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    A Pilot Randomized Controlled Trial Testing the Feasibility and Acceptability of Helping Ease Anxiety and Depression after Stroke (HEADS: UP):an Online Mindfulness-Based Intervention for Stroke Survivors

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    Objectives: To assess feasibility and acceptability of a stroke-specific mindfulness-based intervention called Helping Ease Anxiety and Depression after Stroke (HEADS: UP). Method: Mixed-methods pilot RCT (randomized controlled trial) comparing HEADS: UP to treatment as usual (TAU). HEADS: UP is a 9-week mindfulness intervention for stroke survivors. UK (United Kingdon)-based stroke survivors were recruited and attended HEADS: UP Online. Psychological functioning outcomes measures and other data were collected online at pre-intervention (week 0), post-intervention (week 9), and follow-up (months 3 and 6). Participants were randomized 1:1 to either HEADS: UP or TAU. Results: Sixty-two participants completed baseline questionnaires and were randomized to HEADS: UP (n = 30) or TAU (n = 32). Retention rates were as follows: HEADS: UP (n = 25, 83.30%) versus TAU (n = 25, 78.10%) at post-intervention, HEADS: UP (n = 24, 80%) versus TAU (n = 26, 81.30%) at 3-month follow-up, and HEADS: UP (n = 20, 66.70%) versus TAU (n = 25, 78.10%) at 6-month follow-up. The mean age for HEADS: UP was 56.0 years versus 56.80 for TAU. The HEADS: UP group was 30% male, while the TAU group was 56% male. Depression Anxiety Stress Scales (DASS)-21 total mean score for HEADS: UP improved in the direction of expected effect (baseline 46.20, SD (standard deviation) = 24.00; post-intervention 24.00, SD = 16.10) indicating ‘recovery’ versus ‘no reliable change’ for TAU (baseline 36.10, SD = 18.70; post-intervention 31.60, SD = 20.40). HEADS: UP and TAU scores continued to improve over time. Between-group effect sizes (Cohen’s d) at post-intervention were large for BAI (Beck Anxiety Inventory) (d = 0.91), DASS-21 total (d = 0.89), and BDI (Beck Depression Inventory)-II (d = 0.86), highlighting the potential of HEADS: UP for improving depression and anxiety symptoms. At the six-month follow-up, the attrition rate was higher in the HEADS: UP group (33.30%) compared with TAU (21.90%).Conclusions: HEADS: UP is feasible and acceptable and has potential to improve depression and anxiety symptoms for stroke survivors.Preregistration: Preregistered with ClinicalTrials.gov: NCT04985838Keywords: stroke, anxiety, depression, online MBSR (Mindfulness Based Stress Reduction), pilot RCT<br/

    Healthy linguistic diet:A framework for people, planet and social justice

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    Healthy Linguistic Diet (HLD) model emerged from interdisciplinary collaboration and has evolved into a comprehensive framework for understanding the cognitive benefits of multilingualism. Rooted in the metaphor of language learning as essential nourishment for cognitive functioning and well-being, HLD has been widely recognised in European educational policy and international initiatives. Over time, the model has expanded beyond its initial cognitive and educational focus to incorporate the interaction between plurilingual individuals and multilingual environments. It addresses key global challenges through its core categories, such as environment and sustainability (including linguistic habitats, rootedness and intercultural competence) and inclusion and social justice (including epistemic habitats, belonging and academic plurilingualism). This paper traces the development of HLD, presents its more comprehensive, expanded model and examines its theoretical foundations and real-world applications in education, policy, healthy aging and community engagement. In the context of living in a world where 90 percent of languages are considered endangered, HLD model offers a framework of resilience for individuals and communities, ensuring that linguistic diversity is not only preserved, but actively nurtured for the benefit of individuals and societies

    A mathematical model of corneal endothelium pump function

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    The corneal endothelium plays a critical role in maintaining the transparency of the cornea by regulating water transport through the ‘pump and leak’ mechanism. This study presents a mathematical model to analyse fluid and ion pumping across the endothelium, accounting for two proposed mechanisms of the endothelial pump: local osmosis and electro-osmosis. The model incorporates four key ions (Na +, K +, Cl − and HCO⁣−3) and considers transcellular and paracellular transport pathways. The model predicts a water flux from the stroma to the anterior chamber as observed in experiments with isolated endothelium. Electro-osmosis is found to contribute minimally to water transport compared with local osmosis, which is the dominant mechanism. The magnitude of water flux depends on the cell membrane and tight junction permeability to water. Global sensitivity analysis reveals that water flux is also highly influenced by the tight junction permeability to different ion species, and to a smaller extent, to the permeability of cell membrane to some ions, with the specific effect depending on the ion species. The model captures experimental observations, including responses to ion channel inhibitors. This work provides a framework for understanding the factors governing fluid regulation in the cornea

    An NADH-controlled gatekeeper of ATP synthase

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    Summary ATP fuels crucial cellular processes and is obtained mostly by oxidative phosphorylation (OXPHOS) at the inner mitochondrial membrane. While significant progress has been made in mechanistic understanding of ATP production, critical aspects surrounding its substrate supply logistics are poorly understood. We identify an interaction between mitochondrial apoptosis-inducing factor 1 (AIFM1) and adenylate kinase 2 (AK2) as gatekeeper of ATP synthase. This interaction is NADH dependent and influenced by glycolysis, linking it to the cell’s metabolic state. Genetic interference with AIFM1/AK2 association impedes the ability of Caenorhabditis elegans animals to handle altered metabolic rates and nutrient availability. Together, the results imply AIFM1 as a cellular NADH sensor, placing AK2 next to the OXPHOS complexes for local ADP regeneration as the substrate for ATP synthesis. This metabolic signal relay balances ATP synthase substrate supply against ATP conservation, enabling cells to adapt to fluctuating energy availability, with possible implications for AIFM1-related mitochondrial diseases

    Adaptive teaching and the interactional order of classrooms

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    Responding to the need for fine-grained investigation of what adaptive teaching entails, this article reports on 88 qualitative lesson observations with highly competent teachers. The findings illustrate how, amidst the unpredictable flow of classroom life, the participant teachers fashioned a power dynamic with students that was asymmetric and cooperative in nature. This power dynamic was central to understanding how these teachers made responsive adaptations to practice, which were largely achieved through the strategic negotiation of learning journeys with students and the deployment of a broad teaching repertoire. These findings allowed us to broaden the conception of adaptive teaching in a novel way: by integrating dynamics of power into our account of adaptive teaching; by recognising that responsive adaptations are also targeted at longer term trajectories for student learning; and by delineating distinct strategies of teacher adaptations to practice that could incorporate students within the shifting interactional order of classrooms

    Identification and replication of sex-dimorphic protein quantitative trait loci across multiple ancestries and their associations with diseases

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    Males and females exhibit differences in proteome profiles associated with disease risk. However, sex-dimorphic protein quantitative trait loci (SD-pQTL) and their effects on sex differences in health disorders have not been thoroughly investigated. We conducted a sex-stratified, genome-wide association study on 2,922 proteins using data from 30,272 individuals of Caucasian ancestry from the UK Biobank and compared the estimated effects on protein levels of these variants in the men and women to identify SD-pQTLs. The identified SD-pQTLs were replicated using data from two Japanese cohorts (comprising 2,886 and 1,394 individuals, respectively), as well as from 1,990 Finnish, 630 South Asian, and 662 Black ancestry individuals. Sex-dimorphic pleiotropy and the causal relationship between protein levels and health disorders were assessed using the identified SD-pQTLs. We identified 113 SD-pQTLs associated with 65 proteins. Of the 113 SD-pQTLs, 52 were significant in both sexes, five were not significant in either sex, and 42 and 14 were significant only in males and females, respectively. Variant rs2270416 was significantly associated with the CDH15 protein in both sexes but showed opposite effect direction in men and women. Of the 113 SD-pQTLs identified, a total of 41 were replicated in a meta-analysis encompassing Japanese, South Asian, and Black ancestry individuals. SD-pQTLs for proteins APOE (rs157581) and SNAP25 (rs4420638) exhibited sex-dimorphic associations with dementia, indicating sex dimorphic pleiotropy in both proteins and health disorders. From sex-stratified Mendelian randomization using the SD-pQTLs, proteins NCAM1 and PZP showed significant causal relationship with dementia in males and females, respectively. The present study provides evidence of sex-dimorphic genetic architecture in protein-level regulation, elucidating the proteo-genetic architecture for sex differences in human variation.</p

    ARTIC RSV amplicon sequencing reveals global RSV genotype dynamics: [version 1; peer review: awaiting peer review]

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    BackgroundRespiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LTRIs) in young children and adults over 65, contributing significantly to global healthcare burdens. With the recent approval of multiple pharmacological interventions for RSV, there is an increased demand for efficient, high-throughput sequencing methods to monitor RSV genetic diversity and any potential impact these interventions may have.MethodTo address this, we introduce two novel amplicon-based sequencing schemes designed for RSV A and B, optimised for integration with widespread existing ARTIC sequencing workflows. To examine their effectiveness at sequencing RSV samples from across the globe, eight external laboratories used these primers in their sequencing workflows, using both Illumina and Nanopore sequencing technologies.ResultsWe demonstrate that these primer schemes can produce high quality genomes from a diverse range of RSV samples, with eight laboratories in five countries generating complete genomes on both Nanopore and Illumina sequencing platforms. The ability to effectively multiplex these RSV A and B primer schemes, enables streamlined, high-throughput sequencing without prior subtyping. Furthermore, these results provide a snapshot of the circulating diversity of RSV. Phylogenetic analysis of the 882 samples sequenced for this study suggests only minimal geographic clustering of RSV sequences, underscoring the global nature of RSV spread. It also highlights the distinct lineage dynamics seen between RSV A and B.ConclusionsThis study represents an advancement in RSV genomics, providing robust tools for global sequencing efforts aimed at tracking RSV evolution and assessing the efficacy of new therapeutic interventions both rapidly and at scale

    Platelets sequester extracellular DNA, capturing tumor-derived and free fetal DNA

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    Platelets are anucleate blood cells vital for hemostasis and immunity. During cell death and aberrant mitosis, nucleated cells release DNA, resulting in ‘cell free’ DNA in plasma (cfDNA). An excess of cfDNA is deleterious. Given their ability to internalize pathogen-derived nucleic acids, we hypothesized that platelets may also clear endogenous cfDNA. We found that despite lacking a nucleus, platelets contained a repertoire of DNA fragments mapping across the nuclear genome. We detected fetal DNA in maternal platelets and cancer-derived DNA in platelets from patients with pre-malignant and cancerous lesions. As current liquid biopsy approaches utilize platelet-depleted plasma, important genetic information contained within platelets is being missed. This study establishes a physiological role for platelets that has not previously been highlighted, with broad translational relevance

    Key conservation actions for European steppes in the context of the Post-2020 Global Biodiversity Framework

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    The Kunming–Montreal Global Biodiversity Framework (KM–GBF) envisions a world living in harmony with nature by 2050, with 23 intermediate targets to be achieved by 2030. However, aligning international policy and national and local implementation of effective actions can be challenging. Using steppe birds, one of the most threatened vertebrate groups in Europe, as a model system, we identified 36 conservation actions for the achievement of the KM–GBF targets and we singled out—through an expert-based consensus approach—ten priority actions for immediate implementation. Three of these priority actions address at least five of the first eight KM–GBF targets, those related to the direct causes of biodiversity loss, and collectively cover all the targets when implemented concurrently. These actions include (i) effectively protecting priority areas, (ii) implementing on-the-ground habitat management actions, and (iii) improving the quality and integration of monitoring programmes. Our findings provide a blueprint for implementing effective strategies to halt biodiversity loss in steppe-like ecosystems. Our approach can be adapted to other taxonomic groups and ecosystems and has the potential to serve as a catalyst for policy-makers, prompting a transition from political commitment to tangible actions, thereby facilitating the attainment of the KM–GBF targets by 2030

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