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The aim of this paper is to contribute to a better understanding of musician identity learning. Identity is a significant driving-force behind many artistic vocations. However, identity may also pose challenges such as vulnerability, burnout and conflict of commitment. The paper focuses on musician identity, based on interviews with classical and rock musicians during the COVID-19 pandemic. Analyses reveal that the musicians are either in integrating or situating musician identity learning, two different processes discussed as dynamically interrelated and depending on life situation. The paper argues that breaks of normality accentuate challenges stemming from musician identity and that the proposed learning processes are responses to those challenges, which is previously under-explored. The paper concludes that many musicians or other artistic practitioners likely struggle to de-centralize their identity in order to foster a sustainable vocational career and personal growth, and that temporary career breaks may provide necessary relief and learning space.

Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p

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.

Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5.

Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.

Given that camouflaging has been suggested to contribute to delayed diagnosis and mental health problems among autistic people, validated measures of the construct are needed. This study describes the psychometric evaluation of the Swedish adaptation of the self-reported Camouflaging Autistic Traits Questionnaire (CAT-Q) in autistic (n = 100) and general population (n = 539) samples aged 10 to 83 years. Analyses indicated good-to-excellent internal consistency and test-retest reliability. Construct validity was supported by autistic participants scoring higher than non-autistic, and autistic females scoring higher than autistic males on the measure. Also as expected, camouflaging was associated with theoretically linked traits, including autistic behaviors and depressive symptoms. On the other hand, the factor structure of the original CAT-Q did not provide a good fit in the Swedish data set, and validity issues were found, particularly in children younger than 15 years, warranting further investigation of the construct validity of the scale. Different age trajectories were observed, where camouflaging behaviors decreased during adulthood in non-autistic people but remained at an elevated level among autistic people.

BackgroundThere are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder.MethodsThis is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles.DiscussionThis trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Introduction The rapid development of COVID-19 vaccines has provided crucial tools for pandemic control, but the occurrence of vaccine-related adverse events (AEs) underscores the need for comprehensive monitoring.Methods This study analyzed the Vaccine Adverse Event Reporting System (VAERS) data from 2020–2022 using statistical methods such as zero-truncated Poisson regression and logistic regression to assess associations with age, gender groups, and vaccine manufacturers.Results Logistic regression identified 26 System Organ Classes (SOCs) significantly associated with age and gender. Females displayed especially higher odds in SOC 19 (Pregnancy, puerperium and perinatal conditions), while males had higher odds in SOC 25 (Surgical and medical procedures). Older adults (>65) were more prone to symptoms like Cardiac disorders, whereas those aged 18–65 showed susceptibility to AEs like Skin and subcutaneous tissue disorders. Moderna and Pfizer vaccines induced fewer SOC symptoms compared to Janssen and Novavax. The zero-truncated Poisson regression model estimated an average of 4.243 symptoms per individual.Conclusion These findings offer vital insights into vaccine safety, guiding evidence-based vaccination strategies and monitoring programs for precise and effective outcomes.

Abstract Background Leadership and access to structural empowerment are known to influence the work life experiences of staff and quality of care. Knowledge about relationships between specific factors of structural empowerment, leadership and management, staff well-being and quality of care at both an individual and unit level is scarce. Aim To study the relationship between staff-rated access to empowering structures, leadership and management performance, well-being, and quality of care in hospital settings measured at the individual level and aggregated at the unit level. Methods A cross-sectional correlative design was applied. Questionnaire data from 331 randomized hospital nursing staff working at 38 units in 25 hospitals in Sweden were analyzed using bivariate correlations and general estimation equation (GEE) models. Results Results from the bivariate analysis of relationships confirmed earlier research. In the GEE models, some unexpected results were found and differences between the individual and unit levels. Adding management and leadership as independent factors in the second model showed few relationships of significance to the outcome variables. Conclusion Results confirm the importance of staff access to empowering structures in relation to well-being and quality of care. Differences and similarities were shown when studying these relationships at both the individual and unit level. The findings feature implications for hospital management to promote staff access to empowering structures. The findings provide information on how these structures relate to the individual and the unit; information that could be useful when planning or implementing strategies with the aim to promote staff well-being and care quality. The non-significant results for leadership and management in relation to staff outcomes in the GEE-models, raise questions for further research where a shift from individual to organizational focused performances within the field of leadership is implied.

Abstract In this study we examined the effect of simultaneously elevated levels of parathyroid hormone (PTH) (≥ 65 ng/mL) and high levels of insulin-like growth factor-binding protein 1 (IGFBP-1) on the 10-year risk of all-cause mortality and hip fractures. Blood tests for levels of PTH and IGFBP-1 was collected at baseline in 338 community-dwelling women in Stockholm aged between 69 and 79 years. Data on hip fractures and all-cause mortality over the next 10 years were retrieved from healthcare registers. The participants were divided into four groups depending on their levels of PTH and IGFBP-1: (A) normal PTH and low IGFBP-1; (B) normal PTH and high IGFBP-1; (C) elevated PTH and low IGFBP-1; (D) elevated PTH and high IGFBP-1. Group D was used as reference. Cox proportional hazard regression (HR) model was used to compare age-adjusted association with hip fractures and all-cause mortality of the four groups. The group with elevated levels of PTH and high IGFBP-1 had a two to three times higher risk of all-cause mortality compared to the other groups but we found no association with hip fractures.

Speaking with an artificial counterpart in simulated environments has been shown beneficial for foreign language learning. Still, few studies have explored how it is experienced by younger students. We report on a study of Swedish students (N = 22) speaking English with embodied conversational agents (ECAs) in everyday-life scenarios. Data were collected on students' rankings, choices, and open-response items in logbooks and questionnaires. Self-reported data on experiences were analyzed through three dimensions: cognitive, emotional, and social. Findings show that students were generally satisfied with the activity and emotionally engaged with large individual differences within the social dimension. We unpack aspects regarding social relating to the ECA, analyzing the space between experiencing the ECA as a socially distant "deadpan machine" to humanizing and relating socially.

Abstract Williams syndrome (WS) is associated with atypical social communication and cognition reminiscent of the behaviours observed in autism. Nonetheless, WS also differs significantly from autism, such as regarding social motivation, which is typically enhanced in WS and reduced in autism. This study sought to examine the conditions’ transdiagnostic similarities and differences for autistic symptoms and social functioning, and their developmental trajectories, by comparing individuals with WS (n = 24) and those diagnosed with idiopathic autism (n = 24) and attention deficit hyperactivity disorder (ADHD; n = 24), aged 9 to 53 years, on measures of autism, social functioning, IQ and cooccurring psychiatric conditions. Although only 12.5% in the WS group met the criteria for an autism diagnosis, a majority exhibited distinct difficulties within social communication, social cognition, repetitive behaviours, and atypical sensory reactivity resembling autism. Conversely, elevated social motivation and a high number of social initiatives accompany these characteristics. No group differences in the developmental trajectories of autism symptoms were found. Our results demonstrate that autistic behaviours are more frequent in individuals with WS, than in individuals with idiopathic ADHD, and emphasize the need for clinical management of these behaviours.

The tall cell subtype (TC-PTC) is an aggressive subtype of papillary thyroid carcinoma (PTC). The TC-PTC is defined as a PTC comprising at least 30% epithelial cells that are three times as tall as they are wide. In practice, this definition is difficult to adhere to, resulting in high inter-observer variability. In this multicenter study, we validated a previously trained deep learning (DL)-based algorithm for detection of tall cells on 160 externally collected hematoxylin and eosin (HE)-stained PTC whole-slide images. In a test set of 360 manual annotations of regions of interest from 18 separate tissue sections in the external dataset, the DL-based algorithm detected TCs with a sensitivity of 90.6% and a specificity of 88.5%. The DL algorithm detected non-TC areas with a sensitivity of 81.6% and a specificity of 92.9%. In the validation datasets, 20% and 30% TC thresholds correlated with a significantly shorter relapse-free survival. In conclusion, the DL algorithm detected TCs in unseen, external scanned HE tissue slides with high sensitivity and specificity without any retraining.

Summary: Background: Findings regarding the protective effect of Angiotensin II receptor blockers (ARBs) against Alzheimer’s disease and related dementias (AD/ADRD) and cognitive decline have been inconclusive. Methods: Individuals with hypertension who do not have any prior ADRD diagnosis were included in this retrospective cohort study from Optum’s de-identified Clinformatics® Data Mart. We identified antihypertensive medication (AHM) drug classes and subclassified ARBs by blood–brain barrier (BBB) permeability. We compared baseline characteristics and used the Kaplan–Meier (KM) survival curve and adjusted Cox proportional hazards (PH) model for survival analyses. Findings: From 6,390,826 individuals with hypertension, there were 1,839,176 ARB users, 3,366,841 non-ARB AHM users, and 1,184,809 AHM non-users. The unadjusted KM curve showed that ARB users had lower cumulative hazard than other AHM users or AHM non-users (P

Aerobic ribonucleotide reductases (RNRs) initiate synthesis of DNA building blocks by generating a free radical within the R2 subunit; the radical is subsequently shuttled to the catalytic R1 subunit through proton-coupled electron transfer (PCET). We present a high-resolution room temperature structure of the class Ie R2 protein radical captured by x-ray free electron laser serial femtosecond crystallography. The structure reveals conformational reorganization to shield the radical and connect it to the translocation path, with structural changes propagating to the surface where the protein interacts with the catalytic R1 subunit. Restructuring of the hydrogen bond network, including a notably short O-O interaction of 2.41 angstroms, likely tunes and gates the radical during PCET. These structural results help explain radical handling and mobilization in RNR and have general implications for radical transfer in proteins.

Genetic factors influence medication response (pharmacogenetics), affecting the pharmacodynamics and pharmacokinetics of many medicaments used in clinical care. The ability of medications to cross the blood–brain barrier (BBB) represents a critical putative factor in the effectiveness and tolerability of various medications relevant to central nervous system disorders (CNS), cancer, and broader medical conditions at a pharmacokinetic (dosing) level. Pharmacogenetics has the potential to personalise medicine to a greater extent than has been possible, with the potential to help reduce heuristic delays to effective tolerable pharmacotherapy. Here, we critically examine and summarise the evidence, particularly for ABCB1 polymorphisms associated with drug transportation and other clinical relevance. These transporters appear to have a role in BBB pharmacogenetics and may indicate new avenues of research that extend beyond the current paradigm of CYP450 polymorphisms. We identify some of the most promising variants for clinical translation while spotlighting the complexities of the involved systems and limitations of the current empirical literature.

Abstract Background Individuals with non-celiac gluten/wheat sensitivity (NCGWS) experience improvement in gastrointestinal symptoms following a gluten-free diet. Although previous results have indicated that fructo-oligosaccharides (FOS), a type of short-chain fructans, were more likely to induce symptoms than gluten in self-reported NCGWS patients, the underlying mechanisms are unresolved. Methods Our main objective was therefore to investigate whether FOS-fructans and gluten affect the composition and diversity of the faecal microbiota (16S rRNA gene sequencing), faecal metabolites of microbial fermentation (short-chain fatty acids [SCFA]; gas chromatography with flame ionization detector), and a faecal biomarker of gut inflammation (neutrophil gelatinase-associated lipocalin, also known as lipocalin 2, NGAL/LCN2; ELISA). In the randomised double-blind placebo-controlled crossover study, 59 participants with self-reported NCGWS underwent three different 7-day diet challenges with gluten (5.7 g/day), FOS-fructans (2.1 g/day), and placebo separately (three periods, six challenge sequences). Results The relative abundances of certain bacterial taxa were affected differently by the diet challenges. After the FOS-fructan challenge, Fusicatenibacter increased, while Eubacterium (E.) coprostanoligenes group, Anaerotruncus, and unknown Ruminococcaceae genera decreased. The gluten challenge was primarily characterized by increased abundance of Eubacterium xylanophilum group. However, no differences were found for bacterial diversity (α-diversity), overall bacterial community structure (β-diversity), faecal metabolites (SCFA), or NGAL/LCN2. Furthermore, gastrointestinal symptoms in response to FOS-fructans were generally not linked to substantial shifts in the gut bacterial community. However, the reduction in E. coprostanoligenes group following the FOS-fructan challenge was associated with increased gastrointestinal pain. Finally, correlation analysis revealed that changes in gastrointestinal symptoms following the FOS-fructan and gluten challenges were linked to varying bacterial abundances at baseline. Conclusions In conclusion, while FOS-fructans induced more gastrointestinal symptoms than gluten in the NCGWS patients, we did not find that substantial shifts in the composition nor function of the faecal microbiota could explain these differences in the current study. However, our results indicate that individual variations in baseline bacterial composition/function may influence the gastrointestinal symptom response to both FOS-fructans and gluten. Additionally, the change in E. coprostanoligenes group, which was associated with increased symptoms, implies that attention should be given to these bacteria in future trials investigating the impact of dietary treatments on gastrointestinal symptoms. Trial registration Clinicaltrials.gov as NCT02464150.

Abstract Pupillary contagion occurs when one’s pupil size unconsciously adapts to the pupil size of an observed individual and is presumed to reflect the transfer of arousal. Importantly, when estimating pupil contagion, low level stimuli properties need to be controlled for, to ensure that observations of pupillary changes are due to internal change in arousal rather than the external differences between stimuli. Here, naturalistic images of children’s faces depicting either small or large pupils were presented to a group of children and adolescents with a wide range of autistic traits, a third of whom had been diagnosed with autism. We examined the extent to which pupillary contagion reflects autonomic nervous system reaction through pupil size change, heart rate and skin conductance response. Our second aim was to determine the association between arousal reaction to stimuli and degree of autistic traits. Results show that pupil contagion and concomitant heart rate change, but not skin conductance change, was evident when gaze was restricted to the eye region of face stimuli. A positive association was also observed between pupillary contagion and autistic traits when participants’ gaze was constrained to the eye region. Findings add to a broader understanding of the mechanisms underlying pupillary contagion and its association with autism.

Abstract Background Diarrhoea kills 500,000 children every year despite availability of cheap and effective treatment. In addition, a large number are inappropriately treated with antibiotics, which do not benefit the patient but can contribute to the development of antibiotic resistance. We investigated whether the prevalence of antibiotic use among children under the age of five with diarrhoea in Uganda changed following a national intervention to increase the use of oral rehydration salts (ORS), and whether any socioeconomic characteristics were associated with antibiotic use. Methods A cross-sectional survey was conducted among caregivers of children under the age of five and among private health care providers and drug sellers in Uganda in 2014. This was compared to a similar survey among private health care providers, and the national demographic and health survey in Uganda in 2016. Logistic regression was used to find associations between antibiotic use and socioeconomic characteristics, and chi-square test and independent sample t-test were used to find significant differences between groups. Results The prevalence of antibiotic use among children under the age of five with diarrhoea in Uganda decreased from 30.5% in 2014 to 20.0% (p