Translational research: A concept emerged from health sciences and exportable to education sciences

The objective of this paper was to analyze the concept and evolution of translational research in order to explore if it can be used in fields other than health sciences such as higher education. A mini review was conducted using Medline as a main source for identifying papers. We selected papers that appeared to be relevant according to our objective. Data extraction of these papers was made by summarizing documents using short textual descriptions. Search results yielded 1186 papers, 28 of which were finally selected for the mini review. The main aim of translational research is bridging the know do gap. Several multiphase models have been identified. The first described model had two phases (T1, T2) but there are models with three (T1-T3) or four phases (T1-T4). However, regardless of the model used, three main gaps exist that can be placed in the knowledge chain underpinning translational research. Translational research could be seen as a bidirectional bridge connecting the laboratory to practice either in health or in education. Its interdisciplinary back and forth ultimately contributes to improved health or education outcomes. This improvement can be achieved if the three gaps of the knowledge chain are overcome. Namely, these gaps are located: (1) between the discovery of new knowledge and dissemination to potential users of that knowledge; (2) between knowledge dissemination to potential users and its routine application to health or education practice; and (3) between clinical or educational practice and improvement of health or education outcomes.L'objectiu d'aquest treball va ser analitzar el concepte i l'evolució de la investigació translacional per tal d'explorar si es pot utilitzar en altres àmbits a part de les ciències de la salut com ara l'educació superior.El objetivo de este trabajo fue analizar el concepto y la evolución de la investigación translacional para explorar si se puede utilizar en otros ámbitos aparte de las ciencias de la salud como la educación superior

Wet and dry African dust episodes over eastern Spain

The impact of the African dust on levels of atmospheric suspended particulate matter (SPM) and on wet deposition was evaluated in eastern Iberia for the period 1996-2002. An effort was made to compile both the SPM and wet episodes. To this end, the time series of levels of TSP and PM10 in Levantine air quality monitoring stations were evaluated and complemented with the computation of back trajectories, satellite images, and meteorological analysis. Wet deposition frequency was obtained from weekly collected precipitation data at a rural background station in which the African chemical signature was identified (mainly pH and Ca2+ concentrations). A number of African dust episodes (112) were identified (16 episodes per year). In 93 out of the 112 (13 episodes per year) the African dust influence caused high SPM levels. In 49 out of 112 (7 episodes per year), wet deposition was detected, and the chemistry was influenced by dust. There is a clear seasonal trend with higher frequency of dust outbreaks in May-August, with second modes in March and October. Wet events followed a different pattern, with a marked maximum in May. Except for one event, December was devoid of African air mass intrusions. On the basis of seasonal meteorological patterns affecting the Iberian Peninsula, an interpretation of the meteorological scenarios causing African dust transport over Iberia was carried out. Four scenarios were identified with a clear seasonal trend. The impact of the different dust outbreak scenarios on the levels of PM10 recorded at a rural site (Monagrega, Teruel, Spain) in the period 1996-2002 was also evaluated

Effects of teleconnection patterns on the atmospheric routes, precipitation and deposition amounts in the north-eastern Iberian Peninsula

The North Atlantic Oscillation (NAO) has been identified as one of the atmospheric patterns which mostly influence the temporal evolution of precipitation and temperature in the Mediterranean area. Recently, the Western Mediterranean Oscillation (WeMO) has also been proposed to describe the precipitation variability in the eastern Iberian Peninsula. This paper examines whether the chemical signature and/or the chemical deposition amounts recorded over NE Iberian Peninsula are influenced by these climatic variability patterns. Results show a more relevant role of the WeMO compared to NAO in the deposition of either marine (Cl⁻, Na⁺, Mg²⁺) or anthropogenic pollutants (H⁺, NH⁺/4, NO-/3 and SO2/4−). A cluster classification of provenances indicated that in winter (December to March) fast Atlantic air flows correspond to positive WeMO indices, while negative WeMOi are associated to Northeastern and Southwestern circulations. The negative phase of WeMO causes the entry of air masses from the Mediterranean into the Iberian Peninsula, that are enriched with marine ions and ions of anthropogenic origin (NH⁺/4, NO-/3 and SO2/4−). For these later, this suggests the advection over the Mediterranean of polluted air masses from southern Europe and the scavenging and deposition of this pollution by precipitation during the WeMO negative phases. This will carry transboundary pollutants to the NE Iberian Peninsula. However, local pollutants may also contribute, as precipitation events from the Mediterranean and the Atlantic (associated to both WeMO phases) may incorporate emissions that accumulate locally during the winter anticyclonic episodes typical of the region

A novel gene signature unveils three distinct immune- metabolic rewiring patterns conserved across diverse tumor types and associated with outcomes

Existing immune signatures and tumor mutational burden have only modest predictive capacity for the efficacy of immune check point inhibitors. In this study, we developed an immune-metabolic signature suitable for personalized ICI therapies. A classifier using an immune-metabolic signature (IMMETCOLS) was developed on a training set of 77 metastatic colorectal cancer (mCRC) samples and validated on 4,200 tumors from the TCGA database belonging to 11 types. Here, we reveal that the IMMETCOLS signature classifies tumors into three distinct immune-metabolic clusters. Cluster 1 displays markers of enhanced glycolisis, hexosamine byosinthesis and epithelial-to-mesenchymal transition. On multivariate analysis, cluster 1 tumors were enriched in pro-immune signature but not in immunophenoscore and were associated with the poorest median survival. Its predicted tumor metabolic features suggest an acidic-lactate-rich tumor microenvironment (TME) geared to an immunosuppressive setting, enriched in fibroblasts. Cluster 2 displays features of gluconeogenesis ability, which is needed for glucose-independent survival and preferential use of alternative carbon sources, including glutamine and lipid uptake/β-oxidation. Its metabolic features suggest a hypoxic and hypoglycemic TME, associated with poor tumor-associated antigen presentation. Finally, cluster 3 is highly glycolytic but also has a solid mitochondrial function, with concomitant upregulation of glutamine and essential amino acid transporters and the pentose phosphate pathway leading to glucose exhaustion in the TME and immunosuppression. Together, these findings suggest that the IMMETCOLS signature provides a classifier of tumors from diverse origins, yielding three clusters with distinct immune-metabolic profiles, representing a new predictive tool for patient selection for specific immune-metabolic therapeutic approaches

Table_4_A novel gene signature unveils three distinct immune-metabolic rewiring patterns conserved across diverse tumor types and associated with outcomes.docx [Dataset]

Supplementary Table S4: Important features identified by One-way ANOVA and post-hoc analysis (Fisher’s LSD) comparing the expression of immune signatures in the IMMETCOLS Clusters.Existing immune signatures and tumor mutational burden have only modest predictive capacity for the efficacy of immune check point inhibitors. In this study, we developed an immune-metabolic signature suitable for personalized ICI therapies. A classifier using an immune-metabolic signature (IMMETCOLS) was developed on a training set of 77 metastatic colorectal cancer (mCRC) samples and validated on 4,200 tumors from the TCGA database belonging to 11 types. Here, we reveal that the IMMETCOLS signature classifies tumors into three distinct immune-metabolic clusters. Cluster 1 displays markers of enhanced glycolisis, hexosamine byosinthesis and epithelial-to-mesenchymal transition. On multivariate analysis, cluster 1 tumors were enriched in pro-immune signature but not in immunophenoscore and were associated with the poorest median survival. Its predicted tumor metabolic features suggest an acidic-lactate-rich tumor microenvironment (TME) geared to an immunosuppressive setting, enriched in fibroblasts. Cluster 2 displays features of gluconeogenesis ability, which is needed for glucose-independent survival and preferential use of alternative carbon sources, including glutamine and lipid uptake/β-oxidation. Its metabolic features suggest a hypoxic and hypoglycemic TME, associated with poor tumor-associated antigen presentation. Finally, cluster 3 is highly glycolytic but also has a solid mitochondrial function, with concomitant upregulation of glutamine and essential amino acid transporters and the pentose phosphate pathway leading to glucose exhaustion in the TME and immunosuppression. Together, these findings suggest that the IMMETCOLS signature provides a classifier of tumors from diverse origins, yielding three clusters with distinct immune-metabolic profiles, representing a new predictive tool for patient selection for specific immune-metabolic therapeutic approaches.Peer reviewe

Table_5_A novel gene signature unveils three distinct immune-metabolic rewiring patterns conserved across diverse tumor types and associated with outcomes.docx [Dataset]

Supplementary Table S5: Important features identified by One-way ANOVA and post-hoc analysis (Fisher’s LSD) comparing the expression of immune genes in the IMMETCOLS Clusters.Existing immune signatures and tumor mutational burden have only modest predictive capacity for the efficacy of immune check point inhibitors. In this study, we developed an immune-metabolic signature suitable for personalized ICI therapies. A classifier using an immune-metabolic signature (IMMETCOLS) was developed on a training set of 77 metastatic colorectal cancer (mCRC) samples and validated on 4,200 tumors from the TCGA database belonging to 11 types. Here, we reveal that the IMMETCOLS signature classifies tumors into three distinct immune-metabolic clusters. Cluster 1 displays markers of enhanced glycolisis, hexosamine byosinthesis and epithelial-to-mesenchymal transition. On multivariate analysis, cluster 1 tumors were enriched in pro-immune signature but not in immunophenoscore and were associated with the poorest median survival. Its predicted tumor metabolic features suggest an acidic-lactate-rich tumor microenvironment (TME) geared to an immunosuppressive setting, enriched in fibroblasts. Cluster 2 displays features of gluconeogenesis ability, which is needed for glucose-independent survival and preferential use of alternative carbon sources, including glutamine and lipid uptake/β-oxidation. Its metabolic features suggest a hypoxic and hypoglycemic TME, associated with poor tumor-associated antigen presentation. Finally, cluster 3 is highly glycolytic but also has a solid mitochondrial function, with concomitant upregulation of glutamine and essential amino acid transporters and the pentose phosphate pathway leading to glucose exhaustion in the TME and immunosuppression. Together, these findings suggest that the IMMETCOLS signature provides a classifier of tumors from diverse origins, yielding three clusters with distinct immune-metabolic profiles, representing a new predictive tool for patient selection for specific immune-metabolic therapeutic approaches.Peer reviewe

Clinical and Pathological Characterization of Lynch-Like Syndrome

Background & aims: Lynch syndrome is characterized by DNA mismatch repair (MMR) deficiency. Some patients with suspected Lynch syndrome have DNA MMR deficiencies but no detectable mutations in genes that encode MMR proteins-this is called Lynch-like syndrome (LLS). There is no consensus on management of patients with LLS. We collected data from a large series of patients with LLS to identify clinical and pathology features. Methods: We collected data from a nationwide-registry of patients with colorectal cancer (CRC) in Spain. We identified patients whose colorectal tumors had loss of MSH2, MSH6, PMS2, or MLH1 (based on immunohistochemistry), without the mutation encoding V600E in BRAF (detected by real-time PCR), and/or no methylation at MLH1 (determined by methylation-specific multiplex ligation-dependent probe amplification), and no pathogenic mutations in MMR genes, BRAF, or EPCAM (determined by DNA sequencing). These patients were considered to have LLS. We collected data on demographic, clinical, and pathology features and family history of neoplasms. The χ2 test was used to analyze the association between qualitative variables, followed by the Fisher exact test and the Student t test or the Mann-Whitney test for quantitative variables. Results: We identified 160 patients with LLS; their mean age at diagnosis of CRC was 55 years and 66 patients were female (41%). The Amsterdam I and II criteria for Lynch syndrome were fulfilled by 11% of cases and the revised Bethesda guideline criteria by 65% of cases. Of the patients with LLS, 24% were identified in universal screening. There were no proportional differences in sex, indication for colonoscopy, immunohistochemistry, pathology findings, or personal history of CRC or other Lynch syndrome-related tumors between patients who met the Amsterdam and/or Bethesda criteria for Lynch syndrome and patients identified in universal screening for Lynch syndrome, without a family history of CRC. Conclusions: Patients with LLS have homogeneous clinical, demographic, and pathology characteristics, regardless of family history of CRC

Impact of the COVID-19 pandemic in the early-onset colorectal cancer

COVID-19 pandemic; Early-onset colorectal cancerPandemia de COVID-19 Cáncer colorrectal precozPandèmia de COVID-19; Càncer colorectal precoçThe COVID19 pandemic has affected the spectrum of cancer care worldwide. Early onset colorectal cancer (EOCRC) is defined as diagnosis below the age of 50. Patients with EOCRC faced multiple challenges during the COVID19 pandemic and in some institutions it jeopardized cancer diagnosis and care delivery. Our study aims to identify the clinicopathological features and outcomes of patients with EOCRC in our Centre during the first wave of the pandemic in comparison with the same period in 2019 and 2021. Patients with EOCRC visited for the first time at Vall d'Hebron University Hospital in Spain from the 1st March to 31st August of 2019, 2020 and 2021 were included in the analysis. 177 patients with EOCRC were visited for the first time between 2019 and 2021, of which 90 patients met the inclusion criteria (2019: 30 patients, 2020: 29 patients, 2021: 31 patients). Neither differences in frequency nor in stage at diagnosis or at first visit during the given periods were observed. Of note, indication of systemic therapy in the adjuvant or metastatic setting was not altered. Days to treatment initiation and enrollment in clinical trials in this subpopulation was not affected due to the COVID-19 outbreak.This work was supported by the Cancer Research UK (CRUK) grant OPTIMISTICC (C10674/A27140)

High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods

HepatitisCvirus(HCV)is classified into seven major genotypesand67 subtypes. Recent studies haveshownthat inHCVgenotype 1-infected patients, response rates to regimens containingdirect-acting antivirals(DAAs)are subtype dependent. Currently available genotypingmethods have limited subtyping accuracy.Wehave evaluated theperformanceof adeep-sequencing-basedHCVsubtyping assay, developed for the 454/GS-Junior platform, in comparisonwith thoseof two commercial assays (VersantHCVgenotype 2.0andAbbott Real-timeHCVGenotype II)andusingdirectNS5Bsequencing as a gold standard (direct sequencing), in 114 clinical specimenspreviously tested by first-generation hybridization assay (82 genotype 1and32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype 1 callingbypopulation Sanger sequencing(69%1b,31%1a) in 81 specimensandidentified amixed-subtype infection (1b/3a/1a) in one sample. Similarly,amongthe 32previously indeterminate specimens, identical genotypeandsubtype results were obtained by directanddeep sequencing in all but four samples with dual infection. In contrast, both VersantHCVGenotype 2.0andAbbott Real-timeHCVGenotype II failed subtype 1 calling in 13 (16%) samples eachandwere unable to identify theHCVgenotype and/or subtype inmore than half of the nongenotype 1 samples.Weconcluded that deep sequencing ismore efficient forHCVsubtyping than currently available methodsandallows qualitative identificationofmixed infectionsandmay bemorehelpfulwith respect to informing treatment strategies withnewDAA-containing regimens across allHCVsubtypesThis study has been supported by CDTI (Centro para el Desarrollo Tecnológico Industrial), Spanish Ministry of Economics and Competitiveness (MINECO), IDI-20110115; MINECO projects SAF 2009-10403; and also by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS) projects PI10/01505, PI12/01893, and PI13/00456. CIBERehd is funded by the Instituto de Salud Carlos III, Madrid, Spain. Work at CBMSO was supported by grant MINECO-BFU2011-23604, FIPSE, and Fundación Ramón Areces. X. Forns received unrestricted grant support from Roche and has acted as advisor for MSD, Gilead, and Abbvie. M. Alvarez-Tejado, J. Gregori, and J. M. Muñoz work in Roche Diagnostic