Valor pronóstico de la biopsia líquida peritoneal y en plasma en pacientes con carcinomatosis peritoneal de origen colorrectal y apendicular sometidos a citorreducción y HIPEC

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Cirugía. Fecha de lectura: 30-11-202

The role of mucin cell-free DNA detection as a new marker for the study of acellular pseudomyxoma peritonei of appendicular origin by liquid biopsy

Background: Acellular pseudomyxoma peritonei (aPMP) is a rare peritoneal malignancy characterized by the accumulation of large amounts of mucin (lacking tumor cells) in the peritoneum. Many cases account for several kilograms of mucin to be screened by the pathologist. This is a comprehensive study of three patients with aPMP, whose tumors showed KRAS mutation, allowing for the tracking of this marker by liquid biopsy. Methods: Pre and post-surgery plasma, and mucin removed during cytoreductive surgery were collected from the patients. KRAS mutations were analyzed using droplet digital polymerase chain reaction (ddPCR). Mucin was injected in mice. KRAS and cytokine levels were measured in plasma of the mice using ddPCR and a magnetic bead-based assay. Mucin microbiome was analyzed by 16S rRNA sequencing. Results: KRAS mutations were detected in mucin cell-free DNA (cfDNA) from the three patients but not in the pre or post-surgery plasma. Electron microscopy detected microparticles (diameter <0.4 µm) in mucin. Mucin from one patient grew up inside the peritoneal cavity of mice and human KRAS was identified in mucin cfDNA, but not in plasma. All mucins showed the same bacterial profile. Cytokine levels were slightly altered in mice. Conclusions: The three aPMP patients included in this study shared some common aspects: the absence of tumor cells in mucin, the presence of KRAS mutated cfDNA in mucin, and the absence of this tumor-derived mutation in the bloodstream, providing additional information to the routine pathological examinations and suggesting that mucin cfDNA could potentially play a role in aPMP recurrence and prognosis.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by a grant from the ‘FIS-ISCIII-FEDER’ [Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (European Regional Development Fund)], Ministry of Health, Spain (grant number PI17/01233)

Formation of titanium monoxide (001) single-crystalline thin film induced by ion bombardment of titanium dioxide (110)

© 2015 Macmillan Publishers Limited. All rights reserved. A plethora of technological applications justify why titanium dioxide is probably the most studied oxide, and an optimal exploitation of its properties quite frequently requires a controlled modification of the surface. Low-energy ion bombardment is one of the most extended techniques for this purpose and has been recently used in titanium oxides, among other applications, to favour resistive switching mechanisms or to form transparent conductive layers. Surfaces modified in this way are frequently described as reduced and defective, with a high density of oxygen vacancies. Here we show, at variance with this view, that high ion doses on rutile titanium dioxide (110) induce its transformation into a nanometric and single-crystalline titanium monoxide (001) thin film with rocksalt structure. The discovery of this ability may pave the way to new technical applications of ion bombardment not previously reported, which can be used to fabricate heterostructures and interfaces.Peer Reviewe

Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals

The rapid development of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has not been investigated in detail. In this study, we characterize SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during and after two doses of BNT162b2 vaccination. Our results demonstrate that, while the second dose increases both the humoral and cellular immunity in naive individuals, COVID-19 recovered individuals reach their peak of immunity after the first dose. These results suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.Funding: Research reported in this publication was supported in part by the National Cancer Institute of the NIH (5R01HD102614-02; R01CA249204 and R01CA248984) and an ISMMS seed fund to E.G. The authors gratefully acknowledge use of the services and facilities of the Tisch Cancer Institute supported by a NCI Cancer Center Support Grant (P30 CA196521). M.S. was supported by a NCI training grant (T32CA078207). This work was supported by an ISMMS seed fund to J.O.; Instituto de Salud Carlos III (COV20-00668) to R.C.R.; the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 research call COV20/00181) co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ to E.P.; the Instituto de Salud Carlos III, Spain (COV20/00170); the Government of Cantabria, Spain (2020UIC22-PUB-0019) to M.L.H.; the Instituto de Salud Carlos III (PI16CIII/00012) to P.P.; the Fondo Social Europeo e Iniciativa de Empleo Juvenil YEI (Grant PEJ2018-004557-A) to M.P.E.; and by REDInREN 016/009/009 ISCIII. This project has received funding from the European Union Horizon 2020 research and innovation programs VACCELERATE and INsTRuCT under grant agreements 101037867 and 860003

Corpus y construcciones: perspectivas hispánicas

Los trabajos que integran este volumen constituyen una muestra significativa de las aportaciones actuales de la lingüística de corpus en el ámbito hispánico. La primera parte está dedicada al análisis de fenómenos gramaticales con datos de corpus. La segunda se centra en el diseño y elaboración de corpus textuales de diverso tipo, con especial atención a las posibilidades de recuperación y explotación de los datos que contienen. En ambos bloques se pone de manifiesto la variedad de recursos y métodos de análisis propiciados por el desarrollo de corpus tanto del español como de otras lenguas (gallego, portugués, alemán). Varios capítulos muestran la necesidad de un enfoque plurilingüe, bien para dar cuenta de fenómenos de variación y cambio en situaciones de contacto, bien para desarrollar recursos lingüísticos para la enseñanza de lenguas extranjeras o para la traducción. La autoría plural de la obra configura un panorama diverso y estimulante de las posibilidades que ofrece la lingüística de corpus para profundizar en el conocimiento de las lenguas.Axencia Galega de Innovación, ref. nº ED431B 2017/3

Alimentación y salud. Una experiencia de aprendizaje e innovación para la comunidad universitaria UCM a través de la Agenda 2030

Los desequilibrios políticos, económicos y sociales que presenta Colombia y la Región de Antioquia han derivado en altas tasas de inseguridad alimentaria. Este hecho, junto al elevado consumo de alimentos ultraprocesados en detrimento de la alimentación tradicional, está afectando gravemente la salud de la población. A todo ello hay que añadir el impacto del cambio climático y los eventos derivados extremos que comprometen la producción y distribución de alimentos. A través de cinco webinars, el público asistente conocerá de primera mano la importancia de la Cooperación Internacional al Desarrollo y la Agenda 20-30 como pretexto para afrontar la problemática de la inseguridad alimentaria en Antioquia, fenómeno que, pese a haberse hecho más evidente en los últimos años, permanece casi invisible por la mayoría de la población española. Asimismo, se hará especial hincapié en las políticas llevadas a cabo por Colombia para mejorar la alimentación, sin olvidar las consecuencias que están teniendo el cambio climático, los conflictos armados, los estragos generados por la pandemia por COVID-19 o la geopolítica mundial sobre la situación nutricional en la región colombiana

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

COVID-19 outbreaks in a transmission control scenario: challenges posed by social and leisure activities, and for workers in vulnerable conditions, Spain, early summer 2020

Severe acute respiratory syndrome coronavirus 2 community-wide transmission declined in Spain by early May 2020, being replaced by outbreaks and sporadic cases. From mid-June to 2 August, excluding single household outbreaks, 673 outbreaks were notified nationally, 551 active (>6,200 cases) at the time. More than half of these outbreaks and cases coincided with: (i) social (family/friends’ gatherings or leisure venues) and (ii) occupational (mainly involving workers in vulnerable conditions) settings. Control measures were accordingly applied