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Exercise during 14 days of head down tilt bedrest attenuates motor unit impairments in older humans
Head-down tilt bedrest (HDBR) models the effects of mechanical unloading on neuromuscular function. The efficacy of exercise in preserving motor unit (MU) function in older adults during HDBR remains unclear. This study investigated the effects of 14-day HDBR on MU properties in older adults and the protective role of exercise. Fifteen participants aged 55–65 years were randomized to Control group (n = 7, passive mobilization only) or Exercise group (n = 8, daily mixed resistance and aerobic training) during 14 days of strict HDBR. Knee extensor strength and leg lean mass were measured, and intramuscular EMG was used to record MU firing rate (MUFR), MU potential (MUP) area and complexity, and neuromuscular junction (NMJ) transmission instability during contractions normalized to 25% of pre-bedrest strength. Plasma C-terminal agrin fragment (CAF) was also measured. Following HDBR, knee extensor strength decreased more in the Control group (−33.4 N m; P < 0.001; ∼18% decrease) than in the Exercise group (−14.5 N m; P = 0.027; ∼8% decrease; interaction P = 0.045). Leg lean mass decreased similarly in both groups (−0.418 kg; P = 0.013). Exercise prevented the decrease in MUP area observed in Controls (−65 mV·ms, P = 0.240 vs. −253 mV·ms, P < 0.001) and led to a reduction in MUFR (−1.05 pulses/s, P < 0.001) not seen in Controls. NMJ transmission stability and CAF levels were unchanged in both groups. HDBR reduced leg lean mass and strength. Exercise attenuated declines in strength and MUP area, likely by preserving muscle fibre size despite reduced MUFR, without evidence of NMJ disruption. Exercise effectively attenuates neuromuscular decrements following HDBR in older adults, with implications for clinical care and spaceflight
Towards primary prevention of multiple sclerosis
Multiple sclerosis (MS) is among the most common causes of disability in the young and, despite the advent of highly effective disease-modifying therapies, remains an incurable disease. Prevention of MS before the onset of demyelination is a feasible, albeit ambitious, goal. Currently, preventive interventions with adequate evidence of efficacy are lacking, and evaluating such interventions with traditional trial designs is challenging. Additionally, the high frequency and low effect sizes of putative MS risk factors, a limited window of opportunity to intervene, and the relatively low incidence of MS in the general population make prevention studies conceptually and practically difficult. Nevertheless, studies in radiologically isolated syndrome have generated momentum within the MS prevention space, and novel trial designs offer the potential for reimagining traditional randomized controlled trials. In this Perspective, we discuss the challenges in developing and testing preventive interventions in MS and, drawing on progress in other diseases, we propose strategies and solutions. We discuss pragmatic approaches to risk stratification and illustrate the importance of considering statistical power and outcome definitions. Prevention studies require careful thought with respect to risk stratification, communication, intervention and outcomes but, given the current knowledge, the time to set up and start MS prediction and prevention studies is now
A decuple crossover scheme in genetic algorithms: a step toward deep evolution
Genetic Algorithms (GAs) are widely used for solving complex optimization problems thanks to their ability to explore vast solution spaces and adapt to diverse constraints. Among the key components of GAs, the crossover operator critically influences the balance between exploration and exploitation, by combining promising genetic material and exploring new regions of the solution space. However, traditional crossover operators typically apply a single recombination per parent pair, which limits their ability to deeply exploit high-quality gene patterns and often leads to premature convergence. To address this limitation, we propose the Decuple Crossover Scheme (DCS), a novel hierarchical crossover scheme that intensifies intra-generational recombination. In DCS, a pair of parents initially produce two offspring, which then undergo multiple recombinations with the original parents, resulting in promising candidate offspring. From this pool, the two best individuals are selected for the next generation, enabling deeper exploitation of genetic material and improved population diversity. The effectiveness of DCS is demonstrated through a proof-of-concept application on the Traveling Salesman Problem (TSP) and the Vehicle Routing Problem (VRP), showcasing its potential for enhancing solution quality and convergence speed. These results highlight the broader applicability of DCS to diverse optimization challenges, making it a promising tool for advancing the field of evolutionary computation
Responsible Generative AI for SMEs in UK and Africa (RAISE) - A Research and Development AI Case Study
This report presents a series of case studies developed under the Responsible Generative AI for SMEs in the UK and Africa (RAISE) project, examining how small and medium-sized enterprises (SMEs) understand, adopt, and operationalise generative AI in practice. Drawing on in-depth qualitative engagement with participating organisations across diverse sectors, the case studies explore anticipated benefits, technical and organisational challenges, and the ethical, legal, and social considerations shaping AI integration. The RAISE case studies demonstrate how responsible AI principles are interpreted pragmatically by SMEs and illustrate the value of context-sensitive, actionable guidance in supporting responsible adoption. Collectively, the cases provide empirical insight into the realities of generative AI use in resource-constrained environments and inform the development of practical frameworks for responsible AI implementation in SMEs
Distinct T and innate-like lymphocyte reprogramming following lyophilized fecal microbiota transplantation in recurrent C. difficile infection
Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI), yet its immunological mechanisms remain poorly defined. While bacterial engraftment and recovery of microbial diversity are central to FMT efficacy, accumulating evidence suggests that host immune reprogramming is involved. In murine models, regulatory CD4⁺ T cells are indispensable for clearing C. difficile. To address this mechanistic gap, we examined systemic immune reprogramming following FMT by performing flow cytometry and single-cell RNA sequencing (scRNA-seq) on a subset of successfully treated participants from a clinical trial comparing lyophilized FMT (LFMT) with lyophilized sterile fecal filtrate (LSFF, no live bacteria) for preventing rCDI. Flow cytometry was performed on peripheral mononuclear cells from 19 LFMT recipients and 18 LSFF recipients, and scRNA-seq analysis was performed on two LFMT recipients. Although flow cytometry results did not show significant changes in the assessed markers after rCDI resolution in either treatment group, exploratory scRNA-seq in the two LFMT recipients revealed distinct LFMT-associated transcriptional signatures across adaptive and innate-like lymphocyte populations. LFMT was associated with upregulated activation and regulatory genes (CD69, STAT1, TOX, RORA, FOXP3) in CD4⁺ and CD8⁺ T cells, suggesting enhanced immune regulation with reduced cytotoxic gene expression (GZMB, PRF1, GNLY). Innate-like lymphocytes displayed broad activation, with natural killer cells showing increased KLRD1, PRF1, and IL2RB and mucosal-associated invariant T cells (MAIT cells) upregulating STAT1, JUN, and RORA while downregulating KLRB1 and STAT3. These transcriptional programs are consistent with recalibration of T cell homeostasis and innate-like lymphocyte activation, potentially driven by microbial restoration. Collectively, this exploratory study provides the first single-cell immune atlas of LFMT in rCDI, identifying coordinated activation of regulatory, effector, and innate immune pathways. Given the small sample size, these findings should be considered hypothesis-generating, requiring validation in larger cohorts
Mapping compassion in the general adult population: religious and secular compassionate acts in social relationships and organizational culture
Background: Compassion, defined as recognizing suffering and acting to alleviate it, is increasingly acknowledged as a public health asset that enhances resilience, trust, and cooperation. Shown through interpersonal care, ethical leadership, and institutional backing, compassion influences social relationships and organizational culture, although interpretations differ across religious, secular, and cultural contexts. Clarifying how compassion is understood is crucial for fostering inclusive, supportive communities and workplaces, with existing literature linking it to mental health and community-rooted resilience.Objectives: This study examined how religious and secular ethics shape individuals’ perceptions of compassion received from others, and how these experiences inform social relationships and collective activities. It further explored how compassionate behaviors in workplace settings contribute to organizational climate, an area of growing relevance in public health. Rather than measuring health outcomes directly, the study focused on identifying mechanisms and ingredients for cultivating compassion as a key enabler of public health, with its broader link to well-being supported by existing literature.Methods: Three rounds of online surveys were conducted with 877 working-age adults in the United States between January and April 2025. Participants represented diverse religious backgrounds, including Christianity, Islam, Buddhism, Hinduism, Judaism, and others. To preserve the conceptual breadth of “organization,” no specific profession was defined, ensuring generalizability across public health contexts. Quantitative analyses employed frequency distributions, chi-square tests, and ANOVA, supplemented by path analysis to aggregate results. Qualitative data were examined through thematic narrative analysis and integrated with set theory models to theorize compassion’s broader role.Results: Participants reported that compassion was rarely visible in public discourse, particularly in media (χ2 = 75.30, p < 0.001), despite its perceived importance in healthcare (χ2 = 27.11, p < 0.001), education, and family life. Receiving compassion in workplaces was strongly linked to improved team cohesion, ethical leadership, and support during personal crises (χ2 = 364.32; χ2 = 138.29, both p < 0.001). Qualitative narratives revealed that compassion was interpreted as empathic acknowledgment, shaped by both religious traditions and secular experiences, and embedded in the social fabric of public and professional life.Conclusion: This study identifies receiving compassion as a valuable social and organizational resource, positioning it as a potential public health asset. Compassion strengthens social bonds within communities and workplaces, contributing to trust, cooperation, and resilience. Religious frameworks often interpreted compassion as sacred obligation, while secular frameworks emphasized fairness and civic responsibility, together illuminating compassion’s versatility as both spiritual and civic resource. Limitations include reliance on self-reported data, broad framing of “organization,” and a U.S.-based sample. Future research should employ longitudinal and observational designs to validate findings and explore how cultural contexts and intersecting identities shape interpretations of compassion
Increased cytoplasmic and nuclear S100A6 expression is associated with improved prognosis in ovarian cancer
BackgroundOvarian cancer is one of the most common gynaecological cancers affecting more than 300,000 women worldwide each year. S100 calcium-binding protein A6 (S100A6) is a member of the S100 family of calcium-binding proteins. Upon activation by calcium (Ca2+) signalling, S100A6 regulates numerous cellular processes including cell proliferation and metastasis. The role of S100A6 is well established across multiple tumour types where increased S100A6 expression contributes to tumourigenesis and worse patient outcome. However, the role of S100A6 in ovarian cancer is not well established. MethodsThe impact of cytoplasmic and nuclear S100A6 expression on overall survival and clinicopathological criteria was investigated in 462 ovarian tumours by immunohistochemistry. Additionally, S100A6 expression in an ovarian cancer cohort from The Cancer Genome Atlas (TCGA) PanCancer dataset (n=299) was evaluated and associations with overall survival and progression-free survival were identified. ResultsImmunohistochemical staining revealed that high cytoplasmic expression of S100A6 was significantly associated with better overall survival (p=0.014). Additionally, high nuclear expression was significantly associated with better overall survival (p=0.036). In contrast, analysis of mRNA S100A6 suggests no significant association of mRNA levels for overall survival (p=0.903) and progression free survival (p=0.278).ConclusionsOur data provides novel insights regarding the clinical implications of S100A6 expression in ovarian cancer, providing strong rationale for functional investigations of S100A6 in ovarian cancer
The impact of green credit guidelines on green lending and environmental outcomes: Evidence from Chinese banks
In line with global trends, China introduced the Green Credit Guidelines (GCGs) in 2012 to promote green lending and advance environmental protection. This study shifts the analytical focus from borrowing firms, the primary subject of prior research, to lending institutions and examines how banks have responded to the GCGs. Using panel data from 34 A-share listed Chinese banks between 2008 and 2020, we find a general increase in green lending following the implementation of the GCGs. However, this growth is predominantly driven by state-controlled banks, suggesting that institutional constraints limit broader industry uptake. Further analysis reveals that state-controlled banks benefit financially from green lending post-GCGs and the regions with better GCG implementation experience a decrease in pollution emission levels. Our findings support both institutional theory and relationship banking theory, highlighting the perspectives of the lending institutions and the shortcomings of the current GCGs. To enhance the effectiveness of GCGs, we recommend that the GCGs be supplemented with mechanisms that promote practices across the banking sector
Exploring Responsible Research and Innovation (RRI) in youth mental health: reflections from researchers and young people
BackgroundResponsible Research and Innovation (RRI) promotes inclusive, anticipatory, and reflexive research practices that respond to societal needs. While widely applied in technological fields, its application in youth mental health remains limited. This study aimed to explore how RRI principles are understood and enacted within a large interdisciplinary programme on digital youth mental health in the United Kingdom, focusing on the perspectives of both researchers and young people.MethodsAn online survey was conducted with 21 researchers and 5 young people (mean age = 21 years, standard deviation = 2.74) involved in the programme. The survey included open-ended questions exploring knowledge, attitudes, and practices related to RRI and youth mental health. Responses were analysed using Reflexive Thematic Analysis to identify patterns of meaning across the dataset and to generate themes.ResultsSix themes were developed, reflecting participants’ knowledge, attitudes, and practices. Both researchers and young people conceptualised youth mental health as multifaceted, shaped by personal, social, and cultural factors, and existing along a continuum from flourishing to struggling. Young people highlighted digital harms and economic precarity, while researchers emphasised biopsychosocial determinants, offering complementary perspectives. Involving young people was seen as essential for challenging adult assumptions, improving clarity and relevance of tools, and strengthening ethical integrity. Barriers included communication gaps, entrenched hierarchies, inconsistent involvement, and the resource-intensive nature of participation. Key facilitators included mutual respect, care, flexibility, and procedural structures such as youth co-chairs (i.e., a young person co-leading the project/grant with the principal investigator/s) and regular collaborative meetings. Together, these elements demonstrated how RRI values can be embedded to foster meaningful and equitable youth–researcher partnerships.ConclusionsThis study shows that applying RRI in youth mental health research enhances co-production by integrating diverse perspectives, addressing ethical concerns, and strengthening the quality and social relevance of research. To fully realise this potential, RRI must be embedded as an ongoing practice supported by intentional infrastructures, such as youth leadership roles, communication training, and opportunities for intergenerational dialogue. Crucially, funders must recognise and resource the relational, iterative, and time-intensive nature of responsible youth involvement. Embedding RRI in this field provides a valuable framework for moving beyond tokenistic consultation towards inclusive, future-oriented, and ethically grounded research