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In recent years, the use of artificial intelligence (AI) has significantly increased in the field of workplace well-being. This study systematically reviews the most common applications of AI in this context, covering literature published between 2018 and 2023, and evaluates both its current and potential impact. The research involved a comprehensive search in the Scopus and Web of Science databases, following PRISMA guidelines, resulting in 31 articles that met the inclusion criteria. The qualitative synthesis reveals that AI is being utilized in areas such as mental health monitoring, emotional support, personalized well-being programs, identification of psychosocial risk factors, and training and development. This review contributes to the existing literature by offering a detailed categorization of AI applications in workplace well-being, and it highlights the practical utility of AI in enhancing employee mental health and overall well-being. The findings suggest that AI has the potential to revolutionize the management of workplace well-being, providing actionable insights for both researchers and practitioners. Recommendations for future research are also discussed.

Abstract Background Carboplatin and paclitaxel (CP) have been the standard of care for advanced/recurrent endometrial cancer (EC) for many years. However, this chemotherapy combination shows limited efficacy and recurrences often occur in less than 12 months. ABTL0812 is a novel drug that selectively kill cancer cells by cytotoxic autophagy and has shown anticancer efficacy in preclinical models of EC in combination with CP. Methods ENDOLUNG was an open-label, phase 1/2 clinical trial designed to determine the safety and efficacy of Ibrilatazar (ABTL0812) with CP in patients with advanced/recurrent EC and non-irradiable stage III and IV squamous non-small cell lung cancer (sq-NSCLC). The phase 1 part consisted of a 3 + 3 de-escalation design followed by an expansion cohort with 12 patients. The primary endpoint was safety. ABTL0812 starting dose was 1300 mg tid combined with carboplatin at area under the curve (AUC) 5 and paclitaxel at 175 mg/m2 both administered every 21 days for up to 8 cycles. The phase 2 part included a total of 51 patients. The primary endpoint was overall response rate (ORR) and the secondary endpoints included duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results During the phase 1 only one dose limiting toxicity (DLT), a grade 4 neutropenia, was observed in 1 out of 6 patients, thus no de-escalation was applied. One additional DLT, a grade 3 febrile neutropenia, was observed in the expansion cohort, thus the recommended phase 2 dose (RP2D) for ABTL0812 was established at 1300 mg tid. Most frequent hematological adverse events (AE) of the combination were neutropenia (52.9%), anemia (37.3%) and thrombocytopenia (19.6%). Nausea (66.7%), asthenia (66.7%), diarrhea (54.9%) and vomiting (54.9%) were the most frequent non-hematological adverse events (AEs). The combination of ABTL0812 plus CP showed an ORR of 65.8% (13.2% complete response and 52.6% partial response) with a median DOR of 7.4 months (95% CI: 6.3–10.8 months). Median PFS was 9.8 months (95% CI: 6.6–10.6) and median OS 23.6 months (95% CI 6.4-ND). Pharmacokinetic parameters were compatible with target engagement observed in preclinical studies, and blood pharmacodynamic biomarkers indicated sustained target regulation during, at least, 28 days after starting the treatment. Conclusions This study suggests that the combination of ABTL0812 with CP is safe and feasible with an encouraging activity in patients with advanced/recurrent EC. Our data warrant further confirmation in prospective randomized trials. Trial registration EU Clinical Trial Register, EudraCT number 2016-001352-21 and National Clinical Trials Number, NCT03366480. Registration on 19 September 2016.

The utilisation of bio-based materials has significantly increased in recent years, driven by a growing awareness of environmentally friendly alternatives in the construction industry. This study introduces innovative natural fibre pultruded profiles for load-bearing applications in structural systems. By employing pultrusion technology with flax fibres and customised plant-based matrix, linear and unidirectional biocomposite profiles were developed. These profiles were used in the creation of LightPRO Shell, an active-bending structure combining biocomposite profiles with a membrane outer skin, demonstrating their mechanical properties and suitability for such applications. The paper focuses on the geometrical and structural design development of the structure employing computational design tools for optimisation, ensuring design parameters and performance requirements were met. The final structure, a 10-m span doubly curved gridshell, features a continuous perimeter beam and consists of 44 profiles ranging from 6 to 12.5 m, showcasing the potential of natural fibre biocomposites as sustainable alternatives in construction.

Introducción: El escaso control y seguimiento que se hace, en ocasiones, durante la dispensación de medicamentos que no necesitan prescripción, unido al aumento de su adquisición por internet, genera una preocupación importante acerca del uso que se esté haciendo de ellos. El objetivo de este estudio fue analizar el uso actual y real de los medicamentos que no requieren de prescripción para su adquisición en la farmacia comunitaria. Método: se llevó a cabo un estudio observacional de tipo transversal en pacientes que acudían a la farmacia para retirar un medicamento que no necesita prescripción. Se elaboró un cuestionario en el que se analizaron variables demográficas, datos de los medicamentos dispensados, el conocimiento que tiene el paciente sobre el medicamento y los problemas relacionados. Resultados: La mayoría de los participantes fueron mujeres, con una edad comprendida entre 31-45 años. Los medicamentos más dispensados fueron analgésicos/antinflamatorios, analgésicos/antipiréticos, antihistamínicos, expectorantes, antigripales, laxantes, descongestivos y fármacos para el insomnio. El 71% de los encuestados afirmó tener información sobre el medicamento dispensado, habiendo sido proporcionada en un 50% de los casos por un farmacéutico. No se observaron errores de indicación ni efectos adversos, pero en un 18% de los casos la duración del tratamiento fue superior al tiempo recomendado. Conclusiones: Este estudio muestra un uso correcto de los medicamentos que no necesitan prescripción en la mayor parte de la muestra de estudio como consecuencia, al menos en parte, del alto grado de conocimiento de los pacientes acerca de su tratamiento, proporcionado mayoritariamente por los farmacéuticos.

Cornelia de Lange syndrome (CdLS, OMIM #122470, #300590, #300882, #610759, and #614701) is a rare congenital disorder that affects the development of multiple organs and is characterized by physical abnormalities and cognitive and behavioral disabilities. Its molecular basis is mainly based on alterations in genes encoding structural and regulatory proteins related to the cohesin complex. Moreover, other transcriptional regulatory factors have been linked to this syndrome. However, additional causative genes are still unknown, since many patients still lack a molecular diagnosis. Herein, we describe a case with multiple affected family members presenting with an intragenic duplication in the AFF2 gene. The direct tandem intragenic duplication of exons 10, 11 and 12 was detected through high-resolution array Comparative Genomic Hybridization and next-generation sequencing technologies. Confirming the X-linked inheritance pattern, the duplication was found in the patient, his mother and his maternal aunt affected (dizygotic twins). Targeted sequencing with Oxford Nanopore Technologies revealed an aberrant transcript which is predominantly expressed in the patient and his aunt. Along with these results, a significant reduction in AFF2 gene expression levels was detected in these two individuals. Clinically both subjects exhibit a classic CdLS phenotype, whereas the mother is mostly unaffected. Consistent with the phenotypical differences observed between the mother and the aunt, there is a marked difference in X-inactivation patterns skewing. Given the crucial role of AFF2 in transcriptional regulation, it is not surprising that AFF2 variants can give rise to CdLS phenotypes. Therefore, the AFF2 gene should be considered for the molecular diagnosis of this syndrome.

ABSTRACT Aim To implement shared decision‐making (SDM) through a patient decision aid (PtDA) for the initiation of palliative care (PC) in end‐of‐life (EOL) cancer patients. Methodology A comprehensive Scoping Review was conducted on SDM in PubMed, CINAHL and PsycInfo. An evidence‐based implementation of PtDAs was created using the Joanna Briggs Institute framework, which followed rigorous pillars: (1) context, (2) facilitation and (3) evaluation. Results Fifteen studies were identified and categorised into (1) Implementation characteristics and (2) Strategies for implementing SDM in terminally ill cancer patients. SDM should consider the decision‐making location, optimal timing, participants and decision type. Strategies include professional training, PtDAs and implementation programmes. A PtDA implementation protocol in video format for deciding to initiate PC is proposed, following International Patient Decision Aid Standards (IPDAS) and Clinical Practice Guidelines (CPG). Conclusions SDM implementation should be guided by evidence‐based methodological models justifying and structuring its execution, especially in complex and interdisciplinary contexts. National or international frameworks facilitate the adoption of health innovations, such as PtDAs, benefiting patients and improving their usage. Practice Implications SDM is not just a concept but an important approach to the Care of cancer patients at EOL, enhancing patient satisfaction and improving care quality. The success and sustainability of SDM hinge on the fundamental aspects of staff training, interdisciplinary collaboration and ongoing evaluation. The lack of specific aid in Spanish underscores the immediate need for local development. Further research is needed in this area, as most reviewed studies did not measure SDM effectiveness in diverse hospital settings. Patient or Public Contribution This proposal was developed based on the experience and input of the nursing staff from the healthcare service where it is intended to be implemented.

IntroductionThe 2030 Agenda and the principles of Corporate Social Responsibility (CSR) define companies and public authorities as agents for social change sharing objectives such as promotion of health, personal development and social engagement, among others. Care homes for the older adult are an example of organizations that should be particularly aware of these priorities. Since they work with vulnerable groups, collaboration with the families is essential in ensuring residents' wellbeing.MethodsThe objective of this study is to analyse the factors that condition the satisfaction of relatives of residents in a care home for the older adult located in a rural environment in the province of Huesca (Spain).Results and discussionThe 51 relatives interviewed rated the following points very positively: location and accessibility, food service, medical resources, communication with the staff and management team. A high percentage, however, did not know about the channels for volunteer work and institutional involvement. Some psychosocial indicators related to families' interaction and communication with the staff and their potential involvement in the dynamics of the institution have considerable weight in how they explain their satisfaction. These results may lead to new lines of research and intervention that contribute to improving the quality of this type of resources and their commitment to the Sustainable Development Goals (SDGs) and social responsibility.

This study embarks on the synthesis of activated carbon (AC) from cashew nut shells using a potassium carbonate (K2CO3) activation process, with a specific focus on its practical application in high-pressure gas adsorption. Among the synthesized samples, MCAK85 emerged as the most efficient, demonstrating a specific surface area of 1693 m2/g and total and micropore volumes of 0.839 cm3/g and 0.641 cm3/g, respectively. Importantly, this bioorganic activated carbon exhibited high sorption capacities for CO2 and CH4, with uptake values of 11.0 mmol/g and 5.5 mmol/g at 10 bar at 25°C, and a CO2/CH4 selectivity range between 9.1 and 1.8. A comprehensive range of characterization techniques were employed to analyze the structural and chemical properties of the synthesized AC, providing valuable insights into the functional groups and molecular structure. The morphology of the AC was examined using SEM, while the point of zero charge was determined to understand the surface charge characteristics. Additionally, TGA was utilized to assess the thermal stability and composition of the AC. This study underscores the potential of utilizing agricultural waste, specifically cashew nut shells, in the creation of effective materials for gas storage and purification applications. The high-pressure adsorption capacity of the produced AC, coupled with its sustainable and eco-friendly nature, underscores its suitability for environmental and industrial applications, particularly in areas focusing on greenhouse gas capture and air purification, thereby inspiring further research and development in this field.

Efficiency of expanded genomic profiling (EGP) programmes in terms of final inclusion of patients in genomically matched therapies is still unknown. Fit patients with advanced and refractory colorectal cancer (CRC) were selected for an EGP programme. Next‐generation sequencing (NGS) analysis from formalin‐fixed paraffin‐embedded tumour samples was performed. The purpose was to describe the prevalence of genomic alterations defined by the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT), as well as the percentage of patients finally included in genomically guided clinical trials. In total, 187 patients were recruited. Mutational profile was obtained in 177 patients (10 patients were failure due to insufficient tumour sample), copy number alterations in 41 patients and fusions in 31 patients. ESCAT‐defined alterations were detected in 28.8% of the intention‐to‐analyse population. BRAF V600E was clustered in ESCAT I, with a prevalence of 3.7%, KRAS G12C and ERBB2 amplification were clustered in ESCAT II, whose prevalence was 4.2% and 1.6%, respectively. Most alterations were classified in ESCAT III (mutations in ERBB2, PIK3CA or FGFR genes and MET amplification) and IV (mutations in BRAF non‐V600E, ERBB3, FBXW7, NOTCH, RNF43), with a single prevalence under 5%, except for PIK3CA mutation (9%). The final rate of inclusion into genomically guided clinical trials was 2.7%, including therapies targeting BRAF V600E or RNF43 mutations in two patients each, and ERBB2 mutation in one patient. In conclusion, EGP programmes in patients with advanced CRC are feasible and identify a subset of patients with potentially druggable genomic alterations. However, further efforts must be made to increase the rate of patients treated with genomically guided therapies.

Introducción: Los anticoagulantes orales directos (ACOD) han demostrado ser una opción de tratamiento más segura, eficaz y cómoda, pero significativamente más cara que los antagonistas de vitamina K (AVK). El objetivo de este trabajo fue analizar el perfil de uso actual y la seguridad de los anticoagulantes orales (ACOs) en pacientes de Farmacia Comunitaria. Método: Se realizó un estudio observacional transversal en pacientes de tres Farmacias de la Comunidad Autónoma de Andalucía. Se elaboró un cuestionario que incluía diversas variables sociodemográficas, datos relativos al tratamiento de los encuestados, al grado de conocimiento sobre su tratamiento y a la seguridad de este. Resultados: En el estudio participaron hombres y mujeres en proporción similar (49% vs 51%), siendo más del 50% de los participantes mayores de 70 años. La mayoría de los pacientes se encontraban en tratamiento con ACOD (80%). Sin embargo, al disgregar los datos por indicaciones se detectó un porcentaje superior de pacientes en tratamiento con ACOD para fibrilación auricular no valvular (FANV; 92%), pero inferior en pacientes con prótesis valvulares (40%). La incidencia de efectos adversos fue menor en los pacientes tratados con ACOD. Aunque el 89% de los pacientes afirmaron haber recibido información acerca de su tratamiento, esta sólo fue proporcionada por un farmacéutico en el 13% de los encuestados. Conclusiones: Este estudio demuestra un cambio en el perfil de prescripción de los ACOs en favor de los ACOD, lo que supone una mejora en la seguridad y comodidad del paciente anticoagulado y, en consecuencia, de su calidad de vida.

IntroductionSo far, both for the general and older population, research on human values and wellbeing mainly shows correlational associations but does not inquire about the direction of this relationship. This is also true for values and civic participation. Therefore, our objective is to identify the directional association between civic participation and Schwartz values, and between values and wellbeing, among older Europeans.MethodsA pseudo-panel was created from the cross-sectional data of the European Social Survey (ESS 2002-2018), controlling for gender, age-group, country and level of studies (n = 3926). The data analysis was performed using a cross-lagged model, applying both random-effects and fixed-effects models.ResultsOn the one hand, the relationship between participation and values is bidirectional, but the effect of civic participation on values is more significant since participating stimulates the development of certain values. On the other hand, although the relationship between values and wellbeing is also bidirectional, the effect of wellbeing on values is stronger since a given level of wellbeing favors the development of particular values.DiscussionWe conclude that civic participation should be promoted within the older population since it directly increases wellbeing, and moreover reinforces those (Growth-oriented) values that positively influence the health, happiness and life satisfaction of older people.

Las normas internacionales, como la Convención sobre los Derechos de las Personas con Discapacidad, suponen un avance hacia la equidad. Asimismo, im­plican tanto un incremento de la legislación nacional y autonómica, como una mayor complejidad institucional, para hacer efectivos estos derechos. Por ello, queremos conocer cómo se ha implementado el derecho a la accesibilidad univer­sal en la legislación. Se realizó un análisis de contenido de 36 normas relaciona­das con la discapacidad y la dependencia en Aragón. Finalmente, se detectó que, a pesar de ciertos avances, la adaptación de la normativa no se ha consolidado, afectando al reconocimiento de derechos de las personas con discapacidad, espe­cialmente de las más jóvenes y aquellas con grandes necesidades de apoyo.

Recent studies have demonstrated the value that the Internet and web applications bring to businesses. Among other tools are those that enable the analysis and monitoring of searches, such as Google Trends, which is currently used by the fashion industry to guide experiential practices in a context of augmented reality and/or virtual reality, and even to predict purchasing behaviours through the metaverse. Data from this tool provide insight into fashion consumer search patterns. Understanding and managing this digital tool is an essential factor in rethinking businesses’ marketing strategies. The aim of this study is to analyse online user search behaviour by analysing and monitoring the terms “metaverse” and “fashion” on Google Trends. A quantitative descriptive cross-sectional method was employed. The results show that there is growing consumer interest in both concepts on the Internet, despite the lack of homogeneity in the behaviour of the five Google search tools.

The dynamics of fibroadipogenic progenitors (FAPs) after muscle injury are crucial to ensure efficient regeneration. Here the authors show that a pool of FAPs originates from adipose tissue and are necessary for effective muscle regeneration.

Abstract Respiratory viral infections (RVIs) are frequent in preterm infants possibly inducing long-term impact on respiratory morbidity. Immune response and respiratory barriers are key defense elements against viral insults in premature infants admitted to Neonatal Intensive Care Units (NICUs). Our main goals were to describe the local immune response in respiratory secretions of preterm infants with RVIs during NICU admission and to evaluate the expression and synthesis of lung barrier regulators, both in respiratory samples and in vitro models. Samples from preterm infants that went on to develop RVIs had lower filaggrin gene and protein levels at a cellular level were compared to never-infected neonates (controls). Filaggrin, MIP-1α/CCL3 and MCP-1 levels were higher in pre-infection supernatants compared to controls. Filaggrin, HIF-1α, VEGF, RANTES/CCL5, IL-17A, IL-1β, MIP-1α and MIP-1β/CCL5 levels were higher during and after infection. ROC curve and logistic regression analysis shows that these molecules could be used as infection risk biomarkers. Small airway epithelial cells stimulated by poly:IC presented reduced filaggrin gene expression and increased levels in supernatant. We conclude that filaggrin gene and protein dysregulation is a risk factor of RVI in newborns admitted at the NICU.

Long-term potentiation (LTP) induced by theta-burst stimulation (TBS) undergoes postweaning developmental changes partially linked to GABAergic circuit maturation. Endogenous vasoactive intestinal peptide (VIP) acting on its VPAC1 receptor strongly influences LTP induced by theta-burst stimulation (TBS), an effect dependent on GABAergic transmission. Although VPAC1 receptor levels are developmentally regulated during embryogenesis, their variation along postweaning development is unknown, as is the VPAC1 modulation of LTP or its relation to hippocampal GABAergic circuit maturation. As such, we investigated how VPAC1 modulation of LTP adjusts from weaning to adulthood along with GABAergic circuit maturation. As described, LTP induced by mild TBS (5 bursts, 4 pulses delivered at 100 Hz) was increasingly greater from weaning to adulthood. The influence of the VPAC1 receptor antagonist PG 97-269 (100 nM) on TBS-induced LTP was much larger in juvenile (3-week-old) than in young adult (6–7-week-old) or adult (12-week-old) rats. This effect was not associated with a developmental decrease in synaptic VPAC1 receptor levels. However, an increase in pre and post-synaptic GABAergic synaptic markers suggests an increase in the number of GABAergic synaptic contacts that is more prominent than the one observed in glutamatergic connections during this period. Conversely, endogenous VPAC2 receptor activation did not significantly influence TBS-induced LTP. VPAC2 receptor levels enhance pronouncedly during postweaning development, but not at synaptic sites. Given the involvement of VIP interneurons in several aspects of hippocampal-dependent learning, neurodevelopmental disorders, and epilepsy, this could provide important insights into the role of VIP modulation of hippocampal synaptic plasticity during normal and altered brain development potentially contributing to epileptogenesis.

(1) Background: Eosinophilia has traditionally been linked to eosinophilic asthma, for which it is the gold-standard prognostic biomarker. However, the association between eosinophilia and the presence of other diseases and comorbidities is yet unclear. (2) Methods: For this retrospective study, we reviewed the electronic medical records of 49,909 subjects with blood eosinophilia to gather data on the presence of asthma, COPD, sleep apnea, tuberculosis, dyslipidemia, hypertension, and other cardiovascular diseases and severe CRSwNP among these subjects. Demographic features including age, sex, and smoking habits were collected, as well as the number of hospitalizations and emergency department visits. T-tests, ANOVA, Fisher test, and logistic regression models were used. (3) Results: For all age groups studied, eosinophilia was significantly more prevalent among asthmatic subjects than nonasthmatics, especially in patients also presenting CRSwNP, hypertension, and dyslipidemia. The likelihood of developing asthma, COPD, and CRSwNP, and hospitalization, was increased when BEC was above 600 eosinophils/μL. The association between asthma, CRSwNP, and BEC was corroborated by multiple logistic regressions models. (4) Conclusions: We demonstrated the association of having over 600 blood eosinophils/μL with a higher number of hospitalizations and comorbidities (CRSwNP and COPD), which proves that BEC is a highly useful parameter to consider in subjects who present blood eosinophilia.

Context: Cardiovascular disease (CVD) is one of the leading causes of morbidity and premature mortality across Spain. According to the World Health Organization (WHO), 80% of these premature deaths are preventable by controlling cardiovascular risk factors. Community pharmacists (CPs) are well situated to provide professional educational advice and implement interventions for the reduction of CVD. Aims: To analyze the impact of community pharmacists’ interventions on cardiovascular risk factors and CVD prevention in Spain. Methods: Two independent reviewers searched PubMed/MEDLINE; SCOPUS; Cochrane Central Register of Controlled Trials (CENTRAL); EMBASE; National Regional Database (LILACS BIREME); CINAHL; Pharm-line; ClinicalTrials.gov; ISRCTN; DOAJ (Directory of Open Access Journals), International Pharmaceutical Abstracts (IPA), the Spanish National Research Council (CSIC), WHO ICTRP, SCIELO and opengrey.eu and Google Scholar and considered research published between January 2000 and August 2020. The Cochrane risk of bias (RoB2) and ROBINS-I tools were used to evaluate the randomised/quasi-randomised controlled trials and the nonrandomised studies of interventions (NRSI), respectively. Results: The database search resulted in 457 items from which fourteen met our inclusion criteria. A total of 4,250 participants, aged 18 to 85, were included in the pharmacists’ interventions offered in the form of medication reconciliation and patient education. Studies showed a beneficial effect of CPs intervention on medication reconciliation and the control of hypertension, dyslipidaemias, obesity, and diabetes. However, evidence on smoking cessation and alcohol advice services is meager. Conclusions: This study suggests that community pharmacist counselling and personalized intervention could contribute to improving cardiovascular outcomes in Spain.

La asociación española de Mujeres en la Industria de la Animación MIA, nace en 2018 con el objetivo de visibilizar el trabajo de las mujeres en la animación y de cambiar la situación actual de desigualdad que hay en el sector. En este artículo se presentan los factores que motivan la creación de la asociación y se presentan las acciones realizadas en sus casi cinco años de trayectoria, particularmente el Informe MIA, el cual recoge los datos de la representación femenina en la industria española de la animación, y el programa de mentoría MIANIMA, cuyo fin es impulsar proyectos de mujeres líderes de España y Latinoamérica.

Abstract Endothelial adenosine monophosphate-activated protein kinase (AMPK) plays a critical role in the regulation of vascular tone through stimulating nitric oxide (NO) release in endothelial cells. Since obesity leads to endothelial dysfunction and AMPK dysregulation, AMPK activation might be an important strategy to restore vascular function in cardiometabolic alterations. Here, we report the identification of a novel AMPK modulator, the indolic derivative IND6, which shows affinity for AMPKα1β1γ1, the primary AMPK isoform in human EA.Hy926 endothelial cells. IND6 shows inhibitory action of the enzymatic activity in vitro, but increases the levels of p-Thr174AMPK, p-Ser1177eNOS and p-Ser79ACC in EA.Hy926. This paradoxical finding might be explained by the ability of IND6 to act as a mixed-type inhibitor, but also to promote the enzyme activation by adopting two distinct binding modes at the ADaM site. Moreover, functional assays reveal that IND6 increased the eNOS-dependent production of NO and elicited a concentration-dependent vasodilation of endothelium-intact rat aorta due to AMPK and eNOS activation, demonstrating a functional activation of the AMPK–eNOS–NO endothelial pathway. This kinase inhibition profile, combined with the paradoxical AMPK activation in cells and arteries, suggests that these new chemical entities may constitute a valuable starting point for the development of new AMPK modulators with therapeutic potential for the treatment of vascular complications associated with obesity.

This paper presents a single-frequency reflective-mode phase-variation microwave sensor devoted to the dielectric characterization of materials. The device is implemented in coplanar waveguide (CPW) technology and consists of two parts: (i) the sensing region, a step-impedance resonator (SIR) as termination of a CPW transmission line, and (ii) the design region, a cascade of high/low impedance quarter-wavelength inverters, used to boost up the sensitivity. By placing the so-called material under test (MUT) on top of the sensing region, the capacitance of the SIR is altered due to the effects of the dielectric constant of the MUT. This modifies the phase of the reflection coefficient seen from the input port, the output variable. From a circuit analysis, it is demonstrated that the sensitivity for small perturbations in the vicinity of the dielectric constant of a reference (REF) material can be optimized by setting the operation frequency of the sensor to the resonance frequency of the SIR loaded with such REF material. The maximum sensitivity in one of the reported sensors is as high as 66.5°, and the main figure of merit, defined as the ratio between the maximum sensitivity and the area of the sensing region expressed in terms of the squared guided wavelength, is $\text {FoM} = 3643^{\circ }/\lambda ^{2}$ . Such figure of merit represents a significant improvement as compared to the one of the equivalent sensor implemented by means of an open-ended quarter-wavelength sensing line. Such equivalence between the semi-lumped element (i.e., SIR-based) sensor and the fully distributed counterpart is also analyzed in the paper.

En este artículo se presenta la evaluación eudaimonista como una articulación entre el agente y los objetos del mundo. Sostendremos que, gracias a esta noción, la teoría de las emociones de Nussbaum es adecuada para dar cuenta de la función adaptativa de las emociones, por lo que las teorías no cognitivas no resultarían superiores en este aspecto. Esta noción serviría, asimismo, para no dejar de lado los aspectos cognitivos de la emoción. Veremos cómo las ideas de Nussbaum se basan en las de las teorías evaluativas provenientes de la psicología, para después desplegar su propuesta en detalle. En la exposición, también trataremos otras cuestiones, entre ellas, la racionalidad de las emociones, la relación entre éstas y el florecimiento humano, o la vinculación de las mismas con nuestra condición vulnerable.

Abstract Clinical management of endometrial cancer (EC) is handicapped by the limited availability of second line treatments and bona fide molecular biomarkers to predict recurrence. These limitations have hampered the treatment of these patients, whose survival rates have not improved over the last four decades. The advent of coordinated studies such as The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA_UCEC) has partially solved this issue, but the lack of proper experimental systems still represents a bottleneck that precludes translational studies from successful clinical testing in EC patients. Within this context, the first study reporting the generation of a collection of endometrioid‐EC‐patient‐derived orthoxenograft (PDOX) mouse models is presented that is believed to overcome these experimental constraints and pave the way toward state‐of‐the‐art precision medicine in EC. The collection of primary tumors and derived PDOXs is characterized through an integrative approach based on transcriptomics, mutational profiles, and morphological analysis; and it is demonstrated that EC tumors engrafted in the mouse uterus retain the main molecular and morphological features from analogous tumor donors. Finally, the molecular properties of these tumors are harnessed to assess the therapeutic potential of trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor with growing interest in EC, using patient‐derived organotypic multicellular tumor spheroids and in vivo experiments.

Esta investigación determina cuál es el papel que juegan las redes sociales en la organización del movimiento social durante la "Revolución de los Frijoleros" en Guatemala en 2020. A través de un enfoque mixto que combina el análisis de contenido y el análisis crítico del discurso, se analizan cuatro perfiles representativos en la conformación del movimiento en Facebook y Twitter. Los resultados apuntan a que ambas plataformas tienen efectos positivos en la movilización ciudadana, conformándose como espacios de disidencia, de articulación del movimiento y de organización de acciones-protesta.

Context: Spain was at the epicenter of the pandemic. Health centers across Spanish territory were not able to respond to non-emergency enquiries, leaving community pharmacies as the first point of patient’s contact. Aims: To investigate the impact of COVID-19 on the mental and physical health of community pharmacy teams across Spain. Methods: A cross-sectional observational study was performed with community pharmacy professionals throughout Spain. A questionnaire designed by our collaborator from the United Kingdom was adapted to the Spanish population and launched between October 2020 and February 2021. Results: A total of 98 participants responded to the questionnaire. The survey showed an 80% increase in workload. The pandemic had negatively impacted the well-being of community pharmacy professionals. The survey indicated a national shortage of medicines and personal protective equipment across Spain, particularly during the first peak. To adapt to this pandora’s box of COVID-19, 96% of the pharmacies changed their settings to improve patients and staff’s safety. Most of these changes were self-financed by the pharmacy owner. The pharmacists kept up to date with information released from the pharmacists’ college, General Pharmaceutical Council and the Spanish Society of Community Pharmacists. The Public domain purchased more (79%) immune booster supplements. Conclusions: Community pharmacy professionals have faced tremendous mental, physical and professional pressure in providing adequate personal protective equipment and medication supply to their communities. They have provided more pharmaceutical services during the crisis, although they have not been recognized as essential workers by the healthcare system.

Brazilian education faces difficulties relating to performance and illness, suggesting that the characteristics of the work can affect both variables. This study aims to describe the work characteristics that increase the odds of having happy–productive patterns in education workers. A total of 4,598 employees of the Secretariat of Education of the Federal District (SEEDF) participated in the research, answering questionnaires about work design (Brazilian version, with 18 factors), wellbeing (containing three factors), and performance. The results showed that task, social, and contextual characteristics increase the probability of being in the happy–productive pattern, and specifically, Social Support, Feedback from Others, Task Significance, Task Identity, and Autonomy, in this order, should be considered for intervention purposes.

The complex situation that global society is facing as a result of COVID-19 has highlighted the importance of companies committing to the principles of social responsibility. Among the internal initiatives, those related to the health of workers are, obviously, highly topical. The objective of our research is to provide concise knowledge of the relationship between workplace health promotion (WHP) and corporate social responsibility (CSR) so that the relevant specialized research was gathered in a single document that lays the foundations of its applicability. A systematic review, following the PRISMA method, has been carried out. Twenty-seven articles have been selected from the main scientific databases. Their qualitative analysis concludes that CSR and WHP are linked, have beneficial reciprocal effects, need committed leadership respectful of autonomy and voluntariness, and require the establishment of specific goals within the framework of the organizations' sustainability policies. Future studies should establish the impact of the pandemic on these aspects.

Abstract Postzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families.

Ultimate advances in genetic technologies have permitted the detection of transmitted cases of congenital diseases due to parental gonadosomatic mosaicism. Regarding Cornelia de Lange syndrome (CdLS), up to date, only a few cases are known to follow this inheritance pattern. However, the high prevalence of somatic mosaicism recently reported in this syndrome (∼13%), together with the disparity observed in tissue distribution of the causal variant, suggests that its prevalence in this disorder could be underestimated. Here, we report a new case of parental gonadosomatic mosaicism in SMC1A gene that causes inherited CdLS, in which the mother of the patient carries the causative variant in very low allele frequencies in buccal swab and blood. While the affected child presents with typical CdLS phenotype, his mother does not show any clinical manifestations. As regards SMC1A, the difficulty of clinical identification of carrier females has been already recognized, as well as the gender differences observed in CdLS expressivity when the causal variant is found in this gene. Currently, the use of DNA deep-sequencing techniques is highly recommended when it comes to molecular diagnosis of patients, as well as in co-segregation studies. These enable us to uncover gonadosomatic mosaic events in asymptomatic or oligosymptomatic parents that had been overlooked so far, which might have great implications regarding genetic counseling for recurrence risk.

Membership in voluntary organizations is associated with individual and social benefits. Due to the negative consequences of the global pandemic on older people, and the governmental challenges posed by population aging, voluntary membership is of great importance to society. To effectively promote volunteering among older people, it is necessary to understand the determinants of voluntary membership. This study analyses the influence of individual values—secular/traditional and survival/self-expression–on voluntary membership among European adults (N = 31,985). Specifically, it examines which values orient two age groups (middle age: 50–64 and old age: 65–79), as well as men and women toward a certain type of association (Social Awareness; Professional and Political; Education and Leisure; Religion). The sample of 31,985 comprises 60% of adults aged 50–64 and 40% aged 65–79; of which 56% are women and 44% men. The empirical estimation considers different levels of data aggregation: individual, national and welfare system, therefore multilevel analysis is used as an analytical strategy. Individual-level variables from the Integrated Values Survey (2005/09, 2010/14, and 2017/20) and national-level variables (Gini Index and Gross Domestic Product Per Capita) from the World Bank and Eurostat are used. The results indicate that traditional and self-expression values promote membership in voluntary organizations in general more than secular and survival values. However, there are differences according to the type of organization. Furthermore, values are found to moderate the effect of age and gender on voluntary membership.

El rédito que el infoentretenimiento político ha generado al ámbito televisivo está, hoy en día, constatado; sin embargo, el contexto digital ha supuesto la multiplicidad de los canales de comunicación y ha diversificado, más aún si cabe, la audiencia. Esta investigación se propone comprobar si el politainment es también un reclamo en el consumo de información política digital. Desde una perspectiva exploratoria, se plantea el análisis, tanto cuantitativo como cualitativo, del contenido más popular en YouTube sobre las elecciones a la Comunidad de Madrid de 2021, a través del examen de dos de los elementos que resultan determinantes en la visualización o no de los vídeos publicados: los títulos y las imágenes de portada. Las evidencias apuntan al infoentretenimiento como un componente significativo en el consumo de comunicación electoral en esta red social; si bien las especificidades de esté género en la plataforma de vídeos online difieren de las que se aplican en televisión. En el tipo de politainmet que se emplea en YouTube, el humor, seña de identidad del origen y la evolución del fenómeno en la pequeña pantalla, deja paso a un tratamiento de los elementos textuales y visuales más enfocados a la espectacularización mediante el uso de la personalización política y la polémica como clave narrativa.

Abstract Background X-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate. Rickets and growth retardation are the major manifestations of XLH in children, but there is a broad phenotypic variability. Few publications have reported large series of patients. Current data on the clinical spectrum of the disease, the correlation with the underlying gene mutations, and the long-term outcome of patients on conventional treatment are needed, particularly because of the recent availability of new specific medications to treat XLH. Results The RenalTube database was used to retrospectively analyze 48 Spanish patients (15 men) from 39 different families, ranging from 3 months to 8 years and 2 months of age at the time of diagnosis (median age of 2.0 years), and with XLH confirmed by genetic analysis. Bone deformities, radiological signs of active rickets and growth retardation were the most common findings at diagnosis. Mean (± SEM) height was − 1.89 ± 0.19 SDS and 55% (22/40) of patients had height SDS below—2. All cases had hypophosphatemia, serum phosphate being − 2.81 ± 0.11 SDS. Clinical manifestations and severity of the disease were similar in both genders. No genotype—phenotype correlation was found. Conventional treatment did not attenuate growth retardation after a median follow up of 7.42 years (IQR = 11.26; n = 26 patients) and failed to normalize serum concentrations of phosphate. Eleven patients had mild hyperparathyroidism and 8 patients nephrocalcinosis. Conclusions This study shows that growth retardation and rickets were the most prevalent clinical manifestations at diagnosis in a large series of Spanish pediatric patients with XLH confirmed by mutations in the PHEX gene. Traditional treatment with phosphate and vitamin D supplements did not improve height or corrected hypophosphatemia and was associated with a risk of hyperparathyroidism and nephrocalcinosis. The severity of the disease was similar in males and females.

This paper presents a one-port reflective-mode phase-variation microwave sensor consisting of a coplanar waveguide (CPW) transmission line terminated with a grounded open complementary split ring resonator (OCSRR). The sensor is useful for measuring the dielectric constant of the so-called material under test (MUT), which should be placed in contact with the OCSRR, the sensitive element. The output variable is the phase of the reflection coefficient. Design guidelines for the implementation of highly sensitive sensors are derived in the paper, and validated through simulation and experiment. As compared to other reflective mode phase-variation sensors based on open-ended sensing lines, the designed and fabricated devices exhibit a very small sensitive region by virtue of the use of an electrically small resonant element, the OCSRR. The relevant figure of merit, defined as the ratio between the maximum sensitivity and the size of the sensing area (expressed in terms of the squared wavelength), is as high as FoM = 5643°/λ2 in one of the reported prototypes. Moreover, the paper analyzes the effects of losses. From this study, it is concluded that MUT losses do not significantly affect the output variable, provided losses are small. It is also demonstrated that the sensor is useful to estimate the loss tangent of the considered MUT samples.

Coreless filament winding (CFW) is a novel fabrication technique that utilises fibre-polymer composite materials to efficiently produce filament wound structures in architecture while reducing manufacturing waste. Previous projects have been successfully built with glass and carbon fibre, proving their potential for lightweight construction systems. However, in order to move towards more sustainable architecture, it is crucial to consider replacing carbon fibre’s high environmental impact with other material systems, such as natural fibre. This paper evaluates several fibres, resin systems, and their required CFW fabrication adjustments towards designing and fabricating a bio-composite structure: the LivMatS Pavilion. The methods integrate structural design loops with material evaluation and characterisation, including small-scale and large-scale structural testing at progressive stages. The results demonstrate the interactive decision-making process that combines material characterisation with structural simulation feedback, leveraged to evaluate and optimise the structural design. The built pavilion is proof of the first successful coreless filament wound sustainable natural fibres design, and the developed methods and findings open up further research directions for future applications.

MicroRNAs are non-coding molecules that act both as regulators of the epigenetic landscape and as biomarkers for diseases, including asthma. In the era of personalized medicine, there is a need for novel disease-associated biomarkers that can help in classifying diseases into phenotypes for treatment selection. Currently, severe eosinophilic asthma is one of the most widely studied phenotypes in clinical practice, as many patients require higher and higher doses of corticosteroids, which in some cases fail to achieve the desired outcome. Such patients may only benefit from alternative drugs such as biologics, for which novel biomarkers are necessary. The objective of the study was to study the expression of miR-144-3p in order to discover its possible use as a diagnostic biomarker for severe asthma. For this purpose, miR-144-3p was evaluated in airway biopsies and serum from asthmatics and healthy individuals. mRNA was studied in asthmatic biopsies and smooth muscle cells transfected with miR-144-3p mimic. An in silico regulation of miR-144-3p was performed using miRSystem, miRDB, STRING, and ShinyGO for pathway analysis. From our experimental procedures, we found that miR-144-3p is a biomarker associated with asthma severity and corticosteroid treatment. MiR-144-3p is increased in asthmatic lungs, and its presence correlates directly with blood eosinophilia and with the expression of genes involved in asthma pathophysiology in the airways. When studied in serum, this miRNA was increased in severe asthmatics and associated with higher doses of corticosteroids, thereby making it a potential biomarker for severe asthma previously treated with higher doses of corticosteroids. Thus, we can conclude that miR-144-3p is associated with severe diseases in both the airways and serum of asthmatics, and this association is related to corticosteroid treatment.

Aim: The description of rare malignant ovarian tumours and the most suitable treatments. Alternative therapies different from intravenous chemotherapy are also explained. Methods: Literature review and ongoing trial information have been used to elaborate this guide. Results: Each ovarian cancer type must be identified and treated properly from diagnostic to surgery, adjuvant treatment and metastatic disease. Hormonotherapy can be useful as an alternative treatment, especially in low-grade ovarian cancer and endometrioid subtype. Tumour characterisation is appropriated for treatment selection when targeted therapy is indicated. MEK inhibitors, tyrosine-kinase inhibitors, EGFR inhibitors, therapies against integrins, antibody–drug conjugates and other strategies are described. Antiangiogenics, PARP inhibitors and immunotherapy are discussed in other parts of this publication. Conclusion: Different ovarian cancer types must receive the appropriated treatment. Alternative therapies may be evaluated beyond the standard therapy, frequently in a clinical trial, and an individualised molecular study may help to find the best treatment.

Abstract Background The concept of health-related quality of life and education integrates the bio-psychosocial perspective of health and the multidimensional potentialities of education for wellbeing. This present work is especially relevant to young people because understanding the interaction between health and education can facilitate the design of preventive policies. The research examines the way in which the educational level of young people from an urban district in the city of Zaragoza (Casablanca) has an influence on their health-related quality of life (HRQOL). Methods A cross sectional survey was undertaken in the Casablanca district of Zaragoza (Spain). Participants were not randomly selected; their numbers reflected the areas where they lived with respect to age and sex distribution. It comprised 122 boys and 122 girls, aged between16 and 29, living in the neighbourhood are: Viñedo Viejo, Las Nieves and Fuentes Claras. These three residence zones are markedly different in terms of socioeconomic composition. The questionnaire included the following information: socioeconomic characteristics (sex, age, educational level, employment status, residence zone), an assessment of health (health problems, diagnosis and medication in the last 2 weeks) and HRQOL (WHOQOL-BREF dimensions: mental health; physical health; social relations; and environment). ANOVA and four regression models were used to assess the role, direction and intensity of educational level on HRQOL. Results The results show that the higher the level of education, the better the level of HRQOL. The biggest impact of education was on the mental health dimension, but this influence was modulated by sex and residence zone. The value of the interaction of education and residence zone was more significant than educational level alone. HRQOL of girls is more sensitive to education, being a student and residence zone than the HRQOL of boys. Conclusions The dimensions of HRQOL are influenced by educational level. The influence is greatest among girls and the youngest members of the poorest area of the district. Public authorities should contemplate the development of an equitable education system from the beginning of the life cycle as a public health strategy.

In this paper, a displacement sensor based on an open-ended step-impedance transmission line is reported. The sensor operates in reflection, and the output variable is the phase of the reflection coefficient. The static part of the sensor is the step-impedance transmission line, where the open-ended line section is the sensitive part (sensing line). The movable part is a dielectric slab, e.g., an uncladded microwave substrate. When such slab, located on top of the sensing line, is in relative motion to the line, in the direction of the line axis, the portion of the sensing line covered by the slab varies, and this results in a change in the phase of the reflection coefficient of the line. The step impedance discontinuity contributes to optimize the sensor sensitivity, the key parameter. A detailed analysis providing the design guidelines is carried out and used to design a prototype displacement sensor. The characterization of the fabricated device points out the potential of the approach to implement highly sensitive displacement sensors. The sensor is a one-port device and operates at a single frequency.

Background VCN-01 is an oncolytic adenovirus (Ad5 based) designed to replicate in cancer cells with dysfunctional RB1 pathway, express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. This phase I clinical trial was aimed to find the maximum tolerated dose/recommended phase II dose (RP2D) and dose-limiting toxicity (DLT) of the intravenous delivery of the replication-competent VCN-01 adenovirus in patients with advanced cancer.Methods Part I: patients with advanced refractory solid tumors received one single dose of VCN-01. Parts II and III: patients with pancreatic adenocarcinoma received VCN-01 (only in cycle 1) and nab-paclitaxel plus gemcitabine (VCN-concurrent on day 1 in Part II, and 7 days before chemotherapy in Part III). Patients were required to have anti-Ad5 neutralizing antibody (NAbs) titers lower than 1/350 dilution. Pharmacokinetic and pharmacodynamic analyses were performed.Results 26% of the patients initially screened were excluded based on high NAbs levels. Sixteen and 12 patients were enrolled in Part I and II, respectively: RP2D were 1×1013 viral particles (vp)/patient (Part I), and 3.3×1012 vp/patient (Part II). Fourteen patients were included in Part III: there were no DLTs and the RP2D was 1×1013 vp/patient. Observed DLTs were grade 4 aspartate aminotransferase increase in one patient (Part I, 1×1013 vp), grade 4 febrile neutropenia in one patient and grade 5 thrombocytopenia plus enterocolitis in another patient (Part II, 1×1013 vp). In patients with pancreatic adenocarcinoma overall response rate were 50% (Part II) and 50% (Part III). VCN-01 viral genomes were detected in tumor tissue in five out of six biopsies (day 8). A second viral plasmatic peak and increased hyaluronidase serum levels suggested replication after intravenous injection in all patients. Increased levels of immune biomarkers (interferon-γ, soluble lymphocyte activation gene-3, interleukin (IL)-6, IL-10) were found after VCN-01 administration.Conclusions Treatment with VCN-01 is feasible and has an acceptable safety. Encouraging biological and clinical activity was observed when administered in combination with nab-paclitaxel plus gemcitabine to patients with pancreatic adenocarcinoma.Trial registration number NCT02045602.

A series of N-Boc ketimines derived from pyrazolin-5-ones have been used as electrophiles in enantioselective Mannich reactions with different 1,3-dicarbonyl compounds. This method provides a direct pathway to access the 4-amino-5-pyrazolone derivatives bearing a quaternary substituted stereocenter and containing two privileged structure motifs, the β-diketone and pyrazolinone substructures. The adducts were obtained in excellent yields (up to 90%) and enantioselectivities (up to 94:6 er) by employing a very low loading of 2 mol% of a quinine-derived bifunctional squaramide as an organocatalyst for a wide range of substrates. In addition, the utility of the obtained products was demonstrated through one step transformations to enantioenriched diheterocyclic systems (4-pyrazolyl-pyrazolone and 4-isoxazolyl-pyrazolone), potentially promising candidates for drug discovery.

In this report, we analyse the benthic hydroids collected on the Vema and Valdivia seamounts during a survey conducted in 2015 in the SEAFO Convention Area, focused on mapping and analysing the occurrence and abundance of benthopelagic fish and vulnerable marine ecosystem (VMEs) indicators on selected Southeast Atlantic seamounts. A total of 27 hydroid species were identified, of which 22 belong to Leptothecata and only five to Anthoathecata. Monostaechoides gen. nov. was erected within the family Halopterididae to accommodate Plumularia providentiae Jarvis, 1922, and a new species, Monotheca bergstadi sp. nov., is also described. Campanularia africana is recorded for the first time from the Atlantic Ocean, and the Northeast Atlantic species Amphinema biscayana, Stegopoma giganteum and Clytia gigantea are also recorded from the South Atlantic. Three species were identified to the genus level only, due to the absence of their gonosomes. None of the reported species are endemic, and the hydroid community is clearly dominated by species with a wide geographical distribution in the three major oceans. Only Monotheca bergstadi sp. nov. presently has its distribution restricted to the Vema Seamount and the South African coast.

Background Probody® therapeutics are antibody prodrugs that are activated in the tumor microenvironment by tumor-associated proteases, thereby restricting the activity to the tumor microenvironment and minimizing ‘off-tumor’ toxicity. We report dose-escalation and single-agent expansion phase data from the first-in-human study of CX-072 (pacmilimab), a Probody checkpoint inhibitor directed against programmed death-ligand 1 (PD-L1).Methods In the dose-escalation phase of this multicenter, open-label study (NCT03013491), adults with advanced solid tumors (naive to programmed-death-1/PD-L1 or cytotoxic T-lymphocyte-associated antigen 4 inhibitors) were enrolled into one of seven dose-escalation cohorts, with pacmilimab administered intravenously every 14 days. The primary endpoints were safety and determination of the maximum tolerated dose (MTD). In the expansion phase, patients with one of six prespecified malignancies (triple-negative breast cancer [TNBC]; anal squamous cell carcinoma [aSCC]; cutaneous SCC [cSCC]; undifferentiated pleomorphic sarcoma [UPS]; small bowel adenocarcinoma [SBA]; and thymic epithelial tumor [TET]); or high tumor mutational burden (hTMB) tumors were enrolled. The primary endpoint was objective response (Response Evaluation Criteria In Solid Tumors v.1.1).Results An MTD was not reached with doses up to 30 mg/kg. A recommended phase 2 dose (RP2D) of 10 mg/kg was chosen based on pharmacokinetic and pharmacodynamic findings in the expansion phase. Ninety-eight patients enrolled in the expansion phase: TNBC (n=14), aSCC (n=14), cSCC (n=14), UPS (n=20), SBA (n=14), TET (n=8), and hTMB tumors (n=14). Of 114 patients receiving pacmilimab at the RP2D, grade ≥3 treatment-related adverse events (TRAEs) were reported in 10 patients (9%), serious TRAEs in six patients (5%), and treatment discontinuation due to TRAEs in two patients (2%). Grade ≥3 immune-related AEs occurred in two patients (rash, myocarditis). High PD-L1 expression (ie, >50% Tumor Proportion Score) was observed in 22/144 (19%) patients. Confirmed objective responses were observed in patients with cSCC (n=5, including one complete response), hTMB (n=4, including one complete response), aSCC (n=2), TNBC (n=1), UPS (n=1), and anaplastic thyroid cancer (n=1).Conclusions Pacmilimab can be administered safely at the RP2D of 10 mg/kg every 14 days. At this dose, pacmilimab had a low rate of immune-mediated toxicity and showed signs of antitumor activity in patients not selected for high PD-L1 expression.Trial registration number NCT03013491.

Respiratory diseases such as bronchiolitis, and those with wheezing episodes, are highly important during infancy due to their potential chronicity. Immune response dysregulation is critical in perpetuating lung damage. Epigenetic modifications including microRNA (miRNA) post-transcriptional regulation are among the factors involved in alleviating inflammation. We evaluated the expression of miR-146a-5p, a previously described negative regulator of immunity, in infants with respiratory diseases, in order to study epigenetic regulation of the immune response. Nasopharyngeal aspirate (NPA) was obtained from infants with bronchiolitis (ongoing and post-disease) or with wheezing episodes in addition to healthy controls. Virus presence was determined by nested PCR, while miRNA and gene expression were studied in cells from NPAs using qPCR. Healthy small airway epithelial cells (SAECs) were used as an in vitro model. We observe a reduction in miR-146a-5p expression in infants with either of the two diseases compared to controls, suggesting the potential of this miRNA as a disease biomarker. Post-bronchiolitis, miR-146a-5p expression increases, though without reaching levels of healthy controls. MiR-146a-5p expression correlates inversely with the immune-related gene PTGS2, while its expression correlates directly with TSLP. When heathy donor SAECs are stimulated by poly:IC, we observe an increase in miR-146a-5p, with wounds having a synergistic effect. In conclusion, infants with respiratory diseases present reduced miR-146a-5p expression, possibly affecting immune dysregulation.

Introduction: Due to its aggressiveness, cutaneous melanoma (CM) is responsible for most skin cancer-related deaths worldwide. The origin of CM is closely linked to the appearance of UV-induced somatic mutations in melanocytes present in normal skin or in CM precursor lesions (nevi or dysplastic nevi). In recent years, new NGS studies performed on CM tissue have increased the understanding of the genetic somatic changes underlying melanomagenesis and CM tumor progression. Methods: We reviewed the literature using all important scientific databases. All articles related to genomic mutations in CM as well as normal skin and nevi were included, in particular those related to somatic mutations produced by UV radiation. Conclusions: CM development and progression are strongly associated with exposure to UV radiation, although each melanoma subtype has different characteristic genetic alterations and evolutionary trajectories. While BRAF and NRAS mutations are common in the early stages of tumor development for most CM subtypes, changes in CDKN2A, TP53 and PTEN, together with TERT promoter mutations, are especially common in advanced stages. Additionally, large genome duplications, loss of heterozygosity, and copy number variations are hallmarks of metastatic disease. Finally, the mutations driving melanoma targeted-therapy drug resistance are also summarized. The complete sequential stages of clonal evolution leading to CM onset from normal skin or nevi are still unknown, so further studies are needed in this field to shed light on the molecular pathways involved in CM malignant transformation and in melanoma acquired drug resistance.

Este artículo propone, a partir de una amplia revisión bibliográfica, reflexionar sobre el concepto de Comunicación Política y sobre la incidencia que, en el rol de los tres actores que en ella intervienen —políticos, medios de comunicación y ciudadanía—, ha tenido el entorno digital. A través de un repaso por la evolución del concepto posicionamos la comunicación política en una cuarta fase caracterizada por el desapego y descrédito hacia las instancias políticas y mediáticas, la desmasificación, la diversificación mediática, la desintermediación y la emancipación de la ciudadanía digital. El fenómeno de la comunicación política se aborda desde su vinculación a los conceptos clásicos de Espacio Público y Opinión Pública que se extrapolan al contexto de la ciberdemocracia para cuestionar si los procesos de interacción que en ella se desarrollan conducen haciaun modelo de democracia deliberativa. En respuesta a ello, este estudio evidencia la necesidad de mayores niveles de intercambio y consenso, especialmente entre las esferas política y ciudadana, en relación a los mensajes, símbolos y opiniones que, a través de la comunicación política, construyen la Opinión Pública digital. La posibilidad de una democracia deliberativa se vislumbra lejana. La confrontación discursiva propia de la comunicación política tradicional se traslada al entorno online, con la única salvedad de que, ahora y de momento, está más equiparada entre los tres elementos que en ella intervienen.