A New Route of Valorization of Petrochemical Wastewater: Recovery of 1,3,5-Tris (4-tert-butyl-3-hydroxy-2,6-dimethyl benzyl)¿1,3,5-triazine-2,4,6-(1H,3H,5H)-trione (Cyanox 1790) and Its Subsequent Application in a PP Matrix to Improve Its Thermal Stability

[EN] The various chemicals in industrial wastewater can be beneficial for improving its circularity. If extraction methods are used to capture valuable components from the wastewater and then recirculate them throughout the process, the potential of the wastewater can be fully exploited. In this study, wastewater produced after the polypropylene deodorization process was evaluated. These waters remove the remains of the additives used to create the resin. With this recovery, contamination of the water bodies is avoided, and the polymer production process becomes more circular. The phenolic component was recovered by solid-phase extraction and HPLC, with a recovery rate of over 95%. FTIR and DSC were used to evaluate the purity of the extracted compound. After the phenolic compound was applied to the resin and its thermal stability was analyzed via TGA, the compound's efficacy was finally determined. The results showed that the recovered additive improves the thermal qualities of the material.This research was partially funded by the Ministry of Science, Innovation, and Universities (MICIU) project number MAT2017-84909-C2-2-R Nanolignin.Hernández-Fernández, J.; Ortega-Toro, R.; López-Martínez, J. (2023). A New Route of Valorization of Petrochemical Wastewater: Recovery of 1,3,5-Tris (4-tert-butyl-3-hydroxy-2,6-dimethyl benzyl)¿1,3,5-triazine-2,4,6-(1H,3H,5H)-trione (Cyanox 1790) and Its Subsequent Application in a PP Matrix to Improve Its Thermal Stability. Molecules. 28(5). https://doi.org/10.3390/molecules2805200328

Two-Dimensional-Based Hybrid Shape Optimisation of a 5-Element Formula 1 Race Car Front Wing under FIA Regulations

Front wings are a key element in the aerodynamic performance of Formula 1 race cars. Thus, their optimisation makes an important contribution to the performance of cars in races. However, their design is constrained by regulation, which makes it more difficult to find good designs. The present work develops a hybrid shape optimisation approach to obtain an optimal five-element airfoil front wing under the FIA regulations and 17 design parameters. A first baseline design is obtained by parametric optimisation, on which the adjoint method is applied for shape optimisation via Mesh Morphing with Radial Basis Functions. The optimal front wing candidate obtained outperforms the parametric baseline up to a 25% at certain local positions. This shows that the proposed and tested hybrid approach can be a very efficient alternative. Although a direct 3D optimisation approach could be developed, the computational costs would be dramatically increased (possibly unaffordable for such a complex five-element front wing realistic shape with 17 design parameters and regulatory constraints). Thus, the present approach is of strong interest if the computational budget is low and/or a fast new front wing design is desired, which is a frequent scenario in Formula 1 race car design.The authors want to acknowledge the financial support from the Ramón y Cajal 2021 Excellence Research Grant action from the Spanish Ministry of Science and Innovation (FSE/AGENCIA ESTATAL DE INVESTIGACIÓN), the UMA18-FEDERJA-184 grant, and the Andalusian Research, Development and Innovation Plan (PAIDI—Junta de Andalucia) fundings. Partial funding for open access charge: Universidad de Málag

Compreender crianças com inibição emocional: Uma abordagem com múltiplos informadores do contexto educacional e familiar

Behavioral inhibition (BI) is a temperament trait characterized by extreme fear in the face of novelty. BI has been associated with the development of mental disorders. However, there is a lack of research examining the socioemotional and behavioral characteristics of behaviorally inhibited children both in family and school settings. For a more comprehensive and in-depth overview of children’s behavior in each of these contexts, this study has collected data from both parents (mother and father – family setting) and from teachers (educational environment). The sample consisted of 109 children aged between four and six years old. Multi-informant approach was used: all fathers, mothers and teachers completed both the Preschool Behavioral Inhibition Scales, the Child Behavior Checklist for parents and teachers, and the Behavior Assessment System for Children and Adolescents. Our findings revealed that children classified as BI exhibit less socioemotional and behavioral adjustments than their uninhibited peers both in family and school contexts. Further, the shyness variable seemed to be strongly associated with behavioral inhibition, regardless of informant and context.A inibição comportamental (IC) é um traço de temperamento caracterizado por medo extremo face a situações novas. A IC tem sido associada ao desenvolvimento de perturbações mentais. No entanto, é escassa a investigação que examina as características socio-emocionais e comportamentais de crianças com inibição comportamental em contextos educacionais e familiares. Para uma visão global mais compreensiva e aprofundada do comportamento da criança em cada um destes contextos, este estudo recolheu dados com os pais (mãe e pai – contexto familiar) e com os professores (contexto educacional). A amostra foi constituída por 109 crianças, entre os quatro e os seis anos de idade. Foi utilizada uma abordagem com múltiplos informadores: todos os pais, mães e professores completaram as Escalas de Inibição Comportamental para o Pré-Escolar, o Questionário de Comportamento da Criança para pais e professores (CBCL e TRF), e o Sistema de Avaliação do Comportamento para Crianças e Adolescentes (BASC). Os resultados revelaram que crianças consideradas com IC apresentavam níveis mais baixos de ajustamento socio-emocional e comportamental comparativamente a crianças não inibidas, tanto no contexto familiar como no contexto educacional. Adicionalmente, a variável de timidez pareceu ser a que mais fortemente se associou à inibição comportamental, independentemente do informador e do contexto

Protocol to generate a patient derived xenograft model of acquired resistance to immunotherapy in humanized mice

Cancer; Cell isolation; Stem cellsCàncer; Aïllament cel·lular; Cèl·lules mareCáncer; Aislamiento celular; Células madreImmunotherapy has revolutionized cancer treatment, but preclinical models are required to understand immunotherapy resistance mechanisms underlying patient relapse. This protocol describes how to generate an acquired resistance humanized in vivo model to immunotherapies in patient-derived xenografts (PDX). We detail steps to inject human CD34+ cells into NSG mice, followed by generation of immunoresistant PDX in humanized mice. This approach recapitulates the human immune system, allowing investigators to generate preclinical resistance models to different immunotherapies for identifying the resistant phenotype. For complete details on the use and execution of this protocol, please refer to Martínez-Sabadell et al., 2022 and Arenas et al. (2021).This work was supported by Asociación Española Contra el Cancer (GCAEC19017ARRI), Breast Cancer Research Foundation (BCRF-21-008), and Instituto de Salud Carlos III (PI19/01181). A.M.S. was funded by the Spanish Government (PFIS FI20/00188). P.O.R. was funded by the BBVA. E.J.A. was funded by the AECC (POSTD211413AREN). VHIO would like to acknowledge the Cellex Foundation for providing research facilities and equipment and the Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) from the Institute of Health Carlos III (ISCIII) for their support on this research. Authors acknowledge financial support for the Cancer Immunology and Immunotherapy (CAIMI-2) program funded by BBVA Foundation. The Graphical abstract was created with BioRender.com

First data of the Colombia Lightning Mapping Array - COLMA

The first data set of VHF lightning mapping using a Lightning Mapping Array system - LMA in a tropical region is presented in this paper. Six sensors were installed at the north of Colombia near Santa Marta city. Since the installation of the LMA network in 2015, up to 7000 intra-cloud (IC) discharges from September to November 2015 have been analyzed. The data suggests that, the electrical charge distribution in tropical thunderstorms shows higher vertical development reaching higher altitudesPreprin

Targeting HER2-AXL heterodimerization to overcome resistance to HER2 blockade in breast cancer

Breast cancer; HeterodimerizationCáncer de mama; HeterodimerizaciónCàncer de mama; HeterodimeritzacióAnti-HER2 therapies have markedly improved prognosis of HER2-positive breast cancer. However, different mechanisms play a role in treatment resistance. Here, we identified AXL overexpression as an essential mechanism of trastuzumab resistance. AXL orchestrates epithelial-to-mesenchymal transition and heterodimerizes with HER2, leading to activation of PI3K/AKT and MAPK pathways in a ligand-independent manner. Genetic depletion and pharmacological inhibition of AXL restored trastuzumab response in vitro and in vivo. AXL inhibitor plus trastuzumab achieved complete regression in trastuzumab-resistant patient-derived xenograft models. Moreover, AXL expression in HER2-positive primary tumors was able to predict prognosis. Data from the PAMELA trial showed a change in AXL expression during neoadjuvant dual HER2 blockade, supporting its role in resistance. Therefore, our study highlights the importance of targeting AXL in combination with anti-HER2 drugs across HER2-amplified breast cancer patients with high AXL expression. Furthermore, it unveils the potential value of AXL as a druggable prognostic biomarker in HER2-positive breast cancer.A.A.-A., E.J.A., and F.B.-M. were supported by Asociación Española contra el Cáncer AECC (PRDVA18013LLUC to A.A.-A., POSTD211413AREN to E.J.A., and AECC_Postdoctoral17-1062 to F.B.-M.). A.M.-S. was funded by the Spanish Government (PFIS FI20/00188). J.Ar. is supported by Breast Cancer Research Foundation (BCRF-20-08), Instituto de Salud Carlos III Project reference number AC15/00062, and the EC under the framework of the ERA-NET TRANSCAN-2 initiative cofinanced by FEDER, Instituto de Salud Carlos III (CB16/12/00449 and PI19/01181), and Asociación Española Contra el Cáncer (AECC). A.P. was supported by Instituto de Salud Carlos III—PI19/01846, Breast Cancer Now—2018NOVPCC1294. P.E. and A.L. were funded by Instituto de Salud Carlos III and cofinanced by FEDER (PI18/01219 to P.E. and CB16/12/00481 to A.L.). J.M.C. was funded by Sociedad Española de Oncología Médica (Rio Hortega-SEOM) and Compromiso ADAMED

The target antigen determines the mechanism of acquired resistance to T cell-based therapies

Cancer; Antigen; ResistanceCáncer; Antígeno; ResistenciaCàncer; Antigen; ResistènciaDespite the revolution of immunotherapy in cancer treatment, patients eventually progress due to the emergence of resistance. In this scenario, the selection of the tumor antigen can be decisive in the success of the clinical response. T cell bispecific antibodies (TCBs) are engineered molecules that include binding sites to the T cell receptor and to a tumor antigen. Using gastric CEA+/HER2+ MKN45 cells and TCBs directed against CEA or HER2, we show that the mechanism of resistance to a TCB is dependent on the tumor antigen. Acquired resistant models to a high-affinity-CEA-targeted TCB exhibit a reduction of CEA levels due to transcriptional silencing, which is reversible upon 5-AZA treatment. In contrast, a HER2-TCB resistant model maintains HER2 levels and exhibit a disruption of the interferon-gamma signaling. These results will help in the design of combinatorial strategies to increase the efficacy of cancer immunotherapies and to anticipate and overcome resistances.This work was supported by Asociación Española Contra el Cancer (AECC), Breast Cancer Research Foundation (BCRF-21-008), and Instituto de Salud Carlos III (PI19/01181). A.M.S. was funded by the Spanish Government (PFIS FI20/00188). B.M. was funded by a fellowship from PERIS (Departament de Salut, Generalitat de Catalunya). M.R.A. was funded by Agency for Management of University and Research Grants (AGAUR, 2022 FI_B2 00080). P.O.R. was funded by the BBVA. E.J.A. was funded by the AECC (POSTD211413AREN). VHIO acknowledges the Cellex Foundation for providing research facilities and equipment, the Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) from the Institute of Health Carlos III (ISCIII), and the Department of Health (Generalitat de Catalunya, SLT008/18/00198 SLT008/18/00205) for their support on this research. The authors acknowledge financial support from the State Agency for Research (Agencia Estatal de Investigación) (CEX2020-001024-S/AEI/10.13039/501100011033) and for the Cancer Immunology and Immunotherapy (CAIMI-2) program funded by BBVA Foundation. We would like to remark the funding from B.M PERIS (Spain). The authors thank Dr. Anne Freimoser-Grundschober and Roche for helping provide the TCBs. The graphical abstract was created with BioRender.com

High-Intensity Interval Training (HIIT) on Biological and Body Composition Variables in Patients with Musculoskeletal Disorders: A Systematic Review and Meta-Analysis

In order to assess the impact of high-intensity interval training (HIIT) on biological and body composition variables in patients with musculoskeletal disorders (MSKD), a systematic search on PubMed (Medline), CENTRAL, CINAHL, Web of Science, SPORTDiscus, and Scopus was conducted. Standardized mean differences (SMD) and 95% confidence intervals were calculated and pooled in a meta-analysis using the random-effects model. The effectiveness of HIIT on waist circumference, muscle mass, resting heart rate, resting systolic and diastolic blood pressure, C-reactive protein, body weight, and body fat were determined. GRADE, risk of bias 2, and PEDro scales were employed. HIIT compared to no intervention, minimal intervention, or usual care did not show significant results in its favor on any of the variables studied, except for the resting heart rate when compared with no intervention (SMD = −0.33; 95% CI: −0.63, −0.04; heterogeneity Q value: 0.14; p = 0.93; I2 = 0%). In addition, HIIT also does not seem to be more effective than moderate-intensity continuous training. Based on the results, it seems that HIIT has almost no significant effects on biological and body composition variables, except for resting heart rate, in patients with MSKD

Sterilization Procedure for Temperature-Sensitive Hydrogels Loaded with Silver Nanoparticles for Clinical Applications

Anti-bacterial agents; Post-operative infections; Silver nanoparticlesAgents antibacterians; Infeccions postoperatòries; Nanopartícules de plataAgentes antibacterianos; Infecciones postoperatorias; Nanopartículas de plataHydrogels (HG) have recognized benefits as drug delivery platforms for biomedical applications. Their high sensitivity to sterilization processes is however one of the greatest challenges regarding their clinical translation. Concerning infection diseases, prevention of post-operatory related infections is crucial to ensure appropriate patient recovery and good clinical outcomes. Silver nanoparticles (AgNPs) have shown good antimicrobial properties but sustained release at the right place is required. Thus, we produced and characterized thermo-sensitive HG based on Pluronic® F127 loaded with AgNPs (HG-AgNPs) and their integrity and functionality after sterilization by dry-heat and autoclave methods were carefully assessed. The quality attributes of HG-AgNPs were seriously affected by dry-heat methods but not by autoclaving methods, which allowed to ensure the required sterility. Also, direct sterilization of the final HG-AgNPs product proved more effective than of the raw material, allowing simpler production procedures in non-sterile conditions. The mechanical properties were assessed in post mortem rat models and the HG-AgNPs were tested for its antimicrobial properties in vitro using extremely drug-resistant (XDR) clinical strains. The produced HG-AgNPs prove to be versatile, easy produced and cost-effective products, with activity against XDR strains and an adequate gelation time and spreadability features and optimal for in situ biomedical applications

Allogeneic Stem Cell Transplantation in Mature T Cell and Natural Killer/T Neoplasias: A Registry Study from Spanish GETH/GELTAMO Centers

Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia, current therapies, even the most innovative ones, are still far from ensuring its cure. The only treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias performed in centers from our national GELTAMO/GETH (Grupo Español de Linfoma y Trasplante de Médula Ósea/Grupo Español de Trasplante Hematopoyético y Terapia Celular) over the past 25 years. As a secondary objective, we analyzed the results of alloSCT from haploidentical donors. We performed a retrospective analysis of all patients who received an alloSCT in Spanish centers (n = 201) from September 1995 to August 2018. The 2-year overall survival (OS) and disease-free survival (DFS) were 65.5% and 58.2%, respectively. The univariate for OS and DFS showed statistically different hazard ratios for conditioning intensity, response pre-alloSCT, comorbidity index, donor/receptor cytomegalovirus status and Eastern Cooperative Oncology Group (ECOG) pre-alloSCT, but only a better ECOG pre-alloSCT remained significant in the multivariate analysis. There was an increased incidence of relapse in those patients who did not develop chronic graft-versus-host disease (GVHD) and an increased risk of death in those developing moderate to severe acute GVHD. The 1-year nonrelapse mortality was 21.9% and was mainly due to GVHD (30%) and bacterial infections (17%). When comparing unrelated donors with haploidentical donors, we found similar results in terms of OS and DFS. There was, however, a reduction of acute GVHD in the haploidentical group (P = .04) and trend to a reduction of chronic GVHD. In conclusion, alloSCT is the only curative option for most aggressive T cell neoplasias. Haploidentical donors offer similar results to related donors in terms of survival with a reduction of acute GVHD