Abstract Neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) has emerged to play parallel roles in both neurobiology and oncology. Apart from receptor-mediated signaling transduction pattern, serotonin can be covalently integrated into histone (the post-translational modification known as histone serotonylation) and serve as an epigenetic mark associated with permissive gene expression. However, how histone serotonylation influences tumorigenesis is yet to be understood. In this study, we observe the higher levels of histone serotonylation (H3K4me3Q5ser) and transglutaminases 2 (TGM2, the enzyme catalyzing serotonylation) in both pancreatic ductal adenocarcinoma (PDAC) tissues and cell lines in comparison with their normal counterparts, and inhibition of histone serotonylation suppresses PDAC development. Mechanistically, we demonstrate that TGM2-mediated histone serotonylation at promoter of the gene encoding stearoyl-CoA desaturase (SCD) up-regulates its expression and drives PDAC development by lipid metabolism remodeling. Collectively, this study reveals histone serotonylation as an important driver of PDAC tumorigenesis.
Abstract Background Tanzania is among the countries in sub-Saharan Africa with the highest under-five mortality rate. The leading causes of mortality among these children include vaccine-preventable infections. Strategies for reducing under-five mortality in hospital settings require a good knowledge of driving factors, which are largely unknown in Tanzania. This study was conducted at Muhimbili National Hospital to determine mortality and its predictors among under-five admitted in the general paediatric wards. Methods We conducted a prospective cohort study among children aged between 1 and 59 months admitted in the paediatric wards at Muhimbili National Hospital from 2nd October 2017 to 13th April 2018. We recruited eligible children consecutively and followed them up until discharge or death. We calculated the mortality rate as the incidence density rate and determined the causes and predictors of mortality. We analyzed data to identify and quantify predictors of deaths and used Kaplan-Meir and Cox regression analyses to determine predictors of survival. A P-value of < 0.05 was considered statistically significant. Results We recruited 925 children aged 1–59 months with a median age of 13 and (IQR) of (20) months, females constituted 40.8%. The overall mortality rate was 12.2% (95% CI: 10.2%-14.5%). We found septicaemia (27%), malnutrition (12%), congenital heart disease (12%), pneumonia (11%), and Human Immunodeficiency Virus infection (9%) to be leading causes of mortality. More deaths were observed at night, during the first 24 h of admission, and on weekends. Independent factors for mortality were found to be low wealth quintiles (lowest quintile (AOR = 4.0; 95% CI: 1.19–13.51), second quintile (AOR = 5.2; 95% CI: 1.65–16.69) and middle quintile (AOR = 3.6; 95% CI: 1.14–11.33), unconsciousness on admission (AOR = 18; 95% CI: 6.70–56.82), inability to feed (AOR = 5.7; 95% CI: 1.97–16.51), lethargy (AOR = 4.9; 95% CI: 2.32–10.40), severe wasting (AOR = 4.5; 95% CI: 2.49–8.10), and respiratory distress (AOR = 2.6; 95% CI: 1.40–4.97). Conclusion A high mortality rate was noted in this study and low wealth quantile, low parental education, and lack of health insurance were associated with high mortality. Patients had the highest risk of mortality within 24 h of admission, therefore it is important to raise awareness among clinicians regarding the need for improvement in the monitoring of patients, especially within 24 h of admission.
In the current higher education context, the development of academics’ competencies seems to be a crucial issue, with a strong focus on teaching, learning and assessment digital skills (Redecker & Punie, 2017). In connection with the framework of DigCompEdu (2017), it seems important to understand how to better sustain academics’ new professionalisation as Digital Scholars (Weller, 2011) in order to structure efficient and effective academic development models aimed at fostering new teaching skills required at university in the post pandemic era.
Background: Doctor-patient conflict is trending in social attention research. However, the existing literature rarely explores whether a patient's hostile attribution bias (HAB) in the doctor-patient interaction affects the aggression level against doctors. Objective: This study aimed to explore the relationship and mechanism between different types of HAB and aggression in patients. Method: In Study 1, 80 patients completed the word sentence association paradigm for hostility (WSAP-Hostility), and their explicit and implicit aggression levels were measured using the hot sauce paradigm and the single-category implicit association test (SC-IAT), respectively. In Study 2, 63 patients were randomly divided into an experimental (rejection) and a control group. Their state hostile attribution bias (SHAB) was activated through social rejection materials. They completed the SHAB questionnaire and anger expression inventory, and their explicit and implicit aggression levels were measured as in Study 1. Results: In both studies, results indicated that patients' trait and state HAB were significantly related to explicit aggression but not implicit aggression. Hostile interpretation positively predicted explicit aggression, whereas benign interpretation had a negative predictive effect on explicit aggression. Patients’ anger played a mediating role between SHAB and explicit aggression. Conclusions: These findings suggest that patients' HAB affects explicit aggression toward doctors and anger plays a mediating role.
The paper analyzes the importance and contribution of Serbian pedagogues to the affirmation of upbringing and education, based on national values. In Serbian pedagogy, several prominent pedagogues, through general reflections on upbringing and education, considered the importance of national education and national values. Accordingly, the paper presents the understanding of Serbian pedagogues in the period from 1918 to 1945, namely: Miloša R. Milošević, Vojislav Bakić, Ljubomir Protić, Sreten Adžić, Jovan Miodragović, Vojislav Mladenović, Miloš B. Janković and Vićentije Rakić. In the indicated historical moment, Serbia was marked by various school reforms, which also affected the content of upbringing and education. The importance of individual pedagogues, who created and acted at that time, is particularly impressive precisely because of the problematization of the idea of the nation and national values in the context of the process of upbringing and education, which is described and shown in more detail in the paper.
History (General) and history of Europe, Social sciences (General)
Ilham habibi Sormin, Muhammad Dalimunthe , Syahrul Abidin
The development of the film world is very diverse and produces films with various styles. Broadly speaking, films can be grouped by story, making orientation, and by genre. This study aims to determine the representation of feminism contained in the science fiction film entitled Level 16. This study uses a qualitative method with the semiotic analysis technique of Ferdinand De Saussure's model which examines the signs in life. Through this method, several scenes are selected in the level 16 film, then these scenes are revealed into denotative and connotative meanings and then interpreted in signifier and signified. In this study, the researcher found ten scenes that presented feminism in level 16 films.
Abstract Interferon-gamma (IFN-γ) exerts anti-tumor effects by inducing ferroptosis. Based on CRISPR/Cas9 knockout screening targeting genome-wide protein encoding genes in HepG2 and SK-Hep-1 cell lines, we found that cAMP response element-binding protein (CREB) regulated transcription coactivator 3 (CRTC3) protects tumor cells from drug-induced ferroptosis and significantly inhibits the efficacy of IFN-γ treatment in hepatocellular carcinoma (HCC). Mechanistically, CRTC3 knockout altered tumor cell lipid patterns and increased the abundance of polyunsaturated fatty acids (PUFAs), which enables lipid peroxidation and enhances the susceptibility of HCC cells to ferroptosis inducers. To scavenge for accumulated lipid peroxides (LPO) and maintain redox equilibrium, HCC cells up-regulate SLC7A11 and glutathione peroxidase 4 (GPx4) expressions to enhance the activities of glutamate-cystine antiporter (system xc−) and LPO clearance. As IFN-γ inhibiting system xc−, simultaneous treatment with IFN-γ disrupts the compensatory mechanism, and generates a synergistic effect with CRTC3 knockout to facilitate ferroptosis. Sensitizing effects of CRTC3 depletion were confirmed using typical ferroptosis inducers, including RSL3 and erastin. Sorafeinib, a commonly used target drug in HCC, was repeatedly reported as a ferroptosis inducer. We then conducted both in vitro and vivo experiments and demonstrated that CRTC3 depletion sensitized HCC cells to sorafenib treatment. In conclusion, CRTC3 is involved in the regulation of PUFAs metabolism and ferroptosis. Targeting CRTC3 signaling in combination with ferroptosis inducers present a viable approach for HCC treatment and overcoming drug resistance.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cytology
The post-pandemic school receives the strong digital push as a dowry from the previous two years and is called upon to implement the integration of the new modes (digital and remote) of teaching/learning with classical schooling. A task that brings skills, roles, and places into play. At school, in the classroom, teachers are called to a close confrontation with digitization, a process, after the pandemic, that can no longer be procrastinated: the opportunity to bring to life a real 4.0 school.
This paper analyses the educational regulations produced during the pandemic in Argentina during the years 2020 and 2021 for the secondary level. It presents a characterisation and categorisation of the regulations surveyed. Then, some jurisdictional appropriations are analysed. The way in which the regulations responded to an exceptional situation is discussed, as part of a longer-term process that takes into account the historical configuration of the education system (organizational model, job positions, previous reforms and available knowledge). Without losing sight of the fact that some of these features operated as obstacles to the implementation of these proposals, it was observed how the new normative framework used previous normative production as points of support, while using exceptionality as an opportunity to implement and deepen many of the pedagogical proposals already present in those regulations.
O presente artigo objetivou abordar as prescrições legais federais concernentes à organização e utilização dos espaços externos das instituições de Educação Infantil brasileiras, atinentes à faixa etária de 0 a 3 anos. O recorte temporal de análise foi de 1996 a 2018. As fontes analisadas foram os Referenciais Curriculares Nacionais para a Educação Infantil, os Parâmetros Básicos de Infraestrutura para Instituições de Educação Infantil, as Diretrizes Curriculares Nacionais para a Educação Infantil, o estudo propositivo sobre a organização dos espaços externos das unidades do Proinfância e a Base Nacional Comum Curricular. Optou-se pelo método de Análise Categorial Temática de Bardin (2010) e pelo diálogo com aportes teóricos advindos da História Cultural, como Chartier (1991) e Frago (1995). Utilizou-se, ainda, a literatura especializada sobre o tema dos espaços da primeira infância, com ênfase nos espaços externos. Foi possível observar que as prescrições legais buscam sensibilizar os docentes sobre a importância lúdico-pedagógica das áreas externas, assim como os documentos federais prescrevem modos de organização e práticas consideradas ideais. O pátio defendido legalmente é educativo, lugar de práticas desafiadoras, emancipatórias, interativas, democráticas, baseadas no aprendizado ativo e sensorial e, especificamente, na livre movimentação dos corpos e do contato com a natureza. Porém, a literatura recente tem destacado a permanência de históricas segmentações, que marcam a trajetória das instituições educativas.
Trifa Murad Mohammed, Hanaw Hasan Mohammedhkan, Delan Jamal Qader
Objective: Like Iraq and neighboring countries, the Kurdistan region was affected by the epidemic which gradually led to a lockdown in March and April and a wide-spread disruption of people’s life and activates. In this study, the researcher investigated the psychological hardiness and its relation to health awareness among citizens of the Kurdistan region during the Corona epidemic. Methods: This study followed a cross-sectional design quantitative survey that was conducted online from 1 to 18 April 2020. After two months of lockdown due to coronavirus pandemic in the Kurdistan Region. A questionnaire of 25 questioners to measure psychological hardiness, later the researchers got the psychometric qualities. Results: The researcher observed high psychological hardiness levels in the study, because of the Covid-19 pandemic. It has shown the non-significant association between psychological hardiness and health awareness and identified several significant factors associated with this psychological hardiness and health awareness. Conclusion: Using contractive tools, the study showed that the psychological hardiness of the citizens of the Kurdistan region is at a low level during the COVID-19 pandemic. The results could serve as a framework for future research to examine the influence of the pandemic on the population's association of psychological hardiness with health awareness.
Sharing a well-written care plan allows individuals, carers, emergency care providers and primary care teams to access information about managing patients’ problems in line with their wishes. It allows the documentation and sharing of information from conversations with patients, relatives and carers. There are multiple formats for patient care plans, but this article will focus on care planning for patients with frailty or in end of life care. A care plan is only as good as the conversation that informs it. A good care plan requires clear documentation and effective sharing of the information with easy access for all care givers.
ANA MARIA MORAIS COSTA , Simone Cabral Marinho dos Santos, Elizabete Carlos do Vale
A provocação para dialogar sobre os 50 anos do livro Pedagogia do Oprimido comunga com o desafio de pensar a educação brasileira num contexto caracterizado como “tempo de incerteza”, instaurado no país desde 2016. De caráter teórico, discutimos nesse artigo, a pedagogia freriana que se reinventa na dinâmica da realidade social, encontrando inspiração e renovação ao longo dos anos. Uma pedagogia que se alimenta da transformação objetiva da condição de opressão e da ação dos sujeitos sociais sobre o mundo para transformá-lo. Daí, partimos da seguinte pergunta: Quem são os oprimidos hoje? Por ela, enveredamos o texto com reflexões sobre o contexto atual no Brasil e os desafios que se apresentam no “que fazer” como ponto crucial da ação educativa. Dessas reflexões, enfatizamos a atualidade do livro em questão e por que Paulo Freire continua incomodando, ao mesmo tempo que desperta o interesse e o compromisso sócio/político/educativo de educadores e ativistas sociais.