La investigación en el aula a través de las redes sociales: co-diseño de un blog como herramienta de innovación y mejora de la docencia

[ES] El nuevo Espacio Europeo de Educación ha supuesto la incorporación de nuevas metodologías y dinámicas digitales en entornos formales como el ámbito universitario, motivando al alumnado a involucrarse en sus procesos de aprendizaje colaborativo dentro del aula. A través de la asignatura Investigación en Sistemas de Bienestar Social del grado de Trabajo Social de la Universitat de València se ha llevado a cabo un proyecto de innovación docente, financiado por dicha universidad, con el objetivo de mejorar la docencia a través del uso de las redes sociales para la construcción e intercambio de conocimiento superior en materia de investigación. Concretamente, se ha co-diseñado junto al alumnado un blog grupal didáctico de acceso libre, “Investiblog”, que permite el uso colectivo de un espacio virtual de encuentro, que contribuye a estrechar la brecha digital debido a su bajo coste y sencillez de uso. El proyecto se ha implementado en el curso académico 2019-2020, en tres grupos de tercer curso, con un total de 124 estudiantes, a través de una metodología colaborativa de co-creación de materiales de aprendizaje compartidos. En la fase pre, se administró un cuestionario ad hoc para establecer los conocimientos previos del alumnado sobre el uso de la herramienta blog. Y en la fase post, se les preguntó por la utilidad y el impacto de la herramienta en el proceso de aprendizaje. Los resultados indican que la nueva herramienta impacta positivamente al facilitar compartir contenidos comunes, obtener información de interés y optar a ayudas para iniciarse en la investigación. Respecto al profesorado, Investiblog aumentó su implicación en el desarrollo de nuevas metodologías docentes co-creadas. En conclusión, las herramientas de aprendizaje co-creadas con el alumnado facilitan el aprendizaje colaborativo y estimulan la creatividad, estas herramientas pueden ser muy útiles para la docencia en situaciones como la provocada por la crisis COVID-19.Este proyecto ha sido financiado por el Servei de Formació Permanent i Innovació Educativa de la Universitat de Valencia, dentro del “Programa de Innovación Docente, 2019” (ref. UV-SFPIE_PID19-1096293).Llop-Medina, L.; Bueno-Sanchez, L.; Sigalat Signes, E.; Ródenas-Rigla, F. (2021). La investigación en el aula a través de las redes sociales: co-diseño de un blog como herramienta de innovación y mejora de la docencia. En Proceedings INNODOCT/20. International Conference on Innovation, Documentation and Education. Editorial Universitat Politècnica de València. 451-458. https://doi.org/10.4995/INN2020.2020.11843OCS45145

Prevalence of severe/morbid obesity and other weight status and anthropometric reference standards in Spanish preschool children: The PREFIT project

BACKGROUND: Childhood obesity has become a major health problem in children under the age of 5 years. Providing reference standards would help paediatricians to detect and/or prevent health problems related to both low and high levels of body mass and to central adiposity later in life. Therefore, the aim of this study was to examine the prevalence of different weight status categories and to provide sex- and age-specific anthropometry reference standards for Spanish preschool children. METHODS: A total of 3178 preschool children (4.59±0.87 years old) participated in this study. Prevalence of different degrees of obesity (mild, severe, and morbid) and other weight status categories were determined. RESULTS: Reference standards were obtained. Prevalence of overweight and obese preschool children in the Spanish population ranged from 21.4 to 34.8%. Specifically, the obesity prevalence was 3.5, 1.2, and 1.3% of these subjects were categorized as mild, severe, and morbid obese. Sex- and age-specific reference standards for anthropometric parameters are provided for every 0.25 years (i.e. every trimester of life). CONCLUSION: Our results show a high prevalence of overweight/obese preschoolers. The provided sex- and age-specific anthropometric reference standards could help paediatricians to track and monitor anthropometric changes at this early stage in order to prevent overweight/obesity.We thank the participation of the preschoolers, parents, and teachers in this study. We are grateful to Ms. Carmen Sainz-Quinn for assistance with the English language. This work is part of a Ph.D. Thesis conducted in the Biomedicine Doctoral Studies of the University of Granada, Spain. The PREFIT project takes place owing to the funding of the Ramón y Cajal grant held by FBO (RYC-2011-09011). C.C.-S. is supported by a grant from the Spanish Ministry of Economy and Competitiveness (BES-2014-068829). E.G.A. and F.B.O. are supported by a grant from the Spanish Ministry of Science and Innovation (RYC-2014-16390 and RYC-2011-09011, respectively). C.A.-B., A.P.-B., and G.S.-D. are supported by the Spanish Ministry of Education (FPU13/03137, FPU15/ 05337, and FPU13/04365, respectively). Additional funding was obtained from the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES) and by the Junta de Andalucia, Consejería de Conocimiento, Investigación y Universidades. In addition, funding was provided by the SAMID III network, RETICS, the PN I+D+I 2017-2021 (Spain), ISCIII-Sub-Directorate General for Research Assessment and Promotion, the European Regional Development Fund (ERDF) (RD16/0022, SOMM17/6107/UGR), the EXERNET Research Network on Exercise and Health in Special Populations (DEP2005- 00046/ACTI), the University of the Basque Country (GIU14/21), and the University of Zaragoza (JIUZ-2014-BIO-08)

Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared the transcriptional profile of PDGFRα + CAFs isolated from genetically engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to identify genes potentially implicated in their protumorigenic properties. We report that the most differentially expressed gene, Saa3, a member of the serum amyloid A (SAA) apolipoprotein family, is a key mediator of the protumorigenic activity of PDGFRα + CAFs. Whereas Saa3-competent CAFs stimulate the growth of tumor cells in an orthotopic model, Saa3-null CAFs inhibit tumor growth. Saa3 also plays a role in the cross talk between CAFs and tumor cells. Ablation of Saa3 in pancreatic tumor cells makes them insensitive to the inhibitory effect of Saa3-null CAFs. As a consequence, germline ablation of Saa3 does not prevent PDAC development in mice. The protumorigenic activity of Saa3 in CAFs is mediated by Mpp6, a member of the palmitoylated membrane protein subfamily of the peripheral membrane-associated guanylate kinases (MAGUK). Finally, we interrogated whether these observations could be translated to a human scenario. Indeed, SAA1, the ortholog of murine Saa3, is overexpressed in human CAFs. Moreover, high levels of SAA1 in the stromal component correlate with worse survival. These findings support the concept that selective inhibition of SAA1 in CAFs may provide potential therapeutic benefit to PDAC patients.This work was supported by European Research Council Grants ERC-AG/250297-RAS AHEAD and ERC-AG/695566-THERACAN, Spanish Ministry of Economy and Competitiveness Grant SAF2014-59864-R, and Asociación Española contra el Cáncer Grant GC16173694BARB (to M. Barbacid). M.D. was supported by a fellowship from La Caixa International Fellowship Program. M. Barbacid is the recipient of an Endowed Chair from the AXA Research Fun

Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study

BACKGROUND Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments. OBJECTIVE The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies. METHODS A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations. RESULTS Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of I-Na and I-caL (P < .01), with no significant differences in the remaining currents. I-caL blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors because of an increase in rotor meandering (1.71 +/- 2.01cm(2)) and presented an increased efficacy in models with a depressed INa (P < .01). CONCLUSION Mathematical simulations based on a population of models representing intersubject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacologic strategies. Our results suggest that the underlying mechanism of the diverging success of I-caL block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities.Supported by the Spanish Ministry of Education (FPU2010); the Wellcome Trust Fellowship 100246/Z/12/Z; Universitat Politecnica de Valencia; the Spanish Health Research Fund (PI13/00903); the Spanish Society of Cardiology; the Spanish Ministry of Science; Generalitat Valenciana Grants (ACIF/2013/021); and Innovation (Red RIC, PLE2009-0152). Drs. Rodriguez and Climent are equally contributing senior authors.Liberos Mascarell, A.; Bueno-Orovio, A.; Rodrigo Bort, M.; Ravens, U.; Hernández-Romero, I.; Fernández-Avilés, F.; Guillem Sánchez, MS.... (2016). Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study. Heart Rhythm. 13(12):2358-2365. https://doi.org/10.1016/j.hrthm.2016.08.028S23582365131

CD133-directed CAR T-cells for MLL leukemia: on-target, off-tumor myeloablative toxicity

This work has been supported by the European Research Council (CoG-2014-646903, PoC-2018-811220) to PM, the Spanish Ministry of Economy and Competitiveness (MINECO, SAF-SAF2016-80481- R, BIO2017-85364-R) to PM and EE, the Generalitat de Catalunya (SGR330, SGR102 and PERIS) to PM and EE, the Spanish Association against cancer (AECC-CI-2015) to CB, and the Health Institute Carlos III (ISCIII/FEDER, PI14-01191) to CB. PM also acknowledges financial support from the Obra Social La Caixa-Fundaciò Josep Carreras. SRZ and TV are supported by a Marie Curie fellowships. OM is supported by the Catalan Government through a Beatriu de Pinos fellowship. MB is supported by MINECO through a PhD scholarship. PM is an investigator of the Spanish Cell Therapy cooperative network (TERCEL)

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

HLA association with the susceptibility to anti-synthetase syndrome

Objective: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). Methods: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. Results: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P=1.56E-09, odds ratio-OR [95% confidence interval-CI]=2.54 [1.84-3.50] and 21.4% versus 5.5%, P=18.95E-18, OR [95% CI]=4.73 [3.18-7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P=0.0003, OR [95% CI]=0.48 [0.31-0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P=0.001, OR [95% CI]=2.54 [1.39-4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. Conclusions: Our results support the association of the HLA complex with the susceptibility to ASSD

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO