Expression and Clinical Significance of CLCA2 in Pan-Cancer

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.

An extensive analysis of the prognostic and immune role of FOXO1 in various types of cancer

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.

The uniqueness of the human brain: a review / A singularidade do cérebro humano: uma revisão

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.

Maintaining the Region of the Americas free of polio: best practices for incident management support teams / Mantener a la Región de las Américas libre de poliomielitis: mejores prácticas para los equipos de apoyo a la gestión de incidentes / Mantendo a Região das Américas livre da poliomielite: melhores práticas para as equipes de apoio à gestão de incidentes

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.

Effect of N-acetyl cysteine, rifampicin, and ozone on biofilm formation in pan-resistant Klebsiella pneumoniae: an experimental study

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.

Role of Ferroptosis-related Gene GLS2 in Pan-cancer Prognosis and Immunity / 肿瘤防治研究

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.

Rendimiento en los juegos panamericanos de Santiago 2023: predicción mediante método de suavización exponencial simple / Performance at the Santiago 2023 pan american games: prediction using a simple exponential smoothing method / Desempenho nos jogos pan-americanos de Santiago 2023: predição usando o método de suavização exponencial simples

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.

Aprovechamiento alternativo de calamar (Dosidicus gigas) como fuente de proteína para la fortificación de pan tipo baguette / Alternative use of squid (Dosidicus gigas) flour as a protein source to improve the nutritional quality of baguette bread

Introducción. Los cereales tienen aminoácidos limitantes y mezclarlos con harinas de origen marino presentan un mejor equilibrio en éstos mejorando la composición nutricional en productos de panificación, principalmente de proteína y aminoácidos. Objetivo. Desarrollar panes tipo "baguette" sustituyendo parcialente harina de trigo (HT) por harina de calamar (HC) y evaluar su calidad física, química y sensorial. Materiales y métodos. Se utilizó la técnica de masa esponja incorporando 7,5, 10 y 12,5 % de HC. Análisis físicos: tiempo de amasado, peso y fermentación de la masa, volumen específico, peso de los panes (g), % pérdida humedad y color de miga; análisis químicos: humedad, proteína cruda, cenizas, extracto etéreo, fibra cruda, carbohidratos, aminoácidos indispensables y energía bruta y evaluación sensorial: textura, olor, color y sabor. Resultados. Las propiedades físicas no presentaron diferencias (p>0,05), pero sí (p<0,05) para las variables de color en todos los panes, al igual que en los análisis químicos y perfil de aminoácidos (p<0,05), incrementándose la proteína (15,63 % pan con 7,5 % de HC hasta 23,27 % pan con 12,5 % de HC) y mismo comportamiento de aminoácidos indispensables conforme aumentó la inclusión de HC. Los resultados de la evaluación sensorial fueron similares (p>0,05) para 7,5 % de HC (me gusta), para 10,0 y 12,5 % fue indiferente. Conclusiones. La inclusión de HC (7,5 %) en baguette logró un aumento de proteínas y aminoácidos esenciales mejorando la calidad nutricional, con buena aceptación de acuerdo con la prueba de carácter exploratorio con consumidores que se empleó(AU)

Introduction. Cereals have limiting amino acids and mixing them with flours of marine origin could provide a better balance in these improving the nutritional composition in bakery products, mainly protein and amino acids. Objective. To develop and evaluate the physical, chemical, and sensory quality of three white breads of baguette type by partially substitution of wheat flour (HT) with squid flour (HC). Materials and methods. The sponge dough technique was used incorporating 7,5, 10,0 and 12,5 % of HC. Physical analysis: kneading time, dough weight, dough fermentation, specific volume, bread weight (g), % loss of moisture and crumb color; chemical analysis: moisture, crude protein, ash, ether extract, crude fiber, carbohydrates, indispensable amino acids and sensory evaluation: texture, odor, color, and flavor. Results. Physical properties did not show differences (p>0.05), differences (p<0.05) for color variables in all breads as well as in chemical analysis and amino acid profile (p<0.05), the protein show an increase (15,63 % for bread with HT to 23,27 % for bread with 12.5 % of HC) and the same behavior for indispensable amino acids, that increase as inclusion of HC increases. The results of the sensory evaluation were similar (p>0.05) in control and 7,5 % of HC (I like it), for 10 and 12,5% it was indifferent. Conclusions. The inclusion of squid flour (7,5 %) in the preparation of baguette bread achieved an increase of proteins and essential amino acids that improved the nutritional quality of this food, which also presented a good acceptance according to an exploratory test with consumers(AU)

Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (REGISTRO ECCOVID) / Comparative analysis of clinical characteristics, evolu tion and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID STUDY)

Resumen Introducción : Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos : Registro multicéntrico y prospectivo de pacientes ≥ 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolu ción a 30 días. Resultados : Se incluyeron un total de 1691 pacien tes (primera ola n = 809, segunda ola n = 882). Los pa cientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospi talización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p <0,001) y presen taron mayor mortalidad (11% vs. 26%, p < 0.001). Compa rando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión : Comparados con los pacientes interna dos durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

Abstract Introduction : Clinical features and outcomes of SARS-CoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. Methods : Multicenter and prospective registry of patients ≥18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. Results : A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized pa tients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hos pitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hos pitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. Conclusion : Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 dur ing the second wave in Argentina were more seriously ill and had a higher mortality.

Knowledge and perception of health-care professionals on clinical trials in India: A pan-Indian cross-sectional survey

Purpose: The purpose of the study was to evaluate the knowledge and perception of health-care professionals (HCPs), such as doctors/surgeons, pharmacists, nurses, optometrists, and lab technicians, on clinical trials (CTs) in India. Methods: The study was a pan-Indian cross-sectional survey initiated by the Indian Ophthalmology Clinical Trial Network (IOCTN) by using a previously validated questionnaire for three months of data collection. An online survey was used to record information regarding demographics, CT knowledge, and CT perception among HCPs. Results: A total of 630 responses were recorded from HCPs: 207 doctors and surgeons, 159 pharmacists, and 264 laboratory technicians, nurses, and optometrists across India. Over 90% of HCPs had a clear knowledge on the purpose of CTs, the informed consent (IC) process, ethical approval by the Drugs Controller General of India (DCGI). About 80% and 90% were aware of confidentiality of patients, voluntariness of participation, and good clinical practice. Surprisingly, less than 50% had lesser knowledge regarding monetary incentives of CT participants (CTPs). A slightly positive perception was observed regarding the potential benefits of CTPs, compensation related to injury, and importance of obtaining IC. Less than 50% had a negative perception that monetary compensation to CTPs led to bias and deprivation of standard treatments. However, no significant difference was observed between other aspects of demographics and perception regarding CTs. Conclusion: We observed doctors and surgeons to be having the highest regarding CTs, followed by pharmacists. The survey highlighted the necessity of scheduling awareness programs among the HCPs, which would improve their misconceptions and perception of CTs while interacting with patients for CT enrollment.

Evolución histórica de la Organización Mundial de la Salud y la resistencia a los antimicrobianos / Historical evolution of World Health Organization guidelines on antimicrobial resistance / Evolução histórica da Organização Mundial da Saúde e a resistência aos antimicrobianos

RESUMEN Objetivo. Mostrar la evolución de los lineamientos sobre políticas públicas en salud enfocadas en farmacorresistencia microbiana o resistencia a los antimicrobianos (RAM) que la Organización Mundial de la Salud (OMS) ha emitido desde 1948 hasta 2022. Además, se mencionan otras acciones gubernamentales relacionadas. Métodos. Se llevó a cabo una revisión detallada de los archivos de la Asamblea Mundial de la Salud y el Consejo Ejecutivo de la OMS. Se realizó un análisis textual de resoluciones sobre la RAM, que dan pauta al diseño de políticas y acciones gubernamentales para los Estados Miembros de la OMS. También se realizó una búsqueda sistemática en SCOPUS, Pubmed y literatura gris con categoría de análisis: políticas públicas en salud sobre la RAM. Resultados. La RAM se ha convertido en la mayor amenaza para la salud pública, y compromete el cumplimiento de los objetivos de desarrollo sostenible. Presentamos resoluciones de la OMS como evidencia de lineamientos para combatir la RAM. En consonancia, se menciona el enfoque "Una salud", estrategias, iniciativas, planes y programas relacionados. Se identificó una brecha en la investigación y el desarrollo de antimicrobianos nuevos, que requiere un análisis más profundo. Conclusiones. La OMS ha realizado esfuerzos para combatir la RAM. Esto ha generado un desarrollo integral de políticas públicas en salud, para que los Estados Miembros las apliquen según la soberanía de sus gobiernos.

ABSTRACT Objective. Show the evolution of guidelines on public health policies focused on antimicrobial resistance (AMR) issued by the World Health Organization (WHO) between 1948 and 2022. Other related government actions are also mentioned. Methods. A detailed review was conducted of World Health Assembly and WHO Executive Board archives. A textual analysis was conducted of AMR-related resolutions that guide the design of government policies and actions for WHO Member States. A systematic search was carried out in SCOPUS, PubMed, and grey literature under the category of public health policies on AMR. Results. AMR has become the greatest threat to public health, putting at risk the achievement of the Sustainable Development Goals. WHO resolutions are presented as evidence of guidelines to combat AMR. The One Health approach and related strategies, initiatives, plans, and programs are mentioned. A gap was identified in the research and development of new antimicrobials, requiring further analysis. Conclusions. WHO has made efforts to combat AMR. This has generated comprehensive development of public health policies to be implemented by the governments of Member States as they see fit.

RESUMO Objetivo. Apresentar a evolução das diretrizes sobre políticas públicas de saúde voltadas para a resistência microbiana a medicamentos ou resistência aos antimicrobianos (RAM) publicadas pela Organização Mundial da Saúde (OMS) de 1948 a 2022. Além disso, mencionam-se outras ações governamentais relacionadas. Métodos. Procedeu-se a uma revisão detalhada dos arquivos da Assembleia Mundial da Saúde e do Conselho Executivo da OMS. Realizou-se uma análise textual das resoluções sobre RAM, que orientam a formulação de políticas e ações governamentais para os Estados Membros da OMS. Fez-se também uma busca sistemática nas plataformas SCOPUS e Pubmed e na literatura cinzenta, com a categoria de análise "políticas públicas de saúde sobre RAM". Resultados. A RAM tornou-se a maior ameaça à saúde pública e prejudica o cumprimento dos Objetivos de Desenvolvimento Sustentável. Apresentamos as resoluções da OMS como evidência de diretrizes para combater a RAM. Nesses termos, mencionam-se a abordagem "Saúde Única" e estratégias, iniciativas, planos e programas relacionados. Identificou-se uma lacuna na pesquisa e no desenvolvimento de novos antimicrobianos, o que requer uma análise mais aprofundada. Conclusões. A OMS envidou esforços para combater a RAM, o que levou ao desenvolvimento integral de políticas públicas de saúde a serem aplicadas pelos Estados Membros, em conformidade com a soberania de seus governos.

Equity throughout the life course and the evolving role of the Pan American Health Organization / Equidad a lo largo del curso de vida y la evolución del papel de la Organización Panamericana de la Salud / Equidade ao longo da vida e a evolução do papel da Organização Pan-Americana da Saúde

ABSTRACT The objective of this article is to summarize the evolution of the regional commitments of the Pan American Health Organization (PAHO) on health promotion and strategies to improve the health and well-being of women, children, adolescents, and older persons. PAHO regional strategies approved by Member States in the last 20 years are used as the main source of information. The article presents the challenges of making health promotion a public health strategy widely applied in the Region of the Americas and the efforts to renew Member States' collective actions. The article also describes current PAHO efforts to include the positive aspects of health (i.e., well-being, optimal development, and functional ability) and the life course approach as opportunities to advance equity. The article reflects on immunization as a public good and the urgency to address the current challenges as a core element of the regional efforts to transform health systems after more than two years of the COVID-19 pandemic.

RESUMEN El objetivo de este artículo es resumir la evolución de los compromisos regionales de la Organización Panamericana de la Salud (OPS) en materia de promoción de la salud y estrategias para mejorar la salud y el bienestar de mujeres, niños y niñas, adolescentes y personas mayores. Se han empleado como principal fuente de información las estrategias regionales de la OPS aprobadas por los Estados Miembros en los últimos 20 años. En el artículo se presentan los desafíos de convertir la promoción de la salud en una estrategia de salud pública de amplia ejecución en la Región de las Américas y los esfuerzos para renovar las medidas colectivas de los Estados Miembros. Asimismo, se describe la labor actual de la OPS para incluir los aspectos positivos de la salud (como el bienestar, el desarrollo óptimo y la capacidad funcional) y el enfoque del curso de vida como oportunidades para fomentar la equidad. Finalmente, se reflexiona sobre la inmunización como bien público y la urgencia de abordar los desafíos actuales como elemento central de los esfuerzos regionales para transformar los sistemas de salud tras más de dos años de pandemia de COVID-19.

RESUMO O objetivo deste artigo é resumir a evolução dos compromissos regionais da Organização Pan-Americana da Saúde (OPAS) relativos à promoção da saúde e estratégias para melhorar a saúde e o bem-estar de mulheres, crianças, adolescentes e pessoas idosas. As estratégias regionais da OPAS aprovadas pelos Estados Membros nos últimos 20 anos são a principal fonte de informação. O artigo apresenta os desafios enfrentados para fazer da promoção da saúde uma estratégia de saúde pública amplamente aplicada na Região das Américas e os esforços para renovar as ações coletivas dos Estados Membros. O artigo também descreve os atuais esforços da OPAS para incluir os aspectos positivos da saúde (isto é, bem-estar, desenvolvimento ideal e habilidade funcional) e a abordagem de curso da vida como oportunidades para promover a equidade. O artigo faz reflexões sobre a imunização como um bem público e a urgência de abordar os desafios atuais como um elemento central dos esforços regionais para transformar os sistemas de saúde após mais de dois anos da pandemia de COVID-19.

El Fondo Rotatorio para el acceso a las vacunas de la Organización Panamericana de la Salud: 43 años respondiendo al programa regional de inmunizaciones / The Pan American Health Organization's Revolving Fund for access to vaccines: 43 years responding to the regional immunization program / O Fundo Rotativo para Acesso a Vacinas da Organização Pan-Americana da Saúde: 43 anos respondendo ao Programa Regional de Imunizações

RESUMEN El Fondo Rotatorio para el acceso a las vacunas (FR) de la Organización Panamericana de la Salud es un fondo común de capital y compra mancomunada de vacunas, jeringas y equipo de cadena de frío para los Estados Miembros de la Organización. Con el objetivo de evaluar los resultados obtenidos durante su funcionamiento y analizar su contribución a los logros de inmunización, se llevó a cabo una revisión de documentos históricos y literatura gris relacionados con la historia del FR, y se revisaron los procesos actuales, los datos de plataformas alimentadas por los informes anuales de los países, los indicadores de crecimiento, la carga de enfermedades prevenibles por vacunación, la introducción de nuevas vacunas en la Región de las Américas, y lecciones aprendidas. Se encontró que, en sus 43 años de funcionamiento, el FR ha crecido y ha contribuido a la introducción de nuevas vacunas, y que la Región ha avanzado de manera acelerada en el ámbito de las inmunizaciones. Sin embargo, varios países y territorios de la Región todavía no han introducido ciertas vacunas debido a sus altos precios y al impacto económico del mantenimiento de su administración. La cláusula del precio más bajo posible y del precio uniforme para todos los Estados Miembros participantes ha sido fundamental para la contribución del FR a las metas de vacunación de los programas nacionales de inmunización, así como para la planeación oportuna de la demanda acompañada por la asesoría técnica. El abordaje interprogramático y la planeación de insumos auxiliares son necesarios para el éxito de los programas. La preparación ante pandemias, la producción regional de vacunas y la protección de presupuestos nacionales para la compra de vacunas de alto costo y su sostenibilidad constituyen aún retos en el presente y el futuro.

ABSTRACT The Pan American Health Organization's Revolving Fund for Access to Vaccines (the Revolving Fund) is a shared pool of funds for the procurement of vaccines, syringes, and cold-chain equipment for the Member States of the Organization. With a view to evaluating the results obtained during the Revolving Fund's operation and analyzing its contributions to achievements in immunization, a review was conducted of historical documents and grey literature related to the Fund's history and current processes, as well as data from platforms fed by countries' annual reports, with reference to growth indicators, burden of vaccine-preventable diseases, introduction of new vaccines in the Region of the Americas, and lessons learned. In its 43 years of operation, the Revolving Fund has grown and contributed to the introduction of new vaccines, and the Region has made rapid progress in the field of immunization. However, several countries and territories in the Region have not yet introduced certain vaccines due to their high cost and the economic impact of sustainably administering them. The requirement to obtain the lowest possible price and to set a uniform price for all participating Member States has been instrumental in the Revolving Fund's contribution to the vaccination goals of national immunization programs, and for timely planning of demand, accompanied by technical advice. An interprogrammatic approach and the planning of auxiliary inputs are key to the success of the programs. Pandemic preparedness, regional vaccine production, and the protection of national budgets for sustainable procurement of high-cost vaccines are current and future challenges.

RESUMO O Fundo Rotativo para Acesso a Vacinas (FR) da Organização Pan-Americana de Saúde é um fundo comum de capital e compra conjunta de vacinas, seringas e equipamento da cadeia de frio para os Estados Membros da Organização. Com o objetivo de avaliar os resultados obtidos durante sua operação e analisar sua contribuição para os êxitos da imunização, procedeu-se a uma revisão de documentos históricos e da literatura cinzenta relacionados à história do FR e revisaram-se os processos atuais, os dados de plataformas alimentadas pelos relatórios anuais dos países, os indicadores de crescimento, a carga de doenças imunopreveníveis, a introdução de novas vacinas na Região das Américas e as lições aprendidas. Constatou-se que, em seus 43 anos de operação, o FR cresceu e contribuiu para a introdução de novas vacinas e a região avançou com rapidez no campo da imunização. Entretanto, vários países e territórios da região ainda não introduziram determinadas vacinas em razão dos altos preços e do impacto econômico de manter sua administração. A cláusula do menor preço disponível e do preço uniforme para todos os Estados Membros participantes foi fundamental para a contribuição do FR para as metas de vacinação dos programas nacionais de imunização, bem como para o planejamento oportuno da demanda acompanhado pela assessoria técnica. A abordagem interprogramática e o planejamento de insumos auxiliares são necessários para o êxito dos programas. A preparação para pandemias, a produção regional de vacinas e a proteção dos orçamentos nacionais para a compra de vacinas de alto custo e sua sustentabilidade ainda constituem desafios atuais e futuros.

Cien años de la Revista Panamericana de Salud Pública: visualización de sus contenidos / One hundred years of the Pan American Journal of Public Health: visualizing its content / Cem anos da Revista Pan-Americana de Saúde Pública: visualização do seu conteúdo

RESUMEN Objetivos. Explorar la alineación del contenido de los artículos publicados por la Revista Panamericana de Salud Pública durante sus 100 años de existencia, con los temas sanitarios claves de la Organización Panamericana de la Salud (OPS). Métodos. Se llevó a cabo un análisis bibliométrico con visualización de sus resultados. Se recuperó la información sobre los artículos publicados en la Revista a partir del Repositorio Institucional para Intercambio de Información (IRIS) de la OPS para los primeros 75 años y de Scopus para los últimos 25 años hasta febrero del 2022; para establecer los temas claves de la OPS se usaron referencias a documentos de los Cuerpos Directivos y declaraciones de los directores. Resultados. Se obtuvieron inicialmente 12 573 publicaciones y se consideraron para el análisis 9 289 para el período 1922 a 1996 y 3 208 para el período 1997 a 2022. Para el análisis bibliométrico de la información de Scopus se tuvieron en cuenta indicadores como los autores y su procedencia, el idioma de las publicaciones, y el número y la procedencia de las citas. Para las visualizaciones, se dividieron las publicaciones en cinco períodos a fin de que estos coincidieran con los períodos establecidos para el análisis de los temas prioritarios de la OPS. Se realizaron mapas de coocurrencia de palabras claves para observar la evolución de los temas de las publicaciones y relacionarlos con los enfoques de la salud pública en cada período. Conclusión. Las temáticas publicadas en la Revista Panamericana de Salud Pública y sus boletines precursores reflejan la historia de la salud pública regional y su evolución a lo largo del tiempo, así como los temas sanitarios claves de la Organización Panamericana de la Salud.

ABSTRACT Objectives. Explore how the content of the articles published by the Pan American Journal of Public Health during its 100 years of existence has aligned with the key health issues of the Pan American Health Organization (PAHO). Methods. A bibliometric analysis was carried out, with visualization of its results. Information on articles published in the Journal was retrieved from PAHO's Institutional Repository for Information Sharing (IRIS) for the first 75 years and Scopus for the last 25 years, until February 2022; References to Governing Bodies documents and statements by the directors were used to establish PAHO's key themes. Results. Initially, 12 573 publications were obtained and 9 289 were considered for analysis for the period 1922 to 1996, and 3 208 for the period 1997 to 2022. For the bibliometric analysis of the Scopus information, indicators such as the authors and their origin, language of publication, and number and origin of citations were considered. For the visualizations, publications were divided into five periods so that they coincided with the periods established for the analysis of PAHO's priority themes. Keyword co-occurrence maps were made to observe the evolution of published topics and relate them to public health approaches in each period. Conclusion. The topics published in the Pan American Journal of Public Health and its precursor bulletins reflect the history of regional public health and its evolution over time, as well as the key health issues of the Pan American Health Organization.

RESUMO Objetivos. Explorar o alinhamento do conteúdo dos artigos publicados na Revista Pan-Americana de Saúde Pública em seus 100 anos de existência com os principais temas de saúde da Organização Pan-Americana da Saúde (OPAS). Métodos. Fez-se uma análise bibliométrica com visualização de seus resultados. Informações sobre os artigos publicados na revista foram recuperadas do Repositório Institucional para o Intercâmbio de Informações (IRIS, na sigla em inglês) da OPAS para os primeiros 75 anos, e da base de dados Scopus para os últimos 25 anos, até fevereiro de 2022. Para estabelecer os principais temas da OPAS, foram usadas referências a documentos dos órgãos diretores e declarações dos diretores. Resultados. Inicialmente, foram obtidas 12 573 publicações - 9 289 foram consideradas na análise para o período de 1922 a 1996, e 3 208 para o período de 1997 a 2022. Para a análise bibliométrica das informações da Scopus, foram levados em consideração indicadores como os autores e sua procedência, o idioma das publicações e o número e a procedência das citações. Para as visualizações, as publicações foram divididas em cinco períodos para que coincidissem com os períodos estabelecidos para a análise dos temas prioritários da OPAS. Mapeou-se a co-ocorrência de palavras-chave para observar a evolução dos temas das publicações e para relacioná-los com os enfoques de saúde pública em cada período. Conclusão. Os temas publicados na Revista Pan-Americana de Saúde Pública e nos boletins que a antecederam refletem o histórico da saúde pública regional e sua evolução ao longo do tempo, bem como os principais temas de saúde da Organização Pan-Americana da Saúde.

Noncommunicable diseases in the Americas: a review of the Pan American Health Organization's 25-year program of work / Enfermedades no transmisibles en la Región de las Américas: revisión del programa de trabajo de la Organización Panamericana de la Salud tras 25 años de actividades / Doenças não transmissíveis nas Américas: uma revisão do programa de trabalho de 25 anos da Organização Pan-Americana da Saúde

ABSTRACT This article describes progress in tackling noncommunicable diseases (NCDs) in the Americas since the Pan American Health Organization (PAHO) started its NCD program 25 years ago. Changes in the epidemiology of NCDs, NCD policies, health service capacity, and surveillance are discussed. PAHO's NCD program is guided by regional plans of action on specific NCDs and risk factors, as well as a comprehensive NCD plan. Its work involves implementing evidence-based World Health Organization technical packages on NCDs and their risk factors with the aim of achieving the Sustainable Development Goal target of a one third reduction in premature mortality caused by NCDs by 2030. Important advances have been made in the past 25 years in implementation of: policies on NCD risk factors; interventions to improve NCD diagnosis and treatment; and NCD surveillance. Premature mortality from NCDs decreased by 1.7% a year between 2000 and 2011 and 0.77% a year between 2011 and 2019. However, policies on risk factor prevention and health promotion need to be strengthened to ensure more countries are on track to achieving the NCD-related health goals of the Sustainable Development Goals by 2030. Actions are recommended for governments to raise the priority of NCDs by: making NCDs a core pillar of primary care services, using revenues from health taxes to invest more in NCD prevention and control; and implementing policies, laws, and regulations to reduce the demand for and availability of tobacco, alcohol, and ultra-processed food products.

RESUMEN En este artículo se describe el progreso en la lucha contra las enfermedades no transmisibles (ENT) en la Región de las Américas desde que la Organización Panamericana de la Salud (OPS) iniciara su programa contra las ENT hace 25 años. Se abordan los cambios en las características epidemiológicas, las políticas, la capacidad de los servicios de salud y la vigilancia de estas enfermedades. Este programa de la OPS se rige por planes regionales de acción sobre enfermedades y factores de riesgo específicos, así como por un plan integral de ENT. Su labor consiste en poner en práctica paquetes técnicos de la Organización Mundial de la Salud basados en la evidencia sobre las ENT y sus factores de riesgo con el objetivo de alcanzar la meta de los Objetivos de Desarrollo Sostenible (ODS) de reducir en un tercio la mortalidad prematura causada por las ENT para el 2030. En los últimos 25 años se han logrado importantes avances en la ejecución de políticas sobre los factores de riesgo de estas enfermedades, en las intervenciones para mejorar su diagnóstico y tratamiento, y en la vigilancia. La mortalidad prematura por ENT disminuyó 1,7% anual entre el 2000 y el 2011 y 0,77% anual entre los años 2011 y 2019. Sin embargo, es necesario fortalecer las políticas de prevención de factores de riesgo y promoción de la salud para garantizar que más países estén bien encaminados para lograr las metas de salud de los ODS relacionadas con las ENT para el 2030. Se recomiendan medidas para que los gobiernos prioricen más las ENT y las conviertan en un pilar central de los servicios de atención primaria, al usar los ingresos generados por los impuestos en el sector de la salud para incrementar las inversiones en la prevención y control de las ENT, y ejecutar políticas, leyes y regulaciones para reducir la demanda y la disponibilidad de tabaco, alcohol y alimentos ultraprocesados.

RESUMO Este artigo descreve o progresso no combate às doenças não transmissíveis (DNTs) nas Américas desde que a Organização Pan-Americana da Saúde (OPAS) iniciou seu programa para essas doenças há 25 anos. Discute-se como evoluíram a epidemiologia das DNTs, as políticas contra essas doenças, a capacidade dos serviços de saúde e a vigilância. O programa da OPAS para as DNTs é orientado por planos de ação regionais sobre DNTs específicas e fatores de risco, bem como por um plano integral contra essas doenças. O trabalho envolve a implementação de pacotes técnicos da Organização Mundial da Saúde baseados em evidências sobre as DNTs e seus fatores de risco, no intuito de alcançar a meta do Objetivo de Desenvolvimento Sustentável de reduzir em um terço a mortalidade prematura causada pelas DNTs até 2030. Avanços importantes foram obtidos nos últimos 25 anos na implementação de políticas sobre fatores de risco das DNTs, intervenções para melhorar o diagnóstico e o tratamento das DNTs, e vigilância das DNTs. A mortalidade prematura causada pelas DNTs diminuiu 1,7% ao ano entre 2000 e 2011 e 0,77% ao ano entre 2011 e 2019. Contudo, as políticas sobre a prevenção dos fatores de risco e a promoção da saúde precisam ser fortalecidas para que mais países estejam no rumo certo para alcançar as metas de saúde relacionadas a essas doenças, no âmbito dos Objetivos de Desenvolvimento Sustentável até 2030. São recomendadas medidas para que os governos elevem a prioridade das DNTs ao torná-las um pilar central dos serviços de atenção primária, usando a receita dos tributos saudáveis para investir mais na prevenção e no controle das DNTs, e ao implementar políticas, leis e regulamentos para reduzir a demanda e a disponibilidade de álcool, tabaco e produtos alimentícios ultraprocessados.

Mining Novel Anti-Nocardia Drug Targets Based on Pan-genomics and Subtractive Proteomics / 中山大学学报(医学科学版)

ObjectiveNocardia is an apathogen that causes opportunistic infections in humans and has a global distribution. In recent years， resistance of Nocardia to commonly used drugs have been observed， highlighting the urgent need for the identification of new drug targets and the development of novel antimicrobial agents against Nocardia. MethodsThirty-one complete genome sequences of Nocardia strains were retrieved from the GenBank database. Pan-genomic analysis was performed using BPGA， and drug target candidates were screened using subtractive proteomics. Homology modeling was employed to predict the 3D structures of target proteins， and potential drugs targeting these proteins were predicted using DrugBank. Molecular docking techniques were utilized to validate the binding activity between the drugs and target proteins. ResultsThe pan-genomic analysis of the 31 Nocardia strains revealed 1 421 core proteins. Fifteen candidate drug target proteins were identified through subtractive proteomics analysis. Among them， the physicochemical properties of the OG1493 protein （such as amino acid count， molecular weight， isoelectric point， grand average of hydropathicity， fat index，and instability index Ⅱ） were found to be most suitable for a drug target protein. Using the DrugBank database， seven compounds， namely Adenosine-5'-Rp-Alpha-Thio-Triphosphate， alpha，beta-Methyleneadenosine 5'-triphosphate， Phosphoaminophosphonic Acid-Adenylate Ester ，Radicicol，2-Hydroxyestradiol， p-Coumaric acid， and Ethylmercurithiosalicylic acid were identified as potential compounds capable of exerting anti-Nocardia effects by targeting this protein. Molecular docking results indicated a strong binding affinity between the target protein and these compounds. The experimental result showed that that Radicicol could be a potential antibacterial drug targeting this particular protein. ConclusionPan-genomic analysis and subtractive proteomics are valuable approaches for mining novel anti-Nocardia drug targets.

STIP1 correlates with tumor immune infiltration and prognosis as a potential immunotherapy target: a pan-cancer bioinformatics analysis / 南方医科大学学报

OBJECTIVE@#To investigate the correlation of stress-inducible phosphoprotein 1 (STIP1) expression level with prognosis of different cancers and its potential role in immunotherapy.@*METHODS@#TCGA, TARGET and GTEx databases were used for bioinformatic analysis of STIP1 expression level and its prognostic value in different cancers. We also detected STIP1 expression immunohistochemically in 10 pairs of colorectal cancer and adjacent tissues. We further analyzed the correlation of STIP1 expression level with tumor mutational burden, microsatellite instability, immune cell infiltration, immune regulators and outcomes of different cancers. STIP1- related proteins were identified using protein- protein interaction (PPI) network analysis, and functional enrichment analysis was performed to analyze the regulatory pathways involving STIP1.@*RESULTS@#Bioinformatics analysis showed that STIP1 was highly expressed in most tumors compared with the normal tissues (P < 0.05), which was confirmed by immunohistochemistry of the 10 pairs of colorectal cancer tissues. STIP1 expression level was correlated with clinical stages of multiple cancers (P < 0.05), and in some cancer types, an upregulated STIP1 expression was correlated with a poor prognosis of the patients in terms of overall survival, disease-specific survival, disease-free survival and progression-free survival (P < 0.05). STIP1 expression was significantly correlated with tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors in most tumors (P < 0.05). PPI network analysis indicated that STIP1-related proteins included HSPA4, HSPA8, and HSP90AA1. KEGG enrichment analysis suggested that the high expression of STIP1 in liver cancer was related mainly with valerate metabolism, tryptophan metabolism, and butyrate metabolism pathways; HALLMARK enrichment analysis suggested high STIP1 expression in liver cancer was involved in bile acid and fatty acid metabolism.@*CONCLUSION@#STIP1 is up-regulated in multiple cancer types and its expression level is correlated with clinical tumor stage, tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors.

Value of brain-expressed X-linked family genes in the diagnosis and prognosis prediction of pan-cancer / 肿瘤研究与临床

Objective:To investigate the differential expression of brain-expressed X-linked (BEX) family genes in pan-cancer and its value in diagnosis and prognosis of pan-cancer.Methods:RNA sequencing (RNA-seq) data, survival data, immune subtypes, the stem cell scores based on RNA and DNA methylation of 33 different tumors from The Cancer Genome Atlas (TCGA) database were downloaded from the online database of University of California, Santa Cruz (UCSC Xena) on April 10, 2022. The limma package of R software (V.4.2.0) was used to analyze the expression of BEX family genes in the TCGA database. The differential expression of BEX family genes in pan-cancer tissues and normal tissues was compared by using Wilcox test. Pan-cancer patients were divided into high expression group and low expression group according to the median expression level of BEX family genes; Kaplan-Meier survival analysis was used to evaluate the relationship between the expression of BEX family genes and the overall survival (OS) of patients; Cox proportional risk model was used to analyze the effect of the expression of BEX family genes on OS in pan-cancer patients and then the forest map was drawn. The correlation of the expression of BEX family genes with tumor microenviroment and tumor stem cells in pan-cancer patients was analyzed based on the correlation index Cor value. Spearman correlation analysis was used to analyze the correlation between the expression of BEX family genes and tumor microenviroment and cancer stem cell index in gastric cancer tissues. The RNA-seq of different tumor cell lines and drug sensitivity data download from the CellMiner database were used to analyze the correlation between the expression of BEX family genes and drug sensitivity. The correlation of pan-cancer and gastric cancer immune subtypes with the expression of BEX family genes was analyzed by using Kruskal test.Results:BEX3 was highly expressed in pan-cancer tissues in TCGA database, BEX2 and BEX4 were moderately expressed in pan-cancer tissues, and BEX1 and BEX5 were relatively low expressed in pan-cancer tissues. The expressions of BEX2, BEX3 and BEX4 were the highest in cholangiocarcinoma, the expression of BEX5 was the highest in endometrial neoplasms, and the expression of BEX1 was the highest in invasive breast cancer. Compared with normal tissue samples, the expressions of BEX family genes were up-regulated or down-regulated in various cancers (all P < 0.05). Survival analysis showed that the expressions of BEX family genes were associated with the OS of various cancers. Some tumor patients with high expressions of BEX1, BEX3, BEX4 and BEX5 had better OS compared with those with low expressions, and the differences were statistically significant (all P < 0.05). Other patients with high expression of BEX family genes had worse OS compared with those with low expressions, and the differences were statistically significant (all P < 0.05). Cox regression analysis showed that the high expression of BEX1 for stomach neoplasms; the high expression of BEX2 for acute myeloid leukemia, thymoma and endometrial neoplasms; the expression high of BEX3 for squamous cell carcinoma of head and neck,sarcoma, stomach neoplasms and endometrial neoplasms; the high expression of BEX4 for rectal adenocarcinoma, stomach neoplasms and endometrial neoplasms; the high expression of BEX5 for renal suspicious cell carcinoma and thymoma were risk factors for OS (all P < 0.05).The expression of BEX family genes was negatively correlated with the stromal score of most cancers (all P < 0.05), and positively correlated with the stem cell score (all P < 0.05). The expression of BEX family genes was negatively correlated with cancer stem cell index of gastric cancer ( P < 0.05), and was positively correlated with matrix score and estimated total score (all P < 0.05). Among different tumor cell lines in CellMiner database, BEX family genes were closely related to drug resistance of vemurafenib (Cor = -0.368, P = 0.004), Kahalide f (Cor = -0.391, P = 0.002), O-6-benzylguanine (Cor = -0.375, P = 0.003) and other drugs. All genes in the BEX family were related to the immune subtypes of pan-cancer and were highly expressed in C5 subtype (all P < 0.05).For gastric cancer, all genes showed high expression in the C3 subtype (all P < 0.05), except BEX5 ( P = 0.24). Conclusions:The expression of BEX family genes is closely related to the prognosis of pan-cancer patients, and has an impact on the tumor microenvironment, cancer stem cells and drug sensitivity. BEX family genes may be potential biomarkers for diagnosis and prognosis of pan-cancer.

Outcome of a Simple Novel Technique to Reduce Soft Tissue Complications in Open Tendoachilles Injury: A Series of 20 Patients

@#Introduction: Open tendoachilles injuries are rare and associated with significant soft tissues complications. The objective of the present study was to assess the clinical outcome and safety of a simple and minimally invasive technique, with a goal to assess if it may help minimise flap and wound related complications in open tendoachilles injuries. Materials and methods: This prospective study of four years duration included 20 patients with open tendoachilles injuries managed with a simple minimally invasive tunnel technique. The primary outcome variable was occurrence of a major soft tissue complication. The secondary outcome variables included functional outcome measured using AOFAS Ankle hind foot score, re-rupture of tendoachilles and need for revision surgery. Results: None of the patients in the present series developed a serious soft tissue complication. Based upon the AOFAS hind foot scoring system, good to excellent outcome was achieved in 19 (95%) patients. All the patients were able to perform tip toe walking at six months post-surgery. None of the patients had a re-rupture of the tendoachilles and no patient needed a revision surgery. The complications encountered include thickening of the tendon at the repair site (15%), superficial wound infection (5%), stitch granuloma (5%) and hypertrophic scar (5%). Conclusion: This technique seems to be promising in reducing the soft tissue complications associated with the surgical management of open tendoachilles injuries. Most patients had a good final clinical outcome. The technique is safe, simple and reproducible. However, further randomised control studies with a larger sample size assessing the technique are recommended.

Research on fungal culturomics based on different universal media / 中国热带医学

@#Abstract: Objective To screen out a more universally applicable culture medium for the isolation and culturing of pathogenic fungi through comparing the performance of various universal fungal culture media, to optimize the fungal culturomics technique, and to better apply it to the culturomics research of pathogenic fungi. Methods Multiple common fungal culture media Sabouraud dextrose agar (SDA), potato dextrose agar (PDA), modified Dixon (mDixon), modified LeemingNotman agar (MLNA), etc., and a new pan-fungal medium (PF) were used to culture 40 strains of common pathogenic fungi to determine the growth states of strains under different conditions. Based on that, PF, SDA, PDA, mDixon and MLNA, a total of 5 culture media, were used to isolate and culture a simulated sample (suspension of Candida albicans and Aspergillus fumigatus), 10 human samples (4 fecal samples and 6 vaginal secretion samples) and 3 environmental samples. Results The positive growth rates of 40 strains of pathogenic fungi in the 7 media were as follows: PDA 95.0% (38/40), SDA 95.0% (38/40), BHI 95.0% (38/40), YPD 90.0% (36/40), mDixon 95.0% (38/40), MLNA 87.5% (35/40), PF 100.0% (40/40). For the simulated samples, PF could effectively promote the self-limited growth of filamentous fungi, performing better in isolation and culture. For the human samples and environmental samples, PF showed the same versatility as SDA and PDA. Conclusions In the isolation and culturing of pathogenic fungi, PF medium can effectively isolate and culture most fungal species. Meanwhile, PF can make the fast-growing fungi show self-limited growth and clear edges, and not easy to cross-contamination, which indicates it is conducive to the isolation and identification of single colonies. PF medium outperforms other common media in isolating strains from unknown samples in culturomics, which illustrates PF medium can be effectively used for the study of fungal culturomics.