bluuebunny/crossref_metadata_2025 huggingface dataset:
Arte hí­brida, computação e espaço: da zero-dimensionalidade à multidimensionalidade
Authors: Nespoli Eduardo
Published: March 2023

O presente texto possui como proposta explorar as relações entre som, imagem e espaço em processos artí­sticos realizados a partir do uso de tecnologias eletrônicas e computacionais. Partindo da concepção de aparelho na teoria do filósofo Vilém Flusser, observa-se o uso de diferentes tecnologias enquanto suportes que possibilitam a convergência do audí­vel e do visí­vel. O texto investiga como, em certos processos artí­sticos, as tecnologias eletrônicas foram fragmentadas e remontadas com intuito de criar máquinas que produzem percepções de espaço e tempo singulares. Neste contexto, o computador é observado como máquina multimí­dia capaz de produzir a convergência entre diversos meios e materiais, possibilitando a geração de espaços multidimensionais. Destaca-se, deste modo, que no século XXI a arte incorpora a tecnologia enquanto metalinguagem, evocando processos de singularização do imaginário.
Rompendo o silêncio: animação Passages de Marie-Josée Saint-Pierre
Authors: Macêdo Silvana Barbosa , Queiroz Araújo Pamella Emília
Published: March 2023

Neste artigo nos debruçaremos sobre o documentário-animação autobiográfico Passages (2008) da cineasta canadense Marie-Josée Saint-Pierre (1978 –), que denuncia a violência obstétrica que a artista sofreu no Hospital Saint Luc, Montreal, Canadá. Para tanto, articularemos questões disparadas por esta obra, como silenciamento feminino e autobiografia, considerando perspectivas teóricas feministas. Abordaremos ainda a discussão em torno da medicalização do parto e o movimento de humanização do parto no Brasil. Por fim, examinaremos aspectos técnicos e poéticos da narrativa de Passages e sua contribuição para debates feministas sobre maternalismos contemporâneos.
Processos de formação de professores das licenciaturas em Ciências da Natureza: uma revisão sistemática
Authors: Sganzerla Francieli Luana , Soares Renata Godinho , Soruco Thais Menezes de Oliveira , Ruppenthal Raquel
Published: March 2023

A formação de professores aos poucos tem ganhado força, com o intuito de transformações na forma de ensinar, modelos didáticos utilizados, práticas pedagógicas facilitando que a interdisciplinaridade seja inserida de maneira que aconteça a interação e interligação entre as disciplinas, para melhor compreensão dos fenômenos do cotidiano. Buscou-se mapear as estratégias e abordagens metodológicas utilizadas para a formação inicial e continuada, em licenciaturas interdisciplinares na área de Ciências da Natureza. Realizou-se uma pesquisa bibliográfica, no portal de periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), segundo os descritores: ("formação de professor*") AND ("ciências") AND ("natureza"), selecionando apenas artigos com atividades realizadas com licenciatura em Ciências da Natureza ou Licenciatura Interdisciplinar (licenciaturas em Educação do Campo), com foco na área de Ciências da Natureza. Dos achados, selecionou-se 11 artigos publicados entre os anos de 2015 a 2020, sendo os mesmos divididos em dois tópicos: Formação de professores com estratégias ativas para os trabalhos que apresentassem alguma atividade prática em que o professor mostrasse ser sujeito ativo, e Formação de professores com abordagens teórico-reflexivo, as atividades práticas eram demonstradas aos professores participantes, seguida de teoria o que torna o envolvido um sujeito passivo. Conclui-se que discutir temas interdisciplinares de forma que haja trocas de conhecimento e experiências, na formação inicial e continuada, têm importância significativa do papel do professor para a construção do conhecimento.
Investigação sobre as percepções dos professores em relação ao processo de ensino mais inclusivo no contexto escolar
Authors: De Fatima Franzin Rozelaine , Dos Santos Antonio Vanderlei , Zandona Alioha Caetano
Published: March 2023

O presente estudo justifica-se pelas inquietações dos pesquisadores perante ao ensino de alunos surdos, pois tem-se resultados de estudos de outros autores, que muitas vezes os professores não têm qualificação adequada para atender a demanda de alunos com algum tipo de deficiência. Assim as perguntas que envolvem essa pesquisa estão centradas em: como está a qualificação docente perante questões inclusivas? A prática pedagógica está centrada em metodologias inclusivas? Nesse sentido, o objetivo principal é investigar de que forma o professor está atuando no contexto inclusivo a fim de contribuir com o processo de ensino aprendizagem de alunos surdos, que convivem num contexto escolar regular com diversas realidades. A metodologia está baseada na análise das informações supracitadas, que foram organizadas por meio da realização de um questionário e os resultados demonstraram que a maioria dos professores já tiveram ou tem alunos com alguma deficiência e que na sua maioria, não usam metodologias diferenciadas para ensino, mas se mostraram preocupados em querer se qualificar e melhorar o processo de ensino aprendizagem dos alunos com deficiência auditiva. Conclui-se que existe diversas metodologias que podem ser utilizadas pelos professores em sala de aula para trabalhar com alunos surdos e que possibilita a construção do conhecimento e melhoria no processo de ensino, além de disponibilizar aos professores novas formas de organizar sua prática pedagógica.
O uso de história de mulheres em aulas do ensino fundamental: existir, resistir e persistir é preciso
Authors: Salete Casagrande Lindamir
Published: March 2023

Estamos saindo de um período no qual os direitos humanos foram duramente atacados por um governo sustentado por uma parcela da população que se mostrou extremamente conservadora e violenta. Falar sobre gênero e sexualidade passou a ser arriscado e ofensivo à família brasileira. Cabe lembrar que a maioria das violações sexuais contra crianças e adolescentes são praticadas por familiares próximos. Precisamos existir, resistir e persistir na busca de formas diferenciadas para abordar estas temáticas com as/os estudantes. O uso de história de mulheres pode ser uma boa alternativa, além de ser uma atividade lúdica e interessante para as crianças. O objetivo deste artigo é refletir sobre o uso de história das mulheres em aulas do Ensino Fundamental para abordar diversos temas do currículo escolar. No decorrer do artigo apresentaremos algumas sugestões de atividades que as/os professoras/es podem desenvolver com os/as estudantes, bem como, faremos algumas indicações de livros e outros materiais que podem servir de ponto de partida para tais atividades. Convidamos as/os docentes a refletir sobre esta possibilidade e a proporcionar aulas diferenciadas para seus/suas alunos/as.
As cartas de apresentação do programa nacional do livro didático: uma análise discursiva
Authors: Santana Medeiros Lucas Matheus , Alves Márcia Regina , De Freitas Silvane Aparecida
Published: March 2023

Este artigo tem por objetivo apresentar alguns preceitos teóricos da Análise do Discurso de linha francesa (ADF), tais como discurso, sujeito e identidade, os quais são de suma relevância para se analisar os textos de nossa cultura. Em especial, para analisar as representações do professor nas cartas do Programa Nacional do Livro Didático (PNLD), as quais acompanham os livros didáticos para apresentar os guias, que direcionam o olhar do professor, quando se tem de fazer a escolha do livro didático nas escolas. Trata-se de uma pesquisa de caráter qualitativo com base nos pressupostos teóricos da Análise do Discurso de orientação francesa, com o recurso da revisão bibliográfica e análise discursiva das cartas de apresentação do Programa Nacional do Livro Didático (PNLD), em especial a carta de apresentação destinada ao ensino médio no ano de 2021. Sabemos que a Análise do Discurso é uma área do conhecimento heterogênea, levando em consideração o contexto sócio histórico ideológico de elaboração dessas cartas, visa maior compreensão das formações discursivas, da heterogeneidade, do jogo de imagens e dos diversos outros que constitui o discurso das Cartas do Livro Didático, destinadas ao professor. Assim sendo, concluímos que as cartas funcionam como um dispositivo institucional que marca um discurso autoritário, que busca controlar a representação do professor, mesmo sendo uma “simples” carta de apresentação do Guia, ali mesmo já tece a “falsa autonomia” que o docente tem ao escolher um livro didático.
Mini-Review: The importance of an integrated approach to assess trace mineral feeding practices in dairy cows
Authors: Duplessis Mélissa , Royer Isabelle
Published: March 2023

This mini-review was undertaken to demonstrate the impact of trace mineral feeding management of dairy cows on the ecosystem by discussing their role in the animal metabolism, dietary recommendations, current feeding practices, and their excretion in manure pertaining to five trace minerals, i.e., cobalt, copper, iron, manganese, and zinc. The first part of this mini-review relates the importance of trace minerals in dairy cow metabolism, and how recommendations are obtained. The following section showed that the transition period from the dry to the lactating phase is challenging for dairy cattle, and current trace mineral recommendations have been questioned for this period due to the role of some trace minerals in immunity and oxidative metabolism. Furthermore, trace mineral overfeeding is a common practice in intensive dairy production system in Canada, the USA, and the UK, which is far from precision nutrition. Trace minerals in excess of requirements are directly excreted into the manure. The practice of trace mineral overfeeding could have detrimental effects on the ecosystem when manure with high trace mineral concentrations is repeatedly spread on fields. In conclusion, an integrative approach assessing the impact of trace mineral overfeeding in cow diets on the ecosystem is needed.
Synthesis, radiolabeling, and evaluation of a (4-quinolinoyl)glycyl-2-cyanopyrrolidine analogue for fibroblast activation protein (FAP) PET imaging
Authors: Zhang Ni , Pan Fei , Pan Lili , Diao Wei , Su Feijing , Huang Rui , Yang Bo , Li Yunchun , Qi Zhongzhi , Zhang Wenjie , Wu Xiaoai
Published: March 2023

Fibroblast activation protein (FAP) is regarded as a promising target for the diagnosis and treatment of tumors as it was overexpressed in cancer-associated fibroblasts. FAP inhibitors bearing a quinoline scaffold have been proven to show high affinity against FAP in vitro and in vivo, and the scaffold has been radio-labeled for the imaging and treatment of FAP-positive tumors. However, currently available FAP imaging agents both contain chelator groups to enable radio-metal labeling, making those tracers more hydrophilic and not suitable for the imaging of lesions in the brain. Herein, we report the synthesis, radio-labeling, and evaluation of a 18F-labeled quinoline analogue ([18F]3) as a potential FAP-targeted PET tracer, which holds the potential to be blood–brain barrier-permeable. [18F]3 was obtained by one-step radio-synthesis via a copper-mediated SNAR reaction from a corresponding boronic ester precursor. [18F]3 showed moderate lipophilicity with a log D7.4 value of 1.11. In cell experiments, [18F]3 showed selective accumulation in A549-FAP and U87 cell lines and can be effectively blocked by the pre-treatment of a cold reference standard. Biodistribution studies indicated that [18F]3 was mainly excreted by hepatic clearance and urinary excretion, and it may be due to its moderate lipophilicity. In vivo PET imaging studies indicated [18F]3 showed selective accumulation in FAP-positive tumors, and specific binding was confirmed by blocking studies. However, low brain uptake was observed in biodistribution and PET imaging studies. Although our preliminary data indicated that [18F]3 holds the potential to be developed as a blood–brain barrier penetrable FAP-targeted PET tracer, its low brain uptake limits its application in the detection of brain lesions. Herein, we report the synthesis and evaluation of [18F]3 as a novel small-molecule FAPI-targeted PET tracer, and our results suggest further structural optimizations would be needed to develop a BBB-permeable PET tracer with this scaffold.
Recent advances in the theoretical studies on the electrocatalytic CO2 reduction based on single and double atoms
Authors: Meng Yuxiao , Huang Hongjie , Zhang You , Cao Yongyong , Lu Hanfeng , Li Xi
Published: March 2023

Excess of carbon dioxide (CO2) in the atmosphere poses a significant threat to the global climate. Therefore, the electrocatalytic carbon dioxide reduction reaction (CO2RR) is important to reduce the burden on the environment and provide possibilities for developing new energy sources. However, highly active and selective catalysts are needed to effectively catalyze product synthesis with high adhesion value. Single-atom catalysts (SACs) and double-atom catalysts (DACs) have attracted much attention in the field of electrocatalysis due to their high activity, strong selectivity, and high atomic utilization. This review summarized the research progress of electrocatalytic CO2RR related to different types of SACs and DACs. The emphasis was laid on the catalytic reaction mechanism of SACs and DACs using the theoretical calculation method. Furthermore, the influences of solvation and electrode potential were studied to simulate the real electrochemical environment to bridge the gap between experiments and computations. Finally, the current challenges and future development prospects were summarized and prospected for CO2RR to lay the foundation for the theoretical research of SACs and DACs in other aspects.
Video abstract production guide
Authors: Ferreira Miguel , Lopes Betina , Granado António , Siopa Catarina , Gaspar Hugo , Castro Helena , Castro Sílvia , Loureiro João
Published: March 2023

Video abstracts are audio-visual representations of a scientific abstract that a researcher can use to complement an article. As a science communication tool, they stand as a novel and exciting way to present scientific discoveries, explore new formats, and reach new audiences. In this practice insight, we share the experience of creating a video abstract in Ecology, explaining and exemplifying the different stages of the process: selecting the paper, writing the script, producing the video, editing the video and promoting the film. Sharing the setbacks and wins of a video collaboration between researchers and science communicators, we hope to be a valuable contribution to all the people starting and already working in the field.
Communication-free shepherding navigation with multiple steering agents
Authors: Li Aiyi , Ogura Masaki , Wakamiya Naoki
Published: March 2023

Flocking guidance addresses a challenging problem considering the navigation and control of a group of passive agents. To solve this problem, shepherding offers a bio-inspired technique for navigating such a group of agents using external steering agents with appropriately designed movement law. Although most shepherding research is mainly based on the availability of centralized instructions, these assumptions are not realistic enough to solve some emerging application problems. Therefore, this paper presents a decentralized shepherding method where each steering agent makes movements based on its own observation without any inter-agent communication. Our numerical simulations confirm the effectiveness of the proposed method by showing its high success rate and low costs in various placement patterns. These advantages particularly improve with the increase in the number of steering agents. We also confirm the robustness and resilience properties of the proposed method via numerical simulations.
Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literature
Authors: Gehlen Rachel , Vandevelde Arne , de Laat Bas , Devreese Katrien M. J.
Published: March 2023

Background

The antiphospholipid syndrome (APS) is classified by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or adverse obstetric outcomes. The diagnosis and risk assessment of APS is challenging. This systematic review investigated if the thrombin generation (TG) assay could be helpful for APS diagnosis and risk assessment.

Methods

A systemic review was performed by searching two databases (MEDLINE and Embase) until March 31, 2022, using a search strategy with two concepts: APS and TG, and related keywords. Two reviewers independently screened the articles based on predefined inclusion and exclusion criteria. Data extraction and quality assessment with the Newcastle-Ottawa Scale (NOS) were performed independently. Synthesis Without Meta-analysis guidelines were followed for data synthesis reporting.

Results

Fourteen studies with 677 APS and 1,349 control subjects were included with variable quality according to the NOS. Twelve studies measured TG via the calibrated automated thrombogram (CAT) method using a fluorogenic substrate, whereas two used a chromogenic substrate-based TG assay. One study compared the CAT assay to the fully-automated ST Genesia® (Stago, France). Two studies initiated TG using platelet-rich plasma, whereas the rest of the studies used platelet-poor plasma. Resistance to activated protein C (aPC) was examined in ten studies. They reported a significant increase in aPC-resistance in APS patients compared to healthy controls, aPL-carriers, and thrombotic controls. Based on two studies, the prevalence of aPC-resistance was higher in APS patients compared to healthy controls and thrombotic controls with odds ratios of 5.9 and 6.8–12.8, respectively (p < 0.05). In contrast, no significant difference in aPC-resistance was found between APS patients and autoimmune disease controls. Furthermore, 7/14 studies reported TG-parameters including peak height, endogenous thrombin potential, lag time, and time to peak, but these outcomes were highly variable between studies. Furthermore, TG methodology between studies differed greatly, impacting the comparability of the studies.

Conclusion

aPC-resistance measured with TG was increased in APS patients compared to healthy and thrombotic controls, but the diagnostic and prognostic value is unclear compared to current diagnostic strategies. Studies of other TG-parameters were heterogeneous and more research is needed to identify their potential added value in APS diagnosis.

Systematic Review Registration

https://www.PROSPERO/, identifier: CRD42022308363
Early growth response-1: Key mediators of cell death and novel targets for cardiovascular disease therapy
Authors: Xie Yixin , Li Yongnan , Chen Jianshu , Ding Hong , Zhang Xiaowei
Published: March 2023

Significance

Cardiovascular diseases are seen to be a primary cause of death, and their prevalence has significantly increased across the globe in the past few years. Several studies have shown that cell death is closely linked to the pathogenesis of cardiovascular diseases. Furthermore, many molecular and cellular mechanisms are involved in the pathogenesis of the cardiac cell death mechanism. One of the factors that played a vital role in the pathogenesis of cardiac cell death mechanisms included the early growth response-1 (Egr-1) factor.

Recent Advances

Studies have shown that abnormal Egr-1 expression is linked to different animal and human disorders like heart failure and myocardial infarction. The biosynthesis of Egr-1 regulates its activity. Egr-1 can be triggered by many factors such as serum, cytokines, hormones, growth factors, endotoxins, mechanical injury, hypoxia, and shear stress. It also displays a pro-apoptotic effect on cardiac cells, under varying stress conditions. EGR1 mediates a broad range of biological responses to oxidative stress and cell death by combining the acute changes occurring in the cellular environment with sustained changes in gene expression.

Future Directions

The primary regulatory role played by the Egr-1-targeting DNAzymes, microRNAs, and oligonucleotide decoy strategies in cardiovascular diseases were identified to provide a reference to identify novel therapeutic targets for cardiovascular diseases.
Resolving the 1886 White Terraces riddle in the Taupō Volcanic Zone
Authors: Bunn A. Rex
Published: March 2023

Among the Seven Wonders of the Ancient World, only the Great Pyramid of Giza survives. Yet there is another, older than the seven, that was found and then lost again in the 19th century and once more located by the research herein: the White Terraces, named Te Tarata by indigenous peoples, of the Taupō Volcanic Zone in New Zealand. The greatest geoscience and tourist attractions in the southern hemisphere were the siliceous Pink and White Terraces. European, American, and British tourists bypassed the calcareous terraces at Saturnia, Yellowstone, and Pamukkale for the long sea voyage down to New Zealand. The 1886 Mount Tarawera eruption buried the siliceous terraces, decimating their indigenous owners and their tourism. An eruption crater lake now occupies much of the Rotomahana Basin in the Taupō Volcanic Zone, leading to assumptions that the Terraces were lost. However, no evidence was produced. The indigenous Māori owners did not believe they were lost. Controversy ensued. The resolution of this controversy is of economic and cultural importance as well as scientific interest. In 2011, a joint New Zealand-American project claimed to have found the Pink and White Terraces underwater in crater lake but produced no sinter samples. Recently, their claims were refuted. In Europe, terrestrial survey documents were unearthed, including compass bearings to the terraces by the German geologist Ferdinand Hochstetter. His survey records were digitally repatriated, and the reconstruction of his 1859 survey showed that the terrace springs lay outside the eruption crater. This renewed research in the Rotomahana Basin which has resolved the controversy. By studying topography and with the aid of Māori navigation knowledge, the geographic coordinates of the White Terraces have been triangulated and lie on land, on the shoreline outside the 1886 crater. Surprisingly, this evidence demonstrates that the White Terraces could have been located after the 1886 eruption by observation of the Rotomahana Basin with mapping available since 1864. Exploration and excavation of the Terraces are now possible. Even if degraded by the 1886 eruption, the White Terraces may earn a World Heritage listing and a second life in global tourism.
Deep semantic segmentation of unmanned aerial vehicle remote sensing images based on fully convolutional neural network
Authors: Zheng Guoxun , Jiang Zhengang , Zhang Hua , Yao Xuekun
Published: March 2023

In the era of artificial intelligence and big data, semantic segmentation of images plays a vital role in various fields, such as people’s livelihoods and the military. The accuracy of semantic segmentation results directly affects the subsequent data analysis and intelligent applications. Presently, semantic segmentation of unmanned aerial vehicle (UAV) remote-sensing images is a research hotspot. Compared with manual segmentation and object-based segmentation methods, semantic segmentation methods based on deep learning are efficient and highly accurate segmentation methods. The author has seriously studied the implementation principle and process of the classical deep semantic segmentation model—the fully convolutional neural network (FCN), including convolution and pooling in the encoding stage, deconvolution and upsampling, etc., in the decoding stage. The author has applied the three structures (i.e., FCN-32s, FCN-16s, and FCN-8s) to the UAV remote sensing image dataset AeroScapes. And the results show that the accuracy of vegetation recognition is stable at about 94%. The accuracy of road recognition can reach up to more than 88%. The mean pixel accuracy rate of the whole test dataset is above 91%. Applying full convolution neural network to semantic segmentation of UAV remote sensing images can improve the efficiency and accuracy of semantic segmentation significantly.
Seismic prediction of shale reservoir quality parameters: A case study of the Longmaxi–Wufeng formation in the WY area
Authors: Hu Xiuquan , Yu Wanli , Yi Chi , Xiao Chenjing , Li Jianghan , Wang Boqiang
Published: March 2023

Shale is a crucial natural gas resource, attracting global exploration and development interest. China has abundant shale gas resources that will drive future oil and gas exploration advances by increasing reserves and production. The WY shale gas field is the most productive and has the greatest potential for exploration and development. This study analyzed high-quality shale logging response characteristics and drilling logging, seismic, and analytical test data in the WY area to establish a rock physical model of seismic attribute parameters and shale reservoir quality parameters. Seismic elastic parameters were converted into indicators that directly reflect shale reservoir quality, such as total organic carbon (TOC), high-quality reservoir thickness, porosity, brittleness index, and crack development strength. Corresponding regression equations were established to predict quality parameters.The results showed that shale reservoir quality parameters have a good correlation with seismic parameters. The TOC distribution ranged from 2% to 5% in the study area and was generally high in the north but low in the south. The high-quality shale reserve had a thickness of over 40 meters, and except for the northwest region, the porosity was nearly over 4%. The overall brittleness of the study area was favorable, and the brittleness index was over 35%, which is suitable for network fractures formation in subsequent fracturing operations. The anisotropy of shale in S1l1I was small, and the overall fractures were underdeveloped in the study area. Drilling verifications showed that the prediction results of the quality parameters of high-quality shale reservoirs were consistent with actual drilling test results with high reliability. This study provides guidance for comprehensive prediction of sweet spots and subsequent fracturing and well location deployment.In summary, this study provides valuable insights into shale gas exploration and development in the WY area by establishing a rock physical model, predicting quality parameters, and offering guidance for fracturing and well location deployment.
Ba, Sr, and Rb feldspar/melt partitioning in recent eruptions from Teide-Pico Viejo volcanic complex, Tenerife: New insights into pre-eruptive processes
Authors: Dorado Olaya , Wolff John A. , Ramos Frank C. , Martí Joan
Published: March 2023

The behaviour of Group I and II elements during the petrogenesis of felsic igneous rocks is largely controlled by feldspar-liquid relationships. Numerous experimental studies have addressed plagioclase/melt element partitioning, with fewer studies devoted to potassium feldspar, and very few to albite-rich ternary-composition feldspar (An ∼ Or < Ab). However, the partition coefficient for Ba is known to increase by at least an order of magnitude through the crystallisation sequence sodic plagioclase–anorthoclase–potassium feldspar that is typical of sodic alkaline suites. Feldspars, glasses, and whole rocks in such suites may exhibit strong enrichments and depletions that can be used to track processes of crystal fractionation, cumulate formation, and cumulate recycling. Here, we review experimental feldspar/melt partitioning data for Ba, Sr, and Rb for all feldspars. Regression of available data provides expressions that appear to adequately model the compositional and temperature dependence of partition coefficients for albite-rich compositions. We have applied this model to feldspar and melt compositions of the products of several Holocene eruptions (Pico Viejo C, Pico Viejo H, Teide J2, Lavas Negras, Arenas Blancas, Montaña Rajada and Montaña Reventada) of the basanitic-phonolitic suite of the Teide-Pico Viejo volcanic system (Tenerife, Spain), using EPMA and LA-ICP-MS analyses. Comparing analysed feldspar/groundmass pairs with predicted partition coefficients obtained with the models provides a way of distinguishing between feldspars that are in or out of equilibrium with their host melt, and of reconstructing feldspar histories. The results demonstrate the existence of a distinct population of feldspars that had undergone accumulation, fusion and recrystallisation events, in Lavas Negras and Arenas Blancas flows. In addition, the anomalous trachytic composition of Montaña Reventada is due to melting of a feldspar-dominated cumulate. Application of these techniques to active magmatic systems will allow us a better understanding of different pre-eruptive processes, and ultimately improve volcanic hazard assessment.
Pubertal induction in Turner syndrome without gonadal function: A possibility of earlier, lower-dose estrogen therapy
Authors: Hasegawa Yukihiro , Hasegawa Tomonobu , Satoh Mari , Ikegawa Kento , Itonaga Tomoyo , Mitani-Konno Marie , Kawai Masanobu
Published: March 2023

Delayed and absent puberty and infertility in Turner syndrome (TS) are caused by primary hypogonadism. A majority of patients with TS who are followed at hospitals during childhood will not experience regular menstruation. In fact, almost all patients with TS need estrogen replacement therapy (ERT) before they are young adults. ERT in TS is administered empirically. However, some practical issues concerning puberty induction in TS require clarification, such as how early to start ERT. The present monograph aims to review current pubertal induction therapies for TS without endogenous estrogen production and suggests a new therapeutic approach using a transdermal estradiol patch that mimics incremental increases in circulating, physiological estradiol. Although evidence supporting this approach is still scarce, pubertal induction with earlier, lower-dose estrogen therapy more closely approximates endogenous estradiol secretion.
KATP channel mutations in congenital hyperinsulinism: Progress and challenges towards mechanism-based therapies
Authors: ElSheikh Assmaa , Shyng Show-Ling
Published: March 2023

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy/childhood and is a serious condition associated with severe recurrent attacks of hypoglycemia due to dysregulated insulin secretion. Timely diagnosis and effective treatment are crucial to prevent severe hypoglycemia that may lead to life-long neurological complications. In pancreatic β-cells, adenosine triphosphate (ATP)-sensitive K+ (KATP) channels are a central regulator of insulin secretion vital for glucose homeostasis. Genetic defects that lead to loss of expression or function of KATP channels are the most common cause of HI (KATP-HI). Much progress has been made in our understanding of the molecular genetics and pathophysiology of KATP-HI in the past decades; however, treatment remains challenging, in particular for patients with diffuse disease who do not respond to the KATP channel activator diazoxide. In this review, we discuss current approaches and limitations on the diagnosis and treatment of KATP-HI, and offer perspectives on alternative therapeutic strategies.
Transcriptional regulation of innate lymphoid cells and T cells by aryl hydrocarbon receptor
Authors: Helm Eric Y. , Zhou Liang
Published: March 2023

The aryl hydrocarbon receptor (Ahr) is a ligand-dependent transcription factor and facilitates immune cell environmental sensing through its activation by cellular, dietary, and microbial metabolites, as well as environmental toxins. Although expressed in various cell types, Ahr in innate lymphoid cells (ILCs) and their adaptive T cell counterparts regulates essential aspects of their development and function. As opposed to T cells, ILCs exclusively rely on germ-line encoded receptors for activation, but often share expression of core transcription factors and produce shared effector molecules with their T cell counterparts. As such, core modules of transcriptional regulation are both shared and diverge between ILCs and T cells. In this review, we highlight the most recent findings regarding Ahr’s transcriptional regulation of both ILCs and T cells. Furthermore, we focus on insights elucidating the shared and distinct mechanisms by which Ahr regulates both innate and adaptive lymphocytes.
Gene signature and prediction model of the mitophagy-associated immune microenvironment in renal ischemia-reperfusion injury
Authors: Chen Ruo-Yang , Li Da-Wei , Xie Hui , Liu Xiao-Wen , Zhuang Shao-Yong , Wu Hao-Yu , Wu Jia-Jin , Sun Nan , Qu Jun-Wen , Miao Jia-Yi , Zhong Chen , Huang Yu-Hua , Yuan Xiao-Dong , Zhang Ming , Zhang Wei-Jie , Hou Jian-Quan
Published: March 2023

Background

Renal ischemia-reperfusion injury (IRI) is an inevitable occurrence during kidney transplantation. Mitophagy, ferroptosis, and the associated immune microenvironment (IME) have been shown to play important roles in renal IRI. However, the role of mitophagy-associated IME genes in IRI remains unclear. In this study, we aimed to construct a prediction model of IRI prognosis based on mitophagy-associated IME genes.

Method

The specific biological characteristics of the mitophagy-associated IME gene signature were comprehensively analyzed using public databases such as GEO, Pathway Unification, and FerrDb. Correlations between the expression of prognostic genes and immune-related genes and IRI prognosis were determined by Cox regression, LASSO analysis, and Pearson’s correlation. Molecular validation was performed using human kidney 2 (HK2) cells and culture supernatant as well as the serum and kidney tissues of mice after renal IRI. Gene expression was measured by PCR, and inflammatory cell infiltration was examined by ELISA and mass cytometry. Renal tissue damage was characterized using renal tissue homogenate and tissue sections.

Results

The expression of the mitophagy-associated IME gene signature was significantly correlated with IRI prognosis. Excessive mitophagy and extensive immune infiltration were the primary factors affecting IRI. In particular, FUNDC1, SQSTM1, UBB, UBC, KLF2, CDKN1A, and GDF15 were the key influencing factors. In addition, B cells, neutrophils, T cells, and M1 macrophages were the key immune cells present in the IME after IRI. A prediction model for IRI prognosis was constructed based on the key factors associated with the mitophagy IME. Validation experiments in cells and mice indicated that the prediction model was reliable and applicable.

Conclusion

We clarified the relationship between the mitophagy-related IME and IRI. The IRI prognostic prediction model based on the mitophagy-associated IME gene signature provides novel insights on the prognosis and treatment of renal IRI.
Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups
Authors: Hurler Lisa , Szilágyi Ágnes , Mescia Federica , Bergamaschi Laura , Mező Blanka , Sinkovits György , Réti Marienn , Müller Veronika , Iványi Zsolt , Gál János , Gopcsa László , Reményi Péter , Szathmáry Beáta , Lakatos Botond , Szlávik János , Bobek Ilona , Prohászka Zita Z. , Förhécz Zsolt , Csuka Dorottya , Kajdácsi Erika , Cervenak László , Kiszel Petra , Masszi Tamás , Vályi-Nagy István , Würzner Reinhard ,   Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Lyons Paul A. , Toonen Erik J. M. , Prohászka Zoltán
Published: March 2023

Introduction

While complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.

Methods

We therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.

Results

We show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.

Conclusion

In conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted.
Design and performance of a 3D-Printed magnetorheological fluid-based adaptive vibration isolator
Authors: Choi Young T. , Yoo Byungseok , Park Jungjin , Pines Darryll J. , Wereley Norman M.
Published: March 2023

Emerging additive manufacturing (or 3D printing) can be advantageous for developing magnetorheological fluid (MRF)-based vibration isolators (MRVIs) because their designs can be easily and efficiently customized and also in-situ fabrication and repairing can be possible. In this study, a simple and compact adaptive MRVI was fabricated by using a 3D printing method. A masked stereolithography (MSLA) 3D printer was used for the fabrication of the rubber bellow and plastic lid parts of the MRVI. The electromagnet was mounted onto the lid, the reservoir was filled with an MRF, and the lid was simply assembled with the reservoir using a 3D-printed large thread without traditionally machined components. Using a material testing machine, the damper forces of the 3D-printed MRVI were measured under a constant velocity loading condition for different magnetic fields. From these tests, the magnetic field-controllable performances of the MRVI such as the MR yield force, the dynamic force range, the dissipated energy, and the secant stiffness were obtained. For the evaluation of the long-term performance reliability of the MRVI due to the MRF sedimentation, its magnetic field-controllable performances were tracked for 156 days with the variable testing intervals. Finally, the feasibility of the 3D-printed MRVI was experimentally confirmed.
The pathogenesis of zoonotic viral infections: Lessons learned by studying reservoir hosts
Authors: Begeman Lineke , van Riel Debby , Koopmans Marion P. G. , Kuiken Thijs
Published: March 2023

Zoonotic viral infections that cause severe disease or even death in some people may be asymptomatic or mild in reservoir hosts. Comparison of the pathogenesis of these two host categories may potentially explain the difference in disease. However, infections in reservoir hosts are often neglected. Therefore, we compared the pathogenesis of rabies virus, macacine alphaherpesvirus, West Nile virus, Puumala orthohantavirus, monkeypox virus, Lassa mammarenavirus, H5N1 highly pathogenic avian influenza, Marburg virus, Nipah virus, Middle East respiratory syndrome, and simian/human immunodeficiency viruses in both humans and reservoir hosts. We showed that most aspects of the pathogeneses were remarkably similar. The remaining differences lead to the identification of tipping points in the pathogeneses that are important for explaining the disease outcome in severe human cases. Further elucidating these tipping points by studying zoonotic viral infections in their reservoir hosts may teach us how to reduce the severity of zoonotic viral diseases in humans.
Serum cystatin C and mild cognitive impairment: The mediating role of glucose homeostasis
Authors: Li Kai , Xu Jing , Zhao Meiduo , Wu Jingtao , Mei Yayuan , Zhou Quan , Zhao Jiaxin , Li Yanbing , Yang Ming , Xu Qun
Published: March 2023

Background

This study explored the mediating role of glucose homeostasis indicators in the relationship between serum cystatin C and mild cognitive impairment (MCI).

Methods

The present study used a cross-sectional design and included 514 participants aged ≥50 years in Beijing, China. The Mini-Mental State Examination was used to assess cognitive function. Serum cystatin C and a comprehensive set of glucose homeostasis indicators were detected, including fasting blood glucose (FBG), glycosylated albumin percentage (GAP), glycated hemoglobin (HbAlc), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-β). Generalized linear models were used to investigate the associations among cystatin C, glucose homeostasis indicators, and cognitive function. Mediation analysis was conducted to explore potential mediator variables.

Results

In this study of 514 participants, 76 (14.8%) had MCI. Those with cystatin C levels ≥1.09 mg/L had a 1.98-fold higher risk of MCI than those with levels <1.09 mg/L (95% CI, 1.05–3.69). FBG, GAP, and HbA1c increased the risk of MCI, while HOMA-β decreased the risk. Notably, the associations between MCI risk and cystatin C or glucose homeostasis were only founded in diabetes patients. Serum cystatin C was found to be positively associated with HOMA-β (beta (95% CI): 0.20 [0.06, 0.34]), HOMA-IR (0.23 [0.09, 0.36]), and insulin (0.22 [0.09, 0.34]) levels. Moreover, HOMA-β was identified as playing a negative mediating role (proportion mediated: −16%) in the relationship between cystatin C and MCI.

Conclusion

Elevated levels of cystatin C are associated with an increased risk of MCI. The glucose homeostasis indicator, HOMA-β, plays a negative mediating role in the relationship between cystatin C and MCI risk.
Case report: A novel STXBP1 splice variant and the landscape of splicing-involved STXBP1-related disorders
Authors: Wang Haiping , Chen Xiuli , Liu Zhanli , Chen Chen , Liu Xin , Huang Mingwei , Zhou Zhuying
Published: March 2023

STXBP1 variants are one of the most common genetic causes of neurodevelopmental disorders and epilepsy, wherein STXBP1-related disorders are characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of affected patients. However, the spectrums of both genotype and phenotype are quite wide and diverse, with a high baseline variability even for recurrent STXBP1 variants. Until now, no clear genotype–phenotype correlations have been established and multiple disease mechanisms have been proposed for STXBP1-related disorders. Without an ascertained disease cause for many cases of STXBP1 variants, it is challenging to manage this disease in an effective manner and current symptom-based treatments are focused on seizure control only, which has a minimal impact on global development. A novel STXBP1 canonical splice variant, NM_001032221.4:c.578+2T>C, was reported in this study, together with detailed documentation of disease manifestations and treatment management. Further RNA expression analysis revealed abnormal intron retention and possible production of truncated STXBP1 proteins as a likely pathogenic mechanism. More importantly, the landscape of previously understudied STXBP1 splice variants and functional investigations was assessed for the first time to provide a context for the discussion of the complicated genotype–phenotype relationship of STXBP1-related disorders. Future cases of this disorder and a deeper mechanism-based understanding of its pathogenic cause are required for precision medicine and better disease management.
Oxygen gradient generator to improve in vitro modeling of ischemic stroke
Authors: Santiago João , Kreutzer Joose , Bossink Elsbeth , Kallio Pasi , le Feber Joost
Published: March 2023

Introduction

In the core of a brain infarct, perfusion is severely impeded, and neuronal death occurs within minutes. In the penumbra, an area near the core with more remaining perfusion, cells initially remain viable, but activity is significantly reduced. In principle, the penumbra can be saved if reperfusion is established on time, making it a promising target for treatment. In vitro models with cultured neurons on microelectrode arrays (MEAs) provide a useful tool to investigate how ischemic stroke affects neuronal functioning. These models tend to be uniform, focusing on the isolated penumbra, and typically lack adjacent regions such as a core and unaffected regions (normal perfusion). However, processes in these regions may affect neuronal functioning and survival in the penumbra.

Materials and methods

Here, we designed, fabricated, and characterized a cytocompatible device that generates an oxygen gradient across in vitro neuronal cultures to expose cells to hypoxia of various depths from near anoxia to near normoxia. This marks a step in the path to mimic core, penumbra, and healthy tissue, and will facilitate better in vitro modeling of ischemic stroke.

Results

The generator forms a stable and reproducible gradient within 30 min. Oxygen concentrations at the extremes are adjustable in a physiologically relevant range. Application of the generator did not negatively affect electrophysiological recordings or the viability of cultures, thus confirming the cytocompatibility of the device.

Discussion

The developed device is able to impose an oxygen gradient on neuronal cultures and may enrich in vitro stroke models.
A retrospect and outlook on the neuroprotective effects of anesthetics in the era of endovascular therapy
Authors: Zhang Tianhao , Deng Daling , Huang Shiqian , Fu Daan , Wang Tingting , Xu Feng , Ma Lulin , Ding Yuanyuan , Wang Kaixin , Wang Yafeng , Zhao Wenjing , Chen Xiangdong
Published: March 2023

Studies on the neuroprotective effects of anesthetics were carried out more than half a century ago. Subsequently, many cell and animal experiments attempted to verify the findings. However, in clinical trials, the neuroprotective effects of anesthetics were not observed. These contradictory results suggest a mismatch between basic research and clinical trials. The Stroke Therapy Academic Industry Roundtable X (STAIR) proposed that the emergence of endovascular thrombectomy (EVT) would provide a proper platform to verify the neuroprotective effects of anesthetics because the haemodynamics of patients undergoing EVT is very close to the ischaemia–reperfusion model in basic research. With the widespread use of EVT, it is necessary for us to re-examine the neuroprotective effects of anesthetics to guide the use of anesthetics during EVT because the choice of anesthesia is still based on team experience without definite guidelines. In this paper, we describe the research status of anesthesia in EVT and summarize the neuroprotective mechanisms of some anesthetics. Then, we focus on the contradictory results between clinical trials and basic research and discuss the causes. Finally, we provide an outlook on the neuroprotective effects of anesthetics in the era of endovascular therapy.