Core Features Research Articles

Symptoms and functional impairments in patients with Internet Use Disorders participating in an online short-term therapy

BackgroundInternet use disorders (IUD) have been recognized as a serious mental health concern. In order to promote consensus on core features of IUD, further studies involving clinical samples are required. AimsA clinical evaluation of patients with IUD was conducted as part of the scientific monitoring of a novel online short-term therapy, embedded in the randomized controlled trial Stepped Care Approach for Problematic Internet use Treatment (SCAPIT; ID: DRKS00025994). MethodsAn online diagnostic and a clinical assessment were performed at the baseline measurement of the online intervention. The self-report version of the Assessment of Internet and Computer Game Addiction (AICA-S) was applied to assess symptom severity of IUD. The impact of psychopathological symptoms and impairments of functioning on IUD symptomatology was examined in the sample of patients. Based on a dichotomous classification of the symptom severity of IUD, differences among participants presenting moderate compared to severe addictive Internet behavior were analyzed. ResultsThe sample of this an analysis consisted of 57 patients (57.9% males, mean age of 29.12 years) participating in the online short-term therapy for IUD. Based on the AICA-S sum score (M = 11.60; SD = 3.30) participants exhibited moderate (n = 44; 77.2%) to severe (n = 13; 22.8%) symptoms of addictive Internet use. Psychopathological symptoms and impairments of psychosocial functioning had an effect on symptom severity of IUD. Participants with severe symptoms of IUD showed higher psychopathological strains compared to patients with moderate addictive Internet behavior. ConclusionsThe clinical evaluation of patients participating in a novel online short-term therapy for IUD indicated that psychopathological symptoms and impairments of functioning have an impact on addictive Internet behaviors and consequently, need to be addressed in the treatment of IUD. Based on the results, further implications for clinical practice and research on addictive Internet behavior are derived.

The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China.

Colony-stimulating factor 1 receptor (CSF1R)-related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated. The objective of the study is to clarify the core features and influence factors of CRD patients in China. Clinical and genetic-related data of CRD patients in China were collected. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Sundal MRI Severity Score were evaluated. Whole exome sequencing was used to analyze the CSF1R mutation status. Patients were compared between different sexes, mutation types, or mutation locations. A total of 103 patients were included, with a male-to-female ratio of 1:1.51. The average age of onset was (40.75 ± 8.58). Cognitive impairment (85.1%, 86/101) and parkinsonism (76.2%, 77/101) were the main clinical symptoms. The most common imaging feature was bilateral asymmetric white matter changes (100.0%). A total of 66 CSF1R gene mutants (22 novel mutations) were found, and 15 of 92 probands carried c.2381 T > C/p.I794T (16.30%). The MMSE and MoCA scores (17.0 [9.0], 11.90 ± 7.16) of female patients were significantly lower than those of male patients (23.0 [10.0], 16.36 ± 7.89), and the white matter severity score (20.19 ± 8.47) of female patients was significantly higher than that of male patients (16.00 ± 7.62). There is no statistical difference in age of onset between male and female patients. The core manifestations of Chinese CRD patients are progressive cognitive decline, parkinsonism, and bilateral asymmetric white matter changes. Compared to men, women have more severe cognitive impairment and imaging changes. c.2381 T > C/p.I794T is a hotspot mutation in Chinese patients. © 2024 International Parkinson and Movement Disorder Society.

Responsive facilitation: validating constructs to support in-service science teacher professional development

ABSTRACT In the United States, science education has experienced substantial shifts in the last decade. For in-service teachers, professional development programs (PDPs) play an important role in reform success. Despite well-known core features of effective PDPs, research still suggests a range of results among programs that claim to use those features. An analysis of the nuances associated with these core features has emerged as an important step in bridging the gap between conceptual and actual effective PD. This article presents the validation of constructs for responsive facilitation, which may serve as a source of these nuances. Using an adapted Delphi Method, constructs were validated by multiple expert groups. A 10-construct consensus is presented with an eleventh remaining under dispute. All constructs have connections to current literature and may support the gap noted above. Implications include a structure that may provide nuance to the core features and support more consistently effective PD.

Oxytocin-induced increases in cytokines and clinical effect on the core social features of autism: Analyses of RCT datasets

Although oxytocin may provide a novel therapeutics for the core features of autism spectrum disorder (ASD), previous results regarding the efficacy of repeated or higher dose oxytocin are controversial, and the underlying mechanisms remain unclear. The current study is aimed to clarify whether repeated oxytocin alter plasma cytokine levels in relation to clinical changes of autism social core feature. Here we analyzed cytokine concentrations using comprehensive proteomics of plasmas of 207 adult males with high-functioning ASD collected from two independent multi-center large-scale randomized controlled trials (RCTs): Testing effects of 4-week intranasal administrations of TTA-121 (A novel oxytocin spray with enhanced bioavailability: 3U, 6U, 10U, or 20U/day) and placebo in the crossover discovery RCT; 48U/day Syntocinon or placebo in the parallel-group verification RCT. Among the successfully quantified 17 cytokines, 4 weeks TTA-121 6U (the peak dose for clinical effects) significantly elevated IL-7 (9.74, 95 % confidence interval [CI] 3.59 to 15.90, False discovery rate corrected P (PFDR) < 0.001), IL-9 (56.64, 20.46 to 92.82, PFDR < 0.001) and MIP-1b (18.27, 4.96 to 31.57, PFDR < 0.001) compared with placebo. Inverted U-shape dose–response relationships peaking at TTA-121 6U were consistently observed for all these cytokines (IL-7: P < 0.001; IL-9: P < 0.001; MIP-1b: P = 0.002). Increased IL-7 and IL-9 in participants with ASD after 4 weeks TTA-121 6U administration compared with placebo was verified in the confirmatory analyses in the dataset before crossover (PFDR < 0.001). Furthermore, the changes in all these cytokines during 4 weeks of TTA-121 10U administration revealed associations with changes in reciprocity score, the original primary outcome, observed during the same period (IL-7: Coefficient = −0.05, −0.10 to 0.003, P = 0.067; IL-9: −0.01, −0.02 to −0.003, P = 0.005; MIP-1b: −0.02, −0.04 to −0.007, P = 0.005). These findings provide the first evidence for a role of interaction between oxytocin and neuroinflammation in the change of ASD core social features, and support the potential role of this interaction as a novel therapeutic seed.Trial registration: UMIN000015264, NCT03466671/UMIN000031412.

The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders.

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals; the largest single cohort to date. Core clinical features were developmental delay or intellectual disability (DD/ID, 90%), seizures (83%), hypotonia (72%) and motor symptoms (64%). Prognostic and biologically significant neuroimaging features included cerebral atrophy (75%), cerebellar atrophy (60%), callosal anomalies (57%) and symmetric restricted diffusion of the central tegmental tracts (60%). Sixty-one individuals had multisystem involvement including gastrointestinal (66%), cardiac (19%) and renal (14%) anomalies. Though dysmorphic features were appreciated in 82%, no single dysmorphic feature had a prevalence >30%, indicating substantial phenotypic heterogeneity. Follow-up data were available for all individuals, 15 of whom were deceased at the time of writing. Median age at seizure onset was 6 months. Individuals with variants in synthesis stage genes of the GPI-AP exhibited a significantly shorter time to seizure onset than individuals with variants in transamidase and remodelling stage genes of the GPI-AP (P = 0.046). Forty individuals had intractable epilepsy. The majority of individuals experienced delayed or absent speech (95%), motor delay with non-ambulance (64%), and severe-to-profound DD/ID (59%). Individuals with a developmental epileptic encephalopathy (51%) were at greater risk of intractable epilepsy (P = 0.003), non-ambulance (P = 0.035), ongoing enteral feeds (P < 0.001) and cortical visual impairment (P = 0.007). Serial neuroimaging showed progressive cerebral volume loss in 87.5% and progressive cerebellar atrophy in 70.8%, indicating a neurodegenerative process. Genetic analyses identified 93 unique variants (106 total), including 22 novel variants. Exploratory analyses of genotype-phenotype correlations using unsupervised hierarchical clustering identified novel genotypic predictors of clinical phenotype and long-term outcome with meaningful implications for management. In summary, we expand both the mild and severe phenotypic extremities of the IGDs, provide insights into their neurological basis, and vitally, enable meaningful genetic counselling for affected individuals and their families.

Julearn: an easy-to-use library for leakage-free evaluation and inspection of ML models.

The fast-paced development of machine learning (ML) and its increasing adoption in research challenge researchers without extensive training in ML. In neuroscience, ML can help understand brain-behavior relationships, diagnose diseases and develop biomarkers using data from sources like magnetic resonance imaging and electroencephalography. Primarily, ML builds models to make accurate predictions on unseen data. Researchers evaluate models' performance and generalizability using techniques such as cross-validation (CV). However, choosing a CV scheme and evaluating an ML pipeline is challenging and, if done improperly, can lead to overestimated results and incorrect interpretations. Here, we created julearn, an open-source Python library allowing researchers to design and evaluate complex ML pipelines without encountering common pitfalls. We present the rationale behind julearn's design, its core features, and showcase three examples of previously-published research projects. Julearn simplifies the access to ML providing an easy-to-use environment. With its design, unique features, simple interface, and practical documentation, it poses as a useful Python-based library for research projects.

Creativity Through Embodied Movement in Expressive Activities: Conceptualising a New Pedagogical Model

ABSTRACT This work aimed to outline the first stages for the development of a pedagogical model for teaching-learning of expressive content within physical education (creative body movement). Drawing on several suggestions from previous models’ conceptualizations, we explore and present the theoretical foundations, practical considerations, and assumptions that align and support their core features. The major theme of the model is that students explore new expressive movements and develop capabilities through expressive games or tasks that nurture their creativity and ease their embodied movements. This implies that teachers should provide students with several resources and stimuli to nurture their creativity. Also, teachers should promote students’ embodiment through the exploration of new movements that allow knowing themselves in different movement situations. The affective and cognitive domains will be prominent in this model. The teachers’ and students’ assumptions, implementation needs, and enactment about how to apply this model are also proposed.

Fear of negative evaluation and intolerance of uncertainty: Assessing potential internalizing correlates of eating disorder-related clinical impairment and differences across diagnostic presentations

The Hierarchical Taxonomy of Internalizing Dimensions for Eating Disorders model positions eating disorder (ED) symptoms on an internalizing dimension alongside anxiety and mood symptoms. Symptom dimensions falling under the internalizing subfactors of distress (e.g., social anxiety) and fear/avoidance (e.g., panic, compulsions, checking) may differentially guide treatment. We examined relations between fear of negative evaluation and intolerance of uncertainty (core features of social anxiety and obsessive-compulsive disorder, respectively) and ED-related impairment and potential diagnostic differences. We hypothesized that: (a) fear of negative evaluation and intolerance of uncertainty would be related to ED-related impairment, (b) the relation between fear of negative evaluation and impairment would be strongest among individuals with “binge-eating syndromes” (i.e., bulimia nervosa [BN], binge-eating disorder [BED]), and (c) the relation between intolerance of uncertainty and impairment would be strongest among individuals with “weight-phobic syndromes” (i.e., anorexia nervosa [AN], BN, atypical AN). Participants (N = 236) included children/adolescents and adults evaluated for outpatient ED treatment. Participants completed questionnaires and semi-structured diagnostic interviews. Greater fear of negative evaluation and greater intolerance of uncertainty were related to greater clinical impairment, and the strength of these relations depended on ED diagnosis. Fear of negative evaluation was related to impairment among individuals with AN and atypical AN, and intolerance of uncertainty was related to impairment for individuals with AN, BN, and atypical AN. We identified fear of negative evaluation and intolerance of uncertainty as correlates of clinical impairment, highlighting the potential utility of developing treatments to target these internalizing constructs, especially for individuals with weight-phobic syndromes.

Characterizing Large-Scale Human Circuit Development with In Vivo Neuroimaging.

Large-scale coordinated patterns of neural activity are crucial for the integration of information in the human brain and to enable complex and flexible human behavior across the life span. Through recent advances in noninvasive functional magnetic resonance imaging (fMRI) methods, it is now possible to study this activity and how it emerges in the living fetal brain across the second half of human gestation. This work has demonstrated that functional activity in the fetal brain has several features in keeping with highly organized networks of activity, which are undergoing a highly programmed and rapid sequence of development before birth, in which long-range connections emerge and core features of the mature functional connectome (such as hub regions and a gradient organization) are established. In this review, the findings of these studies are summarized, their relationship to the known changes in developmental neurobiology is considered, and considerations for future work in the context of limitations to the fMRI approach are presented.

Psychometric evaluation and linking of the PHQ-9, QIDS-C, and VQIDS-C in a real-world population with major depressive disorder.

Major depressive disorder (MDD) is a leading cause of disability worldwide. An accurate assessment of depressive symptomology is crucial for clinical management and research. This study assessed the convergent validity, reliability, and total scale score interconversion across the 9-item Patient Health Questionnaire (PHQ-9) self-report, the 16-item Quick Inventory of Depressive Symptomatology-clinician report (QIDS-C) (two widely used clinical ratings) and the 5-item Very Brief Quick Inventory of Depressive Symptoms-clinician report (VQIDS-C), which evaluate the core features of MDD. This study leveraged electronic health record (EHR)-derived, de-identified data from the NeuroBlu Database (Version 23R1), a longitudinal behavioural health real-world platform. Classical Test Theory (CTT) and Item Response Theory (IRT) analyses were used to evaluate the reliability, validity of, and conversions between the scales. The Test Information Function (TIF) was calculated for each scale, with greater test information reflecting higher precision and reliability in measuring depressive symptomology. IRT was also used to generate conversion tables so that total scores on each scale could be compared to the other. The study sample (n = 2,156) had an average age of 36.4 years (standard deviation [SD] = 13.0) and 59.7% were female. The mean depression scores for the PHQ-9, QIDS-C, and VQIDS-C were 12.9 (SD = 6.6), 12.0 (SD = 4.9), and 6.18 (SD = 3.2), respectively. The Cronbach's alpha coefficients for PHQ-9, QIDS-C, and VQIDS-C were 0.9, 0.8, and 0.7, respectively, suggesting acceptable internal consistency. PHQ-9 (TIF = 30.3) demonstrated the best assessment of depressive symptomology, followed by QIDS-C (TIF = 25.8) and VQIDS-C (TIF = 17.7). Overall, PHQ-9, QIDS-C, and VQIDS-C appear to be reliable and convertible measures of MDD symptomology within a US-based adult population in a real-world clinical setting.

Repeating and growing patterns in early mathematics textbooks

ABSTRACT There has been increased attention to the role of explicit pattern tasks in early mathematics learning, with growing recommendations to incorporate more pattern tasks in standards and curricula. One critical piece of this discussion is to consider whether the pattern tasks currently presented in formal curricula materials align with the research on the development of children’s early patterning skills. In the current paper, we quantified the prevalence of patterns and their core features in five early mathematics curricula used in the United States in kindergarten and first grade. Explicit patterns were rare—with one pattern every 20 pages in kindergarten and one pattern every 60 pages in first grade. Most of these explicit pattern tasks included repeating patterns (73%) instead of growing patterns (27%), though this trend was prominent in kindergarten texts and slightly reversed in the first-grade texts. The features of the pattern tasks were often misaligned with research recommendations; most tasks were simplistic, and there was little variability in the complexity of the pattern materials and structures. These findings highlight the need to pinpoint the specific features of pattern tasks that optimize children’s learning opportunities and how best to align these with real-world learning materials.

IoT-Enabled Health Monitoring Systems: Transforming Healthcare Delivery

Abstract: The Internet of Things (IoT) technology integrated with healthcare has revolutionized the way we monitor and manage health. This research paper presents a comprehensive study and exploration of a Health Monitoring System (HMS) built upon using IoT technologies and principles. The HMS offers numerous advantages, which includes, reduced healthcare cost increased accessibility to healthcare services, enhanced patient outcomes, ultimately improving the quality of life. The core features of the HMS include a diverse array of IoT devices such as wearable sensors, smart medical equipment, and smartphones, which collect real-time health data. This data is then seamlessly transmitted, using advanced communication protocols, to centralized servers for analysis and interpretation. The system employs sophisticated data analytics and machine learning algorithms, providing healthcare professionals with invaluable insights into patient health. The technical architecture of the HMS is clarifying, illuminate on how these components synergic operate to create a robust system. However, we also address potential challenges and limitations, encompassing security concerns, data privacy, and scalability issues. These challenges underscore the importance of a balanced approach to ensure patient data confidentiality and system reliability. In conclusion, this research highlights the transformative potential of IoT-driven Health Monitoring Systems. The implications of integrating these two field helps not only improved healthcare outcomes but also hefty cost savings and increased access to healthcare services.

Coherent modal transition systems refinement

Modal Transition Systems (MTS) are a well-known formalism that extend Labelled Transition Systems (LTS) with the possibility of specifying necessary and permitted behaviour. Coherent MTS (CMTS) have been introduced to model Software Product Lines (SPL) based on a correspondence between the necessary and permitted modalities of MTS transitions and their associated actions, and the core and optional features of SPL. In this paper, we address open problems of the coherent fragment of MTS and introduce the notions of refinement and thorough refinement of CMTS. Most notably, we prove that refinement and thorough refinement coincide for CMTS, while it is known that this is not the case for MTS. We also define (thorough) equivalence and strong bisimilarity of both MTS and CMTS. We show their relations and, in particular, we prove that also strong bisimilarity and equivalence coincide for CMTS, whereas they do not for MTS. Finally, we extend our investigation to CMTS equipped with Constraints (MTSC), originally introduced to express alternative behaviour, and we prove that novel notions of refinement and strong thorough refinement coincide for MTSC, and so do their extensions to strong (thorough) equivalence and strong bisimilarity.

Mapping gender networks of music self-concept and music emotions: A network analysis study of music majors in China.

Students' music self-concept and music emotions are becoming prominent topics within the area of music education. The majority of previous research on self-concept and music emotions has examined the two constructs independently and focused on gender differences in externalizing behaviours in music learning, but has neglected the internal interactions between individual music self-concept and music emotions. Network analysis is a promising method for visually examining music self-concept and music emotions as part of a network of interactions to identify core features and interrelationships among nodes in the network. In this study, 515 students majoring in music from a Chinese university were recruited. The results showed that high music self-concept and boredom were the common features at the core of the network for both men and women college students. The boredom exhibited by women differed from that of men in that men's boredom was directed at the entire music course, while boredom in women manifested as daydreaming and boredom with learning materials. This study is the first to explore gender differences in the music self-concept and music emotions from a holistic perspective. The findings could help music teachers gain insight into the complex system of music self-concept and music emotions. Music teachers could capture the respective features of men and women to design individualized teaching strategies.

Protein aggregates containing wild-type and mutant NOTCH3 are major drivers of arterial pathology in CADASIL.

Loss of arterial smooth muscle cells (SMCs) and abnormal accumulation of the extracellular domain of the NOTCH3 receptor (Notch3ECD) are the 2 core features of CADASIL, a common cerebral small vessel disease caused by highly stereotyped dominant mutations in NOTCH3. Yet the relationship between NOTCH3 receptor activity, Notch3ECD accumulation, and arterial SMC loss has remained elusive, hampering the development of disease-modifying therapies. Using dedicated histopathological and multiscale imaging modalities, we could detect and quantify previously undetectable CADASIL-driven arterial SMC loss in the CNS of mice expressing the archetypal Arg169Cys mutation. We found that arterial pathology was more severe and Notch3ECD accumulation greater in transgenic mice overexpressing the mutation on a wild-type Notch3 background (TgNotch3R169C) than in knockin Notch3R170C/R170C mice expressing this mutation without a wild-type Notch3 copy. Notably, expression of Notch3-regulated genes was essentially unchanged in TgNotch3R169C arteries. We further showed that wild-type Notch3ECD coaggregated with mutant Notch3ECD and that elimination of 1 copy of wild-type Notch3 in TgNotch3R169C was sufficient to attenuate Notch3ECD accumulation and arterial pathology. These findings suggest that Notch3ECD accumulation, involving mutant and wild-type NOTCH3, is a major driver of arterial SMC loss in CADASIL, paving the way for NOTCH3-lowering therapeutic strategies.

Repression and growth in the periphery of Europe: The politics of changing growth regime in Turkey

This study shows that in peripheral economies that are linked into circuits of global capital on unequal terms, attempts to change the core features of an existing growth regime without broader political support intensify externally induced conflict among the ruling coalition. Under these circumstances, a transition to a new demand regime within a short time frame is more likely to take place via authoritarian intervention when the political cost of repression is lower than the cost of redistribution. In developing these points, the analysis builds on evidence from Turkey: following the 2008 global credit crunch, the Justice and Development Party’s (Adalet ve Kalkinma Partisi, AKP) domestic demand-led and credit-fueled growth under dependent financialization has experienced a major crisis. However, the subsequent push to replace this regime with a profit-led model with an emphasis on exports worsened the conflict among the political coalition supporting the party as their preferences over monetary policy began to diverge. A temporary resolution of this deepening rift has been possible by way of an authoritarian intervention under R. T. Erdogan’s presidential bid in 2017–18. By situating the debate on the relationship between growth regimes and political institutions, the study further unpacks the nexus between democratic backsliding, dominant social blocs, and economic growth in the periphery of Europe.

Combining transcranial magnetic stimulation with training to improve social cognition impairment in schizophrenia: a pilot randomized controlled trial.

Schizophrenia is a severe, chronic mental disorder that profoundly impacts patients' everyday lives. The illness's core features include positive and negative symptoms and cognitive impairments. In particular, deficits in the social cognition domain showed a tighter connection to patients' everyday functioning than the other symptoms. Social remediation interventions have been developed, providing heterogeneous results considering the possibility of generalizing the acquired improvements in patients' daily activities. In this pilot randomized controlled trial, we investigated the feasibility of combining fifteen daily cognitive and social training sessions with non-invasive brain stimulation to boost the effectiveness of the two interventions. We delivered intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex (DLPFC). Twenty-one patients were randomized into four groups, varying for the assigned stimulation condition (real vs. sham iTBS) and the type of cognitive intervention (training vs. no training). Clinical symptoms and social cognition tests were administered at five time points, i.e., before and after the treatment, and at three follow-ups at one, three, and six months after the treatments' end. Preliminary data show a trend in improving the competence in managing emotion in participants performing the training. Conversely, no differences were found in pre and post-treatment scores for emotion recognition, theory of mind, and attribution of intentions scores. The iTBS intervention did not induce additional effects on individuals' performance. The methodological approach's novelty and limitations of the present study are discussed.

PySAGES: flexible, advanced sampling methods accelerated with GPUs

Molecular simulations are an important tool for research in physics, chemistry, and biology. The capabilities of simulations can be greatly expanded by providing access to advanced sampling methods and techniques that permit calculation of the relevant underlying free energy landscapes. In this sense, software that can be seamlessly adapted to a broad range of complex systems is essential. Building on past efforts to provide open-source community-supported software for advanced sampling, we introduce PySAGES, a Python implementation of the Software Suite for Advanced General Ensemble Simulations (SSAGES) that provides full GPU support for massively parallel applications of enhanced sampling methods such as adaptive biasing forces, harmonic bias, or forward flux sampling in the context of molecular dynamics simulations. By providing an intuitive interface that facilitates the management of a system’s configuration, the inclusion of new collective variables, and the implementation of sophisticated free energy-based sampling methods, the PySAGES library serves as a general platform for the development and implementation of emerging simulation techniques. The capabilities, core features, and computational performance of this tool are demonstrated with clear and concise examples pertaining to different classes of molecular systems. We anticipate that PySAGES will provide the scientific community with a robust and easily accessible platform to accelerate simulations, improve sampling, and enable facile estimation of free energies for a wide range of materials and processes.

Understanding the impacts of chronic pain on autistic adolescents and effective pain management: a reflexive thematic analysis adolescent-maternal dyadic study.

Sensory elements are core features in chronic pain and autism, yet knowledge of the pain experience in autistic adolescents is limited. Little is known regarding how autistic adolescents experience chronic pain, manage their pain and perceive psychological treatment for their chronic pain. Ten autistic adolescents (6 female, 3 male, and 1 self-identified as agender) with chronic pain and their mothers (n = 10) participated in semistructured interviews concerning their perceptions of living with chronic pain. Participants were recruited from U.K. pain management services. According to preference, interviews were conducted individually (n = 10) or dyadically (n = 10 participants across 5 dyads). Data were analyzed using inductive reflexive thematic analysis. Two themes were generated. Theme 1, "overstimulated and striving for control" described how adolescents' experience of heightened sensitivity enhanced adolescents' levels of anxiety and subsequent pain, illustrating a reciprocal relationship between anxiety, pain, and sensory elements. Theme 2, "not everyone fits the mold" captured how autistic adolescents positioned themselves as distinct from others due to the unique nature of being autistic and living with pain. This sense of difference negatively impacted adolescents' ability to engage with and benefit from the standard treatment for chronic pain. Findings suggest that autistic adolescents living with pain experience pain and face barriers to effective pain treatment. Our results identify the need for educational resources to facilitate clinicians to better understand the experience of autistic adolescents living with pain. In turn, such understanding may improve treatment and outcomes in this population.

Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores

Poxviruses are among the largest double-stranded DNA viruses, with members such as variola virus, monkeypox virus and the vaccination strain vaccinia virus (VACV). Knowledge about the structural proteins that form the viral core has remained sparse. While major core proteins have been annotated via indirect experimental evidence, their structures have remained elusive and they could not be assigned to individual core features. Hence, which proteins constitute which layers of the core, such as the palisade layer and the inner core wall, has remained enigmatic. Here we show, using a multi-modal cryo-electron microscopy (cryo-EM) approach in combination with AlphaFold molecular modeling, that trimers formed by the cleavage product of VACV protein A10 are the key component of the palisade layer. This allows us to place previously obtained descriptions of protein interactions within the core wall into perspective and to provide a detailed model of poxvirus core architecture. Importantly, we show that interactions within A10 trimers are likely generalizable over members of orthopox- and parapoxviruses.