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Transcription co-activator factor 20 (TCF20) is a regulator of transcription factors involved in extracellular matrix remodelling. In addition, TCF20 genomic variants in humans have been associated with impaired intellectual disability. Therefore, we hypothesized that TCF20 has several functions beyond those described in neurogenesis, including the regulation of fibrogenesis.

Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinicalbiological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the non-leukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined worse-outcome genetic signature and MRD on day +35 allowed risk stratification of T-ALL into standard or high-risk groups with significantly different 5- year overall survival (OS) of 52% (95% confidence interval: 37-67) and 17% (95% confidence interval: 1-33), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients.

The purpose of this study is to analyze the experiences of a group of higher education students in order to understand how they lived the construction of masculinity during their formative stage. Through A/r/tography methodology, we analyzed, using a qualitative method based on a biographical and interpretative perspectives, 72 bodygrafies performed by students of the Master of Psychopedagogy of the Universidad xxx as part of an exercise in visual self-representation. The results of the analysis allowed us to identify two great pedagogies in the construction process of masculinities: an anesthetic pedagogy and other sensitive and/or resistance pedagogy. The results obtained from the analysis of visual narratives show valuable experiences that encourage critical dialogues, from which useful guidelines are derived in order to overcome educational practices that perpetuate the model of traditional masculinity. In this way, the text reveals, by using the visual arts, a latent social reality and rises the reflection on how to promote a critical and transformative citizenship that overcome the conceptions of masculinity of traditional archetype, El presente texto tiene por objetivo analizar las experiencias vividas por un grupo de alumnado universitario con la intención de comprender cómo han vivido la construcción de la masculinidad durante su etapa formativa. Desde la metodología denominada ‘a/r/tografía’, empleando un enfoque cualitativo, y adoptando una perspectiva biográfica e interpretativa, se analizan 72 corpografías que fueron entregadas por alumnadodel Máster de Psicopedagogía de la Universidad xxx, como parte de un ejercicio de auto-representación visual. Los resultados del análisis permiten identificar dos grandes pedagogías en la formación de masculinidades por parte de los participantes: una pedagogía anestesiante y otra pedagogía sensible y/o de la resistencia. Los resultados obtenidos del análisis de las narraciones visuales permiten dar a conocer valiosas experiencias que fomentan diálogos críticos, de las que se derivan pautas útiles con el objeto de superar prácticas educativas que perpetúen el modelo de masculinidad tradicional. De esta forma, el presente texto revela, a través de las artes visuales, una realidad social latente y da pie a reflexionar sobre cómo cimentar una ciudadanía crítica y transformadora que deje atrás las concepciones de masculinidad de arquetipo tradicional

La ponencia trata sobre el cuerpo y las cosas en educación y lo hace en forma de collage, combinando ideas y postulados procedentes de diferentes tradiciones de pensamiento y culturas científicas desde un núcleo ordenador común: la educación entendida como una acción de apertura al mundo que reposa, como señala Le Breton (2000, p. 41), en «un saber estar, un saber ver, un saber escuchar, una apertura al mundo del sentido y de los sentidos». Como una acción corporeizada y, por ello, afectiva, sensorial y móvil en diálogo con las cosas. En primer lugar, trataremos sobre los términos cuerpo y cosas con la intención de acotar mínimamente la rica red semántica que ambos vocablos comportan. Seguidamente, se abordarán las claves que podrían explicar el giro corporal y material en las agendas de la investigación sociohumanística y en la educativa. A continuación, nos detendremos en el cuerpo como cosa para inferir, a partir de ellos, algunas implicaciones socioantropológicas y educativas. La última parre de la ponencia reflexiona acerca de las pedagogías sensibles en clave fenomenológica. Finalmente, en apretada síntesis, se resaltarán algunas conclusiones en un intento de involucrar a nuestros lectores en nuestras reflexiones y dialogar con ellos.

Promising results have been shown with the combination of ponatinib and chemotherapy in adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). The PONALFIL (Ponatinib With Chemotherapy for Young Adults Ph Positive Acute Lymphoblastic Leukemia) trial combined ponatinib (30 mg/d) with standard induction and consolidation chemotherapy followed by allogeneic hematopoietic stem cell transplant (alloHSCT) in newly diagnosed Ph+ ALL patients aged 18 to 60 years. Ponatinib was only given pre-emptively after alloHSCT. Primary end points were hematologic and molecular response before alloHSCT and event-free survival (EFS), including molecular relapse as event. Thirty patients (median age, 49 years; range, 19-59 years) entered the trial. All exhibited hematologic response, and alloHSCT was performed in 26 patients (20 in complete molecular response and 6 in major molecular response). Only 1 patient died (of graft-versus-host disease), and 5 patients exhibited molecular relapse after alloHSCT. No tyrosine kinase inhibitor was given after HSCT in 18 of 26 patients. Twenty-nine patients are alive (median follow-up, 2.1 years; range, 0.2-4.0 years), with 3-year EFS and overall survival (OS) of 70% (95% confidence interval, 51-89) and 96% (95% confidence interval, 89-100), respectively. Comparison of the PONALFIL and the ALLPh08 (Chemotherapy and Imatinib in Young Adults With Acute Lymphoblastic Leukemia Ph [BCR-ABL] Positive; same schedule, using imatinib as the tyrosine kinase inhibitor) trials by propensity score showed significant improvement in OS for patients in PONALFIL (3-year OS, 96% vs 53%; P = .002). The most frequent grade 3 to 4 adverse events were hematologic (42%), infectious (17%), and hepatic (22%), with only one vascular occlusive event. The combination of chemotherapy with ponatinib followed by alloHSCT is well tolerated, with encouraging EFS in adults with newly diagnosed Ph+ ALL. Cross-trial comparison suggests improvement vs imati

Context: B-cell precursor acute lymphoblastic leukemia (BCP ALL) is a genetically heterogeneous neoplasm with >20 biologic subtypes. Each subtype shows specific genetic traits that determine relapse risk and patients' survival. Objectives: To establish the genetic subtype (primary alteration) of adult BCP ALL patients enrolled in the PETHEMA LAL19 trial (NCT 04179929) and to correlate them with measurable residual disease (MRD) level and survival. Patients and Methods: In the LAL19 trial (NCT04179929), Ph-negative patients (18–65 y) with MRD≥0.01% at day+35 or high-risk genetics receive alloHSCT and MRD<0.01% patients with standard-risk genetics receive maintenance chemotherapy. The genetic analyses are centralized: FISH and NGS DNA panel (Hospital de Salamanca), RNAseq panel (Hospital 12 de Octubre), FISH panel (Hospital La Fe), and SNP array (Josep Carreras Institute/ICO-Hospital Germans Trias i Pujol). MRD determinations are centrally done by next-generation flow cytometry in the Cytometry Service, NUCLEUS, University of Salamanca. Results: The genetic subtype was identified in 54% (82/152) of patients. The most recurrent subtypes were KMT2Ar (11%), Ph-like (mostly CRLF2::IGH, 11%), low-hypodiploid (7%), PAX5 P80R (7%), high-hyperdiploid (6%), and t(1;19)/TCF3::PBX1 (6%). In addition, t(12;21)/ETV6::RUNX1, ZNF384r, and iAMP21 subtypes (1.5% each) and MEF2Dr, MYCr, IDH1 R132 subtypes (<1% each) were found. Regarding secondary alterations, NRAS (15%), TP53 (13%), PAX5 (13%), and KRAS (10%) mutations were the most frequently observed. Twelve patients were refractory (mainly low-hypodiploid, Ph-like, MYCr, and B-other/unclassified patients). Statistically significant differences were observed for day+35 MRD levels between genetic subtypes. Ph-like, low-hypodiploid, and KMT2Ar showed lower frequencies of MRD<0.01% (17%, 33%, and 57%, respectively) than patients with PAX5P80R (100%), t(1;19)/TCF3::PBX1 (83%), and high-hyperdiploid (75%) (P=0.006). Despite the short med

The prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBX1 showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients. However, patients with TCF3-PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation).

Cerium oxide nanoparticles (CeO2NPs) possess powerful antioxidant properties, thus emerging as a potential therapeutic tool in non-alcoholic fatty liver disease (NAFLD) progression, which is characterized by a high presence of reactive oxygen species (ROS). The aim of this study was to elucidate whether CeO2NPs can prevent or attenuate oxidant injury in the hepatic human cell line HepG2 and to investigate the mechanisms involved in this phenomenon. The effect of CeO2NPs on cell viability and ROS scavenging was determined, the differential expression of pro-inflammatory and oxidative stress-related genes was analyzed, and a proteomic analysis was performed to assess the impact of CeO2NPs on cell phosphorylation in human hepatic cells under oxidative stress conditions. CeO2NPs did not modify HepG2 cell viability in basal conditions but reduced H2O2- and lipopolysaccharide (LPS)-induced cell death and prevented H2O2-induced overexpression of MPO, PTGS1 and iNOS. Phosphoproteomic analysis showed that CeO2NPs reverted the H2O2-mediated increase in the phosphorylation of peptides related to cellular proliferation, stress response, and gene transcription regulation, and interfered with H2O2 effects on mTOR, MAPK/ERK, CK2A1 and PKACA signaling pathways. In conclusion, CeO2NPs protect HepG2 cells from cell-induced oxidative damage, reducing ROS generation and inflammatory gene expression as well as regulation of kinase-driven cell survival pathways.

When addressing the issue of disabled people, the image that society has on this topic emerges as an element to analyze. Currently, the perception of an anthropological fact such as this one is not conceived without the assumption of the realities that certain discursive and audiovisual constructs promote. The objective of this article is to analyze the cinema's treatment of disability based on the case of the film Campeones. After a brief analysis of the treatment of disability in the history of cinema, we carry out an eco-narrative analysis of the film, fixed in an etic position, on which both, the representation of disability through the characters, and the way in which stereotypes and prejudices are reflected in their stories are examined. Results. Campeones promotes a phenomenological approach to the plot. The way the story is narrated helps to overcome the superficial understanding of the events, masterfully promoting the comprehension of social phenomena related to disability from a pedagogical approach. In conclusion, Campeones tries to minimize the established social binomial "capacity-disability" to build an image that does not present disabled people as a correlate of deficiency., Cuando abordamos la cuestión de las personas con discapacidad emerge como elemento de análisis la imagen que la sociedad ha tenido de ellas a lo largo de la historia.  En la actualidad la percepción de un hecho antropológico como este no se concibe sin la asunción de las realidades que ciertos constructos discursivos y audiovisuales impulsan. El presente trabajo tiene por objetivo analizar el tratamiento que el cine hace de la discapacidad a partir del caso de la película Campeones. Tras un breve recorrido por el tratamiento de la discapacidad en la historia del cine, se despliega un análisis eco-narrativo de la película, fijado en una posición etic, sobre el que se examina la representación de la discapacidad a través de los personajes que aparecen en ella, así como la manera en que se plasman los estereotipos y prejuicios en sus historias. Campeones insta a realizar un acompañamiento fenomenológico de la trama. El relato promueve, con maestría, que se trascienda la superficialidad de los acontecimientos narrados, promoviendo la comprensión de los fenómenos sociales relativos a la discapacidad desde un enfoque pedagógico. En conclusión, Campeones trata de minimizar el establecido binomio social “capacidad-discapacidad” para construir una imagen que no presente a las personas con discapacidad como correlato de deficiencia.

When addressing the issue of disabled people, the image that society has on this topic emerges as an element to analyze. Currently, the perception of an anthropological fact such as this one is not conceived without the assumption of the realities that certain discursive and audiovisual constructs promote. The objective of this article is to analyze the cinema's treatment of disability based on the case of the film Campeones. After a brief analysis of the treatment of disability in the history of cinema, we carry out an eco-narrative analysis of the film, fixed in an etic position, on which both, the representation of disability through the characters, and the way in which stereotypes and prejudices are reflected in their stories are examined. Results. Campeones promotes a phenomenological approach to the plot. The way the story is narrated helps to overcome the superficial understanding of the events, masterfully promoting the comprehension of social phenomena related to disability from a pedagogical approach. In conclusion, Campeones tries to minimize the established social binomial "capacity-disability" to build an image that does not present disabled people as a correlate of deficiency., Cuando abordamos la cuestión de las personas con discapacidad emerge como elemento de análisis la imagen que la sociedad ha tenido de ellas a lo largo de la historia. En la actualidad la percepción de un hecho antropológico como este no se concibe sin la asunción de las realidades que ciertos constructos discursivos y audiovisuales impulsan. El presente trabajo tiene por objetivo analizar el tratamiento que el cine hace de la discapacidad a partir del caso de la película Campeones. Tras un breve recorrido por el tratamiento de la discapacidad en la historia del cine, se despliega un análisis eco-narrativo de la película, fijado en una posición etic, sobre el que se examina la representación de la discapacidad a través de los personajes que aparecen en ella, así como la manera en que se plasman los estereotipos y prejuicios en sus historias. Campeones insta a realizar un acompañamiento fenomenológico de la trama. El relato promueve, con maestría, que se trascienda la superficialidad de los acontecimientos narrados, promoviendo la comprensión de los fenómenos sociales relativos a la discapacidad desde un enfoque pedagógico. En conclusión, Campeones trata de minimizar el establecido binomio social “capacidad-discapacidad” para construir una imagen que no presente a las personas con discapacidad como correlato de deficiencia.

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9–8.6) months, with a 4-year OS probability of 18% (95% CI, 9%–27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109–3.362), 2.958 (1.640–5.334), and 2.976 (1.157–7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL.

DHX15 is a downstream substrate for Akt1, which is involved in key cellular processes affecting vascular biology. Here, we explored the vascular regulatory function of DHX15. Homozygous DHX15 gene deficiency was lethal in mouse and zebrafish embryos. DHX15 zebrafish also showed downregulation of VEGF-C and reduced formation of lymphatic structures during development. DHX15 mice depicted lower vascular density and impaired lymphatic function postnatally. RNAseq and proteome analysis of DHX15 silenced endothelial cells revealed differential expression of genes involved in the metabolism of ATP biosynthesis. The validation of these results demonstrated a lower activity of the Complex I in the mitochondrial membrane of endothelial cells, resulting in lower intracellular ATP production and lower oxygen consumption. After injection of syngeneic LLC1 tumor cells, DHX15 mice showed partially inhibited primary tumor growth and reduced lung metastasis. Our results revealed an important role of DHX15 in vascular physiology and pave a new way to explore its potential use as a therapeutical target for metastasis treatment.

The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.