Comparative Analysis of Chromatin-Delivered Biomarkers in the Monitoring of Sepsis and Septic Shock: A Pilot Study

[EN] Sepsis management remains one of the most important challenges in modern clinical practice. Rapid progression from sepsis to septic shock is practically unpredictable, hence the critical need for sepsis biomarkers that can help clinicians in the management of patients to reduce the proba-bility of a fatal outcome. Circulating nucleoproteins released during the inflammatory response to infection, including neutrophil extracellular traps, nucleosomes, and histones, and nuclear pro-teins like HMGB1, have been proposed as markers of disease progression since they are related to inflammation, oxidative stress, endothelial damage, and impairment of the coagulation response, among other pathological features. The aim of this work was to evaluate the actual potential for decision making/outcome prediction of the most commonly proposed chromatin-related bi-omarkers (i.e., nucleosomes, citrullinated H3, and HMGB1). To do this, we compared different ELISA measuring methods for quantifying plasma nucleoproteins in a cohort of critically ill pa-tients diagnosed with sepsis or septic shock compared to nonseptic patients admitted to the inten-sive care unit (ICU), as well as to healthy subjects. Our results show that all studied biomarkers can be used to monitor sepsis progression, although they vary in their effectiveness to separate sepsis and septic shock patients. Our data suggest that HMGB1/citrullinated H3 determination in plasma is potentially the most promising clinical tool for the monitoring and stratification of septic patients.This activity received funding from the European Institute of Innovation and Technology (EIT). This body of the European Union receives support from the European Union's Horizon 2020 research and innovation program. C.R-M. thanks GVA for starting grant (GV/2018/127) and Spanish Ministry of Science and Innovation for research project (PID2020-119127RA-I00); J.B-G thanks ISCIII, AES2018 for iPFIS fellowship (IFI18/00015) and GVA for APOTI fellowship (APOTIP/2017/012); CG thanks Spanish Ministry of Universities for fellowship FPU18/03969; J.L.G-G and F.V.P thank INCLIVA, GVA and AES2016 and AES2019 (ISCIII) for starting grant (GV/2014/132), project PI16/01036 and PI19/00994 and project DTS17/00132 (co-financed by the ERDF). The project leading to these results has received funding from "la Caixa" Foundation (ID 100010434), under agreement CI18-0009. C.R-M., F.V.P. and A.M. thank Grand Challenges Canada. : We want to particularly acknowledge the patients and the INCLIVA Biobank (PT17/0015/0049; B.000768 ISCIII) integrated in the Valencian Biobanking Network and the Spanish National Biobanks Network for their collaboration.Beltrán-García, J.; Manclus Ciscar, JJ.; García-López, EM.; Carbonell, N.; Ferreres, J.; Rodríguez-Gimillo, M.; Garcés, C.... (2021). Comparative Analysis of Chromatin-Delivered Biomarkers in the Monitoring of Sepsis and Septic Shock: A Pilot Study. International Journal of Molecular Sciences. 22(18):1-15. https://doi.org/10.3390/ijms22189935115221

Using competency maps for embedding and assessing sustainability in engineering degrees

This paper features a methodology for embedding and assessing a competency in an academic curriculum using competency maps. This methodology enables embedding and assessment of any competency in any curriculum, regardless of the educational level, as long as the competency is correctly described by means of a competency map. As an example of the application of this methodology, a proposal for embedding and assessing sustainability in engineering degrees is presented. A competency map embodies the set of learning outcomes of the competency that students should have acquired upon completion of their studies. This information allows the designers of the curriculum to determine the learning outcomes that should be developed in the degree and to distribute them appropriately among the subjects. The presence map can be constructed from the competency map. It contains information regarding the extent to which each learning outcome of the competency map is being developed in the degree. This paper proposes the construction of a presence map in two steps: (1) perform a survey and (2) conduct a semi-structured interview with professors. The interview, which is conducted by one or several experts in the competency, allows the different criteria used by the professors when filling out the questionnaire to be unified, whereas the presence map shows whether a particular competency is correctly embedded in the curriculum and the aspects that could be improved. Finally, to validate that the students are achieving the learning outcomes of the competency map, we propose a survey to measure the students’ perception about their own learning in the competency. These results can be compared with the presence map to help determine whether, from the students’ point of view, the expected learning outcomes are being achieved in the corresponding subjects. The aim of this process is to provide the information necessary to indicate any changes in the curriculum that may improve the embedding of the competency.This research was funded by the Spanish Ministerio de Ciencia, Innovación y Universidades, the Spanish Agencia Estatal de Investigación (AEI), and the Fondo Europeo de Desarrollo Regional (FEDER), from study design to submission, under grant number RTI2018-094982-B-I00.Peer ReviewedPostprint (published version

Updating the National Baseline of Non-Indigenous Species in Spanish Marine Waters

The introduction of new non-indigenous species (NIS) in Spanish marine waters is addressed under Descriptor 2 of the European Union’s Marine Strategy Framework Directive. National baseline inventories of NIS have been compiled and updated for the three subregions (Western Mediterranean Sea, WMED; Bay of Biscay–Iberian Coast, ABI; Macaronesia, AMA) with data from 1800 to 2021. An overall of 574 species were identified with an alien, cryptogenic, crypto-expanding, or debatable status, mostly invertebrates (~65%) and primary producers (~22%). Of 412 alien species, 80.51% were reported in ABI, 67.82% in WMED, and 66.67% in AMA. Cryptogenic species are more abundant in the WMED (25.25%), compared to AMA (19.77%) and ABI (18.46%). ABI harbors more established species (62.56%) than AMA (45.2%) and WMED (43.56%), contrary to casual records (AMA 31.64%, WMED 23.76%, ABI 13.85%). Invasive species are more abundant (14.36%) in WMED. The ‘transport-stowaway’ pathway accounted for 142 (79.33%), 123 (67.58%), and 169 (85.21%) records in WMED, ABI, and AMA, respectively. The second most common pathway was ‘transport-contaminant’ related to mariculture (~10% of the total), prevalently in ABI with 42 species (23.08%). The Canary Islands stand out for species introduced through oil platforms from throughout the world. ‘Unaided’ was a relevant pathway of secondary introduction into the WMED, particularly of Lessepsian species progressing westwards. Temporal trends in newly introduced species show similar behavior among subregions.This research was funded by Ministerio para la Transición Ecológica y el Reto Demográfico, grant number 11_MM_ESMARES2. The APC was funded by the ESMARES2-C3 project

The modular network structure of the mutational landscape of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is associated with the sequential accumulation of acquired genetic alterations. Although at diagnosis cytogenetic alterations are frequent in AML, roughly 50% of patients present an apparently normal karyotype (NK), leading to a highly heterogeneous prognosis. Due to this significant heterogeneity, it has been suggested that different molecular mechanisms may trigger the disease with diverse prognostic implications. We performed whole-exome sequencing (WES) of tumor-normal matched samples of de novo AML-NK patients lacking mutations in NPM1, CEBPA or FLT3-ITD to identify new gene mutations with potential prognostic and therapeutic relevance to patients with AML. Novel candidate-genes, together with others previously described, were targeted resequenced in an independent cohort of 100 de novo AML patients classified in the cytogenetic intermediate-risk (IR) category. A mean of 4.89 mutations per sample were detected in 73 genes, 35 of which were mutated in more than one patient. After a network enrichment analysis, we defined a single in silico model and established a set of seed-genes that may trigger leukemogenesis in patients with normal karyotype. The high heterogeneity of gene mutations observed in AML patients suggested that a specific alteration could not be as essential as the interaction of deregulated pathways

Herramientas para integrar los objetivos de desarrollo sostenible en las ingenierías

En este trabajo se presenta una herramienta desarrollada en el marco del proyecto EDINSOST2-SDG orientada a integrar la educación para el Desarrollo Sostenible (ESD) en los currículos de Ingeniería. Esta herramienta es el mapa de sostenibilidad de las ingenierías, la cual contiene los resultados de aprendizaje relacionados con la ESD que cualquier estudiante de ingeniería debe haber adquirido al finalizar sus estudios. Los resultados de aprendizaje se describen a partir de cuatro competencias en sostenibilidad: (1) Contextualización crítica del conocimiento, (2) Uso sostenible de los recursos, (3) Participación en procesos comunitarios y (4) Aplicación de principios éticos. Esta herramienta ha sido sometida a un proceso de validación y se está utilizando actualmente en un conjunto de titulaciones de ingeniería relacionadas con el proyecto EDINSOST2-SDG.This paper presents a tool developed in the framework of the EDINSOST2-SDG project aimed at integrating education for Sustainable Development (ESD) in engineering curricula. This tool is the engineering sustainability map, which contains the ESD-related learning outcomes that any engineering student should have acquired by the end of his or her studies. The learning outcomes are described on the basis of four sustainability competencies: (1) Critical contextualization of knowledge, (2) Sustainable use of resources, (3) Participation in community processes, and (4) Application of ethical principles. This tool has undergone a validation process and is currently being used in a set of engineering degrees related to the EDINSOST2-SDG project

Alterations in leukocyte DNA methylome are associated to immunosuppression in severe clinical phenotypes of septic patients

IntroductionSepsis patients experience a complex interplay of host pro- and anti-inflammatory processes which compromise the clinical outcome. Despite considering the latest clinical and scientific research, our comprehension of the immunosuppressive events in septic episodes remains incomplete. Additionally, a lack of data exists regarding the role of epigenetics in modulating immunosuppression, subsequently impacting patient survival.MethodsTo advance the current understanding of the mechanisms underlying immunosuppression, in this study we explored the dynamics of DNA methylation using the Infinium Methylation EPIC v1.0 BeadChip Kit in leukocytes from patients suffering from sepsis, septic shock, and critically ill patients as controls, within the first 24 h after admission in the Intensive Care Unit of a tertiary hospital.Results and discussionEmploying two distinct analysis approaches (DMRcate and mCSEA) in comparing septic shock and critically ill patients, we identified 1,256 differentially methylated regions (DMRs) intricately linked to critical immune system pathways. The examination of the top 100 differentially methylated positions (DMPs) between septic shock and critically ill patients facilitated a clear demarcation among the three patient groups. Notably, the top 6,657 DMPs exhibited associations with organ dysfunction and lactate levels. Among the individual genes displaying significant differential methylation, IL10, TREM1, IL1B, and TNFAIP8 emerged with the most pronounced methylation alterations across the diverse patient groups when subjected to DNA bisulfite pyrosequencing analysis. These findings underscore the dynamic nature of DNA methylation profiles, highlighting the most pronounced alterations in patients with septic shock, and revealing their close association with the disease

Database of spatial distribution of non indigenous species in Spanish marine waters

Research in marine Spanish waters are focused on several actions to achieve an effectively management on protected areas, with the active participation of the stakeholders and research as basic tools for decision-making. Among these actions, there is one about the knowledge and control on NIS. One of its objectives is the creation of NIS factsheets, which are going to be added to the National Marine Biodiversity Geographical System (GIS) providing complementary information about taxonomic classification, common names, taxonomic synonyms, species illustrations, identification morphological characters, habitat in the native and introduced regions, biological and ecological traits, GenBank DNA sequences, world distribution, first record and evolution in the introduced areas, likely pathways of introduction, effects in the habitats and interaction with native species, and potential management measures to apply. The database will also provide data for (1) the European online platforms, (2) the environmental assessment for the Descriptor 2 (D2-NIS) of the EU Marine Strategy Framework Directive (MSFD), as well as (3) supporting decisions made by stakeholders. It is the result of extensive collaboration among scientist, manager’s and citizen science in the Spanish North-Atlantic, South-Atlantic, Gibraltar Strait-Alboran, Levantine-Balearic and Canary Islands marine divisions, providing an updated overview of the spatial distribution of relevant extended and invasive NIS of recent and established NIS introduced by maritime transport and aquaculture pathways, as well as on cryptogenic or native species in expansion due to the climatic water warming trend

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 +/- 20.6% vs 93.6 +/- 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 +/- 5.2 mm vs 19.9 +/- 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Inclusión de los ODS en las asignaturas de la materia Experimentación en Ingeniería Química en el Grado en Ingeniería Química

[ES] En la presente comunicación se presenta la estrategia seguida para dar visibilidad a los Objetivos de Desarrollo Sostenible (ODS) así como poder incluirlos en las asignaturas de la materia “Experimentación en Ingeniería Química” (EIQ) del Grado en Ingeniería Química (GIQ) de la UPV, tanto para el Grado impartido en la Escuela Técnica Superior de Ingeniería Industrial (ETSII) como para el impartido en la Escuela Politécnica Superior de Alcoy (EPSA). Esta materia incluye tres asignaturas experimentales que son continuativas (Experimentación en Ingeniería Química I, II y III). Durante el primer año (curso 22-23), se hará un diagnóstico del estado actual de conocimiento e implicación que tiene el alumnado sobre los ODS a través de encuestas de opinión con la herramienta Google Drive (una encuesta a principio de curso y otra a final de curso). Además, se planteará en cada asignatura una breve sesión formativa de los ODS. Durante el segundo año (curso 23-24), se decidirán qué ODS se van a trabajar en cada asignatura y se plantearán diferentes actividades en cada una de las asignaturas incluidas en la materia Experimentación en Ingeniería Química. De la misma forma, en esta segunda anualidad, se realizarán dos encuestas (una a principio y otra a final de curso) donde se evaluará el grado de aprendizaje, adquisición e implicación del alumnado sobre los ODS.[EN] This article presents the strategy followed to give visibility to the Sustainable Development Goals (SDG) as well as to be able to include them as a part of the content of the matter "Experimentación en Ingeniería Química" of the Degree in Chemical Engineering of the Universitat Politècnica de València (UPV), both for the Degree taught at the Escuela Técnica Superior de Ingenieros Industriales (ETSII) and for the one taught at the Escuela Politécnica Superior de Alcoy (EPSA). This matter includes three experimental subjects that are continuing (Experimentación en Ingeniería Química I, Experimentación en Ingeniería Química II and Experimentación en Ingeniería Química III). During the first year (academic year 22-23) a diagnosis will be made of the current state of knowledge and involvement that students have about the SDG through opinion surveys with Google Drive tool (a survey at the beginning and another one at the end of the course). In addition, a brief training session on the SDG will be proposed in each subject. During the second year (academic year 23-24) it will be decided which SDG are going to be worked on and different activities will be proposed in each of the subjects studied. In the same way, in this second year, two surveys will be carried out (one at the beginning and the other one at the end of the course) where the degree of learning, acquisition and involvement of the students on the SDG will be evaluated.Los autores de esta comunicación agradecen a la convocatoria de Proyectos de Innovación y Mejora Educativa de la UPV 2022 y al Proyecto Docente PIME/22-23/348 con título: ''Visibilización e inclusión de los ODS en las asignaturas de la materia Experimentación en Ingeniería Química en el Grado en Ingeniería Química'' a partir del cual se basa esta publicación.Luján Facundo, MJ.; Cuartas Uribe, BE.; García Fayos, B.; Arnal Arnal, JM.; Iborra Clar, A.; Sánchez Arévalo, CM.; Rodríguez López, AD.... (2023). Inclusión de los ODS en las asignaturas de la materia Experimentación en Ingeniería Química en el Grado en Ingeniería Química. Editorial Universitat Politècnica de València. 1061-1076. https://doi.org/10.4995/INRED2023.2023.166571061107