bluuebunny/crossref_metadata_2025 huggingface dataset:
Cittŕ dei Morti: slum o scenario del patrimonio immateriale egiziano?
Authors: Tozzi Di Marco Anna
Published: June 2021

- Cairo's City of the Dead consists of an ancient urban Muslim cemetery (642 AD). Al Qarafa, its Arabic name, still functions today as a burying place, but with the peculiarity that it has as many as eighteen urban neighbourhoods with approximately one million residents. Sector studies which rubber stamp the different areas as a single milieu, classify it as a slum. In reality this necropolis, one of the more liveable working class metropolitan districts, represents a stratification of traditions and customs that have accumulated in Egypt from the time of the Pharaohs until today. To unravel the complexity of that body of demographic, ethnic and anthropological values that are closely interwoven with the City's monumental heritage might be useful for further reflection on the future destiny of the City of the Dead. Under the government urban redevelopment project ‘Vision 2050', it is to be demolished, partly for the construction of a park. Basically it is a question of valuing this co-existence of the living and the dead as a distinctive feature, the product of a historical and cultural heritage that is unique in the world.
Incontri con gli abitanti di Cittŕ dei Morti
Authors: Sambati Simona
Published: June 2021

- The monumental cemetery of Cairo, Al Qarafa, is an anomaly in the urban area of the city. For the citizens of Cairo it is a foreign entity, but for those who inhabit it, it is where they live. The architectures of the mausolea and the sepulchres of the deceased bring together the paths, the fragrances and objects of the occupants. Their life stories, their experiences and their adventures fill the space with a completely new meaning as occupation is transformed into housing and living.
Sakan Project. Strategie e governance per uno sviluppo urbano cultural based nella Cittŕ dei Morti
Authors: La Mantia Costanza
Published: June 2021

- In a world in which the classification of cities, disguised under the word development, hides the slavish acquisition of heterotopic models, it is important to defend uniqueness and differences and to explain to local and national governments that a framework of development policies based on cultural resources and identity is the only path to follow for real and sustainable development. In this respect there are many and varied references in the theoretical literature to the direct and indirect ways in which the presence of cultural institutions and the enhancement of cultural heritage can bring widespread benefits, by strengthening the image of a city and above all by defining new development scenarios which combine economic, social and cultural dimensions and local resources with governance and community involvement processes. This is the approach that is taken in an attempt to define a new ‘Vision for the City of the Dead'.
Cittŕ dei Morti: quartiere del Cairo. Cinque interventi per la sua valorizzazione
Authors: Colli Alessandro , Daglia Maria Luisa
Published: June 2021

- The City of the Dead is to all intents and purposes a district of Cairo! Free from all the laws which seem to regulate other areas, it represents a possible exception and above all a great potential pool of resources for the sustainable development of all the city. Five specific and independent interventions, that form part of a single strategy, regulate the flows of people which connect the cemetery to what lies around it, locally enhancing resources that had never been considered: the urban districts (catalysers of activities, people and events) and the empty areas within them come into symbiosis with five autonomous systems (large on a metropolitan scale) which surround it, drawing advantages from processes already in progress.
Cairo, mega-city o mega-slum? Evoluzione demografica ed elementi della forma urbana della capitale egiziana
Authors: Chiodelli Francesco , Fini Giulia
Published: June 2021

- The paper gives an overview of the development of the main elements which various attempts at planning in the twentieth century had to face up to: the urbanisation of increasingly greater proportions of the population for which the quantitative (demographic) and qualitative (elements of the urban form) framework is given. The first part schematically reconstructs the demographic trends for the city since the middle of the twentieth century, when the urban explosion commenced which brought the population of the Egyptian capital up from 2.2 million in 1947 to twelve million today. The second part looks at the distribution of the population in space, identifying the main elements that characterise the present day urban form of the metropolitan area.
Cinque zoom sul Cairo. I progetti attuati e quelli in via di attuazione
Authors: Falletti Maddalena
Published: June 2021

- The article considers five cases, the Sixth of October new town, the City of the Dead, the Zabbaleen neighbourhood, the Al Azhar park and finally the Nile Tower project by Zaha Hadid to give a review of current tendencies in the transformation of urban Cairo, looking at critical issues, the methodologies commonly employed and the large scale consequences. Although they appear very different, the cases reveal a common matrix and respond to an approach to the management of space which seems to move towards the consolidation of a policy of social exclusion.
Gio Ponti, Hotel Paradiso in Val Martello
Authors: Denti Giovanni , Toscani Chiara
Published: June 2021

- In 1930 Gio Ponti designed a cable car system to cross the Dolomites, which also involved the construction of hotels of three different types at the stations. One of these was built in 1936 at the bottom of the Val Martello valley at an altitude of 2,160 metres in front of Mount Cevedale. It was a facility designed to take customers belonging to different social classes with a careful hierarchy of communal and private services which gave rise to much criticism and debate at the time. The body of the building was partly linear and partly curved in shape, rising to three storeys with the main rooms located in the convex curve of the front. One distinctive feature of the interiors was the use of colour (Ponti developed his study of this in that period), which identified spatial fields and suggested visual lines and directions. In the years after the war the hotel was purchased by a Venetian shipowner Benati, who added two floors and partially enlarged it. It operated for a few years and has been closed down since 1955. Today it is in a serious state of disrepair, although the structure is still standing.
La piana fiorentina: la crescita urbana e il riassetto attorno ai nodi del trasporto collettivo
Authors: Facchinetti Marco
Published: June 2021

- This research study sought to understand the real dynamics of urban growth, the forecasts existing in local urban plans and supra-local plans, the development projects and hypotheses of growth in infrastructure networks in a limited but central area of the general plan in the western province of Florence and the province of Prato. While there has been a substantial increase in planned infrastructures, for which the programmes have been verified by research studies, there has been no equally important co-ordination of forecasts of growth, expansion or urban transformation. On the basis of these assumptions, the research conducted asked whether it was possible to design a type of development with respect to the forecasts of current plans, which attempts to reorganise the Florentine metropolitan area by means of collective transport networks. This would be done by identifying a sustainable growth strategy, by examining which urban planning model would best meet that objective and at the same time by addressing issues such as containing land use and reducing the demand for private transport by increasing densities around the nodes.
Conservazione e fruizione del patrimonio architettonico: un problema etico
Authors: Bellini Amedeo
Published: June 2021

Critical thinking still today addresses the issues of the conservation and reuse of our architectural heritage from different viewpoints which are not compared, as if the recognition of historical, communicative and formal values and thinking on how it is used and on the inevitable changes needed to satisfy vital needs belong to totally different spheres of thought and work. More specifically, time is lost within that disciplinary area traditionally defined as history and criticism in advancing hypotheses to summarise the debate that has taken place in recent decades, with no acknowledgement of the radical change that has taken place, caused by new historical and aesthetic perspectives of the relative nature of all value judgements and of the extension of protection to unofficial building, which inevitably highlight political and economical aspects, which in the final analysis are ethical questions.
Social impacts, prons and cons of hosting mega sporting events, focusing on a global south city: Rio de Janeiro
Authors: Costa Giuliana
Published: June 2021

The organisation and hosting of major events, whether cultural, political, sports, economic or social, forms part of a broader strategy adopted by cities to compete in the global arena and to attract capital and investments and to boost tourism and at the same time to address their economic and social problems. This paper reviews the sociological, economic and planning literature in order to discuss to what extent these complex events represent an opportunity to stimulate the economies of cities and to transform their socio-economic and geographical structure. It does this by analysing the most critical aspects of the changes and redevelopment carried out in Rio de Janeiro to host the 2014 World Cup and the 2016 Olympics. The analysis focuses on the negative social and economic effects which these events are already having on the city.
From culture to spectacle, the new logics of Brazilian football
Authors: Gaffney Christopher
Published: June 2021

Twelve large size stadiums are currently under construction in Brazil to host the 2014 World Cup for a total cost of around Euro 20 billion of which 97% met by public funding. This is taking place in urban contexts that are lacking in basic sports facilities for public use. The paper holds that the construction of these new stadiums constitutes the culmination of a project lasting several decades, the objective of which is to change the socio-economic profile of Brazilian football. The changes in progress relating to the mega sports events to be held in the next few years are not compatible with the cultural environment of this sport; an outline is given of its nature and history. It is shown that the projects underway do not adequately meet the needs of the city after the events, but rather support processes to further commercialise the sport and its culture from a show business viewpoint.
Mega sporting events in Brazil: transformation and mercantilisation of cities
Authors: de Queiroz Ribeiro Luiz Cesar , Alves Dos Santos Junior Orlando
Published: June 2021

This paper illustrates the background against which preparations are being made in Brazil to host these mega sports events in the next few years and how the events are positioned in the global market today, hit by the financial and economic crisis. The authors describe the various paths taken by the country and its metropolises since 1980. They employ varied and many faceted theoretical concepts and highlight the specificities of the Brazilian contest compared to other areas of the world. The hypothesis is advanced that the historical transition of this South American giant holds contradictory dynamics, the resolution of which is defined in the field of national and local public policies designed to facilitate new forms of capitalist accumulation, but with strong ‘path dependency' mechanisms and processes which partly diverge between the state and the metropolitan plans.
Costruire la cittŕ dei ceti medi
Authors: Zanfi Federico , Caramellino Gaia
Published: June 2021

This section reports the first results of a research project which examines residential architecture built for the middle classes from the 1950s until the 1970s in the cities of Turin, Milan and Rome. These essays - which focus mainly on Milan and Turin - dwell on various aspects of the phenomenon which include the following: the relationship between urban planning and the contraction of middle class cities, the role of private sector operators; the involvement of the public sector through forms of housing that are subsidised with concessions by government; the role of property developers; the issue of the ‘translation' of high-end and standard international architectural models towards a broader market connected with consumer models and tastes expressed by the growing middle classes.
Costruire per il ceto medio a Milano. Note sulla filiera imprenditoriale
Authors: Gaeta Luca
Published: June 2021

The precise boundaries of the supply chain for the production of housing for the middle classes in Milan during the boom years are not clearly defined. And yet its activity is of crucial importance to an understanding of the social and tangible forms of the middle class city. Construction companies constituted the key link in relations between land owners, clients, architects and end users of the asset that is a home. This paper offers a provisional picture which documents the firms most active in the sector, the prevailing operating practices and two businessmen who were interviewed. The conclusions identify two lines for further research into the middle class city: the role of non-professional mediators in the property market and the high concentration of up-market new housing construction within the ‘cerchia dei bastioni' (inner part of the city).
Edilizia pubblica per i ceti medi: contributi al dibattito sulle case per gli impiegati nel secondo dopoguerra
Authors: Caramellino Gaia
Published: June 2021

Although history has frequently identified subsidised housing with economical popular housing, this paper reconsiders the role played by some public sector actors in the construction of housing for white collar workers in Italy in the 1950s and 1960s. The paper attempts a preliminary and brief account of the work of Incis (Istituto Nazionale per la Casa degli Impiegati dello Stato - national housing institute for state office workers) in Italy in the post-war period. It focuses in particular on the contribution of this institution to collective imagery, symbols and housing models - ranging from the urban scale to domestic interiors - and to the places where those models were formulated and transmitted, the result of a meeting of institutional programmes, professional cultures and the housing aspirations of public sector office workers.
DETERMINATION OF TRACE ELEMENTS IN SOME BRANDS OF GREEN TEA USING WET DIGESTION, INFUSION AND DRY ASHING METHODS
Authors: Imrana Ibrahim , Aminu Salisu , Bilal Umar , Mujitafa Bello Sada
Published: June 2021

The concentrations of trace elements (Cu, Zn, Fe, Mn and Ni) in some commercially available brands of green tea sold within Katsina metropolis coded (SGT, HGT, LGT, AGT and GGT) were determined using wet acid digestion, water infusion, and Dry Ashing methods by Atomic Absorption Spectroscopy (AAS).  Among the trace elements analyzed Nickel and Manganese recorded the highest value ranged 1.0 – 3.5 mg kg-1 and1.0 – 5.5 mg kg-1 in dry ashing and wet digestion respectively. Fortunately, almost all the elements analyzed were within the standard permissible limit of WHO. The content of trace elements was found highest in the Dry Ashing method and lowest values recorded in tea infusion. The contributory factors responsible for the differences found in tea samples could be from a varying concentration of metals in the soil, conditions of cultivation and preparations, and these vary between both countries of origin and for the type of tea. Further work is recommended on these brands to study other important parameters
Training synchronization of medical students by using information and communication technologies
Authors:   Poltava Basic Medical Professional College, Ukraine, Synenko Olena , Vakhnenko Nataliіa ,   Poltava Basic Medical Professional College, Ukraine, Chemisova Tetyana ,   Poltava Basic Medical Professional College, Ukraine, Yefimenko Nataliіa ,   Poltava Basic Medical Professional College, Ukraine
Published: June 2021

The article describes and summarizes the experience of using Internet information in the work of an educational institution, its role in improving the information provision of students. The peculiarities of individualization and differentiation of learning in the conditions of the application of multimedia resources and constructing a student dialogue with a computer are analyzed. The main tendencies and perspectives of use of the Internet information on classes of different cycles are highlighted.The current article reveals the potential of synchronization of medical students’ learning by using information and communication technologies both during classroom classes and in the conditions of distance and blended learning.Monitoring of ICT competence of teachers as subjects of information educational space of educational institution is promising, as it allows to more effectively influence the content, forms, methods and means of methodological training of different categories of pedagogical and medical workers, which optimizes the use of educational resources to improve education and self-realization of teachers and medical students
Pedagogical potential of gestalt therapy in the context of future primary school teachers’ professional training
Authors:   Poltava V.G. Korolenko National Pedagogical University, Ukraine, Halyna Tetiana
Published: June 2021

The article reveals the pedagogical potential of gestalt therapy in the context of professional training of future primary school teachers. The influence of gestalt therapy on the development of the emotional sphere of the personality of a primary school pupil is revealed. The main tasks of gestalt therapy in the educational process of primary education are determined. The expediency of using the methods of gestalt therapy in the process of the development of self-awareness and self-worth of the personality of primary school pupils is revealed
Methods of terms-phrases translation in IT
Authors:   National University «Yuri Kondratyuk Poltava Polytechnic», Ukraine, Pavelieva Anna , Lobko Iryna ,   National University «Yuri Kondratyuk Poltava Polytechnic», Ukraine, Sotnichenko Inna ,   National University «Yuri Kondratyuk Poltava Polytechnic», Ukraine
Published: June 2021

The article is devoted to the translation of English terms-phrases into Ukrainian according to their models. It is determined that as for the structure, one-component terms prevail in IT texts, but compound terms also make up a large proportion of terminological units. Among compound terms, the most common are two-component phrases (they make up 76.46% of terms), followed by three-component phrases (19.4%), while four-, five-, and six-component terminological phrases make up a small percentage of IT phrases in this terminology (4.14%). It is stated that separate elements of terms-phrases are translated with the help of transcoding, loan translation, descriptive translation, or translation by equivalents, but compound terms can contain various units that should be translated using different methods, and therefore for the analysis of such terminological units it is necessary to first identify their structural models that will allow research on ways to translate specific elements of terminological phrases. It is proved in the article that the most common models of compound terms in IT are two-component models N1 + N2 (42% of the total number), Adj + N (20%), Part.II + N (7%), which are translated into Ukrainian using the appropriate terms-phrases or compound terms that contain the elements of the original phrase, and other types of compound terms depending on the specific model. The most common three-component models N + N + N and (Adj + N) + N are also considered in the article.
On the question of dyslalia correction in primary school-age children
Authors:   Rivne Regional Institute of Postgraduate Pedagogical Education, Ukraine, Оliinyk Iryna , Tyshchenko Liliia ,   Rivne Regional Institute of Postgraduate Pedagogical Education, Ukraine, Yatseniuk Larissa ,   Rivne Regional Institute of Postgraduate Pedagogical Education, Ukraine
Published: June 2021

The article discloses the problem of dyslalia treatment in primary school-age children. It highlights the scientific views of Ukrainian and foreign scientists concerning the diagnosis of dyslalia as a speech disorder. In particular, the author investigates various approaches to the classification of dyslalia in domestic and foreign literature and reveals the methodological foundations of dyslalia correction in the context of the formation of speech competence of primary school-age children of the New Ukrainian School.The study characterizes primary forms and types of dyslalia depending on the causes of its occurrence and the number of groups of disturbing sounds. Following the stages of speech therapy, the author describes a method for correcting violations of sound pronunciation and the formation of skills for accurate reproduction of sounds within children of primary school age.Particular attention is focused on the timely detection and correction of dyslalia in elementary school students to prevent the manifestation of violation processes in reading and writing, problems with communication in society, and the formation of the personality as a whole. The need to improve the competence of teachers, including primary school teachers working with children of this category, is noted in connection with the transition of primary schools to the new State Standard and the active introduction of inclusive education.The author substantiates the expediency of close cooperation of all participants in the educational process regarding the awareness of the shared responsibility for the child’s speech development
Didactic fundamentals of organization of tourist local history activity of future geographers
Authors:   V. N. Karazin Kharkiv National University, Ukraine, Yuliia Prasul
Published: June 2021

The organization of tourist local lore activities of future geographers is a holistic, integrative, mobile, complex system that meets modern educational and social requirements, labor market demands, individual educational needs of students, which effectiveness is provided by the methodological basis: at the philosophical level – principles of philosophy awareness of the value of achieving professional results; on general scientific – conceptual bases of future geographers training for the organization of tourist local lore activity in the conditions of the information and globalization world; the essence of information and cartographic support of tourist and local lore activity within the administrative district and its features are covered. The necessity of developing a tourist and local lore guide of the following structure is proved: introduction, general acquaintance with the territory, complex page-by-page tourist and local lore map, tourist and local lore routes, plans of the largest settlements, list of settlements of the district. Approbation was carried out on the example of Balakliia district of Kharkiv region. The main scientific provisions of the Program of regional mapping of natural and historical-cultural territories, objects and complexes of the region developed at the Department of Physical Geography and Cartography of V. N. Karazin Kharkiv National University are devoted to the current problems of development of a new direction of thematic mapping. Within its limits the basic theoretical questions are defined: information base, mathematical basis, structure and content of original experimental maps and atlases of natural and historical and cultural heritage; The approach to the structure and content of sports and tourism practice is appropriate to improve the level of mastery of the necessary skills, knowledge, broadening horizons and students in the 1st year to test their ability to manage the group in non-standard and emergencies
Komissiosta sopimustyyppinä – Komitentin ja komissionäärin oikeusasemasta arvopaperien julkisessa vaihdannassa sekä komissio-opin kehitystarpeesta
Authors: Wirén Karri
Published: June 2021

Suomenkielinen tiivistelmä puuttuu.
Saved by the shell: Oyster reefs can shield juvenile blue crabs Callinectes sapidus
Authors: Longmire KS , Seitz RD , Smith A , Lipcius RN
Published: June 2021

Juvenile blue crabs Callinectes sapidus use seagrass and other structured habitats as refuges from predation. Oyster reef habitats provide structural complexity that may offer refuge, but the value of these habitats for juvenile blue crabs has not been examined. We quantified survival of juvenile C. sapidus in structured oyster reef habitat versus unstructured soft-bottom habitat. In a field tethering experiment in the York River, lower Chesapeake Bay (USA), juvenile C. sapidus (10-50 mm carapace width [CW]) were tethered in sand (n = 40) or oyster reef (n = 39) habitats at subtidal sites 1-2 m deep. An underwater camera system was used to record predation activity during 24 h trials. Juvenile crab survival was significantly higher on the oyster reef habitat (53.8%) than on bare sand (15.0%), and tended to increase with crab CW in both habitats. The main successful predators on juvenile blue crabs were northern pufferfish Sphoeroides maculatus in the oyster reef habitat and adult blue crabs in the sand habitat. The high survival rate of juvenile C. sapidus in oyster reef habitats suggests that oyster reefs include physical habitat complexity that may offer refuge from predators. Restored and natural oyster reefs could provide an alternative nursery habitat for juvenile blue crabs, expanding the ecosystem services provided by restored oyster reefs.
Notch1 and Galectin-3 Modulate Cortical Reactive Astrocyte Response After Brain Injury
Authors: Ribeiro Tais Novaki , Delgado-García Lina Maria , Porcionatto Marimelia A.
Published: June 2021

After a brain lesion, highly specialized cortical astrocytes react, supporting the closure or replacement of the damaged tissue, but fail to regulate neural plasticity. Growing evidence indicates that repair response leads astrocytes to reprogram, acquiring a partially restricted regenerative phenotype in vivo and neural stem cells (NSC) hallmarks in vitro. However, the molecular factors involved in astrocyte reactivity, the reparative response, and their relation to adult neurogenesis are poorly understood and remain an area of intense investigation in regenerative medicine. In this context, we addressed the role of Notch1 signaling and the effect of Galectin-3 (Gal3) as underlying molecular candidates involved in cortical astrocyte response to injury. Notch signaling is part of a specific neurogenic microenvironment that maintains NSC and neural progenitors, and Gal3 has a preferential spatial distribution across the cortex and has a central role in the proliferative capacity of reactive astrocytes. We report that in vitro scratch-reactivated cortical astrocytes from C57Bl/6J neonatal mice present nuclear Notch1 intracellular domain (NICD1), indicating Notch1 activation. Colocalization analysis revealed a subpopulation of reactive astrocytes at the lesion border with colocalized NICD1/Jagged1 complexes compared with astrocytes located far from the border. Moreover, we found that Gal3 increased intracellularly, in contrast to its extracellular localization in non-reactive astrocytes, and NICD1/Gal3 pattern distribution shifted from diffuse to vesicular upon astrocyte reactivation. In vitro, Gal3–/– reactive astrocytes showed abolished Notch1 signaling at the lesion core. Notch1 receptor, its ligands (Jagged1 and Delta-like1), and Hes5 target gene were upregulated in C57Bl/6J reactive astrocytes, but not in Gal3–/– reactive astrocytes. Finally, we report that Gal3–/– mice submitted to a traumatic brain injury model in the somatosensory cortex presented a disrupted response characterized by the reduced number of GFAP reactive astrocytes, with smaller cell body perimeter and decreased NICD1 presence at the lesion core. These results suggest that Gal3 might be essential to the proper activation of Notch signaling, facilitating the cleavage of Notch1 and nuclear translocation of NICD1 into the nucleus of reactive cortical astrocytes. Additionally, we hypothesize that reactive astrocyte response could be dependent on Notch1/Jagged1-Hes5 signaling activation following brain injury.
Making Virtual Learning Environments Accessible to People with Disabilities in Universities in Uganda
Authors: Baguma Rehema , Wolters Maria K.
Published: June 2021

Public and private universities in Uganda have been using Virtual Learning Environments (VLEs) since early 2000s to support delivery of blended learning owing to the increased uptake of technology in many aspects of life, and the benefits of blended learning/eLearning. eLearning is of particular benefit to people with disabilities, since they may find it difficult to attend classes on a university campus. Accessibility of a VLE has a strong impact on user engagement and adoption and consequently on students’ learning outcomes. Current research on use of VLEs and eLearning in general in Ugandan universities focuses on sensitization and training, the potential of social media like WhatsApp and Facebook, and required resources like Internet connectivity, and change management. In stark contrast, there is no investigation of accessibility to people with disabilities, even though about 12.4% of the population have some form of disability. This paper examines the extent to which Uganda’s policy environment promotes making eLearning accessible, reviews the accessibility of a sample of VLEs of public and private universities in Uganda, and suggests recommendations on addressing the existing accessibility gaps in policy and implementation of VLEs.
Cardiac Safety of Kinase Inhibitors – Improving Understanding and Prediction of Liabilities in Drug Discovery Using Human Stem Cell-Derived Models
Authors: Ziegler Ricarda , Häusermann Fabian , Kirchner Stephan , Polonchuk Liudmila
Published: June 2021

Many small molecule kinase inhibitors (SMKIs) used to fight cancer have been associated with cardiotoxicity in the clinic. Therefore, preventing their failure in clinical development is a priority for preclinical discovery. Our study focused on the integration and concurrent measurement of ATP, apoptosis dynamics and functional cardiac indexes in human stem cell-derived cardiomyocytes (hSC-CMs) to provide further insights into molecular determinants of compromised cardiac function. Ten out of the fourteen tested SMKIs resulted in a biologically relevant decrease in either beating rate or base impedance (cell number index), illustrating cardiotoxicity as one of the major safety liabilities of SMKIs, in particular of those involved in the PI3K–AKT pathway. Pearson's correlation analysis indicated a good correlation between the different read-outs of functional importance. Therefore, measurement of ATP concentrations and apoptosis in vitro could provide important insight into mechanisms of cardiotoxicity. Detailed investigation of the cellular signals facilitated multi-parameter evaluation allowing integrative assessment of cardiomyocyte behavior. The resulting correlation can be used as a tool to highlight changes in cardiac function and potentially to categorize drugs based on their mechanisms of action.
Cardiac Fibroblast-Specific Knockout of PGC-1α Accelerates AngII-Induced Cardiac Remodeling
Authors: Chen Hong-jin , Pan Xiao-xi , Ding Li-li-qiang , Ruan Cheng-chao , Gao Ping-jin
Published: June 2021

Cardiac remodeling consisted of ventricular hypertrophy and interstitial fibrosis is the pathological process of many heart diseases. Fibroblasts as one of the major cells in the myocardium regulate the balance of the generation and degeneration of collagen, and these cells transform toward myofibroblasts in pathological state, contributing to the remodeling of the heart. Peroxisome proliferator-activated receptor-γ (PPAR-γ) coactivator-1α (PGC-1α) is vital to the function of mitochondria, which contributes to the energy production and reactive oxidative species (ROS)-scavenging activity in the heart. In this study, we found that fibroblast-specific PGC-1α KO induced cardiac remodeling especially fibrosis, and Angiotensin II (AngII) aggravated cardiac fibrosis, accompanied with a high level of oxidative stress response and inflammation.
Personalized Antiplatelet Therapy Based on CYP2C19 Genotypes in Chinese ACS Patients Undergoing PCI: A Randomized Controlled Trial
Authors: Shi Xiujin , Zhang Yunnan , Zhang Yi , Zhang Ru , Lin Baidi , Han Jialun , Li Wenzheng , Fang Zhenwei , Yan Jialin , Wang Yifan , Zheng Ze , Lv Yuan , Lin Yang
Published: June 2021

Background: The clinical benefits of cytochrome P450 (CYP) 2C19 genotype-guided antiplatelet therapy in Asians remain unclear. In this study, we aimed to investigate the clinical outcomes of pharmacogenomic antiplatelet therapy in Chinese patients.

Methods: Patients with acute coronary syndrome planning to undergo percutaneous coronary intervention were eligible for this study and were randomly divided into a genotype-guided treatment (GT) group and routine treatment (RT) group, with a ratio of 2:1. Patients in the GT group underwent CYP2C19 genotyping (*2 and *3 alleles), and the results were considered in selecting P2Y12 receptor inhibitors. Patients in the RT group were treated with P2Y12 receptor inhibitors according to their clinical characteristics. The primary endpoint was a composite of major adverse cardiovascular or cerebrovascular events (MACCE). The secondary endpoint was significant bleeding events.

Results: Finally, 301 patients were enrolled; 75.1% were men and the mean age was 59.7 ± 9.8 years. In total, 281 patients completed the follow-up procedure. The primary endpoint occurred in 16 patients, 6 patients in the GT group and 10 in the RT group. The GT group showed lower MACCE rates than the RT group (6/189 vs. 10/92, 3.2 vs. 10.9%, hazard ratio: 0.281, 95% confidence interval: 0.102–0.773, P = 0.009). There was no statistically difference in significant bleeding events between the GT and RT groups (4.2 vs. 3.3%, hazard ratio: 1.315, 95% confidence interval: 0.349–4.956, P = 0.685).

Conclusion: Personalized antiplatelet therapy that is based on CYP2C19 genotypes could decrease MACCE within a 12-month period in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Clinical Trial Registration:http://www.chictr.org.cn, identifier: ChiCTR2000034352.
Amelogenin Peptide-Chitosan Hydrogel for Biomimetic Enamel Regrowth
Authors: Mukherjee Kaushik , Chakraborty Amrita , Sandhu Garima , Naim Sohaib , Bauza Nowotny E. , Moradian-Oldak Janet
Published: June 2021

We designed synthetic peptides that have demonstrated an effective remineralization potential to restore incipient enamel decay. In order to develop a clinically viable approach we incorporated the amelogenin-derived peptides P26 and P32 into chitosan hydrogel and examined their efficacy in the remineralization of enamel. Peptides in chitosan exhibited increased stability in vitro as compared to peptides in solution at room temperature and at 37°C. Tooth models for enamel erosion (sections) and white spot lesions (blocks) were subject to periods of demineralization. Treatment groups were subjected to remineralization in artificial saliva in the presence of P26 and P32 in solution and in chitosan hydrogel (P26-CS and P32-CS). Quantitative light-induced fluorescence (QLF) was employed to analyze mineral density following demineralization and remineralization across all the treatment groups. Scanning electron microscopy and nanoindentation were used to characterize the surface structure and mechanical strength of regrown enamel. Control enamel sections treated in artificial saliva demonstrated randomly distributed, tiny, needle-shaped crystals with a low packing density and porosities displaying mineralization defects. In samples treated with P26-CS or P32-CS a denser coating of organized hydroxyapatite (HAP) crystals was formed covering the entire surfaces of demineralized enamel window. The hardness and modulus of enamel surfaces were increased after treatment with P26-CS and P32-CS with no significant difference in the mechanical properties between the two peptide hydrogels. Analysis of mineral density by QLF showed that in enamel sections P26 peptide alone or P26-CS significantly enhanced the remineralization. In enamel blocks P26 in solution had a better efficacy than P26-CS.
Increasing Compound Heat and Precipitation Extremes Elevated by Urbanization in South China
Authors: Wu Sijia , Chan Ting On , Zhang Wei , Ning Guicai , Wang Peng , Tong Xuelin , Xu Feng , Tian Hao , Han Yu , Zhao Yongquan , Luo Ming
Published: June 2021

Compared with individual events, compound weather and climate extremes may impose more serious influences on natural systems and human society, especially in populated areas. In this study, we examine the changes in the compound precipitation events that follow extremely hot weather within several days during 1961–2017 in South China by taking the Guangdong Province as an example. Additionally, we assess the impacts of urbanization on these changes. It is found that extreme precipitation events in Guangdong are often preceded by hot weather, with an average fraction of 28.25%. The fraction of such compound events is even larger in more populated and urbanized areas such as the Pearl River Delta (PRD) region. Moreover, our results reveal significant increases in the frequency and fraction of the compound extreme heat and precipitation events. These increases are especially stronger in more developed areas (e.g., PRD), and their increasing trends tend to accelerate in recent decades. Furthermore, the local urbanization contributes to 40.91 and 49.38% of the increases in the frequency and fraction of the compound events, respectively. Our findings provide scientific references for policy-makers and urban planners to mitigate the influences of the compound heat and precipitation extremes by considering their increasing risks under the context of global climate change and local urbanization.
Exploiting Thermochronology to Quantify Exhumation Histories and Patterns of Uplift Along the Margins of Tibet
Authors: Furlong Kevin P. , Kirby Eric , Creason C. Gabriel , Kamp Peter J. J. , Xu Ganqing , Danišík Martin , Shi Xuhua , Hodges Kip V.
Published: June 2021

The utilization of thermal-chronological data to constrain mountain building processes exploits the links among rock uplift, exhumation, and cooling during orogenesis. Conceptually, periods of rapid uplift and associated denudation will lead to cooling of rocks as they approach Earth’s surface. The linkage between uplift and exhumation can be complex, but in practice exhumation is often assumed to directly track uplift. The reconstruction of temperature-time histories via thermochronologic systems provides a proxy method to relate the cooling of rock as it is exhumed toward the surface to orogenesis. For the rapid exhumation rates that can occur in active orogenic systems the thermal history will be complex as a result of heat advection, rates of propagation of thermal perturbations, and other processes that affect the cooling behavior. These effects become amplified as exhumation rates increase, and in regions experiencing exhumation rates greater than ∼0.2–0.3 mm/yr (0.2–0.3 km/Ma) simple assumptions of cooling through a constant geotherm will bias the subsequent interpretation. Here we explore, through a suite of generalized models, the impact of exhumation rate and duration on the resulting thermal history and apparent age results. We then apply lessons from these simple exhumation systems to data sets from the high-relief ranges along the eastern margin of the Tibetan Plateau to determine exhumation histories constrained by those data. The resulting exhumation histories provide constraints on the onset of Cenozoic exhumation, the subsequent pace of exhumation, and on the tectonic history of one of the major fault systems in the central Longmen Shan.
Covid-19 and Growth Hormone/Insulin-Like Growth Factor 1: Study in Critically and Non-Critically Ill Patients
Authors: Ilias Ioannis , Diamantopoulos Aristidis , Botoula Efthymia , Athanasiou Nikolaos , Zacharis Alexandros , Tsipilis Stamatios , Jahaj Edison , Vassiliou Alice G. , Vassiliadi Dimitra A. , Kotanidou Anastasia , Tsagarakis Stylianos , Dimopoulou Ioanna
Published: June 2021

Objective

We aimed to measure insulin-like growth factor 1 (IGF1) and growth hormone (GH) in critically and non-critically ill patients with Covid-19 and assess them vis-a-vis clinical and laboratory parameters and prognostic tools.

Subjects and Methods

We included patients who were admitted to the wards or the ICU of the largest Covid-19 referral hospital in Greece; patients with non-Covid-19 pneumonia served as controls. Apart from the routine laboratory work-up for Covid-19 we measured GH and IGF1 (and calculated normalized IGF-1 values as standard deviation scores; SDS), after blood sampling upon admission to the wards or the ICU.

Results

We studied 209 critically and non-critically ill patients with Covid-19 and 39 control patients. Patients with Covid-19 who were ICU non-survivors were older and presented with a worse hematological/biochemical profile (including white blood cell count, troponin, glucose, aminotransferases and lactate dehydrogenase) compared to ICU survivors or Covid-19 survivors in the wards. Overall, IGF-1 SDS was higher in Covid-19 survivors compared to non-survivors (-0.96 ± 1.89 vs -2.05 ± 2.48, respectively, p=0.030). No significant differences were noted in GH between the groups. Nevertheless, in critically ill patients with Covid-19, the prognostic value of IGF-1 (raw data), IGF-1 (SDS) and GH for survival/non-survival was on a par with that of APACHE II and SOFA (with a marginal difference between GH and SOFA).

Conclusion

In conclusion, our findings suggest that there might be an association between low IGF1 (and possibly GH) and poor outcome in patients with Covid-19.
Extent of Surgery and the Prognosis of Unilateral Papillary Thyroid Microcarcinoma
Authors: Zhao Hengqiang , Cui Le
Published: June 2021

It remains controversial whether patients with papillary thyroid microcarcinoma (PTMC) benefit from total thyroidectomy (TT) or thyroid lobectomy (TL). We aimed to investigate the impact of extent of surgery on the prognosis of patients with unilateral PTMC. Patients were obtained from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. Cancer-specific survival (CSS) and overall survival (OS) were evaluated by Cox regression and Kaplan–Meier curves with propensity score matching. Of 31167 PTMC patients enrolled, 22.2% and 77.8% of which underwent TL and TT, respectively. Patients with TT were more likely to be younger, females, present tumors of multifocality, extrathyroidal extension, cervical lymph node metastasis (CLNM), distant metastasis, and receive radioactive iodine (RAI) compared with those receiving TL. The multivariate Cox regression model showed that TT was not associated with an improved CSS and OS compared with TL with hazard ratio (HR) and 95% confidence interval (CI) of 0.53 (0.25-1.12) and 0.86 (0.72-1.04), respectively. In addition, the Kaplan–Meier curves further confirmed the similar survival between TL and TT after propensity score matching. The subgroup analysis showed that TT was associated with better CSS for patients < 55 years, those with tumors of gross extrathyroidal extension, CLNM (N1b), and cases not receiving RAI with HR 95% CI of 0.13 (0.02-0.81), 0.12 (0.02-0.66), 0.11 (0.02-0.64) and 0.36 (0.13-0.90), respectively. TT predicted a trend of better OS for patients with N1b and distant metastasis after adjustment. In addition, TT was associated with better CSS than TL for patients with risk factors like N1b combined with gross extrathyroidal extension, and/or multifocality after matching. In conclusion, TL may be enough for low-risk PTMC patients. TT may improve the prognosis of unilateral PTMC patients with 2 or more risk clinicopathologic factors like CLNM, multifocality, extrathyroidal extension and a younger age compared with TL.
The TP53-Related Signature Predicts Immune Cell Infiltration, Therapeutic Response, and Prognosis in Patients With Esophageal Carcinoma
Authors: Zhang Hongpan , Huang Zheng , Song Yangguang , Yang Zhihao , Shi Qi , Wang Kaige , Zhang Zhiyu , Liu Zheng , Cui Xiaobin , Li Feng
Published: June 2021

TP53 mutation (TP53MUT) is one of the most common gene mutations and frequently occurs in many cancers, especially esophageal carcinoma (ESCA), and it correlates with clinical prognostic outcomes. Nevertheless, the mechanisms by which TP53MUT regulates the correlation between ESCA and prognosis have not been sufficiently studied. Here, in the current research, we constructed a TP53MUT-related signature to predict the prognosis of patients with esophageal cancer and successfully verified this model in patients in the TP53 mutant group, esophageal squamous cell carcinoma group, and adenocarcinoma group. The risk scores proved to be better independent prognostic factors than clinical features, and prognostic features were combined with other clinical features to establish a convincing nomogram to predict overall survival from 1 to 3 years. In addition, we further predicted the tumor immune cell infiltration, chemical drugs, and immunotherapy responses between the high-risk group and low risk group. Finally, the gene expression of the seven-gene signature (AP002478.1, BHLHA15, FFAR2, IGFBP1, KCTD8, PHYHD1, and SLC26A9) can provide personalized prognosis prediction and insights into new treatments.
IL-4-Responsive B Cells Are Detrimental During Chronic Tuberculosis Infection in Mice
Authors: Parihar Suraj P. , Ozturk Mumin , Höft Maxine A. , Chia Julius E. , Guler Reto , Keeton Roanne , van Rensburg Ilana C. , Loxton Andre G. , Brombacher Frank
Published: June 2021

In tuberculosis, T cell-mediated immunity is extensively studied whilst B cells received limited attention in human and mice. Of interest, Mycobacterium tuberculosis (Mtb) does increase IL-4 Receptor-alpha (IL4Rα) expression in murine B cells. To better understand the role of IL4Rα signalling in B cells, we compared wild type mice with B cell-specific IL4Rα deficient mice (mb1creIL-4Rα-/lox mice). Chronic Mtb aerosol infection in mb1creIL-4Rα-/lox mice reduced lung and spleen bacterial burdens, compared to littermate (IL-4Rα-/lox) control animals. Consequently, lung pathology, inflammation and inducible nitric oxide synthase (iNOS) expression were reduced in the lungs of mb1creIL-4Rα-/lox mice, which was also accompanied by increased lung IgA and decreased IgG1 levels. Furthermore, intratracheal adoptive transfer of wild-type B cells into B cell-specific IL4Rα deficient mice reversed the protective phenotype. Moreover, constitutively mCherry expressing Mtb showed decreased association with B cells from mb1creIL-4Rα-/lox mice ex vivo. In addition, supernatants from Mtb-exposed B cells of mb1creIL-4Rα-/lox mice also increased the ability of macrophages to produce nitric oxide, IL-1β, IL-6 and TNF. Together, this demonstrates that IL-4-responsive B cells are detrimental during the chronic phase of tuberculosis in mice with perturbed antibody profiles, inflammatory cytokines and tnf and stat1 levels in the lungs.