bluuebunny/crossref_metadata_2025 huggingface dataset:
The Voice of a Female Rocker Dreaming of Degenderization: A Case of the Frontwoman Hwang So-yoon
Authors:   The Korean Society of Culture and Convergence, Kwon Hyunseok
Published: June 2022

To create the trend of today’s sonic degenderization is ‘gender neutralism.’ This perspective refers to one that aims not to lean on either masculinity or feminity. It is shown in an interesting way in the scene of ‘female-participatory rock’ in the area of popular music that forms part of the sonic world of young people in their twenties. That music has refuted a long-standing gender stereotype that ‘rock is a male genre.’ This movement is subtly sensed in the voice of female rockers. A typical example is offered by Hwang So-yoon, a vocalist and guitarist of the Korean indie rock band Se So Neon(New Boys), Against this background, this paper aims to look at how gender neutralism is displayed through voice, looking at a case study of Hwang. To this end, this study intends to employ an ‘semiotic-vocal approach.’ This is a methodology to examine how a gender-related view of vocalization is shown semiotically and vocally. With this approach, this research finds three things. First, from a ‘vocalism’ seeking degenderization, Hwang forms a ‘sonic semanticity’ of lyrics in a complex way. Second, she produces a ‘convergent and divergent’ voice using a mix of masculine, true voice and feminine falsetto. Third, through those practices, Hwang constructs the self or the other as an ‘existence’ that goes beyond masculinity and feminity. Those practices imply an extension of a boundary area of a rock society pursing degenderization.
Crime Prevention Strategies in Rural Areas of an Aging Society
Authors:   The Korean Society of Culture and Convergence, Huh Koungmi
Published: June 2022

Huh Koungmi(Keimyung University) The purpose of this study was to examine the crime prevention strategies developed and implemented by the United Nations Office on Drugs and Crime and the United States in line with the aging and depopulation of rural areas, and to find ways to supplement and apply them to rural areas in Korea. As a crime prevention strategy in rural areas, the UN Secretariat for Drug Crimes presented local-based crime prevention strategies, life development crime prevention strategies, situational crime prevention strategies, and reintegration strategies as action strategies. In the case of the United States, the federal government, each state government, criminal justice agencies, including local police departments, and regional researchers developed various rural crime prevention strategies together, complementing each other and disseminating it. Representative rural crime prevention strategies include hotspot policing strategy, problemoriented policing, ACTION, Police-Mental Health Provider Co-Responder Model, outreach using social media, and support for criminal recovery through Offender Review Board. This study can be used as a security policy to promote the safety of rural residents, and is expected to trigger follow-up research in related fields.
The Intrinsic Ethics of‘Standing The Human Being Before the AMA’ : Focusing on Instrumentalism of Dewey
Authors:   The Korean Society of Culture and Convergence, Jang Hyejin
Published: June 2022

The purpose of this study is to reveal the “responsibility” of humans in the face of the emergence of “Artificial Moral Agent(AMA)” within the AI ecosystem. The AMA replace human functions and sometimes threaten the status and nature of human existence. The commentator approaches this phenomenon on an ontological level by distinguishing between the AMA and humans. In this study, Dewey’s instrumentalism is a framework for understanding the AI ecosystem. Based on this, the human-AMA relationship is summarized as follows. First, interactive relationships from a factual point of view, second, predominantly species relationships from an ontological point of view, and third, from a functionalist perspective, the humans and AMAs are roles as managers and practitioners, respectively. The key here is that within the AI ecosystem, ‘the human’ is the center of responsibility. Specifically, the realization of this responsibility should be envisioned in three main directions. First, efforts to realize human existence at the ethical level, second, maintenance of the system for the implementation of responsibility that takes into account ethical coherence at the level of science and technology, and third, cooperation at the ethical level and the science and technology level. Through these efforts, we will be able to stand tall as “the human beings in front of the AMA.”
A Strategies for the Production of Stage Arts Contents in Korean Wave: A Study on the Expression Techniques of ‘Seopyonje’ by genre
Authors:   The Korean Society of Culture and Convergence, Choi Hyunkyu
Published: June 2022

This study suggests the planning and production method for the development of original Korean Wave cultural contents based on the expression techniques and characteristics of the novel and movie musical ‘Seopyonje’ made around our traditional folk factor Pansori. By grasping the overall flow of the novel, the author analyzes the message that the artist intends to convey through the work, and examines the metaphorical expression in the article, the situation of reality, and the way of development about the environment. Also, the difference of expression techniques in plot composition of works is examined through genre characteristics of movies and musicals produced by the original works. In addition, through the inner image shown in the poster, I recall the implication of only genre. Especially, the characteristics of stage composition in musical works are analyzed by comparing the meaning of music and dance as a basic framework for constructing traditional madanggeuk. The ‘Seopyonje’, a Madanggeuk designed through this analysis and research, is a Korean Wave cultural product designed for communication with the public, and has the advantage of enjoying various performances regardless of the place. Also, based on the ease of access, it will be possible to increase satisfaction with contents that can experience cultural experiences through participation. Through this, it will be an opportunity to develop into a culture of relative embrace and sharing that directly feels and sympathizes with the culture of indirect approach to seeing and enjoying our culture.,In addition, it creates a creative framework based on the popularity of Korean Wave contents that can easily communicate through the fusion of traditional art and modern art.
Disgust, Race and Ideology in Carl Franklin’sDevil in a Blue Dress
Authors: Flory Dan
Published: June 2022

This article uses Carl Plantinga’s and Noël Carroll’s theorizations regarding cinematic disgust to analyze Carl Franklin’s 1995 film noir, Devil in a Blue Dress. Plantinga argues for a link between disgust and ideology that helps to reveal deeper cultural significance in film, which Carroll’s work likewise supports. Plantinga further argues that disgust in art may be strangely attractive as well as repulsive, thereby eliciting reflection. I argue that combining these elements with philosopher Kwame Anthony Appiah’s explanation of how moral revolutions happen by means of honor codes helps to clarify not only viewer sympathy and solidarity for this film’s African-American protagonist, but also viewer moral disgust at another important white character’s racism. In particular, the film encourages its more thoughtful white viewers to reconsider as well as potentially change their affective responses, ideological predispositions, and habits of perception and attention regarding race, thereby facilitating fundamental moral change and even the possibility of moral revolution.
Humility and Greatness in Damien Chazelle’s First Man
Authors: Magerstaedt Sylvie
Published: June 2022

While philosophical debates about the ethical dimension of cinema have flourished over the last few decades, discussions of cinema and virtues are still limited. And, even if virtues are explored with regard to film, humility is not often the most obvious virtue that comes to mind. As this article argues, this might in part be due to humility’s lack of expressive action and its tendency to remain in the background. In addition, the wide range of philosophical views on what actually counts as virtuous humility, if it is to be considered a virtue at all, further problematises the discussion. One aspect of these disagreements is the question of humility’s compatibility with great achievement. This article aims to demonstrate both how humility can be shown on screen and reveal greatness and humility can go together in practice. For this, the author draws on contemporary philosophical accounts of the virtue of humility to examine Damien Chazelle’s 2018 film First Man, a Neil Armstrong biopic based on James R. Hansen’s biography of the same name. The article outlines how both the distinct portrayal of its main protagonist and the film’s aesthetic features, such as mise-en-scène, sound and editing, are used to convey an idea of humility that reconciles achievement, ambition and greatness with a recognition of sacrifice, serendipity and sometimes the futility of human endeavours. Consequently, First Man is not only a film about a humble main character, but also indicates how cinematic techniques can be used effectively to enable us to experience humility, thus demonstrating how films can make a distinct contribution to philosophical debates about virtues beyond mere illustration.
Hegel and Hitchcock’s Vertigo: On Reconciliation
Authors: Shaul Dylan
Published: June 2022

This article reconstructs and evaluates a debate between Pippin and Žižek over the proper interpretation of Hitchcock’s Vertigo, in relation to Hegel’s concept of reconciliation. Both Pippin and Žižek agree that Vertigo exemplifies Hegelian reconciliation: Scottie exhibits Hegel’s reconciliatory “negation of negation” when he realizes that his lost love Madeleine had really been Judy all along, thereby losing his original loss. Yet Pippin and Žižek disagree on the precise significance of the concept of reconciliation both for the film and for the contemporary world. Žižek argues for a revolutionary reading of reconciliation in Vertigo: we learn from reconciliation that we must make a revolutionary break from the present world, in order to bring about a wholly new world. Pippin argues for a reformist reading of reconciliation in Vertigo: we learn from reconciliation that we must find the “traces of reason” latent in the present world, in order to gradually reform it for the better. Ultimately, I argue that Žižek’s reading offers the more authentically Hegelian approach to interpreting Hitchcock’s Vertigo. But if nothing else, the Pippin-Žižek debate demonstrates the profound intellectual fecundity of the intersections between film and philosophy for understanding our current historical moment.
Receptivity, Simultaneity: The Thin Red Line as Ecological Cinematic Poesis
Authors: Burch Paul W.
Published: June 2022

I adapt Robert Sinnerbrink's notion of cinematic poesis by arguing that Terrence Malick's The Thin Red Line constitutes an example of ecological cinematic poesis: a style of filmmaking that works in concert with the limits and potentialities of the filmmaking as a medium. This cinematic bearing emerges in a new way following Malick's return to Hollywood, where a combination of factors spur the emergence of a radical Emersonian practice of cinematic receptivity. I draw on oral histories, and the film itself, to demonstrate how Malick's creative process consistently tends towards an ethos of poverty. To further pattern and illuminate the ecological stakes of this Emersonian stance, I draw on the complementary framework of second-order systems theory, and in particular, on Niklas Luhmann's concept of simultaneity. In so doing, I outline the layered nature of Malick's cinematic praxis – a doubled Emersonian receptivity which not only invites defamiliarizing depictions of warfare and the nonhuman, but also welcomes, and toys with, the otherness haunting technical images and human cognition. As such, The Thin Red Line, and its immediate counterparts, perform the ecological work of reframing the conditions of wonder, asking us to marvel not at what we have seen, but what we haven’t.
William Popple's Horatian Satires: Further Texts from the Osborn Manuscript
Authors: Gillespie Stuart
Published: June 2022

Samples of William Popple's unprinted Horatian imitations of the 1750s appeared in this journal in 2007 (Vol. 16 Part 2), their texts taken from two manuscript volumes at the Beinecke Rare Books and Manuscripts Library. The best of Popple's remaining, and still unpublished, Satires of Horace are here edited and printed: Satires 1.4, 1.6, 1.9, 2.1, and 2.3. At the same time, fuller information now available on Popple, and on the social and professional circles to which these works make reference, allows some further account of the historical and biographical context of these Horatian imitations.
Problems faced by the crop farmers related to extension services provided by department of agricultural extension in Bangladesh
Authors: Rahman Saifur , Hoque Mohammad J. , Uddin Mohammed N.
Published: June 2022

The Department of Agricultural Extension (DAE) has a long history of providing extension services to Bangladesh's crop farmers. This study attempted to explore the extent of problems that crop farmers faced regarding acquiring the extension services provided by DAE. This study was conducted in three villages of Gauripur Upazila (sub-district) in Mymensingh district, Bangladesh. A face-to-face interview was conducted with 100 sampled farmers for the data collection on a pre-tested and structured interview schedule. The key variable, named as the extent of problems was measured using a 4-point rating scale. Both enter and step-wise regression models were employed on the data. Results indicated that half of the respondents faced a moderate level of problems while 40% faced a high level of problems. The extension workers' poor communication skill was the most critical issue, followed by insufficient resources and maintaining contact with resource-rich farmers as perceived by the respondents. Crop farmers' education, perceived economic return, the experience of participating in extension activities, training, and fatalism were significantly associated with the problems faced by them. Education, perceived economic return, the experience of participating in extension activities, and training were discovered to be essential determinants of the degree of problems related to extension services. The study identified several chances for the policymakers to address influential factors for improving crop extension services of DAE. Furthermore, improved coordination and providing crop farmers with need-based training and resources may help mitigate the identified issues.
Problematic issues of determining the object of criminal offences against agro-industry
Authors: Sobko Ganna , Khovpun Oleksii , Dei Maryna O. , Frantsuz Anatoliy Y. , Yermakova Hanna
Published: June 2022

Active support for agro-industry development is reflected in the harmonization of the interests of government and business. The organization of interaction between government and agro-industrial structures for the purpose of consistent socio-economic development creates the foundation of Ukraine's stability in general and its food security in particular, but against this background, not everyone is a bona fide entrepreneur and sometimes tries to profit by obtaining loans for non-existent firms. The article is aimed at understanding and studying the object of protection of public relations in the field of agro-industry, as well as the subject of encroachment. Criminal offences against the environment were considered and conclusions were drawn regarding the object of protection, location and subject matter. The place of the agro-industrial complex in the country's economy is analyzed. The statistical indicators on criminal offences in the field of environment related to agro-industry for the last three years are studied, in addition, the regional indicators of criminality on the specified criminal offences are focused, and also attention is paid to convictions on general and special signs of committing criminal offences against the environment and related agro-industrial criminal offences. The world experience in support of the agro-industrial complex in different countries is investigated. Some conclusions have been drawn on the differences between Ukrainian legislation and the legislation of other countries, for example on the sectoral affiliation of criminal offences in the field of the agro-industrial complex to criminology, which according to statistics can identify risks and thus prevent subsidies to certain enterprises.
Tourism enterprise creation management electronically online
Authors: Maliar Dmytro , Mytrofanova Hanna Y. , Kovtun Nataliia S. , Yedynak Volodymyr , Yedynak Tetiana S.
Published: June 2022

The e-commerce growth, the increasing role of social networks in promoting the image and products of enterprises, the automation of technological processes in the enterprises, and the spread of remote work around the world lead to the digitalization of economic entities. The purpose of the article is to study the peculiarities of the tourism enterprise creation in an electronic way while minimizing the founding organizational actions carried out in person, in the traditional way. The study is based on a systematic analysis of all organizational actions for enterprise creation exclusively with the use of information and communication technologies based on the differentiated digitization of founding activities. All organizational actions for the establishment of an enterprise, without any exception, are divided into two categories: a) traditional, carried out in the usual way, i.e. by visiting all the necessary government agencies, holding a founding meeting, visiting banks to open a current account, etc. (offline mode); b) electronic, conducted solely remotely, i.e. with the help of information and communication technologies without attending any institutions and meetings (online mode). The comparison of the scope and content of such measures allows us to emphasize the introduction of the concept of "electronic enterprises" into scientific use by the criterion of their origin, as well as the introduction of indicators of average and marginal propensity to digitize. In the study, it was found out that the criterion of enterprise creation is followed by the next pattern of enterprise digitalization. The practical value of this article is the proposed methods for calculating the average and marginal propensity of tourism enterprises to digitize by the criterion of their creation, as well as proposed specific areas for further in-depth enterprise digitization at the stage of their formation.
Legal regulation of investment and innovation in the tourism sphere
Authors: Aparov Andrii M. , Ivanii Olena M. , Kolyshkin Oleksandr V. , Hvozdetska Svitlana V. , Shapovalova Olha V.
Published: June 2022

The realities of today’s life of Ukrainian society, the pro-European course of development and activity chosen by the nation, the favourable geopolitical position of Ukraine, etc. along with other strategically important circumstances in the development of state-legal and social institutions of our state and nation naturally led to the emergence of the need to improve analytical approaches to the development of investment and innovative support for the tourism sphere of life of Ukrainian society. The research aims to analyse the features of the legal content of the categories that are within the framework of research on the subject of work and the legal forms that social relations acquire, which in this regard develop in society. The aim of the work is also to try to form our own legal view on the current state and prospects for the development of legal support for the relevant issue. The leading research methods are theoretical – analysis-synthesis, induction-deduction, abstraction. The scope of issues raised in this work concerns a fairly complex framework of sectoral and legal regulation: administrative, international, civil, economic, etc.
Organization of financial and economic security management of port activities
Authors: Shyriaieva Liudmyla , Chiz Liudmyla , Koretska Olga , Khoteyeva Natalia , Petrova Anastasiia
Published: June 2022

The purpose of this article is to develop a model and proposals for the organization of management of financial and economic security (FESM) of port enterprises (PE). Improvement of the management of financial and economic security we propose to begin with the development of methodological approaches to assessment of the level of financial and economic security. To do this, the article makes a proposal to use a functional criterion, which is defined as the ratio of costs for the organization and operation of the financial security service to the profit obtained during the period of the study. Also, a set of indicators is developed that, unlike existing ones, take into account specifics of the industry. The article also proposes optimal plans for cargo processing, which result in a minimum cost and maximum profit. Through the function of process management, a comprehensive statistical model of managing the system of financial and economic security of port enterprises is proposed. This model takes into account specific factors of PE operation and developed approaches that ensure the organization of PE FES management by embracing traditional financial approaches and their alternatives. The authors state that for the effective organization of financial and economic security of port enterprises it is necessary to conduct timely monitoring of external and internal threats, assess and analyze the level of financial and economic security and develop strategic ways of enterprise development. And the recommendation to the management is to carry out well-timed control and audit of financial condition.
Determining the role of agriculture towards urbanization: testing the hypothesis
Authors: Riaz Noman , Akram Waseem , Javed Iqbal
Published: June 2022

The current study has examined the role of agriculture in urbanization. The study used time series data from 1983-2017. The order of integration of data suggested the estimation of an autoregressive distributed lag model for analysis. The study also used (Bayer and Hanck, 2012) combine cointegration to check the consistency of the cointegration relationship between agriculture growth and urbanization in the presence of other regressors. The empirical results showed that growth in the agriculture sector decreased urbanization. Whereas, problematic urbanization can be controlled through the development of the agriculture sector of the economy. The government can improve the agriculture sector by providing incentives to the farming community in the selected potential areas of agriculture, Like value addition and livestock. Improvement of the agricultural financial system of Pakistan can play a significant role.
Electrostatic quantum dark energy in a seven-dimensional universe
Authors: Kesanasetty Sasidhar
Published: June 2022

This paper explains the dark energy and acceleration of the universe by quantizing the space in the hidden dimensions and provides the basis and background for the gravitational force through the curvature of space-time. Space-time is considered to be made of a four-dimensional elastic grid in a seven-dimensional universe in which matter also expands along with the universe. Each cube of the grid is considered a quantum of hidden three-dimensional space of Planck volume containing Planck charge, which makes the universe seven-dimensional. The dark energy is explained by the electrostatic repulsion between the Planck charges in each quantum of the hidden space. Mathematically, this electrostatic repulsion is related to the Hubble constant to explain the accelerated expansion due to dark energy and the increase in mass of matter.
SLAVERY, SLAVE TRADE AND MANUMISSION IN GOJJAM, ETHIOPIA, 1940S-1950S.
Authors:   DebreMarkos University, Department of History and Heritage Management, SEYOUM AYENEW MAMMO
Published: June 2022

Like in other African countries, in Ethiopia slavery and slave trade were practiced for centuries and had been endemic to the society In this article, I have made an attempt to bring out the efforts of different emperors, particularly Emperor Haile Sellassie’s period in order to regulate and prohibit slavery and slave trade in Ethiopia and to discuss the existence of the institutions and the practice until the 1950s. The attempt of the Ethiopian rulers to regulate or prohibit the slave trade in slaves failed to owe to several reasons. Anyway, the most serious laws making the beginning of the end for the institution of slavery in Ethiopia came in the 1920s. In an attempt to counter European criticism, Rastafari issued an edict in 1923 and 1924 imposing heavy penalties on the slave trade without, however, abolishing the legal status of slavery itself. Later, Ethiopia became a signatory to the ‘Slavery Convention of 1926.’ The official policy of the Ethiopian government against the slave trade, however, did little to stop the regional warlords from continuing to raid the borderlands for slaves. The continuation of slave trading and slavery itself in Ethiopia into the 1930s, the involvement of the state in the trade, and the continued use of slaves in the royal court were directly contrary to the public statements of Emperor Haile Sellassie I and the legal commitments of the Ethiopian state. Immediately after the evacuation of the Italian although Emperor Haile Sellassie made efforts to prohibit the trade in slaves, it continued to flourish. Even in 1942, he issued an edict imposing heavy punishment on those who were involved either in capturing or kidnapping, or selling slaves. Nonetheless, this does not mean that it came to an end. For this, I have discovered archival evidence in the Debre Markos Administrative Office and Higher Court House of Eastern Gojjam Zone, and in Dangla and Metekel administrative offices. Accordingly, the archives I discovered have three categories: the first deals with people who were accused of catching, kidnapping, and selling slaves on the basis of an eyewitness who was punished from seven to twenty years of imprisonment. The second category is dealing with people who were accused of kidnapping and selling individuals as slaves for money but for lack of witnesses, who were pardoned and set free. The third phase is connected with the people who after capturing and kidnapping individuals with the intent to sell them to slavery but because of the absence of a purchaser, treated them brutally. The sources are critically collected, scrutinize, and analyzed and their validities are cross-checked one against the other. Finally, as historical research, the paper is based on a systematic selection, collection, and analysis of archival documents, manuscripts, and secondary sources both published and unpublished.
DISTRAKSI VISUAL VIDEO ANIMASI DAN VIRTUAL REALITY DALAM MENGURANGI KECEMASAN ANAK USIA 7-10 TAHUN PADA TINDAKAN ANESTESI INFILTRASI
Authors: Lubis Ika Anisyah , Wibisono Witriana Latifa , Sjamsul Rini Triani , Oewen Roosje Rosita
Published: June 2022

Introduction: Dental practitioners have numerous methods to control anxiety and pain in children, and distracting the child appears to be the most command technique used for behavior management during dental procedures. The audiovisual technique is used as a distraction method for reducing anxiety. This study aimed to compare the efficacy of using an audiovisual animation video and virtual reality distraction toward anxiety alteration on children age 7-10 years old on infiltration anesthesia. Method: The design of this study was pretest and post-test, thirty-two children were divided into two groups namely animation video group (n=16) and virtual reality groups distraction (n=16). Result: The efficacy of animation video distraction by 48,9% while using virtual reality is 43,75%. Data analysis using an independent t-test which results in a p-value less than 0,05 in which it was showed non-significant differences between the two groups. Conclusion: The two methods of distraction both animation video and virtual reality have the same effect on reducing anxiety in children age 7-10 years old on filtration anesthesia.
A Review of Transition Metal Dichalcogenides-Based Biosensors
Authors: Sun Hongyu , Li Dujuan , Yue Xiaojie , Hong Rui , Yang Weihuang , Liu Chaoran , Xu Hong , Lu Jun , Dong Linxi , Wang Gaofeng , Li Dongyang
Published: June 2022

Transition metal dichalcogenides (TMDCs) are widely used in biosensing applications due to their excellent physical and chemical properties. Due to the properties of biomaterial targets, the biggest challenge that biosensors face now is how to improve the sensitivity and stability. A lot of materials had been used to enhance the target signal. Among them, TMDCs show excellent performance in enhancing biosensing signals because of their metallic and semi-conducting electrical capabilities, tunable band gap, large specific surface area and so on. Here, we review different functionalization methods and research progress of TMDCs-based biosensors. The modification methods of TMDCs for biosensor fabrication mainly include two strategies: non-covalent and covalent interaction. The article summarizes the advantages and disadvantages of different modification strategies and their effects on biosensing performance. The authors present the challenges and issues that TMDCs need to be addressed in biosensor applications. Finally, the review expresses the positive application prospects of TMDCs-based biosensors in the future.
Calreticulin Identified as One of the Androgen Response Genes That Trigger Full Regeneration of the Only Capable Mammalian Organ, the Deer Antler
Authors: Guo Qianqian , Zheng Junjun , Ba Hengxing , Sun Hongmei , Zhai Jingjie , Wang Wenying , Li Chunyi
Published: June 2022

Deer antlers are male secondary sexual characters that develop to become bone; they are unique appendages that, once lost, can fully regenerate from the permanent bony protuberances or pedicles. Pedicle periosteum (PP) is the tissue that gives rise to the regenerating antlers with three differentiation stages, namely, dormant (DoPP), potentiated (PoPP), and activated (AcPP). Thus far, the transition from the PoPP to the AcPP has not been studied. Our results showed that the AcPP cells maintained their original stem cell features by expressing mesenchymal stem cell (MSC) markers CD73, CD90, and CD105, although they had entered the proliferation mode. The differentially expressed genes (DEGs) in the AcPP compared with those of the PoPP were mainly involved in protein processing, cell cycle, and calcium signaling pathways. Calreticulin (CALR), an androgen response gene, was significantly differentially upregulated in the AcPP cells, and its expression level was negatively regulated by androgens, in contrast to the currently known model systems where all regulation is positive. The downregulation of CALR expression in the AcPP cells in vitro inhibited cell proliferation, induced apoptosis, and inhibited cell cycle progression at G1-S transition. Therefore, CALR is likely a downstream mediator of androgen hormones for triggering initiation of antler regeneration. We believe that the identification of CALR has not only discovered “one critical piece” of the “jigsaw puzzle” in the initiation of antler regeneration but also helps in revealing the mechanism underlying this unique mammalian epimorphic regeneration and has also opened a new avenue for the study of the nature of CALR regulation by androgen (putative binding partners), thus facilitating the identification of potential molecule(s) for investigation as targets for clinical evaluation.
Telomere Attrition in Induced Pluripotent Stem Cell-Derived Neurons From ALS/FTD-Related C9ORF72 Repeat Expansion Carriers
Authors: Robinson Hayley , Ali Sk Imran , Diaz-Hernandez Martha Elena , Lopez-Gonzalez Rodrigo
Published: June 2022

The GGGGCC (G4C2) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dysregulated DNA damage response and the generation of reactive oxygen species (ROS) have been postulated as major drivers of toxicity in C9ORF72 pathogenesis. Telomeres are tandem-repeated nucleotide sequences that are located at the end of chromosomes and protect them from degradation. Interestingly, it has been established that telomeres are sensitive to ROS. Here, we analyzed telomere length in neurons and neural progenitor cells from several induced pluripotent stem cell (iPSC) lines from control subjects and C9ORF72 repeat expansion carriers. We found an age-dependent decrease in telomere length in two-month-old iPSC-derived motor neurons from C9ORF72 carriers as compared to control subjects and a dysregulation in the protein levels of shelterin complex members TRF2 and POT1.
Epigenetic DNA Methylation Signatures Associated With the Severity of Paget’s Disease of Bone
Authors: Diboun Ilhame , Wani Sachin , Ralston Stuart H. , Albagha Omar M. E.
Published: June 2022

Background: Paget’s disease of bone (PDB) is characterized by focal areas of dysregulated bone turnover resulting in increased bone loss and abnormal bone formation with variable severity. PDB has a complex etiology and both genetics and environmental factors have been implicated. A recent study has identified many differentially methylated loci in PDB compared to healthy subjects. However, associations between DNA methylation profiles and disease severity of PDB have not been investigated.

Objectives: To investigate the association between DNA methylation signals and PDB severity.

Methods: Using 232 well-characterized PDB subjects from the PRISM trial, a disease severity score was devised based on the clinical features of PDB. DNA methylation profiling was performed using Illumina Infinium HumanMethylation 450K array.

Results: We identified 100 CpG methylation sites significantly associated with PDB severity at FDR <0.05. Additionally, methylation profiles in 11 regions showed Bonferroni-significant association with disease severity including six islands (located in VCL, TBX5, CASZ1, ULBP2, NUDT15 and SQSTM1), two gene bodies (CXCR6 and DENND1A), and 3 promoter regions (RPL27, LINC00301 and VPS29). Moreover, FDR-significant effects from region analysis implicated genes with genetic variants previously associated with PDB severity, including RIN3 and CSF1. A multivariate predictor model featuring the top severity-associated CpG sites revealed a significant correlation (R = 0.71, p = 6.9 × 10−16) between observed and predicted PDB severity scores. On dichotomizing the severity scores into low and high severity, the model featured an area under curve (AUC) of 0.80, a sensitivity of 0.74 and a specificity of 0.68.

Conclusion: We identified several CpG methylation markers that are associated with PDB severity in this pioneering study while also highlighting the novel molecular pathways associated with disease progression. Further work is warranted to affirm the suitability of our model to predict the severity of PDB in newly diagnosed patients or patients with family history of PDB.
FBXO38 Ubiquitin Ligase Controls Sertoli Cell Maturation
Authors: Dibus Nikol , Zobalova Eliska , Monleon Mario A. M. , Korinek Vladimir , Filipp Dominik , Petrusova Jana , Sedlacek Radislav , Kasparek Petr , Cermak Lukas
Published: June 2022

The ubiquitin ligase SCFFBXO38 controls centromeric chromatin by promoting the degradation of the ZXDB protein. To determine the importance of this pathway during development, Fbxo38-deficient mice were generated. The loss of FBXO38 resulted in growth retardation affecting several organs, including the male reproductive system. A detailed analysis of the mutant testes revealed pathological changes in the seminiferous tubules, accompanied by a significant decrease in sperm production and reduced fertility. In adult testes, FBXO38 was specifically expressed in Sertoli cells, a somatic population essential for spermatogenesis initiation and progression. Sertoli cells lacking FBXO38 exhibited stabilized ZXDB protein and upregulated centromeric chromatin. Furthermore, the gene expression profile revealed that the absence of FBXO38 led to a defect in Sertoli cell maturation, specifically characterized by dysregulation in genes controlling retinoic acid metabolism and intercellular communication. Consequently, we documented significant changes in their ability to initiate spermatogonial differentiation. In conclusion, we show that FBXO38 acts as a Sertoli cell maturation factor, affecting the Sertoli cell transcription program, centromere integrity, and, subsequently, the ability to control spermatogenesis.
Lipidic Profile Changes in Exosomes and Microvesicles Derived From Plasma of Monoclonal Antibody-Treated Psoriatic Patients
Authors: Paolino Giovanni , Buratta Sandra , Mercuri Santo R. , Pellegrino Roberto M. , Urbanelli Lorena , Emiliani Carla , Bertuccini Lucia , Iosi Francesca , Huber Veronica , Brianti Pina , Prezioso Caterina , Di Nicola Matteo R. , Federici Cristina , Lugini Luana
Published: June 2022

Psoriasis is a chronic immune-mediated inflammatory skin disorder affecting children and adults. To date no approved biomarkers for diagnosis of this disease and follow up of patients have been translated into clinical practice. Recently, extracellular vesicles (EVs) secreted by all cells and present in almost all biological fluids are playing a crucial role in diagnosis and follow up of several diseases, including psoriasis. Since many psoriatic patients show altered plasma lipid profiles and since EVs have been involved in psoriasis pathogenesis, we studied the phospholipid profile of EVs, both microvesicles (MV) or exosomes (Exo), derived from plasma of psoriatic patients undergoing systemic biological treatment (secukinumab, ustekinumab, adalimumab), in comparison with EVs of untreated patients and healthy donors (HD). EVs were evaluated by immune electronmicroscopy for their morphology and by NanoSight for their amount and dimensions. EV phospholipid profiling was performed by High Resolution Liquid Chromatography-Mass Spectrometry and statistical Partial Least Squares Discriminant Analysis. Our results demonstrated that psoriatic patients showed a higher concentration of both MV and Exo in comparison to EVs from HD. The phospholipid profile of Exo from psoriatic patients showed increased levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol and lysoPC compared to Exo from HD. Sphingomyelin (SM) and phosphatidylinositol (PI) are the only phospholipid classes whose levels changed in MV. Moreover, the therapy with ustekinumab seemed to revert the PE and PC lipid composition of circulating Exo towards that of HD and it is the only one of the three biological drugs that did not alter SM expression in MV. Therefore, the determination of lipid alterations of circulating EVs could harbor useful information for the diagnosis and drug response in psoriatic patients.
Molecular Interactions From the Density Functional Theory for Chemical Reactivity: The Interaction Energy Between Two-Reagents
Authors: Miranda-Quintana Ramón Alain , Heidar-Zadeh Farnaz , Fias Stijn , Chapman Allison E. A. , Liu Shubin , Morell Christophe , Gómez Tatiana , Cárdenas Carlos , Ayers Paul W.
Published: June 2022

Reactivity descriptors indicate where a reagent is most reactive and how it is most likely to react. However, a reaction will only occur when the reagent encounters a suitable reaction partner. Determining whether a pair of reagents is well-matched requires developing reactivity rules that depend on both reagents. This can be achieved using the expression for the minimum-interaction-energy obtained from the density functional reactivity theory. Different terms in this expression will be dominant in different circumstances; depending on which terms control the reactivity, different reactivity indicators will be preferred.
Genome Sequence Analysis and Characterization of Shiga Toxin 2 Production by Escherichia coli O157:H7 Strains Associated With a Laboratory Infection
Authors: Eppinger Mark , Almería Sonia , Allué-Guardia Anna , Bagi Lori K. , Kalalah Anwar A. , Gurtler Joshua B. , Fratamico Pina M.
Published: June 2022

A laboratory-acquired E. coli O157:H7 infection with associated severe sequelae including hemolytic uremic syndrome occurred in an individual working in the laboratory with a mixture of nalidixic acid-resistant (NalR) O157:H7 mutant strains in a soil-biochar blend. The patient was hospitalized and treated with an intravenous combination of metronidazole and levofloxacin. The present study investigated the source of this severe laboratory acquired infection and further examined the influence of the antibiotics used during treatment on the expression and production of Shiga toxin. Genomes of two Stx2a-and eae-positive O157:H7 strains isolated from the patient’s stool were sequenced along with two pairs of the wt strains and their derived NalR mutants used in the laboratory experiments. High-resolution SNP typing determined the strains’ individual genetic relatedness and unambiguously identified the two laboratory-derived NalR mutant strains as the source of the researcher’s life-threatening disease, rather than a conceivable ingestion of unrelated O157:H7 isolates circulating at the same time. It was further confirmed that in sublethal doses, the antibiotics increased toxin expression and production. Our results support a simultaneous co-infection with clinical strains in the laboratory, which were the causative agents of previous O157:H7 outbreaks, and further that the administration of antibiotics may have impacted the outcome of the infection.
Science Communication in Public Radio: The Case Study of MindTap
Authors: Greeves Scott B. , Ledbetter Rhesa N.
Published: June 2022

Radio broadcasting is an integral medium for the public understanding of science. Yet, as a poorly recognized health disorder, mental health was not commonly discussed in U.S radio broadcasts until the early 1980s. Since then, mental health has increasingly been the subject of societal discourse and is now frequently the topic of focus for radio programming. Despite the increased attention on mental health, little academic inquiry has considered how science communicators may navigate locally complex and sensitive themes, such as those related to mental health. To address this gap, we discuss our experiences in producing a radio series on mental health called MindTap. Using the exemplar of MindTap, we explore models of science communication and their application within radio communication. Specifically, we suggest that topics, such as mental health, are best approached using the dialogue model of communication, which recognizes the value of integrating experiential and culturally situated knowledge with that of expert knowledge. We also illustrate how this form of communication supports narrative creation, and as such, identify practical insights for practitioners seeking to produce a mental health radio series.
Low-Voltage Area at the Anterior Wall of the Left Atrium Is Associated With Thromboembolism in Atrial Fibrillation Patients With a Low CHA2DS2-VA Score
Authors: Ding Xiangwei , Li Mingfang , Chen Hongwu , Yang Gang , Zhang Fengxiang , Ju Weizhu , Gu Kai , Li Jianqing , Chen Minglong
Published: June 2022

Background

Non-valvular atrial fibrillation (NVAF) in patients at low risk of thromboembolism (TE) does not mean “no risk.” We sought to assess the risk factors associated with TE in clinically low-risk AF patients with a non-gender CHA2DS2-VASc score (CHA2DS2-VA score) of 0 or 1.

Methods

In this single-center cross-sectional study, NVAF patients with a CHA2D-VA score of 0 or 1 who underwent index high-density bipolar voltage mapping of the left atrium (LA) and AF ablation were consecutively enrolled from 2017 to 2020. The population was divided into patients with and without TE history before voltage mapping. AF patients with CHA2DS2-VA score of 0 to 1 before TE (TE group) were analyzed and compared with clinically low-risk AF patients without TE history (non-TE group). The association among LA low voltage area (LVA), other clinical factors and TE history was analyzed with logistic regression.

Results

In the TE group, LVA was more prevalent [15/25 (60%) vs. 105/359 (29.2%), p = 0.003] and more preferentially located at the anterior wall [8/15 (53%) vs. 24/105 (23%), p = 0.025]. Among patients with LVA, the activation time from the sinus node to the left atrial appendage was significantly longer in the TE group (77.09 ± 21.09 vs. 57.59 ± 15.19 ms, p < 0.001). Multivariate analysis demonstrated that LVA at the anterior wall of the LA [OR: 4.17 (95% CI: 1.51 to 11.51); p = 0.006] and being female [OR: 3.40 (95% CI: 1.36 to 8.51); p = 0.009] were associated with TE history.

Conclusions

LVA at the anterior wall of the LA is associated with TE history in NVAF patients with a low CHA2DS2-VA score.
Trends in Ezetimibe Prescriptions as Monotherapy or Fixed-Dose Combination in Germany 2012–2021
Authors: Katzmann Julius L. , Kieble Marita , Enners Salka , Böhm Michael , Mahfoud Felix , Laufs Ulrich , Schulz Martin
Published: June 2022

Aims

Addition of ezetimibe to statin therapy is recommended by current guidelines when low-density lipoprotein cholesterol (LDL-C) targets are not achieved with statin monotherapy. Fixed-dose combinations (FDC) improve medication adherence and facilitate risk factor control. We assessed prescription trends of ezetimibe as monotherapy or FDC with statins.

Methods

Data from the German Institute for Drug Use Evaluation (DAPI) containing dispensing data of >80% of community pharmacies were analyzed. Prescriptions over time of lipid-lowering agents at the expense of the statutory health insurance (SHI) were extrapolated to all SHI-insured persons, representing approximately 88% of the total German population. Drug utilization was expressed as defined daily doses per 1,000 SHI-insured persons per day (DID).

Results

Of all lipid-lowering drug prescriptions in 2021, 91.2% were statin monotherapy. Ezetimibe was prescribed as monotherapy or FDC with statin in 4.4 and 2.9%, respectively. DID steadily increased for statin (69%) and ezetimibe (424%) monotherapies between 2012 and 2021. In contrast, statin-ezetimibe FDC prescriptions exhibited only a minor increase (29%). The proportion of statin-ezetimibe FDC among all statin prescriptions was stable over time at approximately 3%. FDC prescription rates by specialists were higher compared to general practitioners and varied considerably between geographic areas.

Conclusion

Combination lipid-lowering therapy is prescribed to a minority of patients. Prescriptions of ezetimibe as monotherapy increased to a much greater extent than statin-ezetimibe FDC. Considering the low proportion of patients achieving their LDL-C target and improved adherence to FDC compared to separate pills, statin-ezetimibe FDC may be utilized to improve the management of dyslipidemia.