMs, men showed the highest scores, followed by gender-diverse individuals, and women. However, for self-exploration, gender-diverse individuals had higher average scores than men. For all PUMs, women’s average scores were the lowest. After controlling for frequency of masturbation, for all genders, sexual pleasure, sexual curiosity and boredom avoidance were significant positive predictors of sexual satisfaction, while lack of sexual satisfaction PUM was a significant negative predictor. Fantasy, stress reduction and self-exploration PUMs were positive significant predictors of sexual satisfaction, and fantasy was a negative significant predictor, but only for women. Findings highlight important gender differences in regards to the main motivations underlying pornography use and their relations to sexual satisfaction. While men and gender diverse individuals show similar motivation profiles, woman report a particularly unique experience, with fantasy, stress reduction and self-exploration being associated to their sexual satisfaction. This work outlines the importance of considering the role of pornography use motivations when studying the links between pornography viewing and sexual well-being, and may provide basis for gender-based considerations when working with individuals seeking help for their pornography use or sexual satisfaction.

Keywords: pornography, sexual satifsaction, cross-cultural, gender diversity

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Authors: Marie Alexandre, Jean Bernatchez

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This paper focuses on the complexity of the face-to-face-to-distance learning transition process. Our research action aims to support the process of transition from classroom to distance learning for teachers in higher education with regard to pedagogical practices that can meet the various needs of students using digital learning environments. In Quebec and elsewhere in the world, the advent of digital education is helping to transform teaching, which is significantly changing the role of teachers. While distance education implies a dissociation of teaching and learning to a variable degree in space and time, distance education (DE) is becoming more and increasingly becoming a preferred option for maintaining the delivery of certain programs and providing access to programs and to provide access to quality activities throughout Quebec. Given the impact of teaching practices on educational success, this paper reports on the results of three research objectives: 1) To document teachers' knowledge of teaching in distance education through the design, experimentation and production of a repertoire of the determinants of pedagogical practices in response to students' needs. 2) Explain, according to a gendered logic, the adequacy between the pedagogical practices implemented in distance learning and the response to the profiles and needs expressed by students using digital learning environments; 3) Produce a model of a support approach during the process of transition from classroom to distance learning at the college level. A mixed methodology, i.e., a quantitative component (questionnaire survey) and a qualitative component (explanatory interviews and living lab) was used in cycles that were part of an ongoing validation process. The intervention includes the establishment of a professional collaboration group, webinars training webinars for the participating teachers on the didactic issue of knowledge-teaching in FAD, the didactic use of technologies, and the differentiated socialization models of educational success in college education. All of the tools developed will be used by partners in the target environment as well as by all teacher educators, students in initial teacher training, practicing teachers, and the general public. The results show that access to training leading to qualifications and commitment to educational success reflects the existing links between the people in the educational community. The relational stakes of being present in distance education take on multiple configurations and different dimensions of learning testify to needs and realities that are sometimes distinct depending on the life cycle. This project will be of interest to partners in the targeted field as well as to all teacher trainers, students in initial teacher training, practicing college teachers, and to university professors. The entire educational community will benefit from digital resources in education. The scientific knowledge resulting from this action research will benefit researchers in the fields of pedagogy, didactics, teacher training and pedagogy in higher education in a digital context.

Keywords: action research, didactics, digital learning environment, distance learning, higher education, pedagogy technological, pedagogical content knowledge

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Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

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Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

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Authors: A. F. G. Van Woezik, L. M. A. Braakman-Jansen, O. A. Kulyk, J. E. W. C. Van Gemert-Pijnen

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Background: Zoonoses pose a serious threat to public health and economies worldwide, especially as antimicrobial resistance grows and newly emerging zoonoses can cause unpredictable outbreaks. In order to prevent and control emerging and re-emerging zoonoses, collaboration between veterinary, human health and public health domains is essential. In reality however, there is a lack of cooperation between these three disciplines and uncertainties exist about their tasks and responsibilities. The objective of this ongoing research project (ZonMw funded, 2014-2018) is to develop an online education and communication One Health platform, “eZoon”, for the general public and professionals working in veterinary, human health and public health domains to support the risk communication of non-alimentary zoonoses in the Netherlands. The main focus is on education and communication in times of outbreak as well as in daily non-outbreak situations. Methods: A participatory development approach was used in which stakeholders from veterinary, human health and public health domains participated. Key stakeholders were identified using business modeling techniques previously used for the design and implementation of antibiotic stewardship interventions and consisted of a literature scan, expert recommendations, and snowball sampling. We used a stakeholder salience approach to rank stakeholders according to their power, legitimacy, and urgency. Semi-structured interviews were conducted with stakeholders (N=20) from all three disciplines to identify current problems in risk communication and stakeholder values for the One Health platform. Interviews were transcribed verbatim and coded inductively by two researchers. Results: The following key values were identified (but were not limited to): (a) need for improved awareness of veterinary and human health of each other’s fields, (b) information exchange between veterinary and human health, in particularly at a regional level; (c) legal regulations need to match with daily practice; (d) professionals and general public need to be addressed separately using tailored language and information; (e) information needs to be of value to professionals (relevant, important, accurate, and have financial or other important consequences if ignored) in order to be picked up; and (f) need for accurate information from trustworthy, centrally organised sources to inform the general public. Conclusion: By applying a participatory development approach, we gained insights from multiple perspectives into the main problems of current risk communication strategies in the Netherlands and stakeholder values. Next, we will continue the iterative development of the One Health platform by presenting key values to stakeholders for validation and ranking, which will guide further development. We will develop a communication platform with a serious game in which professionals at the regional level will be trained in shared decision making in time-critical outbreak situations, a smart Question & Answer (Q&A) system for the general public tailored towards different user profiles, and social media to inform the general public adequately during outbreaks.

Keywords: ehealth, one health, risk communication, stakeholder, zoonosis

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is a low-grade inflammatory state. Childhood obesity is a multisystem disease, which is associated with a number of complications as well as potentially negative consequences. Gender is an important universal risk factor for many diseases. Hematological indices differ significantly by gender. This should be considered during the evaluation of obese children. The aim of this study is to detect hematologic indices that differ by gender in morbid obese (MO) children. A total of 134 MO children took part in this study. The parents filled an informed consent form and the approval from the Ethics Committee of Namik Kemal University was obtained. Subjects were divided into two groups based on their genders (64 females aged 10.2±3.1 years and 70 males aged 9.8±2.2 years; p ≥ 0.05). Waist-to-hip as well as head-to-neck ratios and body mass index (BMI) values were calculated. The children, whose WHO BMI-for age and sex percentile values were > 99 percentile, were defined as MO. Hematological parameters [haemoglobin, hematocrit, erythrocyte count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red blood cell distribution width, leukocyte count, neutrophil %, lymphocyte %, monocyte %, eosinophil %, basophil %, platelet count, platelet distribution width, mean platelet volume] were determined by the automatic hematology analyzer. SPSS was used for statistical analyses. P ≤ 0.05 was the degree for statistical significance. The groups included children having mean±SD value of BMI as 26.9±3.4 kg/m² for males and 27.7±4.4 kg/m² for females (p ≥ 0.05). There was no significant difference between ages of females and males (p ≥ 0.05). Males had significantly increased waist-to-hip ratios (0.95±0.08 vs 0.91±0.08; p=0.005) and mean corpuscular hemoglobin concentration values (33.6±0.92 vs 33.1±0.83; p=0.001) compared to those of females. Significantly elevated neutrophil (4.69±1.59 vs 4.02±1.42; p=0.011) and neutrophil-to-lymphocyte ratios (1.70±0.71 vs 1.39±0.48; p=0.004) were detected in females. There was no statistically significant difference between groups in terms of C-reactive protein values (p ≥ 0.05). Adipose tissue plays important roles during the development of obesity and associated diseases such as metabolic syndrom and cardiovascular diseases (CVDs). These diseases may cause changes in complete blood cell count parameters. These alterations are even more important during childhood. Significant gender effects on the changes of neutrophils, one of the white blood cell subsets, were observed. The findings of the study demonstrate the importance of considering gender in clinical studies. The males and females may have distinct leukocyte-trafficking profiles in inflammation. Female children had more circulating neutrophils, which may be the indicator of an increased risk of CVDs, than male children within this age range during the late stage of obesity. In recent years, females represent about half of deaths from CVDs; therefore, our findings may be the indicator of the increasing tendency of this risk in females starting from childhood.

Keywords: children, gender, morbid obesity, neutrophil-to-lymphocyte ratio

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Authors: Vanessa H. S. Zago, Ana Maria H. de Avila, Paula P. Costa, Welington Corozolla, Liriam S. Teixeira, Eliana C. de Faria

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Objectives: The outcome of cardiovascular disease is affected by environment and climate. This study evaluated the possible relationships between climatic and environmental changes and the occurrence of biological rhythms in serum lipids and lipoproteins in a large population sample in the city of Campinas, State of Sao Paulo, Brazil. In addition, it determined the temporal variations of death due to atherosclerotic events in Campinas during the time window examined. Methods: A large 8-year retrospective study was carried out to evaluate the lipid profiles of individuals attended at the University of Campinas (Unicamp). The study population comprised 27.543 individuals of both sexes and of all ages. Normolipidemic and dyslipidemic individuals classified according to Brazilian guidelines on dyslipidemias, participated in the study. For the same period, the temperature, relative humidity and daily brightness records were obtained from the Centro de Pesquisas Meteorologicas e Climaticas Aplicadas a Agricultura/Unicamp and frequencies of death due to atherosclerotic events in Campinas were acquired from the Brazilian official database DATASUS, according to the International Classification of Diseases. Statistical analyses were performed using both Cosinor and ARIMA temporal analysis methods. For cross-correlation analysis between climatic and lipid parameters, cross-correlation functions were used. Results: Preliminary results indicated that rhythmicity was significant for LDL-C and HDL-C in the cases of both normolipidemic and dyslipidemic subjects (n =respectively 11.892 and 15.651 both measures increasing in the winter and decreasing in the summer). On the other hand, for dyslipidemic subjects triglycerides increased in summer and decreased in winter, in contrast to normolipidemic ones, in which triglycerides did not show rhythmicity. The number of deaths due to atherosclerotic events showed significant rhythmicity, with maximum and minimum frequencies in winter and summer, respectively. Cross-correlation analyzes showed that low humidity and temperature, higher thermal amplitude and dark cycles are associated with increased levels of LDL-C and HDL-C during winter. In contrast, TG showed moderate cross-correlations with temperature and minimum humidity in an inverse way: maximum temperature and humidity increased TG during the summer. Conclusions: This study showed a coincident rhythmicity between low temperatures and high concentrations of LDL-C and HDL-C and the number of deaths due to atherosclerotic cardiovascular events in individuals from the city of Campinas. The opposite behavior of cholesterol and TG suggest different physiological mechanisms in their metabolic modulation by climate parameters change. Thus, new analyses are underway to better elucidate these mechanisms, as well as variations in lipid concentrations in relation to climatic variations and their associations with atherosclerotic disease and death outcomes in Campinas.

Keywords: atherosclerosis, climatic variations, lipids and lipoproteins, associations

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Authors: Mohamed Naser Zainol, P. P. Angeline Song

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Over the years, the profile of end-stage renal patients placed under The National Kidney Foundation Singapore (NKFS) dialysis program has evolved, with a gradual incline in the number of patients with behavior-related issues. With these challenging profiles, social workers and counsellors are often expected to oversee behavior management, through referrals from its partnering colleagues. Due to the segregation of tasks usually found in many hospital-based multi-disciplinary settings, social workers’ and counsellors’ interventions are often seen as an endpoint, limiting other stakeholders’ involvement that could otherwise be potentially crucial in managing such patients. While patients’ contact in local hospitals often leads to eventual discharge, NKFS patients are mostly long term. It is interesting to note that these patients are regularly seen by a team of professionals that includes doctors, nurses, dietitians, exercise specialists in NKFS. The dynamism of relationships presents an opportunity for any of these professionals to take ownership of their potentials in leading interventions that can be helpful to patients. As such, it is important to have a framework that incorporates the strength of these professionals and also channels empowerment across the multi-disciplinary team in working towards wholistic patient care. This paper would like to suggest a new framework for NKFS’s multi-disciplinary team, where the group synergy and dynamics are used to encourage ownership and promote empowerment. The social worker and counsellor use group work skills and his/her knowledge of its members’ strengths, to generate constructive solutions that are centered towards patient’s growth. Using key ideas from Karl’s Tomm Interpersonal Communications, the Communication Management of Meaning and Motivational Interviewing, the social worker and counsellor through a series of guided meeting with other colleagues, facilitates the transmission of understanding, responsibility sharing and tapping on team resources for patient care. As a result, the patient can experience personal and concerted approach and begins to flow in a direction that is helpful for him. Using seven case studies of identified patients with behavioral issues, the social worker and counsellor apply this framework for a period of six months. Patient’s overall improvement through interventions as a result of this framework are recorded using the AB single case design, with baseline measured three months before referral. Interviews with patients and their families, as well as other colleagues that are not part of the multi-disciplinary team are solicited at mid and end points to gather their experiences about patient’s progress as a by-product of this framework. Expert interviews will be conducted on each member of the multi-disciplinary team to study their observations and experience in using this new framework. Hence, this exploratory framework hopes to identify the inherent usefulness in managing patients with behavior related issues. Moreover, it would provide indicators in improving aspects of the framework when applied to a larger population.

Keywords: behavior management, end-stage renal failure, satellite dialysis, multi-disciplinary team

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Authors: Eric Pla Erra, Mariana Jimenez Martinez

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While aggregated loads at a community level tend to be easier to predict, individual household load forecasting present more challenges with higher volatility and uncertainty. Furthermore, the drastic changes that our behavior patterns have suffered due to the COVID-19 pandemic have modified our daily electrical consumption curves and, therefore, further complicated the forecasting methods used to predict short-term electric load. Load forecasting is vital for the smooth and optimized planning and operation of our electric grids, but it also plays a crucial role for individual domestic consumers that rely on a HEMS (Home Energy Management Systems) to optimize their energy usage through self-generation, storage, or smart appliances management. An accurate forecasting leads to higher energy savings and overall energy efficiency of the household when paired with a proper HEMS. In order to study how COVID-19 has affected the accuracy of forecasting methods, an evaluation of the performance of a state-of-the-art LGBM (Light Gradient Boosting Model) will be conducted during the transition between pre-pandemic and lockdowns periods, considering day-ahead electric load forecasting. LGBM improves the capabilities of standard Decision Tree models in both speed and reduction of memory consumption, but it still offers a high accuracy. Even though LGBM has complex non-linear modelling capabilities, it has proven to be a competitive method under challenging forecasting scenarios such as short series, heterogeneous series, or data patterns with minimal prior knowledge. An adaptation of the LGBM model – called “resilient LGBM” – will be also tested, incorporating a concept drift detection technique for time series analysis, with the purpose to evaluate its capabilities to improve the model’s accuracy during extreme events such as COVID-19 lockdowns. The results for the LGBM and resilient LGBM will be compared using standard RMSE (Root Mean Squared Error) as the main performance metric. The models’ performance will be evaluated over a set of real households’ hourly electricity consumption data measured before and during the COVID-19 pandemic. All households are located in the city of Barcelona, Spain, and present different consumption profiles. This study is carried out under the ComMit-20 project, financed by AGAUR (Agència de Gestiód’AjutsUniversitaris), which aims to determine the short and long-term impacts of the COVID-19 pandemic on building energy consumption, incrementing the resilience of electrical systems through the use of tools such as HEMS and artificial intelligence.

Keywords: concept drift, forecasting, home energy management system (HEMS), light gradient boosting model (LGBM)

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Authors: Salma A. Mahmoud

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Epigenetic, or alteration in gene expression influenced by extragenetic factors, has emerged as one of the most promising areas that will address some of the gaps in our current knowledge in understanding patterns of human variation. In the last decade, the research investigating epigenetic mechanisms in many fields has flourished and witnessed significant progress. It paved the way for a new era of integrated research especially between anthropology/archeology and life sciences. Skeletal remains are considered the most significant source of information for studying human variations across history, and by utilizing these valuable remains, we can interpret the past events, cultures and populations. In addition to archeological, historical and anthropological importance, studying bones has great implications in other fields such as medicine and science. Bones also can hold within them the secrets of the future as they can act as predictive tools for health, society characteristics and dietary requirements. Bones in their basic forms are composed of cells (osteocytes) that are affected by both genetic and environmental factors, which can only explain a small part of their variability. The primary objective of this project is to examine the epigenetic landscape/signature within bones of archeological remains as a novel marker that could reveal new ways to conceptualize chronological events, gender differences, social status and ecological variations. We attempted here to address discrepancies in common variants such as methylome as well as novel epigenetic regulators such as chromatin remodelers, which to our best knowledge have not yet been investigated by anthropologists/ paleoepigenetists using plethora of techniques (biological, computational, and statistical). Moreover, extracting epigenetic information from bones will highlight the importance of osseous material as a vector to study human beings in several contexts (social, cultural and environmental), and strengthen their essential role as model systems that can be used to investigate and construct various cultural, political and economic events. We also address all steps required to plan and conduct an epigenetic analysis from bone materials (modern and ancient) as well as discussing the key challenges facing researchers aiming to investigate this field. In conclusion, this project will serve as a primer for bioarcheologists/anthropologists and human biologists interested in incorporating epigenetic data into their research programs. Understanding the roles of epigenetic mechanisms in bone structure and function will be very helpful for a better comprehension of their biology and highlighting their essentiality as interdisciplinary vectors and a key material in archeological research.

Keywords: epigenetics, archeology, bones, chromatin, methylome

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Authors: Sneha Shankar, Orlando Buendia, Will Evans

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Alpha-1 antitrypsin deficiency (AATD) is a rare, genetic, and multisystemic condition. Underdiagnosis is common, leading to chronic pulmonary and hepatic complications, increased resource utilization, and additional costs to the healthcare system. Currently, there is limited evidence of the direct medical costs of AATD diagnosis in the UK. This study explores the economic impact of AATD patients during the 3 years before diagnosis and to identify the major cost drivers using primary and secondary care electronic health record (EHR) data. The 3 years before diagnosis time period was chosen based on the ability of our tool to identify patients earlier. The AATD algorithm was created using published disease criteria and applied to 148 known AATD patients’ EHR found in a primary care database of 936,148 patients (413,674 Biobank and 501,188 in a single primary care locality). Among 148 patients, 9 patients were flagged earlier by the tool and, on average, could save 3 (1-6) years per patient. We analysed 101 of the 148 AATD patients’ primary care journey and 20 patients’ Hospital Episode Statistics (HES) data, all of whom had at least 3 years of clinical history in their records before diagnosis. The codes related to laboratory tests, clinical visits, referrals, hospitalization days, day case, and inpatient admissions attributable to AATD were examined in this 3-year period before diagnosis. The average cost per patient was calculated, and the direct medical costs were modelled based on the mean prevalence of 100 AATD patients in a 500,000 population. A deterministic sensitivity analysis (DSA) of 20% was performed to determine the major cost drivers. Cost data was obtained from the NHS National tariff 2020/21, National Schedule of NHS Costs 2018/19, PSSRU 2018/19, and private care tariff. The total direct medical cost of one hundred AATD patients three years before diagnosis in primary and secondary care in the UK was £3,556,489, with an average direct cost per patient of £35,565. A vast majority of this total direct cost (95%) was associated with inpatient admissions (£3,378,229). The DSA determined that the costs associated with tier-2 laboratory tests and inpatient admissions were the greatest contributors to direct costs in primary and secondary care, respectively. This retrospective study shows the role of EHRs in calculating direct medical costs and the potential benefit of new technologies for the early identification of patients with AATD to reduce the economic burden in primary and secondary care in the UK.

Keywords: alpha-1 antitrypsin deficiency, costs, digital health, early diagnosis

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Authors: Danna Jia, Bin Li

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Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

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Authors: Srinivas Bathini, Duraichelvan Raju, Simona Badilescu, Muthukumaran Packirisamy

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A bio-sensing method, based on the plasmonic property of gold nano-islands, has been developed for detection of exosomes in a clinical setting. The position of the gold plasmon band in the UV-Visible spectrum depends on the size and shape of gold nanoparticles as well as on the surrounding environment. By adsorbing various chemical entities, or binding them, the gold plasmon band will shift toward longer wavelengths and the shift is proportional to the concentration. Exosomes transport cargoes of molecules and genetic materials to proximal and distal cells. Presently, the standard method for their isolation and quantification from body fluids is by ultracentrifugation, not a practical method to be implemented in a clinical setting. Thus, a versatile and cutting-edge platform is required to selectively detect and isolate exosomes for further analysis at clinical level. The new sensing protocol, instead of antibodies, makes use of a specially synthesized polypeptide (Vn96), to capture and quantify the exosomes from different media, by binding the heat shock proteins from exosomes. The protocol has been established and optimized by using a glass substrate, in order to facilitate the next stage, namely the transfer of the protocol to a microfluidic environment. After each step of the protocol, the UV-Vis spectrum was recorded and the position of gold Localized Surface Plasmon Resonance (LSPR) band was measured. The sensing process was modelled, taking into account the characteristics of the nano-island structure, prepared by thermal convection and annealing. The optimal molar ratios of the most important chemical entities, involved in the detection of exosomes were calculated as well. Indeed, it was found that the results of the sensing process depend on the two major steps: the molar ratios of streptavidin to biotin-PEG-Vn96 and, the final step, the capture of exosomes by the biotin-PEG-Vn96 complex. The microfluidic device designed for sensing of exosomes consists of a glass substrate, sealed by a PDMS layer that contains the channel and a collecting chamber. In the device, the solutions of linker, cross-linker, etc., are pumped over the gold nano-islands and an Ocean Optics spectrometer is used to measure the position of the Au plasmon band at each step of the sensing. The experiments have shown that the shift of the Au LSPR band is proportional to the concentration of exosomes and, thereby, exosomes can be accurately quantified. An important advantage of the method is the ability to discriminate between exosomes having different origins.

Keywords: exosomes, gold nano-islands, microfluidics, plasmonic biosensing

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Authors: J. Jessa

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Background: Autism is a pervasive developmental disorder, the incidence of which has significantly increased in recent years. Children with autism have impairments in social skills, communication, and imagination. Children with autism has more common than healthy children feeding problems: food selectivity, problems with gastrointestinal tract: diarrhea, constipations, abdominal pain, reflux and others. Many parents of autistic children report that after implementation of gluten-, casein- and sugar free diet those symptoms disappear and even cognitive functions become better. Some children begin to understand speech and to communicate with parents, regain eye contact, become more calm, sleep better and has better concentration. Probably at the root of this phenomenon lies elimination from the diet peptides construction of which is similar to opiates. Enhanced permeability of gut causes absorption of not fully digested opioid-like peptides from food, like gluten and casein and probably others (proteins from soy and corn) which impact on brain of autistic children. Aim of the study: The aim of the study is to assess the safety of gluten-free diet in children with autism, aged 2,5-7. Methods: Participants of the study (n=70) – children aged 2,5-7 with autism are divided into 3 groups. The first group (research group) are patients whose parents want to implement a gluten-free diet. The second group are patients who have been recommended to eliminate from the diet artificial substances, such as preservatives, artificial colors and flavors, and others (control group 1). The third group (control group 2) are children whose parents did not agree for implementation of the diet. Caregivers of children on the diet are educated about the specifics of the diet and how to avoid malnutrition. At the start of the study we exclude celiac disease. Before the implementation of the diet we performe a blood test for patients (morphology, ferritin, total cholesterol, dry peripheral blood drops to detect some genetic metabolic diseases), plasma aminogram) and urine tests (excretion of ions: Mg, Na, Ca, the profile of organic acids in urine), which assess nutritional status as well as the psychological test assessing the degree of the child's psychological functioning (PEP-R). All of these tests will be repeated after one year from the implementation of the diet. Results: To the present moment we examined 42 children with autism. 12 of children are on gluten- free diet. Our preliminary results are promising. Parents of 9 of them report that, there is a big improvement in child behavior, concentration, less aggression incidents, better eye contact and better verbal skills. Conclusion: Our preliminary results suggest that dietary intervention may positively affect developmental outcome for some children diagnosed with ASD.

Keywords: gluten free diet, autism spectrum disorder, autism, blood test

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Authors: Samuele Viaro, Pierre Ricco

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Görtler instabilities generate in boundary layers from an unbalance between pressure and centrifugal forces caused by concave surfaces. Their spatial streamwise evolution influences transition to turbulence. It is therefore important to understand even the early stages where perturbations, still small, grow linearly and could be controlled more easily. This work presents a rigorous theoretical framework for compressible flows using the linearized unsteady boundary region equations, where only the streamwise pressure gradient and streamwise diffusion terms are neglected from the full governing equations of fluid motion. Boundary and initial conditions are imposed through an asymptotic analysis in order to account for the interaction of the boundary layer with free-stream turbulence. The resulting parabolic system is discretize with a second-order finite difference scheme. Realistic flow parameters are chosen from wind tunnel studies performed at supersonic and subsonic conditions. The Mach number ranges from 0.5 to 8, with two different radii of curvature, 5 m and 10 m, frequencies up to 2000 Hz, and vortex spanwise wavelengths from 5 mm to 20 mm. The evolution of the perturbation flow is shown through velocity, temperature, pressure profiles relatively close to the leading edge, where non-linear effects can still be neglected, and growth rate. Results show that a global stabilizing effect exists with the increase of Mach number, frequency, spanwise wavenumber and radius of curvature. In particular, at high Mach numbers curvature effects are less pronounced and thermal streaks become stronger than velocity streaks. This increase of temperature perturbations saturates at approximately Mach 4 flows, and is limited in the early stage of growth, near the leading edge. In general, Görtler vortices evolve closer to the surface with respect to a flat plate scenario but their location shifts toward the edge of the boundary layer as the Mach number increases. In fact, a jet-like behavior appears for steady vortices having small spanwise wavelengths (less than 10 mm) at Mach 8, creating a region of unperturbed flow close to the wall. A similar response is also found at the highest frequency considered for a Mach 3 flow. Larger vortices are found to have a higher growth rate but are less influenced by the Mach number. An eigenvalue approach is also employed to study the amplification of the perturbations sufficiently downstream from the leading edge. These eigenvalue results are compared with the ones obtained through the initial value approach with inhomogeneous free-stream boundary conditions. All of the parameters here studied have a significant influence on the evolution of the instabilities for the Görtler problem which is indeed highly dependent on initial conditions.

Keywords: compressible boundary layers, Görtler instabilities, receptivity, turbulence transition

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Authors: I. Hosni, L. Bennaceur Farah, N. Saber, R Bennaceur

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Soil moisture content is a key variable in many environmental sciences. Even though it represents a small proportion of the liquid freshwater on Earth, it modulates interactions between the land surface and the atmosphere, thereby influencing climate and weather. Accurate modeling of the above processes depends on the ability to provide a proper spatial characterization of soil moisture. The measurement of soil moisture content allows assessment of soil water resources in the field of hydrology and agronomy. The second parameter in interaction with the radar signal is the geometric structure of the soil. Most traditional electromagnetic models consider natural surfaces as single scale zero mean stationary Gaussian random processes. Roughness behavior is characterized by statistical parameters like the Root Mean Square (RMS) height and the correlation length. Then, the main problem is that the agreement between experimental measurements and theoretical values is usually poor due to the large variability of the correlation function, and as a consequence, backscattering models have often failed to predict correctly backscattering. In this study, surfaces are considered as band-limited fractal random processes corresponding to a superposition of a finite number of one-dimensional Gaussian process each one having a spatial scale. Multiscale roughness is characterized by two parameters, the first one is proportional to the RMS height, and the other one is related to the fractal dimension. Soil moisture is related to the complex dielectric constant. This multiscale description has been adapted to two-dimensional profiles using the bi-dimensional wavelet transform and the Mallat algorithm to describe more correctly natural surfaces. We characterize the soil surfaces and sub-surfaces by a three layers geo-electrical model. The upper layer is described by its dielectric constant, thickness, a multiscale bi-dimensional surface roughness model by using the wavelet transform and the Mallat algorithm, and volume scattering parameters. The lower layer is divided into three fictive layers separated by an assumed plane interface. These three layers were modeled by an effective medium characterized by an apparent effective dielectric constant taking into account the presence of air pockets in the soil. We have adopted the 2D multiscale three layers small perturbations model including, firstly air pockets in the soil sub-structure, and then a vegetable canopy in the soil surface structure, that is to simulate the radar backscattering. A sensitivity analysis of backscattering coefficient dependence on multiscale roughness and new soil moisture has been performed. Later, we proposed to change the dielectric constant of the multilayer medium because it takes into account the different moisture values of each layer in the soil. A sensitivity analysis of the backscattering coefficient, including the air pockets in the volume structure with respect to the multiscale roughness parameters and the apparent dielectric constant, was carried out. Finally, we proposed to study the behavior of the backscattering coefficient of the radar on a soil having a vegetable layer in its surface structure.

Keywords: multiscale, bidimensional, wavelets, backscattering, multilayer, SPM, air pockets

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Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin

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Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.

Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis

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Authors: Anna-Maria Ramezanzadeh

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Demand for Arabic language is growing worldwide, driven by increased interest in the multifarious purposes the language serves, both for the population of heritage learners and those studying Arabic as a foreign language. The diglossic, or indeed multiglossic nature of the language as used in Arabic speaking communities however, is seldom represented in the content of classroom courses. This disjoint between the nature of provision and students’ expectations can severely impact their engagement with course material, and their motivation to either commence or continue learning the language. The nature of motivation and its relationship to multiglossia is sparsely explored in current literature on Arabic. The theoretical framework here proposed aims to address this gap by presenting a model and instruments for the measurement of Arabic learners’ motivation in relation to the multiple strands of the language. It adopts and develops the Second Language Motivation Self-System model (L2MSS), originally proposed by Zoltan Dörnyei, which measures motivation as the desire to reduce the discrepancy between leaners’ current and future self-concepts in terms of the second language (L2). The tripartite structure incorporates measures of the Current L2 Self, Future L2 Self (consisting of an Ideal L2 Self, and an Ought-To Self), and the L2 Learning Experience. The strength of the self-concepts is measured across three different domains of Arabic: Classical, Modern Standard and Colloquial. The focus on learners’ self-concepts allows for an exploration of the effect of multiple factors on motivation towards Arabic, including religion. The relationship between Islam and Arabic is often given as a prominent reason behind some students’ desire to learn the language. Exactly how and why this factor features in learners’ L2 self-concepts has not yet been explored. Specifically designed surveys and interview protocols are proposed to facilitate the exploration of these constructs. The L2 Learning Experience component of the model is operationalized as learners’ task-based engagement. Engagement is conceptualised as multi-dimensional and malleable. In this model, situation-specific measures of cognitive, behavioural, and affective components of engagement are collected via specially designed repeated post-task self-report surveys on Personal Digital Assistant over multiple Arabic lessons. Tasks are categorised according to language learning skill. Given the domain-specific uses of the different varieties of Arabic, the relationship between learners’ engagement with different types of tasks and their overall motivational profiles will be examined to determine the extent of the interaction between the two constructs. A framework for this data analysis is proposed and hypotheses discussed. The unique combination of situation-specific measures of engagement and a person-oriented approach to measuring motivation allows for a macro- and micro-analysis of the interaction between learners and the Arabic learning process. By combining cross-sectional and longitudinal elements with a mixed-methods design, the model proposed offers the potential for capturing a comprehensive and detailed picture of the motivation and engagement of Arabic learners. The application of this framework offers a number of numerous potential pedagogical and research implications which will also be discussed.

Keywords: Arabic, diglossia, engagement, motivation, multiglossia, sociolinguistics

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Authors: Georgios Samaras

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New media such as Facebook, YouTube and Twitter introduced the world to a new era of instant communication. An era where online interactions could replace a lot of offline actions. Technology can create a mediated environment in which participants can communicate (one-to-one, one-to-many, and many-to-many) both synchronously and asynchronously and participate in reciprocal message exchanges. Currently, social networks are attracting similar academic attention to that of the internet after its mainstream implementation into public life. Websites and platforms are seen as the forefront of a new political change. There is a significant backdrop of previous methodologies employed to research the effects of social networks. New approaches are being developed to be able to adapt to the growth of social networks and the invention of new platforms. Golden Dawn was the first openly neo-Nazi party post World War II to win seats in the parliament of a European country. Its racist rhetoric and violent tactics on social networks were rewarded by their supporters, who in the face of Golden Dawn’s leaders saw a ‘new dawn’ in Greek politics. Mainstream media banned its leaders and members of the party indefinitely after Ilias Kasidiaris attacked Liana Kanelli, a member of the Greek Communist Party, on live television. This media ban was seen as a treasonous move by a significant percentage of voters, who believed that the system was desperately trying to censor Golden Dawn to favor mainstream parties. The shocking attack on live television received international coverage and while European countries were condemning this newly emerged neo-Nazi rhetoric, almost 7 percent of the Greek population rewarded Golden Dawn with 18 seats in the Greek parliament. Many seem to think that Golden Dawn mobilised its voters online and this approach played a significant role in spreading their message and appealing to wider audiences. No strict online censorship existed back in 2012 and although Golden Dawn was openly used neo-Nazi symbolism, it was allowed to use social networks without serious restrictions until 2017. This paper used qualitative methods to investigate Golden Dawn’s rise in social networks from 2012 to 2019. The focus of the content analysis was set on three social networking platforms: Facebook, Twitter and YouTube, while the existence of Golden Dawn’s website, which was used as a news sharing hub, was also taken into account. The content analysis included text and visual analyses that sampled content from their social networking pages to translate their political messaging through an ideological lens focused on extreme-right populism. The absence of hate speech regulations on social network platforms in 2012 allowed the free expression of those heavily ultranationalist and populist views, as they were employed by Golden Dawn in the Greek political scene. On YouTube, Facebook and Twitter, the influence of their rhetoric was particularly strong. Official channels and MPs profiles were investigated to explore the messaging in-depth and understand its ideological elements.

Keywords: populism, far-right, social media, Greece, golden dawn

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