Experimental verification of acuros XB in the presence of lung-equivalent heterogeneities

Acuros XB (AXB) is a deterministic algorithm that directly accounts for the effects of heterogeneities and improves the accuracy of photon dose calculations in radiotherapy. Nevertheless, the accuracy of AXB inside lung has not been yet fully examined by means of experimental measurements. The aim of this study was to evaluate the accuracy of AXB in the presence of lung using 7Li-based thermoluminescent dosimeters (TLD-700). Percentage depth-dose distributions (PDD) obtained by AXB on a slab water-equivalent phantom with a lung-equivalent heterogeneity were compared with the TLD-700 measurements for 6 MV and 18 MV photon beams and a set of field sizes ranging from View the MathML source2×2cm2to20×20cm2. Dose distributions obtained by the Anisotropic Analytical Algorithm (AAA) were also included in the comparison as a reference to a non-deterministic dose calculation algorithm. The agreement between AXB and the TLD results was kept within clinical tolerance levels (3%) for all beam configurations. On the contrary, AAA failed at correctly predicting the absorbed dose when the lateral electronic equilibrium was lost. AXB is capable of providing reliable dose estimations in the presence of lung and clearly outperforms AAA.Postprint (author's final draft

Relación entre los estilos de aprendizaje según el modelo de cerebro total y la inteligencia emocional

Durante las últimas décadas ha existido un profundo interés en la literatura por ahondar en los estilos de aprendizaje a fin de desarrollar las metodologías más eficaces en el proceso de enseñanza/aprendizaje. Sin embargo, pocos estudios han analizado la relación existente entre los estilos de aprendizaje según el Modelo de Cerebro Total y la Inteligencia Emocional en alumnos universitarios, siendo esta la propuesta implícita en este trabajo. Para la medición de los estilos de aprendizaje dominantes se utiliza una adaptación del instrumento de medida elaborado por Jiménez (2006). En relación a la medición de la Inteligencia Emocional se utiliza una adaptación simplificada de la versión castellana del Trait Meta-Mood Scale (TMMS-24; Fernández-Berrocal et al., 2004). Los estilos de aprendizaje basados en dominancias mixtas influyen de forma positiva en el desarrollo de la Inteligencia Emocional. Por otro lado, se observa una contribución más pronunciada de los estilos de aprendizaje asociados al hemisferio derecho en el desarrollo de la Inteligencia Emocional. Existen una necesidad de entrenar a los estudiantes en el uso de un estilo de aprendizaje que permita el uso de dominancias mixtas contribuyendo así al desarrollo de su IE.During the last decades there has been a deep interest in the literature to delve into learning styles in order to develop the most effective methodologies in the teaching / learning process. However, few studies have analyzed the relationship between learning styles according to the Total Brain Model and Emotional Intelligence in university students, which is the implicit proposal in this work. For the measurement of dominant learning styles an adaptation of the measurement instrument elaborated by Jiménez (2006) is used. In relation to the measurement of Emotional Intelligence, a simplified adaptation of the Spanish version of the Trait Meta-Mood Scale (TMMS-24; Fernández-Berrocal et al., 2004) is used. Learning styles based on mixed dominance have a positive influence on the development of Emotional Intelligence. On the other hand, there is a more pronounced contribution of learning styles associated with the right hemisphere in the development of Emotional Intelligence. There is a need to train students in the use of a learning style that allows the use of mixed dominance thus contributing to the development of their IE

Prevalence of Protein-Energy Wasting in Dialysis Patients Using a Practical Online Tool to Compare with Other Nutritional Scores: Results of the Nutrendial Study

Diàlisi; Puntuació d'inflamació de desnutrició; Valoració nutricionalDiálisis; Puntuación de inflamación de desnutrición; Valoración nutricionalDialysis; Malnutrition inflammation score; Nutritional assessmentThis cross-sectional study aims to explore the prevalence of protein-energy wasting (PEW) in dialysis patients in Catalonia, Spain, using a new and practical online tool which enables rapid calculation and comparison with other nutritional scores. Methods: A web tool (Nutrendial) was created to introduce different variables and automatically calculate PEW, Malnutrition inflammation Score (MIS) and Subjective Global Assessment (SGA) in 1389 patients (88% in haemodialysis (HD)), 12% in peritoneal dialysis (PD) from different regions of Catalonia. Results: A prevalence of 23.3% (26% HD, 10.2% PD) of PEW was found, with a mean MIS score of 6 and SGA score of C in 7% of the patients. ROC analysis showed MIS as the best nutritional score to diagnose PEW (AUC 0.85). Albumin delivered lower diagnostic precision (AUC 0.77) and sensitivity (66%). A cut off point of 7 (86% sensitivity and 75% specificity) for MIS and 3.7 mg/dL for albumin were found to predict the appearance of PEW in this population. SGA B or C showed an 87% sensitivity and 55% specificity to diagnose PEW. Very low nutritional intervention (14%) was recorded with this tool in patients with PEW. Conclusions: This new online tool facilitated the calculation of PEW, enabling different professionals-including nephrologists, dieticians and nurses-to efficiently obtain insights into the nutritional status of the Catalonian dialysis population and implement the required nutritional interventions. MIS is the score with more sensitivity to diagnose PEW

Evaluation of a Clinical Decision Support System for Dyslipidemia Treatment (HTE-DLPR) by QoE questionnaire

Introduction: Clinical decision support systems (CDSS) are computer systems designed to assist clinicians with patient-related decision making, such as diagnosis and treatment. CDSS have shown to improve both patient outcomes and cost of care.Methods: A multi-center observational prospective study was conducted. Ten physicians agreed to participate. Seventy-seven patients with high or very high cardiovascular risk were included. After using CDSS for dyslipidemia (HTE-DLPR) for a 3 months period, participants were asked to evaluate their experience with HTE-DLPR using a quality of experience questionnaire (QoE) tool for mHealth applications.Results: Total score on the QoE was 3.89 out of 5. The highest scores were received for precision, ease of use and content quality. The lowest scores were given to security, appearance and performance. Physicians were in strong agreement with the 1st HTEDLPR recommendation in 86.1% and the system’s use was described as comfortablein 85% of cases. Users positively evaluated the development of a new version of HTEDLPR in the future receiving a total score of 4.25 out of 5.Conclusions: A CDSS for dyslipidemia (HTE-DLP) has been positively evaluated by physicians using QoE questionnaire

The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2

Chemotherapy; Intratumoral senescent cellsQuimioterapia; Células senescentes intratumoralesQuimioteràpia; Cèl·lules senescents intratumoralsChemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the immune checkpoint inhibitor programmed cell death 1 ligand 2 (PD-L2) is highly upregulated upon induction of senescence in different types of cancer cells. PD-L2 is not required for cells to undergo senescence, but it is critical for senescent cells to evade the immune system and persist intratumorally. Indeed, after chemotherapy, PD-L2-deficient senescent cancer cells are rapidly eliminated and tumors do not produce the senescence-associated chemokines CXCL1 and CXCL2. Accordingly, PD-L2-deficient pancreatic tumors fail to recruit myeloid-derived suppressor cells and undergo regression driven by CD8 T cells after chemotherapy. Finally, antibody-mediated blockade of PD-L2 strongly synergizes with chemotherapy causing remission of mammary tumors in mice. The combination of chemotherapy with anti-PD-L2 provides a therapeutic strategy that exploits vulnerabilities arising from therapy-induced senescence.We thank the IRB Core Facilities (Functional Genomics Core, Biostatistics/Bioinformatics and Histopathology), the Parc Científic de Barcelona Animal Facility and the University of Barcelona/Centros Científicos y Tecnológicos de la Universidad de Barcelona Flow Cytometry Facility for their contribution to this work. J.A.L-D. was supported by the Spanish Ministry of Science through a Juan de la Cierva-Incorporación fellowship and by the Asociación Española Contra el Cáncer (AECC) through an AECC Investigador fellowship. I.M. was funded by an FPI fellowship from the Spanish Ministry of Science. Work in the laboratory of M.S. was funded by the IRB and ‘la Caixa’ Foundation, and by grants from the Spanish Ministry of Science cofunded by the European Regional Development Fund (ERDF) (no. SAF2017-82613-R), European Research Council (no. ERC-2014-AdG/669622) and Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement of Catalonia (Grup de Recerca consolidat 2017 SGR 282). J.L.K., T.T. and S.C. were supported by the National Institutes of Health (grant nos. R37AG13925, R33AG61456, R01AG072301, R01AG61414, P01AG62413 and UH3AG56933), the Connor Fund, Robert J. and Theresa W. Ryan and the Noaber Foundation. A.G. received funding from the Spanish Ministry of Science cofunded by the ERDF (no. RTC-2017-6123-1), from the Instituto de Salud Carlos III (no. MS15/00058) and from CAIMI-II (grant no. 53/2021) supported by the BBVA Foundation. A.G.-G. was the recipient of a PERIS grant (no. SLT017/20/000131) from the Generalitat de Catalunya. The laboratory of M. Abad received funding from the Spanish Ministry of Science and Innovation (nos. RTI2018-102046-B-I00A and RTC-2017-6123-1) and the AECC (no. PRYCO211023SERR). M.A. was the recipient of a Ramón y Cajal contract from the Spanish Ministry of Science and Innovation (no. RYC-2013-14747). O.B. was the recipient of a FPIAGAUR fellowship from Generalitat de Catalunya. Work in the laboratory of J.A. is supported by the Breast Cancer Research Foundation (no. BCRF-21-008), Instituto de Salud Carlos III (project refs. AC15/00062, CB16/12/00449 and PI19/01181) and the European Commission (under the Framework of the ERA-NET TRANSCAN-2 initiative cofinanced by FEDER), AECC and Fundació La Caixa (no. HR22-00776)

Invasive pulmonary aspergillosis in heart transplant recipients: Is mortality decreasing

Introduction: Infection remains a major complication among heart transplant (HT) recipients, causing approximately 20% of deaths in the first year after transplantation. In this population, Aspergillus spp. can have various clinical presentations including invasive pulmonary aspergillosis (IPA), with high mortality (53-78%). Objectives: To establish the characteristics of IPA infection in HT recipients and their outcomes in our center. Methods: Among 328 HTs performed in our center between 1998 and 2016, we identified five cases of IPA. Patient medical records were examined and clinical variables were extracted. Results: All cases were male, and mean age was 62 years. The most common indication for HT was non-ischemic dilated cardiomyopathy. Productive cough was reported as the main symptom. The radiological assessment was based on chest X-ray and chest computed tomography. The most commonly reported radiographic abnormality was multiple nodular opacities in both techniques. Bronchoscopy was performed in all patients and Aspergillus fumigatus was isolated in four cases on bronchoalveolar lavage culture. Treatment included amphotericin in four patients, subsequently changed to voriconazole in three, and posaconazole in one patient, with total treatment lasting an average of 12 months. Neutropenia was found in only one patient, renal failure was observed in two patients, and concurrent cytomegalovirus infection in three patients. All patients were alive after a mean follow-up of 18 months. Conclusions: IPA is a potentially lethal complication after HT. Early diagnosis and prompt initiation of aggressive treatment are the cornerstone of better survival

Validación del Cuestionario de Orientación a la Vida (OLQ-13) de Antonovsky en una muestra de estudiantes universitarios en Navarra

Fundamento. El sentido de coherencia interna (SOC), concepto central del modelo salutogénico descrito por Aaron Antonovsky, se ha empleado como predictor de medidas de salud percibida y objetiva, se relaciona fuerte y positivamente con comportamientos saludables, y se desarrolla principalmente en la juventud y en la época de estudiante. Los universitarios son un grupo de jóvenes diana para aplicar medidas promotoras de salud en función de su nivel SOC, siendo necesario comprobar la calidad de la medición de la escala. El objetivo es validar y estudiar las propiedades psicométricas de la escala SOC en los estudiantes de la Universidad de Navarra, y conocer su evolución temporal. Sujetos y método. Se analizaron los estudiantes de nuevo acceso de la Universidad de Navarra. Estudio de cohortes con seguimiento a los tres años. Los instrumentos utilizados fueron el cuestionario de orientación a la vida (OLQ-13), la Escala del Estrés Percibido (EEP) y el Índice de malestar. Se estudiaron la calidad de los datos y viabilidad, asunciones escalares, estabilidad temporal, fiabilidad, validez de criterio concomitante y clínica, y estructura factorial y análisis confirmatorio de los datos obtenidos. Se utilizaron los paquetes estadísticos SPSS v. 19 y Amos v.7. Resultados. La muestra ha sido de 508 estudiantes, 33,5% varones y el 65,9% mujeres. Fiabilidad alta (Alfa de Cronbach de 0,814). Adecuada validez convergente con la EEP. Inadecuada validez clínica. Análisis de componentes principales con tres factores que explican el 50,73% de la varianza. Conclusiones. Instrumento válido que permite proponerlo como herramienta para aplicar medidas promotoras de salud en jóvenes.Background. The sense of coherence (SOC), the central concept of the salutogenesis model described by Aaron Antonovsky, has been employed as a predictor of measures of perceived and objective health. It is strongly and positively related to healthy behaviour and is mainly developed while young and studying. University students are a target youth group for applying measures promoting health according to their SOC level; it is therefore necessary to check the quality of the scale’s measurement. The goal is to validate and study the psychometric properties of the SOC scale in students at the University of Navarre and determine their temporal evolution. Methods. Newly enrolled students at the University of Navarre were analysed. Cohort study with a 3 year follow-up. The instruments used were the Orientation to Life Questionnaire (OLQ-13), Perceived Stress Scale (PSS) and the Discomfort Index. The following were studied: the quality and viability of the data, scale assumptions, temporal stability, reliability, concurrent and clinical validity, as well as factorial structure and confirmatory analysis of the data obtained. SPSS v. 19 and Amos v.7 statistical software were used. Results. The study sample consisted of 508 students, 33.5% male and 65.9% female. High reliability (Cronbach Alpha 0.814). Adequate validity converging with the PSS. Inadequate clinical validity. Analysis of main components with three factors that explain 50.73% of the variation. Conclusions. A valid instrument that makes it possible to propose it as a tool for applying measures promoting health in young people

Functional identification of cis-regulatory long noncoding RNAs at controlled false discovery rates.

A key attribute of some long noncoding RNAs (lncRNAs) is their ability to regulate expression of neighbouring genes in cis. However, such 'cis-lncRNAs' are presently defined using ad hoc criteria that, we show, are prone to false-positive predictions. The resulting lack of cis-lncRNA catalogues hinders our understanding of their extent, characteristics and mechanisms. Here, we introduce TransCistor, a framework for defining and identifying cis-lncRNAs based on enrichment of targets amongst proximal genes. TransCistor's simple and conservative statistical models are compatible with functionally defined target gene maps generated by existing and future technologies. Using transcriptome-wide perturbation experiments for 268 human and 134 mouse lncRNAs, we provide the first large-scale survey of cis-lncRNAs. Known cis-lncRNAs are correctly identified, including XIST, LINC00240 and UMLILO, and predictions are consistent across analysis methods, perturbation types and independent experiments. We detect cis-activity in a minority of lncRNAs, primarily involving activators over repressors. Cis-lncRNAs are detected by both RNA interference and antisense oligonucleotide perturbations. Mechanistically, cis-lncRNA transcripts are observed to physically associate with their target genes and are weakly enriched with enhancer elements. In summary, TransCistor establishes a quantitative foundation for cis-lncRNAs, opening a path to elucidating their molecular mechanisms and biological significance

Safety of Drugs Used during the First Wave of COVID-19: A Hospital-Registry-Based Study

COVID-19; Adverse drug reactions; HydroxychloroquineCOVID-19; Reaccions adverses als medicaments; HidroxicloroquinaCOVID-19; Reacciones adversas a los medicamentos; HidroxicloroquinaThe emergency of the coronavirus disease 2019 (COVID-19) pandemic led to the off-label use of drugs without data on their toxicity profiles in patients with COVID-19, or on their concomitant use. Patients included in the COVID-19 Patient Registry of a tertiary hospital during the first wave were analyzed to evaluate the adverse drug reactions (ADRs) with the selected treatments. Twenty-one percent of patients (197 out of 933) had at least one ADR, with a total of 240 ADRs. Patients with ADRs were more commonly treated with multiple drugs for COVID-19 infection than patients without ADRs (p < 0.001). They were younger (median 62 years vs. 70.1 years; p < 0.001) and took less medication regularly (69.5% vs. 75.7%; p = 0.031). The most frequent ADRs were gastrointestinal (67.1%), hepatobiliary (10.8%), and cardiac disorders (3.3%). Drugs more frequently involved included lopinavir/ritonavir (82.2%), hydroxychloroquine (72.1%), and azithromycin (66.5%). Although most ADRs recovered without sequelae, fatal cases were described, even though the role of the disease could not be completely ruled out. In similar situations, efforts should be made to use the drugs in the context of clinical trials, and to limit off-label use to those drugs with a better benefit/risk profile in specific situations and for patients at high risk of poor disease prognosis

Case report: Diffuse cutaneous leishmaniasis by Leishmania infantum in a patient undergoing immunosuppressive therapy: risk status in an endemic Mediterranean area.

This case report highlights the risk of severe cutaneous leishmaniasis (CL) by Leishmania infantum in patients undergoing immunosuppressant therapy who either live in an endemic area or are visiting in the transmission season. The case patient, resident in Majorca (Balearic Islands), presented 12 disseminated erythematous skin lesions, 1 to 6 cm in diameter, located on the scalp, cheek, umbilical region and lower extremities eight years after undergoing anti-TNF therapy. Parasite presence in peripheral blood and high levels of specific antibodies were also observed, indicating a possible risk of CL shifting toward a visceral infection (VL). However, once CL was diagnosed, anti-TNF therapy was discontinued and liposomal amphotericin B was administered, resulting in a complete healing of lesions, no Leishmania DNA detection in blood and an important serological decrease in antibodies. The lack of data on the supposed epidemiological association between leishmaniasis and immunosuppressive therapy highlights the importance of implementing surveillance systems in endemic areas. No obvious relationship was found based on the data provided by the Balearic Islands Epidemiological System, in contrast with data reported in nearby endemic areas. This indicates that, if the suspected association is to be clarified, greater efforts are needed to report information about concomitant diseases and therapies in leishmaniasis patients