bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementasi Pemberian Layanan Bantuan Hukum Secara Cuma-Cuma Oleh Posbantuan Hukum pada Perkara Pidana di Pengadilan Negeri Gedong Tataan (Studi Kasus di Posbakum Adin Lampung)
Authors: Baharudin Baharudin , Perdana Iqbal Alin
Published: June 2021

In legal cases, namely legal cases experienced by someone, there are often problems with one's inability to be able to hire a lawyer to handle the trial process in court, in fact a suspect still has his rights in a trial, one of which is to get assistance before the law of course for defend the rights of the suspect, in cases like this if someone does not have the ability to hire a lawyer POSBAKUM or the Legal Aid Post plays an important role in helping a suspect in providing legal services in the form of consultation, legal advice and the preparation of legal documents that are really needed by a suspect based on statutory regulations, in defending a suspect the trial is carried out for free, that way every suspect from being able or not entitled to get legal assistance
Climate Change Adaptation in Coastal Cities: A Guidebook for Citizens, Public Officials and Planners
Authors: Major David C. , Juhola Sirkku K.
Published: June 2021

This guidebook presents a framework for climate adaptation planning for coastal cities, large and small, focused on the central roles of citizens, public officials, and planners. The book is designed to help all stakeholders in coastal cities understand and develop effective adaptation measures in a sustainable way. Within a framework of eight key planning steps, guidance is provided for stakeholders in the adaptation process from initial assessments of climate impacts to final planning. The work sets out general principles and methods of adaptation to climate change for many types of coastal communities. Adaptation is seen throughout the work as a process that should take into account all coastal assets, including economic, environmental, social, cultural and historical assets, with due attention to disadvantaged communities. Among the adaptation elements covered in the book are: a review of the current climate situation; climate impacts and vulnerabilities; climate models and future scenarios; physical, economic, social and other characteristics of coastal cities and towns; the range of available adaptations, including management, infrastructure, and policy adaptations; evaluation of projects and programs; and working together to develop and finance adaptations. Numerous tables are presented to help organize information and guide planning, and examples of adaptation challenges and opportunities are provided from both developed and developing coastal cities and towns. The volume is copiously illustrated, with extensive up-to-date references to provide the reader with additional sources of information.
Library Services to Diverse Communities in Europe
Authors: Agustín-Lacruz Carmen , Saurin-Parra Julia
Published: June 2021

Public libraries have developed standards to provide reading and information services to diverse populations. This has helped the public library to fulfil an informal educational and social role, particularly in engaging traditionally excluded groups, such as the Roma minority in Spain. However, well-developed library initiatives in Spain are scarce; in addition, culturally sensitive services do not thrive, and research and reflection on this reality from the library standpoint are rare. The overarching goal of this article is to provide librarians with suggestions for improved services for the Roma community in Spain. It is achieved through the critical analysis of public library services to the Roma community that currently exist in the European Union. Based on this analysis, practical suggestions are offered.
Composição corporal e desempenho físico de escolares em instituições distintas
Authors: Martinez Caroline Sirí­aco , Madureira Fabricio , Mineiro Aurea dos Santos , Souza Ivanildo Alves de , Santos Roberto Melchior Soares dos , Guedes Jr Dilmar Pinto , Colantonio Emilson , Silva Rodrigo Pereira da
Published: June 2021

Introdução: O avanço tecnológico, a má alimentação e a inatividade física são alguns dos responsáveis pelo aumento no número de crianças que apresentam doenças de caráter crônico degenerativas, problema atual de saúde pública em diferentes instituições de ensino particular e público. Objetivo:  Analisar, classificar e comparar a composição corporal e desempenho físico de escolares de instituições da rede privada e pública de uma cidade litorânea paulista. Métodos: Foram avaliadas 117 crianças, 58 voluntários de escolas públicas e 59 voluntários de escola particular com idade entre 8 e 11 anos. Foram realizadas as seguintes avaliações: antropometria: massa corporal, estatura, índice de massa corpórea (IMC), e percentual de gordura corporal (%GC) obtido por meio da utilização da medida das dobras cutâneas (tricipital e subescapular). Desempenho físico: flexibilidade, força de preensão manual, força e resistência abdominal. Análise estatística: após a confirmação da não normalidade dos dados, optou-se pelo teste de Mann- -Whitney U para comparação entre os grupos e o teste t Student para comparação entre o valor obtido e normativo de referência. Resultados: As crianças da escola privada quando comparadas às da escola pública revelaram diferenças estatísticas significativas para IMC, %GC, força de preensão manual e força e resistência abdominal. Conclusão: Esses achados denotam valores elevados em relação aos valores de referência para as variáveis antropométricas e valores abaixo dos valores de referência para as variáveis de desempenho físico, o que pode ser prejudicial à saúde de crianças em fase de crescimento e desenvolvimento.
Efeito agudo da suplementação de creatina em parâmetros morfofuncionais em mulheres veganas
Authors: Lisboa Juliana de Araújo , Gomes João Henrique , Santana Lorena Izabel Oliveira de , Barbosa Welmo Alcantara , Rica Roberta Luksevicius , Bocalini Danilo Sales , Mendes Renata Rebello
Published: June 2021

Introdução: A creatina tem sido considerada agente ergogênico para indivíduos onívoros e vegetarianos, porém, nota-se lacuna importante sobre o efeito dessa suplementação sobre a performance de veganos, grupo que apresenta maiores restrições nutricionais dentre os vegetarianos. Objetivo: Analisar o efeito da suplementação de creatina sobre performance em teste de força e composição corporal de veganas. Métodos: Quatorze veganas não-atletas foram randomicamente distribuídas em grupo creatina (n = 7) e placebo (n = 7). Antes e depois da suplementação (0,3 g kg-1 d-1 por 7 dias) foram realizados testes de performance em leg press (3 séries de repetições máximas até falha, a 80% de uma repetição máxima, 60 segundos de intervalo), e antropometria. Resultados: Após suplementação, houve diferenças significativa no número de repetições na primeira série e no somatório das três séries para ambos grupos, porém, com o o tamanho do efeito (effect size) e delta percentual superiores para grupo creatina. Na segunda série, não houve diferenças significativas entre grupos e momentos, porém, effect size e delta percentual também foram superiores para grupo creatina. Não foi observada alteração significativa na composição corporal. Conclusão: A suplementação de creatina apresentou maior efeito sobre performance em teste de força para membros inferiores, quando comparadas ao placebo, sem alterar composição corporal.
Efeito do alongamento estático pré-exercício pliométrico sobre marcadores indiretos de danos musculares
Authors: Santos Geovani Alves dos , Moreira Sérgio Rodrigues Moreira , Santos Danilo França Conceição dos Santos , Santos Fabiana Rodrigues , Teixeira-Coelho Francisco
Published: June 2021

Introdução: O alongamento estático é comumente utilizado como parte da rotina de preparação para o exercício físico, no entanto ainda é controversa a sua influência sobre a inibição e ou redução dos danos musculares ocasionados pelo exercício excêntrico. Objetivo: Analisar o efeito do uso de um protocolo de alongamento estático com duração de 5 min (5 x 60 s) pré-exercício na resposta da concentração de creatina quinase ([CK]) e dor muscular de início tardio (DMIT) 24 e 48 horas após exercício de saltos pliométricos. Métodos: Trata-se de um estudo quase-experimental contrabalanceado de medidas repetidas e a amostra foi composta por 10 voluntários saudáveis que foram submetidos a duas sessões experimentais: 1) sem alongamento prévio ao exercício (controle) e; 2) com alongamento estático prévio ao exercício (alongamento estático). Em ambas as sessões os participantes foram submetidos a um exercício de saltos pliométricos para indução de dano muscular. Previamente às sessões experimentais e 24 e 48 horas pós-exercício foi mensurada a [CK], bem como a DMIT 24 e 48 horas pós-exercício. Resultados: Não houve diferença significativa para [CK] e DMIT quando comparadas as sessões experimentais, controle e alongamento estático, (p > 0,05). Além disso, ambas obtiveram pico da [CK] 24 horas pós-exercício, e a DMIT foi classificada como irritante para ambas as sessões. Conclusão: O protocolo de alongamento estático com duração de cinco minutos (5 x 60s) prévio ao exercício de saltos pliométricos não minimizou ou inibiu os danos musculares associados às ações excêntricas avaliadas pela [CK] e DMIT.
Análise sérica e urinária de biomarcadores de dano muscular em atletas profissionais de futsal
Authors: Siqueira Luciano de Oliveira , Ramos Maria Eduarda Kegler , Schwarzbach Daniel , Marostica Lucas Lourenço , MOreira Jose Claudio Fonseca
Published: June 2021

Introdução: Diante das alterações metabólicas advindas do esporte e as consequências da superação dos limites individuais nos esportes coletivos de elite, faz-se necessária a compreensão bioquímica dos fenômenos ocorridos nessa modalidade a fim de minimizar danos, aperfeiçoar o desempenho atlético e fornecer protocolos mais adequados para cada esporte e indivíduo. Objetivo: O presente estudo objetivou analisar o metabolismo de atletas profissionais durante o treinamento mediante determinação de biomarcadores sanguíneos e urinários de proteólise, lipólise, hemólise e microtrauma muscular. Métodos: A avaliação foi realizada com 12 atletas que participam na série Ouro da liga de futsal. Todos foram submetidos a um protocolo padrão de treinamento e amostras de sangue e urina foram coletadas em repouso e 15 minutos após a sessão de treinamento. Resultados: A análise estatística dos resultados mostra um aumento significativo (p < 0,05) nas contagens relativa (células/ %) e absoluta (células/μL) de neutrófilos, bem como na concentração sérica de ácido úrico, colesterol total e frações HDL, ALT, LDH e CK-MM. Por outro lado, apresentaram uma diminuição estatisticamente significativa (p < 0,05) na concentração de magnésio, glicose, ureia urinária, contagem relativa de linfócitos, contagem absoluta de monócitos e eosinófilos (células /% e células/μL). Conclusão: Os resultados aqui obtidos permitem concluir que a compreensão bioquímica pode minimizar dano muscular, aperfeiçoar o desempenho atlético e oferecer formação de protocolos mais adequados para cada esporte.
Metabolic responses during practice of exergames in adults according to sex
Authors: Krug Moane Marchesan , Barbosa Aline Rodrigues
Published: June 2021

Objective: To analyze the metabolic responses occurring during the practice of exergames in terms of energy expenditure, oxygen consumption rate, metabolic equivalent and heart rate in adult men and women. Methods: The present study sample was comprised of 102 adults (52 males). Energy expenditure, oxygen consumption rate and metabolic equivalent were assessed with a portable gas analyzer (K4b2). Heart rate was measured with a frequencymeter. All dependent variables were assessed at rest and during the exergame session, which was comprised of four X-box 360 games (volleyball, boxing, athletics, and bowling). Results: Mean age was 34.8 ± 13.4 years. There was a significant increase in resting values during exergame sessions for energy expenditure (male: 467.52%; p < 0.001; female: 393.72%; p < 0.001), oxygen consumption rate (male: 453.97%; p < 0.01; female: 384.74%; p < 0.001), metabolic equivalent (male: 457.40%; p < 0.001; female: 384.74%; p < 0.001) and heart rate (male: 95.10%; p < 0.001; female: 92.26; p < 0.001). When compared to women, men showed significantly higher values for energy expenditure (95% confidence interval = -12.53; -6.67), oxygen consumption rate (95% confidence interval = -4.01; -0.80) and metabolic equivalent (95% confidence interval = -1.18; 0.27) during exergames. Conclusion: A session of exergames is capable of increasing energy expenditure, oxygen consumption rate, metabolic equivalent and heart rate in adults. Men showed higher values in metabolic parameters when compared to women.
Síndrome de Ícaro: a vaidade caiada na ciência
Authors: Sacramento Marvyn de Santana do , Fontes Rodrigo de Freitas , Jesus Edileuza Ferreira de
Published: June 2021

O texto editorial traz uma metáfora entre o mito grego de Ícaro e assunto relacionado no âmbito da pesquisa científica, no que tange a tomada de decisões na prática clínica. Os pesquisadores são comparados com os personagens do conto, fazendo uma alusão aos diferentes tipos de escolhas que podem resultar em uma decisão incoerente e sem benefícios garantidos para um determinado tratamento ou problema, quando esta não é baseada em valendo-se do método científico. Dessa forma, o exercício físico (devido às suas limitações), também sofre a influência de uma boa ou má conduta de prescrição, devido ao embasamento científico atribuído pelo profissional de saúde ou por uma preconceito já obtido, que pode causar um desfecho indesejável para o objetivo proposto. É necessário que este profissional, bem como um pesquisador, atente para estas questões ligadas a vaidade, despertando sempre a humildade em seu desenvolvimento pessoal.
Coercion or Cost-Decrease: Why Do Firms Pay Influences?
Authors: Israel Odion E. Idewele  , Peter Eriki  , Murad A. Bein
Published: June 2021

It has been observed that Firms Influence Government Authorities by paying Bribe to them. This paper examines how gift is related with the potential for the firm to discover legitimate government authorities. This paper attempts to ascertain why firms pay bribes. More specifically, does it appear that firms are being extorted or is it more likely that they are using bribes as a tool to avoid regulation?  In the event that organizations that report more prominent chances to discover government authority pay bribe, at that point this is an indication that rewards originated from coercion in light of the fact that the nearness of such authorities ought not make any difference for firms needing to pay bribe to reduced costs. We find out that influences emerge because of coercion in spite of the fact that result fairly debilitate in the most current study. If corrupt individuals are more likely to enter into environments that allow them to extract bribes, then honest could be endogenous and driven by the prevalence and magnitude of bribery.
Penerapan Pendidikan Karakter Gemar Membaca Melalui Program Literasi di Sekolah Dasar
Authors: Priasti Silvia Nur , Suyatno Suyatno
Published: June 2021

This study aims to find a model for the application of character education for reading fondness through literacy programs. This research is a type of qualitative research with a case study approach. The research subjects consisted of the principal, teachers, and students at SD Negeri Sidareja 01 Cilacap. In collecting data, researchers used instruments in the form of interview guidelines, observation guidelines, and document analysis guidelines. The data analysis technique used is the interactive data analysis technique of Miles and Huberman which consists of data reduction, data presentation, and conclusion drawing. The results showed that character education for reading fondness through the School Literacy Program at SD Negeri Sidareja 01 was carried out through: 1) The habituation phase which includes reading habit for 10-15 minutes and other activities that can build literacy culture and literacy-friendly physical environment conditioning. 2) The development phase which includes the development of literacy skills through various non-academic activities as well as the promotion of the social and affective environment as a model of literate communication and interaction. 3) The learning phase which includes the implementation of learning using a variety of literacy strategies and making schools a literate academic environment through professional development.
Neurosurgical robots and ethical challenges to medicine
Authors: Saniotis A , Henneberg M
Published: June 2021

Over the last 20 yr, neurosurgical robots have been increasingly assisting in neurosurgical procedures. Surgical robots are considered to have noticeable advantages over humans, such as reduction of procedure time, surgical dexterity, no experience of fatigue and improved healthcare outcomes. In recent years, neurosurgical robots have been developed to perform various procedures. Public demand is informing the direction of neurosurgery and placing greater pressure on neurosurgeons to use neurosurgical robots. The increasing diversity and sophistication of neurosurgical robots have received ethical scrutiny due to the surgical complications that may arise as well as the role of robots in the future. In this paper, we address 3 ethical areas regarding neurosurgical robots: (1) Loss of neurosurgical skills due to increasing dependency on robots; (2) How far do we want to go with neurosurgical robots? (3) Neurosurgical robots and conflict of interest and medical bias.
MODERN GEORGIAN COMPARATIVE STUDIES: DIRECTIONS OF RESEARCH, MAIN ISSUES
Authors: Hrytsyk Liudmyla , Mchedeladze Ivane
Published: June 2021

Taking into account the factual material, research methods, and tasks, the authors trace the evolution/changes in Georgian comparative studies. It is notable that typological approaches, along with contact-genetic ones, are now actively used. These changes become firmly established due to the studies of iconic figures and periods, which attract the special attention of the scholars. Eurocentric concepts give place to other ones that have their basis in the study of the national literature and include philosophical, anthropological, psychological, and religious factors in the field of research. A lot of attention has been given to the principles of selecting literary texts for translation. The field of Georgian comparative studies has been remarkably changed/updated in the late 20th — early 21st centuries. Along with historians of literature, the theorists, critics, translators, and specialists in European and Oriental languages have been involved, which affected the level of comparative studies. Among the raised issues are reception, imagology, typology of anti-colonial narratives, genre transformations, postmodern discourse, etc. The character of Georgian-Ukrainian comparative studies changed drastically: it is obvious in the approaches/assessments of literary translation and in all connecting issues in general. Comparative studies came as close as possible to the theory of literature, which let the researchers (R. Khvedelidze, N. Naskidashvili, S. Chkhatarashvili, I. Mchedeladze) update the methodology and intensify their work on the diff erent levels of research, regardless of the presence/absence of contexts. The present surge in Georgian comparative studies started in the 2010s. It is connected to the organization of effective specialized research centers. Of great interest are the comparative studies aiming to show the history of Georgian literature as an individual version of the world literature (I. Ratiani), to identify the features of the Georgian literary canon based on the three main literary models (Middle Ages, Romanticism, post-Soviet), with a focus on the combination of ‘canonical’ and ‘non-canonical’ in innovative writing.
INTERPRETATION OF THE BIBLICAL PROTOTEXT IN LEONID MOSENDZ’S NOVEL “THE LAST PROPHET”
Authors: Hryhorchuk Yuliіa
Published: June 2021

The paper deals with the biblical prototext in L. Mosendz’s novel “Th e Last Prophet”. This work focuses on the figure of John the Baptist making the most full coverage of the prophet’s personality in Ukrainian literature. Besides the historical sources, the novel is based on the ideological and aesthetic pattern of the Holy Scripture. However, the canonical text has been significantly rethought. The specifics of interpreting the biblical prototext in L. Mosendz’s novel have not yet been the subject of special research, although many scholars paid attention to the biblical basis of the work. Therefore, the purpose of the present paper is to highlight the peculiarities of the biblical prototext embodied in the novel “The Last Prophet”. The analysis of the plot, figurative and stylistic levels was necessary for achieving this goal. At the plot level, the common and distinctive features of the biblical and fictional stories of the John the Baptist’s life have been indicated. The distinctive features appeared to be more numerous as the text of the novel complements rather than repeats the prototext (the Gospel of Luke). Psychologization, the scholarly motivation of events, the manner of filling “semantic gaps” with both oneiric visions and historical narrations are the specific features in reproducing the biblical story. The main characters of the work Jehohanan and Elizabeth, unlike original biblical characters, are endowed with portrait characteristics and shown in the dynamics of age and spiritual growth. Creating them, the author combines the Old and New Testament prototypes: Eliseba — Sarah, the Mother of God; Jehohanan — David, Elijah, Isaiah, Moses, and Messiah. In this context, the figure of Elizabeth appears as a generalized image of the Mother, and the figure of Jehohanan — as a common image of the Prophet. Th e sacred vocabulary, biblical anthroponyms, toponyms, aphorisms, stylistic figures of inversion, amplification, gradation, etc. form the stylistic level of implementing the aesthetic means of the Holy Scripture. Some biblical quotations are given as poetically modified and emotionally characterized by the writer. The biblical prototext secures ideological and aesthetic integrity for the novel but doesn’t give the plot a strict direction. Although deeply rooted in the Holy Scripture, the novel by Mosendz is a completely independent work on the search for values of a man, people, and humanity.
SOME ISSUES ON PROTECTION OF NATIONAL INTERESTS CONCEMING INTELLECTUAL PROPERTY IN THE PROCESS OF EURO-ATLANTIC INTEGRATION
Authors: Олександр Зайківський  , Олександр Оністрат
Published: June 2021

Some issues of protection of national interests concerning intellectual property in the process of Euro-Atlantic integration are considered, in particular features of protection of intellectual property in the implementation of international military-technical cooperationof Ukraine, depending on the specifics of this activity. The legislation of Ukraine regulating activities related to military-technical cooperation is analyzed. The importance of intellectual property protection at all stages of military-technical cooperation and the need to improve the legislation on the regulation of intellectual property protection in the defense sphere are outlined.The Constitution and major legislative acts of Ukraine in the field of national security and defense have clearly defined the strategic course for achieving NATO membership. However, to achieve this strategic goal requires persistence and political will, as well as an understanding of the various tactical issues that need to be resolved along the way.New members are being trained in the process of performing the NATO Membership Action Plan. On the long-term path of Euro-Atlantic integration, Ukraine has developed an annual NATO-Ukraine national program. Traditionally, the Annual National Program is structurally constructed by analogy with a typical Membership Action Plan andincludes almost all areas of reformation and modernization of Ukraine.In particular, great attention is paid to reforming and comprehensive support of Ukraine's security and defense sector. It includes a wide range of measures to maintain combat capabilities, modernize and upgrade weapons and military equipment, reform and develop the defense-industrial complex of Ukraine, implement the government qualityassurance system of defense products, revitalize the scientific and military-technical cooperation. Even measures to ensure gender equality in the security and defense sector of Ukraine are being envisaged.It is stated that defense and technical cooperation with NATO will be focused, in particular, on the use of the best modern world technologies. However, the issues of intellectual property protection of all entities and protection of national interests in this field are not considered at all, although almost all the envisaged measures cannot be implementedwithout the use of intellectual property rights.In our view, intellectual property issues should be decided in conjunction with other issues. However, in order to determine the position of the state and development of appropriate proposals and recommendations for securing national interests in intellectual property in the process of Euro-Atlantic integration, it is appropriate to consider these issuesin the following areas: legal cooperation between Ukraine and NATO;scientific cooperation; military-technical cooperation.
Legal Profession in Major Legal System
Authors: Acharya Suman
Published: June 2021

Legal education and profession are interconnected issues. Each and every country of the world set minimum academic qualification to become a lawyer, which is bachelor’s degree in law. Then, they can participate in Bar Examination and successful candidate will get license with apprenticeship training. However, other superior degree is preferable. Legal education is considered as interdisciplinary and multidisciplinary issues. Curriculum of legal education is set in the same basis. In the context of legal profession, civil legal system prefers specialization of lawyer whereas common legal system accepts generalization in legal field. Socialist country prefers to impart communist doctrine for lawyer so that they can work for social justice and collective benefit. Nevertheless, Covid-19 has made hardest hit for the legal professional because of the lockdown and related situation. Employment of online system in case hearing system may resume their legal profession as usual even in crisis period.
Leishmania spp Epitopes in Humans Naturally Resistant to the Disease: Working Toward a Synthetic Vaccine
Authors: Flórez Magda Melissa , Rodríguez Rocío , Cabrera José Antonio , Robledo Sara M. , Delgado Gabriela
Published: June 2021

Vaccines are one of the most effective strategies to fight infectious diseases. Reverse vaccinology strategies provide tools to performin silicoscreening and a rational selection of potential candidates on a large scale before reachingin vitroandin vivoevaluations.Leishmaniainfection in humans produces clinical symptoms in some individuals, while another part of the population is naturally resistant (asymptomatic course) to the disease, and therefore their immune response controls parasite replication. By the identification of epitopes directly in humans, especially in those resistant to the disease, the probabilities of designing an effective vaccine are higher. The aim of this work was the identification ofLeishmaniaepitopes in resistant humans. To achieve that, 11 peptide sequences (fromLeishmaniaantigenic proteins) were selected using epitope prediction tools, and then, peripheral blood mononuclear cells (PBMCs) were isolated from human volunteers who were previously divided into four clinical groups: susceptible, resistant, exposed and not exposed to the parasite. The induction of inflammatory cytokines and lymphoproliferation was assessed using monocyte-derived dendritic cells (moDCs) as antigen-presenting cells (APCs). The response was evaluated after exposing volunteers’ cells to each peptide. As a result, we learned that STI41 and STI46 peptides induced IL-8 and IL-12 in moDCs and lymphoproliferation and low levels of IL-10 in lymphocytes differentially in resistant volunteers, similar behavior to that observed in those individuals toL. panamensislysate antigens. We conclude that,in silicoanalysis allowed for the identification of naturalLeishmaniaepitopes in humans, and also STI41 and STI46 peptides could be epitopes that lead to a cellular immune response directed at parasite control.
Roflumilast Suppresses Adipogenic Differentiation via AMPK Mediated Pathway
Authors: Xu Wan , Zhang Jingjing , Xiao Jing
Published: June 2021

Obesity and related disorders have increasingly become global health problems over the years. In recent years, obesity has been recognized as the most important risk factor for a variety of diseases including cardiovascular diseases, type 2 diabetes, steatohepatitis, and cancer. The medical anti-obesity treatment is to intervene in the metabolic process of adipocytes by suppressing adipogenesis and promoting lipolysis. The Phosphodiesterase-4 (PDE4) pathway is involved in fat mass control and metabolic regulation. The present study aimed to investigate the effects of Roflumilast, a selective PDE4 inhibitor, on the differentiation of 3T3-L1 cells and the high fat diet-induced obesity in mice. We showed that treatment with Roflumilast inhibited lipid accumulation and triglycerides storage in mature 3T3-L1 cells, suggesting that Roflumilast suppressed adipogenesis. Mechanistically, we found that Roflumilast decreased the differentiation-induced expression of the adipogenesis genes including SREBP1C, FABP4, and Glut4, as well as their regulators including PPAR-γ and C/EBPα. Moreover, we proved that the effect of Roflumilast was dependent on the activation of the metabolic regulator AMPKα. The treatment with Roflumilast remarkably decreased the animals’ body weight, visceral adipose tissue weight, and adipocyte size in high fat diet-induced obese mice. In conclusion, our study revealed that Roflumilast suppressed adipogenesis and promoted lipolysis in cell culture and mice models via AMPK-mediated inhibition of PPAR-γ and C/EBPα. These findings imply roflumilast could have therapeutic potential in obesity-related diseases.
Accurate Solar Cell Modeling via Genetic Neural Network-Based Meta-Heuristic Algorithms
Authors: Wang Long , Chen Zhuo , Guo Yinyuan , Hu Weidong , Chang Xucheng , Wu Peng , Han Cong , Li Jianwei
Published: June 2021

Accurate solar cell modeling is essential for reliable performance evaluation and prediction, real-time control, and maximum power harvest of photovoltaic (PV) systems. Nevertheless, such a model cannot always achieve satisfactory performance based on conventional optimization strategies caused by its high-nonlinear characteristics. Moreover, inadequate measured output current-voltage (I-V) data make it difficult for conventional meta-heuristic algorithms to obtain a high-quality optimum for solar cell modeling without a reliable fitness function. To address these problems, a novel genetic neural network (GNN)-based parameter estimation strategy for solar cells is proposed. Based on measured I-V data, the GNN firstly accomplishes the training of the neural network via a genetic algorithm. Then it can predict more virtual I-V data, thus a reliable fitness function can be constructed using extended I-V data. Therefore, meta-heuristic algorithms can implement an efficient search based on the reliable fitness function. Finally, two different cell models, e.g., a single diode model (SDM) and double diode model (DDM) are employed to validate the feasibility of the GNN. Case studies verify that GNN-based meta-heuristic algorithms can efficiently improve modeling reliability and convergence rate compared against meta-heuristic algorithms using only original measured I-V data.
Footprints in the Sand: Deep Taxonomic Comparisons in Vertebrate Genomics to Unveil the Genetic Programs of Human Longevity
Authors: Treaster Stephen , Karasik David , Harris Matthew P.
Published: June 2021

With the modern quality, quantity, and availability of genomic sequencing across species, as well as across the expanse of human populations, we can screen for shared signatures underlying longevity and lifespan. Knowledge of these mechanisms would be medically invaluable in combating aging and age-related diseases. The diversity of longevities across vertebrates is an opportunity to look for patterns of genetic variation that may signal how this life history property is regulated, and ultimately how it can be modulated. Variation in human longevity provides a unique window to look for cases of extreme lifespan within a population, as well as associations across populations for factors that influence capacity to live longer. Current large cohort studies support the use of population level analyses to identify key factors associating with human lifespan. These studies are powerful in concept, but have demonstrated limited ability to resolve signals from background variation. In parallel, the expanding catalog of sequencing and annotation from diverse species, some of which have evolved longevities well past a human lifespan, provides independent cases to look at the genomic signatures of longevity. Recent comparative genomic work has shown promise in finding shared mechanisms associating with longevity among distantly related vertebrate groups. Given the genetic constraints between vertebrates, we posit that a combination of approaches, of parallel meta-analysis of human longevity along with refined analysis of other vertebrate clades having exceptional longevity, will aid in resolving key regulators of enhanced lifespan that have proven to be elusive when analyzed in isolation.
RIPK1-Associated Inborn Errors of Innate Immunity
Authors: Zhang Jiahui , Jin Taijie , Aksentijevich Ivona , Zhou Qing
Published: June 2021

RIPK1 (receptor-interacting serine/threonine-protein kinase 1) is a key molecule for mediating apoptosis, necroptosis, and inflammatory pathways downstream of death receptors (DRs) and pattern recognition receptors (PRRs). RIPK1 functions are regulated by multiple post-translational modifications (PTMs), including ubiquitination, phosphorylation, and the caspase-8-mediated cleavage. Dysregulation of these modifications leads to an immune deficiency or a hyperinflammatory disease in humans. Over the last decades, numerous studies on the RIPK1 function in model organisms have provided insights into the molecular mechanisms of RIPK1 role in the maintenance of immune homeostasis. However, the physiological role of RIPK1 in the regulation of cell survival and cell death signaling in humans remained elusive. Recently, RIPK1 loss-of-function (LoF) mutations and cleavage-deficient mutations have been identified in humans. This review discusses the molecular pathogenesis of RIPK1-deficiency and cleavage-resistant RIPK1 induced autoinflammatory (CRIA) disorders and summarizes the clinical manifestations of respective diseases to help with the identification of new patients.
Serum Complement C3 and C4 and COVID-19 Severity and Mortality: A Systematic Review and Meta-Analysis With Meta-Regression
Authors: Zinellu Angelo , Mangoni Arduino A.
Published: June 2021

Activation of the complement system has been observed in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression to investigate possible differences in the serum concentrations of two routinely measured complement components, C3 and C4, in COVID-19 patients with different severity and survival status. We searched PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting serum complement C3 and C4, measures of COVID-19 severity, and survival. Eligibility criteria were a) reporting continuous data on serum C3 and C4 concentrations in COVID-19 patients, -b) investigating COVID-19 patients with different disease severity and/or survival status, c) adult patients, d) English language, e) ≥10 patients, and f) full-text available. Using a random-effects model, standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated to evaluate differences in serum C3 and C4 concentrations between COVID-19 patients with low vs. high severity or survivor vs. non-survivor status. Risk of bias was assessed using the Newcastle-Ottawa scale whereas publication bias was assessed with the Begg’s and Egger’s tests. Certainty of evidence was assessed using GRADE. Nineteen studies in 3,764 COVID-19 patients were included in the meta-analysis. Both C3 and C4 concentrations were significantly lower in patients with high disease severity or non-survivor status than patients with low severity or survivor status (C3 SMD=-0.40, 95% CI -0.60 to -0.21, p<0.001; C4 SMD=-0.29, 95% CI -0.49 to -0.09, p=0.005; moderate certainty of evidence). Extreme between-study heterogeneity was observed (C3, I2 = 82.1%; C4, I2 = 84.4%). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. There was no publication bias. In meta-regression, the SMD of C3 was significantly associated with white blood cell count, C-reactive protein (CRP), and pro-thrombin time, whereas the SMD of C4 was significantly associated with CRP, pro-thrombin time, D-dimer, and albumin. In conclusion, lower concentrations of C3 and C4, indicating complement activation, were significantly associated with higher COVID-19 severity and mortality. C3 and C4 might be useful to predict adverse clinical consequences in these patients.

Systematic Review Registration: PROSPERO, Registration number: CRD42021239634.
A Systematic Analysis of Hand Movement Functionality: Qualitative Classification and Quantitative Investigation of Hand Grasp Behavior
Authors: Liu Yuan , Jiang Li , Liu Hong , Ming Dong
Published: June 2021

Understanding human hand movement functionality is fundamental in neuroscience, robotics, prosthetics, and rehabilitation. People are used to investigate movement functionality separately from qualitative or quantitative perspectives. However, it is still limited to providing an integral framework from both perspectives in a logical manner. In this paper, we provide a systematic framework to qualitatively classify hand movement functionality, build prehensile taxonomy to explore the general influence factors of human prehension, and accordingly design a behavioral experiment to quantitatively understand the hand grasp. In qualitative analysis, two facts are explicitly proposed: (1) the arm and wrist make a vital contribution to hand movement functionality; (2) the relative position (relative position in this paper is defined as the distance between the center of the human wrist and the object center of gravity) is a general influence factor significantly impacting human prehension. In quantitative analysis, the significant influence of three factors, object shape, size, and relative position, is quantitatively demonstrated. Simultaneously considering the impact of relative position, object shape, and size, the prehensile taxonomy and behavioral experiment results presented here should be more representative and complete to understand human grasp functionality. The systematic framework presented here is general and applicable to other body parts, such as wrist, arm, etc. Finally, many potential applications and the limitations are clarified.
Learning Transferable Push Manipulation Skills in Novel Contexts
Authors: Howard Rhys , Zito Claudio
Published: June 2021

This paper is concerned with learning transferable forward models for push manipulation that can be applying to novel contexts and how to improve the quality of prediction when critical information is available. We propose to learn a parametric internal model for push interactions that, similar for humans, enables a robot to predict the outcome of a physical interaction even in novel contexts. Given a desired push action, humans are capable to identify where to place their finger on a new object so to produce a predictable motion of the object. We achieve the same behaviour by factorising the learning into two parts. First, we learn a set of local contact models to represent the geometrical relations between the robot pusher, the object, and the environment. Then we learn a set of parametric local motion models to predict how these contacts change throughout a push. The set of contact and motion models represent our internal model. By adjusting the shapes of the distributions over the physical parameters, we modify the internal model's response. Uniform distributions yield to coarse estimates when no information is available about the novel context. We call this an unbiased predictor. A more accurate predictor can be learned for a specific environment/object pair (e.g., low friction/high mass), called a biased predictor. The effectiveness of our approach is demonstrated in a simulated environment in which a Pioneer 3-DX robot equipped with a bumper needs to predict a push outcome for an object in a novel context, and we support those results with a proof of concept on a real robot. We train on two objects (a cube and a cylinder) for a total of 24,000 pushes in various conditions, and test on six objects encompassing a variety of shapes, sizes, and physical parameters for a total of 14,400 predicted push outcomes. Our experimental results show that both biased and unbiased predictors can reliably produce predictions in line with the outcomes of a carefully tuned physics simulator.
Altered Functional Connectivity and Cognition Persists 4 Years After a Transient Ischemic Attack or Minor Stroke
Authors: Nicolas Korinne , Goodin Peter , Visser Milanka M. , Michie Patricia T. , Bivard Andrew , Levi Christopher , Parsons Mark W. , Karayanidis Frini
Published: June 2021

Background and Purpose: Altered executive functions and resting-state functional connectivity (rsFC) are common following a minor stroke or transient ischemic attack (TIA). However, the long-term persistence of these abnormalities is not well-studied. We investigated whether there were cognitive and rsFC differences between (a) controls and minor cerebrovascular event (CVE) patients and (b) between CVE patients with and without an imaging confirmed infarct (i.e., minor stroke and TIA, respectively) at an average of 3.8 years following their event.

Methods: Structural and resting-state imaging and cognitive assessments including the Montreal Cognitive Assessment, the Trail Making Task and the National Institute of Health (NIH) Cognition Toolbox were conducted on 42 patients (minor stroke = 17, TIA = 25) and 20 healthy controls (total N = 62).

Results: Controls performed better than patients on two measures of executive functioning (both p < 0.046) and had reduced rsFC between the frontoparietal and default mode networks (FPN and DMN, respectively; p = 0.035). No cognitive differences were found between minor stroke and TIA patients, however, rsFC differences were found within the FPN and the DMN (both p < 0.013). Specifically, increased connectivity within the FPN was associated with faster performance in the minor stroke group but not the TIA group (p = 0.047).

Conclusions: These findings suggest that transient or relatively minor cerebrovascular events are associated with persistent disruption of functional connectivity of neural networks and cognitive performance. These findings suggest a need for novel interventions beyond secondary prevention to reduce the risk of persistent cognitive deficits.
Anticoagulation Therapy Reduces Recurrent Stroke in Embolic Stroke of Undetermined Source Patients With Elevated Coagulation Markers or Severe Left Atrial Enlargement
Authors: Patel Kishan , Mikhael Elio , Liu Michael , Rangaraju Srikant , Ellis Deandra , Duncan Alexander , Belagaje Samir , Belair Trina , Henriquez Laura , Nahab Fadi
Published: June 2021

Background: The objective of this study was to evaluate if anticoagulation therapy reduces recurrent stroke in embolic stroke of undetermined source (ESUS) patients with left atrial enlargement (LAE) or abnormal markers of coagulation and hemostatic activity (MOCHA) compared to antiplatelet therapy.

Methods: ESUS patients from January 1, 2017, to June 30, 2019, underwent outpatient cardiac monitoring and the MOCHA profile (serum d-dimer, prothrombin fragment 1.2, thrombin–antithrombin complex, and fibrin monomer). Anticoagulation was offered to patients with abnormal MOCHA (≥2 elevated markers) or left atrial volume index 40 mL/m2. Patients were evaluated for recurrent stroke or major hemorrhage at routine clinical follow-up. We compared this patient cohort (cohort 2) to a historical cohort (cohort 1) who underwent the same protocol but remained on antiplatelet therapy.

Results: Baseline characteristics in cohort 2 (n = 196; mean age = 63 ± 16 years, 59% female, 49% non-White) were similar to cohort 1 (n = 42) except that cohort 2 had less diabetes (43 vs. 24%, p = 0.01) and more tobacco use (26 vs. 43%, p = 0.04). Overall, 45 patients (23%) in cohort 2 initiated anticoagulation based on abnormal MOCHA or LAE. During mean follow-up of 13 ± 10 months, cohort 2 had significantly lower recurrent stroke rates than cohort 1 (14 vs. 3%, p = 0.009) with no major hemorrhages.

Conclusions: Anticoagulation therapy in a subgroup of ESUS patients with abnormal MOCHA or severe LAE may be associated with a reduced rate of recurrent stroke compared to antiplatelet therapy. A prospective, randomized study is warranted to validate these results.
The Impact of Temporally Coherent Visual Cues on Speech Perception in Complex Auditory Environments
Authors: Yuan Yi , Lleo Yasneli , Daniel Rebecca , White Alexandra , Oh Yonghee
Published: June 2021

Speech perception often takes place in noisy environments, where multiple auditory signals compete with one another. The addition of visual cues such as talkers’ faces or lip movements to an auditory signal can help improve the intelligibility of speech in those suboptimal listening environments. This is referred to as audiovisual benefits. The current study aimed to delineate the signal-to-noise ratio (SNR) conditions under which visual presentations of the acoustic amplitude envelopes have their most significant impact on speech perception. Seventeen adults with normal hearing were recruited. Participants were presented with spoken sentences in babble noise either in auditory-only or auditory-visual conditions with various SNRs at −7, −5, −3, −1, and 1 dB. The visual stimulus applied in this study was a sphere that varied in size syncing with the amplitude envelope of the target speech signals. Participants were asked to transcribe the sentences they heard. Results showed that a significant improvement in accuracy in the auditory-visual condition versus the audio-only condition was obtained at the SNRs of −3 and −1 dB, but no improvement was observed in other SNRs. These results showed that dynamic temporal visual information can benefit speech perception in noise, and the optimal facilitative effects of visual amplitude envelope can be observed under an intermediate SNR range.