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Functioning is a construct capturing how an individual's engagement in everyday life emerges from the interaction between the individual and their environment. The World Health Organization's International Classification of Functioning, Disability and Health (ICF) provides a biopsychosocial framework of functioning. Previously, the ICF was adapted for use in autism by developing Core Sets, a selection of ICF codes from the entire classification for specific conditions. Here, we present the first revision of the ICF of the Core sets for autism from a Delphi-like technique, based on evidence from Core Sets validation/linking studies, stakeholder feedback, and the development and piloting of the autism ICF Core Sets platform. Two ICF second-level codes were removed, and 12 were added to the comprehensive autism Core Set. The added codes reflect body functions in various sensory domains, fine hand use, and environmental factors. Changes were extensive for the age-appropriate brief Core Sets where ICF codes from the initial Core Sets were added or removed. The revisions conducted indicate a continued need for regularly updating Core Sets, based on empirical evidence and stakeholder involvement. We recommend the updated Core Sets for future use in autism research and practice in different age groups and contexts.

Recent studies have reported that strengths-based programs, leveraging autistic adolescents' abilities and interests, could improve their skills and facilitate social engagement. However, little is known about the long-term impact of strengths-based approaches. This study aimed to explore the long-term outcomes of community strengths-based programs designed to support autistic adolescents in developing interests and skills in Science, Technology, Engineering, Arts, and Mathematics (STEAM) and the factors influencing their participation in these programs. A repeated cross-sectional survey study over three years recruited 52 parents in 2018, 52 parents in 2019, and 38 parents in 2020. Results highlighted the positive impact of these programs on autistic adolescents' health and well-being, social relationships and interactions, self-confidence and self-esteem, sense of belonging, and activities and participation. Five key elements influencing participation included the enthusiasm of the participants, their self-perception, the approach of the programs, the learning environment, and the attitudes of the mentors. This study implies that strengths-based approaches to intervention and support for autistic adolescents in a supported environment are a social model solution that could potentially have positive participant outcomes. Findings from this study could provide a framework underpinning future strengths-based interventions.

Caregivers of children with neurodiverse needs are known to experience challenges and hardship due to the increased needs of the child and the lack of support available. This study aimed to explore the support needs and well-being of caregivers of children with neurodiverse needs in Australia. Sixty-six caregivers participated in an online survey asking questions about support needs. The results highlighted five main themes that caregivers commonly experienced including: barriers to community engagement, impact on close relationships, negative impact on mental health and identity, financial hardship, and identified support needs. Findings identified multiple unmet needs existing amongst caregivers and further emphasises the importance of addressing these needs to improve the quality of life of caregivers of children with neurodiverse needs.

Abstract Background Between 2006 and 2016 the prevalence of overweight and obesity among children and adolescents aged 5–19 years in Peru increased from 22.7 to 27.0%. This investment case quantifies the economic impacts of childhood and adolescent overweight and obesity in Peru. It identifies and quantifies the potential impact of a set of new or expanded interventions that can strengthen current national efforts to prevent and reduce child and adolescent overweight and obesity. Methods A deterministic Markov cohort model with a societal cost perspective estimated reductions in mortality and morbidity from implementing interventions to prevent and reduce child and adolescent overweight and obesity and the impact in savings in healthcare costs and gains in wages and productivity. Interventions identified through a review of published literature includes a school-based social marketing campaign, exclusive breastfeeding promotion and support, a healthy food and drink policy for school premises, and a 20% subsidy on fruits and vegetables for people living below the national poverty line. The return on investment (ROI) was calculated along with the estimated cost savings associated with the interventions. Analysis was conducted to test ROI sensitivity to changes in the key parameters and assumptions. Results Between 2025 and 2092, the expected combined direct and indirect healthcare costs attributable to child and adolescent overweight and obesity in Peru are 210.6 billion USD. The direct healthcare costs are 1.8 billion USD, and the indirect costs are 208.8 billion USD. Expected savings for all interventions combined is 13.9 billion USD with a per-person savings of 12,089.8 USD. The expected ROI of the four interventions combined is 39.3 USD (30-years), 64.6 USD (50-years), and 164.1 USD (66-years) per one USD invested. Conclusions The overweight and obesity epidemic among children and adolescents in Peru requires wide-ranging and expanded implementation of policies to achieve long-term reductions in prevalence. This study’s findings show that the four priority interventions have high ROIs and can be used to guide policy to address the complex interplay of factors that contribute to the obesogenic environment.

Abstract The majority of available climate data in global digital archives consist of data only from the 1940s or 1950s onwards, and many of these series have gaps and/or are available for only a subset of the variables which were actually observed. However, there exist billions of historical weather observations from the 1700s, 1800s, and early 1900s that are still in hard‐copy form and are at risk of being lost forever due to deterioration. An assessment of changes in climate extremes in several IPCC regions was not possible in IPCC AR6 WGI owing, in many cases, to the lack of available data. One such region is Africa, where the climate impact research and the ability to predict climate change impacts are hindered by the paucity of access to consistent good‐quality historical observational data. The aim of this innovative project was to use classroom‐based participatory learning to help transcribe some of the many meteorological observations from Africa that are thus far unavailable to researchers. This project transcribed quickly and effectively station series by enrolling the help of second‐year undergraduate students at Maynooth University in Ireland. The newly digitized African data will increase the temporal and spatial coverage of data in this important data‐sparse region. Students gained new skills while helping the global scientific community unearth new insight into past African climate. The project managed to transcribe 79 months of data at Andapa in Madagascar and 56 months of data for Macenta in Guinea. The digitized data will be openly and freely shared with the scientific and wider community via the Pangaea data repository, the C3S Climate Data Store, and the National Oceanic and Atmospheric Administration's (NOAA) National Centers for Environmental Information (NCEI) data centre in the US. The project model has the potential for a broader roll‐out to other educational contexts and there is no shortage of data to be rescued. This paper provides details of the project, and all supporting information such as project guidelines and templates to enable other organizations to instigate similar programs.

Abstract Background Cannabis use can generate potential avoidable harms, hence the need for effective preventive measures and treatment. Studies show the efficacy of harm reduction (HR) in minimizing undesirable consequences associated with this use. Despite its proven efficacy, HR in cannabis use remains poorly applied by many health and social services (HSS) practitioners, especially with young people. However, knowledge regarding the underlying reasons for this is limited. To fill this gap, we aimed to identify facilitators of and obstacles to HSS practitioners’ adoption of HR in cannabis use across OECD countries. Methods We conducted a scoping review, guided by Arksey and O’Malley’s model. The search strategy, executed on health databases and in the grey literature, captured 1804 studies, of which 35 were retained. Data from these studies were extracted in summary sheets for qualitative and numerical analysis. Results Facilitators and obstacles were grouped into four themes: stakeholders’ characteristics (e.g., education, practice experience); clients’ characteristics (e.g., personal, medical); factors related to HR (e.g., perceived efficacy, misconceptions); factors related to the workplace (e.g., type of workplace). Data were also extracted to describe the populations recruited in the selected studies: type of population, clientele, workplace. Conclusion Several factors might facilitate or hinder HSS practitioners’ adoption of HR in cannabis use. Taking these into consideration when translating knowledge about HR can improve its acceptability and applicability. Future research and action should focus on this when addressing practitioners’ adoption of HR.

Abstract Laboratory evolution studies have demonstrated that parallel evolutionary trajectories can lead to genetically distinct enzymes with high activity towards a non-preferred substrate. However, it is unknown whether such enzymes have convergent conformational dynamics and mechanistic features. To address this question, we use as a model the wild-type Homo sapiens kynureninase (HsKYNase), which is of great interest for cancer immunotherapy. Earlier, we isolated HsKYNase_66 through an unusual evolutionary trajectory, having a 410-fold increase in the k cat/KM for kynurenine (KYN) and reverse substrate selectivity relative to HsKYNase. Here, by following a different evolutionary trajectory we generate a genetically distinct variant, HsKYNase_93D9, that exhibits KYN catalytic activity comparable to that of HsKYNase_66, but instead it is a “generalist” that accepts 3’-hydroxykynurenine (OH-KYN) with the same proficiency. Pre-steady-state kinetic analysis reveals that while the evolution of HsKYNase_66 is accompanied by a change in the rate-determining step of the reactions, HsKYNase_93D9 retains the same catalytic mechanism as HsKYNase. HDX-MS shows that the conformational dynamics of the two enzymes are markedly different and distinct from ortholog prokaryotic enzymes with high KYN activity. Our work provides a mechanistic framework for understanding the relationship between evolutionary mechanisms and phenotypic traits of evolved generalist and specialist enzyme species.

Abstract Radio-frequency particle accelerators are engines of discovery, powering high-energy physics and photon science, but are also large and expensive due to their limited accelerating fields. Plasma-wakefield accelerators (PWFAs) provide orders-of-magnitude stronger fields in the charge-density wave behind a particle bunch travelling in a plasma, promising particle accelerators of greatly reduced size and cost. However, PWFAs can easily degrade the beam quality of the bunches they accelerate. Emittance, which determines how tightly beams can be focused, is a critical beam quality in for instance colliders and free-electron lasers, but is particularly prone to degradation. We demonstrate, for the first time, emittance preservation in a high-gradient and high-efficiency PWFA while simultaneously preserving charge and energy spread. This establishes that PWFAs can accelerate without degradation—an essential step toward energy boosters in photon science and multistage facilities for compact high-energy particle colliders.

Abstract The proteasome-associated deubiquitinase USP14 is a potential drug target. Using an inducible USP14 knockout system in colon cancer cells, we found that USP14 depletion impedes cellular proliferation, induces cell cycle arrest, and leads to a senescence-like phenotype. Transcriptomic analysis revealed altered gene expression related to cell division and cellular differentiation. USP14 knockout cells also exhibited changes in morphology, actin distribution, and expression of actin cytoskeletal components. Increased ubiquitin turnover was observed, offset by upregulation of polyubiquitin genes UBB and UBC. Pharmacological inhibition of USP14 with IU1 increased ubiquitin turnover but did not affect cellular growth or morphology. BioGRID data identified USP14 interactors linked to actin cytoskeleton remodeling, DNA damage repair, mRNA splicing, and translation. In conclusion, USP14 loss in colon cancer cells induces a transient quiescent cancer phenotype not replicated by pharmacologic inhibition of its deubiquitinating activity.

IntroductionNeonatal encephalopathy (NE) is a condition with multifactorial etiology that causes multiorgan injury to neonates. The severity of multiorgan dysfunction (MOD) in NE varies, with therapeutic hypothermia (TH) as the standard of care. The aim is to identify current approaches used to assess and determine an optimum scoring system for MOD in NE.MethodsThe systematic review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search was conducted using PubMed, EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Scopus, and CINAHL for studies of scoring systems for MOD in NE.ResultsThe search yielded 628 articles of which 12 studies were included for data extraction and analysis. Five studies found a positive correlation between the severity of NE and MOD. There was significant heterogeneity across the scoring systems, including the eligibility criteria for participants, the methods assessing specific organ systems, the length of follow-up, and adverse outcomes. The neurological, hepatic, cardiovascular, respiratory, hematological, and renal systems were included in most studies while the gastrointestinal system was only in three studies. The definitions for hepatic, renal, and respiratory systems dysfunction were most consistent while the cardiovascular system varied the most.DiscussionA NE multiorgan scoring system should ideally include the renal, hepatic, respiratory, neurological, hematological, and cardiovascular systems. Despite the heterogeneity between the studies, these provide potential candidates for the standardization of MOD scoring systems in NE. Validation is needed for the parameters with adequate length of follow-up beyond the neonatal period. Additionally, the evaluation of MOD may be affected by TH considering its multiorgan effects.

We investigated objective brain vital signs derived from event-related potentials (ERPs) for mixed martial arts (MMA) athletes and matched controls (N = 24). Brain vital sign scans were acquired from 9 MMA athletes and 15 age-and sex-matched controls. Our analysis specifically compared differences in brain vital signs between MMA athletes and controls at baseline. We predicted that MMA athletes would show significant differences relative to controls due to their ongoing exposure to repetitive head impacts. Participants were scanned to extract three well-established ERPs: N100 for auditory sensation; P300 for basic attention; and N400 for cognitive processing. Scans were verified using automated reports, with N100, P300, and N400 amplitudes and latencies manually identified by a blinded reviewer. Brain vital signs were compared across groups with a Kruskal-Wallis H-test for independent samples, with FDR correction for multiple comparisons. We identified significant differences between MMA athletes and controls. Specifically, there were significant N400 amplitude reductions, indicating that exposure to repetitive head impacts in MMA may be associated with changes in brain function.

Abstract Background Evidence has shown that the risk of transmission of SARS-CoV-2 is much higher in prisons than in the community. The release of the COVID-19 vaccine and the recommendation by WHO to include prisons among priority settings have led to the inclusion of prisons in national COVID-19 vaccination strategies. Evidence on prison health and healthcare services provision is limited and often focuses on a single country or institution due to the multiple challenges of conducting research in prison settings. The present study was done in the framework of the EU-founded project RISE-Vac. It aimed to analyse the best practices and challenges applied in implementing COVID-19 universal vaccination services during the pandemic to support future expansion of routine life course vaccination services for people living in prison (PLP). Methods Two online cross-sectional surveys were designed and piloted: survey1 on prison characteristics and (non-COVID-19) immunisation practices; survey2 on the implementation and coverage of COVID-19 vaccination with open-ended questions for thematic analysis. Each RISE-Vac project partner distributed the questionnaire to one or two prisons in their country. Answers were collected from eight European prisons’ directors or medical directors between November 2021-May 2022. Results According to our findings, the implementation modalities of COVID-19 vaccination services in the surveyed prisons were effective in improving PLP vaccination coverage. Strategies for optimal management of the vaccination campaign included: periodic time slot for PLP vaccination; new staff recruitment and task shifting; distribution of informational material both to PLP and prison staff. Key challenges included continuity of care after release, immunisation information system, and vaccine hesitancy. Conclusions To the best of our knowledge, this is the first study describing the implementation of COVID-19 vaccination services in European prisons, suggesting that the expansion of vaccination provision in prison is possible. There is no unique solution that will fit every country but commonalities likely to be important in the design and implementation of future vaccination campaigns targeting PLP emerged. Increased availability of vaccination services in prison is not only possible, but feasible and highly desirable, and can contribute to the reduction of health inequalities.

Increasing vaccination knowledge is effective in addressing hesitancy and is particularly important in populations deprived of liberty who may not routinely have access to health information, ensuring health equity. RISE-Vac is a European Union–funded project aiming to promote vaccine literacy, offer, and uptake in prisons in Europe. We consulted persons living in prisons in the United Kingdom (through the Prisoner Policy Network), France, and Moldova to determine their vaccination knowledge gaps, the information they would like to receive, and how they would like to receive it. We received 344 responses: 224 from the United Kingdom, 70 from France, and 50 from Moldova. Participants were particularly interested in learning about the effectiveness, side effects, and manufacturing of vaccines. Their responses guided the development of educational materials, including a brochure that will be piloted in prisons in Europe. Persons with experience of imprisonment were involved at every stage of this project.

Abstract Magnetic resonance imaging (MRI) has increasingly been used to characterize structure–function relationships during white matter neuroplasticity. Biological sex differences may be an important factor that affects patterns of neuroplasticity, and therefore impacts learning and rehabilitation. The current study examined a participant cohort before and after visuo-motor training to characterize sex differences in microstructural measures. The participants (N = 27) completed a 10-session (4 week) complex visuo-motor training task with their non-dominant hand. All participants significantly improved movement speed and their movement speed variability over the training period. White matter neuroplasticity in females and males was examined using fractional anisotropy (FA) and myelin water fraction (MWF) along the cortico-spinal tract (CST) and the corpus callosum (CC). FA values showed significant differences in the middle portion of the CST tract (nodes 38–51) across the training period. MWF showed a similar cluster in the inferior portion of the tract (nodes 18–29) but did not reach significance. Additionally, at baseline, males showed significantly higher levels of MWF measures in the middle body of the CC. Combining data from females and males would have resulted in reduced sensitivity, making it harder to detect differences in neuroplasticity. These findings offer initial insights into possible female versus male differences in white matter neuroplasticity during motor learning. This warrants investigations into specific patterns of white matter neuroplasticity for females versus males across the lifespan. Understanding biological sex-specific differences in white matter neuroplasticity may have significant implications for the interpretation of change associated with learning or rehabilitation.