bluuebunny/crossref_metadata_2025 huggingface dataset:
Jogos digitais na elaboração conceitual de alunos com transtorno do espectro autista
Authors: Gomes Alves Adriana , Prado Santana Santos Adriana , Coelho Neto João
Published: March 2023

Aborda-se, neste artigo, o uso de jogos digitais na Educação Inclusiva como ferramenta para elaboração conceitual de estudantes com Transtorno do Espectro Autista (TEA), contextualizada no Atendimento Educacional Especializado (AEE). O problema de pesquisa partiu das dificuldades cognitivas e emocionais apresentadas por estudantes com TEA, o que, muitas vezes, os impede de organizar suas ideias na elaboração de conceitos. A pesquisa, de caráter colaborativo, centrou-se na Teoria Sóciohistórica, nos estudos do desenvolvimento humano como processo nas interações sociais e nas contribuições de Vygotski e Luria, com base na metodologia da prova do quarto excluído. A pesquisa de campo foi realizada por meio de intervenções pedagógicas com o jogo digital Dr. Baguncinha, com um participante dos anos iniciais do Ensino Fundamental, em atendimento na sala do AEE. Foram feitas cinco intervenções com duração de 50 minutos cada, contando com a participação da professora. Os resultados da pesquisa foram fundamentados na resposta do sujeito participante frente à metodologia aplicada durante as atividades, e a avaliação deu-se a partir de critérios da Escala de Envolvimento e seus níveis, baseados em características como interesse, capacidade de seguir procedimentos, capacidade de organizar suas ideias, criatividade, entre outros. As práticas desenvolvidas durante as intervenções propiciaram ao estudante novas formas de aprender e de internalizar conceitos, mediado pelo jogo e pelas educadoras. Para a professora colaboradora do AEE, foram apresentadas alternativas de atividades, as quais potencializaram sua práxis pedagógica. Constatou-se a preferência da criança pelas atividades com o jogo digital, cuja avaliação revelou a importância de elementos de acessibilidade, apresentando as informações de diferentes formas – visual, auditiva, escrita –, com desafios que se tornam gradualmente complexos.
Elementos constitutivos da formação do professor da Educação Básica a partir da polinização psicopedagógica
Authors: Alves Machado Celine , Dos Santos Taborda Evandro , Müller Wolf Verediane , Simão Vera Lúcia
Published: March 2023

A Educação Básica é composta por diferentes níveis, sendo a Educação Infantil, o Ensino Fundamental e o Ensino Médio. A permanência dos estudantes nas instituições de ensino ao longo da Educação Básica é sublinhada, por vezes, por diferentes acontecimentos, aprendizados e emoções. Ao considerar o estudante como um ser singular, multicultural, com diferentes histórias, condição social, física, afetiva, o olhar para com este estudante se transforma, o reconhecemos como uma pessoa imbuída de sentimentos que sonha, que busca por uma mudança a partir da realidade da qual é parte. Para tanto, o objetivo deste estudo é identificar elementos constitutivos da formação do professor da Educação Básica a partir da polinização psicopedagógica. Metodologicamente, decidiu-se pelo uso da pesquisa documental e bibliográfica, amparadas na abordagem qualitativa, dando ênfase a Linha de Pesquisa -Cultura, Ensino, Saúde e Formação Docente, pertencente ao Programa de Pós-graduação Mestrado Profissional em Educação Básica (PPGEB) da Universidade Alto Vale do Rio do Peixe (UNIARP). Os resultados assinalam elementos constitutivos da formação do professor da Educação Básica a partir da polinização psicopedagógica em que considera o estudante como protagonista de uma educação humanizada e integral.
Formação continuada em tempos pandêmicos: um estudo do processo formativo de professores dos anos iniciais de uma rede municipal de ensino
Authors: Dos Santos Junges Kelen , Schupel Maidel Fabíola , Melnyk de Castilho Elizabeth
Published: March 2023

O período da pandemia da COVID-19 suscitou de forma eminente a reorganização do trabalho docente para adequação ao ensino remoto, trazendo novas formas e metodologias ao ensino e à aprendizagem. Neste viés, o presente artigo apresenta um recorte de um estudo mais amplo, vinculado ao Grupo de Estudos e Pesquisas em Práxis Educativa (GEPPRAX), que tem como objetivo identificar e analisar o contexto e percepções da formação continuada de professores dos anos iniciais da rede municipal de ensino do município de União da Vitória durante a pandemia e suas necessidades formativas pós-pandemia. Para tanto, foi realizada pesquisa bibliográfica, com base na literatura pertinente e documentos fornecidos pela Secretaria Municipal de Educação (SEMED), que descrevem as ações/contextos de formação continuada ofertados aos professores no período de pandemia. Como apoio de pesquisa de campo, utilizou-se como instrumento de coleta de dados a aplicação de um questionário semiestruturado, por meio do google forms, obtendo-se um total de 124 professores participantes. Constatou-se, a partir da análise dos dados coletados, que a formação da maioria dos professores participantes apresenta fragilidade na utilização de recursos e plataformas digitais. Considerou-se que o processo de formação continuada proposto pela SEMED colaborou para ampliar a gama de aprendizagens dos professores envolvidos e contribuiu para subsidiar as atividades pedagógicas durante o ensino remoto. Destaca-se que é imprescindível que os processos de formação continuada docente oferecidos pós-pandemia contemplem a apropriação de novas práticas de ensino, privilegiando estratégias e metodologias inovadoras, que atendam às necessidades do contexto educacional e estimulem um fazer pedagógico mais criativo e dinâmico.
Escola casa verde e suas práticas pedagógicas
Authors: Suanno João Henrique , Ferreira Mendes Neto Oscar
Published: March 2023

O presente trabalho apresenta análises de práticas pedagógicas desenvolvidas pela Escola Casa Verde – Aprendendo com os Pássaros, que atende crianças na Educação Infantil e nos anos iniciais do Ensino Fundamental. A instituição de ensino parte da teoria socioconstrutivista de Vygotsky, por meio de ações/situações que permitam desenvolver a interação entre o sujeito e meio sócio-histórico-cultural do qual ele faz parte, proporcionando o desenvolvimento do sujeito cognoscente. Tais práticas pedagógicas dialogam com a teoria da transdisciplinaridade e com a teoria da complexidade, em que o conhecimento se apresenta como fruto das relações entre o sujeito e seus pares, entre o sujeito e a sociedade e entre o sujeito e a natureza, por meio do princípio da auto-hetero-ecoformação. Para tal, fez se necessário lançar mão de aportes teóricos que abordassem sobre a teoria socioconstrutivista de Vygotsky e sobre as teorias da complexidade e da transdisciplinaridade (SANTOS, 2009; NICOLESCU, 1999; SUANNO, 2013; MORAES, 2014; SUANNO, 2010), além do princípio da auto-hetero-ecoformação (FREIRE; LEFFA, 2013). O Projeto Político-Pedagógico da instituição de ensino serviu como base para identificar o perfil da escola e os eixos norteadores das práticas pedagógicas desenvolvidas pela Escola Casa Verde. Uma entrevista semi-estruturada foi aplicada com os idealizadores e diretores da instituição Escola Casa Verde, compondo o material de pesquisa em que seus resultados serviram para compor tal estudo. As práticas pedagógicas desenvolvidas pela Escola Casa Verde por meio das interações entre as crianças, em que o par mais experiente contribui para a formação dos demais envolvidos através de práticas colaborativas, em interação com seus pares e com meio ambiente, produzidas a partir das interrelações entre os saberes científicos e culturais são resultados dessa sistematização.
Direito à Educação: relato de experiência com formação inicial de professores usando uma plataforma digital
Authors: Lamim-Guedes Valdir
Published: March 2023

Neste trabalho, descreveram-se uma atividade pedagógica desenvolvida com alunos de cursos de licenciatura da Universidade de São Paulo (USP) que envolveu a temática do Direito à Educação, com o apoio das Tecnologias Digitais da Informação e Comunicação (TDICs). Este estudo trata de umapesquisa qualitativa do tipo relato de experiência. A atividade foi realizada durante a disciplina Política e Organização da Educação Básica no Brasil (POEB), oferecida pelo Departamento de Administração Escolar e Economia da Educação (EDA) da Faculdade de Educação da USP (FEUSP), para todos os cursos de licenciatura do campus Butantã, localizado na zona oeste da cidade de São Paulo-SP. É uma disciplina presencial, com suporte de um Ambiente Virtual de Aprendizagem (Google Classroom), através do qual os alunos tiveram acesso às leituras prévias e enviaram fichamentos, além de operar como espaço para discussões e atividades em grupo. De forma geral, a combinação de várias ferramentas e estratégias permitiu um debate mais qualificado sobre o Direito à Educação, um assunto relevante para uma formação docente que vai além dos conteúdos específicos e pedagógicos.
Implementação da Lei 10.639/03 na Prática Pedagógica da Educação Básica: estudo Mediatizado pela Base de Dados Scielo
Authors: Bertolin Silva Guilherme , Tavares Ujiie Nájela
Published: March 2023

A lei 10.639/03 versa sobre a obrigatoriedade do ensino de História e Cultura Afro-brasileira nas escolas públicas de Educação Básica de todo o Brasil. No entanto, o que promulga a lei nem sempre se desdobra em ação educativa e prática pedagógica. O objetivo deste estudo consiste em investigar, a partir da base de dados Scielo (Biblioteca Eletrônica Científica Online), os artigos e estudos realizados entre 2008 e 2022 tendo como foco a temática da implementação da lei 10.639/03 na prática pedagógica da Educação Básica, que compreende Educação Infantil, Ensino Fundamental e Ensino Médio. A abordagem metodológica é teórico-bibliográfica e documental. Pode-se considerar que, apesar do estabelecimento da lei há aproximadamente vinte anos, a produção científica desse campo ainda é incipiente e demanda engajamento para produção e disseminação de mais estudos e pesquisa, o que torna ainda mais pertinente a investigação pretendida a ser desenvolvida e apresentada neste artigo.
Как охотник из хищника превращается в жертву? Современные охотничьи представления алтайцев о взаимодействии человека и духа-хозяина Алтая /
HOW DOES A HUNTER TURN FROM A PREDATOR INTO A PREY? THE INTERACTION OF A MAN AND THE GUARDIAN SPIRIT IN THE CONTEMPORRAY BELIEFS OF THE ALTAIAN HUNTERS
Authors: Tyukhteneva S. P.
Published: March 2023

В повседневной жизни люди обычно не говорят о смерти. А вот о причине ее, если это смерть не от болезни, не от несчастного случая, алтайцы рассказывают вполне охотно. Характерным для алтайцев является то, что в подобных рассказах — о наказании охотника духами‑хозяевами Алтая за неморальное поведение — сами рассказчики не видят ничего мистического и сверхъестественного. Статья представляет собой попытку исследовать современные представления алтайцев о том, как могут взаимодействовать человек и дух‑хозяин Алтая. Охотничьи практики народа продолжают передаваться от старших младшим, а эти практики, как показывают исследования отечественных и зарубежных ученых, имеют весьма древние корни. Важно отметить, что комплекс верований и представлений о наличии духов‑хозяев Алтая существовал у всех народов, проживающих на территории этой горной системы, в настоящее время разделенной государственными границами четырех стран: России, Казахстана, Китая и Монголии. Точно так же у всех народов большого Алтая имелись или являются живой традицией верования в возможность санкций со стороны духа Алтая. Культурные нормы алтайцев, в частности, предусматривают лишь один способ безопасного взаимодействия с Алтайдыҥ Ээзи: следовать правилам реципрокности, не быть браконьером, воспевать хвалу Алтаю, беречь любую жизнь в каждом ее проявлении.

Death is rarely mentioned in everyday life. However, the Altaians eagerly speak about the causes of death, unless these are illness or accident. Such stories about the guardian spirits’ punishments for the immoral behaviour are rarely seen as mystical or supernatural, which is typical for the Altaians. This article is an attempt to explore the modern Altaians’ beliefs about the ways of interaction of humans and the guardian spirit of Altai. The hunting practices, which, according to Russian and foreign scientists’ research, have rather ancient roots, are passed from the older to the younger generation. Importantly, the complex of beliefs about the guardian spirits of Altai existed among all the peoples who lived within this mountain system, which is currently divided by the borders of four states: Russia, Kazakhstan, China and Mongolia. Similarly, all the peoples of the Great Altai believed or still believe that the guardian spirit could punish for unrighteous conduct. The cultural norms of the Altaians, in particular, suggest only one way to safely interact with Altaidyn Eezi: follow the rules of reciprocity, avoid poaching, sing praises to Altai, protect life in every manifestation.
PERANCANGAN INFRASTRUKTUR KUNCI PUBLIK DENGAN IMPLEMENTASI PEMBANGUNAN SISTEM UJIAN DARING BERBASIS WEB
Authors: Setiawan Hermawan , Kertanegara Adek Muhammad Zulkham Ristiawan
Published: March 2023

Di masa pandemi Covid-19, hampir semua lembaga pendidikan di Indonesia menerapkan Pembelajaran Jarak Jauh (PJJ). Seperti pembelajaran pada umumnya, di setiap semester akan diadakan ujian, baik itu Ujian Tengah Semester maupun Ujian Akhir Semester, dan tentunya ujian tersebut dilakukan secara jarak jauh. Hal ini menimbulkan kekhawatiran dari guru kepada siswanya tentang cara pembagian soal ujian dan pengiriman lembar jawaban ujian. Dengan kata lain, sulit bagi guru untuk memastikan keamanan distribusi soal, serta melakukan pengesahan dan verifikasi pada lembar jawaban ujian yang dikumpulkan oleh siswanya. Pada penelitian ini, penulis membangun infrastruktur kunci publik yang diimplementasikan dalam sistem ujian online berbasis web dengan pendekatan enkripsi dan tanda tangan digital. Enkripsi dan tanda tangan digital adalah dua kriptografi primitif yang umum digunakan yang dapat memberikan layanan keamanan, seperti kerahasiaan, integritas, dan keaslian pesan. Diharapkan dengan penelitian ini dapat diketahui implementasi infrastruktur kunci publik pada sistem ujian online berbasis web.
In silico antibody-peptide epitope prediction for personalized cancer therapy
Authors: Jacobs Ivan , Ming Lim Chwee , Mong Jamie , Maragoudakis Manolis , Malik Nishant
Published: March 2023

The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encodes cell surface proteins responsible for regulating the immune system. Viral peptides presented to cancer cell surfaces by the HLA trigger the immune system to kill the cells, creating antibody–peptide epitopes (APE). This study proposes an in silico approach to identify patient-specific APEs by applying complex networks diagnostics on a novel multiplex data structure as an input for a deep learning model. The proposed analytical model identifies patient- and tumor-specific APEs with as few as 20 labeled data points. In addition, the proposed data structure employs complex network theory and other statistical approaches that can better explain and reduce the black box effect of deep learning. The proposed approach achieves an F1-score of 80% and 93% on patients one and two, respectively, and above 90% on tumor-specific tasks. In addition, it minimizes the required training time and the number of parameters.
Effectiveness of biomechanically stable pergola-like additively manufactured scaffold for extraskeletal vertical bone augmentation
Authors: Yang Wei , Wang Chao , Luo Wenping , Apicella Antonio , Ji Ping , Wang Gong , Liu Bingshan , Fan Yubo
Published: March 2023

Objective: Extraskeletal vertical bone augmentation in oral implant surgery requires extraosseous regeneration beyond the anatomical contour of the alveolar bone. It is necessary to find a better technical/clinical solution to solve the dilemma of vertical bone augmentation. 3D-printed scaffolds are all oriented to general bone defect repair, but special bone augmentation design still needs improvement.

Methods: This study aimed to develop a structural pergola-like scaffold to be loaded with stem cells from the apical papilla (SCAPs), bone morphogenetic protein 9 (BMP9) and vascular endothelial growth factor (VEGF) to verify its bone augmentation ability even under insufficient blood flow supply. Scaffold biomechanical and fluid flow optimization design by finite element analysis (FEA) and computational fluid dynamics (CFD) was performed on pergola-like additive-manufactured scaffolds with various porosity and pore size distributions. The scaffold geometrical configuration showing better biomechanical and fluid dynamics properties was chosen to co-culture for 2 months in subcutaneously into nude mice, with different SCAPs, BMP9, and (or) VEGF combinations. Finally, the samples were removed for Micro-CT and histological analysis.

Results: Micro-CT and histological analysis of the explanted scaffolds showed new bone formation in the “Scaffold + SCAPs + BMP9” and the “Scaffold + SCAPs + BMP9 + VEGF” groups where the VEGF addition did not significantly improve osteogenesis. No new bone formation was observed either for the “Blank Scaffold” and the “Scaffold + SCAPs + GFP” group. The results of this study indicate that BMP9 can effectively promote the osteogenic differentiation of SCAPs.

Conclusion: The pergola-like scaffold can be used as an effective carrier and support device for new bone regeneration and mineralization in bone tissue engineering, and can play a crucial role in obtaining considerable vertical bone augmentation even under poor blood supply.
Nonlinear correlation between fatty liver index and carotid intima media thickness among individuals undergoing health examination
Authors: Zhou Yuanchen , Duan Shaojie , Wang Rongrui , Chen Jialiang , Yao Shukun
Published: March 2023

Background

Fatty liver index (FLI) is a predictor of non-alcohol fatty liver disease (NAFLD). This study aimed to assess the association between FLI and carotid intima media thickness (CIMT).

Methods

In this cross-sectional study, we enrolled 277 individuals for health examination from the China-Japan Friendship Hospital. Blood sampling and ultrasound examinations were conducted. Multivariate logistic regression and restricted cubic spline analyses were performed to evaluate the association between FLI and CIMT.

Results

Overall, 175 (63.2%) and 105 (37.9%) individuals had NAFLD and CIMT, respectively. The multivariate logistic regression analyses results showed that high FLI was independently associated with a high risk of increased CIMT, T2 vs. T1 (odds ratio [OR], 95% confidence interval [CI]): 2.41, 1.10–5.25, p = 0.027; T3 vs. T1 (OR, 95% CI): 1.58, 0.68–3.64, p = 0.285. The association between FLI and increased CIMT exhibited a J-shaped curve (nonlinear, p = 0.019). In the threshold analysis, the OR for developing increased CIMT was 1.031 (95% CI: 1.011–1.051, p = 0.0023) in participants with FLI < 64.247.

Conclusion

The relationship between FLI and increased CIMT in the health examination population is J-shaped, with an inflection point of 64.247.
The monocyte-to-high-density lipoprotein ratio is associated with the occurrence of atrial fibrillation among NAFLD patients: A propensity-matched analysis
Authors: Wang Leigang , Zhang Yao , Yu Bing , Zhao Jianqi , Zhang Wenjing , Fan Hongxuan , Ren Zhaoyu , Liang Bin
Published: March 2023

Background

Accumulating evidence suggests that patients with nonalcoholic fatty liver disease (NAFLD) have a significantly high risk of incident atrial fibrillation (AF). Systemic inflammation, metabolic disorders and oxidative stress could be the potential mechanisms by which NAFLD drives AF. Monocyte-to- high-density lipoprotein ratio (MHR) has emerged as a novel biomarker of inflammation and oxidative stress that has not been studied in AF with NAFLD patients. We aimed to investigate the relationship between MHR and the risk of AF among NAFLD patients.

Methods

A retrospective analysis was performed for the clinical data of the patients with NAFLD in the Second Hospital of Shanxi Medical University from January 2019 to October 2022, among whom 204 patients with AF were enrolled as NAFLD+AF group and 613 patients without AF were enrolled as NAFLD control, and 152 patients were selected from each group based on propensity score matching (PSM) at a ratio of 1:1 to balance the covariates between groups. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. Logistic regression analysis was performed to identify the independent predictor for occurrence of AF among NAFLD patients. Trend chi-square test to analyze the prevalence of AF among MHR tertiles, and then the correlation between MHR and the risk of AF confirmed by restricted cubic splines (RCS). The receiver operating characteristic (ROC) curve analysis was used to determine the optimum MHR cutoff value to predict AF.

Results

Univariate analysis showed that AF patients had higher MHR than non-AF patients (P < 0.001). Meanwhile, compared with pure NAFLD patients, multivariate logistic regression analysis showed that MHR remained to be an independent risk factor for AF after adjusting for confounding risk factors (OR = 10.67, 95% CI 2.17-52.37, P = 0.004). TC、HDL-C were also independent risk factors for AF. Among them, TC and HDL-C are protective factors for AF. The trend chi-square test showed that the risk of AF increased with an increase in MHR (P < 0.05). However, the RCS showed a nonlinear and J-shaped relationship between MHR and the risk of AF (P for non-linearity = 0.023). The occurrence of AF increased with increasing MHR only when MHR > 0.44. The ROC curve showed that MHR combined with traditional risk factors can improve the ability to predict AF.

Conclusion

MHR is an independently associated with incident AF in patients with NAFLD and show a certain predictive value.
The crucial role and mechanism of insulin resistance in metabolic disease
Authors: Zhao Xuefei , An Xuedong , Yang Cunqing , Sun Wenjie , Ji Hangyu , Lian Fengmei
Published: March 2023

Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, and nonalcoholic fatty liver disease, and provides the basis for a common understanding of these chronic diseases. In this study, we provide a systematic review of the causes, mechanisms, and treatments of IR. The pathogenesis of IR depends on genetics, obesity, age, disease, and drug effects. Mechanistically, any factor leading to abnormalities in the insulin signaling pathway leads to the development of IR in the host, including insulin receptor abnormalities, disturbances in the internal environment (regarding inflammation, hypoxia, lipotoxicity, and immunity), metabolic function of the liver and organelles, and other abnormalities. The available therapeutic strategies for IR are mainly exercise and dietary habit improvement, and chemotherapy based on biguanides and glucagon-like peptide-1, and traditional Chinese medicine treatments (e.g., herbs and acupuncture) can also be helpful. Based on the current understanding of IR mechanisms, there are still some vacancies to follow up and consider, and there is also a need to define more precise biomarkers for different chronic diseases and lifestyle interventions, and to explore natural or synthetic drugs targeting IR treatment. This could enable the treatment of patients with multiple combined metabolic diseases, with the aim of treating the disease holistically to reduce healthcare expenditures and to improve the quality of life of patients to some extent.
Effects of physicochemical parameters of water on byproduct formation during electrolysis of ballast water
Authors: Lee Ji-Hyun , Choi Keun-Hyung , Yang Jun Hyuk
Published: March 2023

Introduction: Disinfection byproducts (DBPs) generated during ballast water treatment using active substances have gained increasing interest owing to their potential impact on the marine environment. This study aimed to investigate the occurrence and distribution of DBPs, which are secondary products generated during electrolysis, using land-based tests.

Methods: DBP levels were compared under various water conditions, including chloride and bromide ion compositions, hold time, and organic matter-related parameters.

Results: After electrolysis, trihalomethane (THM) and haloacetic acid (HAA) levels increased from day 0 to day 5 under all salinities, whereas haloacetonitrile (HAN) level decreased. THMs were found to be the most dominant DBP group, followed by HAAs and HANs. In marine water and brackish water, brominated DBPs were dominant owing to high levels of bromide ions, while chlorinated DBP concentrations were relatively high in fresh water.

Discussion: After electrolysis, the specific ultraviolet absorption of the treated water was >4, indicating a high likelihood of generating carbonaceous DBPs such as THMs and HAA. These findings contribute to a better understanding of the general mechanisms through which physicochemical factors affect the formation of DBPs during electrolysis treatment of ballast water. This understanding is valuable in addressing issues related to the treatment and release of treated ballast water into the marine environment, which is an emerging environmental concern.
The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironment
Authors: Gao Lanyang , Zhu Lei , Shen Chen , Hou Xiaoming , Chen Youyou , Zou Linglin , Qiang Huiyan , Teichmann Alexander T. , Fu Wenguang , Luo Yao
Published: March 2023

Background

Treatment of ER+ breast cancer with intramuscular formulation of Formestane (4-OHA) shrinks the tumor within weeks. Since the tedious way of intramuscular administration and side effects are not suited for adjuvant treatment, Formestane was withdrawn from the market. A new transdermal formulation of 4-OHA cream may overcome the defects and retain the effect of shrinking the breast cancer tumor. However, the effects of 4-OHA cream on breast cancer need further confirmatory studies.

Methods

In this work, in vivo, the influence of 4-OHA cream on breast cancer was evaluated using the mode of 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary cancer. We explored the common molecule mechanisms of action of 4-OHA cream and its injection formulation on breast cancer through RNA- sequencing-based transcriptome analysis and several biochemical experiments.

Results

The results showed that the cream substantially reduced the entire quantity, size, and volum of tumors in DMBA-treated rats consistent with 4-OHA injection, and indicated that there were comprehensive signals involved in 4-OHA antitumor activity, such as ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and proteoglycans in cancer. In addition, we observed that both 4-OHA formulations could enhance immune infiltration, especially CD8+ T cells, B cells, natural killer cells, and macrophages infiltration, in the DMBA-induced mammary tumor tissues. The antitumor effects of 4-OHA partly depended on these immune cells.

Conclusion

4-OHA cream could inhibit breast cancer growth as its injection formulation and may provide a new way for neoadjuvant treatment of ER+ breast cancer.
Anti-rituximab antibodies in patients with refractory autoimmune nodopathy with anti-neurofascin-155 antibody
Authors: Bai Yunfei , Li Wei , Yan Chuanzhu , Hou Ying , Wang Qinzhou
Published: March 2023

Background

Recent studies have reported that similar to other IgG4 autoimmune diseases, such as muscle-specific kinase antibody-associated myasthenia gravis, most anti-neurofascin-155 (anti-NF155) nodopathies respond well to rituximab treatment, regardless of the dosage. However, there are still a few patients for which rituximab is ineffective for unknown reasons. Currently, there are no studies on the mechanism of ineffective treatment with rituximab.

Methods

A 33-year-old Chinese man presenting with numbness, tremor, and muscle weakness for 4 years was recruited for this study. Anti-NF155 antibodies were identified by cell-based assay and confirmed by immunofluorescence assay on teased fibers. The anti-NF155 immunoglobulin (IgG) subclasses were also detected by immunofluorescence assay. Anti-rituximab antibodies (ARAs) were quantitatively analyzed using enzyme-linked immunosorbent assay (ELISA), and peripheral B cell counts were determined by flow cytometry.

Results

The patient exhibited anti-NF155 IgG4-antibody positivity. After the first round of rituximab infusion, the patient showed stratified outcomes with improvements in numbness, muscle weakness and ambulation. However, after three rounds of rituximab infusion, the patient’s symptoms deteriorated, and the numbness, tremor and muscle weakness returned. No obvious improvement was found after plasma exchange and another round of rituximab treatment. 14 days after the last treatment with rituximab, ARAs were detected. And the titers gradually decreased on day 28 and 60 but remained higher than normal. Peripheral CD19+ B cell counts were less than 1% within the 2-month period following the final rituximab administration.

Conclusions

In this study, ARAs presented in a patient with anti-NF155 nodopathy undergoing rituximab treatment and showed an unfavorable impact on rituximab efficacy. This is the first case to report the occurrence of ARAs in patients with anti-NF155 antibodies. We suggest that ARAs should be tested early during the initial intervention, especially in patients who respond poorly to rituximab treatment. In addition, we believe it is necessary to investigate the association between ARAs and B cell counts, their effect on clinical efficacy, and their potential adverse reactions in a larger cohort of patients with anti-NF155 nodopathy.
Immune checkpoints on T and NK cells in the context of HBV infection: Landscape, pathophysiology and therapeutic exploitation
Authors: Dumolard Lucile , Aspord Caroline , Marche Patrice N. , Macek Jilkova Zuzana
Published: March 2023

In hepatitis B virus (HBV) infection, the interplay between the virus and the host immune system is crucial in determining the pathogenesis of the disease. Patients who fail to mount a sufficient and sustained anti-viral immune response develop chronic hepatitis B (CHB). T cells and natural killer (NK) cells play decisive role in viral clearance, but they are defective in chronic HBV infection. The activation of immune cells is tightly controlled by a combination of activating and inhibitory receptors, called immune checkpoints (ICs), allowing the maintenance of immune homeostasis. Chronic exposure to viral antigens and the subsequent dysregulation of ICs actively contribute to the exhaustion of effector cells and viral persistence. The present review aims to summarize the function of various ICs and their expression in T lymphocytes and NK cells in the course of HBV infection as well as the use of immunotherapeutic strategies targeting ICs in chronic HBV infection.
Establishment and validation of a novel anoikis-related prognostic signature of clear cell renal cell carcinoma
Authors: Liu Yankuo , Shi Zhiyuan , Zheng Jianzhong , Zheng Zeyuan , Sun Huimin , Xuan Zuodong , Bai Yang , Fu Meiling , Du Yifan , Shao Chen
Published: March 2023

Background

Despite progression in its treatment, the clinical outcome of patients with clear cell renal cell carcinoma (ccRCC) remains not ideal. Anoikis is a unique form of programmed apoptosis, owing to insufficient cell-matrix interactions. Anoikis plays a crucial role in tumor migration and invasion, and tumor cells could protect themselves through the capacity of anoikis resistance.

Methods

Anoikis-related genes (ARGs) were obtained from Genecards and Harmonizome portals. The ARGs related to ccRCC prognosis were identified through univariate Cox regression analysis, then we utilized these ARGs to construct a novel prognostic model for ccRCC patients. Moreover, we explored the expression profile of ARGs in ccRCC using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. We also conducted Real-Time Polymerase Chain Reaction (RT-PCR) to probe ARGs expression of the risk score. Finally, we performed correlation analysis between ARGs and tumor immune microenvironment.

Results

We identified 17 ARGs associated with ccRCC survival, from which 7 genes were chosen to construct a prognostic model. The prognostic model was verified as an independent prognostic indicator. The expression of most ARGs was higher in ccRCC samples. These ARGs were closely correlated with immune cell infiltration and immune checkpoint members, and had independent prognostic value respectively. Functional enrichment analysis demonstrated that these ARGs were significantly associated with multiple types of malignances.

Conclusion

The prognostic signature was identified to be highly efficient in predicting ccRCC prognosis, and these ARGs were closely related to tumor microenvironment.
Tomato chlorosis virus CPm protein is a pathogenicity determinant and suppresses host local RNA silencing induced by single-stranded RNA
Authors: Yang Xiao , Luo Xiangwen , Zhang Yu , Zhang Zhanhong , OuYang Xian , Shi Xiaobin , Lv Xiaoyuan , Li Fan , Zhang Songbai , Liu Yong , Zhang Deyong
Published: March 2023

Introduction

Tomato chlorosis virus (ToCV) is a typical member of the genus Crinivirus, which severely threatens Solanaceae crops worldwide. The CPm protein encoded by ToCV has been reported to be associated with virus transmission by vectors and is involved in RNA silencing suppression, while the mechanisms remain ambiguous.

Methods

Here, ToCV CPm was ectopically expressed by a Potato virus X (PVX) vector and infiltrated into Nicotiana benthamiana wild-type and GFP-transgenic16c plants.

Results

The phylogenetic analysis showed that the CPm proteins encoded by criniviruses were distinctly divergent in amino acid sequences and predicted conserved domains, and the ToCV CPm protein possesses a conserved domain homologous to the TIGR02569 family protein, which does not occur in other criniviruses. Ectopic expression of ToCV CPm using a PVX vector resulted in severe mosaic symptoms followed by a hypersensitive-like response in N. benthamiana. Furthermore, agroinfiltration assays in N. benthamiana wilt type or GFP-transgenic 16c indicated that ToCV CPm protein effectively suppressed local RNA silencing induced by single-stranded but not double-stranded RNA, which probably resulted from the activity of binding double-stranded but not single-stranded RNA by ToCV CPm protein.

Conclusion

Taken together, the results of this study suggest that the ToCV CPm protein possesses the dual activities of pathogenicity and RNA silencing, which might inhibit host post-transcriptional gene silencing (PTGS)-mediated resistance and is pivotal in the primary process of ToCV infecting hosts.
Temporal and spatial characteristics of bone conduction as non-invasive haptic sensory feedback for upper-limb prosthesis
Authors: Mayer Raphael M. , Mohammadi Alireza , Tan Ying , Alici Gursel , Choong Peter , Oetomo Denny
Published: March 2023

Bone conduction is a promising haptic feedback modality for upper-limb prosthesis users, however, its potential and characteristics as a non-invasive feedback modality have not been thoroughly investigated. This study aimed to establish the temporal and spatial characteristics of non-invasive bone conduction as a sensory feedback interface for upper-limb prostheses. Psychometric human-subject experiments were conducted on three bony landmarks of the elbow, with a vibrotactile transducer affixed to each to provide the stimulus. The study characterized the temporal domain by testing perception threshold and resolution in amplitude and frequency. The spatial domain was evaluated by assessing the ability of subjects to detect the number of simultaneous active stimulation sites. The experiment was conducted with ten able-bodied subjects and compared to two subjects with trans-radial amputation. The psychometric evaluation of the proposed non-invasive bone conduction feedback showed results comparable to invasive methods. The experimental results demonstrated similar amplitude and frequency resolution of the interface for all three stimulation sites for both able-bodied subjects and subjects with trans-radial amputation, highlighting its potential as a non-invasive feedback modality for upper-limb prostheses.
Nigella sativa and health outcomes: An overview of systematic reviews and meta-analyses
Authors: Li Zhongyu , Wang Yang , Xu Qing , Ma Jinxin , Li Xuan , Yan Jiaxing , Tian Yibing , Wen Yandong , Chen Ting
Published: March 2023

Background

Nigella sativa (N. sativa) consumption has been associated with various health outcomes; however, the results are not completely consistent.

Objectives

This overview of systematic reviews and meta-analyses aimed to evaluate the reporting and methodological quality, and to grade the available evidence of associations between N. sativa and health outcomes.

Methods

PubMed, Cochrane Library, Embase, and Scopus databases were searched from their inception to September 30, 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 statement, Assessment of Multiple Systematic Reviews (AMSTAR) 2 checklist, and Grades of Recommendations, Assessment, Development and Evaluations (GRADE) systems were used to assess the reporting, methodological, and evidence quality for each meta-analysis, respectively. The results were synthesized in a narrative form.

Results

This overview included 20 eligible meta-analyses published in peer-reviewed journals between 2013 and 2021. The overall methodological quality was relatively poor, with only one moderate quality, four low quality, and 15 critically low quality studies. For reporting quality, items two, five, eight, nine, 15, and 24 need to improve. Among the 110 outcome indicators of the quality of evidence, five were graded as moderate, 17 as low, and 88 as very low. Risk of bias, inconsistency, and imprecision were the main downgrading factors.

Conclusion

This overview suggests that N. sativa is beneficial for various clinical outcomes. However, there are certain limitations to reporting and methodological quality. The clinical efficacy of N. sativa requires confirmation in high-quality, large-sample, randomized controlled trials.
Identification of calcium metabolism related score associated with the poor outcome in papillary thyroid carcinoma
Authors: Hu Chuanxiang , Yan Lijuan , Li Peng , Yu Yang
Published: March 2023

Introduction

Papillary thyroid carcinoma is a type of thyroid cancer that exhibits significant variability in prognosis. Extensive research indicates that the impaired signaling of 1,25(OH)2D3-VDR may be a crucial factor in the development and progression of PTC.

Methods

To investigate this further, Integrated analysis mRNA expression information from The Cancer Genome Atlas and GEO, we compared gene expression in cancer and normal tissues and identified differentially expressed genes (DEGs). Through this analysis, we identified DEGs and calculated risk estimates for seven genetic markers.

Results

Subsequently, we constructed predictive models using LASSO-Cox regression to test the predictive value of these markers. Our results revealed that 64 calcium metabolism-related genes showed significant differences between tumor and normal tissues. Ten of the identified DEGs were significantly associated with overall survival, indicating their potential role in disease progression. Using the average risk score for the seven genetic markers, we divided patients into high- and low-risk groups. We found that patients in the low-risk group had significantly better overall survival than those in the high-risk group, highlighting the importance of these genetic markers in predicting prognosis. Further analysis using Cox regression demonstrated that the risk levels had independent predictive power. Additionally, we conducted functional analysis of the identified genetic markers, which showed significant differences in immune status between the two patient groups. We also investigated the effect of these calcium metabolism-related genes on thyroid cancer biological functions, immune microenvironment, and drug resistance.

Discussion

Our findings provide evidence of a novel genetic signature associated with calcium metabolism, which can predict prognosis in patients with PTC. These results may have significant implications for the development of new diagnostic and therapeutic approaches to improve outcomes for PTC patients.
Development and validation of nomograms for predicting survival outcomes in patients with T1-2N1 breast cancer to identify those who could not benefit from postmastectomy radiotherapy
Authors: Pu Hongyu , Luo Yunbo , Zhang Linxing , Li Xin , Li Fangwei , Chen Jingtai , Qian Shuangqiang , Tang Yunhui , Zhao Xiaobo , Hou Lingmi , Gao Yanchun
Published: March 2023

Purpose

In this study, we aimed to develop and validate nomograms for predicting the survival outcomes in patients with T1-2N1 breast cancer to identify the patients who could not benefit from postmastectomy radiotherapy (PMRT).

Methods

Data from 10191 patients with T1-2N1 breast cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Of them, 6542 patients who had not received PMRT formed the training set. Concurrently, we retrospectively enrolled 419 patients from the Affiliated Hospital of North Sichuan Medical College (NSMC), and 286 patients who did not undergo PMRT formed the external validation set. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were used for selecting prognostic factors in the training set. Using the selected factors, two prognostic nomograms were constructed. The nomograms’ performance was assessed using the concordance index (C-index), calibration curves, decision curve analysis (DCA), and risk subgroup classification. The stabilized inverse probability of treatment weights (IPTWs) was used to balance the baseline characteristics of the different risk groups. Finally, the survival outcomes and effectiveness of PMRT after IPTW adjustment were evaluated using adjusted Kaplan–Meier curves and Cox regression models.

Results

The 8-year overall survival (OS) and breast cancer-specific survival (BCSS) rates for the SEER cohort were 84.3% and 90.1%, with a median follow-up time of 76 months, while those for the NSMC cohort were 84.1% and 86.9%, with a median follow-up time of 73 months. Moreover, significant differences were observed in the survival curves for the different risk subgroups (P < 0.001) in both SEER and NSMC cohorts. The subgroup analysis after adjustment by IPTW revealed that PMRT was significantly associated with improved OS and BCSS in the intermediate- (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.59–0.88, P=0.001; HR = 0.77, 95% CI: 0.62–0.95, P = 0.015) and high- (HR=0.66, 95% CI: 0.52–0.83, P<0.001; HR=0.74, 95% CI: 0.56–0.99, P=0.039) risk groups. However, PMRT had no significant effects on patients in the low-risk groups.

Conclusion

According to the prognostic nomogram, we performed risk subgroup classification and found that patients in the low-risk group did not benefit from PMRT.
Surgical selection and regional lymph node dissection for stage I second primary lung cancer patients following surgery for stage I first primary lung cancer
Authors: Wu Xiao , Jiang Youhua , Chen Qixun , Wang Jiangfeng , Li Jianqiang
Published: March 2023

Introduction

Studies investigating surgery for second primary non-small cell lung cancer (SP) patients are rare. The aim of this study was to explore the effects of surgical methods and regional lymph node (LN) dissection on lung cancer-specific mortality (LCSM) in stage I SP patients following surgery for stage I first primary non-small cell lung cancer (FP).

Methods

Data on patients diagnosed with stage I SP after surgery for stage I FP were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Cumulative incidence function (CIF) curves, a competing risk model and propensity score matching (PSM) were adopted to compare the LCSM among different subgroups (including surgery and regional LN dissection).

Results

A total of 238 stage I SP patients were extracted from the SEER database. Overall, the 5-year LCSM rate was 29.8% (CI: 23.1%-36.5%) for the whole cohort. Both before and after PSM, lobectomy had a similar LCSM incidence as sublobectomy, and ≥4 regional LN dissections had a significantly lower LCSM incidence than 1~3 regional LN dissections.In addition, patients who underwent 1~3 regional LN dissections had a comparable incidence of LCSM to those without LN dissections.

Discussion

Stage I SP patients tended to gain more survival benefits when surgeons dissect ≥4 regional LNs. Allowing for the comparable LCSM incidence of sublobectomy to lobectomy, sublobectomy may be a reasonable choice for thoracic surgeons when performing surgery for these patients.
Acute oral toxicity, apoptosis, and immune response in nurse bees (Apis mellifera) induced by flupyradifurone
Authors: Gao Jing , Guo Yi , Chen Jin , Diao Qing-Yun , Wang Qiang , Dai Ping-Li , Zhang Li , Li Wen-Min , Wu Yan-Yan
Published: March 2023

The potential toxicity of flupyradifurone (FPF) to honey bees has been a subject of controversy in recent years. Understanding the effect of pesticides on nurse bees is important because the fitness of nurse bees is critical for in-hive activities, such as larval survival and performing hive maintenance. In order to evaluate the acute oral toxicity of flupyradifurone on nurse bees, flupyradifurone at five different concentrations was selected to feed both larvae and nurse bees. Our results showed that nurse bees were more sensitive to flupyradifurone than larvae (LD50 of the acute oral toxicity of flupyradifurone was 17.72 μg a.i./larva and 3.368 μg a.i./nurse bee). In addition, the apoptotic rates of neurons in mushroom bodies of nurse bees were significantly induced by flupyradifurone at sublethal concentrations (8 mg/L, 20 mg/L, and 50 mg/L) and the median lethal concentration LC50 (125 mg/L). The expression of immune-related genes (Hsp90, Toll-8/Tollo, and defensin) was significantly changed in exposed nurse bees at the field-realistic concentration of flupyradifurone. However, three detoxifying enzyme genes (CYP9Q1, -2, and -3) were not affected by pesticide exposure. Our data suggest that although flupyradifurone had a relatively lower acute oral toxicity than many other common pesticides, exposures to the field-realistic and other sublethal concentrations of flupyradifurone still have cytotoxicity and immune-responsive effects on nurse bees. Therefore, flupyradifurone should be considered for its application in crops.