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Neuropsychological assessment is essential in patients with cognitive impairment and could be coupled with psychophysiological techniques. Specifically, quantitative electroencephalography may complement data from neuroimage, neurophysiology, and neuropsychology providing relevant information about brain functioning and dynamics. A 77-year-old male consulted for expressive language difficulties that began at age 65. Neuroimaging findings revealed atrophy and hypometabolism of the left temporal and frontal lobe, with cerebral microlesions. Quantitative electroencephalography findings showed decreased absolute and relative power, low alpha peak frequency, and marked inter- and intrahemispheric frontal and temporal asymmetries. The neuropsychological profile showed alteration in executive and expressive language domains, consistent with neuroimaging and psychophysiological findings. A diagnosis of primary progressive aphasia, a form of frontotemporal dementia, as well as a small vessel disease and mild cognitive impairment was concluded. Neuropsychological and quantitative electroencephalography data contribute to the diagnosis and would help determine the disease progression.

Abstract Digital well-being, which refers to a balanced individual experience of digital consumption, has been gaining attention recently in the study of the effects of digital technology use. Social networks are central in debates over digital well-being, as social media overuse is often identified as a primary issue. Teenagers who spend an average of three hours daily on social media especially draw the attention of researchers. Based on statistical evidence, TikTok is the most popular network among young users worldwide. However, there are not many platform-specific studies on its effects on adolescent well-being. One of the most consistent gaps is the lack of research on how different aspects involved in TikTok use impact adolescents’ digital well-being on the app. In light of this, the study aimed to explore the relationship between time spent on TikTok, content consumption, and self-perception of digital well-being. Given the scientific consensus on social media’s greater impact on girls, this study also sought to examine gender differences. For that purpose, a quantitative cross-sectional study was conducted with 737 Spanish adolescents aged 12 to 18, who completed an online questionnaire with validated scales and items on daily usage time, type of content consumption, and digital well-being. Results showed significant gender differences in TikTok usage and content consumption: girls spent more time on TikTok and notably engaged more with beauty and fashion content, while boys with video games and sports content, suggesting that traditional gender roles are still present in their choices of content consumption. Beyond that, a rather positive self-perception of digital well-being on TikTok by teenagers was observed. Despite this, an increased TikTok usage was associated with a reduced ability to set boundaries and limit their time on the app. These findings highlight the need for measures to limit the time adolescents spend on TikTok, such as mandatory parental controls on electronic devices and educational programs aimed at promoting healthy digital habits.

Abstract In recent years, research has progressively increased the importance of considering sex differences in stress and fear memory studies. Many studies have traditionally focused on male subjects, potentially overlooking critical differences with females. Emerging evidence suggests that males and females can exhibit distinct behavioral and neurophysiological responses to stress and fear conditioning. These differences may be attributable to variations in hormone levels, brain structure, and neural circuitry, particularly in regions such as the prefrontal cortex (PFC). In the present study, we explored sex differences in prelimbic cortex (PL) calcium activity in animals submitted to immobilization stress (IMO), fear conditioning (FC), and fear extinction (FE). While no significant sex differences were found in behavioral responses, we did observe differences in several PL calcium activity parameters. To determine whether these results were related to behaviors beyond stress and fear memory, we conducted correlation studies between the movement of the animals and PL activity during IMO and freezing behavior during FC and FE. Our findings revealed a clear correlation between PL calcium activity with movement during stress exposure and freezing behavior, with no sex differences observed in these correlations. These results suggest a significant role for the PL in movement and locomotion, in addition to its involvement in fear-related processes. The inclusion of both female and male subjects is crucial for studies like this to fully understand the role of the PFC and other brain areas in stress and fear responses. Recognizing sex differences enhances our comprehension of brain function and can lead to more personalized and effective approaches in the study and treatment of stress and fear-related conditions.

The Lean Management had its origin in the 50s in the Japanese automobile industry, and is currently used in different production processes, included those related to pharmaceutical production, for which has raised its application in the manufacture of loperamide HCl-orodispersible tablets (HCl-ODT) under the coordination of the Pharmaceutical Quality System (PQS). A theoretical proposal for process reengineering has been carried out both incorporating and applying the different Lean tools in the industrial manufacturing process of HCl-ODT, and their subsequent integration into the PQS, through each one of the processes stages, such as: weighing, screening, mixing, compression, and packaging, under the compliance of the current legislation of the pharmaceutical industry and in compatibility with what is established in the ICHs within the Quality System, in order to increase the effectiveness and efficiency of the process and its profitability. Lean Management under the coordination of the Pharmaceutical Quality System (PQS), is an excellent strategy for manufacturing loperamide HCl-orodispersible tablets since it improves its Quality System, as well as facilitates compliance with the national and international guides, standards and legislation that are suitable to it.

The Antarctic Ice Sheet (AIS) has experienced accelerated loss of ice over the last decades and could become the main contributor to sea level rise in the coming centuries. However, the associated uncertainty is very large. The main sources of this uncertainty lie in the future scenarios, the climatic forcing and, most notably, the structural uncertainty due to our lack of understanding of ice–ocean interaction processes, in particular, the representation of subshelf basal melt. In this study, we use a higher-order ice sheet model to investigate the impact of these three sources of uncertainty on the contribution of the AIS to sea level in the coming centuries in the context of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6) but extending the projections to 2500. We test the sensitivity of the model to basal melting parameters using several forcings and scenarios simulated in the CMIP5 and CMIP6 ensembles. Results show a strong dependency on the values of the parameter that controls the heat exchange velocity between ice and ocean as well as the forcing and scenario. Higher values of the heat exchange parameter lead to higher sea level rise, with the contribution depending on the forcing–scenario configuration and reaching in some cases more than 3 m in sea level equivalent by the end of 2500. Idealized simulations considering the individual effects of the atmospheric and the oceanic forcing have been performed, demonstrating that the oceanic forcing plays a dominant role over the western sector of the AIS, while the atmospheric forcing is more important for the eastern sector and the interior.

Background and purpose: Open reduction is rarely performed in pediatric supracondylar humerus fractures. However, clear evidence is lacking regarding the optimal open approach to achieve satisfactory results. The anterior approach provides direct visualization of the fracture and excellent exposure to neurovascular structures, although its utilization is less common. The objective of this study was to review the indications, outcomes, and complications associated with the anterior approach for open reduction of these fractures. Methods: Our protocol was registered at PROSPERO: CRD42023446923. MEDLINE/PubMed, Embase, Web of Science, Clinicaltrials.gov, and Cochrane Library were searched from database inception to search date (December 2023) and screened in duplicate for relevant studies. Data were collected regarding patient demographics, indications for open reduction, Flynn's functional and cosmetic outcomes, and complications. Study quality was assessed using the Methodological Index for Non-Randomized Studies Criteria. Results: A total of 19 studies involving 483 patients were included. One study was classified as Level 2 evidence, ten as Level 3, and eight as Level 4. The mean MINORS score was 13.05 ± 3.47. The primary indication for open reduction was failed closed reduction, observed in 46% of patients. 97.7% and 98.6% of patients achieved Flynn's functional and cosmetic satisfactory results, respectively. The postsurgical neurovascular injury rate was 1.4%. One patient required reintervention. Conclusion: The anterior approach is safe and effective for managing pediatric supracondylar humerus fractures requiring open reduction. Level of evidence: Systematic review of Level 2–4 evidence studies. Resumen: Antecedentes y objetivo: La reducción abierta rara vez es necesaria en las fracturas supracondíleas de húmero pediátrica. Sin embargo, falta evidencia sobre cuál es el abordaje óptimo para obtener resultados satisfactorios. El abordaje anterior facilita una visión directa de la fractura y una excelente exposición de las estructuras neurovasculares, aunque su uso es poco común. El objetivo de este estudio fue revisar las indicaciones, resultados y complicaciones asociadas con el abordaje anterior para la reducción abierta de estas fracturas. Métodos: Nuestro protocolo se registró en PROSPERO: CRD42023446923. La búsqueda se realizó en MEDLINE/PubMed, Embase, Web of Science, Clinicaltrials.gov y Cochrane Library, desde inicios hasta diciembre de 2023. Se realizó screening por duplicado. Se recogieron datos demográficos, indicaciones para el abordaje abierto, puntuación de Flynn funcional y estética y complicaciones. La calidad de los estudios se evaluó con Methodological Index for Non-Randomized Studies Criteria (MINORS). Resultados: Se incluyeron 19 estudios que agrupaban a 483 pacientes. Un estudio se clasificó con nivel de evidencia 2, 10 con nivel 3, y 8 con nivel 4. La puntuación media MINORS fue 13,05 ± 3,47. La indicación principal para el abordaje abierto fue el fracaso de la reducción cerrada, reportada en 46% de pacientes. El 97,7% y 98,6% de los pacientes lograron un Flynn funcional y cosmético satisfactorio, respectivamente. La tasa de lesiones neurovasculares postquirúrgicas fue 1,4%. Un paciente fue reintervenido. Conclusiones: El abordaje anterior es seguro y efectivo en el maneco de fracturas supracondíleas de húmero pediátricas cuando se requiera un abordaje abierto. Nivel de evidencia: Revisión sistemática de estudios con nivel de evidencia 2-4.

Tipping elements, including the Antarctic Ice Sheet (AIS), are Earth system components that could reach critical thresholds due to anthropogenic emissions. Increasing our understanding of past warm climates can help to elucidate the future contribution of the AIS to emissions. The mid-Pliocene Warm Period (mPWP; ∼ 3.3–3.0 million years ago) serves as an ideal benchmark experiment. During this period, CO2 levels were similar to the present day (PD; 350–450 ppmv), but global mean temperatures were 2.5–4.0 K higher. Sea level reconstructions from that time indicate a rise of 5–25 m compared to the present, highlighting the potential crossing of tipping points in Antarctica. In order to achieve a sea level contribution far beyond 10 m, not only the West Antarctic Ice Sheet (WAIS) needs to largely decrease, but a significant response in the East Antarctic Ice Sheet (EAIS) is also required. A key question in reconstructions and simulations is therefore which of the AIS basins retreated during the mPWP. In this study, we investigate how the AIS responds to climatic and bedrock conditions during the mPWP. To this end, we use the Pliocene Model Intercomparison Project, Phase 2 (PlioMIP2), general circulation model ensemble to force a higher-order ice sheet model. Our simulations reveal that the WAIS experiences collapse with a 0.5 K oceanic warming. The Wilkes Basin shows retreat at 3 K oceanic warming, although higher precipitation rates could mitigate such a retreat. Totten Glacier shows slight signs of retreats only under high-oceanic warming conditions (greater than 4 K oceanic anomaly). If only the WAIS collapses, we simulate a mean contribution of 2.7 to 7.0 ms.l.e. (metres of sea level equivalent). If, in addition, the Wilkes Basin retreats, our simulations suggest a mean contribution of 6.0 to 8.9 ms.l.e. Besides uncertainties related to the climate forcing, we also examine other sources of uncertainty related to initial ice thickness and ice dynamics. We find that the climatologies yield a higher uncertainty than the dynamical configuration if parameters are constrained with PD observations and that starting from Pliocene reconstructions leads to smaller ice sheet configurations due to the hysteresis behaviour of marine bedrocks. Ultimately, our study concludes that marine ice cliff instability is not a prerequisite for the retreat of the Wilkes Basin. Instead, a significant rise in oceanic temperatures can initiate such a retreat.

Abstract B cell chronic lymphocytic leukaemia (B‐CLL) presenting with cutaneous infiltration is rare, and when it occurs, it presents most commonly on the head and neck. We present the case of an 80‐year‐old woman with a 2‐month history of erythema, swelling and pain affecting all her toes. She had a history of B‐CLL diagnosed 20 years previously that had remained stable under observation without treatment. A toe skin biopsy showed a diffuse infiltrate of lymphoid cells occupying the dermis composed of small mature lymphoid cells with a monotonous appearance. On immunohistochemistry, the neoplastic lymphoid cells stained positive for the B‐cell marker CD20. Overall, the morphology and immunophenotype were consistent with cutaneous involvement by chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). We concluded that her symptoms were directly caused by skin infiltration of B‐CLL.

Background: The treatment of psoriasis in patients with a personal history of cancer is a matter of debate and limited evidence is available to guide clinicians. Objectives: To report a multicenter real-life experience of a group of patients with psoriasis undergoing treatment with guselkumab and a history of cancer. Methods: We conducted a multicenter retrospective Spanish study enrolling patients with moderate-to-severe plaque psoriasis and neoplasia being treated with guselkumab for their psoriasis. Results: Twenty patients with moderate-to-severe psoriasis and at least 12 weeks of ongoing treatment were included. For the analysis, a 52 week follow-up period was evaluated in terms of efficacy and safety. Most of the malignancies in these patients were solid tumors. The percentage of patients achieving psoriasis area and severity index ≤3 at week 12 and week 52 was 80% and 87.5%, respectively, whereas 68.8% of patients achieved psoriasis area and severity index ≤1. A 52-week survival rate of 100% in the study population was observed (n = 20), including those patients with concomitant active cancers (n = 14). No adverse effects or dropouts related to guselkumab safety profile were detected. Limitations: Modest sample size and the retrospective nature of the study. Conclusion: Guselkumab not only demonstrates high effectiveness in treating psoriasis but also exhibits a favorable safety profile in patients with neoplasms.

Objectives: Urinary tract infections (UTIs) are common infections within the Emergency Department (ED), causing increased laboratory workloads and unnecessary antibiotics prescriptions. The aim of this study was to improve UTI diagnostics in clinical practice by application of machine learning (ML) models for real-time UTI prediction. Methods: In a retrospective study, patient information and outcomes from Emergency Department patients, with positive and negative culture results, were used to design models – ‘Random Forest’ and ‘Neural Network’ – for the prediction of UTIs. The performance of these predictive models was validated in a cross-sectional study. In a quasi-experimental study, the impact of UTI risk assessment was investigated by evaluating changes in the behaviour of clinicians, measuring changes in antibiotic prescriptions and urine culture requests. Results: First, we trained and tested two different predictive models with 8692 cases. Second, we investigated the performance of the predictive models in clinical practice with 962 cases (Area under the curve was between 0.81 to 0.88). The best performance was the combination of both models. Finally, the assessment of the risk for UTIs was implemented into clinical practice and allowed for the reduction of unnecessary urine cultures and antibiotic prescriptions for patients with a low risk of UTI, as well as targeted diagnostics and treatment for patients with a high risk of UTI. Conclusion: The combination of modern urinalysis diagnostic technologies with digital health solutions can help to further improve UTI diagnostics with positive impact on laboratory workloads and antimicrobial stewardship.

The concept of “codon optimisation” involves adjusting the coding sequence of a target protein to account for the inherent codon preferences of a host species and maximise protein expression in that species. However, there is still a lack of consensus on the most effective approach to achieve optimal results. Existing methods typically depend on heuristic combinations of different variables, leaving the user with the final choice of the sequence hit. In this study, we propose a new statistical-physics model for codon optimisation. This model, called the Nearest-Neighbour interaction (NN) model, links the probability of any given codon sequence to the “interactions” between neighbouring codons. We used the model to design codon sequences for different proteins of interest, and we compared our sequences with the predictions of some commercial tools. In order to assess the importance of the pair interactions, we additionally compared the NN model with a simpler method (Ind) that disregards interactions. It was observed that the NN method yielded similar Codon Adaptation Index (CAI) values to those obtained by other commercial algorithms, despite the fact that CAI was not explicitly considered in the algorithm. By utilising both the NN and Ind methods to optimise the reporter protein luciferase, and then analysing the translation performance in human cell lines and in a mouse model, we found that the NN approach yielded the highest protein expression in vivo. Consequently, we propose that the NN model may prove advantageous in biotechnological applications, such as heterologous protein expression or mRNA-based therapies.

The Continuity of Care Report (CCR) is a fundamental document for ensuring high-quality healthcare and a smooth transition between different levels of care. The aim of this study was to evaluate the impact of optimizing the CCR to improve its completion rate by hospital nurses and its review by primary care nurses. To achieve this, a retrospective observational study was conducted on patients discharged from the University Hospital of La Plana de Vila-real during two three-month periods, one prior to the CCR improvement (2022) and one after (2023). No increase in the completion rate for the CCR was observed following its optimization (p = 0.226). However, a statistically significant improvement was noted in the percentage of reports reviewed (p > 0.001), increasing from 4.4% (n = 49) in 2022 to 30.5% (n = 327) in 2023. These results indicate that the optimization of the Continuity of Care Report enhances the communication between specialized care and primary care professionals.

Determining the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many locations during the first wave of the COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain) in March 2020, a cross-sectional study was performed in June 2020 querying the public health register. Logistic regression models were used. Of a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak through anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), resulting in an underreporting proportion of 92.3% (95% confidence interval [CI], 89.5–94.6%), with 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting included no medical assistance for COVID-19 disease, with an adjusted odds ratio [aOR] of 10.83 (95% CI 2.49–47.11); no chronic illness, aOR = 2.81 (95% CI 1.28–6.17); middle and lower social classes, aOR = 3.12 (95% CI 1.42–6.85); younger age, aOR = 0.97 (95% CI 0.94–0.99); and a shorter duration of illness, aOR = 0.98 (95% CI 0.97–0.99). To improve the surveillance of future epidemics, new approaches are recommended.

Abstract Background SARS-CoV-2 pneumonia can cause significant long-term radiological changes, even resembling pulmonary fibrosis. However, the risk factors for these long-term effects are unknown. This study aims to assess radiological abnormalities and their possible risk factors six months after hospital discharge due to COVID-19 pneumonia. Material and methods This cross-sectional study in a tertiary hospital included adults admitted for COVID-19 pneumonia from March 2020 to February 2021, who underwent high-resolution computed tomography (HRCT) scans of the chest six months after hospital discharge. The primary outcome was radiological abnormalities on HRCT, while the main explanatory variables were drawn from the patient’s medical history along with the disease course, analytical indicators, and the treatment received during admission. Results The 189 included patients had a mean age of 61.5 years; 70.9% were male, and hypertension was the main comorbidity (45%). About two-thirds (67.2%) presented acute respiratory distress syndrome (ARDS). Most (97.9%) received systemic corticosteroid therapy, and 81% presented pathological findings on HRCT, most commonly ground glass (63.5%), followed by bronchial dilatation (36%) and subpleural bands (25.4%). The multivariable analysis showed that age was the main risk factor, associated with most radiological changes. Other factors were the duration of corticosteroid therapy for ground glass (adjusted odds ratio [aOR] 1.020) as well as a longer stay in the intensive care unit (ICU) (aOR 1.290) and high levels of IL-6 for bronchial dilation (aOR 1.002). Conclusion Radiological involvement of the lungs six months after COVID-19 pneumonia is frequent, especially ground glass. Elderly patients with prolonged ICU admission and a significant inflammatory response measured by IL-6 are more likely to present worse radiological evolution and are candidates for radiological follow-up after COVID-19 pneumonia.

RESUMEN Introducción y objetivos: La Asociación de Cardiología Intervencionista de la Sociedad Española de Cardiología (ACI-SEC) y el Grupo de Trabajo de Hemodinámica de la Sociedad Española de Cardiología Pediátrica y Cardiopatías Congénitas (GTH-SECPCC) presentan su informe anual de actividad hemodinámica en cardiopatías congénitas correspondiente al año 2022. Métodos: Se invitó a participar a los centros españoles con laboratorio de hemodinámica y actividad intervencionista en cardiopatías congénitas. La recogida de datos se realizó mediante un cuestionario telemático. Una empresa externa analizó los resultados, que fueron revisados por miembros de la ACI-SEC y el GTH-SECPCC. Resultados: Participaron en el registro 22 centros (19 públicos y 3 privados). Se incorporaron al análisis los datos de intervencionismo en cardiopatías congénitas del adulto aportados por otros 99 hospitales al Registro de Hemodinámica y Cardiología Intervencionista de la ACI-SEC del año 2022. Se registraron 1.141 estudios diagnósticos (un 4,3% más que en 2021) y 2.508 cateterismos intervencionistas (un 61,5% más que en 2021). Las técnicas con mayor casuística fueron el cierre de defectos interauriculares (1.135 casos), el cierre de ductus arterioso (262 casos) y la angioplastia de ramas pulmonares (234 casos). El incremento más significativo se comunicó en la valvuloplastia aórtica (48,9%), el cierre de defectos interauriculares (45,2%) y el cierre de comunicación interventricular (40,7%). La tasa de éxito en los procedimientos intervencionistas fue del 97,6%, con una tasa de complicaciones mayores del 1,4 % y una mortalidad intrahospitalaria del 0,2%. Conclusiones: El presente trabajo es la tercera publicación del Registro Español de Intervencionismo en Cardiopatías Congénitas. Se ha comunicado un aumento muy significativo de la mayoría de los procedimientos terapéuticos, destacando el incremento de la valvuloplastia aórtica, del cierre de defectos interauriculares y del cierre de comunicación interventricular. Todas las técnicas intervencionistas han comunicado excelentes datos de seguridad y eficacia.

ABSTRACT Introduction and objectives: The Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC) and the Interventional Working Group of the Spanish Society of Pediatric Cardiology (GTH-SECPCC) present their annual activity report for 2022. Methods: All Spanish centers with catheterization laboratories and interventional activity in congenital heart diseases were invited to participate. Data were collected online and analyzed by an external company, together with the members of the ACI-SEC and the GTH-SECPCC. Results: A total of 22 centers participated (19 public and 3 private). Interventional data on adult congenital diseases contributed by another 99 hospitals to the Registry of Cardiac Catheterization and Interventional Cardiology of the ACI-SEC in 2022 were incorporated into the analysis. A total of 1141 diagnostic studies (4.3% more than in 2021) and 2508 interventional catheterizations (61.5% more than in 2020) were registered. The most frequent procedures were atrial septal defect closure (1135 cases), percutaneous closure of patent ductus arteriosus (262 cases), and pulmonary branch artery angioplasty (234 cases). The most significant increases in volume were related to balloon aortic valvuloplasty (48.9%), atrial septal defect closure (45.2%), and ventricular septal defect closure (40.7%). Interventional procedures were successful in 97.6%, with major procedural complications occurring in 1.4% and in-hospital mortality in 0.2%. Conclusions: This report is the third publication of the Spanish Cardiac Catheterization in Congenital Heart Diseases Registry. Both diagnostic and interventional procedures substantially increased, particularly in balloon aortic valvuloplasty, atrial septal defect closure, and ventricular septal defect closure. Most interventional techniques continue to demonstrate excellent safety and effectiveness outcomes.

Resumen: Introducción: La enfermedad renal crónica (ERC) de etiología no filiada es una de las principales causas de tratamiento sustitutivo renal en nuestro medio. Estudios previos en otros territorios sugieren que las enfermedades hereditarias podrían ser una de las potenciales causas de esta patología, especialmente en los pacientes más jóvenes. El estudio GENSEN evaluará la presencia de variantes genéticas patogénicas en sujetos que hayan desarrollado ERC categoría G5 antes de los 46 años, de etiología no filiada. Métodos: Estudio observacional, prospectivo y multicéntrico, que evalúa la utilidad diagnóstica de la secuenciación masiva de alto rendimiento (HTS) dirigida a un conjunto de genes, en la identificación de la causa de la ERC. Se incluirán pacientes de todo el territorio español, a los que se extraerá una muestra de sangre o saliva, analizando posteriormente un panel de 529 genes asociados con enfermedad renal hereditaria. Esta publicación comunica el protocolo del estudio. Conclusión: El estudio GENSEN permitirá evaluar el rendimiento diagnóstico del estudio del panel de genes en sujetos jóvenes de nuestro medio con desarrollo de ERC categoría G5 sin causa clara. Un diagnóstico etiológico ofrecería potenciales beneficios para pacientes y familiares (terapias dirigidas, ensayos clínicos, detección manifestaciones extrarrenales, evaluación de familiares para donación de vivo, estimación del riesgo de recurrencia en el injerto renal, consejo genético, entre otros) y permitiría acercar el estudio genético a la nefrología de nuestro país. Abstract: Introduction: Chronic kidney disease (CKD) of unknown etiology is one of the main causes of renal replacement therapy in our environment. Previous studies in other territories suggest that hereditary diseases could be one of the potential causes of this pathology, especially in younger patients. The GENSEN study will evaluate the presence of pathogenic genetic variants in subjects who have developed CKD category G5 before the age of 46, of unknown etiology. Methods: Observational, prospective and multicenter study, which evaluates the diagnostic usefulness of massive high-throughput sequencing (HTS) directed at a set of genes, in identifying the cause of CKD. Patients from all over Spain will be included, from whom a blood or saliva sample will be extracted, subsequently analyzing a panel of 529 genes associated with hereditary kidney disease. This publication communicates the study protocol and design. Conclusion: The GENSEN study will allow to evaluate the diagnostic performance of a gene panel study in young subjects from our environment with the development of category G5 CKD without a clear cause. An etiological diagnosis would offer potential benefits for patients and relatives (targeted therapies, clinical trials, detection of extrarenal manifestations, evaluation of relatives for living kidney donation, estimation of the risk of recurrence in the kidney graft, genetic counseling, among others) and would allow genetic study to be brought closer to nephrology in our country.

Abstract This study examines the biological effects of palbociclib and ribociclib in hormone receptor-positive breast cancer, pivotal to the HARMONIA prospective phase III clinical trial. We explore the downstream impacts of these CDK4/6 inhibitors, focusing on cell lines and patient-derived tumor samples. We treated HR+ breast cancer cell lines (T47D, MCF7, and BT474) with palbociclib or ribociclib (100 nM or 500 nM), alone or combined with fulvestrant (1 nM), over periods of 24, 72, or 144 h. Our assessments included PAM50 gene expression, RB1 phosphorylation, Lamin-B1 protein levels, and senescence-associated β-galactosidase activity. We further analyzed PAM50 gene signatures from the CORALLEEN and NeoPalAna phase II trials. Both CDK4/6 inhibitors similarly inhibited proliferation across the cell lines. At 100 nM, both drugs partially reduced p-RB1, with further decreases at 500 nM over 144 h. Treatment led to reduced Lamin-B1 expression and increased senescence-associated β-galactosidase activity. Both drugs enhanced Luminal A and reduced Luminal B and proliferation signatures at both doses. However, the HER2-enriched signature significantly diminished only at the higher dose of 500 nM. Corresponding changes were observed in tumor samples from the CORALLEEN and NeoPalAna studies. At 2 weeks of treatment, both drugs significantly reduced the HER2-enriched signature, but at surgery, this reduction was consistent only with ribociclib. Our findings suggest that while both CDK4/6 inhibitors effectively modulate key biological pathways in HR+/HER2- breast cancer, nuances in their impact, particularly on the HER2-enriched signature, are dose-dependent, influenced by the addition of fulvestrant and warrant further investigation.

The role of Laboratory Medicine in patient care has evolved in the last decades. The same has occurred to the laboratory model, which has evolved from a traditional model where the laboratory is merely involved in clinical decision-making to a leading model where the laboratory is not only involved but also determines decision-making. The advent of new technologies and automation of processes have enabled laboratory professionals to focus on the first and last phase of the analytical process namely, test ordering and decision-making based on laboratory results. These phases are more error-prone than the analytical phase, and where action must be taken to improve the quality of patient care.

The study intends to identify and analyze different consumer segments. For this purpose, we examine why customers turn to electronic word-of-mouth (eWOM) before making a purchase and how they perceive a hotel’s information and communication technology (ICT) and relational innovation after making a purchase. The objective was empirically tested with data from a panel of consumers who stayed at hotels during the post-pandemic recovery period in Spain. In total, 393 valid questionnaires were obtained. The estimation of a finite mix model was applied to identify guest profiles. Estimation identified three guest profiles where the perceptions of the hotel’s relational innovation and ICT present a high discriminant power in the first two segments. Moreover, compared to the second segment, the first group is characterized by the low impact level of these variables. On the other hand, the motivation to consult eWOM in the prebooking stage significantly influences all three groups; however, the guests of the third segment present less motivation than the rest. Hotel managers may consider ICT, relational innovation, and eWOM factors when segmenting consumers. Understanding this would enhance the company’s service delivery and the hotel’s competitiveness. The contribution of this study lies in considering ICT, relational innovation, and eWOM as novel factors that help identify different guest profiles.

Nile Delta has been historically targeted for various types of human activities since the Pharaohs’ era due to abundance of its natural resources. The increasing land subsidence in the northern delta is a significant concern for the Egyptian government. Moreover, the cumulative subsidence coupled with the scenarios of sea level rise worsens the situation. In the present work, we utilize SNAPPING service on the Geohazards Exploitation Platform (GEP) to measure the spatial and temporal trends, as well as the extent of subsidence in urban areas within the Nile Delta. The study analyzed the period between 2015 and 2020 using 225 Copernicus Sentinel-1 radar imagery using the Persistent Scatterers Interferometry (PSI) technique and reported surface motion with an average of −5 mm/year in the Nile Delta surface. Subsidence is relatively higher in the eastern part with more patterns specific to particular regions. The northern part recorded subsidence ranged from 0 to 7 mm/year. High rates of subsidence up to 17 mm/year localized in locations of Port Said, Damietta, Ad Dakahlia and Al Sharkia governorates and around Manzala Lake. On the other side, medium uplift rates up to 6 mm/year concentrated around Bardaweel Lake, Parts of Ismailia governorate and Baltim city. On-site visual inspections in these areas documented tilting in buildings and clear cracks which confirm the impact of land subsidence on the structural integrity of the buildings. The GEP platform and the SNAPPING service demonstrated the capability of cloud-based solutions to provide precise surface motion information within a short time.

IntroductionBacteremia is a life-threatening condition that can progress to sepsis and septic shock, leading to significant mortality in the emergency department (ED). The standard diagnostic method, blood culture, is time-consuming and prone to false positives and false negatives. Although not widely accepted, several clinical and artificial intelligence-based algorithms have been recently developed to predict bacteremia. However, these strategies require further identification of new variables to improve their diagnostic accuracy. This study proposes a novel strategy to predict positive blood cultures by assessing sepsis-induced immunosuppression status through endotoxin tolerance assessment.MethodsOptimal assay conditions have been explored and tested in sepsis-suspected patients meeting the Sepsis-3 criteria. Blood samples were collected at ED admission, and endotoxin (lipopolysaccharide, LPS) challenge was performed to evaluate the innate immune response through cytokine profiling.ResultsClinical variables, immune cell population biomarkers, and cytokine levels (tumor necrosis factor [TNFα], IL-1β, IL-6, IL-8, and IL-10) were measured. Patients with positive blood cultures exhibited significantly lower TNFα production after LPS challenge than did those with negative blood cultures. The study also included a validation cohort to confirm that the response was consistent.DiscussionThe results of this study highlight the innate immune system immunosuppression state as a critical parameter for sepsis diagnosis. Notably, the present study identified a reduction in monocyte populations and specific cytokine profiles as potential predictive markers. This study showed that the LPS challenge can be used to effectively distinguish between patients with bloodstream infection leading to sepsis and those whose blood cultures are negative, providinga rapid and reliable diagnostic tool to predict positive blood cultures. The potential applicability of these findings could enhance clinical practice in terms of the accuracy and promptness of sepsis diagnosis in the ED, improving patient outcomes through timely and appropriate treatment.

Summary: Background: The World Health Organisation (WHO) has identified a range of symptomatic manifestations to aid in the clinical diagnosis of post-COVID conditions, herein referred to as post-acute COVID-19 symptoms. We conducted an international network cohort study to estimate the burden of these symptoms in North American, European, and Asian populations. Methods: A federated analysis was conducted including 10 databases from the United Kingdom, Netherlands, Norway, Estonia, Spain, France, South Korea, and the United States, between September 1st 2020 and latest data availability (which varied from December 31st 2021 to February 28th 2023), covering primary and secondary care, nationwide registries, and claims data, all mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We defined two cohorts for the main analyses: a SARS-CoV-2 infection cohort [positive polymerase chain reaction (PCR) or rapid lateral flow test (LFT) result or clinical COVID-19 diagnosis] and a general population cohort. Individuals with less than 365 days of prior history or 120 days of follow-up were excluded. We estimated incidence rates (IRs) of the 25 WHO-proposed post-acute COVID-19 symptoms, considering symptoms that occurred ≥90 and ≤365 days after index date, excluding individuals with the respective symptoms 180 days prior to the index event. Stratified analyses were conducted by age and sex. Incidence rate ratios (IRRs) were calculated comparing rates in the infected cohort versus the general population. Results from the different databases were combined using random-effects meta-analyses. Findings: 3,019,408 individuals were included in the infection cohort. 1,585,160 of them were female and 1,434,248 of them male. 929,351,505 individuals were included in the general population group. 461,195,036 of them were female and 466,022,004 of them male. The 1-year IR of any post-acute COVID-19 symptom in the COVID-19 infection cohort varied significantly across databases, from 4.4 (95% CI 3.8–5.1) per 100 person-years to 103.9 (95% CI 103.2–104.7). The five most common symptoms were joint pain (from 1.6 (95% CI 1.3–1.9) to 14.3 (95% CI 14.1–14.6)), abdominal pain (from 0.3 (95% CI 0.1–0.5) to 9.9 (95% CI 9.7–10.1)), gastrointestinal issues (from 0.6 (95% CI 0.4–0.9) to 13.3 (95% CI 13.1–13.6)), cough (from 0.3 (95% CI 0.2–0.5) to 9.1 (95% CI 8.9–9.3)), and anxiety (from 0.8 (95% CI 0.6–1.2) to 11.4 (95% CI 11.2–11.6)); whereas muscle spasms (from 0.01 (95% CI 0.008–0.2) to 1.7 (95% CI 1.6–1.8)), pins and needles (from 0.05 (95% CI 0.03–0.0.9) to 1.5 (95% CI 1.4–1.6)), memory issues (from 0.03 (95% CI 0.02–0.06) to 0.8 (95% CI 0.7–0.8)), cognitive dysfunction (from 0.007 (95% CI 0.004–0.01) to 0.6 (95% CI 0.4–0.8)), and altered smell and/or taste (from 0.04 (95% CI 0.03–0.04) to 0.7 (95% CI 0.6–0.8)) were least common. Incidence rates of any post-acute COVID-19 symptoms generally increased with age, with certain symptoms peaking in middle-aged adults (anxiety, depressive disorders, headache, altered smell and taste) and others in pre-school children (gastrointestinal issues and cough). Females had higher incidence rates for most symptoms. Based on the random-effects model, the infected cohort had a higher incidence of any post-acute COVID-19 symptom than the general population, with a meta-analytic incidence rate ratio (meta-IRR) of 1.4 (1–2). A similar pattern was seen for all individual symptoms. The highest meta-IRRs were depressive disorder, 2.6 (1.7–3.9); anxiety, 2.3 (1.4–3.8); allergy, 2.1 (1.7–2.8) and sleep disorders, 2.1 (1.5–2.6). The meta-IRR for altered smell and/or taste was 1.9 (1.3–2.8). Interpretation: Post-acute COVID-19 symptoms, as listed by the WHO, were commonly observed following COVID-19 infection. However, even after standardising research methods, there was significant heterogeneity in the incidence rates from different healthcare settings and geographical locations. This is the first international study of the epidemiology of post-acute COVID-19 symptoms using the WHO-listed symptoms. Its findings contibute to understand the epidemiology of this condition from a multinational approach. Limitations of this study include the lack of consensus of the post-acute COVID-19 definition, as well as the difficulty to capture the impact on daily life of the post-acute COVID-19 symptoms in the available datasets. Funding: This work has been funded by the European Health Data Evidence Network (EHDEN) through an Evidence Generation Fund Grant and by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC).

En el ámbito de la educación superior, posterior a la pandemia, las universidades chilenas recibieron una generación de estudiantes provenientes de un mundo académico virtual que demandan la articulación entre metodologías activas y el uso de la tecnología en el desarrollo de las clases, ofreciendo la oportunidad al profesorado de aplicar distintas estrategias de enseñanza. El objetivo de la presente investigación es analizar los efectos del uso de dispositivos móviles junto con el software Geogebra en el aprendizaje de estudiantes universitarios validado mediante un modelo de ecuaciones estructurales, en cursos de primer año de Ingeniería, implementado como una estrategia de trabajo alternativa de apoyo para docentes y estudiantes. El enfoque metodológico del estudio es cuantitativo de corte descriptivo correlacional, en el cual participaron 79 estudiantes de Ingeniería de la Universidad Católica del norte obteniendo información mediante el análisis de un cuestionario creado ad-hoc aplicado por dos períodos consecutivos, análisis descriptivos, análisis factorial y un modelo de ecuaciones estructurales. Los principales resultados evidencian una alta motivación con el uso de estos recursos tecnológicos en el aula y un aumento del rendimiento académico del estudiantado mostrando la utilidad y la versatilidad de una forma interactiva de enseñar aplicable a distintos niveles y en diversos cursos de matemáticas.

Objective To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).Design Observational cohort analysis based on a multicentre international registry.Setting Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries.Participants A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins.Methods Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use.Results From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76).Conclusions In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.

Studying bone surface modifications (BSMs) in neotaphonomic research is an important aid to reconstruct agency in the archaeological and palaeontological record. The significance of correctly identifying BSMs has led to extensive debates about adequate methodological and interpretive frameworks to identify taphonomic agents and their bone-modifying patterns in dynamic taphonomic processes; especially those involving inter-agency interactions. Recent analytical innovations in the field have given rise to more updated and less biasing methods, including those rooted in multivariate statistics and artificial intelligence algorithms. Among the latter, convolutional neural networks have demonstrated a substantial potential in precision in the identification and characterization of BSMs. In this study, we present a successful application of these methods to reconstructing taphonomic agency in an archaeological context, specifically in Unit 2 of Tritons Cave (Lleida, Spain). Previous interpretations of this palaeontological layer suggested that it was a natural palimpsest created by carnivores, namely leopards. Through the present research, we objectively tested the original felid-accumulation hypothesis associated with the site’s original taphonomic analysis. Our findings provide additional evidence of the primary leopard agency in the formation of the assemblage and underscores the significant potential of transfer learning for identifying taxon-specific carnivore agency.

Objective The objectives encompassed (1) the creation of Recuerdame, a digital app specifically designed for occupational therapists, aiming to support these professionals in the processes of planning, organizing, developing, and documenting reminiscence therapies for older people with dementia, and (2) the evaluation of the designed prototype through a participatory and user-centered design approach, exploring the perceptions of end-users. Methods This exploratory research used a mixed-methods design. The app was developed in two phases. In the first phase, the research team identified the requirements and designed a prototype. In the second phase, experienced occupational therapists evaluated the prototype. Results The research team determined the app's required functionalities, grouped into eight major themes: register related persons and caregivers; record the patient's life story memories; prepare a reminiscence therapy session; conduct a session; end a session; assess the patient; automatically generate a life story; other requirements. The first phase ended with the development of a prototype. In the second phase, eight occupational therapists performed a series of tasks using all the application's functionalities. Most of these tasks were very easy (Single Ease Question). The level of usability was considered excellent (System Usability Scale). Participants believed that the app would save practitioners time, enrich therapy sessions and improve their effectiveness. The qualitative results were summarized in two broad themes: (a) acceptability of the app; and (b) areas for improvement. Conclusions Participating occupational therapists generally agreed that the co-designed app appears to be a versatile tool that empowers these professionals to manage reminiscence interventions.

Se presenta un conjunto de astrágalos recuperado en un depósito extramuros de La Bastida de les Alcusses (Moixent, València). Está integrado por 644 tabas de caprinos y suidos, 207 de ellas con modificaciones antrópicas y otras 5 realizadas en plomo. También se realiza una valoración de los astrágalos procedentes de otros espacios del asentamiento, tanto en hueso como en otros materiales y se reflexiona sobre su presencia en el mundo ibérico, en contextos de hábitat y funerarios, así como sobre los distintos valores y usos económicos, cotidianos y rituales de estos objetos.

A pesar de que la Comunidad de Madrid no tenga un riesgo elevado de inundación, sí ha tenido en el pasado cierta recurrencia y actualmente mantiene eventos ocasionales que generan elevados costes. Se realiza un exhaustivo inventario a partir de fuentes documentales, recopilando información de 138 inundaciones entre 1836 y 2021. Con ella se explica la causalidad de la distribución espacial de los casos, tanto en cuanto a algunos de sus componentes físicos, como antrópicos. Destaca el enorme peso entre la relación de la pendiente y la red hidrográfica con la ocupación urbana, en la que se toma como indicador la densidad de edificios por hectárea. Se pone de manifiesto que las áreas más vulnerables han sido históricamente Aranjuez y Madrid ciudad, mientras que en la actualidad se incorporan los municipios del sur y este de la Comunidad. El estudio de las causas sinópticas de las inundaciones ha revelado un cambio entre las inundaciones históricas y las actuales. Entre las primeras, dominaban hasta mediados de los años cincuenta del siglo XX los tipos de tiempo zonales y advecciones atlánticas propios del invierno, de varios días de duración, responsables de precipitaciones elevadas en una cuenca del Tajo todavía sin regular. En las últimas décadas, las mejoras de infraestructuras hidráulicas y la intensa expansión urbana ciñen las inundaciones preferentemente a precipitaciones elevadas puntuales asociadas a DANAs en cualquier época del año y a pantanos barométricos, característicos de la estación estival.

Durante los años sesenta, se vivió una evolución de los significados de género dentro del catolicismo de base. Fue de gran relevancia la crítica que este realizó al modelo hegemónico de feminidad y a las formas de relacionarse afectivamente aupados por la dictadura. La juventud católica española puso en práctica un modo genuino de pertenencia social al reflexionar en torno a una intersección de componentes que les interpelaban como la clase, la juventud o el género. Desde los valores del cristianismo primitivo, muchas jóvenes adquirieron una conciencia de clase y, al analizarse desde la propia experiencia, esta se tornó en una conciencia feminista. Utilizando la historia oral como herramienta analítica y la memoria como objeto de estudio, en este artículo indagaremos en los debates internos dentro del movimiento católico de base en torno al feminismo y en la incorporación de las mujeres católicas al movimiento feminista español que comenzó su andadura en el año 1975.

Summary: Background: Early childcare attendance may be related to children's internalizing and externalizing symptoms throughout childhood and young adolescence, however evidence from Europe is limited. We aimed to assess this association across multiple population-based birth cohorts of children recruited in different European countries. Methods: Data come from six parent-offspring prospective birth cohort studies across five European countries within the EU Child Cohort Network. A total of 87,208 parent-child dyads were included in the study. To test associations between childcare attendance (centre-based or informal) anytime between ages 0 and 4 years and children's internalizing and externalizing symptoms in middle childhood and young adolescence (measured at: 5–6 years, 7–9 years, and 10–13 years) a two-stage individual participant data meta-analysis was implemented. Linear regression models were performed in each cohort separately; combined random-effects meta-analysis was then used to obtain overall association estimates. In secondary analyses, we tested interactions between childcare attendance and mother's post-partum depression, low education status, and the child's sex. Findings: Compared to children who were exclusively cared for by their parents prior to school entry, those who attended centre-based childcare had lower levels of internalizing symptoms in all age groups [5–6 years: β: −1.78 (95% CI: −3.39, −0.16); 7–9 years: β: −0.55 (95% CI: −0.88, −0.73); 10–13 years: β: −0.76 (95% CI: −1.15, −0.37)]. Children who attended informal childcare appeared to have elevated levels of internalizing symptoms between 7–9 and 10–13 years, respectively [β: 1.65 (95% CI: 1.25, 2.06); β: 1.25 (95% CI: 0.96, 1.54)]. Informal childcare attendance was also associated with increased levels of children's externalizing symptoms between 7–9 and 10–13 years, respectively [β: 2.84 (95% CI: 1.41, 4.26); β: 2.19 (95% CI: 0.54, 3.84)]. Interpretation: Early centre-based childcare is associated with decreased levels of children's internalizing symptoms compared to exclusive parental care. For informal childcare, opposite associations were observed. Overall, our results suggest that centre-based childcare attendance may be associated with slight positive impacts on children's emotional development and should be encouraged by public policies. In addition, children from socioeconomically disadvantaged families require special attention, as they may not sufficiently benefit from universal early childhood education and care (ECEC). Funding: This research was funded by the ERC Consolidator grant RESEDA (Horizon Europe, 101001420).

Background: To evaluate the anatomical and functional outcomes of high-density subthreshold micropulse laser (HSML) treatment in a cohort of patients diagnosed with chronic central serous chorioretinopathy (CSCR) whose treatment with photodynamic therapy (PDT) was delayed due to the worldwide shortage of verteporfin. Methods: Prospective interventional study which included 42 eyes of 40 patients diagnosed with chronic CSCR and on the waiting list for PDT who received rescue therapy with HSML using the Navilas® System device (OD-OS GmBH, Teltwo, Germany). Best corrected visual acuity (BCVA), subretinal fluid (SRF), and subfoveal choroidal thickness (SFCT) were measured at inclusion and during the follow-up visits at 2, 4, and 6 months. Results: The mean waiting time from the indication of PDT until treatment with HSML was 14.6 ± 9.7 months (range 5–21). There were no differences in the pre-treatment BCVA compared with the 6-month follow-up visit (67 ± 16.7 letters and 67.5 ± 8.2 letters respectively, p = 0.136). However, there was a significant decrease in the mean SFCT of -39.6 ± 37.1 μm (p = 0.030). Additionally, there was a decrease in SRF height between the pre-treatment measure (123.0 ± 49.8 μm) and the 2, 4, and 6-month follow-up visits after HSML of -58.5 ± 68.2 μm, -53.2 ± 76.3 μm, and -65.4 ± 53.6 μm respectively (p < 0.001). A complete resolution of the SRF was observed in 16/42 eyes (38.1 %) and a reduction of the SRF height in 85.7 % of the overall cohort was observed after HSML treatment. Conclusion: A significant anatomical improvement in SRF and a decrease in SFCT were observed in patients with CSCR who were previously waiting for PDT and were rescued by HSML. However, the rate of complete SRF resolution was low.

Abstract 3D printing technologies have matured to produce complex structures, still they are often limited to static materials. Introducing alkoxyamine bonds into 3D printed structures offers unprecedented possibilities for post‐synthetic modification through nitroxide exchange reaction and nitroxide‐mediated polymerization. This study provides a comprehensive molecular and macroscopic characterization of 3D‐printed alkoxyamine‐containing dynamic covalent adaptable networks. The study provides new insights into their dynamic structural and mechanical alterations, making them promising candidates for advanced applications ranging from biomedical engineering to flexible electronics.

This study investigates the Louvre Abu Dhabi as a brand extension of the Louvre in France, focusing on factors influencing brand extension attitude and its impact on visit intention. Data from 934 questionnaires are analyzed using partial least squares in a multi-group study. The research aims to enrich discourse on tourist brands by examining brand image, perceived fit, and perceived brand localness within the context of the Louvre Abu Dhabi project. Results suggest a potential correlation between positive brand extension evaluation and increased future visits, highlighting practical implications for brand management in cultural tourism. The study also raises theoretical questions regarding global marketing research, emphasizing the need for an integrative approach to understand brand extension attitude’s role in enhancing visit intention.

Abstract The Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6) is the primary effort of CMIP6 (Coupled Model Intercomparison Project–Phase 6) focusing on ice sheets, designed to provide an ensemble of process‐based projections of the ice‐sheet contribution to sea‐level rise over the twenty‐first century. However, the behavior of the Antarctic Ice Sheet beyond 2100 remains largely unknown: several instability mechanisms can develop on longer time scales, potentially destabilizing large parts of Antarctica. Projections of Antarctic Ice Sheet evolution until 2300 are presented here, using an ensemble of 16 ice‐flow models and forcing from global climate models. Under high‐emission scenarios, the Antarctic sea‐level contribution is limited to less than 30 cm sea‐level equivalent (SLE) by 2100, but increases rapidly thereafter to reach up to 4.4 m SLE by 2300. Simulations including ice‐shelf collapse lead to an additional 1.1 m SLE on average by 2300, and can reach 6.9 m SLE. Widespread retreat is observed on that timescale in most West Antarctic basins, leading to a collapse of large sectors of West Antarctica by 2300 in 30%–40% of the ensemble. While the onset date of retreat varies among ice models, the rate of upstream propagation is highly consistent once retreat begins. Calculations of sea‐level contribution including water density corrections lead to an additional ∼10% sea level and up to 50% for contributions accounting for bedrock uplift in response to ice loading. Overall, these results highlight large sea‐level contributions from Antarctica and suggest that the choice of ice sheet model remains the leading source of uncertainty in multi‐century projections.

Commercial PEMFC-based micro-CHP systems are operated by rule-based energy management strategies. Each of these strategies constitutes a different way to meet the household energy demand (following the heat demand, following the electricity demand, the maximum of the two, etc.). Previous studies demonstrate that which of them is the best —i.e. the one that manages to meet the demand at the lowest operating cost— depends on the particular scenario in which the micro-CHP system works (gas and electricity prices, annual energy demands, ability to export electricity to the grid, etc.). This paper aims to explore this dependence relationship and to deepen our understanding of it. To this end, a parametric analysis is conducted and the performances achieved by four rule-based operating strategies are compared. The parameters whose influence is studied, and through which the scenario is jointly characterized, are: (1) energy prices (electricity and natural gas), (2) feed-in tariff, (3) stack degradation, (4) climate and (5) heat to power ratio of the demand. The results show this dependence relationship in a clear and more comprehensive way, and offer a better understanding of its nature. From this improved understanding it can be inferred, among other things, that adapting the strategy to the scenario can generate annual savings of up to 14.5 percentage points. Moreover, this enhanced characterization of that dependence relationship can be useful for the design of a new operating strategy, a strategy that, without falling into the complexity that an optimal energy management approach (based on linear programming) involves, manages to exploit the savings potential of micro-CHP systems, thus facilitating their future mass commercialization.

The Pliocene faunas of the northeastern Iberian Peninsula are poorly known due to the scarcity of deposits from this interval. In this context, the site of Sant Nofre-Campredó (Baix Ebre, Catalonia, Spain), comprising two contemporaneous outcrops belonging to geologically correlated sections (Sant Nofre and Campredó-Via Fèrria), makes a significant contribution to the study of Pliocene faunas in this region. The first vertebrate remains were recovered in the late 1970s in clay deposits close to the Sant Nofre Hill. Later, intensive sampling in the 1980s at the Campredó-Via Fèrria outcrop led to the recovery of more than a hundred fossil specimens, including small vertebrates and large mammals. Here, we revise these collections to expand and update the vertebrate list, better constrain the age of the continental deposits, and characterize the environment and climate around the mouth of the Ebro River during the formation of the site. Up to 24 vertebrate species have been identified at Sant Nofre-Campredó, including amphibians, reptiles, and mammals. The presence of the rodents Paraethomys baeticus Piñero & Verzi, 2020, Apocricetus barrierei (Mein & Michaux 1970), and Occitanomys brailloni Michaux, 1969 implies an early Ruscinian age (MN14 unit) for the two outcrops. Biostratigraphic correlations with other well-dated sites in the Iberian Peninsula refine the estimated age of Sant Nofre-Campredó to approximately 4.6 Ma. The ecological affinities of the identified fauna reveal a landscape dominated by woodland habitats in the surroundings of the site during the Early Pliocene, with presence of open humid meadows and water bodies under warm and moist climatic conditions.

Resumen: Antecedentes y objetivo: La reducción abierta rara vez es necesaria en las fracturas supracondíleas de húmero pediátrica. Sin embargo, falta evidencia sobre cuál es el abordaje óptimo para obtener resultados satisfactorios. El abordaje anterior facilita una visión directa de la fractura y una excelente exposición de las estructuras neurovasculares, aunque su uso es poco común. El objetivo de este estudio fue revisar las indicaciones, los resultados y las complicaciones asociadas con el abordaje anterior para la reducción abierta de estas fracturas. Métodos: Nuestro protocolo se registró en PROSPERO: CRD42023446923. La búsqueda se realizó en MEDLINE/PubMed, Embase, Web of Science, Clinicaltrials.gov y Cochrane Library, desde inicio hasta diciembre de 2023. Se realizó screening por duplicado. Se recogieron datos demográficos, indicaciones para el abordaje abierto, puntuación de Flynn funcional y estética y complicaciones. La calidad de los estudios se evaluó con Methodological Index for Non-Randomized Studies Criteria (MINORS). Resultados: Se incluyeron 19 estudios que agrupaban a 483 pacientes. Un estudio se clasificó con nivel de evidencia 2, 10 con nivel 3 y 8 con nivel 4. La puntuación media MINORS fue de 13,05 ± 3,47. La indicación principal para el abordaje abierto fue el fracaso de la reducción cerrada, reportada en el 46% de los pacientes. El 97,7 y el 98,6% de los pacientes lograron un Flynn funcional y cosmético satisfactorio, respectivamente. La tasa de lesiones neurovasculares posquirúrgicas fue del 1,4%. Un paciente fue reintervenido. Conclusiones: El abordaje anterior es seguro y efectivo en el manejo de fracturas supracondíleas de húmero pediátricas, cuando se requiera un abordaje abierto. Nivel de evidencia: Revisión sistemática de estudios con nivel de evidencia 2-4. Abstract: Background and purpose: Open reduction is rarely performed in pediatric supracondylar humerus fractures. However, clear evidence is lacking regarding the optimal open approach to achieve satisfactory results. The anterior approach provides direct visualization of the fracture and excellent exposure to neurovascular structures, although its utilization is less common. The objective of this study was to review the indications, outcomes, and complications associated with the anterior approach for open reduction of these fractures. Methods: Our protocol was registered at PROSPERO: CRD42023446923. MEDLINE/PubMed, Embase, Web of Science, Clinicaltrials.gov, and Cochrane Library were searched from database inception to search date (December 2023) and screened in duplicate for relevant studies. Data were collected regarding patient demographics, indications for open reduction, Flynn's functional and cosmetic outcomes, and complications. Study quality was assessed using the Methodological Index for Non-Randomized Studies Criteria. Results: A total of 19 studies involving 483 patients were included. One study was classified as Level 2 evidence, ten as Level 3, and eight as Level 4. The mean MINORS score was 13.05 ± 3.47. The primary indication for open reduction was failed closed reduction, observed in 46% of patients. 97.7% and 98.6% of patients achieved Flynn's functional and cosmetic satisfactory results, respectively. The postsurgical neurovascular injury rate was 1.4%. One patient required reintervention. Conclusion: The anterior approach is safe and effective for managing pediatric supracondylar humerus fractures requiring open reduction. Level of evidence: Systematic review of Level 2-4 evidence studies.

Contrast-induced encephalopathy is a neurological complication related to contrast used in endovascular procedures or computed tomography (CT). The main risk factors are arterial hypertension, diabetes mellitus, chronic kidney disease (CKD), hyperosmolar contrasts, the amount of infused contrast and its direct infusion in the posterior cerebral territory, or pathologies with blood-brain barrier damage. Symptomatology is non-specific and may present as altered level of consciousness, neurological focality or seizures. Diagnosis is done by exclusion after ischemic or hemorrhagic stroke has been ruled out; CT or MRI are useful for differentiation. Generally, it appears shortly after exposure and the symptoms lasts 48−72h with complete recovery, although cases with persistence of symptoms or longer duration have been described. Treatment consists of monitoring, supportive measures and kidney replacement therapy (KRT) with hemodialysis (HD) in patients in chronic KRT program. It is important for the nephrologist to be aware of this entity given the susceptibility of the patient on HD as well as its potential therapeutic role in these patients. Resumen: La encefalopatía por contraste es una complicación neurológica relacionada con el contraste utilizado en procedimientos endovasculares o tomografía computarizada (TC). Los principales factores de riesgo son la hipertensión arterial, la diabetes mellitus, la enfermedad renal crónica (ERC), contrastes hiperosmolares, cantidad de contraste infundida y su infusión directa en el territorio cerebral posterior, o patologías que cursen con daño de barrera hematoencefálica. La sintomatología es inespecífica y puede presentarse como alteración del nivel de conciencia, focalidad neurológica o crisis comiciales. El diagnóstico es de exclusión tras haber descartado los accidentes cerebro-vasculares isquémicos o hemorrágicos, el TC o la resonancia magnética son de utilidad para su diferenciación. Generalmente, aparece poco tiempo tras la exposición y la sintomatología dura 48−72h con recuperación completa, aunque se han descrito casos con persistencia de los síntomas o mayor duración. El tratamiento es la monitorización con medidas de soporte y la terapia de sustitución renal con hemodiálisis (HD) en aquellos pacientes en programa crónico. Es importante que el nefrólogo conozca esta entidad dada la susceptibilidad del paciente en HD así como su potencial papel terapéutico en estos pacientes.

Abstract Despite significant advances in reconstructing genome-scale metabolic networks, the understanding of cellular metabolism remains incomplete for many organisms. A promising approach for elucidating cellular metabolism is analysing the full scope of enzyme promiscuity, which exploits the capacity of enzymes to bind to non-annotated substrates and generate novel reactions. To guide time-consuming costly experimentation, different computational methods have been proposed for exploring enzyme promiscuity. One relevant algorithm is PROXIMAL, which strongly relies on KEGG to define generic reaction rules and link specific molecular substructures with associated chemical transformations. Here, we present a completely new pipeline, PROXIMAL2, which overcomes the dependency on KEGG data. In addition, PROXIMAL2 introduces two relevant improvements with respect to the former version: i) correct treatment of multi-step reactions and ii) tracking of electric charges in the transformations. We compare PROXIMAL and PROXIMAL2 in recovering annotated products from substrates in KEGG reactions, finding a highly significant improvement in the level of accuracy. We then applied PROXIMAL2 to predict degradation reactions of phenolic compounds in the human gut microbiota. The results were compared to RetroPath RL, a different and relevant enzyme promiscuity method. We found a significant overlap between these two methods but also complementary results, which open new research directions into this relevant question in nutrition.

Resumen: Introducción: La principal complicación de la osteosíntesis percutánea con tornillos iliosacros es la malposición del implante, que puede ocasionar lesiones vasculares y nerviosas. La variabilidad anatómica del sacro puede dificultar la inserción del tornillo bajo control fluoroscópico. De entre los métodos descritos para mejorar la precisión de esta técnica, destaca el uso de la tomografía computarizada (TC). El objetivo del estudio es comparar los resultados de la implantación de tornillos iliosacros con fluoroscopia y TC. Metodología: Estudio de cohortes retrospectivo sobre 66 tornillos iliosacros implantados en 56 pacientes durante 11 años. Los tornillos fueron introducidos con fluoroscopia en el quirófano o con TC en el área de radiodiagnóstico. Recogimos datos sobre las características de los pacientes, sus lesiones, el tratamiento y los resultados clínicos y radiológicos. Resultados: Cuarenta y siete tornillos fueron implantados con fluoroscopia y 19 con TC. El 18,2% de los tornillos perforaba el corredor S1. Todos ellos se intervinieron con fluoroscopia (0 vs. 34%; p

RESUMEN Introducción y objetivos: A pesar de que el cateterismo cardiaco (CC) se ha convertido en una práctica habitual en el trasplante cardiaco (TxC) pediátrico, hay escasez de protocolos globales y de evidencia robusta sobre los procedimientos requeridos y el impacto que tienen en la evolución del propio trasplante y los futuros CC. Este estudio tiene como objetivo analizar la actividad de CC en niños receptores de trasplante cardiaco en un centro terciario y describir los factores de riesgo para un mayor número de procedimientos. Métodos: Estudio retrospectivo con datos obtenidos de los informes médicos y los archivos de hemodinámica. La muestra se dividió en miocardiopatías y cardiopatías congénitas (CAC). El análisis de los factores de riesgo para CC se calculó con regresión lineal y ANOVA. Resultados: Conformaron la muestra 61 niños (36,07% CAC). Las CAC muestran una mayor media de CC antes del TC. Los cateterismos diagnósticos son la actividad más frecuente previa al TxC, seguidos por las biopsias endomiocárdicas en las miocardiopatías y el cierre de colaterales aortopulmonares en las CAC. Hubo 389 CC tras el TC (608 procedimientos), la mayoría (92,75%) por vigilancia del rechazo. El subgrupo de CAC univentriculares tuvo significativamente un mayor número de CC tras el TxC...

Resumen: La encefalopatía por contraste es una complicación neurológica relacionada con el contraste utilizado en procedimientos endovasculares o tomografía computarizada (TC). Los principales factores de riesgo son la hipertensión arterial, la diabetes mellitus, la enfermedad renal crónica (ERC), contrastes hiperosmolares, cantidad de contraste infundida y su infusión directa en el territorio cerebral posterior, o patologías que cursen con daño de barrera hematoencefálica. La sintomatología es inespecífica y puede presentarse como alteración del nivel de conciencia, focalidad neurológica o crisis comiciales. El diagnóstico es de exclusión tras haber descartado los accidentes cerebrovasculares (ACV) isquémicos o hemorrágicos; el TC o la resonancia magnética (RM) son de utilidad para su diferenciación. Generalmente aparece poco tiempo tras la exposición y la sintomatología dura 48-72 h con recuperación completa, aunque se han descrito casos con persistencia de los síntomas o mayor duración. El tratamiento es la monitorización con medidas de soporte y la terapia de sustitución renal con hemodiálisis (HD) en aquellos pacientes en programa crónico. Es importante que el nefrólogo conozca esta entidad, dada la susceptibilidad del paciente en HD, así como su potencial papel terapéutico en estos pacientes. Abstract: Contrast-induced encephalopathy is a neurological complication related to contrast used in endovascular procedures or computed tomography (CT). The main risk factors are arterial hypertension, diabetes mellitus, chronic kidney disease (CKD), hyperosmolar contrasts, the amount of infused contrast and its direct infusion in the posterior cerebral territory, or pathologies with blood–brain barrier damage. Symptomatology is non-specific and may present as altered level of consciousness, neurological focality or seizures. Diagnosis is done by exclusion after ischemic or hemorrhagic stroke has been ruled out; CT or MRI are useful for differentiation. Generally, it appears shortly after exposure and the symptoms lasts 48–72 h with complete recovery, although cases with persistence of symptoms or longer duration have been described. Treatment consists of monitoring, supportive measures and renal replacement therapy (RRT) with hemodialysis (HD) in patients in chronic RRT program. It is important for the nephrologist to be aware of this entity given the susceptibility of the patient on HD as well as its potential therapeutic role in these patients.

En las últimas décadas está evolucionando el posicionamiento de la Medicina de Laboratorio en el proceso médico asistencial de atención al paciente y también el modelo de laboratorio; de un modelo tradicional, con solo intervención, a un modelo líder, que además de intervenir condiciona la decisión clínica. La mejora en tecnología y automatización ha permitido también al profesional de laboratorio centrarse en la primera y última fase del ciclo de laboratorio, la solicitud de pruebas, y la acción tras su resultado, las etapas con más errores, y donde principalmente se debe actuar para conseguir una mejora en la calidad asistencial del paciente.