bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating distribution kinetics and toxicodynamics to assess repeat dose neurotoxicity in vitro using human BrainSpheres: a case study on amiodarone
Authors: Nunes Carolina , Proença Susana , Ambrosini Giovanna , Pamies David , Thomas Aurélien , Kramer Nynke I. , Zurich Marie-Gabrielle 
Published: September 2023

For ethical, economical, and scientific reasons, animal experimentation, used to evaluate the potential neurotoxicity of chemicals before their release in the market, needs to be replaced by new approach methodologies. To illustrate the use of new approach methodologies, the human induced pluripotent stem cell-derived 3D model BrainSpheres was acutely (48 h) or repeatedly (7 days) exposed to amiodarone (0.625–15 µM), a lipophilic antiarrhythmic drug reported to have deleterious effects on the nervous system. Neurotoxicity was assessed using transcriptomics, the immunohistochemistry of cell type-specific markers, and real-time reverse transcription–polymerase chain reaction for various genes involved in the lipid metabolism. By integrating distribution kinetics modeling with neurotoxicity readouts, we show that the observed time- and concentration-dependent increase in the neurotoxic effects of amiodarone is driven by the cellular accumulation of amiodarone after repeated dosing. The development of a compartmental in vitro distribution kinetics model allowed us to predict the change in cell-associated concentrations in BrainSpheres with time and for different exposure scenarios. The results suggest that human cells are intrinsically more sensitive to amiodarone than rodent cells. Amiodarone-induced regulation of lipid metabolism genes was observed in brain cells for the first time. Astrocytes appeared to be the most sensitive human brain cell type in vitro. In conclusion, assessing readouts at different molecular levels after the repeat dosing of human induced pluripotent stem cell-derived BrainSpheres in combination with the compartmental modeling of in vitro kinetics provides a mechanistic means to assess neurotoxicity pathways and refine chemical safety assessment for humans.
Optimal type and dose of hypoxic training for improving maximal aerobic capacity in athletes: a systematic review and Bayesian model-based network meta-analysis
Authors: Feng Xinmiao , Zhao Linlin , Chen Yonghui , Wang Zihao , Lu Hongyuan , Wang Chuangang 
Published: September 2023

Objective: This study aimed to compare and rank the effect of hypoxic practices on maximum oxygen consumption (VO2max) in athletes and determine the hypoxic dose-response correlation using network meta-analysis.Methods: The Web of Science, PubMed, EMBASE, and EBSCO databases were systematically search for randomized controlled trials on the effect of hypoxc interventions on the VO2max of athletes published from inception until 21 February 2023. Studies that used live-high train-high (LHTH), live-high train-low (LHTL), live-high, train-high/low (HHL), intermittent hypoxic training (IHT), and intermittent hypoxic exposure (IHE) interventions were primarily included. LHTL was further defined according to the type of hypoxic environment (natural and simulated) and the altitude of the training site (low altitude and sea level). A meta-analysis was conducted to determine the standardized mean difference between the effects of various hypoxic interventions on VO2max and dose-response correlation. Furthermore, the hypoxic dosage of the different interventions were coordinated using the “kilometer hour” model.Results: From 2,072 originally identified titles, 59 studies were finally included in this study. After data pooling, LHTL, LHTH, and IHT outperformed normoxic training in improving the VO2max of athletes. According to the P-scores, LHTL combined with low altitude training was the most effective intervention for improving VO2max (natural: 0.92 and simulated: 0.86) and was better than LHTL combined with sea level training (0.56). A reasonable hypoxic dose range for LHTH (470–1,130 kmh) and HL (500–1,415 kmh) was reported with an inverted U-shaped curve relationship.Conclusion: Different types of hypoxic training compared with normoxic training serve as significant approaches for improving aerobic capacity in athletes. Regardless of the type of hypoxic training and the residential condition, LHTL with low altitude training was the most effective intervention. The characteristics of the dose-effect correlation of LHTH and LHTL may be associated with the negative effects of chronic hypoxia.
Daily injection of the β2 adrenergic agonist clenbuterol improved poor muscle growth and body composition in lambs following heat stress-induced intrauterine growth restriction
Authors: Gibbs Rachel L. , Swanson Rebecca M. , Beard Joslyn K. , Hicks Zena M. , Most Micah S. , Beer Haley N. , Grijalva Pablo C. , Clement Shawna M. , Marks-Nelson Eileen S. , Schmidt Ty B. , Petersen Jessica L. , Yates Dustin T. 
Published: September 2023

Background: Intrauterine growth restriction (IUGR) is associated with reduced β2 adrenergic sensitivity, which contributes to poor postnatal muscle growth. The objective of this study was to determine if stimulating β2 adrenergic activity postnatal would rescue deficits in muscle growth, body composition, and indicators of metabolic homeostasis in IUGR offspring.Methods: Time-mated ewes were housed at 40°C from day 40 to 95 of gestation to produce IUGR lambs. From birth, IUGR lambs received daily IM injections of 0.8 μg/kg clenbuterol HCl (IUGR+CLEN; n = 11) or saline placebo (IUGR; n = 12). Placebo-injected controls (n = 13) were born to pair-fed thermoneutral ewes. Biometrics were assessed weekly and body composition was estimated by ultrasound and bioelectrical impedance analysis (BIA). Lambs were necropsied at 60 days of age.Results: Bodyweights were lighter (p ≤ 0.05) for IUGR and IUGR+CLEN lambs than for controls at birth, day 30, and day 60. Average daily gain was less (p ≤ 0.05) for IUGR lambs than controls and was intermediate for IUGR+CLEN lambs. At day 58, BIA-estimated whole-body fat-free mass and ultrasound-estimated loin eye area were less (p ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. At necropsy, loin eye area and flexor digitorum superficialis muscles were smaller (p ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. Longissimus dorsi protein content was less (p ≤ 0.05) and fat-to-protein ratio was greater (p ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. Semitendinosus from IUGR lambs had less (p ≤ 0.05) β2 adrenoreceptor content, fewer (p ≤ 0.05) proliferating myoblasts, tended to have fewer (p = 0.08) differentiated myoblasts, and had smaller (p ≤ 0.05) muscle fibers than controls. Proliferating myoblasts and fiber size were recovered (p ≤ 0.05) in IUGR+CLEN lambs compared to IUGR lambs, but β2 adrenoreceptor content and differentiated myoblasts were not recovered. Semitendinosus lipid droplets were smaller (p ≤ 0.05) in size for IUGR lambs than for controls and were further reduced (p ≤ 0.05) in size for IUGR+CLEN lambs.Conclusion: These findings show that clenbuterol improved IUGR deficits in muscle growth and some metabolic parameters even without recovering the deficit in β2 adrenoreceptor content. We conclude that IUGR muscle remained responsive to β2 adrenergic stimulation postnatal, which may be a strategic target for improving muscle growth and body composition in IUGR-born offspring.
Beneficial effects of physical exercise and an orally active mGluR2/3 antagonist pro-drug on neurogenesis and behavior in an Alzheimer's amyloidosis model
Authors: Perez Garcia Georgina , Bicak Mesude , Buros Jacqueline , Haure-Mirande Jean-Vianney , Perez Gissel M. , Otero-Pagan Alena , Gama Sosa Miguel A. , De Gasperi Rita , Sano Mary , Gage Fred H. , Barlow Carrolee , Dudley Joel T. , Glicksberg Benjamin S. , Wang Yanzhuang , Readhead Benjamin , Ehrlich Michelle E. , Elder Gregory A. , Gandy Sam 
Published: September 2023

BackgroundModulation of physical activity represents an important intervention that may delay, slow, or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). One mechanism proposed to underlie the beneficial effect of physical exercise (PE) involves the apparent stimulation of adult hippocampal neurogenesis (AHN). BCI-838 is a pro-drug whose active metabolite BCI-632 is a negative allosteric modulator at group II metabotropic glutamate receptors (mGluR2/3). We previously demonstrated that administration of BCI-838 to a mouse model of brain accumulation of oligomeric AβE22Q (APPE693Q = “Dutch APP”) reduced learning behavior impairment and anxiety, both of which are associated with the phenotype of Dutch APP mice.Methods3-month-old mice were administered BCI-838 and/or physical exercise for 1 month and then tested in novel object recognition, neurogenesis, and RNAseq.ResultsHere we show that (i) administration of BCI-838 and a combination of BCI-838 and PE enhanced AHN in a 4-month old mouse model of AD amyloid pathology (APPKM670/671NL/PSEN1Δexon9= APP/PS1), (ii) administration of BCI-838 alone or with PE led to stimulation of AHN and improvement in recognition memory, (iii) the hippocampal dentate gyrus transcriptome of APP/PS1 mice following BCI-838 treatment showed up-regulation of brain-derived neurotrophic factor (BDNF), PIK3C2A of the PI3K-mTOR pathway, and metabotropic glutamate receptors, and down-regulation of EIF5A involved in modulation of mTOR activity by ketamine, and (iv) validation by qPCR of an association between increased BDNF levels and BCI-838 treatment.ConclusionOur study points to BCI-838 as a safe and orally active compound capable of mimicking the beneficial effect of PE on AHN and recognition memory in a mouse model of AD amyloid pathology.
O Comunismo, a Esquerda e a Família na Folha Universal no ano eleitoral de 2022
Authors: Almendagna Isadora , Costa Oliveira Fabrício Roberto , Da Silva Leite Deivit Henrique 
Published: September 2023

O objetivo deste artigo é apresentar uma análise das edições do jornal “Folha Universal” - mídia física e online da Igreja Universal do Reino de Deus – lançadas entre janeiro e outubro de 2022. O foco da análise é o posicionamento político do jornal frente às pautas ligadas ao comunismo, à esquerda e à família, temas muito mobilizados no contexto eleitoral. O estudo, sobretudo dos editoriais e da seção “Panorama”, evidencia a sustentação de pautas morais alinhadas ao posicionamento político de Jair Bolsonaro, como a defesa da família tradicional cristã e a luta contra a “ideologia de gênero”. Sob o manto da retórica religiosa, a instituição empenhou-se na produção da imagem “diabólica” da esquerda - diametralmente oposta à chamada “direita cristã” -, e divulgou alertas sobre o “risco” da instauração do comunismo no país com a volta de Luiz Inácio Lula da Silva e do Partido dos Trabalhadores ao poder. Desta maneira, o pânico moral foi politicamente instrumentalizado e difundido pela IURD, através da Folha Universal, para impulsionar sua “base militante” na defesa da candidatura de Bolsonaro.
Особливості естетичного виховання підлітків засобами образотворчого мистецтва
Authors: Дем’янчук Олександр 
Published: September 2023

Мета статті полягає у визначенні особливостей та механізмів модернізації педагогічних умов естетичного виховання підлітків засобами образотворчого мистецтва, аналізі сучасних інноваційних технологій, що використовуються при цьому процесі. В статті застосовуються теоретичні методи: порівняння, систематизація та узагальнення наукових джерел з питання використання образотворчого мистецтва як засобу естетичного виховання підлітків. Наукова новизна статті полягає в уточненні змісту поняття «естетичне виховання», запропонуванні організаційно-педагогічних умов, що забезпечують ефективність естетичного виховання підлітків у процесі навчання образотворчому мистецтву. Визнано позитивну роль суб’єктивного сприймання і переживання творів мистецтва, що дозволяють реалізувати їхній об’єктивний естетичний смисл. Виявлено значущість мисленнєвої активності, здатності підлітків до «співдії», «співпереживання» через образне і понятійне узагальнення. Проаналізовано зв’язок одиничного (конкретно-чуттєва форма, образне узагальнення) і загального (чуттєве сприйняття багатогранної сутності зображуваного явища). Обґрунтовано зміст репродуктивного (фрагментарний і сюжетний підрівні); емоційно-художнього; інтуїтивно-художнього; усвідомлено-художнього рівнів сприймання творів образотворчого мистецтва.Результати дослідження можуть бути використані у педагогічній практиці роботи основної школи, а також для розробки навчально-методичних посібників, дидактичних матеріалів педагогічних закладів середньої та спеціальної освіти, ЗВО.
Knowledge Management in Multimedia Communication Using Software Agents
Authors: Kieltyka Leszek 
Published: September 2023

This paper presents the problem of knowledge management related to software agents and agent systems (i.e. systems composed of communicating and cooperating software agents). The author presents basic theoretical issues, but the main focus is on the areas of application of software agents in multimedia communication - both existing and prospective applications. Particular attention has been paid to the applications of software agents for: supporting customer service processes through the Contact Centre system; supporting the distance learning system; creating virtual assistants in the form of conversation bots; searching for information in the Semantic Web, and assisting in setting up a video conference call. Software agents are often referred to as 'intelligent' - due to their intelligent behaviour. At their core, they involve: perception, reasoning, learning, communication and operation in complex environments, using all multimedia techniques and procedures. Software agents and agent systems, as presented in this article, represent a new approach to the analysis, design and implementation of complex (usually decentralised and distributed) computer systems, offering a whole range of concepts, techniques and tools to significantly improve the software development process. The ability of software agents to make autonomous decisions have been a subject of considerations. Among other things, they are based on the example of cognitive sciences, which deal with modelling real processes of information processing in humans and building programmes that imitate these processes. Research on the common understanding of shared knowledge and knowledge management in agent-based systems focuses on ontologies, understood as a description of the relationship between the way knowledge is represented and the concept represented by that knowledge. In contrast, research on knowledge sharing has focused on communication languages and their associated - interaction protocol and message transport protocol.
How to … Lessons Learned - a space sector study of best practice
Authors: Herd Andrew , Piretti Francesca 
Published: September 2023

Abstract: The European Space Agency is a learning organisation committed to gathering experience from its projects and activities as they progress. In setting out its internal processes and means for Lessons Learned in 2017, the Agency took reference of previous best practice of lessons learned available at that time, both from within and outside of the space sector. Now some 6 years later, the Agency is seeking to both continue to learn from others, particularly those in the space sector, and to provide its experience and expertise gained in this area to others in the space domain. The collection of experience and hence lessons include gathering experiences from other organisation through lessons learned, the exchange of experience between the Agency and other organisations and the collaboration and exchange of state-of-the-art approaches to lessons learned means and process. This is needed as the full adoption to experience sharing and learning is not simply a process change (the way we do things – climate), but also one of culture (our belief set, reinforcing why we do things). In this it is recognised that “the hard stuff is easy, and the soft stuff is hard” – meaning that building tools and documenting the process is the easy part, getting the adoption and use, and the belief that it is beneficial is the harder part. Indeed, investment in tools is generally short term, but the investment in people to create a shift in organisational culture takes much more time. This paper will take a fresh and broad look at lessons learned in the space sector, identify best practices, by gathering data from around a dozen significant space players: space agencies, major space industry and new space entities. It will then present the findings and propose the next steps, both for the European Space Agency, but also for others in the space sector to consider applying within their own organisations.
IMPLIKASI EKONOMI DARI POLA KONSUMSI PANGAN DAN NON PANGAN MASYARAKAT KOTA MATARAM TAHUN 2018 - 2022
Authors: ARTIKA IDA BAGUS EKA , MARINI IDA AYU KETUT 
Published: September 2023

The increasing of household income, in general, will tend to change consumption patterns, especially the consumption patterns for food and non-food. According to Engel, in accordance with the research he conducted, it was stated that when income increases, the proportion for food expenditure will decrease, even though in absolute terms the amount increases. A decrease in the proportion of expenditure on food will be followed by an increase in the proportion of expenditure on non-food. This study aims to determine the pattern of consumption of the people of the city of Mataram in terms of consumption of food and non-food and the implications for the economy of the city of Mataram. The results was found that the higher the level of family income, the tendency for the proportion of expenditure on food to decrease, followed by an increase in the proportion of expenditure on non-food. Likewise, from the household size as reflected by the number of family members, the greater the number of family members, the higher the proportion of expenditure for food consumption, and on the other hand, the proportion for non-food expenditure decreases. From the results of the research, it was suggested to the Mataram City Government to conduct research related to mapping community consumption needs, especially non-food needs, to anticipate the supply of goods and services needed by the community, so that the government can anticipate community needs through more careful economic planning.
ANALISA PENGARUH STRUKTUR MODAL, PERPUTARAN ASET TERHADAP NILAI PERUSAHAAN PADA EMITEN BUMN SUBSEKTOR KONSTRUKSI DI BURSA EFEK INDONESIA PERIODE 2019 – 2021
Authors: WIJAYA I KETUT KUSUMA 
Published: September 2023

This research aims to investigate and analyse simultaneous and partial effects of debt equity ratio, asset turn over on value company at stated owned companies in subsector construction in Indonesia stock eschange. Sample of this research covers 4 out of 4 population listed construction companies in Indonesia Stock Exchange. Those samples have been selected using purposive sampling technique. This is a associative research using multiple linear regressions as an analysis method. Partially, only asset turn over effect the value of companies. Simultaneous test of multiple linear regressions indicates that debt equity ratio, asset turn over perform significant effects on value company. The effect is 99,2 % and the rest 0,8 % has been affected by other factors.
INTERAKSI KOMPOSISI MEDIA TANAM DAN ZAT PENGATUR TUMBUH (ZPT) ALAMI TERHADAP PERTUMBUHAN STEK LEMON (CITRUS LIMON L.)
Authors: LANA WAYAN , PUTRA ANAK AGUNG GEDE , APRIASTUTI NI PT EKA 
Published: September 2023

This study aims to determine the effect of the composition of the growing media and natural growth regulators and their interactions on the growth of lemon cuttings. This research was conducted at Banjar Dinas Pangereregan Kaja, Lumbung Village, Selemadeg Barat District, Tabanan Regency. The altitude of the research site is 200 m above sea level. This research was conducted from 23 January 2022 to 20 March 2022 for 8 weeks from planting cuttings. The interaction between the treatment of the composition of the planting medium and the natural growth regulator had a very significant effect on almost all the variables observed, except for the variable plant height (cm) which had no significant effect and plant diameter (cm) which had a significant effect . The highest total plant oven dry weight was obtained for the composition of manure media: soil : sand (1 : 2 : 1) and coconut water zpt which was 5,22 g or an increase of 135,13% and the lowest was obtained in the treatment of the composition of manure media: soil: sand (1 : 2 : 1) and cow urine zpt only 2,22 g. The highest total plant wet weight variable was found in the treatment of manure media composition: soil: sand (1 : 2 : 1) and shallot extract zpt which was 13,87 g or an increase in yield of 144,62% compared to the treatment of the composition of the manure planting medium: soil: sand (2 : 1 : 1) and shallot extract zpt which gave the lowest total plant wet weight, which was only 5,67 g.
AN ANALYSIS OF ENGLISH-SPEAKING ANXIETY ENCOUNTERED BY STUDENTS IN ENGLISH EDUCATION DEPARTMENT
Authors: MARLIANA ELLI , YAYU YAYU 
Published: September 2023

This research focused on analyzing English speaking anxiety that experienced by the second semester students of English education department at STKIP Paracendekia NW Sumbawa. Through a descriptive qualitative method, this research aimed to find out factors that cause English speaking anxiety, students’ efforts to overcome their English-speaking anxiety, and category of anxiety that is experienced in the students. The respondents who are selected purposively in this research consisted of ten students from class A and B second semester in English Education Department at STKIP Paracendekia NW Sumbawa. This research used interview and observation techniques to collect the data which later the data analyzed using three techniques: data reduction, data display and drawing conclusion or verification. The result of this research reveals the factors that cause English speaking anxiety are lack of vocabulary, low English proficiency, lack of practice, lack of preparation and fear of making mistakes and being laughed at. In addition, the strategies used by the students to overcome their English-speaking anxiety are preparation, relaxation and positive thinking. Furthermore, the category of anxiety experienced by the students in this research is state anxiety.
PENGARUH STANDAR OPERASIONAL PROSEDUR DAN KUALITAS KEHIDUPAN KERJA (Quality Of Worklife) TERHADAP EFEKTIFITAS KERJA (Studi Pada Universitas Perjuangan Tasikmalaya)
Authors: Salgangga Selji 
Published: September 2023

This research is motivated by the existence of several problems, including the effectiveness of the work of employees at the University of Perjuangan Tasikmalaya which is still low, this is thought to be caused by the not optimal implementation of SOP carried out by the university so that the work results of employees are not in accordance with the provisions set. In addition, the quality of work life is not supportive so that there are still employees who have not been able to complete a job according to the set time. The purpose of this study was to determine the effect of standard operating procedures and quality of work life on work effectiveness at the University of Perjuangan, Tasikmalaya City. In this study used a descriptive method with a quantitative approach. Respondents in this study were employees at the University of Perjuangan Tasikmalaya as many as 132 people so the authors took samples using simple random sampling technique so that the number of samples in this study were 57 people. Analysis was carried out on the data collected both from the results of observations, interviews, and questionnaires. The data analysis stage begins with validity, reliability, transformation of ordinal values ​​into intervals, and verivicative/quantitative data analysis.

Keywords: Standard Operating Procedures, Quality of Work Life, Work Effectiveness