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SUMMARY: The calcium-activated chloride channel (CLCA2) performs a vital function in the intricate process of tumorigenesis. Using a bioinformatics analysis system, we conducted a pan-cancer investigation on CLCA2 to explore its association with tumor prognosis and its involvement in immunology. In order to achieve this objective, we examined the prognostic significance and expression level of CLCA2 in multiple cancer types using the TIMER and Sangerbox databases. The analysis of protein interaction networks revealed proteins linked to CLCA2. To investigate the potential biological functions and enrichment pathways of CLCA2 in cancer, the SangerBox and GSCA databases were utilized. Furthermore, the expression of CLCA2 in different cancer subtypes was evaluated during the analysis. Various functional conditions of cancer cells were then compared with CLCA2 in the CancerSEA database. Using online tools like TISIDB and Assistant for Clinical Bioinformatics, the investigation explored the link between CLCA2 and immune subtypes. Additionally, it assessed immune cell infiltration as part of the analysis. In addition, the application of GDSA was employed to investigate the predictive significance of CLCA2 in relation to drug sensitivity. The research outcomes uncovered abnormal expression patterns of CLCA2 in diverse tumor categories, with its expression level demonstrating a correlation with distinct subtypes of tumors. Strong associations have been observed between enhanced patient survival rates and CLCA2 in specific tumor types. There is a noteworthy connection observed among diverse tumor types, immune cell infiltration, immune subtypes, and CLCA2. The enrichment analysis of KEGG indicates that there may exist a connection between the expression of CLCA2 and renin secretion, pancreatic secretion, as well as other pathways in pan-cancer. CLCA2 appears to primarily activate pathways such as EMT (epithelial-mesenchymal transition), RAS/MAPK, RTK, apoptosis, TSC/mTOR, and PI3K/ AKT in pan-cancer. On the other hand, it seems to inhibit pathways like cell cycle, DNA damage, hormone AR, and hormone ER. Through single-cell functional analysis, it has been confirmed that CLCA2 is associated with diverse cellular functional states, encompassing DNA repair, EMT, hypoxia, invasion, metastasis, and quiescence. Furthermore, a substantial correlation has been observed between the expression of CLCA2 and drug sensitivity towards bosutinib, tipifarnib-P1, as well as other therapeutic agents. This research affirms that various cancer types express CLCA2 and its involvement in tumor advancement and immune penetration. CLCA2 possesses the capability to function as a noteworthy biomarker and target for therapeutic intervention in diverse cancer forms.
El canal de cloruro activado por calcio (CLCA2) desempeña una función vital en el proceso de tumorigénesis. Utilizando un sistema de análisis bioinformático, llevamos a cabo una investigación pan-cáncer en CLCA2 para explorar su asociación con el pronóstico tumoral y su participación en la inmunología. Para lograr este objetivo, examinamos la importancia pronóstica y el nivel de expresión de CLCA2 en múltiples tipos de cáncer utilizando las bases de datos TIMER y Sangerbox. El análisis de las redes de interacción de proteínas reveló proteínas vinculadas a CLCA2. Para investigar las posibles funciones biológicas y las vías de enriquecimiento de CLCA2 en el cáncer, se utilizaron las bases de datos SangerBox y GSCA. Además, durante el análisis se evaluó la expresión de CLCA2 en diferentes subtipos de cáncer. Luego se compararon varias condiciones funcionales de las células cancerosas con CLCA2 en la base de datos CancerSEA. Utilizando herramientas en línea como TISIDB y Assistant for Clinical Bioinformatics, la investigación exploró el vínculo entre CLCA2 y los subtipos inmunes. Además, evaluó la infiltración de células inmunitarias como parte del análisis y se empleó la aplicación de GDSA para investigar la importancia predictiva de CLCA2 en relación con la sensibilidad al fármaco. Los resultados de la investigación descubrieron patrones de expresión anormales de CLCA2 en diversas categorías de tumores, y su nivel de expresión demuestra una correlación con distintos subtipos de tumores. Se han observado fuertes asociaciones entre mayores tasas de supervivencia de los pacientes y CLCA2 en tipos de tumores específicos. Se observa una conexión notable entre diversos tipos de tumores, infiltración de células inmunitarias, subtipos inmunitarios y CLCA2. El análisis de enriquecimiento de KEGG indica que puede existir una conexión entre la expresión de CLCA2 y la secreción de renina, la secreción pancreática y otras vías en el pancáncer. CLCA2 parece activar principalmente vías como EMT (transición epitelial-mesenquimatosa), RAS/MAPK, RTK, apoptosis, TSC/mTOR y PI3K/AKT en pan-cáncer. Por otro lado, parece inhibir vías como el ciclo celular, el daño del ADN, la hormona AR y la hormona ER. Mediante análisis funcional unicelular, se ha confirmado que CLCA2 está asociado con diversos estados funcionales celulares, que abarcan la reparación del ADN, la EMT, la hipoxia, la invasión, la metástasis y la inactividad. Además, se ha observado una correlación sustancial entre la expresión de CLCA2 y la sensibilidad al fármaco hacia bosutinib, tipifarnib-P1, así como a otros agentes terapéuticos. Esta investigación indica que varios tipos de cáncer expresan CLCA2 y su participación en el avance tumoral y la penetración inmune. CLCA2 posee la capacidad de funcionar como un biomarcador notable y como un objetivo para la intervención terapéutica en diversas formas de cáncer.
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Humanos , Canais de Cloreto/metabolismo , Neoplasias/metabolismo , Prognóstico , Biomarcadores Tumorais , Canais de Cloreto/imunologia , Genômica , Estimativa de Kaplan-Meier , Neoplasias/genética , Neoplasias/imunologiaRESUMO
ABSTRACT Background: Pan-immuno-inflammation value is a new and comprehensive index that reflects both the immune response and systemic inflammation in the body. Objective: The aim of this study was to investigate the prognostic relevance of pan-immuno-inflammation value in predicting in-hospital mortality in acute pulmonary embolism patients and to compare it with the well-known risk scoring system, pulmonay embolism severity index, which is commonly used for a short-term mortality prediction in such patients. Methods: In total, 373 acute pulmonary embolism patients diagnosed with contrast-enhanced computed tomography were included in the study. Detailed cardiac evaluation of each patient was performed and pulmonary embolism severity index and pan-immuno-inflammation value were calculated. Results: In total, 60 patients died during their hospital stay. The multivariable logistic regression analysis revealed that baseline heart rate, N-terminal pro-B-type natriuretic peptide, lactate dehydrogenase, pan-immuno-inflammation value, and pulmonary embolism severity index were independent risk factors for in-hospital mortality in acute pulmonay embolism patients. When comparing with pulmonary embolism severity index, pan-immuno-inflammation value was non-inferior in terms of predicting the survival status in patients with acute pulmonay embolism. Conclusion: In our study, we found that the PIV was statistically significant in predicting in-hospital mortality in acute pulmonay embolism patients and was non-inferior to the pulmonary embolism severity index. (Rev Invest Clin. 2024;76(2):97-102)
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Forkhead Box O1 (FOXO1) has been reported to play important roles in many tumors. However, FOXO1 has not been studied in pan-cancer. The purpose of this study was to reveal the roles of FOXO1 in pan-cancer (33 cancers in this study). Through multiple public platforms, a pan-cancer analysis of FOXO1 was conducted to obtained FOXO1 expression profiles in various tumors to explore the relationship between FOXO1 expression and prognosis of these tumors and to disclose the potential mechanism of FOXO1 in these tumors. FOXO1 was associated with the prognosis of multiple tumors, especially LGG (low grade glioma), OV (ovarian carcinoma), and KIRC (kidney renal clear cell carcinoma). FOXO1 might play the role of an oncogenic gene in LGG and OV, while playing the role of a cancer suppressor gene in KIRC. FOXO1 expression had a significant correlation with the infiltration of some immune cells in LGG, OV, and KIRC. By combining FOXO1 expression and immune cell infiltration, we found that FOXO1 might influence the overall survival of LGG through the infiltration of myeloid dendritic cells or CD4+ T cells. Functional enrichment analysis and gene set enrichment analysis showed that FOXO1 might play roles in tumors through immunoregulatory interactions between a lymphoid and a non-lymphoid cell, TGF-beta signaling pathway, and transcriptional misregulation in cancer. FOXO1 was associated with the prognosis of multiple tumors, especially LGG, OV, and KIRC. In these tumors, FOXO1 might play its role via the regulation of the immune microenvironment.
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Objective To analyze the relationship between expression level of protein O-fucosyltransferase 1(POFUT1)and tumor immune infiltration level and prognosis of patients,and explore the value of POFUT1 in tumor immunotherapy.Methods Based on the pan-cancer data,R software was used to analyze the changes in POFUT1 expression levels of various tumor tissues and their correlation with the risk ratio of various tumor patients,and screen for tumor types related to patient prognosis and POFUT1 expression.Through the String database,a protein interaction network was constructed,POFUT1-associated genes were screened,and functional enrichment analysis was performed.The estimate software package was used to analyze the correlation between POFUT1 expression and immune infiltration score in selected tumor tissues.The TIMER database was used to analyze the correlation between the expression level of POFUT1 and various levels of immune cell infiltration,and the correlation between the infiltration level of immune cells and the prognosis of patients.Results The expression levels of POFUT1 were significantly high in 14 types of tumors(P<0.05),and were associated with poor prognosis of low-grade gliomas,lung adenocarcinoma,and thyroid cancer(Hazard Ratio>1,P<0.05).POFUT1 and its associated genes were highly involved in Notch signaling pathway,lymphocyte activation and immune regulation processes.The expression level of POFUT1 was positively correlated with the infiltration degree of B cells,CD8+T cells,CD4+T cells,macrophages,neutrophils and dendritic cells in low-grade gliomas,as well as positively associated with the infiltration level of neutrophils in LUAD,and B cells,CD4+ T cells and macrophages in thyroid cancer(|r|>0.2,P<0.05).The high infiltration levels of the above 6 types of immune cells were correlated with the poor prognosis of patients with low-grade glioma(Hazard Ratio>1,P<0.05).Conclusion POFUT1 was highly involved in the process of immune regulation,affecting the immune infiltration level of some tumors and further influencing patient prognosis.It may have the potential to become a target for tumor immunotherapy.
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Objective To assess the role of the ferroptosis-associated gene GLS2 in the prognosis of pan-cancer and immunity using bioinformatics methods. Methods GLS2 expression levels in pan-cancer were profiled using publicly available databases: The Cancer Genome Atlas, GTEx, Cancer Cell Line Encyclopedia and the International Cancer Genome Consortium. The aim was to explore the role of GLS2 gene expression, gene variation survival analysis, immune infiltration, immune checkpoint related genes, TMB, and MSI in different tumors. Results Difference in GLS2 expression levels between cancer and paraneoplastic tissues was statistically significant in most cancer types, and the expression level was correlated with survival in these cancer types. A positive correlation was found between GLS2 expression and immune cell infiltration in multiple cancer types, and GLS2 expression level was positively correlated with TMB, MSI, and methylation, and its expression is an indicator for potential therapeutic response. Conclusion Pan-cancer analysis shows that the ferroptosis-related gene GLS2 can be used as a diagnostic and prognostic marker of clear cell carcinoma of kidney, adrenocortical carcinoma, lung adenocarcinoma, and pancreatic cancer.
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ABSTRACT The Pan American Health Organization (PAHO) and its Member States have been leading the efforts to eradicate wild poliovirus in the Region of Americas since smallpox's successful elimination in 1971. The region became the first to be certified free of wild poliovirus in 1994. However, in July 2022, an unvaccinated patient with no recent travel history was diagnosed with poliomyelitis in the United States of America. In response to the emergence of a circulating vaccine-derived poliovirus in the United States, PAHO established the Polio Incident Management Support Team. This team has been coordinating response efforts, focusing on: coordination, planning, and monitoring; risk communication and community engagement; surveillance and case investigation; vaccination; and rapid response. In this paper, we identified and documented best practices observed following establishment of the Incident Management Support Team (September 2022-2023) through a comprehensive review and analysis of various data sources and country-specific data from the polio surveillance dashboard. The aim was to share these best practices, highlighting technical support and implementation of polio measures by Member States. Despite several challenges, the Americas region remains polio-free. Polio risk is declining, with a July 2023 assessment showing fewer countries at medium, high, and very high risk. This progress reflects improved immunization coverage, surveillance, containment, health determinants, and outbreak preparedness and response. The PAHO Polio Incident Management Support Team has played a key role in supporting these efforts.
RESUMEN La Organización Panamericana de la Salud (OPS) y sus Estados Miembros han liderado los esfuerzos para erradicar el poliovirus salvaje en la Región de las Américas desde la eliminación exitosa de la viruela en 1971. En 1994, la Región fue la primera en obtener la certificación de libre del poliovirus salvaje. Sin embargo, en julio del 2022, se diagnosticó poliomielitis a un paciente de Estados Unidos de América no vacunado y sin antecedentes de viajes recientes. Para responder a la aparición de un poliovirus circulante derivado de la vacuna en ese país, la OPS creó el equipo de apoyo a la gestión de incidentes de poliomielitis. Este equipo ha asumido la coordinación de los esfuerzos de respuesta y se ha centrado en la coordinación, la planificación y seguimiento; la comunicación de riesgos y la participación de la comunidad; la vigilancia e investigación de casos; la vacunación; y la respuesta rápida. En este artículo, se determinan y documentan las mejores prácticas observadas después de la creación del equipo de apoyo a la gestión de incidentes (septiembre del 2022-2023) mediante una revisión y un análisis pormenorizados de datos procedentes de diversas fuentes y de datos específicos de los países del panel de vigilancia de la poliomielitis. El objetivo fue poner en común estas mejores prácticas y resaltar el apoyo técnico y la aplicación de medidas contra la poliomielitis por parte de los Estados Miembros. A pesar de los diversos desafíos, la Región de las Américas se mantiene libre de poliomielitis. El riesgo de esta enfermedad es cada vez menor, y la evaluación de julio del 2023 muestra una disminución del número de países con un riesgo medio, alto o muy alto. Este progreso refleja la mejora de la cobertura de inmunización, la vigilancia, la contención, los determinantes de la salud y la preparación y respuesta ante brotes. El equipo de apoyo a la gestión de incidentes relacionados con la poliomielitis de la OPS ha desempeñado un papel fundamental para brindar apoyo a estas iniciativas.
RESUMO Desde a eliminação bem-sucedida da varíola em 1971, a Organização Pan-Americana da Saúde (OPAS) e seus Estados Membros têm estado à frente de iniciativas para erradicar o poliovírus selvagem na Região das Américas. Em 1994, a região foi a primeira do mundo a ser certificada como livre do poliovírus selvagem. Entretanto, em julho de 2022, um paciente não vacinado e sem histórico de viagens recentes foi diagnosticado com poliomielite nos Estados Unidos da América. Em resposta ao surgimento de um poliovírus derivado de vacina circulante nos Estados Unidos, a OPAS criou a Equipe de Apoio à Gestão de Incidentes de Poliomielite. A equipe vem administrando os esforços de resposta, concentrando-se em: coordenação, planejamento e monitoramento; comunicação de risco e envolvimento da comunidade; vigilância e investigação de casos; vacinação; e resposta rápida. Neste documento, identificamos e documentamos as melhores práticas observadas após a criação da Equipe de Apoio à Gestão de Incidentes (setembro de 2022 a 2023) por meio de uma revisão e análise abrangentes de diversas fontes de dados e dados específicos de cada país fornecidos por meio do painel de vigilância da poliomielite. O objetivo foi compartilhar essas melhores práticas, destacando o apoio técnico e a implementação de medidas contra a poliomielite pelos Estados Membros. Apesar de vários desafios, a Região das Américas continua livre da poliomielite. Um levantamento de julho de 2023 demonstrou que o risco da poliomielite vem diminuindo, com menos países com risco médio, alto ou muito alto. Essa evolução é resultado de melhoras na cobertura vacinal, vigilância, contenção, preparação, determinantes de saúde e resposta a surtos. A Equipe de Apoio à Gestão de Incidentes de Poliomielite da OPAS foi fundamental para apoiar esses esforços.
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ABSTRACT BACKGROUND: To the best of our knowledge, this is the first study to evaluate the effectiveness of specific concentrations of antibiofilm agents, such as N-acetyl cysteine (NAC), rifampicin, and ozone, for the treatment of pan-resistant Klebsiella pneumoniae (PRKp). OBJECTIVES: We evaluated the effectiveness of antibiofilm agents, such as NAC, rifampicin, and ozone, on biofilm formation in PRKp at 2, 6, 24, and 72 h. DESIGN AND SETTING: This single-center experimental study was conducted on June 15, 2017, and July 15, 2018, at Istanbul Faculty of Medicine, Istanbul University, Turkey. METHODS: Biofilm formation and the efficacy of these agents on the biofilm layer were demonstrated using colony counting and laser-screened confocal microscopy. RESULTS: NAC at a final concentration of 2 μg/mL was administered to bacteria that formed biofilms (24 h), and no significant decrease was detected in the bacterial counts of all isolates (all P > 0.05). Rifampicin with a final concentration of 0.1 μg/mL was administered to bacteria that formed biofilm (24 h), and no significant decrease was detected in bacterial count (all P > 0.05). Notably, ozonated water of even 4.78 mg/L concentration for 72 h decreased the bacterial count by ≥ 2 log10. CONCLUSION: Different approaches are needed for treating PRKp isolates. We demonstrate that PRKp isolates can be successfully treated with higher concentrations of ozone.
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RESUMEN El desarrollo de la salud pública en América Latina durante el siglo XX combinó, desde el principio, el marco de la medicina social sobre los orígenes sociales, políticos y ambientales de la enfermedad con los aportes del trabajo de campo de la antropología médica. A pesar de la hegemonía del modelo médico, el surgimiento del marco de la medicina preventiva legitimó aún más la participación de los científicos sociales en el estudio de la multicausalidad de la enfermedad. Sin embargo, las limitaciones que trajo consigo la falta de contextualización histórica y política del modelo de la medicina preventiva dieron paso al movimiento latinoamericano de medicina social, basado en el materialismo histórico, y al desarrollo tanto de la epidemiología crítica como de la antropología médica crítica.
ABSTRACT The development of public health in Latin America during the 20th century combined, early on, the social medicine framework on the social, political, and environmental origins of disease with the contributions of medical anthropological fieldwork. Despite the hegemony of the medical model, the surge of the preventive medicine framework further legitimized the involvement of social scientists in the study of the multicausality of disease. However, the limitations brought by the preventive medicine model's lack of historical and political contextualization gave way to the Latin American social medicine movement, which was grounded in historical materialism, and the development of both critical epidemiology and critical medical anthropology.
RESUMO Desde o início, a evolução da saúde pública na América Latina ao longo do século XX combinou o marco teórico da medicina social sobre as origens sociais, políticas e ambientais das doenças com as contribuições derivadas do trabalho de campo da antropologia médica. Apesar da hegemonia do modelo médico, o surgimento do modelo de medicina preventiva legitimou ainda mais a participação dos cientistas sociais no estudo da multicausalidade das doenças. Entretanto, as limitações causadas pela falta de contextualização histórica e política do modelo de medicina preventiva abriram espaço para o movimento latino-americano de medicina social, fundamentado no materialismo histórico, e para o desenvolvimento da epidemiologia crítica e da antropologia médica crítica.
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ABSTRACT The purpose of this review is to highlight the most important aspects of the anatomical and functional uniqueness of the human brain. For this, a comparison is made between our brains and those of our closest ancestors (chimpanzees and bonobos) and human ancestors. During human evolution, several changes occurred in the brain, such as an absolute increase in brain size and number of cortical neurons, in addition to a greater degree of functional lateralization and anatomical asymmetry. Also, the cortical cytoarchitecture became more diversified and there was an increase in the number of intracortical networks and networks extending from the cerebral cortex to subcortical structures, with more neural networks being invested in multisensory and sensory-motor-affective-cognitive integration. These changes permitted more complex, flexible and versatile cognitive abilities and social behavior, such as shared intentionality and symbolic articulated language, which, in turn, made possible the formation of larger social groups and cumulative cultural evolution that are characteristic of our species.
RESUMO Esta revisão se propõe a relatar os aspectos mais importantes da singularidade anatômica e funcional do cérebro humano. Para isso, faz-se uma comparação entre o nosso cérebro e os de nossos parentes evolutivos mais próximos (chimpanzés e bonobos) e os ancestrais humanos. Durante a evolução humana ocorreu aumento absoluto do tamanho do cérebro e do número de neurônios corticais cerebrais, maior grau de lateralização funcional e assimetria anatômica cerebral, citoarquitetura cortical mais diversificada e aumento das redes neurais intracorticais e do córtex cerebral para as estruturas subcorticais acompanhada de mudança em direção ao investimento de redes neurais na integração multissensorial e sensório-motora-afetiva-cognitiva. Essas mudanças possibilitaram capacidades cognitivas e comportamentos sociais complexos, flexíveis e versáteis, destacando-se a intencionalidade compartilhada e a linguagem articulada simbólica, que permitiram a formação de grupos sociais maiores e a evolução cultural cumulativa característica de nossa espécie.
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El objetivo del presente trabajo es analizar el desempeño deportivo de la delegación chilena en los Juegos Panamericanos celebrados entre los años 1951 y 2023, haciendo uso de datos retrospectivos y proyectivos a través de series temporales de tiempo. Para esto se empleó un diseño cuantitativo, no experimental y longitudinal de tendencias y un método de suavización exponencial simple, que utiliza promedios históricos y que permite realizar una predicción o comportamiento futuro basado en una media ponderada de los valores actuales y de los pasados. A partir de los resultados obtenidos, fue posible concluir que, en las últimas décadas, la ubicación de Chile en el ranking de los Juegos Panamericanos se ha estabilizado en torno a un onceavo lugar, posición pronosticada para Santiago 2023. Manteniéndose condiciones similares, el desempeño deportivo general y específico no tendría un quiebre exponencial de la tendencia y los resultados no resultan favorables, específicamente en lo que respecta a la obtención de medallas de oro y la posición general de la delegación.
The objective of this paper is to analyze the sports performance of the Chilean delegation in the Pan American Games held between 1951 and 2023, using retrospective and projective data through time series. For this purpose, a quantitative, non-experimental and longitudinal design of trends and a simple exponential smoothing method was used, which uses historical averages and allows a prediction or future behavior based on a weighted average of current and past values. From the results obtained, it was possible to conclude that, in recent decades, Chile's position in the Pan American Games ranking has stabilized around eleventh place, a position predicted for Santiago 2023. Maintaining similar conditions, the general and specific sporting performance would not have an exponential break in the trend and the results are not favorable, specifically in terms of obtaining gold medals and the overall position of the delegation.
O objetivo deste artigo é analisar o desempenho esportivo da delegação chilena nos Jogos Pan-Americanos realizados entre 1951 e 2023, usando dados retrospectivos e projetivos por meio de séries temporais. Para isso, foi utilizado um desenho quantitativo, não experimental e longitudinal de tendências e um método de suavização exponencial simples, que utiliza médias históricas e permite uma previsão do comportamento futuro com base em uma média ponderada dos valores atuais e passados. Com base nos resultados obtidos, foi possível concluir que, nas últimas décadas, a posição do Chile no ranking dos Jogos Pan-Americanos se estabilizou em torno do 11º lugar, posição prevista para Santiago 2023. Mantendo-se condições semelhantes, o desempenho esportivo geral e específico não teria uma quebra exponencial na tendência e os resultados não são favoráveis, especificamente em termos de conquista de medalhas de ouro e posição geral da delegação.