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This study presents in situ, high-resolution optical measurements of particle size distributions (PSD) within sediment plumes generated by a pre-prototype deep seabed nodule collector vehicle operating in the abyssal Pacific Ocean. These measurements were obtained using a cutting-edge instrument, the LISST-RTSSV sensor. The data collected in situ reveal marked differences compared to previously reported laboratory-based, ex situ measurements. The grain size and other key particle shape characteristics are found to be dependent on multiple factors, including the collector vehicle maneuvers, the time elapsed following sediment discharge, and the complex hydrodynamic processes that generate the sediment in suspension. Significantly, the PSD from a highly complex succession of straight-line maneuvers converges to that of the canonical case of a simple straight-line driving maneuver within a timescale of ten minutes. Our results underscore the importance of parameterizing sediment plume transport models based on well-informed, comprehensive PSDs of detrained suspended sediment measured in situ at adequate timescales and in regions no longer strongly influenced by active and complex hydrodynamic processes.

Motivated by the need to harness the properties of renewable and biodegradable polymers for the design and manufacturing of multi-scale structures with complex geometries, we have employed our additive manufacturing platform that leverages molecular self-assembly for the production of metre-scale structures characterized by complex geometries and heterogeneous material composition. As a precursor material, we used chitosan, a chemically modified form of chitin, an abundant and sustainable structural polysaccharide. We demonstrate the ability to control concentration-dependent crystallization as well as the induction of the preferred orientation of the polymer chains through the combination of extrusion-based robotic fabrication and directional toolpathing. Anisotropy is demonstrated and assessed through high-resolution micro-X-ray diffraction in conjunction with finite element simulations. Using this approach, we can leverage controlled and user-defined small-scale propagation of residual stresses to induce large-scale folding of the resulting structures.

RESUMEN Introducción y objetivos: Actualmente, el acceso radial distal (ARD) para procedimientos coronarios es una alternativa al acceso radial convencional, con algunas ventajas descritas principalmente en términos de complicaciones relacionadas con el acceso. A pesar de la evidencia, pocos centros han establecido el ARD como acceso sistemático para procedimientos coronarios. El objetivo de esta cohorte prospectiva es presentar la experiencia inicial en nuestro centro con el ARD en pacientes con indicación de procedimientos coronarios en cualquier escenario clínico. Métodos: Se incluyeron 1.000 procedimientos de ARD (943 pacientes) realizados en un único centro de agosto de 2020 a noviembre de 2023. El estudio fue realizado con pacientes en cualquier escenario clínico. Se recomendó la valoración por ultrasonido del trayecto de la arteria radial antes y después del procedimiento, así como la punción ecoguiada. El objetivo principal fue el éxito del ARD. Como objetivos secundarios se consideraron el éxito del procedimiento coronario, el desempeño del ARD y las complicaciones relacionadas con el acceso. Resultados: El éxito del ARD fue del 97,4% (n = 974) y el éxito del procedimiento coronario fue del 96,9% (n = 969). El tiempo de acceso del ARD fue de 40 segundos [rango intercuartílico, 30-60]. Se realizaron procedimientos diagnósticos en el 64% (n = 644) e intervencionismo coronario percutáneo (ICP) en el 36% (n = 356), incluyendo ICP primario en el 13% (n = 128) de los pacientes. La valoración por ultrasonido antes del procedimiento se llevó a cabo en el 83% (n = 830) y la punción ecoguiada en el 85% (n = 848). La incidencia de complicaciones relacionadas con el acceso fue del 2,9% (n = 29). Conclusiones: Este estudio muestra la viabilidad y la seguridad del ARD principalmente guiado por ultrasonido para los procedimientos coronarios en cualquier escenario clínico, con un alto porcentaje de éxito del acceso y de éxito del procedimiento, además de una baja incidencia de complicaciones relacionadas con el acceso. El estudio fue registrado en ClinicalTrials.gov (NTC06165406).

ABSTRACT Introduction and objectives: Distal radial access (DRA) for coronary procedures is currently recognized as an alternative to conventional transradial access, with documented advantages primarily related to access-related complications. However, widespread adoption of DRA as the default approach remains limited. Therefore, this prospective cohort study aimed to present our initial experience with DRA for coronary procedures in any clinical settings. Methods: From August 2020 to November 2023, we included 1000 DRA procedures (943 patients) conducted at a single center. The study enrolled a diverse patient population. We recommended pre- and postprocedural ultrasound evaluations of the radial artery course, with ultrasound-guided DRA puncture. The primary endpoint was DRA success, while secondary endpoints included coronary procedure success, DRA performance metrics, and the incidence of access-related complications. Results: The DRA success rate was 97.4% (n = 974), with coronary procedure success at 96.9% (n = 969). The median DRA time was 40 [interquartile range, 30-60] seconds. Diagnostic procedures accounted for 64% (n = 644) of cases, while 36% (n = 356) involved percutaneous coronary intervention (PCI), including primary PCI in 13% (n = 128). Pre-procedure ultrasound evaluation and ultrasound-guided DRA were performed in 83% (n = 830) and 85% (n = 848) of cases, respectively. Access-related complications occurred in 2.9% (n = 29). Conclusions: This study shows the safety and feasibility of DRA for coronary procedures, particularly when performed under ultrasound guidance in a diverse patient population. High rates of successful access and coronary procedure outcomes were observed, together with a low incidence of access-related complications. The study was registered on ClinicalTrials.gov (NTC06165406).

The inclusion of the principle of Policy Coherence for Development (PCD) into the 2030 Agenda and its interrelation with climate induced migration constitutes both a challenge and a commitment for the Spanish foreign policy in addressing the challenges posed by Africa, specifically in the case of Senegal. In this context, the objective of this article is to analyze the degree of alignment between the Spanish development cooperation policy and the Senegal’s National Development Strategies from the perspective of PCD, particularly in relation to issues linked climate induced migration. The results highlight a lack of alignment in the policies of both countries regarding these issues. These discrepancies are influenced by political, geostrategic, and commercial interests within the Africa Plan.

Objetivo: revisar y validar un cuestionario de conocimientos sobre manejo de insulinas inyectables (JH-SEFAC) por pacientes con diabetes para utilización en las farmacias comunitarias (FC). Métodos: diseño del estudio: observacional transversal en FC españolas durante el primer semestre de 2023. Criterios de inclusión: pacientes con diabetes, mayores de edad, en tratamiento con insulina. Diseño del cuestionario: un grupo nominal de FC revisó y pilotó el cuestionario inicial para determinar su viabilidad. Fue aprobado por el CEIC de Aragón (PI22/375). Validación de contenido: por un grupo multidisciplinar de expertos en diabetes, mediante un cuestionario de evaluación ad hoc de 10 preguntas (escala Likert de 1-5). Fiabilidad: mediante el índice de consistencia interna (alfa de Cronbach) y el coeficiente de correlación intraclase (CCI). Reproducibilidad (test/retest): se compararon los resultados del cuestionario administrado dos veces separadas 2-3 semanas al grupo de pacientes. Colaboraron farmacéuticos miembros del Grupo de Trabajo de Diabetes de SEFAC. Muestra: se calculó en 127 sujetos (IC del 95 % y precisión del 10 %). Resultados: 20 FC de 13 CCAA incorporaron 131 pacientes. La valoración de los expertos fue de 4,52 sobre 5 (90,4 %). El test Keiser-Meyer-Olkin fue de 0,626 y la prueba de Bartlett resultó significativa (p

Abstract The influx of refugees, population growth and current agricultural practices have led to an increase in water demand in Jordan, placing pressure on existing water provision. Climate change further exacerbates declining water availability. Against this backdrop, the techno-economic feasibility of four water supply and sanitation alternatives for small and medium scale cities in Jordan were explored, using local unit costs and Al-Mafraq as a case study. City level piped network combined with household rooftop rainwater harvesting and surface runoff collection into local ponds and piped networks with treatment using the nature-based solution of root-zone for sanitation were demonstrated to provide the highest benefits in terms of cost, convenience and water conservation. Our work highlights the need to invest in long-term urban infrastructure networks to promote sustainable future growth of cities. This is vital to address severe water scarcity challenges that ultimately impact those at the urban fringes most.

Abstract This study presents in situ, high-resolution optical measurements of particle size distributions (PSD) within sediment plumes generated by a pre-prototype deep seabed nodule collector vehicle operating in the abyssal Pacific Ocean. These measurements were obtained using a cutting-edge instrument, the LISST-RTSSV sensor. The data collected in situ reveal marked differences compared to previously reported laboratory-based, ex situ measurements. The grain size and other key particle shape characteristics are found to be dependent on multiple factors, including the collector vehicle maneuvers, the time elapsed following sediment discharge, and the complex hydrodynamic processes that generate the sediment in suspension. Significantly, the PSD from a highly complex succession of straight-line maneuvers converges to that of the canonical case of a simple straight-line driving maneuver within a timescale of ten minutes. Our results underscore the importance of parameterizing sediment plume transport models based on well-informed, comprehensive PSDs of detrained suspended sediment measured in situ at adequate timescales and in regions no longer strongly influenced by active and complex hydrodynamic processes.

Abstract Background Sarcopenia, the gradual and generalized loss of muscle mass and function with ageing, is one of the major health problems in older adults, given its high prevalence and substantial socioeconomic implications. Despite the extensive efforts to reach consensus on definition and diagnostic tests and cut‐offs for sarcopenia, there is an urgent and unmet need for non‐invasive, specific and sensitive biomarkers for the disease. Extracellular vesicles (EVs) are present in different biofluids including plasma, whose cargo reflects cellular physiology. This work analysed EV proteome in sarcopenia and robust patients in the search for differentially contained proteins that can be used to diagnose the disease. Methods Plasma small EVs (sEVs) from a total of 29 robust controls (aged 73.4 ± 5.6 years; 11 men and 18 women) and 49 sarcopenic patients (aged 82.3 ± 5.4 years; 15 men and 34 women) aged 65 years and older were isolated and their cargo was analysed by proteomics. Proteins whose concentration in sEVs was different between sarcopenic and robust patients were further validated using ELISA. The concentration of these candidates was correlated to the EWGSOP2 sarcopenia tests for low muscle strength and low physical performance, and receiver operating characteristic (ROC) curve analyses were carried out to evaluate their diagnostic power, sensitivity and specificity. Results Proteomic analysis identified 157 sEVs proteins in both sarcopenic and robust samples. Among them, 48 proteins had never been reported in the ExoCarta nor Vesiclepedia databases. Statistical analysis revealed eight proteins whose concentration was significantly different between groups: PF4 (log2 FC = 4.806), OIT3 (log2 FC = −1.161), MMRN1 (log2 FC = −1.982), MASP1 (log2 FC = −0.627), C1R (log2 FC = 1.830), SVEP1 (log2 FC = 1.295), VCAN (FC = 0.937) and SPTB (log2 FC = 1.243). Among them, platelet factor 4 (PF4) showed the lowest concentration while Complement C1r subcomponent (C1R) increased the most in sarcopenic patients, being these results confirmed by ELISA (P = 1.07E‐09 and P = 0.001287, respectively). The concentrations of candidate proteins significantly correlated with EWGSOP2 tests currently used. ROC curve analysis showed an area under the curve of 0.8921 and 0.7476 for PF4 and C1R, respectively. Choosing the optimal for PF4, 80% sensitivity and 85.71% specificity was reached while the optimal cut‐off value of C1R would allow sarcopenia diagnosis with 75% sensitivity and 66.67% specificity. Conclusions Our results support the determination of EV PF4 and C1R as plasma diagnostic biomarkers in sarcopenia and open the door to investigate the role of the content of these vesicles in the pathogeny of the disease.

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

Abstract The extended period of coexistence between Neanderthals and Homo sapiens in Europe coincided with the emergence of regionally distinctive lithic industries, signalling the onset of the Upper Palaeolithic. The Iberian Peninsula was on the periphery of pioneering Upper Palaeolithic developments, with archaeological remains primarily found in northern territories. We report the discovery of an initial Upper Palaeolithic lithic industry at Cueva Millán in the hinterlands of Iberia. This industry, termed here Arlanzian, not only represents the earliest and southernmost evidence of such industries in Iberia but also lacks a direct counterpart. However, it exhibits chronological and technological parallels with the lithic industries associated with the earliest expansion of Homo sapiens throughout Eurasia. We interpret this as potential evidence of its intrusive nature, but not necessarily associated with a migration event, as more complex scenarios derived from inter-population connectivity must be also considered. The biological identity of the Arlanzian makers remains unknown, but they coexisted with declining Neanderthal groups from neighbouring territories.

Abstract Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify peroxisome proliferator-activated receptor gamma (PPARγ) as a key nuclear receptor mediating CBD’s beneficial effects, while also providing proof of dysregulated PPARγ expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS.

Abstract Background We have previously demonstrated the significant reliance of pancreatic Cancer Stem Cells (PaCSCs) on mitochondrial oxidative phosphorylation (OXPHOS), which enables versatile substrate utilization, including fatty acids (FAs). Notably, dysregulated lipid scavenging and aberrant FA metabolism are implicated in PDAC progression. Methods & results Our bioinformatics analyses revealed elevated expression of lipid metabolism-related genes in PDAC tissue samples compared to normal tissue samples, which correlated with a stemness signature. Additionally, PaCSCs exhibited heightened expression of diverse lipid metabolism genes and increased lipid droplet accumulation compared to differentiated progenies. Treatment with palmitic, oleic, and linolenic FAs notably augmented the self-renewal and chemotherapy resistance of CD133+ PaCSCs. Conversely, inhibitors of FA uptake, storage and metabolism reduced CSC populations both in vitro and in vivo. Mechanistically, inhibition of FA metabolism suppressed OXPHOS activity, inducing energy depletion and subsequent cell death in PaCSCs. Importantly, combining a FAO inhibitor and Gemcitabine treatment enhanced drug efficacy in vitro and in vivo, effectively diminishing the CSC content and functionality. Conclusion Targeting FAO inhibition represents a promising therapeutic strategy against this highly tumorigenic population.

This study investigates how customers co-create value in online banking. The aims of this study were twofold. First, it tests the DART model (dialogue, access, risk assessment, and transparency) as a driver of customer value co-creation. Second, this study investigates trust and reputation as the outcomes of value co-creation in online banking. Exploratory factor analysis was used by applying a Principal Components Analysis with SPSS and SMART PLS to check the model and the relationship between the factors of the DART model, value co-creation, company reputation, and customer trust. Data were collected through a questionnaire sent to 217 online bank customers. The findings show that strategic value co-creation is influenced by dialogue, access to information, risk assessment, and transparency. The results also show that customer value co-creation can result in greater reputation and trust. This study contributes to the literature in two ways. First, this study extends the marketing literature by showing that value co-creation can generate reputation and trust as an outcome, changing the perspective in which the phenomenon is traditionally observed. Second, the study tests the DART model in the online banking industry, showing that the original model also works for bank customers. This study provides managerial guidelines for each variable of the DRAT model.

In this article, we present a methodological approach to address spatial disparity in global data representation, introducing an algorithm called Flexible Mapping to Understand Spatial Analysis (FLEMUSA). We utilize world maps to depict various data points across countries, revealing substantial variation among them. However, conventional choropleth maps often fail to effectively represent regions with sparse data, obscuring valuable insights. To mitigate this issue, we propose interactive graphical methods in both two and three dimensions, implemented through open-source Python code accessible via Google Colab. Our approach includes several contributions such as excluding countries without data from the representation, scaling magnitudes within country borders, focusing on regional analysis, and using logarithmic scales for bubble maps proportional to country sizes. Additionally, we offer interactive 2D and 3D representations, rotatable 3D representations, and zoomable options, facilitating enhanced visualization of regional similarities amidst data heterogeneity. Through this algorithm, we aim to improve the clarity and interpretability of spatial data analysis, integrating solutions for extreme data overdispersion, all programmed with open-source code. - Utilization of world maps for visual representation of data across countries mitigating the overdispersion step by step. - Implementation of graphical methods, including interactive 2D and 3D maps, to address spatial disparity. - Provision of open-source code for customizable graphical representations, facilitating implementation in online journals as interactive code snippets.

Background: Gastroenteritis is the main cause of death in children under five years of age with symptoms of dehydration, which causes high mortality rates. Gastroenteritis risk factors include poor hygiene, unclean water supplies, and lack of parental knowledge. Providing health education regarding gastroenteritis is very important to increase mother’s knowledge. WhatsApp bot and lectures are effective media that can be used in health education. Objectives: To determine the effectiveness of WhatsApp bot-based educational media and lectures in increasing knowledge of Gastroenteritis among housewives. Methods: The research method used was quasi-experimental using a two-group design posttest only. The research was conducted in Singosari, Malang, using two different groups with a sample size of 50. Group 01 was given education using WhatsApp bot media, while group 02 was given education using lecture media. The research data was tested using the Mann-Whitney test in SPSS version 25. Results: The demographic data obtained shows that the average number of respondents is (60%) not working or a housewife. The research results show a difference between giving education using the lecture method and WhatsApp bot media on housewives' knowledge level. Mother’s knowledge about gastroenteritis increased after being given education using two different media. The group using lecture media had a better increase in knowledge than the group using WhatsApp bot media. Conclusion: Health education regarding gastroenteritis based on lecture media is more effective than WhatsApp bot media in increasing mothers' knowledge about preventing gastroenteritis in children