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Abstract The earliest archaeological evidence from northern Africa dates to ca. 2.44 Ma. Nevertheless, the palaeoenvironmental setting of hominins living in this part of the continent at the Plio-Pleistocene transition remains poorly documented, particularly in comparison to eastern and southern Africa. The Guefaït-4 fossil site in eastern Morocco sheds light on our knowledge of palaeoenvironments in northern Africa. Our study reveals the oldest known presence of C4 plants in the northern part of the continent in a mosaic landscape that includes open grasslands, forested areas, wetlands, and seasonal aridity. This diverse landscape and resource availability likely facilitated the occupation of the region by mammals, including potentially hominins. Our regional-scale study provides a complementary perspective to global-scale studies and highlights the importance of considering the diversity of microhabitats within a given region when studying species-dispersal dynamics.

Abstract Translating vascular aging research from bench to bedside presents both significant opportunities and challenges. This paper summarizes insights from a roundtable discussion at the Artery 23 conference, featuring perspectives from basic science, clinical trials, regulation, and industry. The main conclusions of the discussion are as follows: basic science research must align with clinical relevance, using appropriate animal models and standardized measurement techniques. Pragmatic and registry-based clinical trials offer viable alternatives to traditional randomized controlled trials, facilitating real-world applicability. The regulatory landscape, particularly for software medical devices, must evolve to keep pace with technological advancements like artificial intelligence. Industry efforts focus on developing devices or solutions for vascular aging assessment and treatment strategies, yet face hurdles in large-scale adoption and reimbursement. Despite significant progress, the development of pharmacological interventions to mitigate vascular aging remains a critical need. This discussion underscores the importance of interdisciplinary collaboration to overcome barriers and translate scientific discoveries into clinical practice effectively.

In situ and operando investigation of photocatalysts plays a fundamental role in understanding the processes of active phase formation and the mechanisms of catalytic reactions, which is crucial for the rational design of more efficient materials. Using a custom-made operando photocatalytic cell, an in situ procedure to follow the formation steps of Pd/TiO2 photocatalyst by synchrotron-based X-ray absorption spectroscopy (XAS) is proposed. The procedure resulted in the formation of ∼1 nm Pd particles with a much narrower size distribution and homogeneous spreading over TiO2 support compared with the samples generated in a conventional batch reactor. The combination of in situ XAS spectroscopy with high-angle annular dark-field scanning transmission electron microscopy demonstrated the formation of single-atom Pd(0) sites on TiO2 as the initial step of the photodeposition process. Palladium hydride particles were observed for all investigated samples upon exposure to formic acid solutions.

Abstract Background Juvenile idiopathic arthritis (JIA) refers to a heterogeneous group of rheumatic conditions in children. Novel drugs have greatly improved disease outcomes; however, outcomes are impacted by limited awareness of the importance of early diagnosis and adequate treatment, and by differences in access across health systems. As a result, patients with JIA continue to be at risk for short- and long-term morbidity, as well as impacts on virtually all aspects of life of the child and family. Main body Literature on the socioeconomic burden of JIA is largely focused on healthcare costs, and the impact of JIA on patients, families, and communities is not well understood. High quality evidence on the impact of JIA is needed to ensure that patients are receiving necessary support, timely diagnostics, and adequate treatment, and to inform decision making and resource allocation. This commentary introduces the European Joint Programme on Rare Diseases: Producing an Arthritis Value Framework with Economic Evidence: Paving the Way for Rare Childhood Diseases (PAVE) project, which will co-develop a patient-informed value framework to measure the impact of JIA on individuals and on society. With a patient-centered approach, fundamental to PAVE is the involvement of three patient advocacy organizations from Canada, Israel, and Europe, as active research partners co-designing all project phases and ensuring robust patient and family engagement. The framework will build on the findings of projects from six countries: Canada, Germany, Switzerland, Spain, Israel, and Belgium, exploring costs, outcomes (health, well-being), and unmet needs (uveitis, mental health, equity). Conclusion This unique international collaboration will combine evidence on costs (from family to societal), outcomes (clinical, patient and family outcomes), and unmet needs, to co-design and build a framework with patients and families to capture the full impact of JIA. The framework will support the development of high-quality evidence, encompassing economic and clinical considerations, unmet needs, and patient perspectives, to inform equitable resource allocation, health system planning, and quality of care better aligned with the needs of children with JIA, their families, and communities. Knowledge gained from this novel approach may pave the way forward to be applied more broadly to other rare childhood diseases.

Abstract Aims The objective of this study was to perform a cost–benefit analysis of the CardioMEMS HF System (Abbott Laboratories, Abbott Park, IL, USA) in a heart failure (HF) clinic in Spain by evaluating the real‐time remote monitoring of pulmonary artery pressures, which has been shown to reduce HF‐related hospitalizations and improve the quality of life for selected HF patients. Particularly, the study aimed to determine the value of CardioMEMS in Southern Europe, where healthcare costs are significantly lower and its effectiveness remains uncertain. Methods and results This single‐centre study enrolled all consecutive HF patients (N = 43) who had been implanted with a pulmonary artery pressure sensor (CardioMEMS HF System); 48.8% were females, aged 75.5 ± 7.0 years, with both reduced and preserved left ventricular ejection fraction; 67.4% of them were in New York Heart Association Class III. The number of HF hospitalizations in the year before and the year after the sensor implantation was compared. Quality‐adjusted life years gained based on a literature review of previous studies were calculated. The rate of HF hospitalizations was significantly lower at 1 year compared with the year before CardioMEMS implantation (0.25 vs. 1.10 events/patient‐year, hazard ratio 0.22, P = 0.001). At the end of the first year, the usual management outperformed the CardioMEMS HF System. By the end of the second year, the CardioMEMS system is estimated to reduce costs compared with usual management (net benefits of €346). Conclusions Based on the results, we suggest that remote monitoring of pulmonary artery pressure with the CardioMEMS HF System represents a midterm and long‐term efficient strategy in a healthcare setting in Southern Europe.

Abstract Background Juvenile Dermatomyositis (JDM) is the most common chronic idiopathic inflammatory myopathy in children. The diagnosis is clinical. Baseline laboratory and complementary studies trace the phenotype of these patients. The objective of this study was to describe epidemiological, clinical and laboratory characteristics at diagnosis of JDM patients included in the Spanish JDM registry, as well as to identify prognostic factors on these patients. Methods We retrospectively reviewed clinical features, laboratory tests, and complementary studies at diagnosis of JDM patients included on the Spanish JDM registry. These data were analyzed to assess whether there was a relationship with the development of complications and time to disease inactivity. Results One hundred and sixteen patients from 17 Spanish paediatric rheumatology centres were included, 76 girls (65%). Median age at diagnosis was 7.3 years (Interquartile range (IQR) 4.5–10.2). All patients had pathognomonic skin lesions at the beginning of the disease. Muscle weakness was present in 86.2%. Median Childhood Muscle Assessment Scale was 34 (IQR 22–47). Twelve patients (34%) had dysphagia and 3,5% dysphonia. Anti-p155 was the most frequently detected myositis specific antibody, followed by anti-MDA5. Twenty-nine patients developed calcinosis and 4 presented with macrophage activation syndrome. 70% reached inactivity in a median time of 8.9 months (IQR 4.5–34.8). 41% relapsed after a median time of 14.4 months (IQR 8.6–22.8) of inactivity. Shorter time to treatment was associated with better prognosis (Hazard ratio (HR) = 0.95 per month of evolution, p = 0.02). Heliotrope rash at diagnosis correlates with higher risk of development complications. Conclusions We describe heliotrope rash as a risk factor for developing complications in our cohort of JDM patients, an easy-to-evaluate clinical sign that could help us to identify the group of patients we should monitor closely for this complication.

La transformación social contemporánea exige una escuela innovadora para afrontar las nuevas demandas formativas. El objetivo principal de la investigación fue recoger la opinión de los especialistas en educación física, docentes de primaria y secundaria, en relación con una propuesta actualizada de ámbitos de intervención educativa y de los roles consecuentes a asumir. La muestra estuvo formada por 209 especialistas de educación física en un estudio descriptivo de diseño mixto. Se administró un cuestionario cuantitativo en escala de Likert para evaluar la propuesta de 5 ámbitos y de 5 roles. Las correlaciones de Pearson de las puntuaciones de ambas escalas en relación con las puntuaciones totales del cuestionario fueron positivas y fuertes (rcuestionario-ámbito = .884, p < .001 y rcuestionario-roles = .858, p < .001), y la fiabilidad total de los ítems fue buena (α = 0.756). Complementariamente, el 30.6 % de la muestra (64) cumplimentó voluntariamente un cuestionario cualitativo de opinión narrativa. En todos los ámbitos y roles, la nota máxima fue la elección con más frecuencia y destacan, respectivamente, la Actividad física y salud (77.99 %) y la Docencia (86.6 %). No se obtuvo significación estadística en relación con el género ni con los años de experiencia, pero los ámbitos fueron sensibles a las etapas educativas. En coherencia, las respuestas narrativas mostraban percepciones positivas sobre la propuesta de ámbitos y de roles. A pesar de la irrupción de nuevas responsabilidades contemporáneas en la disciplina, los especialistas siguen enfatizando una educación física que promueva la actividad física y la salud desde la responsabilidad docente.

Background: This study’s primary aim was to assess the safety and performance of second-generation all-soft suture anchors following arthroscopic labral tear repair. Methods: This prospective, multicenter study was conducted by 6 surgeons at 6 sites in Europe and the United States between November 2018 and August 2020. Patients who required shoulder arthroscopic repair, for a range of labral injuries, were treated with a second-generation all-soft suture anchor. The primary outcome was clinical success rate (percentage of patients without signs of failure and/or reintervention) at 6 months. Secondary outcomes included clinical success rate at 12 months, intraoperative anchor deployment success rate, and patient-reported outcomes (PROs) at 6 and 12 months, including visual analog scale (VAS) pain assessment, VAS satisfaction assessment, EQ-5D-5L Index Score, EQ-5D-5L VAS Health Score, Rowe Shoulder Score for Instability, American Shoulder and Elbow Surgeons score, and Constant-Murley Shoulder Score. Serious adverse events and serious adverse device effects were collected throughout the study. Results: Forty-one patients were enrolled (mean age, 28.2 years; 87.8% male, 12.2% female). Clinical success was achieved in 27/28 and 31/32 patients at 6 months and 12 months, respectively. Anchor deployment had a 100% success rate. Significant improvements over baseline were reported for all PROs except Constant-Murley Shoulder (6 months) and VAS Satisfaction Score (12 months). One patient experienced 1 serious adverse event and 1 patient experienced 1 serious adverse device effect. Conclusion: Second-generation all-soft suture anchors used in this study demonstrated a high clinical success rate, a favorable safety profile, and patients exhibited significant improvement in PROs.

Mevalonate kinase deficiency (MKD), a rare auto-inflammatory disorder, arises from mutations in the MVK gene, disrupting isoprenoid biosynthesis, and affecting cellular processes. This comprehensive review provides an updated perspective on MKD, including its aetiology, pathogenesis, diagnostic modalities, and therapeutic strategies. Based on recent research and clinical advances, our objective is to bridge the knowledge gaps in the 2015 SHARE guidelines. By describing molecular mechanisms, diagnostic dilemmas, and emerging therapies, this article should serve as a resource for clinicians and researchers, promoting a deeper understanding of MKD and guiding optimal patient care.

IntroductionAttention deficit hyperactivity disorder (ADHD) is a high-prevalent neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity, frequently co-occurring with other psychiatric and medical conditions. Current diagnosis is time-consuming and often delays effective treatment; to date, no valid biomarker has been identified to facilitate this process. Research has linked the core symptoms of ADHD to autonomic dysfunction resulting from impaired arousal modulation, which contributes to physiological abnormalities that may serve as useful biomarkers for the disorder. While recent research has explored alternative objective assessment tools, few have specifically focused on studying ADHD autonomic dysregulation through physiological parameters. This study aimed to design a multiparametric physiological model to support ADHD diagnosis.MethodsIn this observational study we non-invasively analyzed heart rate variability (HRV), electrodermal activity (EDA), respiration, and skin temperature parameters of 69 treatment-naïve ADHD children and 29 typically developing (TD) controls (7-12 years old). To identify the most relevant parameters to discriminate ADHD children from controls, we explored the physiological behavior at baseline and during a sustained attention task and applied a logistic regression procedure.ResultsADHD children showed increased HRV and lower EDA at baseline. The stress-inducing task elicits higher reactivity for EDA, pulse arrival time (PAT), and respiratory frequency in the ADHD group. The final classification model included 4 physiological parameters and was adjusted by gender and age. A good capacity to discriminate between ADHD children and TD controls was obtained, with an accuracy rate of 85.5% and an AUC of 0.95.DiscussionOur findings suggest that a multiparametric physiological model constitutes an accurate tool that can be easily employed to support ADHD diagnosis in clinical practice. The discrimination capacity of the model may be analyzed in larger samples to confirm the possibility of generalization.

Background & Aims: Transforming growth factor β (TGF-β) plays an oncogenic role in advanced cancer by promoting cell proliferation, metastasis and immunosuppression. PMEPA1 (prostate transmembrane protein androgen induced 1) has been shown to promote TGF-β oncogenic effects in other tumour types. Thus, we aimed to explore the role of PMEPA1 in hepatocellular carcinoma (HCC). Methods: We analysed 1,097 tumours from patients with HCC, including discovery (n = 228) and validation (n = 361) cohorts with genomic and clinicopathological data. PMEPA1 levels were assessed by qPCR (n = 228), gene expression data (n = 869) and at the single-cell level (n = 54). Genetically engineered mouse models overexpressing MYC+PMEPA1 compared to MYC were generated and molecular analyses were performed on the HCCs obtained. Results: PMEPA1 was overexpressed in 18% of HCC samples (fold-change >2; n = 201/1,097), a feature associated with TGF-β signalling activation (p

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

The objectives of this paper are to describe the Social Science and Humanities projects involving Spanish participation within the Seventh EU Framework Programme (FP7) (2007-2013), along with the scholarly output generated by these projects, and to compare the findings with the data from FP6 (2002-2006) in order to track their evolution. First, we determine the most significant characteristics of the projects with Spanish participation (duration, funding, topics, type of institution, etc.). Second, we analyse the scholarly production derived from a sample of projects taken from the Scopus database to analyse some bibliometric features. The results show an increase in the leadership and prominence of Spanish institutions, compared to FP6-SSH. In terms of scholarly outputs, none of the sources used (CORDIS, OpenAIRE and SCOPUS) allows a detailed study of scholarly production, although this output is characterized by articles written predominantly in English, published in first-quartile journals. Moreover, data showed that research funding for SSH may have long-term effects, with some outputs acknowledging funding being published a decade after the end of the project.

Objective The objective was to determine the prevalence of peripheral venous catheter (PVC) failure and its association with care complexity individual factors (CCIFs) in emergency department (ED) patients.Design A cross-sectional, descriptive-correlational study was performed.Methods All patients with a PVC inserted in the ED of a tertiary hospital were included. The period of study was from June 2021 to June 2022. The main outcomes were PVC failure (phlebitis, extravasation/infiltration, dysfunction/occlusion and dislodgement/involuntary withdrawal) and 26 CCIFs categorised into 5 domains (psycho-emotional, mental-cognitive, sociocultural, developmental and comorbidity/complications). Other secondary variables were also collected, such as level of triage or nursing care plan. All data were collected retrospectively from the electronic health records. A descriptive and inferential analysis was performed.Results A total of 35 968 patients with one or more PVC inserted during their ED visit were included in the study. The prevalence of PVC failure was 0.9% (n=316). The statistically significant CCIFs associated with PVC failure were: incontinence, haemodynamic instability, transmissible infection, vascular fragility, anxiety and fear, impaired adaptation, consciousness disorders, lack of caregiver support and agitation. In addition, we identified that patients with a higher number of CCIFs were more frequently experienced PVC failure.Conclusion This study identified a prevalence of PVC failure in the ED of around 1%. The most prevalent complication was dysfunction, followed by extravasation and dislodgement. In addition, PVC failure was associated with comorbidity/complications, psycho-emotional and mental-cognitive CCIFs domains.

Abstract Background Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA). Methods Data from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months. Results At baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25–5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48–9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03–8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02–5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57–5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23–5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46–9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76–7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07–3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10–4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15–8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders. Conclusion Lower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.

Abstract This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices.

Abstract Huntington’s disease (HD) is a neurological disorder caused by a CAG expansion in the Huntingtin gene (HTT). HD pathology mostly affects striatal medium-sized spiny neurons and results in an altered cortico-striatal function. Recent studies report that motor skill learning, and cortico-striatal stimulation attenuate the neuropathology in HD, resulting in an amelioration of some motor and cognitive functions. During physical training, extracellular vesicles (EVs) are released in many tissues, including the brain, as a potential means for inter-tissue communication. To investigate how motor skill learning, involving acute physical training, modulates EVs crosstalk between cells in the striatum, we trained wild-type (WT) and R6/1 mice, the latter with motor and cognitive deficits, on the accelerating rotarod test, and we isolated their striatal EVs. EVs from R6/1 mice presented alterations in the small exosome population when compared to WT. Proteomic analyses revealed that striatal R6/1 EVs recapitulated signaling and energy deficiencies present in HD. Motor skill learning in R6/1 mice restored the amount of EVs and their protein content in comparison to naïve R6/1 mice. Furthermore, motor skill learning modulated crucial pathways in metabolism and neurodegeneration. All these data provide new insights into the pathogenesis of HD and put striatal EVs in the spotlight to understand the signaling and metabolic alterations in neurodegenerative diseases. Moreover, our results suggest that motor learning is a crucial modulator of cell-to-cell communication in the striatum.

Abstract TDP-43 proteinopathies are a heterogeneous group of neurodegenerative disorders that share the presence of aberrant, misfolded and mislocalized deposits of the protein TDP-43, as in the case of amyotrophic lateral sclerosis and some, but not all, pathological variants of frontotemporal dementia. In recent years, many other diseases have been reported to have primary or secondary TDP-43 proteinopathy, such as Alzheimer’s disease, Huntington’s disease or the recently described limbic-predominant age-related TDP-43 encephalopathy, highlighting the need for new and accurate methods for the early detection of TDP-43 proteinopathy to help on the stratification of patients with overlapping clinical diagnosis. Currently, TDP-43 proteinopathy remains a post-mortem pathologic diagnosis. Although the main aim is to determine the pathologic TDP-43 proteinopathy in the central nervous system (CNS), the ubiquitous expression of TDP-43 in biofluids and cells outside the CNS facilitates the use of other accessible target tissues that might reflect the potential TDP-43 alterations in the brain. In this review, we describe the main developments in the early detection of TDP-43 proteinopathies, and their potential implications on diagnosis and future treatments.

Abstract Background Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. Methods Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. Results Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. Conclusions Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Abstract Alzheimer's disease (AD) shows a high pathological and symptomatological heterogeneity. To study this heterogeneity, we have developed a patient stratification technique based on one of the most significant risk factors for the development of AD: genetics. We addressed this challenge by including network biology concepts, mapping genetic variants data into a brain-specific protein–protein interaction (PPI) network, and obtaining individualized PPI scores that we then used as input for a clustering technique. We then phenotyped each obtained cluster regarding genetics, sociodemographics, biomarkers, fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, and neurocognitive assessments. We found three clusters defined mainly by genetic variants found in MAPT, APP, and APOE, considering known variants associated with AD and other neurodegenerative disease genetic architectures. Profiling of these clusters revealed minimal variation in AD symptoms and pathology, suggesting different biological mechanisms may activate the neurodegeneration and pathobiological patterns behind AD and result in similar clinical and pathological presentations, even a shared disease diagnosis. Lastly, our research highlighted MAPT, APP, and APOE as key genes where these genetic distinctions manifest, suggesting them as potential targets for personalized drug development strategies to address each AD subgroup individually.

Abstract Post-COVID condition (PCC) and multiple sclerosis (MS) share some clinical and demographic features, including cognitive symptoms and fatigue. Some pathophysiological mechanisms well-known in MS, such as autoimmunity, neuroinflammation and myelin damage, have also been implicated in PCC. In this study, we aimed to compare the cognitive phenotypes of two large cohorts of patients with PCC and MS, and to evaluate the relationship between fatigue and cognitive performance. Cross-sectional study including 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol and were categorized according to the International Classification of Cognitive Disorders system. Fatigue and depression were also assessed. Cognitive profiles of PCC and MS largely overlapped, with a greater impairment in episodic memory in MS, but with small effect sizes. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC. Still, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. There were no differences in the severity of depression among groups. Our study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS. Further comparative studies addressing the mechanisms related to cognitive dysfunction and fatigue may be of interest to advance the knowledge of these disorders and develop new therapies.

Abstract Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We have designed membrane permeant peptide inhibitors that specifically target the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Application of the peptide inhibitors leads to reduced TANGO1 and cTAGE5 protein levels and a corresponding inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish results in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduce secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, targeted interference of the TANGO1-cTAGE5 binding interface could enable therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.

Abstract Healthcare workers (HCWs) were at high risk of experiencing psychological distress during COVID-19 pandemic. The objective of this study was to evaluate the impact on HCWs’ mental health in a Spanish hospital. Cross-sectional study of HCW, active between May and June 2020. A web-based survey assessed probable current mental disorders (major depressive disorder [PHQ-8 ≥ 10], generalized anxiety disorder [GAD-7 ≥ 10], panic attacks, post-traumatic stress disorder [PTSD; PLC-5 ≥ 7], or substance use disorder [CAGE-AID ≥ 2]). The Sheehan Disability Scale (SDS) was used to assess severe impairment and items taken from the modified self‐report version of the Columbia Suicide Severity Rating Scale (C‐SSRS) assessed suicidal thoughts and behaviors. A total of 870 HCWs completed the survey. Most frequent probable mental disorders were major depressive disorder (33.6%), generalized anxiety disorder (25.5%), panic attacks (26.9%), PTSD (27.2%), and substance use disorder (5.0%). Being female, having aged 18–29 years, being an auxiliary nurse, direct exposure to COVID-19-infected patients, and pre-pandemic lifetime mental disorders were positively associated with mental issues. Hospital HCWs presented a high prevalence of symptoms of mental disorders, especially depression, PTSD, panic attacks, and anxiety. Younger individuals and those with lifetime mental disorders have been more vulnerable to experiencing them.

Resumen: Objetivo: Analizar la concordancia entre un hemoglobinómetro con muestra de sangre capilar y el laboratorio clínico con muestra de sangre venosa. Diseño: Estudio transversal de concordancia. Emplazamiento: Centro de Atención Primaria Bufalà-Canyet y Centro de Atención Primaria Dalt la Vila, Badalona, Barcelona. Participantes: Selección aleatoria de los participantes que acudían a analítica de rutina. Mayores de 18 años. Intervenciones y mediciones principales: Se recogieron el sexo, la edad y el motivo de la analítica de la historia clínica, se realizó extracción de sangre venosa y, de forma simultánea, la extracción de sangre capilar. Resultados: Se incluyen 120 individuos, con una media de edad de 58,9 años. El gráfico de Bland-Almant mostró diferencias dentro de los intervalos de confianza para hemoglobina y hematocrito. La media de las diferencias de los valores del hemoglobinómetro Verio Q Red respecto a los del laboratorio clínico, para la hemoglobina fue de −0,42 mg/dl, y para el hematocrito, de −1,25%. El coeficiente de correlación intraclase mostró concordancia excelente para hemoglobina y hematocrito entre el hemoglobinómetro Verio Q Red y el laboratorio clínico. La correlación de Pearson para hemoglobina fue 0,737, y para el hematocrito, 0,787. Conclusiones: El hemoglobinómetro Verio Q es una herramienta válida para el diagnóstico precoz de las anemias y puede ser de gran utilidad en las consultas de atención primaria. Abstract: Objective: To analyze the concordance between a hemoglobinometer with capillary blood sample and the clinical laboratory with a venous blood sample. Design: Cross-sectional concordance study. Location: Care Centre Primary Bufalà-Canyet Primary and Care Centre Primary Dalt la Vila Primary Care Center, Badalona, Barcelona. Participants: Random selection of participants who attended routine blood tests. Over 18 years old. No abandonment or loss was obtained. Main interventions and measurements: Sex, age, and reason for the blood test were collected from the medical history. Venous blood is drawn, and simultaneously, capillary blood is collected. Results: 120 individuals are included, with an average age of 58.9 years. The Bland-Almant graph showed differences within the confidence intervals for hemoglobin and hematocrit. The mean differences between the values of the Verio Q Red hemoglobinometer and those of the clinical laboratory were −0.42 mg/dl for hemoglobin and −1.25% for hematocrit. The intraclass correlation coefficient showed excellent correlation for hemoglobin and hematocrit between the Verio Q Red hemoglobinometer and the clinical laboratory. Pearson's correlation for hemoglobin was 0.737 and for hematocrit 0.787. Conclusions: The Verio Q hemoglobinometer is a valid tool for the early diagnosis of anemias and can be very useful in primary care consultations.

Abstract Introduction Despite the Rowland Universal Dementia Assessment Scale (RUDAS) having significant advantages as a cognitive screening tool, particularly for minority populations, the Mini‐Mental State Examination (MMSE) test is the most widely used test for cognitive screening in Alzheimer's disease (AD). This study aimed to develop a conversion table to predict MMSE scores from observed RUDAS scores, allowing an easy‐to‐use method to compare both screening tests. Methods The equipercentile equating method was used to develop the conversion table using a training sample consisting of cognitively intact participants and individuals with early‐stage AD. The resulting conversion table was validated in two samples, comprising participants from majority and minority populations assessed in Spanish. Results The conversion table demonstrated excellent reliability with intraclass correlation coefficients of.92 in both validation samples. Conclusion This study provides a conversion table between RUDAS and MMSE scores, improving the comparability of these cognitive screening tools for use in clinical and research purposes.

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.

Background:: The prediction of Alzheimer’s disease (AD) progression from its early stages is a research priority. In this context, the use of Artificial Intelligence (AI) in AD has experienced a notable surge in recent years. However, existing investigations predominantly concentrate on distinguishing clinical phenotypes through cross-sectional approaches. This study aims to investigate the potential of modeling additional dimensions of the disease, such as variations in brain metabolism assessed via [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET), and utilize this information to identify patients with mild cognitive impairment (MCI) who will progress to dementia (pMCI). Methods:: We analyzed data from 1,617 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who had undergone at least one FDG-PET scan. We identified the brain regions with the most significant hypometabolism in AD and used Deep Learning (DL) models to predict future changes in brain metabolism. The best-performing model was then adapted under a multi-task learning framework to identify pMCI individuals. Finally, this model underwent further analysis using eXplainable AI (XAI) techniques. Results:: Our results confirm a strong association between hypometabolism, disease progression, and cognitive decline. Furthermore, we demonstrated that integrating data on changes in brain metabolism during training enhanced the models’ ability to detect pMCI individuals (sensitivity=88.4%, specificity=86.9%). Lastly, the application of XAI techniques enabled us to delve into the brain regions with the most significant impact on model predictions, highlighting the importance of the hippocampus, cingulate cortex, and some subcortical structures. Conclusion:: This study introduces a novel dimension to predictive modeling in AD, emphasizing the importance of projecting variations in brain metabolism under a multi-task learning paradigm.

This study aimed to investigate the influence of stick grasping on the performance of elite youth rink hockey players in 10 m linear sprints and 180° change of direction (COD) tasks. Forty-nine rink hockey players (age = 18.40 ± 2.12 year; body mass = 73.52 ± 6.02 kg; height = 1.82 ± 0.07 m; BMI = 23.61 ± 1.69; sports experience = 6.42 ± 1.41 years; 4.89 ± 0.68 years’ post-peak height velocity) participated in this cross-sectional study. Measurements included 10 m sprint time and COD 180° performance with and without stick grasping. Results revealed non-significant differences when carrying a stick in the 10 m linear sprint (1.90 s ± 0.08 with stick vs. 1.89 s ± 0.08 without stick; p = 0.71; d = 0.05), neither did COD 180° for the left limb (2.75s ± 0.11 with stick vs. 2.76 s ± 0.11 without stick; p = 0.91; d = 0.02). However, for the right limb, significantly better performance in COD 180° was found when players held the stick (2.72 s ± 0.11 with stick vs. 2.75 s ± 0.09 without stick; p = 0.03; d = 0.32). These findings imply that the distinctive biomechanics and requirements of rink hockey, especially the lateral movements inherent in skating, might alleviate the negative impacts associated with implement grasping observed in other sports. This study highlights that stick grasping did not hinder COD ability and may even have a facilitating effect on certain movements, emphasizing the importance of considering sport-specific biomechanics in rink hockey performance analysis.

Abstract Background Self-harm presents a significant public health challenge. Emergency departments (EDs) are crucial healthcare settings in managing self-harm, but clinician uncertainty in risk assessment may contribute to ineffective care. Clinical Decision Support Systems (CDSSs) show promise in enhancing care processes, but their effective implementation in self-harm management remains unexplored. Methods PERMANENS comprises a combination of methodologies and study designs aimed at developing a CDSS prototype that assists clinicians in the personalized assessment and management of ED patients presenting with self-harm. Ensemble prediction models will be constructed by applying machine learning techniques on electronic registry data from four sites, i.e., Catalonia (Spain), Ireland, Norway, and Sweden. These models will predict key adverse outcomes including self-harm repetition, suicide, premature death, and lack of post-discharge care. Available registry data include routinely collected electronic health record data, mortality data, and administrative data, and will be harmonized using the OMOP Common Data Model, ensuring consistency in terminologies, vocabularies and coding schemes. A clinical knowledge base of effective suicide prevention interventions will be developed rooted in a systematic review of clinical practice guidelines, including quality assessment of guidelines using the AGREE II tool. The CDSS software prototype will include a backend that integrates the prediction models and the clinical knowledge base to enable accurate patient risk stratification and subsequent intervention allocation. The CDSS frontend will enable personalized risk assessment and will provide tailored treatment plans, following a tiered evidence-based approach. Implementation research will ensure the CDSS’ practical functionality and feasibility, and will include periodic meetings with user-advisory groups, mixed-methods research to identify currently unmet needs in self-harm risk assessment, and small-scale usability testing of the CDSS prototype software. Discussion Through the development of the proposed CDSS software prototype, PERMANENS aims to standardize care, enhance clinician confidence, improve patient satisfaction, and increase treatment compliance. The routine integration of CDSS for self-harm risk assessment within healthcare systems holds significant potential in effectively reducing suicide mortality rates by facilitating personalized and timely delivery of effective interventions on a large scale for individuals at risk of suicide.

Abstract The electrical characterisation of classical and quantum devices is a critical step in the development cycle of heterogeneous material stacks for semiconductor spin qubits. In the case of silicon, properties such as disorder and energy separation of conduction band valleys are commonly investigated individually upon modifications in selected parameters of the material stack. However, this reductionist approach fails to consider the interdependence between different structural and electronic properties at the danger of optimising one metric at the expense of the others. Here, we achieve a significant improvement in both disorder and valley splitting by taking a co-design approach to the material stack. We demonstrate isotopically purified, strained quantum wells with high mobility of 3.14(8) × 105 cm2 V−1 s−1 and low percolation density of 6.9(1) × 1010 cm−2. These low disorder quantum wells support quantum dots with low charge noise of 0.9(3) μeV Hz−1/2 and large mean valley splitting energy of 0.24(7) meV, measured in qubit devices. By striking the delicate balance between disorder, charge noise, and valley splitting, these findings provide a benchmark for silicon as a host semiconductor for quantum dot qubits. We foresee the application of these heterostructures in larger, high-performance quantum processors.

Abstract Background Mental health service providers are increasingly interested in patient perspectives. We examined rates and predictors of patient-reported satisfaction and perceived helpfulness in a cross-national general population survey of adults with 12-month DSM-IV disorders who saw a provider for help with their mental health. Methods Data were obtained from epidemiological surveys in the World Mental Health Survey Initiative. Respondents were asked about satisfaction with treatments received from up to 11 different types of providers (very satisfied, satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied) and helpfulness of the provider (a lot, some, a little, not at all). We modelled predictors of satisfaction and helpfulness using a dataset of patient-provider observations (n = 5,248). Results Most treatment was provided by general medical providers (37.4%), psychiatrists (18.4%) and psychologists (12.7%). Most patients were satisfied or very satisfied (65.9-87.5%, across provider) and helped a lot or some (64.4-90.3%). Spiritual advisors and healers were most often rated satisfactory and helpful. Social workers in human services settings were rated lowest on both dimensions. Patients also reported comparatively low satisfaction with general medical doctors and psychiatrists/psychologists and found general medical doctors less helpful than other providers. Men and students reported lower levels of satisfaction than women and nonstudents. Respondents with high education reported higher satisfaction and helpfulness than those with lower education. Type of mental disorder was unrelated to satisfaction but in some cases (depression, bipolar spectrum disorder, social phobia) was associated with low perceived helpfulness. Insurance was unrelated to either satisfaction or perceived helpfulness but in some cases was associated with elevated perceived helpfulness for a given level of satisfaction. Conclusions Satisfaction with and perceived helpfulness of treatment varied as a function of type of provider, service setting, mental status, and socio-demographic variables. Invariably, caution is needed in combining data from multiple countries where there are cultural and service delivery variations. Even so, our findings underscore the utility of patient perspectives in treatment evaluation and may also be relevant in efforts to match patients to treatments.

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by significant metabolic disruptions, including weight loss and hypermetabolism in both patients and animal models. Leptin, an adipose-derived hormone, displays altered levels in ALS. Genetically reducing leptin levels (Lepob/+) to maintain body weight improved motor performance and extended survival in female SOD1G93A mice, although the exact molecular mechanisms behind these effects remain elusive. Here, we corroborated the sexual dimorphism in circulating leptin levels in ALS patients and in SOD1G93A mice. We reproduced a previous strategy to generate a genetically deficient leptin SOD1G93A mice (SOD1G93ALepob/+) and studied the transcriptomic profile in the subcutaneous adipose tissue and the spinal cord. We found that leptin deficiency reduced the inflammation pathways activated by the SOD1G93A mutation in the adipose tissue, but not in the spinal cord. These findings emphasize the importance of considering sex-specific approaches in metabolic therapies and highlight the role of leptin in the systemic modulation of ALS by regulating immune responses outside the central nervous system.

Abstract The exploration of metal–insulator transitions to produce field-induced reversible resistive switching effects has been a longstanding pursuit in materials science. Although the resistive switching effect in strongly correlated oxides is often associated with the creation or annihilation of oxygen vacancies, the underlying mechanisms behind this phenomenon are complex and, in many cases, still not clear. This study focuses on the analysis of the superconducting performance of cuprate YBa2Cu3O7−δ (YBCO) devices switched to different resistive states through gate voltage pulses. The goal is to evaluate the effect of field-induced oxygen diffusion on the magnetic field and angular dependence of the critical current density and identify the role of induced defects in the switching performance. Transition electron microscopy measurements indicate that field-induced transition to high resistance states occurs through the generation of YBa2Cu4O7 (Y124) intergrowths with a large amount of oxygen vacancies, in agreement with the obtained critical current density dependences. These results have significant implications for better understanding the mechanisms of field-induced oxygen doping in cuprate superconductors and their role on the superconducting performance.

The present study examined the relationship between upper limb muscle power and shooting velocity in elite male youth rink hockey players. Seventeen participants (age: 18.2 ± 1.44 years) underwent assessments of upper limb power and shooting velocity. Upper limb power was evaluated through bench press exercises, including indirect 1RM, mean power, and peak power. Shooting velocity was measured using a shooting test, including static drive shot, static slap shot, dynamic drive shot, and dynamic slap shot techniques. Results showed significant positive correlations between upper limb power and shooting velocity in static slap shot (r = 0.62, p = 0.04) and dynamic slap shot (r = 0.86; p < 0.01). Dynamic slap shot also correlated significantly with peak power (r = 0.63; p = 0.03). Differences in shooting velocity were observed among the techniques (F(3,64) = 23.7; p < 0.01, ηp2 = 0.56), with dynamic slap shot displaying the highest velocity and static drive shot the lowest. These findings highlight the positive association between upper limb muscle power and shooting velocity in elite youth rink hockey players. Developing upper limb power can enhance shooting performance. The choice of shooting technique significantly affects shooting velocity, underscoring the importance of optimizing technique for maximizing performance. These findings provide practical insights for coaches and practitioners, informing the design of targeted training programmes aimed at improving shooting velocity in rink hockey players.

Summary: Developing active and stable catalysts for carbon-free hydrogen production is crucial to mitigate the effects of climate change. Ammonia is a promising carbon-free hydrogen source, as it has a high hydrogen content and is liquid at low pressure, which allows its easy storage and transportation. We have recently developed a nickel-based catalyst with a small content of ruthenium supported on cerium oxide, which exhibits high activity and stability in ammonia decomposition. Here, we investigate mechanochemical milling for its synthesis, a faster and less energy-consuming technique than conventional ones. Results indicate that mechanochemical synthesis increases catalytic activity compared to the conventional incipient wetness impregnation method. The interaction between the metal precursors and the support is key in fine-tuning catalytic activity, which increases linearly with oxygen vacancies in the support. Moreover, the mechanochemical method modifies the oxidation state of Ni and Ru species, with a variation depending on the precursors.

IntroductionTimely and accurate diagnosis of the earliest manifestations of Alzheimer’s disease (AD) is critically important. Cognitive challenge tests such as the Loewenstein Acevedo Scales for Semantic Interference and Learning (LASSI-L) have shown favorable diagnostic properties in a number of previous investigations using amyloid or FDG PET. However, no studies have examined LASSI-L performance against cerebrospinal fluid biomarkers of AD, which can be affected before the distribution of fibrillar amyloid and other changes that can be observed in brain neuroimaging. Therefore, we aimed to evaluate the relationship between LASSI-L scores and CSF biomarkers and the capacity of the cognitive challenge test to detect the presence of amyloid and tau deposition in patients with subjective cognitive decline and amnestic mild cognitive impairment (MCI).MethodsOne hundred and seventy-nine patients consulting for memory loss without functional impairment were enrolled. Patients were examined using comprehensive neuropsychological assessment, the LASSI-L, and cerebrospinal fluid (CSF) biomarkers (Aβ1-42/Aβ1-40 and ptau181). Means comparisons, correlations, effect sizes, and ROC curves were calculated.ResultsLASSI-L scores were significantly associated with CSF biomarkers Aβ1-42/Aβ1-40 in patients diagnosed with MCI and subjective cognitive decline, especially those scores evaluating the capacity to recover from proactive semantic interference effects and delayed recall. A logistic regression model for the entire sample including LASSI-L and age showed an accuracy of 0.749 and an area under the curve of 0.785 to detect abnormal amyloid deposition.ConclusionOur study supports the biological validity of the LASSI-L and its semantic interference paradigm in the context of the early stages of AD. These findings emphasize the utility and the convenience of including sensitive cognitive challenge tests in the assessment of patients with suspicion of early stages of AD.

In Structural Silicone Glazing (SSG) when applied to unitised curtain wall systems typical practice incorporates a pair of dead load plates intended to carry the glass self-weight and so avoid subjecting structural silicone to permanent shear. However in reality, due to the fabrication sequence and system behaviour some loads can occur which will be resisted permanently by the structural silicone. In a hung and sworded system (H&S), designers typically assume that slab deflection, or inter-story drift will cause a unitised panel to lift off from one support and so change the load path within it. To conform with this new load path, shear deformation will occur in the SSG joints. The deformation in the SSG joint will be permanent unless the supporting main structure returns to its original position. The structural performance of SSG joints subjected to permanent shear deformation in combination with short term loads is not adequately covered by any guidance. The aim of this paper is to provide a better understanding of the effect of the permanent shear deformation on SSG joints. Experimental tensile and shear testing has been carried out by Sika on H-specimens (Sikasil® SG-500) while imposing prescribed levels of shear deformation in combination with different accelerated aging conditions. The testing procedure, results and main conclusions are explained and summarised.

Arterial compliance (AC) plays a crucial role in vascular aging and cardiovascular disease. The ability to continuously estimate aortic AC or its surrogate, pulse pressure (PP), through wearable devices is highly desirable, given its strong association with daily activities. While the single-site photoplethysmography (PPG)-derived arterial stiffness indices show reasonable correlations with AC, they are susceptible to noise interference, limiting their practical use. To overcome this challenge, our study introduces a noise-resistant indicator of AC: Katz’s fractal dimension (KFD) of PPG signals. We showed that KFD integrated the signal complexity arising from compliance changes across a cardiac cycle and vascular structural complexity, thereby decreasing its dependence on individual characteristic points. To assess its capability in measuring AC, we conducted a comprehensive evaluation using both in silico studies with 4374 virtual human data and real-world measurements. In the virtual human studies, KFD demonstrated a strong correlation with AC (r = 0.75), which only experienced a slight decrease to 0.66 at a signal-to-noise ratio of 15dB, surpassing the best PPG-morphology-derived AC measure (r = 0.41) under the same noise condition. In addition, we observed that KFD’s sensitivity to AC varied based on the individual’s hemodynamic status, which may further enhance the accuracy of AC estimations. These in silico findings were supported by real-world measurements encompassing diverse health conditions. In conclusion, our study suggests that PPG-derived KFD has the potential to continuously and reliably monitor arterial compliance, enabling unobtrusive and wearable assessment of cardiovascular health.

VPS13A disease and Huntington’s disease (HD) are two basal ganglia disorders that may be difficult to distinguish clinically because they have similar symptoms, neuropathological features, and cellular dysfunctions with selective degeneration of the medium spiny neurons of the striatum. However, their etiology is different. VPS13A disease is caused by a mutation in the VPS13A gene leading to a lack of protein in the cells, while HD is due to an expansion of CAG repeat in the huntingtin (Htt) gene, leading to aberrant accumulation of mutant Htt. Considering the similarities of both diseases regarding the selective degeneration of striatal medium spiny neurons, the involvement of VPS13A in the molecular mechanisms of HD pathophysiology cannot be discarded. We analyzed the VPS13A distribution in the striatum, cortex, hippocampus, and cerebellum of a transgenic mouse model of HD. We also quantified the VPS13A levels in the human cortex and putamen nucleus; and compared data on mutant Htt-induced changes in VPS13A expression from differential expression datasets. We found that VPS13A brain distribution or expression was unaltered in most situations with a decrease in the putamen of HD patients and small mRNA changes in the striatum and cerebellum of HD mice. We concluded that the selective susceptibility of the striatum in VPS13A disease and HD may be a consequence of disturbances in different cellular processes with convergent molecular mechanisms already to be elucidated.

The control of tritium (3H) in liquid-based tritium breeding blankets (TBBs) is one of the key points to assure their correct performance to prove the 3H sufficiency. For that, electrochemical sensors are a good option for tritium quantification since they can perform in-situ and online measurements.One of the multiple challenges for hydrogen detection is to find suitable materials that can operate at high temperatures and in harsh environments. In this context, perovskite-type ceramics, such as BaCe0.6Zr0.3Y0.1O3-α (BCZY), have elevated proton conductivity and exceptional stability even in reducing atmospheres and at elevated temperatures, which make them strong contenders for high-temperature hydrogen sensing applications.In the present study, we describe the development of a dual-mode hydrogen sensors based on 3D-printed BCZY, which allows a high degree of design flexibility. Crucible geometries were tested and characterized using X-ray diffraction and scanning electron microscopy. Electrochemical sensors were constructed and characterized at 400, 450 and 500 °C in both, amperometric and potentiometric configuration. The results demonstrated the capability of 3D-printed BCZY sensors for hydrogen detection in fusion reactors, offering a breakthrough solution for monitoring fusion processes.

Resumen: La teleconsulta es una consulta sanitaria a distancia que se realiza mediante tecnologías de la información y la comunicación (TIC). Existen diferentes modalidades que requieren de habilidades técnicas y comunicativas específicas. Aunque en España la teleconsulta ocupa una posición destacada, la evidencia a su alrededor es limitada.El artículo aborda la aplicabilidad, barreras, facilitadores y retos futuros de la teleconsulta. Aunque tiene el potencial de mejorar el acceso a la atención sanitaria, así como de ahorrar tiempo y costes tanto para los pacientes como para los profesionales sanitarios, debe enfrentar una serie de desafíos como la brecha digital y la resistencia al cambio. Para superar estos obstáculos y abordar nuevos retos es crucial la confianza de pacientes y profesionales, así como mejorar la formación en las competencias necesarias para optimizar su uso.La investigación futura debe centrarse en proporcionar evidencias sólidas en términos de seguridad y coste-efectividad para asegurar su implementación. Abstract: Teleconsultation is a remote health consultation using information and communication technologies. There are different modalities and specific practical and communication skills are required. Notwithstanding its prominence in Spain, there is little evidence on teleconsultation.This article explores the applicability, barriers, facilitators and future challenges of teleconsultation. While it has the potential to improve access to healthcare, as well as save time and costs for both patients and healthcare professionals, it faces a number of challenges such as the digital divide and resistance to change.To address new challenges and overcome obstacles, it is crucial to gain the trust of patients and professionals. Improving training in the skills required to optimize their use is also essential.Future research should aim to provide robust evidence regarding safety and cost-effectiveness to ensure successful implementation.

Resumen: La transformación digital es una realidad. Afecta a los procesos de las organizaciones y también desarrolla servicios para los usuarios. Esta innovación debe seguir las directrices de la Organización Mundial de la Salud (OMS) para todas las personas, en todas las partes del mundo. Tener en cuenta los determinantes sociales de salud (DSS) y considerar los nuevos determinantes digitales en salud (DDS) es básico. También lo es disponer de una legislación adecuada y dotar a las infraestructuras necesarias. La tecnología permite un mejor autocuidado y participación en la toma de decisiones. Por ello, es necesario disminuir la brecha digital y la mejor forma de hacerlo consiste en contar con los ciudadanos, las comunidades, las entidades y los profesionales en el diseño de soluciones. Las campañas nacionales y supranacionales deben desarrollar planes y estrategias comunes. Esto conlleva unas necesidades de formación y creación de programas para profesionales y usuarios, que deberían contemplar sus necesidades y remarcar la importancia de incorporar conocimientos digitales. Abstract: In the last years, the digital transformation, has become a reality influencing organizational processes and advancing services for users. This transformation must align with WHO guidelines, addressing the needs of individuals globally and acknowledging Social Determinants of Health and emerging Digital Determinants of Health and the digital divide thas has been created. To accomplish this, the appropriate legislation and infrastructures are required. Correspondingly technology enables enhanced self-care and increased participation in decision-making across various levels, consequently, addressing the digital divide must not be an exception, and needs to include citizens, communities, entities, and professionals to work on how to diminish it and solve it. As a result of this national and supranational campaigns should formulate unified plans and strategies, that include training requirements and establishing programs for both professionals and users, highlighting the significance of incorporating digital knowledge on both groups.

Pyk2 has been shown previously to be involved in several psychological and cognitive alterations related to stress, Huntington's disease, and Alzheimer's disease. All these disorders are accompanied by different types of impairments in sociability, which has recently been linked to improper mitochondrial function. We hypothesize that Pyk2, which regulates mitochondria, could be associated with the regulation of mitochondrial dynamics and social skills. In the present manuscript, we report that a reduction of Pyk2 levels in mouse pyramidal neurons of the hippocampus decreased social dominance and aggressivity. Furthermore, social interactions induced robust Pyk2-dependent hippocampal changes in several oxidative phosphorylation complexes. We also observed that Pyk2 levels were increased in the CA1 pyramidal neurons of schizophrenic subjects, occurring alongside changes in different direct and indirect regulators of mitochondrial function including DISC1 and Grp75. Accordingly, overexpressing Pyk2 in hippocampal CA1 pyramidal cells mimicked some specific schizophrenia-like social behaviors in mice. In summary, our results indicate that Pyk2 might play a role in regulating specific social skills likely via mitochondrial dynamics and that there might be a link between Pyk2 levels in hippocampal neurons and social disturbances in schizophrenia.

The Fontan circulation, designed for managing patients with a single functional ventricle, presents challenges in long-term outcomes. Computational methods offer potential solutions, yet their application in cardiology practice remains largely unexplored. Our aim was to assess the ability of a patient-specific, closed-loop, reduced-order blood flow model to simulate pulsatile blood flow in the Fontan circulation. Using one-dimensional models, we simulated the aorta, superior and inferior venae cavae, and right and left pulmonary arteries, while lumping heart chambers and remaining vessels into zero-dimensional models. The model was calibrated with patient-specific haemodynamic data from combined cardiac catheterisation and magnetic resonance exams, using a novel physics-based stepwise methodology involving simpler open-loop models. Testing on a 10-year-old, anesthetised patient, demonstrated the model's capability to replicate pulsatile pressure and flow in the larger vessels and ventricular pressure. Average relative errors in mean pressure and flow were 2.9 % and 3.6 %, with average relative point-to-point errors (RPPE) in pressure and flow at 5.2 % and 16.0 %. Comparing simulation results to measurements, mean aortic pressure and flow values were 50.7 vs. 50.4 mmHg and 41.6 vs. 41.9 ml/s, respectively, while ventricular pressure values were 28.7 vs. 27.4 mmHg. The model accurately described time-varying ventricular volume with a RPPE of 2.9 %, with mean, minimum, and maximum ventricular volume values for simulation results vs. measurements at 59.2 vs. 58.2 ml, 38.0 vs. 37.6 ml, and 76.0 vs. 74.4 ml, respectively. It provided physiologically realistic predictions of haemodynamic changes from pulmonary vasodilation and atrial fenestration opening. The new model and calibration methodology are freely available, offering a platform to virtually investigate the Fontan circulation's response to clinical interventions and explore potential mechanisms of Fontan failure. Future efforts will concentrate on broadening the model's applicability to a wider range of patient populations and clinical scenarios, as well as testing its effectiveness.

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

Abstract Bottom-up grown nanomaterials play an integral role in the development of quantum technologies but are often challenging to characterise on large scales. Here, we harness selective area growth of semiconductor nanowires to demonstrate large-scale integrated circuits and characterisation of large numbers of quantum devices. The circuit consisted of 512 quantum devices embedded within multiplexer/demultiplexer pairs, incorporating thousands of interconnected selective area growth nanowires operating under deep cryogenic conditions. Multiplexers enable a range of new strategies in quantum device research and scaling by increasing the device count while limiting the number of connections between room-temperature control electronics and the cryogenic samples. As an example of this potential we perform a statistical characterization of large arrays of identical quantum dots thus establishing the feasibility of applying cross-bar gating strategies for efficient scaling of future selective area growth quantum circuits. More broadly, the ability to systematically characterise large numbers of devices provides new levels of statistical certainty to materials/device development.

Background: In 2021, the Spanish Ministry of Health launched the CIBERPOSTCOVID project to establish what post COVID was. The present study reports the level of agreement among stakeholders on post COVID and its clinical and diagnostic characteristics in the Spanish health system. Methods: The agreement on post COVID among clinicians, public health managers, researchers and patients’ representatives was explored in a real-time, asynchronous online Delphi. In a two-wave consensus, respondents rated from 1 (total disagreement) to 6 (total agreement) 67 statements related to terminology, duration, etiology, symptoms, impact on quality of life, severity, elements to facilitate diagnosis, applicability in the pediatric population, and risk factors. Consensus was reached when 70 % of ratings for a statement were 5 or 6, with an interquartile range equal or less than 1. Findings: A total of 333 professionals and patients participated in this eDelphi study. There was agreement that post COVID was “a set of multi-organic symptoms that persist or fluctuate after acute COVID-19 infection and are not attributable to other causes” with a minimum duration of 3 months. The highest levels of agreement were found in the most frequent symptoms and its impacts on everyday activities. Aspects related to the diagnostic process and the measurement of its severity reached a lower level of consensus. There was agreement on the need to rule out previous health problems and assess severity using validated functional scales. However, no agreement was reached on the risk factors or specific features in the pediatric population. Interpretation: This policy-based consensus study has allowed the characterization of post COVID generating collective intelligence and has contributed to an operational definition applicable in clinical practice, health services management and useful for research purposes in Spain and abroad. Agreements are consistent with existing evidence and reference institutions at European and international level.

This study aimed to report the shooting velocities and to assess the differences in shot velocity according to the techniques used in elite youth male rink hockey players. Fifteen rink hockey players (age = 18.40 ± 1.44 year; body mass = 73.52 ± 6.02 kg; height = 1.76 ± 0.06 m; BMI = 23.61 ± 2.12; sports experience = 6.44 ± 1.76 years) participated in this cross-sectional study. Shooting velocities were assessed for four techniques: slap shot without approach run, drive shot without approach run, slap shot with approach run, and drive shot with approach run. Shooting velocity measurements were conducted using a radar Stalker ATS systemTM. The results demonstrated that drive shots consistently achieved higher velocities compared to slap shots (F(3,56) = 23.9 p < 0.01, ηp2 = 0.58). Additionally, incorporating an approach run significantly increased shooting velocities for both techniques (p < 0.01). These findings hold significant implications for coaches and players seeking to optimize shooting performance in rink hockey.

Appendiceal tumors represent a large amalgam of different tumor lineages. The continuous evolution in their pathological classifications has led to some variable recommended attitudes over time. The aim of this study is to review the incidence, clinicopathological characteristics, therapeutic approach and oncological results in this type of tumor at our institution. This is a single-centre retrospective cohort study. Every pathologic report catalogued as an appendiceal specimen was reviewed for a time period of 5 years (2013–2017) at our institution. Demographic, clinical, pathological and oncologic follow-up data were recorded. A descriptive study of the sample was completed. A total of 1434 appendiceal specimens was analyzed. Appendiceal neoplasms incidence was 3.2%. Epithelial tumors were the predominant histological subtype, making up 68% of the cases. Low-grade appendiceal mucinous neoplasia and neuroendocrine tumors were the most frequent neoplasms with malignant potential, with 13 and 6 cases, respectively. In more than 80% of neoplasia cases, the definitive treatment was appendectomy. Mortality cases were related to tumors with a very poor prognosis and an advanced stage. All patients had adequate oncological follow-up. Although it is still quite rare, the incidence of appendiceal tumors is increasing with an epidemiological change in favor of mucinous neoplasms currently predominating. Therefore, it is necessary to know and use an updated anatomo-pathological classification in order to provide correct treatment in the first or second surgical stage, as well as the correct follow-up of patients.

Abstract Diversity-generating and mobile genetic elements are key to microbial and viral evolution and can result in evolutionary leaps. State-of-the-art algorithms to detect these elements have limitations. Here, we introduce DIVE, a new reference-free approach to overcome these limitations using information contained in sequencing reads alone. We show that DIVE has improved detection power compared to existing reference-based methods using simulations and real data. We use DIVE to rediscover and characterize the activity of known and novel elements and generate new biological hypotheses about the mobilome. Building on DIVE, we develop a reference-free framework capable of de novo discovery of mobile genetic elements.