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Abstract Patients with liver cirrhosis may show minimal hepatic encephalopathy (MHE) with motor incoordination which is reproduced in hyperammonemic rats. Hyperammonemia induces peripheral inflammation which triggers neuroinflammation and enhanced GABAergic neurotransmission in cerebellum and motor incoordination. The mechanisms involved remain unknown. The aims were to assess if the early increase of peripheral IL-17 triggers motor incoordination in hyperammonemic rats and to identify some underlying mechanisms. We assessed if blocking peripheral IL-17 with anti-IL-17 at 2–4 days of hyperammonemia prevents motor incoordination and analyzed underlying mechanisms. Hyperammonemia induces a transient blood IL-17 increase at days 3–4. This is associated with increased IL-17 receptor membrane expression and activation in cerebellum, leading to NADPH oxidase activation, increased superoxide production and MLCK that induce blood–brain barrier (BBB) permeabilization by reducing occludin and ZO-1. BBB permeabilization facilitates the entry of IL-17, which increases in cerebellum and activates microglia. This increases TNFα and the TNFR1-S1PR2-CCL2-BDNF-TrkB pathway. This enhances GABAergic neurotransmission which impairs motor coordination. Blocking peripheral IL-17 with anti-IL-17 prevents all the above process and prevents motor incoordination. Early treatment to reduce blood IL-17 may be a useful treatment to reverse motor incoordination in patients with MHE. Graphical abstract

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.

This paper presents a comprehensive dataset detailing the precise indoor positioning of players from a female amateur handball team across 10 real matches. Utilizing Ultra-Wideband (UWB) technology, the dataset captures each player's x and y coordinates every second throughout the games. Additionally, a preliminary game analysis is included, specifying the initiation and termination times of each team's possession. This analysis provides a variety of labels crucial for training machine learning algorithms, encompassing distinctions such as attack or defense, structured or unstructured play, goal outcomes, and the differentiation between counter-attacks and static phases. In total, the dataset comprises 84691 positioning measurements, offering a valuable resource for in-depth study and analysis of player dynamics and game strategies in female handball.

El Palacio de los Pardo Donlebún es un edificio emblemático de la costa asturiana, cuyo pasado ha sido testigo de numerosos eventos históricos en la frontera astur-galaica. Su rehabilitación se realizó gracias a la intervención de maestros de la construcción provenientes de diversas regiones como Asturias, Galicia, Ávila e incluso un austriaco afincado en Asturias. Estos maestros no solo recuperaron los materiales originales de la obra, sino que también revivieron oficios que habían desaparecido en la región. La localización y utilización de materiales de la época del Palacio, la integración de soluciones constructivas contemporáneas y la ocultación de las instalaciones fueron aspectos clave del proyecto. La intervención respetó los espacios originales, limitándose a sustituir los usos obsoletos por otros de interés en la actualidad.

Due to its inherent flexibility and adaptability, e-learning has become a versatile and effective educational option, with video-based learning (VBL) enabling asynchronous engagement. Despite the wealth of video resources, evaluating their effectiveness remains challenging. This study employs a comprehensive approach, analyzing student behavior and video metadata to assess educational videos’ efficacy. Metrics such as average playback speed, video and course completion rates, and video metadata were examined using the XuetangX dataset, MOOC- CubeX. Results indicate that viewing patterns are more influenced by students’ choices than by video content. Well-conceptualized videos increase viewing time, with 17 % of students engaging with videos over 30 min if they cover focused topics. While shorter videos generally have higher completion rates, many remain untouched. Playback speed analysis shows a preference for standard speed, with positive correlations between speed and both completion percentage and viewing time. Courses under 5 h are likely to be watched for less than an hour, reflecting brief viewing durations. Metadata analysis reveals that generic titles may deter engagement, underscoring the importance of precise tagging and content relevance for enhancing student interaction.

Abstract Abnormal accumulation of misfolded and hyperphosphorylated tau protein in brain is the defining feature of several neurodegenerative diseases called tauopathies, including Alzheimer’s disease (AD). In AD, this pathological change is reflected by highly specific cerebrospinal fluid (CSF) tau biomarkers, including both phosphorylated and non-phosphorylated variants. Interestingly, despite tau pathology being at the core of all tauopathies, CSF tau biomarkers remain unchanged in certain tauopathies, e.g., progressive supranuclear palsy (PSP), Pick’s disease (PiD), and corticobasal neurodegeneration (CBD). To better understand commonalities and differences between tauopathies, we report a multiplex assay combining immunoprecipitation and high-resolution mass spectrometry capable of detecting and quantifying peptides from different tau protein isoforms as well as non-phosphorylated and phosphorylated peptides, including those carrying multiple phosphorylations. We investigated the tau proteoforms in soluble and insoluble fractions of brain tissue from subjects with autopsy-confirmed tauopathies, including sporadic AD (n = 10), PSP (n = 11), PiD (n = 10), and CBD (n = 10), and controls (n = 10). Our results demonstrate that non-phosphorylated tau profiles differ across tauopathies, generally showing high abundance of microtubule-binding region (MTBR)-containing peptides in insoluble protein fractions compared with controls; the AD group showed 12–72 times higher levels of MTBR-containing aggregates. Quantification of tau isoforms showed the 3R being more abundant in PiD and the 4R isoform being more abundant in CBD and PSP in the insoluble fraction. Twenty-three different phosphorylated peptides were quantified. Most phosphorylated peptides were measurable in all investigated tauopathies. All phosphorylated peptides were significantly increased in AD insoluble fraction. However, doubly and triply phosphorylated peptides were significantly increased in AD even in the soluble fraction. Results were replicated using a validation cohort comprising AD (n = 10), CBD (n = 10), and controls (n = 10). Our study demonstrates that abnormal levels of phosphorylation and aggregation do indeed occur in non-AD tauopathies, however, both appear pronouncedly increased in AD, becoming a distinctive characteristic of AD pathology.

Abstract The biomedical research community addresses reproducibility challenges in animal studies through standardized nomenclature, improved experimental design, transparent reporting, data sharing, and centralized repositories. The ARRIVE guidelines outline documentation standards for laboratory animals in experiments, but genetic information is often incomplete. To remedy this, we propose the Laboratory Animal Genetic Reporting (LAG-R) framework. LAG-R aims to document animals’ genetic makeup in scientific publications, providing essential details for replication and appropriate model use. While verifying complete genetic compositions may be impractical, better reporting and validation efforts enhance reliability of research. LAG-R standardization will bolster reproducibility, peer review, and overall scientific rigor.

Our goal was to determine the cellular immune response (CIR) in a sample of the Borriana COVID-19 cohort (Spain) to identify associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case–control study using a randomly selected sample of 225 individuals aged 18 and older, including 36 individuals naïve to the SARS-CoV-2 infection and 189 infected patients. We employed flow-cytometry–based immunoassays for intracellular cytokine staining, using Wuhan and BA.2 antigens, and chemiluminescence microparticle immunoassay to detect SARS-CoV-2 antibodies. Logistic regression models were applied. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3%, respectively. No difference in CIR was found between naïve and infected patients. Patients who experienced sequelae exhibited a higher CIR than those without. A positive correlation was observed between TCR and anti-spike IgG levels. Factors positively associated with the TCR included blood group A, number of SARS-CoV-2 vaccine doses received, and anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and blood group B. These findings contribute valuable insights into the nuanced immune landscape shaped by SARS-CoV-2 infection and vaccination.

Abstract Background Patients with liver cirrhosis may show minimal hepatic encephalopathy (MHE) with mild cognitive impairment and motor incoordination. Rats with chronic hyperammonemia reproduce these alterations. Motor incoordination in hyperammonemic rats is due to increased GABAergic neurotransmission in cerebellum, induced by neuroinflammation, which enhances TNFα-TNFR1-S1PR2-CCL2-BDNF-TrkB pathway activation. The initial events by which hyperammonemia triggers activation of this pathway remain unclear. MHE in cirrhotic patients is triggered by a shift in inflammation with increased IL-17. The aims of this work were: (1) assess if hyperammonemia increases IL-17 content and membrane expression of its receptor in cerebellum of hyperammonemic rats; (2) identify the cell types in which IL-17 receptor is expressed and IL-17 increases in hyperammonemia; (3) assess if blocking IL-17 signaling with anti-IL-17 ex-vivo reverses activation of glia and of the TNFα-TNFR1-S1PR2-CCL2-BDNF-TrkB pathway. Results IL-17 levels and membrane expression of the IL-17 receptor are increased in cerebellum of rats with hyperammonemia and MHE, leading to increased activation of IL-17 receptor in microglia, which triggers activation of STAT3 and NF-kB, increasing IL-17 and TNFα levels, respectively. TNFα released from microglia activates TNFR1 in Purkinje neurons, leading to activation of NF-kB and increased IL-17 and TNFα also in these cells. Enhanced TNFR1 activation also enhances activation of the TNFR1-S1PR2-CCL2-BDNF-TrkB pathway which mediates microglia and astrocytes activation. Conclusions All these steps are triggered by enhanced activation of IL-17 receptor in microglia and are prevented by ex-vivo treatment with anti-IL-17. IL-17 and IL-17 receptor in microglia would be therapeutic targets to treat neurological impairment in patients with MHE.

Abstract Inherited hearing impairment is a remarkably heterogeneous monogenic condition, involving hundreds of genes, most of them with very small ( 90 dB SPL) that correlates with specific structural abnormalities in the cochlea. We show that Gjb2 expression is nearly abolished and its protein product, Cx26, is nearly absent all throughout the cochlea, unlike previous conditional knockouts in which Gjb2 ablation was not obtained in all cell types. The Dfnb1 em274 model recapitulates the clinical presentation of patients harbouring the del(GJB6-D13S1830) variant and thus it is a valuable tool to study the pathological mechanisms of DFNB1 and to assay therapies for this most frequent type of human ARNSHI.

Abstract Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer’s disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Here, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n = 388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a peripherally accessible biomarker of AD pathophysiology.

Abstract Background Novel phosphorylated-tau (p-tau) blood biomarkers (e.g., p-tau181, p-tau217 or p-tau231), are highly specific for Alzheimer’s disease (AD), and can track amyloid-β (Aβ) and tau pathology. However, because these biomarkers are strongly associated with the emergence of Aβ pathology, it is difficult to determine the contribution of insoluble tau aggregates to the plasma p-tau signal in blood. Therefore, there remains a need for a biomarker capable of specifically tracking insoluble tau accumulation in brain. Methods NTA is a novel ultrasensitive assay targeting N-terminal containing tau fragments (NTA-tau) in cerebrospinal fluid (CSF) and plasma, which is elevated in AD. Using two well-characterized research cohorts (BioFINDER-2, n = 1,294, and BioFINDER-1, n = 932), we investigated the association between plasma NTA-tau levels and disease progression in AD, including tau accumulation, brain atrophy and cognitive decline. Results We demonstrate that plasma NTA-tau increases across the AD continuum¸ especially during late stages, and displays a moderate-to-strong association with tau-PET (β = 0.54, p

This article analyses how contemporary Catalan literature deals with the disappearance of the peasantry and proposes new ways of understanding and inhabiting contemporary rural space. Divided into three parts, it will first work on the poetics of the disappearance of the rural world of yesteryear and on the literary proposal of a new way of understanding rurality. The second part will focus on how the historical narrative of the rural past aims to recover a rural collective memory that allows us to understand its disappearance. Finally, we will work on the new narrative forms that allows us to depict condition of rurality nowadays.

Metabolic/neurodegenerative encephalopathies encompass a wide list of conditions that share similar clinical and magnetic resonance imaging (MRI) characteristics, challenging the diagnostic process and resulting in numerous tests performed in order to reach a definitive diagnosis. The aims of this multicentric, retrospective and descriptive study are: (I) to describe the MRI features of dogs and cats with metabolic/neurodegenerative encephalopathies; (II) to attempt an MRI recognition pattern classifying these conditions according to the involvement of grey matter, white matter or both; and (III) to correlate the MRI findings with previous literature. A total of 100 cases were recruited, comprising 81 dogs and 19 cats. These included hepatic encephalopathy (20 dogs and three cats), myelinolysis (five dogs), intoxications (seven dogs and one cat), thiamine deficiency (two dogs and seven cats), hypertensive encephalopathy (three dogs and two cats), neuronal ceroid lipofuscinosis (11 dogs and one cat), gangliosidosis (three dogs and two cats), fucosidosis (one dog), L-2-hydroxyglutaric aciduria (13 dogs and one cat), Lafora disease (11 dogs), spongiform leukoencephalomyelopathy (one dog) and cerebellar cortical degeneration (four dogs and two cats). None of the hepatic encephalopathies showed the previously described T1-weighted hyperintensity of the lentiform nuclei. Instead, there was involvement of the cerebellar nuclei (8/23), which is a feature not previously described. Dogs with myelinolysis showed novel involvement of a specific white matter structure, the superior longitudinal fasciculus (5/5). Thiamine deficiency affected numerous deep grey nuclei with novel involvement of the oculomotor nuclei (3/9), thalamic nuclei, subthalamus and cerebellar nuclei (1/9). Cats with hypertensive encephalopathy had a more extensive distribution of the white matter changes when compared to dogs, extending from the parietal and occipital lobes into the frontal lobes with associated mass effect and increased brain volume. Lysosomal storage disease showed white matter involvement only, with neuronal ceroid lipofuscinosis characterised by severe brain atrophy when compared to gangliosidosis and fucosidosis. All patients with L-2-hydroxyglutaric aciduria had a characteristic T2-weighted hyperintense swelling of the cerebral and cerebellar cortical grey matter, resulting in increased brain volume. Lafora disease cases showed either normal brain morphology (5/11) or mild brain atrophy (6/11). Dogs with cerebellar cortical degeneration had more marked cerebellar atrophy when compared to cats. This study shows the important role of MRI in distinguishing different metabolic/neurodegenerative encephalopathies according to specific imaging characteristics.

En la última década el sexting ha emergido como una práctica cada vez más común en la expresión de la sexualidad, especialmente, entre la adolescencia y juventud. Progresivamente, esta tendencia se ha ido integrando de manera significativa en las interacciones sociales y románticas de las personas, independientemente de encontrarse inmersos en una relación de pareja estable o no, lo que conlleva tanto oportunidades como desafíos y riesgos en términos de privacidad, consentimiento y salud. El objetivo del estudio fue analizar las diferencias en las conductas de sexting y motivaciones para realizarlo en función de la situación de pareja. Para ello, 200 universitarios (72% mujeres), de entre 19 y 30 años (M = 21.64, DT = 3.27), cumplimentaron una batería de preguntas online acerca de su historia afectivo-sexual y diversos cuestionarios sobre sexting. Entre los resultados, cabe destacar que las personas que tenían pareja estable recibían más contenido sexual (x² = 6.31; p =.012), enviaban más (x² = 11.97; p = .001) y recibían más respuestas ante contenido enviado (x² =9.68; p = .002). Teniendo en cuenta los motivos para realizar sexting, se encontraron diferencias estadísticamente significativas en hacerlo por aburrimiento (x² = 3.88; p = .049), sentimiento de soledad (x² = 7.91; p = .005), y no saber lo que hacían por algo que habían tomado (x² = 6.62; p = .010), siendo estas motivaciones más comunes entre las personas sin pareja estable. En conclusión, los resultados muestran la alta prevalencia de esta nueva vía de comunicación sexual y enfatizan la necesidad de considerar el estado relacional a la hora de establecer programas de prevención y/o promoción de la salud que aborden el fenómeno emergente del sexting, especialmente, para fomentar otras motivaciones que promuevan una sexualidad más saludable. Este trabajo ha sido posible gracias a la ayuda UJI-B2021-13 concedida por la Universitat Jaume I de Castellón

La literatura científica ha manifestado que la actitud favorable hacia la violación es uno de los factores explicativos de la violencia sexual, sobre todo hacia la mujer. Sin embargo, los factores que subyacen a este tipo de actitudes han sido poco estudiados en jóvenes en conflicto con la ley. Por tanto, el objetivo principal de esta investigación fue analizar la relación entre la actitud hacia la violación, los conocimientos y actitudes hacia el sexo, y el sexismo en un grupo de hombres jóvenes en conflicto con la ley. Se administró la Escala de Actitud Favorable hacia la Violación, el Cuestionario de Conocimientos y Actitudes Sexuales, y el Inventario de Sexismo Ambivalente a 84 hombres jóvenes de entre 14 y 21 años (M = 16.69, DT = 1.23) que se encontraban bajo el cumplimiento de medidas judiciales en residencias socioeducativas de la Comunidad Valenciana. Se encontró una correlación estadísticamente significativa con signo positivo entre la actitud favorable hacia la violación y el sexismo hostil (r =.38, p =.001) y benévolo (r =.38, p =.001). Asimismo, se encontró esta relación significativa a nivel estadístico con signo negativo entre la actitud favorable hacia la violación y las actitudes hacia la sexualidad (r = -.36, p =.001). Según los análisis de regresión, tanto el sexismo benévolo como el hostil fueron variables explicativas de la actitud favorable hacia la violación. Ambos tipos de sexismo emergieron como factores de riesgo de estas actitudes, explicando un 19% de la varianza. Estos hallazgos muestran la necesidad de diseñar estrategias preventivas que permitan trabajar las actitudes favorables hacia la violación teniendo en cuenta las actitudes sexistas y los estereotipos de género derivados de las mismas, en los que la mujer es percibida como un objeto que puede ser sometido a la voluntad del hombre.

Using multivariate linear regression models, this study estimates the relationship between graduates' self-reported skill improvements from attending a virtual university, the Open University of Catalonia (UOC), and their salaries after obtaining the degree. Our results show that graduates made considerable earnings gains and especially high rates of return to investing in a Master's degree. Reported earnings by male and female UOC students are 31% and 18% higher than their gender-age counterparts to university graduates in the Spanish labour market. They also benefited from unintended returns in terms of enhanced digital skills, even among graduates who were not enrolled in ICT-related degrees. The improvement they reported in these skills contributed to earnings gains, but only for males. As such, acquiring digital skills for women seems to have little impact on how much they are rewarded in the labour market. This suggests that the types of jobs held by women in Catalonia probably do not specifically reward digital skills. Since UOC graduates are generally older and employed during their studies, the gains made by women may be more related to the fact that they obtained a degree that led to a promotion rather than any specific skills acquired in their studies.

Introduction: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. Methods: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. Results: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. Conclusions: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD. Resumen: Introducción: En la actualidad, las alteraciones del neurodesarrollo son la complicación más frecuente en pacientes con cardiopatía congénita (CC) en edad escolar. Analizamos la incidencia de eventos neurológicos agudos (ENA) en pacientes con CC sometidos a cirugía cardiaca y la utilidad de los neuromarcadores para predecir el neurodesarrollo. Métodos: Estudio prospectivo observacional en recién nacidos (RN) con CC diagnosticada prenatalmente sometidos a cirugía el primer año de vida. Se evaluaron: 1) biomarcadores sanguíneos de lesión cerebral (S100B, enolasa neuronal específica) en sangre de cordón y periquirúrgicos; 2) datos clínicos y analíticos perinatales y periquirúrgicos; 3) tratamientos y complicaciones; 4) neurodesarrollo (Escala Bayley III) a los dos años. Resultados: Se incluyeron 84 RN con CC de diagnóstico fetal, confirmada postnatalmente, sometidos a cirugía cardiaca en el primer año de vida. 17 pacientes tenían corazón univentricular, 20 pacientes obstrucción izquierda y 10 síndromes genéticos. Fallecieron en el periodo postquirúrgico 5 pacientes (5,9%) y 9 pacientes presentaron ENA (10,7%). Las puntuaciones medias en el test de Bayley III fueron normales pero el 31% tuvieron alteración cognitiva, motora o en el lenguaje. Los pacientes con síndromes genéticos, ENA y CC univentriculares tuvieron peor neurodesarrollo. La elevación de S100B en el postoperatorio inmediato se correlacionó con peores puntuaciones. Conclusiones: Los pacientes con CC sometidos a cirugía tienen mayor riesgo de sufrir alteraciones del neurodesarrollo. Los pacientes con síndromes genéticos o corazones univentriculares presentan peores resultados. Presentar ENA postquirúrgico puede contribuir a peores resultados. Niveles de s100B elevados en el postoperatorio se correlacionan con peores resultados en los tests de neurodesarrollo a los dos años. Series con más pacientes y con seguimiento a largo plazo nos ayudarán a definir el papel de estos biomarcadores de lesión cerebral en la predicción del neurodesarrollo en pacientes sometidos a cirugía de CC.

Abstract Background Rifaximin is a non-reabsorbable antibiotic which acts at gut level, and improves cognition and inflammatory parameters in minimal hepatic encephalopathy (MHE) patients, but not all patients show the same level of response. This study aims to assess brain activity, both within and between brain networks, following rifaximin treatment, considering the differences between response groups as well. Methods Twenty-two healthy controls and 53 patients with cirrhosis (22 without and 31 with MHE, diagnosed by Psychometric Hepatic Encephalopathy Score, PHES) performed psychometric, attention and coordination tests, and blood inflammatory parameters were measured. Resting-state functional magnetic resonance imaging (fMRI) acquisitions were performed on controls and MHE patients. Eighteen MHE patients underwent a rifaximin treatment for 6 months, after which all measures were repeated. fMRI images were analysed and changes after treatment were assessed. Results After rifaximin treatment, 13 patients improved their PHES score (Responder patients) while 5 did not (Non-responder patients). No significant decrease in blood ammonia was observed after rifaximin treatment, but there was a decrease in plasma inflammatory cytokines in responder patients. A global effect of rifaximin was detected on the sensorimotor and fronto-parietal networks. Responder patients showed a relative increase of thalamic network connectivity in comparison to non-responder patients. Before treatment, responder and non-responder patients showed connectivity differences in basal ganglia network. The connection of the sensorimotor and thalamic networks between them and with other networks suffered changes after treatment. These connections between networks mostly decreased after treatment. All changes and differences showed a significant level of correlation with the performance of psychometric tests and the blood levels of inflammatory biomarkers. Conclusions There was an improvement of the communication between executive, motor and attention-related brain areas, and their functional independence following rifaximin treatment. Patients who respond also show a less deteriorated connection involved in these functions before treatment. Results suggest that the improved inflammatory state of MHE patients, following rifaximin treatment would favour the observed changes in brain function and enhanced cognitive performance.

Abstract Background Antibody-based immunoassays have enabled quantification of very low concentrations of phosphorylated tau (p-tau) protein forms in cerebrospinal fluid (CSF), aiding in the diagnosis of AD. Mass spectrometry enables absolute quantification of multiple p-tau variants within a single run. The goal of this study was to compare the performance of mass spectrometry assessments of p-tau181, p-tau217 and p-tau231 with established immunoassay techniques. Methods We measured p-tau181, p-tau217 and p-tau231 concentrations in CSF from 173 participants from the TRIAD cohort and 394 participants from the BioFINDER-2 cohort using both mass spectrometry and immunoassay methods. All subjects were clinically evaluated by dementia specialists and had amyloid-PET and tau-PET assessments. Bland–Altman analyses evaluated the agreement between immunoassay and mass spectrometry p-tau181, p-tau217 and p-tau231. P-tau associations with amyloid-PET and tau-PET uptake were also compared. Receiver Operating Characteristic (ROC) analyses compared the performance of mass spectrometry and immunoassays p-tau concentrations to identify amyloid-PET positivity. Results Mass spectrometry and immunoassays of p-tau217 were highly comparable in terms of diagnostic performance, between-group effect sizes and associations with PET biomarkers. In contrast, p-tau181 and p-tau231 concentrations measured using antibody-free mass spectrometry had lower performance compared with immunoassays. Conclusions Our results suggest that while similar overall, immunoassay-based p-tau biomarkers are slightly superior to antibody-free mass spectrometry-based p-tau biomarkers. Future work is needed to determine whether the potential to evaluate multiple biomarkers within a single run offsets the slightly lower performance of antibody-free mass spectrometry-based p-tau quantification.

Abstractss The PHYAFB database is a valuable resource for studying the physiological demands of female amateur basketball players during high-stress official games. It contains heart rate data from ten players aged 18 to 26, collected during ten crucial relegation phase matches, with 348,232 HR samples in CSV and Excel formats for easy access and analysis. The database includes Python source code for initial examination. The primary aim of the PHYAFB database is to provide a useful reference for other teams facing similar situations. Furthermore, the database represents a unique and valuable resource for sports scientists, coaches, and trainers seeking to comprehend the physiological demands of female basketball players during official competitions. Through the analysis of heart rate data, coaches and trainers can identify the intensity and duration of physical activity during games, enabling the development of more effective training programs. Additionally, the database can be used to compare the physiological demands placed on male and female basketball players or to investigate the impact of different game strategies on player performance.

The main objective of this study was to analyze the impact of a multifaceted strategy to improve the assessment of functional capacity, risk of pressure injuries, and risk of falls at the time of admission of patients in adult hospitalization units. This was a secondary analysis of the VALENF project databases during two periods (October–December 2020, before the strategy, and October–December 2021, after the strategy). The quantity and quality of nursing assessments performed on patients admitted to adult hospitalization units were evaluated using the Barthel index, Braden index, and Downton scale. The number of assessments completed before the implementation of the new strategy was n = 686 (28.01%), versus n = 1445 (58.73%) in 2021 (p < 0.001). The strategy improved the completion of the evaluations of the three instruments from 63.4% (n = 435) to 71.8% (n = 1038) (p < 0.001). There were significant differences depending on the hospitalization unit and the assessment instrument (p < 0.05). The strategy employed was, therefore, successful. The nursing assessments show a substantial improvement in both quantity and quality, representing a noticeable improvement in nursing practice. This study was not registered.

Abstract Non‐coding RNAs (crRNAs) produced from clustered regularly interspaced short palindromic repeats (CRISPR) loci and CRISPR‐associated (Cas) proteins of the prokaryotic CRISPR‐Cas systems form complexes that interfere with the spread of transmissible genetic elements through Cas‐catalysed cleavage of foreign genetic material matching the guide crRNA sequences. The easily programmable targeting of nucleic acids enabled by these ribonucleoproteins has facilitated the implementation of CRISPR‐based molecular biology tools for in vivo and in vitro modification of DNA and RNA targets. Despite the diversity of DNA‐targeting Cas nucleases so far identified, native and engineered derivatives of the Streptococcus pyogenes SpCas9 are the most widely used for genome engineering, at least in part due to their catalytic robustness and the requirement of an exceptionally short motif (5′‐NGG‐3′ PAM) flanking the target sequence. However, the large size of the SpCas9 variants impairs the delivery of the tool to eukaryotic cells and smaller alternatives are desirable. Here, we identify in a metagenome a new CRISPR‐Cas9 system associated with a smaller Cas9 protein (EHCas9) that targets DNA sequences flanked by 5′‐NGG‐3′ PAMs. We develop a simplified EHCas9 tool that specifically cleaves DNA targets and is functional for genome editing applications in prokaryotes and eukaryotic cells.

Abstract Aims To develop and validate an instrument that integrates functional capacity, risk of pressure ulcers and risk of falling with a more parsimonious approach towards nursing assessments in hospitalization units. Design Cross‐sectional validation multicentre study. Methods Socio‐demographic variables and assessments of Barthel Index, Braden Index and Downton Scale are included via electronic health records. Instrument's development process will include: (i) conceptual assessments; (ii) content validity; (iii) construct validity; (iv) internal consistency and (v) interobserver reliability. The analysis will consider possible differences in medical and surgical hospitalization units, hospitalization type or being a COVID‐19 patient. This study was accepted for funding in November 2020 and approved by the Ethics and Research Committee in January 2021. Results An integrated instrument that lowers the administrative load of nursing assessments and allows at‐risk patients to be detected with at least the same validity and reliability as the original instruments is expected to be obtained.

The European Cooperation in Science and Technology (COST) is an intergovernmental organization dedicated to funding and coordinating scientific and technological research in Europe, fostering collaboration among researchers and institutions across countries. Recently, COST Action funded the ''Genome Editing to treat Human Diseases'' (GenE-HumDi) network, uniting various stakeholders such as pharmaceutical companies, academic institutions, regulatory agencies, biotech firms, and patient advocacy groups. GenE-HumDi’s primary objective is to expedite the application of genome editing for therapeutic purposes in treating human diseases. To achieve this goal, GenE-HumDi is organized in several working groups, each focusing on specific aspects. These groups aim to enhance genome editing technologies, assess delivery systems, address safety concerns, promote clinical translation, and develop regulatory guidelines. The network seeks to establish standard procedures and guidelines for these areas to standardize scientific practices and facilitate knowledge sharing. Furthermore, GenE-HumDi aims to communicate its findings to the public in accessible yet rigorous language, emphasizing genome editing’s potential to revolutionize the treatment of many human diseases. The inaugural GenE-HumDi meeting, held in Granada, Spain, in March 2023, featured presentations from experts in the field, discussing recent breakthroughs in delivery methods, safety measures, clinical translation, and regulatory aspects related to gene editing.