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Introduction: Respiratory distress syndrome (RDS) is the most frequent cause of respiratory distress in preterm neonates. In the management of RDS, surfactant plays a pivotal role, but there are no evidence-based recommendations for moderate/late preterm neonates (32–36 weeks). Methods: A scientific committee developed a questionnaire with 53 questions addressing diagnosis, treatment, potential complications and future trends in RDS specifically focused on moderate and late preterm neonates. This was followed by the performance of a Delphi survey of expert neonatologists. Results: Consensus was reached on 98 of the 109 items. The recommendations for the diagnosis of RDS included performing a lung ultrasound and including mild respiratory distress, transient tachypnoea of the newborn, congenital pneumonia and primary pulmonary hypertension in the differential diagnosis. Most panellists agreed on the need for studies that determine the benefit/harm balance, clinical profile and methods of surfactant administration in moderate/late preterm neonates. All respondents would use the MIST approach with devices specifically designed for surfactant administration. Regarding sedation measures during MIST, most participants agreed on the use of nonpharmacological interventions and, if these proved ineffective, an opioid. All respondents agreed that moderate/late preterm neonates are at increased risk of neonatal morbidity and mortality, particularly respiratory problems, and considered the need for more specialised monitoring in hospital follow-up visits in neonates with associated risk factors or a history of complications in the neonatal period. Finally, all respondents agreed that there is a lack of studies identifying risk factors and medium-term adverse outcomes in moderate/late preterm neonates. Conclusion: This expert consensus will help with the diagnosis and management of RDS and guide decision-making about surfactant administration in moderate/late preterm neonates. Resumen: Introducción: El síndrome de distrés respiratorio (SDR) es la causa más frecuente de distrés respiratorio en los recién nacidos prematuros. El surfactante desempeña un papel fundamental en el tratamiento del SDR, pero no existen recomendaciones basadas en la evidencia en neonatos prematuros moderados/tardíos (32-36 semanas). Métodos: Un Comité Científico diseñó un cuestionario con 53 preguntas que abordaban el diagnóstico, el tratamiento, las posibles complicaciones y las tendencias futuras del SDR, específicamente en los recién nacidos prematuros moderados y tardíos. Posteriormente, se llevó a cabo una encuesta Delphi entre neonatólogos con experiencia en el campo. Resultados: Se alcanzó consenso en 98 de los 109 ítems incluidos. Se recomendó la realización de una ecografía pulmonar y la consideración de la dificultad respiratoria leve, la taquipnea transitoria del recién nacido, la neumonía congénita y la hipertensión pulmonar primaria durante el diagnóstico diferencial. La mayoría de los panelistas coincidieron en la necesidad de realizar estudios para determinar el riesgo/beneficio, el perfil clínico y los métodos de administración de surfactante en neonatos prematuros moderados/tardíos. Se recomendó la técnica MIST con dispositivos específicamente diseñados para la administración de surfactante. La mayoría de los participantes coincidieron en recomendar el uso de procedimientos no farmacológicos de sedación durante el MIST y, en caso de ineficacia, un opiáceo. Todos los encuestados coincidieron en que los prematuros moderados/tardíos presentan mayor riesgo de morbimortalidad neonatal, en particular de problemas respiratorios, y consideraron necesario más monitorización especializada en el seguimiento hospitalario de neonatos con mayor riesgo y/o complicaciones. Por último, todos los encuestados coincidieron en la falta de estudios para identificar factores de riesgo y resultados adversos a medio plazo en neonatos prematuros moderados/tardíos. Conclusiones: Este consenso de expertos será de ayuda en el diagnóstico y manejo del SDR y en la decisión de administrar surfactantes en neonatos prematuros moderados/tardíos.

The Twenty Eyes Aqueduct stands as a monumental hydraulic structure with a rich history spanning several centuries, poised to be designated as a heritage asset of cultural interest (Bien de Interés Cultural, BIC). This infrastructure poses a significant challenge for structural simulation, given the heterogeneous nature of its materials, geometric irregularities and challenging accessibility. Recent advancements in UAV photogrammetry, coupled with the evolution of BIM and the computational capabilities of modern computers for calculating FEM, present a methodology for simulating the behaviour of structures under applied loads. This approach enables us to address the tasks of reconstruction, protection and conservation of our heritage with unprecedented precision, speed and perspective. In this study, the innovative Cloud-to-BIM-to-FEM methodology is applied, which is capable of converting BIM models generated from point clouds into FEM. Obtaining the point cloud was possible using UAV photogrammetry, during which a 3D survey of the current state of the aqueduct was conducted. The point cloud obtained served as the basis for generating an HBIM that accurately represents the geometry of the aqueduct (Cloud-to-BIM). The HBIM was then transformed into a FEM model that respects the monument’s singularity without excessive geometric simplifications (BIM-to-FEM). Finally, various considerations were deduced regarding the stability of the aqueduct and its structural behaviour by applying loads such as wind and earthquake.

Background The global COVID-19 pandemic has shown the vulnerability of some population groups, including persons with intellectual and developmental disabilities (IDD). Aim The present paper will provide more clarity and understanding of the experiences of family members of persons with IDD housed in residential facilities in Catalonia within the period of maximum restrictions during the COVID-19 pandemic. Methods and procedures Semi-structured interviews were conducted using an interpretive phenomenological qualitative approach. Study participants consisted of 14 relatives of IDD individuals who were institutionalized in residence facilities or homes. The guiding questions emerged from group discussions with relatives of those with IDD who did not participate in the subsequent interviews. Drawing from this group, the factors that were identified to have had the greatest impact on their lives were later used to guide the interviews. Data collection was carried out in face-to-face individual interviews that were recorded together with the observations of two researchers between February and October 2022. Results Our analysis identified 4 main themes that developed into additional factors: the decision to stay at home or in the residence, fear, illness, and protocol. Individuals with IDD lost their daily routines, suffered from social isolation, and did not understand the situation. Conclusion The results of this study allow for a better understanding of the experiences of families of persons with IDD in residential centres during the lockdown by identifying their needs and how to better support them in the future. Outcomes and results Knowledge and understanding of these events should allow for better management of similar situations in the future.

The CRISPR/Cas9 system has transformed genome editing by enabling precise modifications for diverse applications. Recent advancements, including base editing and prime editing, have expanded its utility beyond conventional gene knock-out and knock-in strategies. Additionally, several catalytically dead Cas9 (dCas9) proteins fused to distinct activation domains have been developed to modulate endogenous gene expression when directed to their regulatory regions by specific single-guide RNAs. Here, we report the development of the H9 human pluripotent stem cell (hPSC) line expressing an inducible dCas9-SAM activator (H9-iCas9.SAM), designed to activate transcription of endogenous genes. The H9-iCas9.SAM cells were generated through targeted integration of an inducible CRISPR/Cas9-based gene activator cassette into the AAVS1 “safe-harbour” locus. Molecular analyses confirmed precise and specific integration, ensuring minimal off-target effects. Functional characterization revealed that H9-iCas9.SAM cells retain pluripotency and display inducible endogenous gene activation upon doxycycline treatment. The versatility of H9-iCas9.SAM cells was demonstrated in directed in vitro differentiation assays, yielding neural stem cells (ectoderm), hematopoietic progenitor cells (mesoderm), and hepatocytes (endoderm). This underscores their potential in developmental biology studies and cell therapy applications. The engineered H9-iCas9.SAM line provides a robust platform for investigating gene function and advancing next-generation cell-based therapies.

Abstract Mussels (Mytilus spp.) are abundant in the North Atlantic, sessile, and sensitive to environmental change, and suitable as sentinels of environment and climate change of costal ecosystems. We aimed to determine the baseline for the Northeast Atlantic (58–70°N) Mytilus species complex, and to show the present distribution to surveys conducted 60 years ago. Baseline was obtained by investigating a total of 509 stations in the intertidal zone, in four regions comprising the environmental gradient from head of fjord to coast, and distributed over the latitudinal gradient from 58 to 70°N. The baseline shows a range in continuous abundance of mussels from 12% to 36%, patchy abundance from 26% to 57% and no or very limited mussel abundance from 26% to 46% between the four regions. The presence of mussels in the southeast and west region was visualized to previous surveys conducted 60 years ago. The data points to similar past and present presence of mussels in both regions, yet past major mussel fields in the inner section of region southeast was not detected in this study. The baseline of Mytilus spp. in the Northeast Atlantic (58–70°N) is now available for future reference. The baseline, plotted to surveys conducted 60 years ago, points to awareness of the population situated in the southeast section of the investigated region. Continued monitoring and modeling are needed to clarify drivers of temporal and spatial variation in the mussel populations along the Northeastern Atlantic coast.

Facilitating a sustainable transition process, whether on a global or local scale, entails crafting an energy mix tailored to meet the specific needs of users. The objective is to pinpoint the most effective future strategy that optimizes both socio-economic benefits and sustainability. To tackle these challenges, a plethora of modeling tools now exists to evaluate various scenarios prior to implementation. However, it is worth noting that modeling tools are primarily geared towards economic optimization, exemplified by the open-source energy modeling system, OSeMOSYS. This paper proposes an optimization methodology encompassing economic, energetic, and environmental sustainability, introducing the most widely referenced estimator as an economic additional cost using the weight sum and monetization methodology. The ramifications of integrating these different estimators in terms of energy matrix design, costs, and emissions are thoroughly evaluated. Furthermore, the optimal selection criteria are delineated based on users’ anticipated objectives. To ensure the reproducibility of the study, we present an exercise utilizing data from Atlantis framework, which shares characteristics of both developing and developed nations. The main results indicate that implementing sustainability, despite not causing significant variations in overall costs (¡0.5%), leads to a 35% decrease in emissions. However, there is a 14.5% increase in investment costs, while residual costs rise by 6%.

Abstract Background This study aimed to assess the comorbidity profile, use of healthcare resources and medical costs of patients with systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE) treated at the hospital level in Spain. Methods Admission records of patients with SLE and CLE that were registered between January 2016 and December 2020 were obtained from a Spanish hospital discharge database and analyzed in a retrospective multicenter study. Results 329 patients met the criteria; 64.44% were female and 35.56% were male, with a median age of 54.65 years. Mean Charlson comorbidity index (CCI) was 2.75 in the index admission. 31.61% of the patients suffered essential hypertension, 21.96% suffered asthma and 19.76% suffered hyperlipidemia. Mortality rate was 3.95%. The most common medical procedure was heart ultrasound (19.45%) and introduction in peripheral vein of anti-inflammatory with a percutaneous approach (17.93%). Mean admission cost was €6355.99. Conclusions Lupus patients showed a higher incidence and prevalence in the female population, with associated cardiac diseases as the main secondary conditions.

UAV-SfM techniques are in constant development to address the challenges of accurate and precise mapping in terrains with complex morphologies. In contrast with the traditional photogrammetric processes, where only nadir images were considered, the combination of those with oblique imagery, also called off-nadir, has emerged as an optimal solution to achieve higher accuracy in these kinds of landscapes. UAV flights at a constant height above ground level (AGL) have also been considered a possible alternative to improve the resulting 3D point clouds compared to those obtained from constant height above mean sea level (AMSL) flights. The aim of this study is to evaluate the effect of incorporating oblique images as well as the type of flight on the accuracy and precision of the point clouds generated through UAV-SfM workflows for terrains with complex geometries. For that purpose, 58 scenarios with different camera angles and flight patterns for the oblique images were considered, 29 for each type of flight (AMSL and AGL). The 3D point cloud derived from each of the 58 scenarios was compared with a reference 3D point cloud acquired with a terrestrial laser scanner (TLS). The results obtained confirmed that both incorporating oblique images and using AGL flight mode have a positive effect on the mapping. Combination of nadir image blocks, obtained from an AGL crosshatch flight plan, with supplemental oblique images collected with a camera angle of between 20° and 35° yielded the best accuracy and precision records.

IntroductionThe care of people with schizophrenia (PWS) is usually provided in an outpatient setting by community mental health teams. However, PWS frequently require inpatient treatment because of a wide array of clinical, personal and/or social situations. Unfortunately, to our knowledge, there are no guidelines available to help psychiatrists in the decision-making process on hospital discharge for PWS. The aim of this project was to develop an expert consensus on discharge criteria for PWS after their stay in an acute inpatient psychiatric unit.MethodsUsing a modified Delphi method a group of 42 psychiatrists throughout Spain evaluated four areas of interest regarding this issue: clinical symptomatology, treatment-related factors, follow-up health care units after discharge, and physical health and monitoring.ResultsAfter two rounds, among the 64 statements, a consensus was reached for 59 (92.2%) statements. In three (17.7%) of the 17 statements on ‘clinical symptomatology’ and 2 (13.3%) of the 15 statements on ‘follow-up health care units after discharge’, a consensus was not reached; in contrast, a consensus was reached for all statements concerning ‘treatment-related factors’ and those concerning ‘physical health and monitoring’. The consensus results highlight the importance for discharge of the control of symptoms rather than their suppression during admission and of tolerability in the selection of anantipsychotic.DiscussionAlthough there is a lack of relevant data for guiding the discharge of PWS after hospitalization in an acute inpatient psychiatric unit, we expect that this consensus based on expert opinion may help clinicians to take appropriate decisions.

Abstract Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML) and is driven by rare therapy‐resistant leukemia stem cells (LSCs) that reside in specific bone marrow niches. Hypoxia signaling maintains cells in a quiescent and metabolically relaxed state, desensitizing them to chemotherapy. This suggests the hypothesis that hypoxia contributes to the chemoresistance of AML‐LSCs and may represent a therapeutic target to sensitize AML‐LSCs to chemotherapy. Here, we identify HIFhigh and HIFlow specific AML subgroups (inv(16)/t(8;21) and MLLr, respectively) and provide a comprehensive single‐cell expression atlas of 119,000 AML cells and AML‐LSCs in paired diagnostic‐relapse samples from these molecular subgroups. The HIF/hypoxia pathway signature is attenuated in AML‐LSCs compared with more differentiated AML cells but is more expressed than in healthy hematopoietic cells. Importantly, chemical inhibition of HIF cooperates with standard‐of‐care chemotherapy to impair AML growth and to substantially eliminate AML‐LSCs in vitro and in vivo. These findings support the HIF pathway in the stem cell‐driven drug resistance of AML and unravel avenues for combinatorial targeted and chemotherapy‐based approaches to specifically eliminate AML‐LSCs.

Rosacea is an inflammatory skin disease involving diverse symptoms with a variable clinical progress which can severely impact the patient’s quality of life as well as their mental health. The pathophysiological model of rosacea involves an unbalanced immune system predisposed to excessive inflammation, in addition to vascular and nervous alterations, being certain cutaneous microorganisms’ triggers of the symptoms onset. The gut-skin axis explains a bidirectional interaction between skin and gut microbiota in some inflammatory skin diseases such as atopic dermatitis, psoriasis, or rosacea. The introduction and consolidation of the next-generation sequencing in recent years has provided unprecedented information about the microbiome. However, the characterization of the gut and skin microbiota and the impact of the gut-skin axis in patients with rosacea has been little explored, in contrast to other inflammatory skin diseases such as atopic dermatitis or psoriasis. Furthermore, the clinical evolution of patients with rosacea is not always adequate and it is common for them to present a sustained symptomatology with frequent flare-ups. In this context, probiotic supplementation could improve the clinical evolution of these patients as happens in other pathologies. Through this review we aim to establish and compile the basics and directions of current knowledge to understand the mechanisms by which the microbiome influences the pathogenesis of rosacea, and how modulation of the skin and gut microbiota could benefit these patients.

Background: Multiple system atrophy (MSA) is a neurodegenerative disease. It has a fast progression, so early diagnosis is decisive. Two functional imaging tests can be involved in its diagnosis: [123I]Ioflupane SPECT and [123I]MIBG scintigraphy. Our aim is to comparatively analyze the diagnostic performance of both techniques. Methods: 46 patients (24 males and 22 females) with MSA underwent [123I]Ioflupane SPECT and [123I]MIBG scintigraphy. In each of these techniques, qualitative assessment was compared with quantitative assessment. Results: SPECT visual assessment was positive in 93.5% of subjects (S = 95.24%; PPV = 93.02%). A cut-off of 1.363 was established for overall S/O index (S = 85.7%, E = 100%). Visual assessment of scintigraphy was positive in 73.1% (S = 78.57%, PPV = 94.29%). For the delayed heart/medistinum ratio (HMR) a cut-off of 1.43 (S = 85.3, E = 100%) was obtained. For each unit increase in delayed HMR, the suspicion of MSA increased by 1.58 (OR = 1.58, p < 0.05). The quantitative assessment showed an association with the visual assessment for each technique (p < 0.05). Conclusions: Both tests are useful in MSA diagnosis. Comparatively, we did not observe a clear superiority of either. Striatal and myocardial deterioration do not evolve in parallel. Qualitative assessment is crucial in both techniques, together with the support of quantitative analysis. Delayed HMR shows a direct relationship with the risk of MSA.

Background: The global COVID-19 pandemic has shown the vulnerability of some population groups, including persons with intellectual and developmental disabilities (IDD). Aim: The present paper will provide more clarity and understanding of the experiences of family members of persons with IDD housed in residential facilities in Catalonia within the period of maximum restrictions during the COVID-19 pandemic. Methods and procedures: Semi-structured interviews were conducted using an interpretive phenomenological qualitative approach. Study participants consisted of 14 relatives of IDD individuals who were institutionalized in residence facilities or homes. The guiding questions emerged from group discussions with relatives of those with IDD who did not participate in the subsequent interviews. Drawing from this group, the factors that were identified to have had the greatest impact on their lives were later used to guide the interviews. Data collection was carried out in face-to-face individual interviews that were recorded together with the observations of two researchers between February and October 2022. Results: Our analysis identified 4 main themes that developed into additional factors: the decision to stay at home or in the residence, fear, illness, and protocol. Individuals with IDD lost their daily routines, suffered from social isolation, and did not understand the situation. Conclusion: The results of this study allow for a better understanding of the experiences of families of persons with IDD in residential centres during the lockdown by identifying their needs and how to better support them in the future. Outcomes and results: Knowledge and understanding of these events should allow for better management of similar situations in the future. The impact of the present research: This study contributes to a growing body of research that examines the experiences of IDD individuals and their families during the early months of the COVID-19 pandemic. A qualitative phenomenological interpretative approach was used following the recommendations of qualitative research practices in health care. Our findings reveal that relatives of persons with IDD who lived in residential care homes felt that the residents were not adequately cared for by the staff, who applied measures for containment and contagion prevention that were disproportionate, resulting in their needs not being considered; these recommended measures had been developed for elderly care homes. Individuals with IDD lost their daily routines, suffered from social isolation, and did not understand the situation. The present findings show that residential care homes for persons with IDD require specific action protocols in crisis situations that are adapted to the needs and characteristics of each centre,thus adopting a model of care based on human rights. [ABSTRACT FROM AUTHOR]

The hippocampus (HC) is recognized for its pivotal role in memory‐related plasticity and facilitating adaptive behavioral responses to reward shifts. However, the nature of its involvement in the response to reward downshifts remains to be determined. To bridge this knowledge gap, we explored the HC's function through a series of experiments in various tasks involving reward downshifts and using several neural manipulations in rats. In Experiment 1, complete excitotoxic lesions of the HC impaired choice performance in a modified T‐maze after reducing the quantity of sugar pellet rewards. In Experiment 2, chemogenetic inhibition of the dorsal HC (dHC) disrupted anticipatory behavior following a food‐pellet reward reduction. Experiments 3–5 impaired HC function by using peripheral lipopolysaccharide (LPS) administration. This treatment, which induces peripheral inflammation affecting HC function, significantly increased cytokine levels in the dHC (Experiment 3) and impaired anticipatory choice behavior (Experiment 4). None of these dorsal hippocampal manipulations affected consummatory responses in animals experiencing sucrose downshifts. Accordingly, we found no evidence of increased neural activation in either the dorsal or ventral HC, as measured by c‐Fos expression, after a sucrose downshift task involving consummatory suppression (Experiment 6). The results highlight the HC's pivotal role in adaptively modulating anticipatory behavior in response to a variety of situations involving frustrative nonreward, while having no effect on adjustments on consummatory behavior. The data supporting this conclusion were obtained under heterogeneous experimental conditions derived from a multi‐laboratory collaboration, ensuring the robustness and high reproducibility of our findings. Spatial orientation, memory update, choice of reward signals of different values, and anticipatory versus consummatory adjustments to reward downshift are discussed as potential mechanisms that could account for the specific effects observed from HC manipulations. [ABSTRACT FROM AUTHOR]

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This study sets out to analyze residents' support for sustainable tourism through perceived benefits and costs, community attachment and community participation, measuring the influence of the level of education of residents in a tourist destination where three tourism-related typologies coexist. We tested our conceptual model using survey data from 323 residents of the city of Puerto Plata, Dominican Republic. The results based on PLS-SEM show that the perceived benefits, the perceived costs, community attachment and community participation are antecedents to the support for sustainable tourism development, although no significant differences were found between the residents' level of education (university or basic). This study opens an interesting debate, as previous research has found differences between residents and their support for tourism according to their level of education. [ABSTRACT FROM AUTHOR]