The impact of tRNA modifications on translation in cancer: identifying novel therapeutic avenues.

Recent advancements have illuminated the critical role of RNA modifications in post-transcriptional regulation, shaping the landscape of gene expression. This review explores how tRNA modifications emerge as critical players, fine-tuning functionalities that not only maintain the fidelity of protein synthesis but also dictate gene expression and translation profiles. Highlighting their dysregulation as a common denominator in various cancers, we systematically investigate the intersection of both cytosolic and mitochondrial tRNA modifications with cancer biology. These modifications impact key processes such as cell proliferation, tumorigenesis, migration, metastasis, bioenergetics and the modulation of the tumor immune microenvironment. The recurrence of altered tRNA modification patterns across different cancer types underscores their significance in cancer development, proposing them as potential biomarkers and as actionable targets to disrupt tumorigenic processes, offering new avenues for precision medicine in the battle against cancer.

"Long-term oncologic outcomes and risk factors for distant recurrence after pathologic complete response following neoadjuvant treatment for locally advanced rectal cancer. A nationwide, multicentre study".

BACKGROUND: Pathologic complete response (pCR) after multimodal treatment for locally advanced rectal cancer (LARC) is used as surrogate marker of success as it is assumed to correlate with improved oncologic outcome. However, long-term oncologic data are scarce. METHODS: This retrospective, multicentre study updated the oncologic follow-up of prospectively collected data from the Spanish Rectal Cancer Project database. pCR was described as no evidence of tumour cells in the specimen. Endpoints were distant metastases-free survival (DMFS) and overall survival (OS). Multivariate regression analyses were run to identify factors associated with survival. RESULTS: Overall, 32 different hospitals were involved, providing data on 815 patients with pCR. At a median follow-up of 73.4 (IQR 57.7-99.5) months, distant metastases occurred in 6.4% of patients. Abdominoperineal excision (APE) (HR 2.2, 95%CI 1.2-4.1, p = 0.008) and elevated CEA levels (HR = 1.9, 95% CI 1.0-3.7, p = 0.049) were independent risk factors for distant recurrence. Age (years) (HR 1.1; 95%-CI 1.05-41.09; p < 0.001) and ASA III-IV (HR = 2.0; 95%-CI 1.4-2.9; p < 0.001), were the only factors associated with OS. The estimated 12, 36 and 60-months DMFS rates were 96.9%, 91.3%, and 86.8%. The estimated 12, 36 and 60-months OS rates were 99.1%, 94.9% and 89.3%. CONCLUSIONS: The incidence of metachronous distant metastases is low after pCR, with high rates of both DMFS and OS. The oncologic prognosis in LARC patients that achieve pCR after neoadjuvant chemo-radiotherapy is excellent in the long term.

METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer.

Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N7-methylguanosine (m7G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m7G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m7G tRNA methylation in cancer cell translation control and tumour biology.

Anxiety, sleep habits and executive function during the COVID-19 pandemic through parents' perception: a longitudinal study

Abstract The present study therefore aims to examine trait and state anxiety, sleep habits and executive functioning during 1 year and a half of the COVID-19 pandemic in children and adolescents through the lens of parents. Assessments were conducted at three different times: April 2020 (T1), October 2020 (T2) and October 2021 (T3). The main sample included 953 children and adolescents aged 6 to 18 years, and scales were used to assess anxiety (STAIC), sleep habits (BEARS) and executive functioning (BRIEF-2). The results showed that 6 months after the outbreak of the pandemic, state and trait anxiety, sleep disturbances and executive dysfunctions increased significantly. One and a half year later, trait anxiety and sleep disturbances have been maintained, while state anxiety and executive dysfunction have decreased their scores obtaining scores similar to those of April 2020. In conclusion, there has been a further decrease in children and adolescents' mental health since the beginning of the pandemic, and it seems to remain at the present time, such as trait anxiety as a part of the personality.

Assessment Strategies to Evaluate the Mediterranean Lifestyle: A Systematic Review.

The Mediterranean Lifestyle (MLS) has been related to better health and quality of life. However, there is no consensus on how to assess this lifestyle. The main objective of this work was to systematically review the methodology used in different studies on the evaluation of the MLS. The specific objectives were (1) to analyze the MLS components evaluated in previous studies, (2) to explore the assessment instruments available for the analysis of the MLS, and (3) to identify the psychometric properties of these instruments. The search was carried out using the PubMed, Scopus, Web of Science, and ScienceDirect databases with the purpose of identifying those published articles in which the MLS was assessed. The review included 26 studies linked to the assessment of the MLS. Of these studies, only four exclusively used a tool to analyze MLS components globally. These studies included two questionnaires and three different indexes. None of them, however, evaluated all of the recognized MLS components, and food preparation was the least frequently evaluated component. Given the clear importance of analyzing MLS adherence and the lack of consensus in previous research, an evaluation tool needs to be created to comprehensively assess all of the MLS dimensions by means of appropriate psychometric properties.

The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities.

RNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances have been made in understanding the functional role of RNA modifications in regulating coding and non-coding RNA processing and function, which in turn thoroughly shape distinct gene expression programmes. They affect diverse biological processes, and the correct deposition of many of these modifications is required for normal development. Alterations of their deposition are implicated in several diseases, including cancer. In this Review, we focus on the occurrence of N6-methyladenosine (m6A), 5-methylcytosine (m5C) and pseudouridine (Ψ) in coding and non-coding RNAs and describe their physiopathological role in cancer. We will highlight the latest insights into the mechanisms of how these posttranscriptional modifications influence tumour development, maintenance, and progression. Finally, we will summarize the latest advances on the development of small molecule inhibitors that target specific writers or erasers to rewind the epitranscriptome of a cancer cell and their therapeutic potential.

Actitudes y conocimientos sobre la pandemia por la COVID-19 en docentes de Canarias / Teachers' attitudes and knowledge about the COVID-19 pandemic in the Canary Islands

RESUMEN Con el objetivo de estudiar las actitudes y conocimientos sobre la pandemia por la COVID-19 en el personal docente de la región de Canarias en España, se realizó un estudio transversal entre el 14 y el 18 de mayo de 2020, mediante la aplicación de un cuestionario virtual basado en un instrumento validado. Se incluyeron 1503 encuestas, en donde se describe que el personal docente no está dispuesto a trabajar si existe riesgo de infectarse en el centro educativo (76,6%). No obstante, afirman que acudiría a trabajar si dispusieran de las medidas higiénicas (69,2%) y de protección adecuadas (67,0%). En conclusión, resulta pertinente garantizar las medidas preventivas necesarias para evitar el contagio en los centros educativos, propiciando la formación específica de los docentes en prevención primaria.

ABSTRACT A cross-sectional study was carried out to determine the teachers' attitudes and knowledge about the COVID-19 pandemic in the Canary Islands region in Spain, between May 14 - 18, 2020. A virtual questionnaire based on a validated instrument was applied. We included 1,503 surveys, which showed that teachers are unwilling to work if there is risk of infection at the school (76.6%). However, they state that they would go to work if they had the appropriate hygiene (69.2%) and protection (67.0%) measures. In conclusion, it is important to guarantee the necessary preventive measures to avoid contagion in educational centers, promoting specific training of teachers in primary prevention.

Actitudes y conocimientos sobre la pandemia por la COVID-19 en docentes de Canarias / Teachers' attitudes and knowledge about the COVID-19 pandemic in the Canary Islands

RESUMEN Con el objetivo de estudiar las actitudes y conocimientos sobre la pandemia por la COVID-19 en el personal docente de la región de Canarias en España, se realizó un estudio transversal entre el 14 y el 18 de mayo de 2020, mediante la aplicación de un cuestionario virtual basado en un instrumento validado. Se incluyeron 1503 encuestas, en donde se describe que el personal docente no está dispuesto a trabajar si existe riesgo de infectarse en el centro educativo (76,6%). No obstante, afirman que acudiría a trabajar si dispusieran de las medidas higiénicas (69,2%) y de protección adecuadas (67,0%). En conclusión, resulta pertinente garantizar las medidas preventivas necesarias para evitar el contagio en los centros educativos, propiciando la formación específica de los docentes en prevención primaria.

ABSTRACT A cross-sectional study was carried out to determine the teachers' attitudes and knowledge about the COVID-19 pandemic in the Canary Islands region in Spain, between May 14 - 18, 2020. A virtual questionnaire based on a validated instrument was applied. We included 1,503 surveys, which showed that teachers are unwilling to work if there is risk of infection at the school (76.6%). However, they state that they would go to work if they had the appropriate hygiene (69.2%) and protection (67.0%) measures. In conclusion, it is important to guarantee the necessary preventive measures to avoid contagion in educational centers, promoting specific training of teachers in primary prevention.

Creencias y actitudes de trabajadores sanitarios y estudiantes de enfermería de una región de España ante una pandemia de gripe / Beliefs and attitudes of health workers and nursing students toward an influenza pandemic in a region of Spain

RESUMEN Con el objetivo de analizar las creencias y actitudes de trabajadores sanitarios y estudiantes de enfermería de Las Palmas de Gran Canaria en España ante una pandemia por gripe, se aplicó una encuesta durante marzo-mayo del 2017. Un alto porcentaje duda que exista una vacuna que les proteja ante una pandemia por gripe aunque los trabajadores muestran mayor seguridad con respecto al acceso a una vacuna que los estudiantes, los trabajadores sanitarios manifestaron una mayor responsabilidad ante su trabajo que los estudiantes, así un 46,7% estaría de acuerdo en sancionar al que se negase a ir a trabajar, debido a que existe un alto porcentaje lo anteponen a su responsabilidad para sí y su familia. En conclusión, se sugiere la promoción de iniciativas encaminadas a reducir el absentismo, identificando aquellos factores que lo facilitarían y tener preparado un plan de contingencia ante una pandemia por gripe.

ABSTRACT A survey was carried out during March-May 2017 to analyze the beliefs and attitudes of health workers and nursing students in the face of an influenza pandemic in Las Palmas de Gran Canaria, Spain. A high percentage doubted that there is a vaccine to protect them against an influenza pandemic, although workers showed greater certainty than students concerning access to a vaccine. Health workers showed themselves as more responsible for their work than students; i.e., 46.7% would be in favor of penalizing anyone who refused to go to work because there is a high percentage that put work before their responsibility toward themselves and their families. In conclusion, this study suggests promoting initiatives for reducing absenteeism, identifying those factors that would facilitate it, and having a contingency plan prepared in the event of an influenza pandemic.

Medulloblastoma subgroups remain stable across primary and metastatic compartments.

Medulloblastoma comprises four distinct molecular variants with distinct genetics, transcriptomes, and outcomes. Subgroup affiliation has been previously shown to remain stable at the time of recurrence, which likely reflects their distinct cells of origin. However, a therapeutically relevant question that remains unanswered is subgroup stability in the metastatic compartment. We assembled a cohort of 12-paired primary-metastatic tumors collected in the MAGIC consortium, and established their molecular subgroup affiliation by performing integrative gene expression and DNA methylation analysis. Frozen tissues were collected and profiled using Affymetrix gene expression arrays and Illumina methylation arrays. Class prediction and hierarchical clustering were performed using existing published datasets. Our molecular analysis, using consensus integrative genomic data, establishes the unequivocal maintenance of molecular subgroup affiliation in metastatic medulloblastoma. We further validated these findings by interrogating a non-overlapping cohort of 19 pairs of primary-metastatic tumors from the Burdenko Neurosurgical Institute using an orthogonal technique of immunohistochemical staining. This investigation represents the largest reported primary-metastatic paired cohort profiled to date and provides a unique opportunity to evaluate subgroup-specific molecular aberrations within the metastatic compartment. Our findings further support the hypothesis that medulloblastoma subgroups arise from distinct cells of origin, which are carried forward from ontogeny to oncology.

Estudio comparativo entre somatostatina sintética (octreótide) y escleroterapia en el tratamiento de várices esofágicas sangrantes en pacientes cirróticos / comparative Study between synthetic somatostatina (octreótide) and escleroterapia in the processing of bleeding esofágicas várices in cirróticos patients

Expone que en la unidad de cuidados intensivos del Hospital Teodoro Maldonado Carbo del IESS y en el Hospital Luis Vernaza de la Junta de Beneficiencia de Guayaquil, desde febrero de 1995 a enero de 1996 se estudiaron 37 pacientes que presentaron sangrado agudo por ruptura de várices esofágicas, de los cuales 23 pacientes (62 por ciento) fueron sometidos a escleroterapia y 14 (38 por ciento) se les adminsitró el derivado sintético de la somatostatina, el Octreeótide. El objetivo de este estudio fue comparar cada uno de estos tratamientos basándose en diversos parámetros. Como resultado del estudio se obtuvo que el 5.4 por ciento de los pacientes que recibieron Octreótide, y en el 8.1 por ciento de los pacientes que recibieron escleroterapia tuvieron fallas en el tratamiento, considerándose como tal la persistencia del sangrado; el 7.10 por ciento de los pacientes que recibieron Octreótide y en el 8.6 por ciento de los pacientes que recibieron escleroterapia presentaron resangrado temprano; y el 14.2 por ciento de los pacientes qu recibieron Octreótide y 17.3 por ciento a los que se realizó escleroterapia. Al finalizar el estudio se concluyó que los resultados de la observación a cuatro meses son similares para dos tratamiento, que el Octreótide constiuye un buen procedimiento alternativo para el tratamiento de dichas hemorragias, y que su importancia radica en que puede ser empleado inmediatamente y que representa una menor dificultad para su uso...