bluuebunny/crossref_metadata_2025 huggingface dataset:
Da tortura ao corpo torturado: A narrativa como resistência no conto O Leite em Pó da Bondade Humana
Authors: Chaves Maria Genailze de Oliveira Ribeiro , Smith Júnior Francisco Pereira
Published: January 2022

Com uma hermenêutica histórica e social, por meio da interdisciplinaridade entre história, sociologia e literatura, analisa-se no presente artigo a relação temática da tortura e do corpo torturado, a partir da literatura de testemunho, especificamente do teor testemunhal, no conto O Leite em Pó da Bondade Humana, (1983) de Haroldo Maranhão. Nesse viés, o objetivo do trabalho está em explorar a violência diante do corpo torturado na obra supracitada. Assim, a manifestação literária nessa narrativa, no contexto contemporâneo da literatura brasileira, amazônida e paraense, permite perceber que a obra estudada é parte dos acervos narrativos da literatura de testemunho, especificamente de teor testemunhal, que se firmam a partir do século XX, concomitante a isso se conhece a opressão política, bem como expõe as atrocidades que sofriam os presos políticos durante a ditadura militar de 1964 no Brasil, em que descortina um cenário real vivenciado por pessoas que resistiram as repressões dessa época.
Conhecimento dos enfermeiros intensivistas de um hospital público sobre sepse
Authors: Silva Keyla Bispo , Nogueira Valnice de Oliveira
Published: January 2022

Objetivos: avaliar o conhecimento do enfermeiro intensivista sobre sepse, apontar quais ações de enfermagem devem ser precocemente realizadas frente a pacientes com suspeita de sepse na Unidade de Terapia Intensiva e elencar as principais dificuldades dos enfermeiros frente ao cuidado aos pacientes com suspeita/ou diagnóstico de sepse. Método: Tratou-se de um estudo de campo, quantitativo, de caráter descritivo, exploratório. A coleta de dados foi realizada no período de julho a setembro de 2021, por meio virtual, no Google Forms© contendo questões sobre a caracterização da população e da sepse. O estudo contou com uma amostra 24 enfermeiros intensivistas que atuam em um hospital público. Resultados: A média de acertos do questionário aplicado foi de 50.46% e embora a sepse seja um tema frequentemente discutido, os enfermeiros desconhecem a definição atualizada de sepse de acordo com o Instituto Latino Americano de Sepse, bem como identificação de sinais e sintomas precoces. Vale destacar, que os enfermeiros obtiveram respostas assertivas no que tange às ações realizadas cotidianamente na terapia intensiva e está associada a prática assistencial.  Conclusão: Sugere-se a realização de ações de educação permanente bem como a elaboração de protocolos institucionais, com objetivo de promover a atualização dos enfermeiros intensivistas, acerca da sepse na assistência aos pacientes críticos.
Comparação dos perfis bioquímicos e hematológicos de pacientes com COVID-19 em seus diferentes desfechos: alta hospitalar e óbito
Authors: Silva Gabriel Frateschi Rebello da , Callante Alexandra Alejo , Nascimento Débora Pereira do , Araújo Iago Portolani de , Ribeiro Carolina Heitmann Mares Azevedo , Lo Prete Ana Cristina
Published: January 2022

Introdução: O vírus causador da COVID-19, SARS-CoV-2, apresenta como principal foco de comprometimento o trato respiratório, ainda hoje com muitos pacientes evoluindo para a forma mais grave. Por isso, deve-se identificar precocemente sinais e sintomas da COVID-19, além de possíveis fatores de risco e sinais de mau prognóstico envolvidos na progressão da doença. Objetivo: Desta forma, o presente trabalho teve por objetivo avaliar exames bioquímicos, hematológicos e de coagulação em pacientes diagnosticados com a COVID-19, a fim de identificar um padrão de prognóstico para os desfechos de alta hospitalar e óbito a partir de um compilado de dados descritivos de um repositório público. Metodologia: dados de pacientes atendidos entre 26 de fevereiro e 27 de junho de 2020 no Hospital Sírio-Libanês, disponibilizado por um repositório público, foram divididos em duas categorias para análises. Foram analisados os dados demográficos (gênero, idade e cidade onde o paciente reside) e dados clínicos/laboratoriais (resultados de exames), incluindo o desfecho (alta ou óbito). Resultados: Idade mais avançada e gênero masculino foram mais associados com o desfecho de óbito. Dímero-D e glicemia foram mais altas no grupo óbito, enquanto a TFG apresentou piora em ambos os grupos e TTPA, bilirrubina total, creatinina sérica, glicemia, dímero-D e PCR aumentaram no desfecho apenas dos pacientes que vieram à óbito, tendo esse último reduzido no grupo “alta hospitalar”. Além disso, houve menores índices de hemoglobina, eritrócitos e hematócrito, plaquetas e linfócitos, assim como aumento de leucócitos, neutrófilos e basófilos no grupo de pacientes que evoluiu para óbito. Conclusão: As variações encontradas nos parâmetros bioquímicos sugerem especialmente que a hiperglicemia está associada a casos mais graves, enquanto a análise de inflamação confirma pela PCR que esta condição foi mais exacerbada nos pacientes que morreram. Na análise de coagulação, o aumento do dímero-D foi associado a quadros mais graves e, nos hematológicos, os resultados refletem maior risco de anemia e resposta inflamatória sistêmica.
Isolamento social, uso de álcool e as notificações de violência física em uma Região do Nordeste Brasileiro, 2016-2021
Authors: Coelho Ananda Caroline Vasques Dantas , Araujo Gustavo Baroni , Azevedo Maria Janaina Alves de , Oliveira Lourival Veras de , Silva Paulo Thiago Gomes da , Henrique Giuliano Araújo , Ramalho Mariana Ferreira
Published: January 2022

O isolamento social e o uso de álcool relacionam-se com as notificações e, portanto demandam uma vigilância em saúde contínua visto que, eleva o risco da ocorrência dos casos de violência física em mulheres. Objetivou-se então, analisar o isolamento social e as notificações de violência física em uma Região Nordeste Brasileiro. Estudo ecológico descritivo a respeito das notificações de violência física em mulheres no Ceará. A coleta de dados ocorreu na base de dados do SINAN/DATASUS, no período de 2016 a 2021. Foram notificados 8.754 casos de violência física destacando-se o perfil das vítimas na raça parda 6.593, escolaridade: ensino médio incompleto: 1944. Houve predominância de consumo de bebida alcoólica no agressor da violência em 3.714 casos. As notificações apontaram um decréscimo significativo no ano de 2021implicando com o período de isolamento social na pandemia de COVID-19.
Manifestações patológicas em fachadas de construções históricas: estudo de caso da Igreja de Nossa Senhora do Carmo em São Luís – MA
Authors: Costa Luan da Silva , Silva Witson Andrade da
Published: January 2022

Os monumentos históricos são obras importantes para a sociedade, pois guardam parte da história de lugares e pessoas de vários séculos, por isso, é importante que sejam devidamente preservados, para que essa história não se perca. Com isso, este trabalho tem o objetivo de identificar e analisar as manifestações patológicas encontradas em edifícios históricos, através do estudo de caso da fachada da Igreja de Nosssa Senhora do Carmo e propor as possíveis causas e terapias de restauro. Apesar de ter vários séculos de existência, notou-se que a fachada da igreja permanece bem conservada em relação aos demais imóveis da região, no entanto, foi possível encontrar algumas avarias. Foi possível detectá-las através de visitas ao local e de inspeções visuais e fotográficas, além de comparações com as bibliografias estudadas. Com isso, foi possível identificar e examinar as manifestações patológicas encontradas, sugerir alguns restauros, para que a fachada da igreja de Nossa Senhora do Carmo continue com um bom nível de preservação.
Application of chitosan on physalis
Authors: Claus Alexandre , Sato Alessandro Jefferson , Tartaro Eloísa Lorenzetti , Algeri Alessandra , Oliveira Taila Letícia Antunes , Muhlbeier Débora Thaís , Claus Adenise Bottcher , Missio Robson Fernando
Published: January 2022

Cultivation of small fruits such as blackberry, raspberry, blueberry, strawberry, and physalis is rapidly growing in Brazil, mainly due to small producers who seek income diversification. The aim of this study was to evaluate the effect of foliar application of different doses of chitosan on the physicochemical properties of Physalis peruviana L. Two experiments were conducted: i) field (FE); and ii) greenhouse (GE). Four doses of chitosan (0.1, 0.2, 0.3, and 0.4 L 100L-1) and a control were used as treatments. We evaluated fruit diameter (FD), fruit length (FL), calyx length (CL), and calyx diameter (CD) - mm; fruit mass - g; soluble solids content (SS) - °Brix; titratable acidity (TA) - % of citric acid; SS/TA ratio; and fruit firmness - N. Foliar application of chitosan to field-grown physalis plants significantly increased fruit mass, length, and diameter, as well as fruit SS and TA content. However, in a protected environment, the application of chitosan had less effect on the properties evaluated. Fruit firmness was not affected by chitosan application. Negative correlations (P<0.001) between fruit mass and firmness (r=-0.57) and SS/TA ratio (r=-0.61) were observed. SS/TA ratio was also negatively correlated with TA (r=-0.82), FL(r=-0.61), and FD (r=-0.68). High and significant correlations were observed between fruit mass and TA, FL, and FD. Foliar application of chitosan has a positive effect on both agronomic and chemical properties and can be an excellent alternative natural fertilizer for physalis plants when applied in doses up to 0.2 L 100 L-1.
Revisão dos aspectos botânicos, químicos e farmacológicos de Adenium obesum (Forssk.) Roem. & Schult
Authors: Carvalho Renata Rodrigues de , Magalhães Cledson dos Santos , Randau Karina Perrelli
Published: January 2022

Devido as suas propriedades terapêuticas, as plantas são bastante utilizadas pela população para fins medicinais e para estudos científicos a respeito dos constituintes químicos e das ações farmacológicas. A exemplo, pode-se citar a espécie Adenium obesum (Forssk.) Roem. & Schult. pertencente à família Apocynaceae e popularmente conhecida como rosa do deserto. Na medicina tradicional essa espécie é empregada para tratar diferentes doenças venéreas como a gonorreia e para tratar feridas, infecções, rinite, entre outras afecções. Devido a isso, essa narrativa teve como objetivo descrever os aspectos botânicos, químicos e farmacológicos da espécie. Desse modo, observou-se que a variedade dos constituintes químicos de A. obesum engloba a presença de glicosídeos cardíacos, com aproximadamente 50 fitoquímicos pertencentes à classe dos cardenolídeos, pregnanos, triterpenos e flavonoides. Estes, estão relacionados as atividades biológicas e pode-se constatar a atividades anticâncer, antiviral, antibacteriana, tripanocida, acaricida, moluscicida, antioxidante e pesticida. Portanto, esse compilado de informações de A. obesum mostra a grande importância dessa espécie. Entretanto, torna-se necessário mais pesquisas acerca dos componentes fitoquímicos e atividades biológicas realizadas com diferentes partes da espécie, uma vez que tais componentes podem apresentar favorável potencialidade na incorporação de futuros produtos farmacêuticos.
Solução de crimes ambientais pelo Poder Judiciário na Amazônia legal: a utilização da perícia ambiental
Authors: Cunha Maria do Socorro Soares da , Oliveira Danilo Elias de
Published: January 2022

A solução de crimes ambientais, no âmbito de processos judiciais tramitados no Poder Judiciário, muitas das vezes, demanda a necessidade de intervenção de variados campos do conhecimento, entre eles, cita-se a perícia ambiental. Essa modalidade de perícia consiste em um meio de produção de provas capaz de desvendar a extensão do dano ambiental ao meio ambiente e, por consequência, estimar a reparação devida, seja na forma de indenização ou obrigação de fazer. Para além disso, a perícia ambiental subsidia o julgador de conhecimentos específicos que fogem de sua formação acadêmica, auxiliando-o até mesmo na fundamentação da sentença que será proferida. Assim, levando em consideração que a Constituição de 1988, na norma agasalhada no art. 225, assegura que todos têm direito ao meio ambiente ecologicamente equilibrado, bem de uso comum do povo e essencial à sadia qualidade de vida, impondo-se ao Poder Público e à coletividade o dever de defendê-lo e preservá-lo para as presentes e futuras gerações, o combate aos crimes ambientais é um dever do Estado, e para tanto, a perícia ambiental representa uma grande aliada da solução de crimes que viola o meio ambiente (bem ambiental). Isso posto, dada a sua importância, o presente artigo tem como fito apresentar de que modo a perícia ambiental vem contribuindo no Poder Judiciário para solucionar os crimes ambientais, sobretudo na região da Amazônia Legal. O percurso metodológico a ser realizado é o da pesquisa bibliográfica e documental, com consulta a livros, periódicos, artigos, dissertações e diplomas normativos relacionados com o tema.
A relação entre educação e trabalho na perspectiva de Simone Weil: uma proposta para o ensino de filosofia
Authors: Duarte Rodrigo Gonçalves , Duarte Leonardo Felipe Gonçalves
Published: January 2022

A temática abordada nesta investigação pretende analisar a questão da educação e sua relação com o trabalho, de acordo com Simone Weil, que dedicou a sua vida em prol da igualdade da classe trabalhadora. A pesquisa parte de uma indagação norteadora em relação ao método pedagógico chamado de “tradução”, proposto por essa filósofa, para a educação de operários e camponeses, no início do século XX: este método pode ser aplicado para o ensino de filosofia no ensino médio das escolas públicas, no Brasil, nos dias de hoje? Esta pesquisa se caracteriza como uma revisão bibliográfica realizada na base de dados do Google Acadêmico. É expressivo ressaltar que o ensino de filosofia se mostrou importante para a educação, considerando-se que, para os alunos, parece ser necessário apontar uma visão diferenciada, reflexiva e crítica sobre a filosofia, assim como fizeram Weil e outros pensadores, a partir da tradução da fala filosófica de forma a facilitar a aprendizagem dos alunos.
PROBLEMATIK BATAS ANTARA SASTRA LOKAL, SASTRA NASIONAL, DAN SASTRA GLOBAL
Authors: Pertiwi Ratih Tri
Published: January 2022

Abstract: This study aims to expose the vagueness of the boundaries between local, national, and global literature. This research is literature research. This study presents evidence that limiting the boundaries between local, national, and global literature is problematic. The results of this study show that local, national, and global literature presents a intersecting and overlapping. Local literature can be said to be national literature because of some of its characteristics, national literature can also be said to be global literature because of some of its rubber, and vice versa. Based on the results of the study, it can be concluded that the most important thing is not the categorization of that type of literature, but the utilization of the literary work. Keywords: Problematic Boundaries, Literature, Local, Naional, Global
PENGEMBANGAN MODEL MATERI AJAR BAHASA INDONESIA BAGI PENUTUR ASING (BIPA)
Authors: Purbarani Etsa , Muliastuti Liliana , Farah Siti
Published: January 2022

Sampai saat ini, jumlah dan variasi materi ajar BIPA masih minim. Materi ajar BIPA yang sudah disahkan oleh Kementerian Pendidikan dan Kebudayaan RI pun belum dapat dikatakan memenuhi kebutuhan komunikasi yang dimaksud. Materi tata bahasa, keterampilan berbahasa, dan budaya disampaikan secara integratif, tetapi kegiatan belajar di dalamnya belum sepenuhnya menjembatani pemelajar asing untuk dapat berkomunikasi dalam bahasa Indonesia secara layak dengan memperhatikan konteks, masyarakat, dan budaya Indonesia. Hal tersebut menimbulkan masalah bagi pemelajar asing. Pemelajar asing menemukan bahwa bahasa Indonesia yang dipelajari di dalam kelas berbeda dengan penggunaan bahasa Indonesia pada masyarakat. Pemelajar asing bisa saja mendapatkan nilai yang tinggi di dalam kelas, tetapi tidak memiliki kepercayaan diri, pemahaman, dan kompetensi berkomunikasi dalam bahasa Indonesia. Berdasarkan situasi, penelitian ini berfokus pada pengembangan model materi ajar BIPA berbasis CEFR dengan mengintegrasikan aspek-aspek komunikasi (communication), budaya (cultures), keterkaitan (connections), perbandingan (comparison), dan masyarakat/komunitas (communities). Kelima aspek tersebut dikenal dengan istilah 5C dan menjadi landasan penting dalam mempelajari bahasa asing, salah satunya bahasa Indonesia. Dengan mengintegrasikan kelima aspek tersebut dalam materi ajar menyimak, berbicara, membaca, menulis, dan tata bahasa, pemelajar asing dapat menguasai kompetensi berbahasa Indonesia dengan lebih baik serta komprehensif. Selain itu, pemelajar asing juga didorong untuk menguasai kompetensi berkomunikasi dalam bahasa Indonesia secara lebih layak sehingga tidak terjadi missing link antara bahasa Indonesia yang dipelajari di kelas maupun bahasa Indonesia yang secara nyata digunakan dalam masyarakat. Model materi ajar yang dikembangkan akan terfokus pada tingkat B1 atau menengah awal karena pada tingkat tersebut pemelajar BIPA sudah mulai mampu memahami, mendiskusikan, dan berkomunikasi tentang topik-topik yang lebih abstrak seperti topik kebudayaan non-kebendaan yang berkaitan dengan logika kolektif, kebiasaan, dan tradisi.
KESANTUNAN BERBAHASA DAN PELANGGARANNYA DALAM CHANNEL YOUTUBE DEDDY CORBUZIER EDISI “SITI FADILAH : SEBUAH KONSPIRASI”
Authors: Murniatie Itznaniyah Umie
Published: January 2022

Abstrak: Salah satu tujuan berkomunikasi adalah untuk dapat menjalin hubungan sosial dengan masyarakat, sehingga tercipta keberhasilan dalam proses komunikasi. Ungkapan kesopanan dalam sebuah proses komunikasi, dapat menjadi penentu dari kualitas sikap seseorang, utamanya, pembicara. Atau dengan kata lain, karakter, watak, sikap dan pribadi seseorang tercermin dari kalimat yang dia ucapkan kepada lawan tutur. Metode yang digunakan dalam penelitian ini adalah metode kualitatif yang bersifat deskriptif. Metode deskriptif digunakan untuk mendeksripsikan pelaksanaan dan pelanggaran maksim kesantunan pada acara Wawancara Deddy Corbuzier dan Fadilah Supari (Mantan Menteri Kesehatan Republik Indonesia). Berdasarkan hasil analisis dan pembahasan terhadap “Kesantunan Berbahasa dan Pelanggarannya dalam Channel Youtube Deddy Corbuzier Edisi “Siti Fadilah : Sebuah Konspirasi”” ditemukan 13 penggunaan maksim kesantunan berbahasa, dan 10 pelanggaran maksim kesantunan berbahasa. Penggunaan maksim kesantunan berbahasa yang paling banyak ditemukan pada maksim pujian/penghargaan, dan maksim kerendah hatian, yaitu terdapat 3 maksim. Sedangkan pelanggaran maksim kesantunan berbahasa, paling banyak ditemukan pada maksim kebijaksanaan, yaitu terdapat 10 tuturan. Kata kunci: kesantunan berbahasa, pelanggaran, wawancara, youtube, mantan Menteri Kesehatan.
MENDADAK E-LEARNING : STUDI KUALITATIF MAHASASISWA PERGURUAN TINGGI SELAMA MASA PANDEMI COVI-19
Authors: Mazhabi Zobi , Amirudin Yoyok
Published: January 2022

AbstractPandemi Covid 19 membawa gangguan besar pada dunia pendidikan, memberikan tantangan baru bagi dunia pendidikan, dan membuat banyak stake holders lembaga pendidikan menjadi stressl. Penelitian ini bertujuan untuk menganalisis persepsi mahasiswa terhadap peralihan pembelajaran off line ke pembelajaran online pada masa pandemi Covid 19. Penelitian ini dilakukan secara kualitatif melalui pelaksanaan wawancara prastruktur dengan melibatkan 35 mahasiswa yang tersebar di dua fakultas yang berbeda, enam jurusan yang berbeda, dan dipilih dari 245 mahasiswa. Wawancara dilakukan untuk mengumpulkan data dan untuk mendapatkan batasan persepsi dan pengalaman langsung dari mahasiswa yang menjadi salah satu bagian dari elemen utama masalah ini. Itu juga dilakukan berdasarkan pedoman yang dirancang oleh peneliti dan data yang dikumpulkan dianalisis dengan metode analisis isi dalam bentuk analisis isi deskriptif, analisis isi inferensial, analisis isi pssikgometrik, analisis isi prediktif. Temuan penelitian ini menunjukkan bahwa pembelajaran online selama pandemi Covid-19 memberikan kontribusi pengalaman positif dan pengalaman negatif kepada siswa baik dari segi unsur fisik, unsur psikologis, dan unsur kognitif. Temuan tersebut mengarah pada kesimpulan bahwa, dosen perlu melihat peluang, kelemahan, kekuatan, dan ancaman dari isu-isu yang bergeser ini untuk mendapatkan tindakan yang mungkin untuk pengembangan sistem pembelajaran online yang lebih baik.  AbstractThe Covid 19 pandemic brings significant distruption to education, carrying out new challenge for education, and making alot of educational institutions stake holders becoming stressfull. This study aimed at analyzing the college students perception on shifting off line learning to online learning during Covid 19 pandemic . This study was conducted qualitatively through the implemetation of pre-structure interview by involving 35 student who spread in two different kinds of faculties, six different majors, and selected from 245 college students. The Interview was conducted to gather the data and to gain boundaries of direct perception and experiences belong to college students who became one part of primary element to this issue. It also was conducted based on the guidelines designed by the researchers and the data gathered analyzed with content analysis method in term of descriptive content analysis, inferential content analysis, psychometric content analysis, predictive content analysis. The findings of this research showed that on-line learning during Covid-19 pandemic contributed both of positive experience and negative experience to the students in term of physical element, psychological element, and cognitive element. The finding lead to the conclusion that, the lectures need to pretend to the opportunities, weaknesses, strength, and threats of this shifting issues in order to obtain the possible action for better development of the on-line learning system.
PENDIDIKAN TATA KRAMA UNTUK ANAK USIA DINI
Authors: Fadhilah Alya Nur
Published: January 2022

AbstractPendidikan mengenai tata krama merupakan hal yang harus diberikan sejak anak usia dini. Anak usia dini merupakan usia menerima pengaruh disekitar dengan cepat dan menjadi pondasi untuk pendidikan selanjutnya, maka guru memiliki kewajiban untuk mendidik anak termasuk tata krama. Penelitian ini menggunakan kualitatif dengan pendekatan studi kasus. Data dikumpulkan dengan wawancara dan observasi, kemudian uji keabsahan data dilakukan dengan triangulasi. Hasil dari penelitian ini adalah guru di RA Syihabuddin Malang tidak hanya menggunakan video pendukung dalam pendidikan tata krama. Guru menggunakan praktik langsung dengan pembiasaan tata krama dasar seperti mengucapkan kata “maaf, tolong, terimakasih”, mengetuk pintu dan memberi salam, mendengarkan orang lain saat berbicara dan tidak menyela saat orang lain berbicara. Kata kunci: Guru, Pendidikan, Tata Krama, Anak Usia Dini. AbstractThe education about manners is something that must be given to an early childhood. Early childhood is the age of receiving influences around them quickly and it becomes the foundation for their further education. Teachers have an obligation to educate children, including about manners. This research is a qualitative research with case study approached. Data were collected by an observation and an interviews. The validity used a triangulation. The results of this research are the teachers of RA Syihabuddin Malang not depends the manners education with a video, they uses hands-on practice habits for manners education with basic manners such as saying the words “sorry, please, thank you”, knocking on doors before entering the room and greetings, listening to others when they are talking and not interrupting. Key words: Teacher, Education, Manners, Early Childhood,
New Bound on the Chebyshev function and the Riemann Hypothesis
Authors: Vega Frank
Published: January 2022

Under the assumption that the Riemann hypothesis is true, von Koch deduced the improved asymptotic formula $\theta(x) = x + O(\sqrt{x} \times \log^{2} x)$, where $\theta(x)$ is the Chebyshev function. We prove if there exists some real number $x \geq 10^{8}$ such that $\theta(x) > x + \frac{1}{\log \log \log x} \times \sqrt{x} \times \log^{2} x$, then the Riemann hypothesis should be false. In this way, we show that under the assumption that the Riemann hypothesis is true, then $\theta(x) < x + \frac{1}{\log \log \log x} \times \sqrt{x} \times \log^{2} x$ for all $x \geq 10^{8}$.
Ferroptosis Mediation Patterns Reveal Novel Tool to Implicate Immunotherapy and Multi-Omics Characteristics in Bladder Cancer
Authors: Liu Jingchao , Zhang Zhipeng , Zhang Wei , Meng Lingfeng , Wang Jiawen , Lv Zhengtong , Xia Haoran , Wu Meng , Zhang Yaoguang , Wang Jianye
Published: January 2022

Background: The regulatory role of ferroptosis in malignant tumours has been recently demonstrated. However, the potential roles of ferroptosis mediation patterns in bladder cancer remain elusive.

Materials and Methods: The ferroptosis mediation patterns of 889 bladder cancer samples were comprehensively evaluated based on ferroptosis-related genes. The underlying correlations between these mediation patterns and multi-omic characteristics of bladder cancer were systematically analysed. The ferroptosis mediation patterns of individual samples were quantified by ferropscore using the principal component analysis algorithm. The typical ferroptosis-related genes with prognostic roles were further randomly validated using immunohistochemical staining, real-time polymerase chain reaction and western blotting.

Results: Three different ferroptosis mediation patterns were identified. The abundance of infiltration of 23 immune cells was different among the three mediation patterns. The quantification of ferroptosis mediation patterns in individual samples served as a promising tool for predicting patient survival outcomes; immune cell infiltration abundance; tumour mutation burden; oncogenic mutation status and tumour grade, stage and molecular subtypes. Low ferropscore combined with high tumour mutation burden was associated with the best survival prognosis. Expressions of PD-L1 (p < 0.001), PD-1 (p = 0.002) and CTLA-4 (p = 0.003) were all significantly upregulated in the high ferropscore group. Low ferropscores also predicted good immunotherapy response for anti-CTLA4 strategy. The mRNA and protein levels of FADS2, a typical ferroptosis-related gene used in the study, were higher in bladder cancer cell lines than in controlled SV-HUC-1 cells. In addition, immunohistochemical staining revealed significantly higher expression levels of FADS2 in human bladder cancer tumour tissues than in normal tissues.

Conclusion: This study identified three distinct ferroptosis mediation patterns in bladder cancer. Quantification of ferroptosis mediation patterns in individual samples may help to improve the understanding of multiomic characteristics and guide future immunotherapy responses to bladder cancer.
Aolatg1 and Aolatg13 Regulate Autophagy and Play Different Roles in Conidiation, Trap Formation, and Pathogenicity in the Nematode-Trapping Fungus Arthrobotrys oligospora
Authors: Zhou Duanxu , Zhu Yingmei , Bai Na , Xie Meihua , Zhang Ke-Qin , Yang Jinkui
Published: January 2022

Autophagy is a conserved cellular recycling and trafficking pathway in eukaryotes that plays an important role in cell growth, development, and pathogenicity. Atg1 and Atg13 form the Atg1–Atg13 complex, which is essential for autophagy in yeast. Here, we characterized the roles of the Aolatg1 and Aolatg13 genes encoding these autophagy-related proteins in the nematode-trapping fungus Arthrobotrys oligospora. Investigation of the autophagy process by using the AoAtg8-GFP fusion protein showed that autophagosomes accumulated inside vacuoles in the wild-type (WT) A. oligospora strain, whereas in the two mutant strains with deletions of Aolatg1 or Aolatg13, GFP signals were observed outside vacuoles. Similar results were observed by using transmission electron microscopy. Furthermore, deletion of Aolatg1 caused severe defects in mycelial growth, conidiation, conidial germination, trap formation, and nematode predation. In addition, transcripts of several sporulation-related genes were significantly downregulated in the ΔAolatg1 mutant. In contrast, except for the altered resistance to several chemical stressors, no obvious differences were observed in phenotypic traits between the WT and ΔAolatg13 mutant strains. The gene ontology analysis of the transcription profiles of the WT and ΔAolatg1 mutant strains showed that the set of differentially expressed genes was highly enriched in genes relevant to membrane and cellular components. The Kyoto Encyclopedia of Genes and Genomes analysis indicated that differentially expressed genes were highly enriched in those related to metabolic pathways, autophagy and autophagy-related processes, including ubiquitin-mediated proteolysis and SNARE interaction in vesicular transport, which were enriched during trap formation. These results indicate that Aolatg1 and Aolatg13 play crucial roles in the autophagy process in A. oligospora. Aolatg1 is also involved in the regulation of asexual growth, trap formation, and pathogenicity. Our results highlight the importance of Aolatg1 in the growth and development of A. oligospora, and provide a basis for elucidating the role of autophagy in the trap formation and pathogenicity of nematode-trapping fungi.
Paradoxical Association Between Baseline Apolipoprotein B and Prognosis in Coronary Artery Disease: A 36,460 Chinese Cohort Study
Authors: Li Huanqiang , Wang Bo , Mai Ziling , Yu Sijia , Zhou Ziyou , Lu Hongyu , Lai Wenguang , Li Qiang , Yang Yongquan , Deng Jingru , Tan Ning , Chen Jiyan , Liu Jin , Liu Yong , Chen Shiqun
Published: January 2022

Background

Apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) were identified targets for blood lipid management among coronary artery disease (CAD) patients. However, previous studies reported an inverse correlation between baseline LDL-C concentration and clinical outcomes. This study aims to explore the definite association between baseline ApoB and long-term prognosis.

Methods

A total of 36,460 CAD patients admitted to Guangdong Provincial People's Hospital were enrolled and categorized into two groups: high ApoB (≥65 mg/dL) group and low ApoB (<65 mg/dL) group. The association between baseline ApoB and long-term all-cause mortality was evaluated by the Kaplan-Meier method, Cox regression analyses and restricted cubic splines.

Results

The overall mortality was 12.49% (n = 4,554) over a median follow-up period of 5.01 years. Patients with low baseline ApoB levels were paradoxically more likely to get a worse prognosis. There was no obvious difference in risk of long-term all-cause mortality when only adjusted for age, gender, and comorbidity (aHR: 1.07, 95% CI: 0.99–1.16). When CONUT and total bilirubin were adjusted, the risk of long-term all-cause mortality would reduce in the low-ApoB (<65 mg/dL) group (aHR: 0.86, 95% CI: 0.78–0.96). In the fully covariable-adjusted model, patients in the ApoB <65 mg/d group had a 10.00% lower risk of long-term all-cause mortality comparing to patients with ApoB ≥65 mg/dL (aHR: 0.90; 95% CI:0.81–0.99).

Conclusion

This study found a paradoxical association between baseline ApoB and long-term all-cause mortality. Malnutrition and bilirubin mainly mediate the ApoB paradox. Increased ApoB concentration remained linearly associated with an increased risk of long-term all-cause mortality.
Is Covid-19 Severity Associated With ACE2 Degradation?
Authors: Bastolla Ugo , Chambers Patrick , Abia David , Garcia-Bermejo Maria-Laura , Fresno Manuel
Published: January 2022

Covid-19 is particularly mild with children, and its severity escalates with age. Several theories have been proposed to explain these facts. In particular, it was proposed that the lower expression of the viral receptor ACE2 in children protects them from severe Covid-19. However, other works suggested an inverse relationship between ACE2 expression and disease severity. Here we review the seemingly contradicting observations on ACE2 expression at the levels of mRNA, membrane protein and serum protein in humans and rodents and try to reconcile them at the light of the Renin-Angiotensin system (RAS) and bradykinin system, which constitute an integrated inflammatory system connected by common peptidases and interacting receptors. We find that ACE2 level is not monotonically related with age but it reaches a maximum at a young age that depends on the cell type and then decreases, consistently with almost all existing data. The increase with age of the protease Tumor necrosis factor alpha (TNF-α) converting enzyme (TACE), also known as ADAM17 (a disintegrin and metalloproteinase 17) that sheds ACE2 from the cell membrane to the serum predicts that the decrease occurs before and is steeper for ACE2 cell protein than for its mRNA. This negative relation between ACE2 level and Covid-19 severity at old age is not paradoxical but it is consistent with a mathematical model that predicts that higher viral receptor does not necessarily favour virus propagation and it can even slow it down. More importantly, the angiotensin-bradykinin system is characterized by a powerful positive feedback loop that enhances inflammation through the Angiotensin and Bradykinin receptors that upregulate ADAM17, which in turn downregulates ACE2 and upregulates TNF-α and the pro-inflammatory receptor of the cytokine interleukin 6 (IL6). Here we propose that ACE2 contributes essentially to reverse this inflammatory state by downregulating the pro-inflammatory peptides of the angiotensin-bradykinin system, and that failure to do this, possibly induced by the degradation of ACE2 by SARS-COV-2, may underlie both severe CoViD-19 infection and its many post-infection manifestations, including the multi-inflammatory syndrome of children (MIS-C). Within this view, lower severity in children despite lower ACE2 expression may be consistent with their higher expression of the alternative angiotensin II receptor ATR2 and in general of the anti-inflammatory arm of the RAS at young age.
Mass Balance of Four Mongolian Glaciers: In-situ Measurements, Long-Term Reconstruction and Sensitivity Analysis
Authors: Khalzan Purevdagva , Sakai Akiko , Fujita Koji
Published: January 2022

This study describes the in situ observed and modeled mass balances of four representative glaciers in the Mongolian Altai Mountains. Mass-balance stakes and automatic weather stations (AWS) were installed along each glacier to obtain the in situ mass balances and meteorological variables. We calibrate the ERA5 meteorological variables using the observed values, then estimate the precipitation parameters to obtain the observed point mass balances using an energy- and mass-balance model. We evaluate the mass-balance profile and glacier-wide mass balance via a mass-balance model using the calibrated ERA5 data and estimated precipitation parameters to fill in the spatial and temporal gaps in the stake networks and AWS measurements. We demonstrate that almost all of the observed mass balances have been in a negative state since 2003. We also reconstruct the long-term mass balances for the 1980–2018 period, which range from −760 to −160 mm water equivalent under the different climatic conditions (annual precipitation varies from 190 to 860 mm). We further evaluate the mass-balance sensitivities to temperature and precipitation changes. We confirm that both sensitivities correlate significantly with the annual precipitation; increased precipitation yields more negative sensitivity to temperature changes and less positive sensitivity to precipitation changes.
Thermal Recovery of Backfilled Pit in the Gulianhe Strip Coalmine in the Hola Basin in Northern Da Xing’Anling Mountains, NE China
Authors: He Ruixia , Li Yan , Jin Huijun , Wang Hongwei , Jin Xiaoying , Zhu Meiquan , Li Xinyu , Huang Yadong , Jin Doudou , Ma Futing
Published: January 2022

In the northern Da Xing’anling Mountains in Northeast China on the southern margin of the Eastern Asia permafrost body, the ground thermal state and boreal ecological environment are sensitive to climate change and human activities. Since the 1980s, the Hola Basin here has been continuously and extensively developed. In particular, open pits and later backfilling in strip coal mining alters land–atmospheric hydrothermal exchanges in permafrost regions, leading to serious damages to the permafrost environment and boreal forest. After mining, pits need to be backfilled timely and properly for hydrothermal recovery of Xing’an permafrost and the boreal ecological environment. In this study, based on the comparative analysis of monitored ground temperatures in backfilled and undisturbed areas, influencing factors of thermal recovery after backfilling were analyzed through numerical simulations. Results show that the thermal recovery of permafrost in the backfilled area is closely related to temperature, depth, material, and soil moisture content of backfill. The warmer, finer, and thicker the backfill soils, the longer the permafrost recovery. Thermal recovery of permafrost also depends on the moisture content of backfill; the shortest recovery occurs at 15–25% in the backfilled soil moisture content. Based on numerical simulations and combined with enlightenments from features of the ecosystem-protected Xing’an permafrost in Northeast China, a composite configuration of organic soil, crush-rock layer, and proper re-vegetation measures is advised. Based on prudent regulation of heat transfer modes, this composite backfilling method can effectively cool the backfilled ground and can even possibly offset the climate warming.
Content Analysis of LGBTQ Picture Books for Elementary Education Through an Intersectional Lens
Authors: Leung Enoch , Adams-Whittaker Julia
Published: January 2022

Diversity and inclusion have become a critical topic in contemporary society. Children engaging in story time with their family members and teachers can use stories from picture books as an educational tool to illustrate various social settings which provide a window into the wider outside world and a reflection of their own world, a concept known as “mirror and window”. However, LGBTQ representation has not been consistently perceived equitably compared to the heterosexual population, often dehumanized or unrealistic. Many LGBTQ students mentioned the need to see more portrayals of LGBTQ families and increasingly positive and realistic portrayals of LGBTQ characters. One independent publisher, Olly Pike, produces LGBTQ-inclusive picture books to support educators in providing representation and promoting an inclusive space in schools for diversity discussions. This case study utilizes content analysis of five LGBTQ-inclusive picture books from Olly Pike to understand the emerging themes that arise related to the support for LGBTQ and heterosexual students and foster an inclusive space in schools, leading to themes of diversity and representation that benefits critical discussions in schools and classrooms. Inter-rater reliability was established between the two authors for validity of emerging themes. Results revealed seven emerging themes: 1) Diversity and Inclusion (e.g. family structures, sexuality, ethnicity), 2) Daily Life, 3) Anthropomorphism, 4) Stereotypes, and 5) Overarching Educational Goals. Implications of findings reveal the benefit of incorporating LGBTQ-inclusive picture books to facilitate all students’ learning and understanding of SEL skills that largely tie with becoming responsible citizens that is respectful of diversity and specifically for LGBTQ students to see themselves positively represented, fostering a sense of belonging.
Exercise Increases Bone in SEIPIN Deficient Lipodystrophy, Despite Low Marrow Adiposity
Authors: McGrath Cody , Little-Letsinger Sarah E. , Sankaran Jeyantt Srinivas , Sen Buer , Xie Zhihui , Styner Martin A. , Zong Xiaopeng , Chen Weiqin , Rubin Janet , Klett Eric L. , Coleman Rosalind A. , Styner Maya
Published: January 2022

Exercise, typically beneficial for skeletal health, has not yet been studied in lipodystrophy, a condition characterized by paucity of white adipose tissue, with eventual diabetes, and steatosis. We applied a mouse model of global deficiency of Bscl2 (SEIPIN), required for lipid droplet formation. Male twelve-week-old B6 knockouts (KO) and wild type (WT) littermates were assigned six-weeks of voluntary, running exercise (E) versus non-exercise (N=5-8). KO weighed 14% less than WT (p=0.01) and exhibited an absence of epididymal adipose tissue; KO liver Plin1 via qPCR was 9-fold that of WT (p=0.04), consistent with steatosis. Bone marrow adipose tissue (BMAT), unlike white adipose, was measurable, although 40.5% lower in KO vs WT (p=0.0003) via 9.4T MRI/advanced image analysis. SEIPIN ablation’s most notable effect marrow adiposity was in the proximal femoral diaphysis (-56% KO vs WT, p=0.005), with relative preservation in KO-distal-femur. Bone via μCT was preserved in SEIPIN KO, though some quality parameters were attenuated. Running distance, speed, and time were comparable in KO and WT. Exercise reduced weight (-24% WT-E vs WT p<0.001) but not in KO. Notably, exercise increased trabecular BV/TV in both (+31%, KO-E vs KO, p=0.004; +14%, WT-E vs WT, p=0.006). The presence and distribution of BMAT in SEIPIN KO, though lower than WT, is unexpected and points to a uniqueness of this depot. That trabecular bone increases were achievable in both KO and WT, despite a difference in BMAT quantity/distribution, points to potential metabolic flexibility during exercise-induced skeletal anabolism.
Therapy With Different Dose Regimens of Rituximab in Patients With Active Moderate-To-Severe Graves’ Orbitopathy
Authors: Campi Irene , Vannucchi Guia , Muller Ilaria , Lazzaroni Elisa , Currò Nicola , Dainese Martina , Montacchini Benedetta , Covelli Danila , Guastella Claudio , Pignataro Lorenzo , Fugazzola Laura , Arosio Maura , Salvi Mario
Published: January 2022

Background

Immunosuppressive therapy of Graves’ orbitopathy (GO) is indicated during the active phase of disease. Intravenous steroids (IVGC) are effective in about 70% of patients, although unresponsiveness or relapse are observed. In previous studies, rituximab (RTX) has been shown to be effective in inactivating moderate-to-severe GO when used early in the disease, but its optimal dosage has never been studied in randomized clinical trials. Aim of this study was to compare the efficacy and safety of different doses of RTX, based on a post-hoc analysis of two open label studies and one prospective trial randomized to IVGC.

Methods

of 40 patients (35 women, 5 men), with active moderate-to-severe GO treated with RTX, 14 received a single dose of 100 mg (Group 1), 15 a single dose of 500 mg (Group 2) and 11 two 1000 mg doses, administered one week apart (Group 3). Thyroid function, TSH-receptor antibodies (TRAb) and peripheral CD19+ cells were measured. Primary endpoint was disease inactivation, measured as a decrease of the Clinical Activity Score (CAS) of at least two points. Secondary endpoints were improvement of proptosis, diplopia, quality of life and safety.

Results

Baseline CAS decreased significantly in all groups (P<0.0001), independently of GO duration or whether patients had newly occurring or relapsing GO after IVGC. Proptosis did not significantly change. There was an inverse correlation between the Gorman score for diplopia and RTX dose (P<0.01). The appearance score of the GO-QoL improved in Group 1 (P=0.015), and the visual function score, in Group 2 (P=0.04). A reduction of serum TRAb was observed in Group 1 (P=0.002) and Group 2 (P<0.0002), but not in Group 3. CD19+ cell decreased in all groups (P<0.01), independently of the dose.

Conclusions

We studied the optimal dosage of RTX in the treatment of active moderate-to-severe GO. In this analysis, we considered the efficacy of RTX in inactivating GO, in changing its natural course, its effect on disease severity and on the patients’ quality of life. Based on our clinical findings, and balancing the cost of therapy, a single 500 mg dose regimen is suggested in the majority of patients.
Metabolic and Nutritional Disorders Following the Administration of Immune Checkpoint Inhibitors: A Pharmacovigilance Study
Authors: Zhai Yinghong , Ye Xiaofei , Hu Fangyuan , Xu Jinfang , Guo Xiaojing , Zhou Xiang , Zheng Yi , Zhao Xinxin , Xu Xiao , Cao Yang , He Jia
Published: January 2022

Background

Although several metabolic and nutritional disorders (MNDs) have been reported in the recipients of immune checkpoint inhibitors (ICIs), these events have not been fully captured and comprehensively characterized in real-world population.

Objectives

To provide complete metabolic and nutritional toxicity profiles after ICIs (single and combined) initiation through an integrated big database.

Methods

Reporting odds ratios (ROR) and information component (IC) based on statistical shrinkage transformation were utilized to perform disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System. Both ROR and IC were used to calculate disproportionality when compared with the whole database, but only ROR was used when comparison was made for different ICI strategies. Only when both the lower limits of 95% confidence intervals (CIs) for ROR (ROR025) and IC (IC025) exceeded specified threshold values (1 and 0, respectively) was regarded as a signal.

Results

A total of 29,294,335 records were involved and 8,662 records were for MNDs in patients exposed to ICIs. Statistically significant association was detected between ICIs use and total MNDs (IC025/ROR025 = 1.06/2.19). For monotherapy, three ICI monotherapies (anti-PD-1, anti-PDL-1, and anti-CTLA-4) were all disproportionately associated with MNDs. Statistically significant differences in reporting frequencies also emerged when comparing anti-PD-1 with anti-PD-L1/anti-CTLA-4 monotherapy, with RORs of 1.11 (95%CI 1.01-1.21), and 1.35 (95%CI 1.23-1.48), respectively. Notably, combination therapy was associated with a higher reporting frequency of theses toxicities compared to monotherapy with a ROR of 1.56 (95%CI 1.48-1.64). Additionally, disproportionality analysis at High-level Group Term level highlighted eight broad entities of MNDs. Further disproportionality analysis at Preferred Term level indicated a wide range and varied strength of signals. For ICI monotherapy, nivolumab and pembrolizumab showed the broadest spectrum of MNDs. For combination therapy, a variety of signals were detected for nivolumab + ipilimumab therapy even comparable to two PD-1 monotherapies.

Conclusion

Metabolic and nutritional complications could be provoked by ICI monotherapy (especially anti-PD-1) and further reinforced by combination therapy. Clinicians and patients should be informed about these potential risks that might be encountered in real-world practice. Aforehand education and regular monitoring of related biochemical parameters (calcium, sodium, potassium, protein) are recommended to ensure better cancer survivorship.