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How time and risk preferences affect glucose control in type 2 diabetes patients
No full textThe attitude to self-care of individuals with type 2 diabetes (T2D) is commonly influenced by their time preferences (i.e., long-run discounting and time-consistency), and/or risk preference (i.e., risk tolerance). Tailored preference-based self-care management may improve clinical and cost-effectiveness. This study investigates associations between elicited time and risk preferences with diabetes-related outcomes, i.e., Hemoglobin A1c (HbA1c) and blood glucose level. Time and risk preferences of 396 T2D patients were measured by incentivized tasks. Clinical data was retrieved from hospital information systems for diabetes outcomes (HbA1c and blood glucose levels) and clinical factors. We assessed patient diabetes-associated self-care behaviors and other epidemiological factors by questionnaire. Multivariate linear regressions with stepwise model selection were used to evaluate potential associations with T2D outcomes. We found that participants who favored immediate gratification over greater long-term benefits (time-inconsistent towards present or present-biased) had significantly higher HbA1c levels than time-consistent participants, with a coefficient (95% CI) of 0.41 (0.02,0.80). Neither time nor risk preferences were significantly associated with blood glucose levels. These findings suggest the use of tailored diabetes interventions to help present-biased patients overcome self-control problems. This targeted approach may be more cost-effective but requires formal testing.<br/
In depth characterisation of the proteome of MIS-C and post COVID-19 infection in children reveals inflammatory pathway activation and evidence of tissue damage
No full textBackgroundMultisystem inflammatory syndrome in children (MIS-C) is a rare but severe complication that arises between two and six weeks after initial SARS-CoV-2 infection. The mechanisms underlying why only a subset of children develop this hyperinflammatory response remain unclear.MethodsWe performed an in-depth proteomic analysis of plasma samples from children before and after SARS-CoV-2 infection, including those who developed MIS-C. Proteomic profiling was conducted using high-throughput technologies, and findings were validated using publicly available datasets.ResultsHealthy children showed minimal changes in the circulating proteome following SARS-CoV-2 infection, with no evidence of ongoing inflammation. In contrast, children with MIS-C exhibited significant activation of pro-inflammatory pathways and elevated circulating markers of myocardial and vascular injury.ConclusionsOur data suggest that SARS-CoV-2 infection alone does not cause sustained proteomic alterations in most children. However, MIS-C is associated with a distinct inflammatory and vascular injury signature. Several candidate diagnostic biomarkers for MIS-C were identified and validated in silico, offering promising avenues for future diagnostic and therapeutic strategies.<br/
Testing The Temperature 13: What do voters in Northern Ireland think about the Windsor Framework and UK-EU Relations?
No full text'Durable relationships' and duty of care: judgement in the Irish family and care referenda
No full textKeyed randomization with adversarial failure curves and moving target defense
No full textEstablishing the robustness of classifiers against adversarial attacks is crucial in many applications of Machine Learning to Cybersecurity. This paper focuses on evasion attacks, where inputs are selected or modified to evade detection by a learned model under gray-box scenarios, with only partial adversarial knowledge of the classifier. We generalize the adversarial failure rate metric into a continuous curve, by trading it off against the false positive rate for threshold classifiers, analogous to the receiver operating characteristic (ROC) curve. Subsequently, we propose two novel keyed randomization methods, and a moving target defense strategy. We evaluate the proposed methods using two publicly available intrusion detection datasets (BETH-2021 and Kyoto-2015), demonstrating consistently superior results relative to other randomization techniques
Hydroxylation mechanism of lignin-derived aromatic substrates catalyzed by plant P450 cinnamate 4-hydroxylase
No full textCytochrome P450 cinnamate 4-hydroxylase (C4H) is a pivotal enzyme in the phenylpropanoid pathway, playing a critical role in regulating lignin biosynthesis in plants. In contrast to the hydroxylation reactions catalyzed by human P450 enzymes, which have been extensively studied, the mechanistic understanding of plant P450-mediated hydroxylation of aromatic substrates remains limited. In this study, using comprehensive atomistic molecular dynamics (MD) simulations, we elucidated the binding pose of the native substrate trans-cinnamic acid and identified key residues contributing to the substrate specificity of the enzyme, which include Arg213 and a conserved hydrophobic pocket comprising Val118, Phe119, Val301, Ala302, Ile367 and Phe484. Additionally, we investigated the catalytic mechanism using hybrid quantum mechanics/molecular mechanics (QM/MM) calculations, evaluating all plausible C4H-catalysed pathways for aromatic hydroxylation. Our results reveal that among all investigated mechanisms, the most favourable pathway involves direct hydroxylation via electrophilic attack coupled with a proton shuttle. These findings provide valuable insights into the catalytic mechanism of C4H, which would pave the way for modifying lignin biosynthesis to regulate various lignin contents in plants, unlocking its potential applications in sustainable bioremediation and biomanufacturing.<br/
Distal lung organoids derived from adult stem cells as novel tools in deciphering mechanisms of lung regeneration, infection, and cancer
No full textWhile lung research has made great strides in understanding lung physiology, lung pathology still presents a major burden to patients and healthcare systems globally. To develop new effective therapeutics to improve lung regeneration, prevent spread of infections, or treat lung cancers, obscured fundamental processes of the lung must be dissected. Current understanding of lung cell cross talk has been limited due to a lack of accessible and representative models. Since the COVID-19 pandemic, many new foundational methodologies for distal organoid formation have been published, which eliminate difficulty in distal organoid longevity and donor cell extraction efficiency. This review describes how recent advances within distal lung organoid technology have been used to investigate lung regeneration, fibrosis, infection trafficking, personalized medicine, and mechanism of chronic lung pathology using donor cells. Additionally, the applicability of distal lung organoids to investigation of the roles of endothelium and previously unknown distal epithelial and mesenchymal cell populations is discussed. Finally, new techniques and methods for tackling current challenges within the field, such as integration of immune cells and vascularization of organoids are highlighted. This overview will therefore illustrate the potential of distal lung organoids to be tissue representative models, which will be crucial for evolving scientific knowledge of lung physiology.</p
Augmented accountability: data access in the metaverse
No full textThis article examines regulated data access (RDA) in the metaverse—an interconnected and immersive digital ecosystem comprising virtual, augmented, and hyper-physical realities. We organise the argument across taxonomy (Section 2), Digital Services Act (DSA)-anchored doctrine (Section 3), implementation challenges (Section 4), platform practices (Section 5), and a global blueprint (Section 6). Building on the European Union’s DSA, particularly Article 40, the analysis evaluates whether metaverse platforms qualify as Very Large Online Platforms or Very Large Online Search Engines and thus fall within the DSA’s data access rules. Drawing comparative insights from the UK’s Online Safety Act and the United States’ proposed Platform Accountability and Transparency Act, the article highlights differing global approaches to data sharing and the significant governance gaps that persist.This article categorizes metaverse-native data, including spatial, biometric, and eye-tracking data, into personal and non-personal types, stressing the heightened complexity of governing immersive, multidimensional information flows. While existing legal frameworks offer a starting point, the metaverse’s novel data practices demand targeted adaptations to address challenges like decentralised governance, user consent in real-time environments, and the integration of privacy-enhancing technologies. Through an examination of data access regimes across selected metaverse platforms, the article identifies a lack of uniform, transparent processes for external researchers.In this context, the article highlights RDA's broader public-interest function, facilitating external scrutiny of platform activities and ensuring service providers are held accountable. The absence of consistent RDA frameworks obstructs systemic risk research, undermining both risk assessment and mitigation efforts while leaving user rights vulnerable to opaque platform governance. To address these gaps, the article advances a set of policy recommendations aimed at strengthening RDA in the metaverse—adapting regulatory strategies to its evolving, decentralised architecture. By tailoring regulatory strategies to the metaverse’s dynamic nature, policymakers can foster accountability, innovation, and trust—both domestically (in jurisdictions like the UK, where data access provisions remain underdeveloped) and internationally. The analysis extends beyond mere applications to metaverse platforms, providing insights that can be applied to the online platform ecosystem in its entirety. Ultimately, this article charts a path toward harmonized, future-ready data governance frameworks—one that integrates RDA as a core regulatory mechanism for ‘augmented accountability’, essential for safeguarding user rights and enabling independent risk assessment in the metaverse.<br/