The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-19, pub-electronic 2021-10-22Publication status: PublishedFunder: Instituto de Salud Carlos III; Grant(s): PI18/00442Funder: European Commission; Grant(s): ITN-308 2016 721532Funder: Breast Cancer Now; Grant(s): 2012NovSP033Funder: Ministry of Economy, Industry and Competitiveness; Grant(s): RTI2018-094130-B-100Background: Tribbles pseudokinase 3 (TRIB3) has been proposed to both promote and restrict cancer generation and progression. However, the precise mechanisms that determine this dual role of TRIB3 in cancer remain to be understood. In this study we aimed to investigate the role of TRIB3 in luminal breast cancer, the most frequent subtype of this malignancy. Methods: We genetically manipulated TRIB3 expression in a panel of luminal breast cancer cell lines and analyzed its impact on cell proliferation, and the phosphorylation, levels, or subcellular localization of TRIB3 and other protein regulators of key signaling pathways in luminal breast cancer. We also analyzed TRIB3 protein expression in samples from luminal breast cancer patients and performed bioinformatic analyses in public datasets. Results: TRIB3 enhanced the proliferation and AKT phosphorylation in luminal A (HER2-) but decreased them in luminal B (HER2+) breast cancer cell lines. TRIB3 negatively regulated the stability of HER2 in luminal B breast cancer cell lines. TRIB3 expression was associated with increased disease-free survival and a better response to therapy in luminal breast cancer patients. Conclusions: Our findings support the exploration of TRIB3 as a potential biomarker and therapeutic target in luminal breast cancer

Ecos de la academia: Revista de la Facultad de Educación, Ciencia y Tecnología - FECYT Nro 15

Ecos de la academia, Revista de la Facultad de Educación Ciencia y Tecnología es una publicación científica de la Universidad Técnica del Norte, con revisión por pares a doble ciego que publica artículos en idioma español, quichua, portugués e inglés. Se edita con una frecuencia semestral con dos números por año.En ella se divulgan trabajos originales e inéditos generados por los investigadores, docentes y estudiantes de la FECYT, y contribuciones de profesionales de instituciones docentes e investigativas dentro y fuera del país, con calidad, originalidad y relevancia en las áreas de ciencias sociales y tecnología aplicada.Estudio sobre el liderazgo educativo en los directivos de la Unidad Educativa Julio María Mato¬velle de Puerto Bolívar. La gamificación como metodología activa en el proceso de enseñanza-aprendizaje Caso de estu¬dio: estudiantes de la carrera de Pedagogía de las Artes. Enseñanza-aprendizaje en ciencias sociales a través de ilustraciones artísticas: un estudio de caso. Estado del Arte. Investigación formativa en la Educación Superior. Flipped Classroom for enhancing fluency in secondary students from a public school. El territorio del valle del chota: el deporte como motor de desarrollo. de la esperanza al olvido

Revista de Ciencias Sociales (Vol. 24 no. 28 jul 2011)

Territorio, metodologías e imputabilidad penal/ Verónica Filardo Precariedad objetiva y subjetiva en el trabajo rural: nuevas evidencias/ Diego E. Piñeiro Ciudadanía, capital social y mujeres en el enfoque territorial Un estudio en las comunidades de San Pedro y Santa Cruz do Sul/ Rossana Vitelli Martínez Dinámicas de la segregación urbana. Movilidad cotidiana en Montevideo/ Sebastián Aguiar Un quinquenio cargado de futuro: la descentralización y el ordenamiento territorial en Uruguay/ Altair Magri El lugar de la evaluación cualitativa en un diseño combinado. Una experiencia en Uruguay/ Ignacio Pardo, Martín Moreno La discusión legislativa de la edad de imputabilidad en los anales de la recuperación democrática. Cualquier semejanza con la actualidad NO es pura coincidencia/ Gabriel Tenenbaum Reseñas bibliográficas Globalización y perspectivas de la integración regional de Pedro Sánchez Vera y Alberto Riella, ed./ Por Paola Mascheroni La Universidad transformadora Elementos para una teoría sobre educación y género de Adriana Marrero y Natalia Mallada/ Por Karina Batthyány Jóvenes y políticas sociales en foco de Verónica Filardo, coord./ Por Mariana Cabrer

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Biotransformación de diterpenoides por hongos filamentosos nativos :

IP 1203-12-10404Incluye anexos.Javergraf. -- p. ; 28 cm. -- Contribucion al estudio de los hongos filamentosos en la zona de frailejones del;paramo de Guasca - Colombia / Adriana Chitiva ... [et al.]--p.193 -- En: Congreso Nacional de Ciencias;Biologicas. (37 : 2001 oct : Cartagena de Indias, Colombia) --[s.l : s.n], 2001 -- p. ; 23 cm. -- Produccion;de metabolitos secundarios de la cepa EB-406-05 / Ruben DarioTorrenegra,Giovana Salamanca. -- p. 193 -- En:;Congreso Nacional de Ciencias Biologicas. (37 : 2001 oct :Cartagena de Indias, Colombia) -- [s.l : s.n],;2001 -- p. ; 23 cm -- Una cepa nativa colombiana de Penicilliumverrucosumcomo fuente de acido micofenolico /;Ruben D. Torrenegra, Jose E. Baquero. -- p. 108 -- En: CongresoItalo-latinoamericano de etnomedicina Nuno;Alvares Pereira. (12 : 2003 sep. 8-12 : Rio de Janeiro) --[s.l: s.n], 2003 -- p. ; 28 cm. -- Mohos de los;paramos de Guasca y El tablazo / Adriana J. Chitiva. -- En: Congreso la Investigacion en la Pontificia;Universidad Javeriana. (7 : 2003 ago. 26-29 : Bogotá) -- [s.l:s.n], 2003-- p. ; 28 cm. -- Biotransformacion;de diterpenos y voacangina, evaluacion de metabolitos secundarios del Aspergillus niger 511 y su actividad;PONENCIA(S) EN CONGRESO: Metabolitos secundarios del Aspergillusniger 511y su actividad antimicrobiana /;R.D. Torrenegra, P.M. Daza. -- p. 103-104 -- En: CongresoNacional de Fitoquimica. (7 : 2002 : Bogotá) --;antimicrobiana / Ruben D. Torrenegra G. -- En: Congreso laInvestigacion en la Pontificia Universidad;Javeriana. (7 : 2003 ago. 26-29 : Bogotá) -- [s.l : s.n],2003-- p. ; 28cm.;Bogotá : Javergraf., 2002 -- p. ; 28 cm. -- Un metabolitosecundario antimicrobiano / J.E. Baquero, R.D.;Torrenegra, M. Bayona. -- p.124-125 -- En: Congreso NacionaldeFitoquimica. (7 : 2002 : Bogotá) -- Bogotá