Autonomización y funciones del subcampo de la traducción literaria vasca contemporánea : una aproximación sociológica

En el presente artículo trataremos de reflexionar en torno al proceso de autonomización del subcampo de la traducción literaria vasca, anotando algunas de las funciones que ha cumplido la traducción en la literatura vasca. Repasaremos la evolución vivida durante las últimas décadas por los agentes que componen el subcampo de la traducción literaria vasca. Partiremos de los momentos históricos que han condicionado el devenir de la traducción actual en Euskal Herria: la estandarización de la lengua vasca en 1968 y la aceptación de las diversas leyes de bilingüismo en la Euskal Herria peninsular. Completará nuestro análisis una breve reflexión sobre la presencia que la traducción ha tenido en la historiografía literaria vasca, además de un breve comentario en torno a la creciente representación del traductor/traductora en la ficción contemporánea vasca y un esbozo de los flujos de traducción del/al euskera de las últimas décadas.We will try to reflect on the autonomous process within the sub-field of basque literary translation, noting some of the functions fulfilled by translation in basque literature. Likewise, we will review the evolution experienced during recent decades by the agents who make up the sub-field of basque literary translation. We will start from the historical moments that have conditioned the development of current translation in the basque country: the standardization of the basque language in 1968 and the accepting of different laws on bilingualism in the peninsular basque country. Our analysis will finish up with a brief reflection on the presence of translation in basque literary historiography, as well as a brief commentary on the growing representation of the translator in contemporary basque fiction and an outline of the ebb and flow of translation from/to the basque language in recent decades

Aparatos y métodos para el diagnóstico de cáncer colorrectal

Número de Patente: ES 2881 149 B2La presente invención está relacionada con un aparato de extracción y análisis preciso, simple, sensible y eficaz de compuestos orgánicos volátiles (COVs) y de biomarcadores del cáncer colorrectal (CCR) en muestras sólidas y/o semisólidas, más concretamente en muestras de heces. Así mismo, la presente invención está relacionada con un método de diagnóstico y pronóstico de CCR ex vivo que comprende el análisis de COVs que son biomarcadores relacionados con el CCR en muestras de heces, mediante el uso de dicho aparato

Fecal occult blood and calprotectin testing to prioritize primary care patients for colonoscopy referral: The advantage study

AbstractColonoscopy is the gold standard for colorectal cancer (CRC) diagnosis and screening, but endoscopy services are usually overburdened. This study aims to investigate the usefulness of fecal hemoglobin (fHb) and calprotectin (FC) for the identification of patients with high probability of CRC who need urgent referral.MethodsIn a multicenter prospective study, we enrolled symptomatic patients referred from primary care for colonoscopy. Prior to bowel preparation, fHb and FC quantitative tests were performed. The diagnostic performance was estimated for each biomarker/combination. We built a multivariable predictive model based on logistic regression, translated to a nomogram and a risk calculator to assist clinicians in the decision‐making process.ResultsThe study included 1224 patients, of whom 69 (5.6%) had CRC. At the fHb cut‐offs of >0 and 10 μg/g, the negative predictive values for CRC were 98.8% (95% confidence interval 97.8%–99.3%) and 98.6% (95%CI 97.7%–99.1%), and the sensitivities were 85.5% (95%CI 75.0%–92.8%) and 79.7% (95%CI 68.3%–88.4%), respectively. When we added the cut‐off of 150 μg/g of FC to both fHb thresholds, the sensitivity of fecal tests improved. In the multivariate logistic regression model, the concentration of fHb was an independent predictor for CRC; age and gender were also independently associated with CRC.ConclusionsfHb and FC are useful as part of a triage tool to identify those symptomatic patients with high probability of CRC. This can be easily applied by physicians to prioritize high‐risk patients for urgent colonoscopy

Increased Th17-Related Cytokine Serum Levels in Patients With Multiple Polyps of Unexplained Origin

OBJECTIVES: Most patientswith multiple colonic polyps do not have a known genetic or hereditary origin. Our aim was to analyze the presence of inflammatory cytokines and levels of glucose, insulin, and C-reactive protein (CRP) in patients with multiple colonic polyps. METHODS: Eighty-three patients with 10 or more adenomatous or serrated polyps and 53 control people with normal colonoscopy were included. Smoking habits were registered, and glucose, CRP, and basal insulin in the serum/blood weremeasured. Quantification of IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, and IL-23 cytokine levels in the serum was performed by a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: Smoking and diabetesweremore prevalent in those with colonic polyps than in the control people (67% vs 16%, P = 0.001; 11% vs 2%, P = 0.048). In addition, the cytokine serum levels were higher, i.e., IL-2 (P = 0.001), IL-4 (P = 0.001), IL-6 (P = 0.001), IL-17A (P = 0.001), IL-23 (P = 0.014), and CRP (P = 0.003). Adjusting for sex, smoking, and diabetes in amultivariate analysis, IL-2, IL-4, IL-6, IL-17A, and IL-23 remained independently elevated in cases with multiple polyps. DISCUSSION: These results indicate that immune responses mediated by Th17 cells may be involved in the pathogenesis of multiple colonic polyps

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

Búsqueda de biomarcadores para la detección de enfermedades gastrointestinales

El cáncer colorrectal (CCR), hoy en día es una de las neoplasias con mayor incidencia y mortalidad en España. Su etiología es multifactorial, influyendo tanto alteraciones genéticas/epigenéticas como factores ambientales (hábitos, tóxicos, dieta). Estudios demuestran que los programas de cribado actuales como el test inmunológico fecal (FIT), sigmoidoscopia y colonoscopia han disminuido la mortalidad del CCR. Sin embargo, el FIT presenta muchos falsos positivos y negativos, dando lugar a la realización de colonoscopias innecesarias que suponen un gran gasto para la sociedad. Por lo tanto, existe una necesidad de crear un método de detección precoz del CCR no-invasivo y preciso que maximice la correcta identificación de pacientes que tengan que hacerse una colonoscopia y minimice la realización de pruebas innecesarias. Por otro lado, los pacientes con poliposis múltiple de origen desconocido siguen siendo "huérfanos genéticos" hoy en día porque no presentan una mutación constitucional conocida. Por lo tanto la detección de biomarcadores para esta condición también es necesaria. El principal objetivo del primer estudio de la presente tesis doctoral, fue el desarrollo de un método no-invasivo para la detección del CCR mediante el análisis de compuestos orgánicos volátiles (COVs) en heces de pacientes con CCR, adenomas y controles sanos. Los COVs se extrajeron mediante un método y protocolo desarrollado por nuestro grupo de investigación (que está bajo patente) y posterior identificación mediante la cromatografía de gases-espectrometría de masas (GC-MS). Se analizaron muestras de un total de 64 sujetos. Encontramos que 3 COVs se detectaban a distinta concentración entre los distintos grupos de estudio, siendo las diferencias más significativas entre pacientes con CCR y controles sanos. Tras estudiar el potencial de cada compuesto como posible biomarcador de enfermedad, observamos que dos de los tres COVs presentaban diferencias significativas en la abundancia entre CCR y controles, con una sensibilidad y especificidad elevada sugiriendo su potencial como biomarcadores de enfermedad. El segundo estudio de la presente tesis doctoral, se centra en la poliposis colónica múltiple de origen desconocido. El grupo de pacientes seleccionados carecen de mutaciones en genes como APC y MYH (ya que se considerarían Poliposis Adenomatosa Familiar y Poliposis asociada a MYH). En el estudio se incluyeron un total de 135 sujetos (83 enfermos y 52 controles). Se analizaron niveles séricos de citoquinas inflamatorias mediante ensayos ELISA y diversos factores ambientales (DM, hábito tabáquico, IMC, índice HOMA-IR). En este estudio, se detectó por primera vez una asociación entre interleucinas de las Th17 y la PCR con la presencia de polipósis múltiple. Este resultado no descarta la posible implicación de otros genes en la aparición de los pólipos pero el incremento de la IL-17A, IL-23 e IL-6 pertenecientes a la respuesta mediada por las células Th17, sugiere una asociación de esta vía con la aparición de múltiples pólipos colónicos. Nuestro grupo de investigación está llevando a cabo otro estudio para validar estos resultados. En resumen, ambos estudios detectan distintos biomarcadores que podrían ser útiles para diagnosticar; el CCR en el caso del primer estudio mediante el análisis de diversos COVs y la poliposis múltiple de origen desconocido en el caso del segundo estudio analizando la concentración de las tres interleucinas pertenecientes a la vía Th17

A novel non-invasive colorectal cancer diagnostic method: Volatile organic compounds as biomarkers

Introduction: Population-based fecal tests for colorectal cancer (CRC) screening have shown to reduce mortality thanks to the early detection of the disease. However, currently available fecal tests are limited in their sensitivity and specificity. Our aim is to look for volatile organic compounds in fecal samples as biomarkers for CRC detection. Material and Methods: Eighty participants were included; 24 had adenocarcinoma, 24 had adenomatous polyps and 32 presented no neoplasms. Fecal samples were collected 48 h preceding the colonoscopy from all participants, except CRC patient samples that were collected after 3–4 weeks from the colonoscopy. Magnetic headspace adsorptive extraction (Mag-HSAE) followed by thermal desorption-gas chromatography-mass spectrometry (TD-GC–MS) was performed on stool samples to identify volatile organic compounds as biomarkers. Results: p-Cresol was significantly more abundant in the cancer samples (P < 0.001) with an area under the curve (AUC) of 0.85 (CI 95%; 0.737–0.953), having a sensitivity and specificity of 83% and 82%, respectively. In addition, 3(4H)-dibenzofuranone,4a,9b-dihydro-8,9b-dimethyl- (3(4H)-DBZ) was also more abundant in the cancer samples (P < 0.001) with an AUC of 0.77 (CI 95%; 0.635–0.905), sensitivity of 78% and specificity of 75%. When combined (p-cresol and 3(4H)-DBZ), the AUC was 0.86, sensitivity 87% and specificity 79%. p-Cresol also appeared to be promising as a biomarker for pre-malignant lesions with an AUC of 0.69 (CI 95%; 0.534–0.862), sensitivity 83% and specificity 63%, P = 0.045. Conclusions: Volatile organic compounds emitted from feces and determined by a sensitive analytical methodology (Mag-HSAE-TD-GC–MS), employing a magnetic graphene oxide as extractant phase, could be used as a potential screening technology for CRC and pre-malignant lesions.Miren Alustiza would like to thank ISABIAL for her pre-doctoral grant (UGP-16-138/2016/45). This work was supported by the Instituto de Salud Carlos III (PI17/01756, PI20/01527); by Vicerrectorado de Investigación y de Transferencia de Conocimiento (UAUSTI18-04, UAUSTI19-05, UAUSTI20-04), and Conselleria d’Innovació, Universitats, Ciència i Societat Digital (Generalitat Valenciana) (PROMETEO/2018/087; CIPROM/2021/062). The authors extend their appreciation to the Ministry of Science, Innovation and Universities for granting the Spanish Network of Excellence in Sample Preparation (RED2018-102522-T)

Unlocking Preclinical Alzheimer’s: A Multi-Year Label-Free In Vitro Raman Spectroscopy Study Empowered by Chemometrics

Alzheimer’s disease is a progressive neurodegenerative disorder, the early detection of which is crucial for timely intervention and enrollment in clinical trials. However, the preclinical diagnosis of Alzheimer’s encounters difficulties with gold-standard methods. The current definitive diagnosis of Alzheimer’s still relies on expensive instrumentation and post-mortem histological examinations. Here, we explore label-free Raman spectroscopy with machine learning as an alternative to preclinical Alzheimer’s diagnosis. A special feature of this study is the inclusion of patient samples from different cohorts, sampled and measured in different years. To develop reliable classification models, partial least squares discriminant analysis in combination with variable selection methods identified discriminative molecules, including nucleic acids, amino acids, proteins, and carbohydrates such as taurine/hypotaurine and guanine, when applied to Raman spectra taken from dried samples of cerebrospinal fluid. The robustness of the model is remarkable, as the discriminative molecules could be identified in different cohorts and years. A unified model notably classifies preclinical Alzheimer’s, which is particularly surprising because of Raman spectroscopy’s high sensitivity regarding different measurement conditions. The presented results demonstrate the capability of Raman spectroscopy to detect preclinical Alzheimer’s disease for the first time and offer invaluable opportunities for future clinical applications and diagnostic methods.This work was funded by the Basque Government (Ref. KK-2022/00001) and supported by grant CEX2020-001038-M funded by MICIU/AEI/10.13039/501100011033

Effects of Somatic Methylation in Colonic Polyps on Risk of Developing Metachronous Advanced Colorectal Lesions

The utility of molecular markers for predicting the risk of metachronous advanced colorectal lesions (MACLs) remains poorly investigated. We examined the relationship between somatic hypermethylation in polyps at baseline and the risk of developing MACL. This retrospective cohort study included 281 consecutive patients with colonic polyps who were enrolled between 2007 and 2009 and followed-up until 2014. MACLs were defined as adenomas of ≥10 mm, high-grade dysplasia, or with a villous component; and serrated lesions of ≥10 mm or with dysplasia. In total, 595 polyps were removed at baseline colonoscopy and analyzed for pathological characteristics and CpG island methylator phenotype (CIMP) using the MS-MLPA (Methylation-Specific -- Multiplex Ligation-dependent Probe Amplification) technique. Forty-five patients (16.0%) showed at least one CIMP+ polyp. MACL risk was higher in patients with CIMP+ polyps (odds ratio (OR), 4.50; 95% CI, 1.78–11.4; p = 0.002). Patients with CIMP+ polyps also exhibited shorter time to MACL development (33.8 months vs. 50.1 months; p < 0.001), even with adjustment for polyp size and number (OR, 2.40; 95% CI, 1.33–4.34). Adding CIMP analysis improved the sensitivity (57.0% to 70.9%), negative predictive value (71.1% to 77.3%), and overall accuracy (49.8% to 52.0%) for MACL risk estimation. These results highlight that CIMP may be a useful marker for endoscopic surveillance

Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: prognostic implications and response to chemotherapy

OBJECTIVE: The aim of this study was to validate a molecular classification of colorectal cancer (CRC) based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP) status, BRAF, and KRAS and investigate each subtype's response to chemotherapy. DESIGN: This retrospective observational study included a population-based cohort of 878 CRC patients. We classified tumours into five different subtypes based on BRAF and KRAS mutation, CIMP status, and MSI. Patients with advanced stage II (T4N0M0) and stage III tumours received 5-fluoruracil (5-FU)-based chemotherapy or no adjuvant treatment based on clinical criteria. The main outcome was disease-free survival (DFS). RESULTS: Patients with the combination of microsatellite stable (MSS) tumours, BRAF mutation and CIMP positive exhibited the worst prognosis in univariate (log rank P<0.0001) and multivariate analyses (hazard ratio 1.75, 95% CI 1.05-2.93, P = 0.03) after adjusting for age, sex, chemotherapy, and TNM stage. Treatment with 5-FU-based regimens improved prognosis in patients with the combination of MSS tumours, KRAS mutation and CIMP negative (log rank P = 0.003) as well as in patients with MSS tumours plus BRAF and KRAS wild-type and CIMP negative (log-rank P<0.001). After adjusting for age, sex, and TNM stage in the multivariate analysis, only patients with the latter molecular combination had independently improved prognosis after adjuvant chemotherapy (hazard ratio 2.06, 95% CI 1.24-3.44, P = 0.005). CONCLUSION: We confirmed the prognostic value of stratifying CRC according to molecular subtypes using MSI, CIMP status, and somatic KRAS and BRAF mutation. Patients with traditional chromosomally unstable tumours obtained the best benefit from adjuvant 5-FU-based chemotherapy