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Introduction: Clinical practice guidelines in neurorehabilitation for adults with disorders of consciousness by the Spanish Neurorehabilitation Society. This document is based on a review of international clinical practice guidelines published between 2015 and 2022. Method: A total of 7 articles, corresponding to 5 clinical practice guidelines published between 2015 and 2022, were selected by the group of authors from a pool of 48 bibliographic references extracted from various databases in accordance with predefined search criteria. Following this review, forty recommendations were formulated and subjected to evaluation by an expert committee using a 9-point Likert scale: 1–3 (inappropriate recommendation), 4–6 (uncertain recommendation), and 7–9 (appropriate recommendation), following the methodology of the “Modified Nominal Group Technique.” Any recommendation endorsed by at least 75% of the experts as “appropriate” (with a score of 7–9) was considered accepted. Conclusions: This document presents 40 recommendations categorised according to the level of evidence provided by the reviewed studies. These recommendations represent a consensus among experts and pertain to various aspects related to: 1) clinical assessment, 2) complementary diagnostic tests, 3) prognosis, and 4) treatment in this specific population. Resumen: Introducción: Guía para la práctica clínica en neurorrehabilitación de personas adultas en estado alterado de la consciencia (EAC) de la Sociedad Española de Neurorrehabilitación. Documento basado en la revisión de guías de práctica clínica internacionales publicadas entre 2015–2022. Método: Un total de 7 artículos correspondientes a 5 guías de práctica clínica publicadas entre 2015–2022, fueron seleccionadas por el grupo de autores de un total de 48 referencias bibliográficas extraídas de diferentes bases de datos de acuerdo a los criterios de búsqueda. En base a dicha revisión se establecieron cuarenta recomendaciones sometidas a evaluación por un comité de expertos que evaluaron cada recomendación con una escala de 9 puntos de tipo Likert: 1–3 (recomendación inapropiada), 4–6 (recomendación incierta) y 7–9 (recomendación apropiada), de acuerdo a la metodología del Modified Nominal Group Technique. Toda recomendación, valorada por al menos un 75% de los expertos como «apropiada» (puntuación: 7–9) se consideró como aceptada. Conclusiones: Se establecen 40 recomendaciones según el nivel de evidencia que ofrecen los estudios revisados referentes a aspectos consensuados entre expertos dirigidos a definir aspectos relacionados con la: 1) evaluación clínica, 2) pruebas complementarias, 3) pronóstico y 4) tratamiento, en esta población.

Abstract The genetic landscape underlying the transformation of splenic diffuse red pulp small B‐cell lymphoma (SDRPL) is not well understood. The present study aimed to unravel the genomic alterations involved in the progression and transformation of SDRPL. We performed genetic studies on both SDRPL and subsequent or synchronous diffuse large B cell lymphoma (DLBCL) samples in three SDRPL patients who eventually developed DLBCL. Our findings revealed that SDRPL cases progressing to DLBCL acquired genomic alterations in genes related to the cell cycle (CDKN2A/B, TP53, MYC and CCND3) and B cell development (BCL6).

Abstract Mantle cell lymphoma (MCL) is genetically characterized by the IG::CCND1 translocation mediated by an aberrant V(D)J rearrangement. CCND1 translocations and overexpression have been identified in occasional aggressive B-cell lymphomas with unusual features for MCL. The mechanism generating CCND1 rearrangements in these tumors and their genomic profile are not known. We have reconstructed the IG::CCND1 translocations and the genomic profile of 13 SOX11-negative aggressive B-cell lymphomas using whole genome/exome and target sequencing. The mechanism behind the translocation was an aberrant V(D)J rearrangement in three tumors and by an anomalous IGH class-switch recombination (CSR) or somatic hypermutation (SHM) mechanism in ten. The tumors with a V(D)J-mediated translocation were two blastoid MCL and one high-grade B-cell lymphoma. None of them had a mutational profile suggestive of DLBCL. The ten tumors with CSR/SHM-mediated IGH::CCND1 were mainly large B-cell lymphomas, with mutated genes commonly seen in DLBCL and BCL6 rearrangements in 6. Two cases, which transformed from marginal zone lymphomas, carried mutations in KLF2, TNFAIP3 and KMT2D. These findings expand the spectrum of tumors carrying CCND1 rearrangement that may occur as a secondary event in DLBCL mediated by aberrant CSR/SHM and associated with a mutational profile different from that of MCL.

El presente artículo aborda una investigación socio-histórica de cómo el arte, en general, se usó como propaganda para la naturalización de la transición, donde el cine y la música fueron manifestaciones que estuvieron en relación directa con las proyecciones ideológicas del régimen. Con el objetivo de mostrar, específicamente, la entrada del jazz como herramienta subversiva, popular y libre en el territorio español a lo largo del primer franquismo. Metodológicamente, con el análisis de la prensa se observa cómo con la llegada de la Segunda Guerra Mundial se fue produciendo un cambio de paradigma a partir de la propaganda cultural del momento. Como resultados relevantes se destacan cómo el jazz desempeñó un papel significativo en el contexto español en el marco de las restricciones impuestas por la biopolítica del régimen. En conclusión, el jazz fue un medio para la propaganda franquista, en principio con su prohibición y censura siguiendo el modelo de la Alemania nazi y, más tarde, permitiéndolo y programándolo para mostrar la modernidad y apertura de España a los Estados Unidos de América, configurándose, en este aspecto, como una herramienta omnipresente en la escena musical de los años 1940, desmarcándose así más allá de los confines de la música.

El emprendimiento social es un modelo de negocio que integra el ánimo de lucro con el compromiso de abordar problemas sociales y medioambientales. Este enfoque debe transmitirse al estudiantado de Ciencias Sociales, ya que tenemos la responsabilidad de formar a futuros profesionales que gestionen sus actividades empresariales de manera ética y sostenible, promoviendo un impacto positivo en la sociedad. Así, este trabajo pretende identificar cuánto sabe el alumnado universitario acerca de este tipo de emprendimiento, cuánto les interesa y hasta qué punto estarían dispuestos a involucrarse en proyectos empresariales de estas características, capaces de responder adecuadamente a los nuevos retos demandados hoy en día por la sociedad. En particular, estudiamos la influencia de variables sociodemográficas como el género, la edad, el nivel educativo y el nivel de renta a través de una encuesta a una muestra de 600 estudiantes de universidades de la Comunidad de Madrid. Empleando un contraste de comparación de medias y un modelo Probit, los resultados muestran que el género no afecta al conocimiento sobre emprendimiento social, pero sí al interés y a la intención de participar en proyectos de emprendimiento social, más acusado en las mujeres. La edad no afecta en ningún caso; mientras que el nivel educativo afecta al conocimiento y a la intención de participar, pero no al interés. Por su parte, el alumnado de la universidad privada conoce mejor este concepto, pero al de la pública le interesa más, no obstante, la titularidad de la universidad no afecta a la intención de participar en estos proyectos. Concluimos remarcando la importancia de incluir el emprendimiento social en todas las etapas del ciclo educativo y en todas las áreas de conocimiento para que la juventud, al finalizar sus estudios, lo conozca a fondo y esté interesada en participar profesionalmente en este tipo de proyectos que, sin duda, contribuyen a hacer del mundo un lugar mejor.

El tema de las habilidades para la vida es uno de los más estudiados en los últimos años a raíz de la aplicación de la perspectiva del Positive Youth Development al contexto deportivo. Este estudio tiene como objetivo explorar el papel que tienen los entrenadores en el proceso de adquisición de habilidades para la vida en una muestra de estudiantes-deportistas. Se ha seguido una metodología cualitativa desde el paradigma del realismo crítico en el que han participado 13 deportistas-estudiantes (5 de los cuales mujeres) con una media de edad de 20.7 años (DT = 6.8) en dos grupos focales. Tras el análisis temático deductivo se extrajeron 3 temas relevantes: (a) los entrenadores usan estrategias implícitas de enseñanza de habilidades para la vida; (b) ausencia de enseñanza de habilidades transformativas de forma explícita; (c) los deportistas señalan que las experiencias negativas también les han enseñado cosas. Derivado de estos, se propone un abordaje orientado a crear estrategias explícitas por parte de entrenadores que tengan valor para el desarrollo de estudiantes deportistas en las primeras etapas de su carrera y en el transcurso de una carrera dual. El diseño de estrategias explícitas como la reflexión sobre habilidades para la vida o la invitación a realizar la transferencia a otras áreas de la vida del deportista, debería incluirse en la programación de las sesiones deportivas.

Resumen El artículo desgrana algunos de los efectos de la transformación de los espacios industriales en Barcelona desde la segunda mitad de los años ochenta del siglo XX. Describe las fases de la gestión del patrimonio industrial en la ciudad condal desde los inicios de la democracia y analiza las resistencias y acciones ciudadanas que se originan en el contexto de las contradicciones entre la identidad colectiva, el desarrollo local y la proyección global de ciudad que la transformación del espacio industrial genera. Para ilustrar estos procesos se estudian dos casos de complejos fabriles situados en dos de los principales conjuntos industriales de la ciudad: Can Ricart (Distrito X, Sant Martí) y Can Batlló (Distrito III, Sants-Montjuïc).

Abstract Background The increasing incidence of coeliac disease is leading to a growing interest in active search for associated factors, even the intrauterine and early life. The exposome approach to disease encompasses a life course perspective from conception onwards has recently been highlighted. Knowledge of early exposure to gluten immunogenic peptides (GIP) in utero could challenge the chronology of early prenatal tolerance or inflammation, rather than after the infant’s solid diet after birth. Methods We developed an accurate and specific immunoassay to detect GIP in amniotic fluid (AF) and studied their accumulates, excretion dynamics and foetal exposure resulting from AF swallowing. One hundred twenty-five pregnant women with different gluten diets and gestational ages were recruited. Results GIP were detectable in AF from at least the 16th gestational week in gluten-consuming women. Although no significant differences in GIP levels were observed during gestation, amniotic GIP late pregnancy was not altered by maternal fasting, suggesting closed-loop entailing foetal swallowing of GIP-containing AF and subsequent excretion via the foetal kidneys. Conclusions The study shows evidence, for the first time, of the foetal exposure to gluten immunogenic peptides and establishes a positive correlation with maternal gluten intake. The results obtained point to a novel physiological concept as they describe a plausible closed-loop circuit entailing foetal swallowing of GIP contained in AF and its subsequent excretion through the foetal kidneys. The study adds important new information to understanding the coeliac exposome.

Abstract Background Understanding the enduring respiratory consequences of severe COVID-19 is crucial for comprehensive patient care. This study aims to evaluate the impact of post-COVID conditions on respiratory sequelae of severe acute respiratory distress syndrome (ARDS). Methods We examined 88 survivors of COVID-19-associated severe ARDS six months post-intensive care unit (ICU) discharge. Assessments included clinical and functional evaluation as well as plasma biomarkers of endothelial dysfunction, inflammation, and viral response. Additionally, an in vitro model using human umbilical vein endothelial cells (HUVECs) explored the direct impact of post-COVID plasma on endothelial function. Results Post-COVID patients with impaired gas exchange demonstrated persistent endothelial inflammation marked by elevated ICAM-1, IL-8, CCL-2, and ET-1 plasma levels. Concurrently, systemic inflammation, evidenced by NLRP3 overexpression and elevated levels of IL-6, sCD40-L, and C-reactive protein, was associated with endothelial dysfunction biomarkers and increased in post-COVID patients with impaired gas exchange. T-cell activation, reflected in CD69 expression, and persistently elevated levels of interferon-β (IFN-β) further contributed to sustained inflammation. The in vitro model confirmed that patient plasma, with altered levels of sCD40-L and IFN-β proteins, has the capacity to alter endothelial function. Conclusions Six months post-ICU discharge, survivors of COVID-19-associated ARDS exhibited sustained elevation in endothelial dysfunction biomarkers, correlating with the severity of impaired gas exchange. NLRP3 inflammasome activity and persistent T-cell activation indicate on going inflammation contributing to persistent endothelial dysfunction, potentially intensified by sustained viral immune response.

Abstract Background Patient heterogeneity poses significant challenges for managing individuals and designing clinical trials, especially in complex diseases. Existing classifications rely on outcome-predicting scores, potentially overlooking crucial elements contributing to heterogeneity without necessarily impacting prognosis. Methods To address patient heterogeneity, we developed ClustALL, a computational pipeline that simultaneously faces diverse clinical data challenges like mixed types, missing values, and collinearity. ClustALL enables the unsupervised identification of patient stratifications while filtering for stratifications that are robust against minor variations in the population (population-based) and against limited adjustments in the algorithm’s parameters (parameter-based). Results Applied to a European cohort of patients with acutely decompensated cirrhosis (n = 766), ClustALL identified five robust stratifications, using only data at hospital admission. All stratifications included markers of impaired liver function and number of organ dysfunction or failure, and most included precipitating events. When focusing on one of these stratifications, patients were categorized into three clusters characterized by typical clinical features; notably, the 3-cluster stratification showed a prognostic value. Re-assessment of patient stratification during follow-up delineated patients’ outcomes, with further improvement of the prognostic value of the stratification. We validated these findings in an independent prospective multicentre cohort of patients from Latin America (n = 580). Conclusions By applying ClustALL to patients with acutely decompensated cirrhosis, we identified three patient clusters. Following these clusters over time offers insights that could guide future clinical trial design. ClustALL is a novel and robust stratification method capable of addressing the multiple challenges of patient stratification in most complex diseases.

The importance of diet in preventing non-communicable diseases is well established, with polyphenol consumption suggested to impact cardiovascular disease development. Salicornia ramosissima synthesizes high amounts of phytochemicals under environmental stress. In a randomized controlled clinical trial on 90 healthy volunteers, we evaluated the safety of supplementation with 1 g of polyphenol-rich S. ramosissima extracts from salt marshes and hydroponic sources over three months. No differences in adverse effects were observed between extract-treated and placebo subjects. Salicornia extract from marshes (SM) increased glomerular filtration rate and reduced LDL cholesterol. SM treatment also modulated plasma markers related to cardiovascular disease: MERTK, Gal-9, ADM, TF, PRSS27, HAOX1, IL-18, PAPPA, TNFRSF1A, TIE2 and FGF-21 proteins were downregulated while SRC levels were upregulated. Therefore, under the studied conditions of use, Salicornia extracts consumption is safe and SM induced biochemical and proteomic changes related to cardiovascular health.

Background & Aims: In patients with cirrhosis, acute decompensation (AD) correlates with a hyperinflammatory state driven by mitochondrial dysfunction, which is a significant factor in the progression toward acute-on-chronic liver failure (ACLF). Elevated circulating levels of acylcarnitine, indicative of mitochondrial dysfunction, are predictors of mortality in ACLF patients. Our hypothesis posits that acylcarnitines not only act as biomarkers, but also actively exert detrimental effects on circulating immune cells. Methods: Plasma acylcarnitine levels were measured in 20 patients with AD cirrhosis and 10 healthy individuals. The effects of selected medium- and long-chain acylcarnitines on mitochondrial function were investigated in peripheral leucocytes from healthy donors by determining mitochondrial membrane potential (Δψm) and mitochondrial respiration using the JC-1 dye and Agilent Seahorse XF technology. Changes regarding mitochondrial ultrastructure and redox systems were assessed by transmission electron microscopy and gene and protein expression analysis. Results: Plasma levels of several acylcarnitine species were significantly elevated in patients with AD cirrhosis compared with healthy individuals, alongside increased levels of inflammatory mediators (cytokines and chemokines). Notably, the long-chain acylcarnitine palmitoylcarnitine (C16:0-carnitine, 1.51-fold higher, p = 0.0059) impaired Δψm and reduced the spare respiratory capacity of peripheral mononuclear leucocytes. Additionally, C16:0-carnitine induced mitochondrial oxidative stress, suppressed the expression of the antioxidant gene HMOX1, and increased CXCL8 expression and IL-8 release. Etomoxir, which blocks acylcarnitine entry into the mitochondria, reversed the suppression of HMOX1. Similarly, trimetazidine, a fatty acid beta-oxidation inhibitor, prevented C16:0-carnitine-induced CXCL8 expression. Importantly, oxidative stress and Δψm impairment caused by C16:0-carnitine were less severe in the presence of albumin, a standard therapy for AD cirrhosis. Conclusions: Our findings suggest that long-chain acylcarnitines induce mitochondrial injury in immune cells, thereby contributing to the development of immune dysfunction associated with cirrhosis. Impact and implications: Patients with acute decompensation of cirrhosis and acute-on-chronic liver failure (ACLF) display a systemic hyperinflammatory state and leukocyte mitochondrial dysfunction. We discovered that apart from being increased in the circulation of these patients, the long-chain palmitoylcarnitine is able to elicit cytokine secretion paired with mitochondrial dysfunction in leukocytes from healthy donors. In particular, we show that inhibiting the metabolism of palmitoylcarnitine could reverse these detrimental effects. Our findings underline the importance of immunometabolism as a treatment target in patients with acute decompensation of cirrhosis and ACLF.

Background & Aims: Patients with acutely decompensated (AD) cirrhosis are immunocompromised and particularly susceptible to infections. This study investigated the immunomodulatory actions of albumin by which this protein may lower the incidence of infections. Methods: Blood immunophenotyping was performed in 11 patients with AD cirrhosis and 10 healthy volunteers (HV). Bulk and single-cell RNA sequencing (scRNA-seq) and flow cytometry were performed in peripheral blood mononuclear cells (PBMCs) from 20 patients with AD cirrhosis and 34 HV exposed to albumin. Albumin’s effects on degranulation, phagocytosis, chemotaxis, and swarming of neutrophils from six patients with AD cirrhosis and nine HV were assessed by measuring myeloperoxidase enzymatic activity, the engulfment of fluorescent-labeled Escherichia coli and zymosan, and interactions of neutrophils with Candida albicans at single-cell resolution in microfluidic chambers, respectively. Whole blood RNA sequencing (RNA-seq) analyses were performed in 49 patients admitted for severe AD cirrhosis, of whom 30 received albumin during hospitalization. Results: Compared with HV, patients with AD cirrhosis showed severe lymphopenia and defective neutrophil antimicrobial function. Bulk and scRNA-seq analyses revealed significantly (false discovery rate [FDR]

Abstract Testicular large B‐cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune‐privileged site and has recently been recognized as a distinct entity from diffuse large B‐cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B‐cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next‐generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations (p

Summary: CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

La incidència de la pandèmia sobre la mobilitat residencial ha generat nombrosos treballs sobre la intensitat i la direccionalitat dels fluxos, les preferències residencials, els comportaments migratoris i el seu impacte sobre la reconfiguració territorial. Davant d’aquest escenari territorial acabat d’estrenar, convé avaluar quin és el nou paper de l’sprawl urbà. L’objectiu d’aquest treball és determinar el rol de l’urbanisme dispers durant la pandèmia a través de l’anàlisi dels fluxos migratoris intrametropolitans a la Regió Metropolitana de Barcelona com a estudi de cas. A partir de l’anàlisi de les dades de l’Estadística de Mobilitat Residencial es descriuen les dinàmiques migratòries dels municipis dispersos, s’estudien els comportaments segons l’edat i s’aprofundeix en la temporalitat o en la continuïtat dels patrons migratoris, amb la finalitat de contribuir a aprofundir en els factors explicatius dels comportaments residencials durant l’etapa peripandèmica.

Abstract Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred technique for treating pathologies of the bile duct. It has been suggested that this procedure, combined with sphincterotomy, may influence the subsequent development of long-term complications. The main objective of this study was to determine the long-term complications of biliopancreatic disease after ERCP and their potential association with the development of biliopancreatic neoplasms. Methods: This retrospective cohort study included 576 patients who underwent ERCP (referred to as index ERCP) with sphincterotomy for benign biliary disease, with a minimum follow-up period of more than 2 years. Results: The incidence of long-term benign and neoplastic pathologies after ERCP was analyzed. The most common findings were recurrence of choledocholithiasis in 70 patients (12.1%), cholangitis “sine materia” in 27 patients (4.7%), and acute pancreatitis in 8 patients (1.4%). Eight patients (1.4%) developed hepatobiliopancreatic neoplasms, including 4 cases of pancreatic neoplasms (0.7%), 1 cholangiocarcinoma (0.2%), 1 ampulloma (0.2%), and 2 intrahepatic neoplasms (0.3%). Multivariate analysis revealed that factors such as age over 50 years, previous biliary surgery, diversion of the bile duct (BD) to the digestive tract, dilation of the BD, stent placement, biopsy, and cholecystectomy were factors associated with an increased risk of long-term benign complications. Conclusion: Endoscopic retrograde cholangiopancreatography with sphincterotomy is associated with an increased long-term risk of subsequent benign biliopancreatic disease. However, our data do not allow us to establish a direct relationship with the development of biliopancreatic neoplasms.

BackgroundChronic spontaneous urticaria (CSU) is a highly prevalent and difficult to manage cutaneous disease characterized by the presence of recurrent urticaria, angioedema, or both, for a period of 6 weeks or longer. One of the biological treatments used for patients with CSU with an autoimmune background and bad control of the disease is omalizumab, an anti-IgE monoclonal antibody. The understanding of the mechanism of action of this biological drug in CSU along with the identification of potential biomarkers of clinical response can be helpful in the personalized management of the disease.ObjectiveThe purpose of this study was to analyze the effect of omalizumab on peripheral blood lymphocyte subpopulations in patients with CSU in order to identify potential biomarkers of treatment response.MethodsWe analyzed 71 patients with CSU [33 under omalizumab and 38 under non-immunomodulatory drugs (treated with antihistamines; NID)] and 50 healthy controls. An exhaustive immunophenotyping of whole blood T-cell subpopulations, including naïve, central memory, effector memory, effector cells, Th1, Th2, and Th17 was performed by multiparametric flow cytometry. Moreover, in CSU patients, we analyzed markers of inflammation (ESR, DD, CRP), atopy (prick test, IgE quantification), and autoimmunity (anti-thyroid antibodies and indirect basophil activation test).To evaluate the clinical activity, the Urticaria Activity Score 7 (UAS 7) test was used.ResultsIn patients with CSU under treatment with omalizumab, there was a significant decrease in the percentage of naïve and an increase in the percentage of central memory CD4 T cells as well as a decrease in the percentage of naïve and increase in the percentage of effector CD8 T-cell subsets. Moreover, patients under treatment with omalizumab had higher percentages of Th1 and Th2 cells than patients under treatment with NID.ConclusionThe immune monitoring of T-cell subpopulations in patients with CSU starting omalizumab, may be a useful strategy to analyze treatment response in the clinical practice.

IntroductionIn post-COVID survivors, transforming growth factor-beta-1 (TGF-β1) might mediate fibroblast activation, resulting in persistent fibrosis.MethodsIn this study, 82 survivors of COVID-19-associated ARDS were examined at 6- and 24-months post-ICU discharge. At 6-months, quantitative CT analysis of lung attenuation was performed and active TGF-β1 was measured in blood and exhaled breath condensate (EBC).ResultsAt 6-months of ICU-discharge, patients with reduced DmCO/alveolar volume ratio exhibited higher plasma and EBC levels of active TGF-β1. Plasma TGF-β1 levels were elevated in dyspneic survivors and directly related to the high-attenuation lung volume. In vitro, plasma and EBC from survivors induced profibrotic changes in human primary fibroblasts in a TGF-β receptor-dependent manner. Finally, at 6-months, plasma and EBC active TGF-β1 levels discriminated patients who, 24-months post-ICU-discharge, developed gas exchange impairment.DiscussionTGF-β1 pathway plays a pivotal role in the early-phase fibrotic abnormalities in COVID-19-induced ARDS survivors, with significant implications for long-term functional impairment.

ABSTRACT Hypersaline ecosystems display taxonomically similar assemblages with low diversities and highly dense accompanying viromes. The ecological implications of viral infection on natural microbial populations remain poorly understood, especially at finer scales of diversity. Here, we sought to investigate the influence of changes in environmental physicochemical conditions and viral predation pressure by autochthonous and allochthonous viruses on host dynamics. For this purpose, we transplanted two microbiomes coming from distant hypersaline systems (solar salterns of Es Trenc in Spain and the thalassohaline lake of Aran-Bidgol lake in Iran), by exchanging the cellular fractions with the sterile-filtered accompanying brines with and without the free extracellular virus fraction. The midterm exposure (1 month) of the microbiomes to the new conditions showed that at the supraspecific taxonomic range, the assemblies from the solar saltern brine more strongly resisted the environmental changes and viral predation than that of the lake. The metagenome-assembled genomes (MAGs) analysis revealed an intraspecific transition at the ecotype level, mainly driven by changes in viral predation pressure, by both autochthonous and allochthonous viruses.IMPORTANCEViruses greatly influence succession and diversification of their hosts, yet the effects of viral infection on the ecological dynamics of natural microbial populations remain poorly understood, especially at finer scales of diversity. By manipulating the viral predation pressure by autochthonous and allochthonous viruses, we uncovered potential phage–host interaction, and their important role in structuring the prokaryote community at an ecotype level.

Abstract Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. Video Abstract

Abstract Acute infection and chronic infection are the two most common fates of pathogenic virus infections. While several factors that contribute to these fates are described, the critical control points and the mechanisms that underlie infection fate regulation are incompletely understood. Using the acute and chronic lymphocytic choriomeningitis virus (LCMV) infection model of mice, we find that the early dynamic pattern of the IFN-I response is a differentiating trait between both infection fates. Acute-infected mice generate a 2-wave IFN-I response while chronic-infected mice generate only a 1-wave response. The underlying cause is a temporal difference in CD8 T cell-mediated killing of splenic marginal zone CD169+ macrophages. It occurs later in acute infection and thus enables CD169+ marginal zone macrophages to produce the 2nd IFN-I wave. This is required for subsequent immune events including induction of inflammatory macrophages, generation of effector CD8+ T cells and virus clearance. Importantly, these benefits come at a cost for the host in the form of spleen fibrosis. Due to an earlier marginal zone destruction, these ordered immune events are deregulated in chronic infection. Our findings demonstrate the critical importance of kinetically well-coordinated sequential immune events for acute infection control and highlights that it may come at a cost for the host organism.

Objectives: This study aims to determine the association between parental competence (warmth, demandingness, and parental education in fortitude and in privacy) and pornography use. Methods: This study presents cross-sectional data from an ongoing international study (YOURLIFE Project) about the opinions and lifestyles of adolescents with respect to affectivity, love, and sexuality. Adolescents (N = 2516) aged 12–15 from Chile, Mexico, Peru, and Spain were included. Multiple logistic regressions were performed to analyze the association between family assets (parental demandingness, warmth, and parental fortitude and privacy education) and pornography use. Results: The results indicated an association between parental warmth and pornography use among boys and girls. Furthermore, privacy education was highly associated with less pornography use only in girls. Parental demandingness and parental fortitude education were not associated with pornography use. Conclusion: Our findings suggest that new educational perspectives including privacy issues should be considered within programs for pornography use prevention among adolescents. Parents should incorporate these variables when discussing pornography with their adolescents and not only focus on filters or demandingness.

Abstract MALAT1 long non-coding RNA has oncogenic roles but has been poorly studied in indolent B-cell neoplasms. Here, MALAT1 expression was analyzed using RNA-seq, microarrays or qRT-PCR in primary samples from clinico-biological subtypes of chronic lymphocytic leukemia (CLL, n = 266), paired Richter transformation (RT, n = 6) and follicular lymphoma (FL, n = 61). In peripheral blood (PB) CLL samples, high MALAT1 expression was associated with a significantly shorter time to treatment independently from other known prognostic factors. Coding genes expressed in association with MALAT1 in CLL were predominantly related to oncogenic pathways stimulated in the lymph node (LN) microenvironment. In RT paired samples, MALAT1 levels were lower, concordant with their acquired increased independency of external signals. Moreover, MALAT1 levels in paired PB/LN CLLs were similar, suggesting that the prognostic value of MALAT1 expression in PB is mirroring expression differences already present in LN. Similarly, high MALAT1 expression in FL predicted for a shorter progression-free survival, in association with expression pathways promoting FL pathogenesis. In summary, MALAT1 expression is related to pathophysiology and more aggressive clinical behavior of indolent B-cell neoplasms. Particularly in CLL, its levels could be a surrogate marker of the microenvironment stimulation and may contribute to refine the clinical management of these patients.

ABSTRACT: Selection of competent recipients before embryo transfer (ET) is indispensable for improving pregnancy and birth rates in cattle. However, pregnancy prediction can fail when the competence of the embryo is ignored. We hypothesized that the pregnancy potential of biomarkers could improve with information on embryonic competence. In vitro-produced embryos cultured singly for 24 h (from d 6 to 7) were transferred to d 7 synchronized recipients as fresh or after freezing and thawing. Recipient blood was collected on d 0 (estrus; n = 108) and d 7 (4–6 h before ET; n = 107) and plasma was analyzed by nuclear magnetic resonance (1H+NMR). Spent embryo culture medium (CM) was collected and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry in a subset of n = 70 samples. Concentrations of metabolites quantified in plasma (n = 35) were statistically analyzed as a function of pregnancy diagnosed on d 40, d 62 and birth. Univariate analysis with plasma metabolites consisted of a block study with controllable fixed factors (i.e., embryo cryopreservation, recipient breed, and day of blood collection; Wilcoxon test and t-test). Metabolite concentrations in recipients and embryos were independently analyzed by iterations that reclassified embryos or recipients using the support vector machine. Iterations identified some competent embryos, but mostly competent recipients that had a pregnancy incompetent partner embryo. Misclassified recipients that could be classified as competent were reanalyzed in a new iteration to improve the predictive model. After subsequent iterations, the predictive potential of recipient biomarkers was recalculated. On d 0, creatine, acetone and l-phenylalanine were the most relevant biomarkers at d 40, d 62, and birth, and on d 7, l-glutamine, l-lysine, and ornithine. Creatine was the most representative biomarker within blocks (n = 20), with a uniform distribution over pregnancy endpoints and type of embryos. Biomarkers showed higher abundance on d 7 than d 0, were more predictive for d 40 and d 62 than at birth, and the pregnancy predictive ability was lower with frozen-thawed (F-T) embryos. Six metabolic pathways differed between d 40 pregnant recipients for fresh and F-T embryos. Within F-T embryos, more recipients were misclassified, probably due to pregnancy losses, but were accurately identified when combined with embryonic metabolite signals. After recalculation, 12 biomarkers increased receiver operator characteristic-area under the curve (>0.65) at birth, highlighting creatine (receiver operator characteristic-area under the curve = 0.851), and 5 new biomarkers were identified. Combining metabolic information of recipient and embryos improves the confidence and accuracy of single biomarkers.

Resumen Objetivos: Conocer la prevalencia de personas que presentan heridas crónicas en los centros de atención primaria de la Región Sanitaria de Lleida y Alt Pirineu en Catalunya (España), y analizar las características clínicas y demográficas de estos. Metodología: Estudio descriptivo, observacional, de corte transversal, dirigido a los centros de atención primaria durante el 7 y el 14 de junio de 2022. La recogida de datos se realizó mediante formulario seguro online. Se recogió información sobre personas diagnosticadas de heridas crónicas y la tipología de estas. Resultados: La prevalencia de heridas fue del 0,19%. Las úlceras venosas representaron la prevalencia más alta, con un 0,047%, seguidas de las úlceras por presión con un 0,03%. El 51,21% de las personas que presentaban heridas fueron mujeres. La media de edad se situó en los 72 años. La prevalencia según el tipo de lesiones fue: úlceras venosas, 24,91%; lesiones por presión, 15,92%; pie diabético, 9,00%; desgarros cutáneos, 9,17%; úlceras arteriales, 6,40%; dehiscencias de suturas, 6,92%; cicatrización por segunda intención como quistes pilonidales, 4,50%; quemaduras, 3,63%, y dermatitis por incontinencia, 1,21%. Otros tipos de lesiones, 18,34%. Conclusiones: La prevalencia de heridas crónicas fue del 0,19%. Las úlceras venosas fueron las heridas más prevalentes seguidas de las lesiones por presión. La media de edad fue de 72 años, y las mujeres fueron las que presentaron mayor porcentaje de heridas. Estos resultados posibilitan obtener indicadores para valorar los programas de prevención, conocimientos para abordar los distintos tipos de heridas y replantear los recursos destinados a las heridas crónicas.

The usefulness of bronchoalveolar lavage fluid (BALF) to support the diagnosis of acute cellular (ACR) rejection in lung transplant (LTX) recipients remains controversial. ACR has been associated with blood eosinophil counts (EOS) in other solid organ recipients, but there are few studies in relation to lung transplants. Our aim was to assess the usefulness of the combined analysis of BALF cellularity and EOS for the diagnosis of ACR in lung transplant recipients. This is a retrospective study of findings observed simultaneously in 887 transbronchial biopsies (TBB), BALF, and blood samples obtained from 363 LTx patients transplanted between 2014 and 2020. The variables collected were: demographics, ACR degree, BALF cellularity, and simultaneous blood EOS counts. The lymphocyte count in BALF was significantly higher in patients with ACR than in those without (11.35% vs. 6.11%; p < 0.001). In parallel, EOS counts were also significantly higher in patients with ACR than in the non-ACR group (EOS 213 ± 206/mm3 vs. 83 ± 129/mm3; p < 0.001). Increases in both parameters were associated with an increased risk of ACR (lymphocytes OR 1.100; 95% CI 1.080–1.131; EOS OR 1.460; 95% CI 1.350–1.580). The diagnostic specificity of ACR for a lymphocyte count > 12% was 71.1%, which increased to 95.8% when taking into account a simultaneous blood EOS count > 200/mm3. Simultaneous assessment of BALF lymphocyte counts and blood eosinophil counts may be useful for diagnosing ACR in patients with risk factors for TBB or in the presence of inconclusive histological samples.

Augmentative and Alternative Communication (aac) strategies ease communication tasks for people who require accessible solutions. These strategies are usually addressed by technological solutions such as mobile applications. This research seeks clues on the development of such applications by analyzing user interactions with Android application PictoDroid Lite, an aac communicator. This study considered a data set containing more than 85,000 interactions of users from more than 50 countries. The goal was to identify the primary needs reflected in the users’ behavior and how these applications handle them, providing other researchers and developers with relevant information about how users interact with these applications. We detected areas of improvement regarding the adaptation to users’ needs in terms of profiling, smart suggestions, and time habits.

Introduction Human albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and healthcare systems. A precision medicine approach with biomarkers to predict human albumin treatment response, so-called predictive biomarkers, could make this a viable treatment option in patients with cirrhosis and ascites.Methods and analysis ALB-TRIAL is a multinational, double-blind, placebo-controlled randomised controlled trial. We aim to validate a predictive biomarker, consisting of a panel of circulating metabolites, to predict the treatment response to human albumin in patients with cirrhosis and ascites. All enrolled patients are stratified into a high-expected or low-expected effect stratum of human albumin based on the biomarker outcome. After stratification, patients in each group are randomised into either active treatment (20% human albumin) or corresponding placebo (0.9% NaCl) every 10th day for 6 months. The primary outcome is the cumulative number of liver-related events (composite of decompensation episodes, transjugular intrahepatic shunt insertion, liver transplantation and death). Key secondary outcomes include time-to-event analysis of primary outcome components, an analysis of the total healthcare burden and a health economic analysis.Ethics and dissemination The trial obtained ethical and regulatory approval in Denmark, Germany, the Netherlands, Belgium, Hungary and Spain through the Clinical Trials Information System (CTIS) from 13 February 2023, while UK approvals from the Health Regulatory Authority, Medicines and Healthcare products Regulatory Agency and Research Ethics Committee are pending. Findings will be published in peer-reviewed journals, presented at conferences, communicated to relevant stakeholders and in the public registry of CTIS, following trial completion.Trial registration number NCT05056220 EU CT: 2022-501006-34-01

Exotic companion animals have had an important role in our society since ancient times. Preserving animal health is necessary to do a responsible use of veterinary medicines. This study aimed to describe the prescription patterns of drugs in exotic pets and wildlife animals attending the Veterinary Teaching Hospital of the University of León (HVULE). A retrospective study was carried out between 2018 and 2022. Birds were the largest group of exotic animals attending the HVULE. Visits were related to emergency reasons and for musculoskeletal disorders. One-third of the animals were eventually euthanised. Regarding pharmacological treatments, the most frequently active ingredients used were pentobarbital, isoflurane, meloxicam, and within antibiotics, marbofloxacin (category B in the classification of European Medicines Agency).

Abstract BackgroundNew interventions based on motor learning principles and neural plasticity have been tested among patients with ataxia and hemiparesis. Therapies of pedaling exercises have also shown their potential to induce improvements in muscle activity, strength, and balance. Virtual reality (VR) has been demonstrated as an effective tool for improving the adherence to physical therapy, but it is still undetermined if it promotes greater improvements than conventional therapy. ObjectiveOur objective was to compare the effect on lower limb range of motion (ROM) when using VR technology for cycling exercise versus not using VR technology. MethodsA randomized controlled trial with 20 patients with ataxia and hemiparesis was carried out. The participants were divided into 2 groups: the experimental group (n=10, 50%) performed pedaling exercises using the VR system and the control group (n=10, 50%) performed pedaling exercises without using VR. Measurements of the active and passive ROM of the hip and knee joint were taken before and after a cycling intervention, which consisted of 3 sessions of the same duration but with progressively increasing speeds (4, 5, and 6 km/h). Repeated measures ANOVAs were conducted to compare the preintervention (TieΔeit ResultsSignificant improvements were shown in active left hip flexion (PPPPPPPPPPPPPP ConclusionsIn this study, participants who underwent the cycling intervention using the VR system showed similar improvement in lower limb ROM to the participants who underwent conventional training. Ultimately, the VR system can be used to engage participants in physical activity.

Los análisis de huellas de uso, traceológicos o funcionales forman parte de una metodología aplicada a materiales arqueológicos que permite, a través del análisis microscópico de su superficie, determinar las actividades en las que han participado. En este trabajo se lleva a cabo una aproximación historiográfica de la disciplina desde sus orígenes hasta la actualidad, incidiendo en los estudios de huellas de uso aplicados a la industria lítica prehistórica.

Antecedentes: Los trasplantados pulmonares son un grupo con mayor riesgo de desarrollar enfermedad por coronavirus 2019 (COVID-19) grave. El sotrovimab demostró reducir el riesgo de progresión de enfermedad y ha sido utilizado en pacientes con trasplante de órgano sólido, pero no ha sido estudiado en trasplantados pulmonares. Objetivo: Describir la evolución de la COVID-19 en trasplantados pulmonares tratados con sotrovimab. Método: Estudio observacional retrospectivo que incluyó trasplantados pulmonares que recibieron sotrovimab para la COVID-19 entre 2021 y 2022. Resultados: Se estudiaron 33 pacientes, 19 varones, con edad media de 61 años, 24 de ellos trasplantados bipulmonares, siendo las causas más frecuentes la enfermedad pulmonar intersticial difusa y la enfermedad pulmonar obstructiva crónica. El 90% requirieron ingreso. La mayoría necesitó algún tipo de soporte respiratorio, pudiéndose manejar el 39% con bajo flujo. El 42% presentaron sobreinfecciones, el 12% tromboembolia pulmonar y el 58% insuficiencia renal aguda. Seis pacientes fallecieron. Conclusiones: Este estudio presenta resultados similares a otros realizados en pacientes con trasplante de otro órgano sólido que recibieron sotrovimab respecto a tasas de hospitalización, mortalidad y seguridad. Se describe una menor mortalidad respecto a estudios previos de trasplantados pulmonares con infección por coronavirus 2 del síndrome respiratorio agudo grave previo al uso de sotrovimab. Este estudio sugiere que el sotrovimab es una opción terapéutica válida para la COVID-19 en trasplantados pulmonares.

Abstract Dermatological conditions are a relevant health problem. Machine learning (ML) models are increasingly being applied to dermatology as a diagnostic decision support tool using image analysis, especially for skin cancer detection and disease classification. The objective of this study was to perform a prospective validation of an image analysis ML model, which is capable of screening 44 skin diseases, comparing its diagnostic accuracy with that of General Practitioners (GPs) and teledermatology (TD) dermatologists in a real-life setting. Prospective, diagnostic accuracy study including 100 consecutive patients with a skin problem who visited a participating GP in central Catalonia, Spain, between June 2021 and October 2021. The skin issue was first assessed by the GPs. Then an anonymised skin disease picture was taken and uploaded to the ML application, which returned a list with the Top-5 possible diagnosis in order of probability. The same image was then sent to a dermatologist via TD for diagnosis, as per clinical practice. The GPs Top-3, ML model’s Top-5 and dermatologist’s Top-3 assessments were compared to calculate the accuracy, sensitivity, specificity and diagnostic accuracy of the ML models. The overall Top-1 accuracy of the ML model (39%) was lower than that of GPs (64%) and dermatologists (72%). When the analysis was limited to the diagnoses on which the algorithm had been explicitly trained (n = 82), the balanced Top-1 accuracy of the ML model increased (48%) and in the Top-3 (75%) was comparable to the GPs Top-3 accuracy (76%). The Top-5 accuracy of the ML model (89%) was comparable to the dermatologist Top-3 accuracy (90%). For the different diseases, the sensitivity of the model (Top-3 87% and Top-5 96%) is higher than that of the clinicians (Top-3 GPs 76% and Top-3 dermatologists 84%) only in the benign tumour pathology group, being on the other hand the most prevalent category (n = 53). About the satisfaction of professionals, 92% of the GPs considered it as a useful diagnostic support tool (DST) for the differential diagnosis and in 60% of the cases as an aid in the final diagnosis of the skin lesion. The overall diagnostic accuracy of the model in this study, under real-life conditions, is lower than that of both GPs and dermatologists. This result aligns with the findings of few existing prospective studies conducted under real-life conditions. The outcomes emphasize the significance of involving clinicians in the training of the model and the capability of ML models to assist GPs, particularly in differential diagnosis. Nevertheless, external testing in real-life conditions is crucial for data validation and regulation of these AI diagnostic models before they can be used in primary care.

Abstract Background The risk of hypertensive disorders of pregnancy (HDP) varies in women with gestational diabetes mellitus (GDM), depending on the degree of insulin resistance and is also influenced by obesity. The aim of this study was to evaluate clinical features, blood pressure (BP) profiles and inflammatory markers, to identify patients with an elevated risk of developing HDP. Methods A total of 146 normotensive pregnant women were studied. We analysed the relationships of BP profiles detected by ambulatory blood pressure monitoring (ABPM) with serum biomarkers and angiogenic factors and their association with the development of HDP. Results Fourteen (9.6%) women developed HDP, of which 11 had GDM and 8 had obesity. Women with HDP had higher values of 24-h and daytime systolic/diastolic BP (113/69 vs. 104/64; 115/72 vs. 106/66 mmHg, respectively; p

IntroductionAlthough higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy.MethodsThe expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using in vitro models. In addition, PSGL-1 impact on T-cells function was evaluated by ex vivo models.ResultsData showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia.DiscussionIn conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.

Se presenta el caso clínico de un paciente que asocia tres trastornos de sueño diferentes: narcolepsia, apnea obstructiva del sueño (AOS) y trastorno de conducta del sueño REM. El objetivo es resaltar la importancia de la narcolepsia, una patología infradiagnosticada y que a veces puede quedar enmascarada por otros trastornos de sueño. En este caso, el paciente es diagnosticado inicialmente de AOS, pero dado que persiste con hipersomnolencia diurna debemos descartar otras causas.

This paper presents the current state of research on the Early Neolithic flint quarry of Pozarrate (Treviño, Burgos) in the north of Spain. This site is part of the Prehistoric Flint Mining Complex of Treviño. The geological features of the territory made it a suitable place for the exploitation of the Treviño flint since Paleolithic times, especially during the Neolithic. Recent research at the site has revealed interesting findings, such as antler and dolerite mining equipment and different flint tools, among other recoveries. Radiocarbon dates indicate an Early Neolithic activity which makes Pozarrate one of the few flint procurement sites in the Iberian Peninsula from this period. Moreover, a considerable number of elements link Pozarrate to the Early European Neolithic flint mining phenomenon.

Resumen El concepto “mezcla de usos” se ha convertido en un principio de planificación urbana clave en muchos de los actuales paradigmas de desarrollo urbano. Sin embargo, a pesar de su popularidad, el término permanece impreciso en su manera de entenderlo y aplicarlo. Este trabajo parte de la hipótesis de que, en el contexto alemán, la “mezcla de usos” está vinculada a la movilidad peatonal, siendo Alemania un referente de inclusión de esta variable en los planes de desarrollo urbano desde hace décadas, combinándolo con conceptos de movilidad sostenible basados en el modelo de “la ciudad de las distancias cortas”. A partir de una revisión sistemática se explora y analiza la comprensión de la variable “mezcla de usos”, se presentan tres ejemplos de aplicación y se concluye con una definición del concepto, su relación con la movilidad sostenible y peatonal y los elementos clave para su implementación. Abstract The concept of “mixed use” has become a key urban planning principle in many of today's urban development paradigms. Yet despite its popularity, the term remains vague in its understanding and application. This paper starts from the hypothesis that, in the German context, “mixed use” is strongly linked to pedestrian mobility, being Germany a reference where this variable has been included in urban development plans decades ago in combination with sustainable mobility concepts based on the model of "the city of short distances". Based on a systematic review, the understanding of the "mixed use" variable was explored and analyzed. Three examples of the application are presented. It’s concluded with a definition of the concept of “mixed use”, its relation to sustainable and pedestrian mobility and the key elements for its implementation in concrete projects.

Resumen: Antecedentes y objetivo: Tras el trasplante renal se produce de manera global un incremento del peso pudiendo aumentar el riesgo de enfermedad renal crónica (ERC) y de pérdida del injerto. Pero no todos los pacientes ganan peso, y la repercusión sobre el injerto de esta diferente evolución, no está bien estudiado. El objetivo fue determinar las causas de esta diferente evolución y su efecto sobre el injerto. Pacientes y métodos: Estudio de cohortes retrospectivo unicéntrico de 201 pacientes seguidos tras el trasplante, analizando los determinantes de la variación del peso al año mediante regresión logística, y su efecto sobre la pérdida del injerto al final del seguimiento mediante regresión de Cox. Resultados: Globalmente se produjo durante el primer año un aumento de peso de 4,5 kg de media, pero un 26,6% perdieron peso. El 37,2% aumentó su índice de masa corporal (IMC), mientras que el 9,5% lo disminuyó. Los determinantes de la diferente evolución del peso fueron la edad (OR por cada 10 años: 0,6; p = 0,002), la modalidad de diálisis previa (ref. hemodiálisis) (OR: 0,3; p = 0,003) y el IMC previo al trasplante (OR: 0,9; p = 0,003). La diferente evolución del peso no influyó en la pérdida del injerto. Sí influyeron el IMC al año como variable continua (HR: 1,3; p = 0,003) y la obesidad, con peor evolución (HR: 7,0; p = 0,025). Conclusiones: Aunque no todos los pacientes ganan peso tras el trasplante renal, la diferente evolución del peso no influye en la supervivencia del injerto. Abstract: Background and objective: After kidney transplantation, there is an overall increase in weight, which may increase the risk of chronic kidney disease (CKD) and graft loss. But, not all patients gain weight, and the impact on the graft of this different evolution has not been well studied. The objective was to determine the causes of this different evolution and its effect on the graft. Patients and methods: Retrospective single-center cohort study of 201 patients followed up after transplantation, analyzing the determinants of the variation in weight at one year using logistic regression, and its effect on graft survival at the end of follow-up using Cox regression. Results: Globally, there was an average weight gain of 4.5 kg in the first year, but 26.6% lost weight. 37.2% increased their BMI, while 9.5% decreased it. The determinants of the different evolution of weight were age (OR for every 10 years: 0.6, P=.002), previous dialysis modality (ref. hemodialysis) (OR 0.3, P=.003), and BMI before transplantation (OR 0.9, P=.017). The different evolution of weight did not influence the final situation of the graft. The BMI at one year did influence as a continuous variable (HR 1.3, P=.003), and obesity, with a worse evolution (HR 7.0, P=.025). Conclusions: Although not all patients gain weight after kidney transplantation, the different evolution of weight does not influence graft survival.

Background and objective: After kidney transplantation, there is an overall increase in weight, which may increase the risk of chronic kidney disease (CKD) and graft loss. But, not all patients gain weight, and the impact on the graft of this different evolution has not been well studied. The objective was to determine the causes of this different evolution and its effect on the graft. Patients and methods: Retrospective single-center cohort study of 201 patients followed up after transplantation, analyzing the determinants of the variation in weight at one year using logistic regression, and its effect on graft survival at the end of follow-up using Cox regression. Results: Globally, there was an average weight gain of 4.5 kg in the first year, but 26.6% lost weight. 37.2% increased their BMI, while 9.5% decreased it. The determinants of the different evolution of weight were age (OR for every 10 years: 0.6, p = 0.002), previous dialysis modality (ref. hemodialysis) (OR 0.3, p = 0.003), and BMI before transplantation (OR 0.9, p = 0.017). The different evolution of weight did not influence the final situation of the graft. The BMI at one year did influence as a continuous variable (HR 1.3, p = 0.003), and obesity, with a worse evolution (HR 7.0, p = 0.025). Conclusions: Although not all patients gain weight after kidney transplantation, the different evolution of weight does not influence graft survival. Resumen: Antecedentes y objetivo: Tras el trasplante renal se produce de manera global un incremento del peso pudiendo aumentar el riesgo de enfermedad renal crónica (ERC) y de pérdida del injerto. Pero no todos los pacientes ganan peso, y la repercusión sobre el injerto de esta diferente evolución, no está bien estudiado. El objetivo fue determinar las causas de esta diferente evolución y su efecto sobre el injerto. Pacientes y métodos: Estudio de cohortes retrospectivo unicéntrico de 201 pacientes seguidos tras el trasplante, analizando los determinantes de la variación del peso al año mediante regresión logística, y su efecto sobre la pérdida del injerto al final del seguimiento mediante regresión de Cox. Resultados: Globalmente se produjo durante el primer año un aumento de peso de 4,5 kg de media, pero un 26,6% perdieron peso. El 37,2% aumentó su índice de masa corporal (IMC), mientras que el 9,5% lo disminuyó. Los determinantes de la diferente evolución del peso fueron la edad (OR por cada 10 años: 0,6; p = 0,002), la modalidad de diálisis previa (ref. hemodiálisis) (OR: 0,3; p = 0,003) y el IMC previo al trasplante (OR: 0,9; p = 0,003). La diferente evolución del peso no influyó en la pérdida del injerto. Sí influyeron el IMC al año como variable continua (HR: 1,3; p = 0,003) y la obesidad, con peor evolución (HR: 7,0; p = 0,025). Conclusiones: Aunque no todos los pacientes ganan peso tras el trasplante renal, la diferente evolución del peso no influye en la supervivencia del injerto.

Follicular lymphoma (FL), a generally indolent disease that derives from germinal center (GC) B cells, represents around 20–25% of all new lymphomas diagnosed in Western countries. The characteristic t(14;18)(q32;q21) translocation that places the BCL2 oncogene under control of the immunoglobulin heavy-chain enhancer occurs in pro- or pre-B cells. However, additional secondary alterations are required for the development of overt FL, which mainly affects genes involved in epigenetic and transcriptional regulation, signaling and B cell differentiation, the BCR/NF-κB pathway, and proliferation/apoptosis. On the other hand, new insights into the FL pathogenesis suggest that FL lacking the BCL2 translocation might be a distinct biological entity with genomic features different from the classical FL. Although FL is considered an indolent disease, around 10–20% of cases eventually transform to an aggressive lymphoma, usually a diffuse large B cell lymphoma, generally by a divergent evolution process from a common altered precursor cell acquiring genomic alterations involved in the cell cycle and DNA damage responses. Importantly, FL tumor cells require interaction with the microenvironment, which sustains cell survival and proliferation. Although the use of rituximab has improved the outlook of most FL patients, further genomic studies are needed to identify those of high risk who can benefit from innovative therapies. This review provides an updated synopsis of FL, including the molecular and cellular pathogenesis, key events of transformation, and targeted treatments.

IntroductionIn the process of growing societies, and especially in the digital era we live in, there is a need for a strong push for innovation that puts citizens at the center of the process from the beginning to build more resilient, cooperative and flexible communities. Different collaborative design approaches have emerged in recent decades, one of the most interesting being Living Labs, which involves user-centered design and co-creative innovation that bring together different actors and roles. However, although these new methodologies are harnessing creativity, some aspects of this new, more ecosystemic and complex vision are not clearly understood: possible barriers, how to facilitate local and operational solutions, overcoming institutional blockage, integrating new roles, etc.MethodsThe incorporation of the Quintuple Helix as a driver to ensure greater coordinated participation of local actors has proven its usefulness and impact during the re-adaptation of LifeSpace (previously named Smart House Living Lab), managed by the Polytechnic University of Madrid (Spain), a transformation based on the experiences and lessons learned during the large-scale ACTIVAGE pilot funded by the European Commission, more specifically at the Madrid Deployment Site. It involved more than 350 older adult people and other stakeholders from different areas, including family members, formal and informal caregivers, hospital service managers, third-age associations, and public service providers, forming a sense of community, which was called MAHA.ResultsThe living lab infrastructure evolved from a single multi-purpose environment to incorporate three harmoniously competing environments: (1) THE LAB: Headquarters for planning, demonstration, initial design phases and entry point for newcomers to the process, (2) THE CLUB: Controlled interaction environment where returning users validate solutions, focusing mainly on AHA services (MAHA CLUB), such as exergames, social interaction applications, brain training activities, etc. (3) THE NEIGHBOURHOOD: Real-life environments for free and open interaction between actors and implementation of previously validated and tested solutions.ConclusionThe Quintuple Helix model applied in LifeSpace’s new vision allows a coordinated involvement of a more diverse set of actors, beyond the end-users and especially those who are not traditionally part of research and innovation processes.

The present study investigated the qualitative nature of grammatical gender knowledge and processing in heritage speakers (HSs) of Spanish living in the United States. Forty-four adult Spanish HS bilinguals participated, completing a behavioral grammatical gender assignment task and a grammaticality judgment task (GJT) while their brain activity was recorded using electroencephalography (EEG). The EEG GJT task included grammatical and ungrammatical sentences with grammatical gender violations on inanimate nouns, where transparency of the morpho(phono)logical cue and markedness were manipulated. The results of this study revealed that grammatical gender violations elicited the typical P600 effect across all relevant conditions, indicating that the grammatical representations and processing of grammatical gender in HSs are qualitatively similar to those in Spanish-dominant native speakers. Given the experimental manipulation in this study, these findings also suggest that both morphological transparency and markedness play significant roles in how grammatical gender is processed. However, the results of this study differ from those reported in previous studies with Spanish-dominant native speakers, as the P600 effect found was accompanied by a biphasic N400 effect. This pattern of results is interpreted as further evidence that the bilingual experience of HSs modulates certain aspects of morphosyntactic processing, particularly conferring a greater reliance on morphology. Additionally, the results of this study highlight the importance of incorporating neurolinguistic online processing methods to better understand what underlies HS bilingual competence and processing outcomes.

Albumin infusions are therapeutically used to revert hypoalbuminemia and to replace the extensively oxidized albumin molecule circulating in patients with acutely decompensated (AD) cirrhosis. Because albumin has high affinity for lipids, here we characterized the albumin lipidome in patients with AD and explored the albumin effects on the release of fatty acid (FA)–derived lipid mediators by peripheral leukocytes. Lipids and lipid mediators were measured by liquid chromatography–tandem mass spectrometry in albumin‐enriched and albumin‐depleted plasma fractions separated by affinity chromatography and in leukocyte incubations from 18 patients with AD and 10 healthy subjects (HS). Lipid mediators were also measured in 41 patients with AD included in an albumin therapy trial. The plasma lipidome associated with AD cirrhosis was characterized by generalized suppression of all lipid classes except FAs. In contrast to HS, albumin from patients with AD had lower content of polyunsaturated FAs (PUFAs), especially of the omega‐3‐PUFA docosahexaenoic acid. Consistent with this, the PUFA‐derived lipid mediator landscape of albumin from patients with AD was dominated by lower content of monohydroxy FA precursors of anti‐inflammatory/pro‐resolving lipid mediators (i.e., 15‐hydroxyeicosatetraenoic acid [15‐HETE]). In addition, albumin from patients with AD was depleted in prostaglandin (PG) E2, suggesting that this proinflammatory PG primarily travels disassociated to albumin in these patients. Incubation of leukocytes with exogenous albumin reduced PG production while inducing 15‐lipoxygenase expression and 15‐HETE release. Similar effects were seen under lipopolysaccharide plus N‐formylmethionyl‐leucyl‐phenylalanine‐stimulated conditions. Finally, PG levels were lower in patients with AD receiving albumin therapy, whereas 15‐HETE was increased after albumin treatment compared with baseline. Conclusion: Our findings indicate that the albumin lipid composition is severely disorganized in AD cirrhosis and that administration of exogenous albumin has the potential to redirect leukocyte biosynthesis from pro‐inflammatory to pro‐resolving lipid mediators.

This study explored the effects of a modular overground exoskeleton on plantar pressure distribution in healthy individuals and individuals with Acquired Brain Injury (ABI). The research involved 21 participants, including ABI patients and healthy controls, who used a unique exoskeleton with adaptable modular configurations. The primary objective was to assess how these configurations, along with factors such as muscle strength and spasticity, influenced plantar pressure distribution. The results revealed significant differences in plantar pressures among participants, strongly influenced by the exoskeleton’s modularity. Notably, significant distinctions were found between ABI patients and healthy individuals. Configurations with two modules led to increased pressure in the heel and central metatarsus regions, whereas configurations with four modules exhibited higher pressures in the metatarsus and hallux regions. Future research should focus on refining and customizing rehabilitation technologies to meet the diverse needs of ABI patients, enhancing their potential for functional recovery.