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Introduction: Poor quality T1-weighted brain scans systematically affect the calculation of brain measures. Removing the influence of such scans requires identifying and excluding scans with noise and artefacts through a quality control (QC) procedure. While QC is critical for brain imaging analyses, it is not yet clear whether different QC approaches lead to the exclusion of the same participants. Further, the removal of poor-quality scans may unintentionally introduce a sampling bias by excluding the subset of participants who are younger and/or feature greater clinical impairment. This study had two aims: (1) examine whether different QC approaches applied to T1-weighted scans would exclude the same participants, and (2) examine how exclusion of poor-quality scans impacts specific demographic, clinical and brain measure characteristics between excluded and included participants in three large pediatric neuroimaging samples., Methods: We used T1-weighted, resting-state fMRI, demographic and clinical data from the Province of Ontario Neurodevelopmental Disorders network (Aim 1: n = 553, Aim 2: n = 465), the Healthy Brain Network (Aim 1: n = 1051, Aim 2: n = 558), and the Philadelphia Neurodevelopmental Cohort (Aim 1: n = 1087; Aim 2: n = 619). Four different QC approaches were applied to T1-weighted MRI (visual QC, metric QC, automated QC, fMRI-derived QC). We used tetrachoric correlation and inter-rater reliability analyses to examine whether different QC approaches excluded the same participants. We examined differences in age, mental health symptoms, everyday/adaptive functioning, IQ and structural MRI-derived brain indices between participants that were included versus excluded following each QC approach., Results: Dataset-specific findings revealed mixed results with respect to overlap of QC exclusion. However, in POND and HBN, we found a moderate level of overlap between visual and automated QC approaches (r tet =0.52-0.59). Implementation of QC excluded younger participants, and tended to exclude those with lower IQ, and lower everyday/adaptive functioning scores across several approaches in a dataset-specific manner. Across nearly all datasets and QC approaches examined, excluded participants had lower estimates of cortical thickness and subcortical volume, but this effect did not differ by QC approach., Conclusion: The results of this study provide insight into the influence of QC decisions on structural pediatric imaging analyses. While different QC approaches exclude different subsets of participants, the variation of influence of different QC approaches on clinical and brain metrics is minimal in large datasets. Overall, implementation of QC tends to exclude participants who are younger, and those who have more cognitive and functional impairment. Given that automated QC is standardized and can reduce between-study differences, the results of this study support the potential to use automated QC for large pediatric neuroimaging datasets., Competing Interests: Declaration of Competing Interest Other authors report no related funding support, financial or potential conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background/purpose: The diagnosis of autism spectrum disorder (ASD), involving multiple components of clinical assessments, is challenging. The Autism Diagnostic Observation Schedule-Generic (ADOS-G), one of the standardized and validated instruments for ASD diagnostic evaluation, has been widely used in many countries. With the preparation of the Mandarin version of the ADOS-G (Mandarin-ADOS-G), this study aims to examine its psychometric properties, including reliability and validity., Methods: The sample included 554 individuals clinically diagnosed with ASD (477 males, 86.1%) and 50 typically developing (TD) individuals (29 males, 58.0%) who were assessed with different modules of the Mandarin-ADOS-G between 4.1 and 34.0 years old with a mean age of 13.0 years (Module 1, n = 40; Module 2, n = 46; Module 3, n = 275; Module 4, n = 243). We evaluated the inter-rater reliability, test-retest reliability, internal consistency, and concurrent validity with the Chinese Autism Diagnostic Interview-Revised (ADI-R) and Social Responsiveness Scale (SRS) caregiver-report and self-report forms. The discriminative validity of Mandarin-ADOS-G was also examined., Results: The Mandarin-ADOS-G demonstrated good inter-rater reliability (agreement of ADOS classification 0.91), good test-retest reliability (intraclass correlations 0.55-0.73), and low to high good internal consistency (Cronbach's alpha 0.27-0.86). The concurrent validity showed significant correlations with ADI-R (Pearson correlations 0.22-0.37) and the SRS caregiver-report form (Pearson correlations 0.15-0.23). Moreover, all Mandarin-ADOS-G domains successfully differentiated autistic individuals from TD individuals (all p-values <0.001)., Conclusion: The Mandarin-ADOS-G is a reliable and valid instrument for assisting the diagnosis of ASD in the Mandarin-speaking population., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Recent research found that the combination of masculine gender identity and gynephilia was associated with cortical T1 relaxation time, which is considered to reflect gray matter density. We hypothesized that mean diffusivity (MD), a diffusion tensor imaging metric that reflects the degree to which water movement is free versus constrained, in combination with T1 relaxation time would provide further insight regarding cortical tissue characteristics. MD and T1 relaxation time were measured in 76 cortical regions in 15 adolescents assigned female at birth who experience gender dysphoria (GD AFAB) and were not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12-17 years). Sexual orientation was represented by the degree of androphilia-gynephilia and the strength of sexual attraction. In multivariate analyses, cortical T1 relaxation time showed a weak but statistically significant positive association with MD across the cortex, suggesting that macromolecule-rich cortical tissue also tends to show water movement that is somewhat more constrained. In further multivariate analyses, in several left frontal, parietal, and temporal regions, the combination of shorter T1 relaxation time and faster MD was associated with older age and greater gynephilia in GD AFAB individuals and cisgender boys and with stronger attractions in cisgender boys only. Thus, for these cortical regions in these groups, older age, gynephilia, and stronger attractions (cisgender boys only) were associated with macromolecule-rich tissue in which water movement was freer-a pattern that some prior research suggests is associated with greater cell density and size. Overall, this study indicates that investigating T1 relaxation time and MD together can further inform how cortical gray matter tissue characteristics relate to age and psychosexuality.

Many transgender people are autistic. Community expressions of the autism transgender intersection abound. Some commentators have questioned the proportional overrepresentation of autism among gender-diverse people, suggesting these individuals may not be truly autistic or truly transgender. However, increasing evidence challenges assertions that deny the authenticity of co-occurring autistic and transgender identities. Specifically, research by authors of this article indicates autistic transgender people show neurophenotypes generally consistent with cisgender autistic people and implicit gender phenotypes consistent with nonautistic transgender people. This article features a dialogue between eight leading experts in the field of intersectional autism and gender diversity, including clinicians, researchers, community advocates, and experts who are themselves autistic transgender. Key topics of discussion included: how research findings on autism and gender diversity inform respectful and supportive responses to autistic transgender people; the benefits and harms of increased societal attention toward the autism transgender intersection; and research and advocacy priorities. The expert panel concluded the following: (1) it is important to respect transgender autistic people's wellness and resilience, while also acknowledging the pathologization and stigmatization they face; (2) autistic gender-diverse people are experts of their own identity and should be involved in all aspects of research and clinical care; (3) research is needed to understand the disparities autistic transgender people face; (4) attempts to restrict autistic transgender people's access to gender care are unsupported by existing research; (5) adult gender care may benefit from incorporating universal design principles and neurodiversity-affirming strategies to reduce barriers to care and improve clinician-client communication in treatment delivery and the informed consent process; (6) cross-cultural and cross-societal research will improve best care practices in diverse contexts; (7) research and advocacy must be inclusive across ethnoracial identities, including in leadership and perspectives represented; and (8) a life span developmental framework is needed for adult research in this field., Competing Interests: J.F.S. was a coauthor of the Child and Adolescent chapters of the Standards of Care 8 revision through the World Professional Association for Transgender Health (WPATH). F.V.G., J.F.S., and A.I.R.v.d.M. are faculty members with the WPATH Global Education Institute (GEI); they receive financial remuneration for their WPATH GEI services., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

Background: Autistic transgender people face unique risks in society, including inequities in accessing needed care and related mental health disparities. Given the need for specific and culturally responsive accommodations/supports, the characterization of key experiences, challenges, needs, and resilience factors within this population is imperative. This study developed a structured self-report tool for autistic transgender young adults to communicate their experiences and needs in a report format attuned to common autistic thinking and communication styles., Methods: This cross-nation project developed and refined the Gender-Diversity and Autism Questionnaire through an iterative community-based approach using Delphi panel methodology. This proof-of-principle project defined "expertise" broadly, employing a multi-input expert search approach to balance academic-, community-, and lived experience-based expertise., Results: The expert collaborators ( N  = 24 respondents) completed a two-round Delphi study, which developed 85 mostly closed-ended items based on 90% consensus. Final item content falls within six topic areas: the experience of identities; the impact of experienced or anticipated discrimination, bias, and violence toward autistic people and transgender people; tasks and experiences of everyday life; gender diversity- or autism-related care needs and history; the experience of others doubting an individual's gender identity and/or autism; and the experience of community and connectedness. The majority of retained items relate to tasks and experiences of everyday life or the impact of experienced or anticipated discrimination, bias, and violence., Conclusions: This study employed a multipronged multimodal search approach to maximize equity in representation of the expert measure development team. The resulting instrument, designed for clinical, research, and self-advocacy applications, has parallel Dutch and English versions and is available for immediate use. Future cross-cultural research with this instrument could help identify contextual risk and resilience factors to better understand and address inequities faced by this large intersectional population., Competing Interests: No competing financial interests exist., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

The common intersection of autism and transgender identities has been described in clinical and community contexts. This study investigates autism-related neurophenotypes among transgender youth. Forty-five transgender youth, evenly balanced across non-autistic, slightly subclinically autistic, and full-criteria autistic subgroupings, completed resting-state functional magnetic resonance imaging to examine functional connectivity. Results confirmed hypothesized default mode network (DMN) hub hyperconnectivity with visual and motor networks in autism, partially replicating previous studies comparing cisgender autistic and non-autistic adolescents. The slightly subclinically autistic group differed from both non-autistic and full-criteria autistic groups in DMN hub connectivity to ventral attention and sensorimotor networks, falling between non-autistic and full-criteria autistic groups. Autism traits showed a similar pattern to autism-related group analytics, and also related to hyperconnectivity between DMN hub and dorsal attention network. Internalizing, gender dysphoria, and gender minority-related stigma did not show connectivity differences. Connectivity differences within DMN followed previously reported patterns by designated sex at birth (i.e. female birth designation showing greater within-DMN connectivity). Overall, findings suggest behavioral diagnostics and autism traits in transgender youth correspond to observable differences in DMN hub connectivity. Further, this study reveals novel neurophenotypic characteristics associated with slightly subthreshold autism, highlighting the importance of research attention to this group., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Eight gene clusters responsible for synthesizing bioactive metabolites associated with plant growth promotion were identified in the Bacillus cereus strain D1 (BcD1) genome using the de novo whole-genome assembly method. The two largest gene clusters were responsible for synthesizing volatile organic compounds (VOCs) and encoding extracellular serine proteases. The treatment with BcD1 resulted in an increase in leaf chlorophyll content, plant size, and fresh weight in Arabidopsis seedlings. The BcD1-treated seedlings also accumulated higher levels of lignin and secondary metabolites including glucosinolates, triterpenoids, flavonoids, and phenolic compounds. Antioxidant enzyme activity and DPPH radical scavenging activity were also found to be higher in the treated seedlings as compared with the control. Seedlings pretreated with BcD1 exhibited increased tolerance to heat stress and reduced disease incidence of bacterial soft rot. RNA-seq analysis showed that BcD1 treatment activated Arabidopsis genes for diverse metabolite synthesis, including lignin and glucosinolates, and pathogenesis-related proteins such as serine protease inhibitors and defensin/PDF family proteins. The genes responsible for synthesizing indole acetic acid (IAA), abscisic acid (ABA), and jasmonic acid (JA) were expressed at higher levels, along with WRKY transcription factors involved in stress regulation and MYB54 for secondary cell wall synthesis. This study found that BcD1, a rhizobacterium producing VOCs and serine proteases, is capable of triggering the synthesis of diverse secondary metabolites and antioxidant enzymes in plants as a defense strategy against heat stress and pathogen attack.

Severe behavioral problems (SBPs) are common contributors to morbidity and reduced quality of life for adults with intellectual and developmental disabilities (IDD) and their families. Current medications for SBPs show equivocal effectiveness and are associated with a high risk of side effects. New and safe treatments are urgently needed. While preliminary studies suggest that medical cannabinoids, particularly the synthetic cannabinoid nabilone, are plausible treatment options for SBPs in adults with IDD, data on the tolerability, safety and efficacy of nabilone in this population has never been investigated. Thus, we propose this first-ever Phase I pre-pilot open-label clinical trial to obtain preliminary data on the adherence, tolerability and safety profiles of nabilone in adults with IDD, and explore changes in SBPs pre- to post-treatment. We hypothesize that nabilone has favorable tolerability and safety profile for adults with IDD. The preliminary results will inform the next-stage pilot randomized controlled trials, followed by fully powered clinical trials eventually. This research helps fill the evidence gap in the use of cannabinoids in individuals with IDD to meet the needs of patients, families, and service providers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mitochondrial Hsp60 (mtHsp60) plays a crucial role in maintaining the proper folding of proteins in the mitochondria. mtHsp60 self-assembles into a ring-shaped heptamer, which can further form a double-ring tetradecamer in the presence of ATP and mtHsp10. However, mtHsp60 tends to dissociate in vitro, unlike its prokaryotic homologue, GroEL. The molecular structure of dissociated mtHsp60 and the mechanism behind its dissociation remain unclear. In this study, we demonstrated that Epinephelus coioides mtHsp60 (EcHsp60) can form a dimeric structure with inactive ATPase activity. The crystal structure of this dimer reveals symmetrical subunit interactions and a rearranged equatorial domain. The α4 helix of each subunit extends and interacts with its adjacent subunit, leading to the disruption of the ATP-binding pocket. Furthermore, an RLK motif in the apical domain contributes to stabilizing the dimeric complex. These structural and biochemical findings provide new insights into the conformational transitions and functional regulation of this ancient chaperonin., (© 2023 Lai et al.)

Given progress in water-quality analytical technology and the emergence of the Internet of Things (IoT) in recent years, compact and durable automated water-quality monitoring devices have substantial market potential. Due to susceptibility to the influence of interfering substances, which lowers measurement accuracy, existing automated online monitoring devices for turbidity, a key indicator of a natural water body, feature a single light source and are thus insufficient for more complicated water-quality measurement. The newly developed modularized water-quality monitoring device boasts dual light sources (VIS/NIR), capable of measuring the intensity of scattering, transmission, and reference light at the same time. Coupled with a water-quality prediction model, it can attain a good estimate for continuing monitoring of tap water (<2 NTU, error < 0.16 NTU, relative error < 19.6%) and environmental water samples (<400 NTU, error < 3.86 NTU, relative error < 2.3%). This indicates the optical module can both monitor water quality in low turbidity and provide water-treatment information alerts in high turbidity, thereby materializing automated water-quality monitoring.

A set of highly connected brain regions called the "rich-club" are vital in integrating information across the functional connectome. Although the literature has identified some changes in rich-club organization with age, little is known about potential sex-specific developmental trajectories, and neurophysiologically relevant frequency-dependent changes have not been established. Here we examine the frequency- and sex-dependent development of rich-club organization using magnetoencephalography in a large normative sample ( N  = 383) over a wide age span (4-39 years). We report strong divergence between males and females across alpha, beta, and gamma frequencies. While males show increased or no change in rich-club organization with age, females show a consistent, non-linear trajectory that increases through childhood, shifting direction in early adolescence. Using neurophysiological modalities for capturing complex inter-relations between oscillatory dynamics, age, and sex, we establish diverging, sex-specific developmental trajectories of the brain's core functional organization, critically important to our understanding of brain health and disease., Competing Interests: E. Anagnostou has served as a consultant to Roche, Quadrant Therapeutics, ONO, and Impel Pharmaceuticals, holds a patent for the device, “Anxiety Meter,” and has received in kind support from AMO pharma and CRA, royalties from APPI and Springer, and editorial honoraria from Wiley. The remaining authors have reported no financial interests or potential conflicts of interest., (© 2023 The Author(s).)

Glutamate is an essential excitatory neurotransmitter in the central nervous system, playing an indispensable role in neuronal development and memory formation. The dysregulation of glutamate receptors and the glutamatergic system is involved in numerous neurological and psychiatric disorders, especially epilepsy. There are two main classes of glutamate receptor, namely ionotropic and metabotropic (mGluRs) receptors. The former stimulate fast excitatory neurotransmission, are N -methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate; while the latter are G-protein-coupled receptors that mediate glutamatergic activity via intracellular messenger systems. Glutamate, glutamate receptors, and regulation of astrocytes are significantly involved in the pathogenesis of acute seizure and chronic epilepsy. Some glutamate receptor antagonists have been shown to be effective for the treatment of epilepsy, and research and clinical trials are ongoing.

Objective: Autism spectrum disorder (ASD) is significantly over-represented among transgender adolescents. Independently, ASD and gender diversity are associated with increased mental health risks. Yet, mental health in autistic-transgender adolescents is poorly understood. This study investigates mental health in the largest matched sample to date of autistic-transgender, non-autistic (allistic) transgender, and autistic-cisgender adolescents diagnosed using gold-standard ASD diagnostic procedures. In accordance with advancing understanding of sex/gender-related autism phenotypes, slightly subthreshold autistic diagnostic presentations (common in autistic girls/women) are modeled., Method: This study includes 93 adolescents aged 13-21, evenly divided between autistic-transgender, autistic-cisgender, and allistic-transgender groups; 13 transgender adolescents were at the margin of ASD diagnosis and included within a larger "broad-ASD" grouping. Psychological and neuropsychological evaluation included assessment of mental health, IQ, LGBT stigma, ASD-related social symptoms, executive functioning (EF), and EF-related barriers to achieving gender-related needs., Results: Autistic-transgender adolescents experienced significantly greater internalizing symptoms compared to allistic-transgender and autistic-cisgender groups. In addition to stigma-related associations with mental health, ASD-related cognitive/neurodevelopmental factors (i.e., poorer EF and greater social symptoms) were associated with worse mental health: specifically, social symptoms and EF gender barriers with greater internalizing and EF problems and EF gender barriers with greater suicidality. Comparing across all ASD and gender-related groups, female gender identity was associated with greater suicidality., Conclusions: Parsing the heterogeneity of mental health risks among transgender youth is critical for developing targeted assessments and interventions. This study identifies ASD diagnosis, ASD phenotypic characteristics, and EF-related gender barriers as potential risks for poorer mental health in transgender adolescents.

Perovskite light-emitting diodes (LEDs) have attracted broad attention due to their rapidly increasing external quantum efficiencies (EQEs) 1-15 . However, most high EQEs of perovskite LEDs are reported at low current densities (<1 mA cm -2 ) and low brightness. Decrease in efficiency and rapid degradation at high brightness inhibit their practical applications. Here, we demonstrate perovskite LEDs with exceptional performance at high brightness, achieved by the introduction of a multifunctional molecule that simultaneously removes non-radiative regions in the perovskite films and suppresses luminescence quenching of perovskites at the interface with charge-transport layers. The resulting LEDs emit near-infrared light at 800 nm, show a peak EQE of 23.8% at 33 mA cm -2 and retain EQEs more than 10% at high current densities of up to 1,000 mA cm -2 . In pulsed operation, they retain EQE of 16% at an ultrahigh current density of 4,000 mA cm -2 , along with a high radiance of more than 3,200 W s -1  m -2 . Notably, an operational half-lifetime of 32 h at an initial radiance of 107 W s -1  m -2 has been achieved, representing the best stability for perovskite LEDs having EQEs exceeding 20% at high brightness levels. The demonstration of efficient and stable perovskite LEDs at high brightness is an important step towards commercialization and opens up new opportunities beyond conventional LED technologies, such as perovskite electrically pumped lasers., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The origins of the male preponderance in autism incidence remain unclear. The idea that perinatal factors associated with sex differentiation (e.g., steroid hormone pathways) may increase the possibility of the emergence of autism is complementary to the hypothesis that female individuals are intrinsically less likely to develop autism. Empirical evidence for the mechanistic roles of in utero steroid hormones in autism etiology is accumulating but inconsistent. We conducted a systematic review using rigorous criteria for the measurements of steroids and vitamin D exposure, to summarize the potential contributing roles of prenatal and early postnatal steroids and vitamin D alterations to the emergence of autism. We searched PubMed, PsychInfo, Scopus, and included 22 studies for qualitative synthesis. Among them, six studies examined the association of autism diagnoses in offspring and levels of steroids and precursor steroid hormones in the fetal environment, eight studies examined the associations between autism and maternal and fetal blood vitamin D levels during pregnancy and at birth, and eight studies examined the associations between offspring autism diagnoses and maternal hyperandrogenemia diagnosed before pregnancy. We identified promising and complex results regarding the relations between steroid metabolism and autism. The interpretation of findings was limited by the mostly observational study designs, insufficient investigation of the effects of offspring sex, confounders and their cumulative effects on the development of the child, and unclear impact of the timing of steroids exposure and their effects on fetal neurodevelopment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD., Aims: Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD., Method: Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.6 years of age) and 181 typically developing participants (7.6-30.8 years of age)., Results: Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD., Conclusions: Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Health-related conditions often differ qualitatively or quantitatively between individuals of different birth-assigned sexes and gender identities, and/or with different gendered experiences, requiring tailored care. Studying the moderating and mediating effects of sex-related and gender-related factors on impairment, disability, wellbeing and health is of paramount importance especially for neurodivergent individuals, who are diagnosed with neurodevelopmental conditions with uneven sex/gender distributions. Researchers have become aware of the myriad influences that sex-related and gender-related variables have on the manifestations of neurodevelopmental conditions, and contemporary work has begun to investigate the mechanisms through which these effects are mediated. Here we describe topical concepts of sex and gender science, summarize current knowledge, and discuss research and clinical challenges related to autism, attention-deficit/hyperactivity disorder and other neurodevelopmental conditions. We consider sex and gender in the context of epidemiology, behavioural phenotypes, neurobiology, genetics, endocrinology and neighbouring disciplines. The available evidence supports the view that sex and gender are important contributors to the biological and behavioural variability in neurodevelopmental conditions. Methodological caveats such as frequent conflation of sex and gender constructs, inappropriate measurement of these constructs and under-representation of specific demographic groups (for example, female and gender minority individuals and people with intellectual disabilities) limit the translational potential of research so far. Future research and clinical implementation should integrate sex and gender into next-generation diagnostics, mechanistic investigations and support practices., (© 2023. Springer Nature Limited.)

Rapid and low-cost diagnosis of coronavirus disease 2019 (COVID-19) is essential to identify infected subjects, particularly asymptomatic cases, primarily to arrest the spread of the disease through local transmission. Antibody-based chromatographic serological tests, as an alternative to the RT-PCR technique, offer only limited help due to high false positives. We propose to exploit our cholesteric liquid crystal biosensor platform for one-step, wash-free, rapid detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus directly with minimal sample pre-processing. As mentioned above, cholesteric liquid crystals are an effective and innovative approach to healthcare as a rapid test for the diagnosis of COVID-19 and other diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Chung, Chuang, Wang, Lai, Hsu, Lin and Hsiao.)

Status epilepticus (SE) is a neurological emergency with a high mortality rate. When compared to chronic epilepsy, it is distinguished by the durability of seizures and frequent resistance to benzodiazepine (BZD). The Receptor Trafficking Hypothesis, which suggests that the downregulation of γ-Aminobutyric acid type A (GABAA) receptors, and upregulation of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play major roles in the establishment of SE is the most widely accepted hypothesis underlying BZD resistance. NMDA and AMPA are ionotropic glutamate receptor families that have important excitatory roles in the central nervous system (CNS). They are both essential in maintaining the normal function of the brain and are involved in a variety of neuropsychiatric diseases, including epilepsy. Based on animal and human studies, antagonists of NMDA and AMPA receptors have a significant impact in ending SE; albeit most of them are not yet approved to be in clinically therapeutic guidelines, due to their psychomimetic adverse effects. Although there is still a dearth of randomized, prospective research, NMDA antagonists such as ketamine, magnesium sulfate, and the AMPA antagonist, perampanel, are regarded to be reasonable optional adjuvant therapies in controlling SE, refractory SE (RSE) or super-refractory SE (SRSE), though there are still a lack of randomized, prospective studies. This review seeks to summarize and update knowledge on the SE development hypothesis, as well as clinical trials using NMDA and AMPA antagonists in animal and human studies of SE investigations.

Background: Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services., Methods: Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups., Results: Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup., Limitations: Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic., Conclusions: Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis., (© 2023. The Author(s).)

Soybean is highly sensitive to flooding and extreme rainfall. The phenotypic variation of flooding tolerance is a complex quantitative trait controlled by many genes and their interaction with environmental factors. We previously constructed a gene-pool relevant to soybean flooding-tolerant responses from integrated multiple omics and non-omics databases, and selected 144 prioritized flooding tolerance genes (FTgenes). In this study, we proposed a comprehensive framework at the systems level, using competitive (hypergeometric test) and self-contained (sum-statistic, sum-square-statistic) pathway-based approaches to identify biologically enriched pathways through evaluating the joint effects of the FTgenes within annotated pathways. These FTgenes were significantly enriched in 36 pathways in the Gene Ontology database. These pathways were related to plant hormones, defense-related, primary metabolic process, and system development pathways, which plays key roles in soybean flooding-induced responses. We further identified nine key FTgenes from important subnetworks extracted from several gene networks of enriched pathways. The nine key FTgenes were significantly expressed in soybean root under flooding stress in a qRT-PCR analysis. We demonstrated that this systems biology framework is promising to uncover important key genes underlying the molecular mechanisms of flooding-tolerant responses in soybean. This result supplied a good foundation for gene function analysis in further work., (© 2023. The Author(s).)

Degenerative diseases of the brain include Parkinson's disease (PD), which is associated with moveable signs and is still incurable. Hispidin belongs to polyphenol and originates primarily from the medicinal fungi Inonotus and Phellinus, with distinct biological effects. In the study, MES23.5 cells were induced by 1-methyl-4-phenylpyridinium (MPP + ) to build a cell model of PD in order to detect the protective effect of hispdin and to specify the underlying mechanism. Pretreatment of MES23.5 cells with 1 h of hispdin at appropriate concentrations, followed by incubation of 24 h with 2 μmol/L MPP + to induce cell damage. MPP + resulted in reactive oxygen species production that diminished cell viability and dopamine content. Mitochondrial dysfunction in MS23.5 cells exposed to MPP + was observed, indicated by inhibition of activity in the mitochondrial respiratory chain complex I, the collapse of potential in mitochondrial transmembrane, and the liberation of mitochondrial cytochrome c. Enabling C-Jun N-terminal kinase (JNK), reducing Bcl-2/Bax, and enhancing caspase-9/caspase-3/PARP cleavage were also seen by MPP + induction associated with increased DNA fragmentation. All of the events mentioned above associated with MPP + -mediated mitochondrial-dependent caspases cascades were attenuated under cells pretreatment with hispidin (20 µmol/L); similar results were obtained during cell pretreatment with pan-JNK inhibitor JNK-IN-8 (1 µmol/L) or JNK3 inhibitor SR3576 (25 µmol/L). The findings show that hispidin has neuroprotection against MPP + -induced mitochondrial dysfunction and cellular apoptosis and suggest that hispidin can be seen as an assist in preventing PD.

Background: Autism is not always considered for girls and women until later along their clinical diagnostic pathways. Misdiagnosis or late diagnosis can pose significant disadvantages with respect to accessing timely health and autism-related services and supports. Understanding what contributes to roadblocks and detours along clinical pathways to an autism diagnosis can shed light on missed opportunities for earlier recognition., Objective: Our objective was to examine what contributed to roadblocks, detours, and missed opportunities for earlier recognition and clinical diagnosis of autism for girls and women., Design: We conducted a qualitative secondary analysis using data from a Canadian primary study that examined the health and healthcare experiences of autistic girls and women through interviews and focus groups., Methods: Transcript data of 22 girls and women clinically diagnosed with autism and 15 parents were analysed, drawing on reflexive thematic analysis procedures. Techniques included coding data both inductively based on descriptions of roadblocks and detours and deductively based on conceptualizations of sex and gender. Patterns of ideas were categorized into themes and the 'story' of each theme was refined through writing and discussing analytic memos, reflecting on sex and gender assumptions, and creating a visual map of clinical pathways., Results: Contributing factors to roadblocks, detours, and missed opportunities for earlier recognition and diagnosis were categorized as follows: (1) age of pre-diagnosis 'red flags' and 'signals'; (2) 'non-autism' mental health diagnoses first; (3) narrow understandings of autism based on male stereotypes; and (4) unavailable and unaffordable diagnostic services., Conclusion: Professionals providing developmental, mental health, educational, and/or employment supports can be more attuned to nuanced autism presentations. Research in collaboration with autistic girls and women and their childhood caregivers can help to identify examples of nuanced autistic features and how context plays a role in how these are experienced and navigated.

Objective: The male preponderance in prevalence of autism is among the most pronounced sex ratios across neurodevelopmental conditions. The authors sought to elucidate the relationship between autism and typical sex-differential neuroanatomy, cognition, and related gene expression., Methods: Using a novel deep learning framework trained to predict biological sex based on T 1 -weighted structural brain images, the authors compared sex prediction model performance across neurotypical and autistic males and females. Multiple large-scale data sets comprising T 1 -weighted MRI data were employed at four stages of the analysis pipeline: 1) pretraining, with the UK Biobank sample (>10,000 individuals); 2) transfer learning and validation, with the ABIDE data sets (1,412 individuals, 5-56 years of age); 3) test and discovery, with the EU-AIMS/AIMS-2-TRIALS LEAP data set (681 individuals, 6-30 years of age); and 4) specificity, with the NeuroIMAGE and ADHD200 data sets (887 individuals, 7-26 years of age)., Results: Across both ABIDE and LEAP, features positively predictive of neurotypical males were on average significantly more predictive of autistic males (ABIDE: Cohen's d=0.48; LEAP: Cohen's d=1.34). Features positively predictive of neurotypical females were on average significantly less predictive of autistic females (ABIDE: Cohen's d=1.25; LEAP: Cohen's d=1.29). These differences in sex prediction accuracy in autism were not observed in individuals with ADHD. In autistic females, the male-shifted neurophenotype was further associated with poorer social sensitivity and emotional face processing while also associated with gene expression patterns of midgestational cell types., Conclusions: The results demonstrate an increased resemblance in both autistic male and female individuals' neuroanatomy with male-characteristic patterns associated with typically sex-differential social cognitive features and related gene expression patterns. The findings hold promise for future research aimed at refining the quest for biological mechanisms underpinning the etiology of autism.

Advances in stroke treatment have resulted in a dramatic reduction in stroke mortality. Nevertheless, poststroke seizures and epilepsy are issues of clinical importance affecting survivors. Additionally, stroke is the most common cause of epilepsy in older adults. Although numerous antiseizure medications exist, studies are needed to provide robust evidence of the efficacy and tolerability of these medicines for treating poststroke seizures and epilepsy. Crucially, the newer generations of antiseizure medications require testing. Lacosamide, a third-generation antiseizure medication approved for treating localization-related epilepsy, has a novel mechanism of selectively enhancing the slow inactivation of sodium channels. This literature review evaluated whether lacosamide is effective and safe for the treatment of poststroke seizures and epilepsy. This review critically analyzed studies published in major academic databases (Pubmed, Embase, and Cochrane Library) from inception through June 2022 regarding the interaction of lacosamide with poststroke seizures and epilepsy. We included clinical prospective, retrospective, and case studies on patients with poststroke seizure and epilepsy, lacosamide as a treatment for seizures, neuroprotection in animal models of seizures, and the safety of lacosamide when coadministering anticoagulants. Clinical studies revealed lacosamide to be an effective antiseizure medication with high efficacy and tolerability in patients with poststroke seizures and epilepsy. In animal models, lacosamide proved effective at seizure reduction and neuroprotection. Pharmacokinetic studies demonstrated the safety of lacosamide when coadministering conventional and new anticoagulants. The literature suggests that Lacosamide is a promising candidate antiseizure medication for patients with poststroke seizures and epilepsy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Social attention affords learning opportunities across development and may contribute to individual differences in developmental trajectories, such as between male and female individuals, and in neurodevelopmental conditions, such as autism., Methods: Using eye-tracking, we measured social attention in a large cohort of autistic (n = 123) and nonautistic females (n = 107), and autistic (n = 330) and nonautistic males (n = 204), aged 6-30 years. Using mixed Growth Curve Analysis, we modelled sex and diagnostic effects on the temporal dynamics of proportional looking time to three types of social stimuli (lean-static, naturalistic-static, and naturalistic-dynamic) and examined the link between individual differences and dimensional social and nonsocial autistic traits in autistic females and males., Results: In the lean-static stimulus, average face-looking was higher in females than in males of both autistic and nonautistic groups. Differences in the dynamic pattern of face-looking were seen in autistic vs. nonautistic females, but not males, with face-looking peaking later in the trial in autistic females. In the naturalistic-dynamic stimulus, average face-looking was higher in females than in males of both groups; changes in the dynamic pattern of face looking were seen in autistic vs. nonautistic males, but not in females, with a steeper peak in nonautistic males. Lower average face-looking was associated with higher observer-measured autistic characteristics in autistic females, but not in males., Conclusions: Overall, we found stronger social attention in females to a similar degree in both autistic and nonautistic groups. Nonetheless, the dynamic profiles of social attention differed in different ways in autistic females and males compared to their nonautistic peers, and autistic traits predicted trends of average face-looking in autistic females. These findings support the role of social attention in the emergence of sex-related differences in autistic characteristics, suggesting an avenue to phenotypic stratification., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Severe combustion cycle-to-cycle variations (CCVs) in spark ignition (SI) engines significantly increase partial or incomplete combustion cycles, which may result in combustion instability or even misfire under extreme conditions, thereby seriously affecting the engine performance and increasing the unburned hydrocarbon and carbon monoxide emissions. In this study, the consecutive cycle method (CCM) and parallel perturbation method (PPM) are utilized to simulate the CCVs in a natural-gas (NG) SI engine. Specifically, 25 consecutive and concurrent cycles of the SI engine are simulated, and simulation results are compared with the experimental data. Further, the factors affecting the CCVs and exhaust emissions in the NG SI engine are verified by analyzing the low-pressure (LP) and high-pressure (HP) cycles. The results indicate that the simulated in-cylinder pressures of the NG SI engine based on PPM are basically in agreement with the experimental in-cylinder pressure distribution range, which suggests that the PPM can effectively predict the CCVs in NG SI engines. Furthermore, the required wall clock time for the simulation of CCVs is greatly reduced from 1 to 2 months (using CCM) to 2-3 days by using the PPM, which makes it particularly suitable for the industrial applications. Besides, the velocity field of the HP cycle is obviously stronger than that of the LP cycle. During the early stage of flame development, the flame area and volume of LP and HP cycles do not show much difference. However, the flame front surface-volume ratio of the HP cycle is larger than that of the LP cycle at 15 CA after the spark timing. Furthermore, the emissions formation and oxidation of the NG SI engine are strongly depended on the HP and LP cycles due to the combustion rate and flame propagation in the cylinder., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) is a progressive disorder that affects brain nerve cells responsible for body motion and remains incurable. p-Hydroxybenzyl alcohol (HBA) is the primary phenolic compound in Gastrodiae Rhizoma, known for its therapeutic benefits against neurodegeneration. However, the protective effect of HBA against Parkinson's disease (PD) remains unclear. The objective of this study was to evaluate the neuroprotective effects of HBA in vitro 6-hydroxydopamine (6-OHDA)-induced PD model in SH-SY5Y cells. SH-SY5Y cells were pretreated with various concentrations of HBA for 1 h and incubated with 100 μmol/L 6-OHDA for 24 h to induce cellular lesions. 2,5-Diphenyl-2H-tetrazolium bromide was used to detect cellular viability. 2',7'-dichlorofluorescin oxidation detects reactive oxygen species (ROS). The enzyme-linked immunosorbent assay was used to determine the activities of superoxide dismutase, catalase, and glutathione peroxidase. The cellular mitochondrial function was identified through the collapse of the mitochondrial membrane potential, the release of cytochrome c, and the synthesis of mitochondrial ATP. Expression of pro-and anti-apoptotic factors was measured by Western blot. HBA enhanced cell viability, blocked ROS overproduction, and reduced antioxidant activities induced by 6-OHDA. HBA also reduced mitochondrial dysfunction and cell death caused by 6-OHDA. Moreover, HBA reversed the 6-OHDA-mediated activation of c-Jun N-terminal kinase, the downregulation of the Bcl-2/Bax ratio, the Apaf-1 upregulation and the induction of caspase-9, caspase-3, and PARP cleavage. This study shows that the protective effects of HBA against 6-OHDA-induced cell injury provide the potential preventive effects of HBA, making it a promising preventive agent for PD.

Rufinamide (RFM) is a clinically utilized antiepileptic drug that, as a triazole derivative, has a unique structure. The extent to which this drug affects membrane ionic currents remains incompletely understood. With the aid of patch clamp technology, we investigated the effects of RFM on the amplitude, gating, and hysteresis of ionic currents from pituitary GH 3 lactotrophs. RFM increased the amplitude of Ca 2+ -activated K + currents ( I K(Ca) ) in pituitary GH 3 lactotrophs, and the increase was attenuated by the further addition of iberiotoxin or paxilline. The addition of RFM to the cytosolic surface of the detached patch of membrane resulted in the enhanced activity of large-conductance Ca 2+ -activated K + channels (BK Ca channels), and paxilline reversed this activity. RFM increased the strength of the hysteresis exhibited by the BK Ca channels and induced by an inverted isosceles-triangular ramp pulse. The peak and late voltage-gated Na + current ( I Na ) evoked by rapid step depolarizations were differentially suppressed by RFM. The molecular docking approach suggested that RFM bound to the intracellular domain of K Ca 1.1 channels with amino acid residues, thereby functionally affecting BK Ca channels' activity. This study is the first to present evidence that, in addition to inhibiting the I Na , RFM effectively modifies the I K(Ca) , which suggests that it has an impact on neuronal function and excitability.

Epilepsy is a common neurological disorder; 1% of people worldwide have epilepsy. Differentiating epileptic seizures from other acute neurological disorders in a clinical setting can be challenging. Approximately one-third of patients have drug-resistant epilepsy that is not well controlled by current antiepileptic drug therapy. Surgical treatment is potentially curative if the epileptogenic focus is accurately localized. Diffusion-weighted imaging (DWI) is an advanced magnetic resonance imaging technique that is sensitive to the diffusion of water molecules and provides additional information on the microstructure of tissue. Qualitative and quantitative analysis of peri-ictal, postictal, and interictal diffusion images can aid the differential diagnosis of seizures and seizure foci localization. This review focused on the fundamentals of DWI and its associated techniques, such as apparent diffusion coefficient, diffusion tensor imaging, and tractography, as well as their impact on epilepsy in terms of differential diagnosis, epileptic foci determination, and prognosis prediction.

Oxytocin is hypothesized to promote social interactions by enhancing the salience of social stimuli. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to face stimuli in autistic men, effects in autistic women remain unclear. In this study, the influence of intranasal oxytocin on activation and functional connectivity of the basolateral amygdala-the brain's 'salience detector'-while processing emotional faces vs shapes was tested in 16 autistic and 21 non-autistic women by functional magnetic resonance imaging in a placebo-controlled, within-subject, cross-over design. In the placebo condition, minimal activation differences were observed between autistic and non-autistic women. However, significant drug × group interactions were observed for both basolateral amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35-voxel cluster, Montreal Neurological Institute (MNI) coordinates of peak voxel = -22 -10 -28; mean change = +0.079%, t = 3.159, PTukey = 0.0166) but not among non-autistic women (mean change = +0.003%, t = 0.153, PTukey = 0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not in non-autistic women, attenuating group differences in the placebo condition. Taken together, these findings extend evidence of oxytocin's effects on the amygdala to specifically include autistic women and specify the subregion of the effect., (© The Author(s) 2022. Published by Oxford University Press.)

The N-terminal pro-brain natriuretic peptide (NT-proBNP) is considered an important blood biomarker for heart failure. Herein, we report about a fiber optic nanogold-linked immunosorbent assay (FONLISA) method for the rapid, sensitive, and low-cost detection of NT-proBNP. The method is based on a sandwich immunoassay approach that uses two monoclonal NT-proBNP antibodies, a capture antibody (Ab C ), and a detection antibody (Ab D ). Ab D is conjugated to a free gold nanoparticle (AuNP) to form the free AuNP@Ab D conjugate, and Ab C is immobilized on an unclad segment of an optical fiber. The detection of analyte (A), in this case NT-proBNP, is based on the signal change due to the formation of an AuNP@Ab D -A-Ab C complex on the fiber core surface, where a green light transmitted through the optical fiber will decrease in intensity due to light absorption by AuNPs via the localized surface plasmon resonance effect. This method provides a wide linear dynamic range of 0.50~5000 pg·mL -1 and a limit of detection of 0.058 pg·mL -1 for NT-proBNP. Finally, the method exhibits good correlation ( r = 0.979) with the commercial central laboratory-based electrochemiluminescent immunoassay method that uses a Roche Cobas e411 instrument. Hence, our method is potentially a suitable tool for point-of-care testing.

Objectives: Emerging evidence implicates atypical plasticity in the neurophysiology of autism spectrum disorder (ASD). Specifically, autistic people demonstrated hyperplasticity in response to theta-burst stimulation (TBS). We hypothesized that autistic adults would display hyperplasticity to TBS and that repetitive transcranial magnetic stimulation (rTMS) - which potentiates brain inhibitory mechanisms - would 'stabilize' hyperplasticity., Methods: Using a randomized, cross-over design, plasticity was assessed using TBS in the left motor cortex (M1) in 31 autistic adults and 30 sex-, intelligence quotient-, and age-matched controls. Autistic adults (n = 29) were further randomized (1:1) to receive a single session of active (n = 14) or sham (n = 15) rTMS (6000 pulses at 20 Hz) over left M1 and plasticity was reassessed on the next day following rTMS., Results: Both long-term potentiation (LTP) and long-term depression (LTD) were significantly increased in the ASD group, indicating hyperplasticity. Active, but not sham rTMS, attenuated LTD in autistic adults., Conclusions: We provided further evidence for the presence of brain hyperplasticity in ASD. To our knowledge, this is the first study to show preliminary evidence that an excessive LTD in ASD can be 'stabilized' using rTMS. Such 'stabilizing' effect of rTMS on LTP was not observed, likely due to small sample size or a more specific 'attenuating' effect of rTMS on LTD, compared to LTP., Significance: These findings indicate atypical brain inhibitory mechanisms behind hyperplasticity in ASD. Utilizing a larger sample, future replication studies could investigate therapeutic opportunities of 'mechanism-driven' rTMS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Social performances pervade human interactions. Some autistic people describe their social performances as 'camouflaging' and engage in these performances to mitigate social challenges and survive in the neurotypical world. Here, we reconsider autistic camouflaging under the unifying framework of impression management (IM) by examining overlapping and unique motivations, neurocognitive mechanisms, and consequences. Predictive coding and Bayesian principles are synthesized into a computational model of IM that applies to autistic and neurotypical people. Throughout, we emphasize the inherently transactional, context-dependent nature of IM, the distinct computational challenges faced by autistic people, and the psychological toll that compelled IM can take. Viewing camouflaging through this lens highlights the pressing needs to change societal attitudes, destigmatize autism, refine social skills-building programs for autistic individuals, and integrate these programs with environment-focused support., Competing Interests: Declaration of interests We have no conflict of interests to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: ATP-binding cassette transporter G1 (ABCG1) regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity. But, for hepatocellular carcinoma (HCC), the role of ABCG1 has not been investigated. Thus, the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC., Methods: One hundred and four adult patients with HCC were enrolled, and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry. All these patients were stratified by ABCG1 expression, Kaplan-Meier analysis was used to compare the overall survival (OS) and recurrence-free survival (RFS), and Cox regression analysis was used to determine independent predictors of tumor recurrence., Results: Upregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues. Patients with high nuclear ABCG1 expression had lower OS and RFS (P = 0.012 and P = 0.020, respectively). High nuclear ABCG1 expression was related to larger tumor size (P = 0.004) and tumor recurrence (P = 0.027). Although ABCG1 was expressed in the cytoplasm, cytosolic expression could not predict the outcome in patients with HCC. A new stratification pattern was established based on the heterogenous ABCG1 expression pattern: high risk (High nucleus /Low cytosol ), moderate risk (High nucleus /High cytosol or Low nucleus /Low cytosol ), and low risk (Low nucleus /High cytosol ). This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with HCC. Multivariate Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS (P = 0.015)., Conclusions: High nuclear ABCG1 expression indicates poor prognosis in patients with HCC. Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence., (Copyright © 2022 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Research from different countries suggests that autistic adults are more likely to die prematurely than non-autistic adults, but these studies do not always investigate male and female individuals separately and do not consider whether this pattern is unique to autistic people or is also an issue for people with other developmental disabilities. We examined premature mortality in autistic males and females (assigned at birth) in a population-based cohort, compared to males and females with and without other developmental disabilities. Using linked administrative health and social services population data from Ontario, Canada, age-matched males and females aged 19-65 years were followed between 2010 and 2016, and causes of death were determined. Over the 6-year observation period, 330 of 42,607 persons (0.77%) in the group without developmental disabilities had died compared to 259 of 10,646 persons (2.43%) in the autism group and 419 of 10,615 persons (3.95%) in the other developmental disabilities group. Autistic males and females were more likely to die than non-autistic males (adjusted risk ratio, RR 3.13, 95%CI 2.58-3.79) and non-autistic females (adjusted RR 3.12, 95%CI 2.35-4.13) without developmental disabilities, but were less likely to die than adults with other developmental disabilities (males: adjusted RR 0.66, 95%CI 0.55-0.79; females: adjusted RR 0.55, 95%CI 0.43-0.71). Most common causes of death varied depending on a person's sex and diagnosis. Given the greater likelihood of premature mortality in adults with developmental disabilities including autism, greater attention and resources directed toward their health and social care are needed, tailored to their sex and diagnosis-informed needs. LAY SUMMARY: This study looked at how many autistic men and women died over 6 years (2010-2016), along with how they died, and compared this to adults who did not have autism living in Ontario, Canada. It found that autistic men and women were more than three times as likely to die as people of the same age who did not have a developmental disability. However, adults with other developmental disabilities besides autism were even more likely to die than autistic adults. This means that we have to pay more attention and invest in better social and health care for autistic people, along with people who have other types of developmental disabilities., (© 2022 International Society for Autism Research and Wiley Periodicals LLC.)

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Brain functional connectivity in adolescents who experience GD may be associated with experienced gender (vs. assigned sex) and/or brain networks implicated in own-body perception. Furthermore, sexual orientation may be related to brain functional organization given commonalities in developmental mechanisms proposed to underpin GD and same-sex attractions. Here, we applied group independent component analysis to resting-state functional magnetic resonance imaging (rs-fMRI) BOLD timeseries data to estimate inter-network (i.e., between independent components) timeseries correlations, representing functional connectivity, in 17 GD adolescents assigned female at birth (AFAB) not receiving gender-affirming hormone therapy, 17 cisgender girls, and 15 cisgender boys (ages 12-17 years). Sexual orientation was represented by degree of androphilia-gynephilia and sexual attractions strength. Multivariate partial least squares analyses found that functional connectivity differed among cisgender boys, cisgender girls, and GD AFAB, with the largest difference between cisgender boys and GD AFAB. Regarding sexual orientation and age, the brain's intrinsic functional organization of GD AFAB was both similar to and different from cisgender girls, and both differed from cisgender boys. The pattern of group differences and the networks involved aligned with the hypothesis that brain functional organization is different among GD AFAB (vs. cisgender) adolescents, and certain aspects of this organization relate to brain areas implicated in own-body perception and self-referential thinking. Overall, brain functional organization of GD AFAB was generally more similar to that of cisgender girls than cisgender boys., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Skorska, Lobaugh, Lombardo, van Bruggen, Chavez, Thurston, Aitken, Zucker, Chakravarty, Lai and VanderLaan.)

Background: Externalizing and internalizing behaviors contribute to clinical impairment in children with neurodevelopmental disorders (NDDs). Although associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in clinical and non-clinical pediatric samples, no previous study has examined whether similar shared associations are present across children with different NDDs., Methods: Multi-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6-18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging (DWI) and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (total n = 346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined., Results: No significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results., Conclusions: The current study provides evidence towards an absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with different primary NDD diagnoses and TDC. Different methodological approaches, including incorporation of multi-dimensional behavioral data (e.g., task-based fMRI) or clustering approaches may be needed to clarify complex brain-behavior relationships relevant to externalizing/internalizing behaviors in heterogeneous clinical NDD populations., (© 2022. The Author(s).)

Restricted and repetitive behaviors (RRBs) are hallmark characteristics of autism spectrum disorder (ASD). Previous studies suggest that insistence on sameness (IS) characterized as higher-order RRBs may be a promising subgrouping variable for ASD. Cognitive inflexibility may underpin IS behaviors. However, the neuroanatomical correlates of IS and associated cognitive functions remain unclear. We analyzed data from 140 autistic youth and 124 typically developing (TD) youth (mean age = 15.8 years). Autistic youth were stratified by median-split based on three current IS items in the autism diagnostic interview-revised into two groups (high, HIS, n = 70, and low, LIS, n = 70). Differences in cognitive flexibility were assessed by the Cambridge neuropsychological test automated battery (CANTAB). T1-weighted brain structural images were analyzed using voxel-based morphometry (VBM) to identify differences in gray matter (GM) volume among the three groups. GM volume of regions showing group differences was then correlated with cognitive flexibility. The HIS group showed decreased GM volumes in the left supramarginal gyrus compared to the LIS group and increased GM volumes in the vermis VIII and left cerebellar lobule VIII compared to TD individuals. We did not find significant correlations between regional GM volumes and extra-dimensional shift errors. IS may be a unique RRB component and a potentially valuable stratifier of ASD. However, the neurocognitive underpinnings require further clarification. LAY SUMMARY: The present study found parietal, temporal and cerebellar gray matter volume alterations in autistic youth with greater insistence on sameness. The findings suggest that insistence on sameness may be a useful feature to parse the heterogeneity of the autism spectrum yet further research investigating the underlying neurocognitive mechanism is warranted., (© 2022 International Society for Autism Research, Wiley Periodicals LLC.)

The purpose of this study was to understand the effects of a physical activity program and high-protein supplementation on body composition and upper and lower extremity muscle strength in male older adults in rural areas. In this study, 60 healthy male older adults (mean age 77.5 ± 4.6 years) from rural areas were recruited and randomly assigned to experimental group A (intervention of the physical activity program and high-protein supplementation), experimental group B (daily routine, with only intervention of high-protein supplementation), or control group C (daily routine). Experimental group A (EGa) carried out a physical activity plan three times a week, with an exercise intensity and calorie consumption of 250 kcal (5METs × ⅔hr × 75) for 3 months and drank a high-protein supplement (1.3 g/kg BW/day) after each exercise; experimental group B (EGb) followed only the intervention of high-protein supplementation. All the participants underwent pre- and post-tests for body composition, waist-hip circumference (WC, HC), handgrip strength (HS), 30 s dominant arm curl, 30 s sit to stand, and 2 min step tests. The results of the study showed that EGa significantly decreased body mass index (BMI), body fat mass (BFM), body fat percentage (BFP), WC, HC, and waist-to-hip ratio (WHR) and increased basal metabolic rate and muscle mass. Although both EGa and EGb used high-protein supplementation, EGa's added three-month intervention of a physical activity program made it easier for that group to increase muscle mass and muscle strength. The WHR decreased from 1.015 to 0.931, representing a decrease of 8.28%, and an obvious weight loss effect was achieved. Thus, we concluded that the best way to maintain muscle strength in older adults is through physical activity with resistance and protein supplementation, which can reduce muscle loss in older adults.

Suicidality is increased in autism spectrum disorder (ASD), yet effective interventions are lacking. Developing biologically based approaches for preventing and treating suicidality in ASD hinges on the identification of biomarkers of suicidal ideation (SI). Here, we assessed magnetic resonance spectroscopy (MRS) markers of glutamatergic neurotransmission in ASD youth and young adults. Twenty-eight ASD participants (16-33 years) underwent 1 H-MRS, and metabolites were quantified using LCModel. N-acetylaspartate (NAA), glutamate (Glu), and the NAA/Glu ratio from the left dorsolateral prefrontal cortex were compared between ASD SI+ ( n = 13) and ASD SI- ( n = 15) participants. We found that ASD SI+ participants had a higher NAA/Glu ratio compared ASD SI- participants. The NAA/Glu ratio also predicted SI and significantly discriminated between ASD SI+/SI- participants. All analyses including NAA and Glu alone were non-significant. Here, we provide preliminary evidence for the importance of NAA/Glu in ASD with SI, with implications for biomarker discovery. Further mechanistic research into risk and interventional approaches to address SI in ASD are needed.

Epilepsy is a common chronic neurological disorder in modern society. One of the major unmet challenges is that current antiseizure medications are basically not disease-modifying. Among the multifaceted etiologies of epilepsy, the role of the immune system has attracted considerable attention in recent years. It is known that both innate and adaptive immunity can be activated in response to insults to the central nervous system, leading to seizures. Moreover, the interaction between ion channels, which have a well-established role in epileptogenesis and epilepsy, and the immune system is complex and is being actively investigated. Some examples, including the interaction between ion channels and mTOR pathways, will be discussed in this paper. Furthermore, there has been substantial progress in our understanding of the pathophysiology of epilepsy associated with autoimmune encephalitis, and numerous neural-specific autoantibodies have been found and documented. Early recognition of immune-mediated epilepsy is important, especially in cases of pharmacoresistant epilepsy and in the presence of signs of autoimmune encephalitis, as early intervention with immunotherapy shows promise.

Background: Pediatric brain tumor survivors (PBTS) are at risk of experiencing social competence challenges, but only a limited number of studies have used a qualitative approach to understand their social relationships. We examined PBTS responses to social interview questions within the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2), which includes questions related to their understanding of their own relationships, as well as the construct of friendship more generally., Methods: Twenty-four PBTS (ages 9-17 years; M = 14.2 years from diagnosis; 50% male; 42% received radiation treatment) completed the ADOS-2. ADOS-2 social interview responses were recorded and transcribed verbatim. Themes were derived using an inductive thematic analysis approach., Results: PBTS reported that they considered trust, acceptance, respect, emotional support, and spending time together to be important aspects of friendships in general. When describing their own social relationships, some PBTS noted a lack of intimacy or closeness, spending time with their friends almost exclusively at school, with structured activities outside of school being an additional basis for friendship. Challenges to their social relationships included loneliness and reliance on family for social support, experiences of teasing and bullying, social skills deficits, and lack of insight into social situations., Conclusion: Although PBTS were able to acknowledge many important qualities of friendships in general (e.g., trust, emotional support), these were not necessarily reported in their own friendships. PBTS also appeared to have difficulty identifying whether someone was their friend. These findings offer potential opportunities for supporting PBTS in achieving friendships consistent with their conception of this important relationship., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The present study aimed to evaluate the role of diosmetin in alleviating advanced glycation end products (AGEs)-induced Alzheimer's disease (AD)-like pathology and to clarify the action mechanisms. Before stimulation with AGEs (200 μg/mL), SH-SY5Y cells were treated with diosmetin (10 μmol/L), increasing cell viability. The induction of AGEs on the reactive oxygen species overproduction and downregulation of antioxidant enzyme activities, including superoxide dismutase, glutathione peroxidase, and catalase, were ameliorated by diosmetin. Amyloid precursor protein upregulation, accompanied by increased production of amyloid-β, caused by AGEs, was reversed by diosmetin. In the presence of diosmetin, not only β-site amyloid precursor protein cleaving enzyme1 expression was lowered, but the protein levels of insulin-degrading enzyme and neprilysin were elevated. Diosmetin protects SH-SY5Y cells from endoplasmic reticulum (ER) stress response to AGEs by suppressing ER stress-induced glucose regulated protein 78, thereby downregulating protein kinase R-like endoplasmic reticulum kinase, eukaryotic initiation factor 2 α, activating transcription factor 4, and C/EBP homologous protein. Diosmetin-pretreated cells had a lower degree of apoptotic DNA fragmentation; this effect may be associated with B-cell lymphoma (Bcl) 2 protein upregulation, Bcl-2-associated X protein downregulation, and decreased activities of caspase-12/-9/-3. The reversion of diosmetin on the AGEs-induced harmful effects was similar to that produced by pioglitazone. The peroxisome proliferator-activated receptor (PPAR) γ antagonist T0070907 (5 μmol/L) abolished the beneficial effects of diosmetin on AGEs-treated SH-SY5Y cells, indicating the involvement of PPAR γ . We conclude that diosmetin protects neuroblastoma cells against AGEs-induced ER injury via multiple mechanisms and may be a potential option for AD.

Background: Executive functioning (EF) varies in children with autism spectrum disorder (ASD) and is associated with clinical symptoms, academic, and adaptive functioning. Here, we examined whether middle-childhood EF mediates associations between early-childhood autism symptoms and adolescent outcomes in children with ASD., Methods: The Pathways in ASD Cohort comprising children recruited at the time of ASD diagnosis (at 2-4 years-of-age) and followed prospectively across eight subsequent timepoints over ~10 years was used. A subset of Pathways participants (n = 250) with Behavior Rating Inventory of Executive Function (BRIEF)-Parent Form data from at least one timepoint when participants were school-aged was analyzed. A mediation framework was used to examine whether BRIEF-measured EF across age 7-10 years (middle-childhood) mediated associations between early-childhood autism symptoms (measured using the parent-report Social Responsiveness Scale across age 2-6 years) and clinical, academic, and functional outcomes, indexed at age >10-11.8 years (early-adolescence) using the Child Behavior Checklist (CBCL)-Internalizing and Externalizing Scales, Academic Performance from the Teacher's Report Form, and Vineland Adaptive Behavior Scales. Models were rerun substituting clinician-rated and teacher-rated measures, where possible., Results: Mediation models indicated a significant indirect effect of middle-childhood EF on associations between early-childhood autism symptoms and externalizing behavior, academic performance, or adaptive functioning in early adolescence; kappa squared (κ 2 ) effect sizes ranged from large to small. Model findings were stable across raters. Middle-childhood EF did not mediate associations between early-childhood autism symptoms and adolescent internalizing behavior., Conclusions: Among children with an ASD diagnosis, middle-childhood EF may be one pathway through which early-childhood autism symptoms influence a variety of outcomes in early-adolescence. An experimental study targeting middle-childhood EF to improve adolescent academic, emotional/behavioral, and adaptive functioning is needed to evaluate the clinical meaningfulness of these findings., (© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Despite increasing attention on suicidality in autistic people, we know little about suicidal presentations when autistic individuals present to hospital emergency departments (ED). We conducted an exploratory retrospective chart review of suicidal thoughts and behaviours (STB) of autistic adults who presented to a psychiatric ED. The analysis included 16 charts over a 10-week period. Findings highlight that reported STB were not always the presenting issue. Life transitions and interpersonal conflicts were common antecedents, and active rumination about STB was distressing and fatiguing. Findings imply that ED visits serve as important opportunities for suicidal risk reduction for autistic individuals, through implementation of strategies for identification of STB such as active screening, and the provision of suicide resources tailored to autistic people., (© 2021. The Author(s).)

Zingerone (ZO), a nontoxic methoxyphenol, has been demonstrated to exert various important biological effects. However, its action on varying types of ionic currents and how they concert in neuronal cells remain incompletely understood. With the aid of patch clamp technology, we investigated the effects of ZO on the amplitude, gating, and hysteresis of plasmalemmal ionic currents from both pituitary tumor (GH 3 ) cells and hippocampal (mHippoE-14) neurons. The exposure of the GH 3 cells to ZO differentially diminished the peak and late components of the I Na . Using a double ramp pulse, the amplitude of the I Na(P) was measured, and the appearance of a hysteresis loop was observed. Moreover, ZO reversed the tefluthrin-mediated augmentation of the hysteretic strength of the I Na(P) and led to a reduction in the I Ca,L . As a double ramp pulse was applied, two types of voltage-dependent hysteresis loops were identified in the I Ca,L , and the replacement with BaCl 2 -attenuated hysteresis of the I Ca,L enhanced the I Ca,L amplitude along with the current amplitude (i.e., the I Ba ). The hysteretic magnitude of the I Ca,L activated by the double pulse was attenuated by ZO. The peak and late I Na in the hippocampal mHippoE-14 neurons was also differentially inhibited by ZO. In addition to acting on the production of reactive oxygen species, ZO produced effects on multiple ionic currents demonstrated herein that, considered together, may significantly impact the functional activities of neuronal cells.

Purpose of Review: Sex/gender-related factors contribute to contextual issues influencing the recognition of autism and attention-deficit/hyperactivity disorder (ADHD), and modulate how neurodevelopmental characteristics are manifested. This review summarizes the empirical literature to provide directions for improving clinical diagnostic practices., Recent Findings: Timing of autism and/or ADHD diagnosis, particularly in girls/women, is related to the individual's developmental characteristics and co-occurring diagnoses, and expectancy, alongside gender stereotype biases, of referral sources and clinicians. This is further compounded by sex and gender modulations of behavioural presentations. The emerging 'female autism phenotype' concept may serve as a helpful illustration of nuanced autism phenotypes, but should not be viewed as essential features of autism in a particular sex or gender. These nuanced phenotypes that can present across sexes and genders include heightened attention to socially salient stimuli, friendship and social groups, richness in language expression, and more reciprocal behaviours. The nuanced female-predominant ADHD phenotypes are characterized by subtle expressions in hyperactivity-impulsivity (e.g., hyper-verbal behaviours). Optimizing neurodevelopmental diagnoses across sexes and genders also requires an understanding of sex-related and gender-related variations in developmental trajectories, including compensation/masking efforts, and the influences of co-occurring conditions on clinical presentations., Summary: Equitable diagnoses across sexes and genders for autism and ADHD require understanding of the nuanced presentations and the Gestalt clinical-developmental profiles, and addressing contextual biases that influence diagnostic practices., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)