457 results on '"Lai MC"'
Search Results
2. Social adjustment and family function after drug switch from IR -methylphenidate to OROS-methylphenidate in patients with attention-deficit/hyperactivity disorder
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Chou WJ, Wang LJ, Lin CH, Liang SY, Chen VCH, Hou YM, Huang RR, Chou MC, Shang CY, Ho CP, and Lai MC
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ADHD ,central nervous system stimulant ,drug adherence ,family ,social adjustment ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Wen-Jiun Chou,1 Liang-Jen Wang,1 Chien-Ho Lin,2 Sun-Yuan Liang,3 Vincent Chin-Hung Chen,4 Yuh-Ming Hou,5 Rong-Rong Huang,6 Miao-Chun Chou,1 Chi-Yung Shang,7 Chi-Pui Ho,6 Meng-Chuan Lai8 1Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 2Department of Psychiatry, Chimei Medical Center, Tainan, 3Department of Psychiatry, Changhua Hospital, Changhua, 4Department of Psychiatry, Chang Gung Memorial Hospital and University, 5Chia-Yi Christian Hospital, Chiayi, 6Department of Child and Adolescent Psychiatry, Kai-Suan Psychiatric Hospital, Kaohsiung, 7Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 8Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK Purpose: This prospective, single-arm, open-label, 8-week, multicenter study investigated the effectiveness of switching from immediate-release methylphenidate (IR-MPH) to osmotic controlled-release methylphenidate (OROS-MPH) in patients with attention-deficit/hyperactivity disorder (ADHD).Patients and methods: Overall, 296 patients with ADHD (mean age: 9.5 years) already on IR-MPH treatment were enrolled. Upon enrollment, a flexible dose of OROS-MPH was administered, replacing IR-MPH. Patients were assessed at baseline and weeks 2, 4, and 8 using the Swanson, Nolan, and Pelham version IV scale (SNAP-IV) and the Clinical Global Impression for ADHD symptoms. The Social Adjustment Inventory for Children and Adolescents assessed social functions, and the Chinese Health Questionnaire (CHQ) and Family Adaptation, Partnership, Growth, Affection, and Resolve evaluated parental and family functions.Results: Switching from IR-MPH to OROS-MPH yielded significant improvements in all ADHD symptoms, as rated by parents, teachers (SNAP-IV), and study investigators (Clinical Global Impression). CHQ scores and all Social Adjustment Inventory for Children and Adolescents subscores except spare time scores improved significantly. Patients with poor IR-MPH adherence had greater improvements in teacher-rated SNAP-IV and mothers’ mental health (CHQ) after switching. Conclusion: Switching from IR-MPH to OROS-MPH improved patients’ behavioral ADHD symptoms and social adjustment, and mental health of patients’ mothers. This was most evident in patients who previously exhibited poor IR-MPH adherence. Keywords: ADHD, central nervous system stimulant, drug adherence, family, social adjustment
- Published
- 2018
3. Oxytocin enhances basolateral amygdala activation and functional connectivity while processing emotional faces: preliminary findings in autistic versus non-autistic women
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Procyshyn, Tanya, Lombardo, Michael, Lai, MC, Jassim, Nazia, Auyeung, Bonnie, Crockford, Sarah, Deakin, J, Soubramanian, Sentil, Sule, Akeem, Terburg, David, Baron-Cohen, S, Bethlehem, R, Procyshyn, Tanya [0000-0003-1266-6697], Baron-Cohen, Simon [0000-0001-9217-2544], Bethlehem, Richard [0000-0002-0714-0685], and Apollo - University of Cambridge Repository
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Male ,Cross-Over Studies ,emotional face processing ,Basolateral Nuclear Complex ,Emotions ,autism ,salience ,Amygdala ,Oxytocin ,Magnetic Resonance Imaging ,Humans ,Female ,basolateral amygdala ,Administration, Intranasal - Abstract
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 fMRI in a placebo-controlled, within-subjects, 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, MNI coordinates of peak voxel= -22 -10 -28; mean change=+0.079%, t=3.159, ptukey=0.0166), but not 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 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.
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- 2022
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4. Putting on my best normal: Social camouflaging in adults with autism spectrum conditions, journal of autism and developmental disorders
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Hull, L, Petrides, KV, Allison, C, Smith, P, Baron-Cohen, S, Lai, MC, Mandy, W, Allison, Carrie [0000-0003-2272-2090], Baron-Cohen, Simon [0000-0001-9217-2544], and Apollo - University of Cambridge Repository
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- 2018
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5. Relationship Between Cortical Gyrification, White Matter Connectivity, and Autism Spectrum Disorder
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Ecker, C, Andrews, D, Dell'Acqua, F, Daly, E, Murphy, C, Catani, M, Thiebaut De Schotten, M, Baron-Cohen, S, Lai, MC, Lombardo, MV, Bullmore, ET, Suckling, J, Williams, S, Jones, DK, Chiocchetti, A, MRC AIMS Consortium, Murphy, DGM, Dell'Acqua, F [0000-0001-5313-5476], Thiebaut de Schotten, M [0000-0002-0329-1814], and Apollo - University of Cambridge Repository
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Adult ,Cerebral Cortex ,Male ,Adolescent ,Autism Spectrum Disorder ,brain connectivity ,Intelligence ,multimodal neuroimaging ,brain development ,Organ Size ,Magnetic Resonance Imaging ,White Matter ,Pattern Recognition, Automated ,Young Adult ,Diffusion Tensor Imaging ,Imaging, Three-Dimensional ,Neural Pathways ,Humans ,Gray Matter ,brain anatomy - Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, which is accompanied by differences in gray matter neuroanatomy and white matter connectivity. However, it is unknown whether these differences are linked or reflect independent aetiologies. Using a multimodal neuroimaging approach, we therefore examined 51 male adults with ASD and 48 neurotypical controls to investigate the relationship between gray matter local gyrification (lGI) and white matter diffusivity in associated fiber tracts. First, ASD individuals had a significant increase in gyrification around the left pre- and post-central gyrus. Second, white matter fiber tracts originating and/or terminating in the cluster of increased lGI had a significant increase in axial diffusivity. This increase in diffusivity was predominantly observed in tracts in close proximity to the cortical sheet. Last, we demonstrate that the increase in lGI was significantly correlated with increased diffusivity of short tracts. This relationship was not significantly modulated by a main effect of group (i.e., ASD), which was more closely associated with gray matter gyrification than white matter diffusivity. Our findings suggest that differences in gray matter neuroanatomy and white matter connectivity are closely linked, and may reflect common rather than distinct aetiological pathways.
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- 2016
6. Soft Tissue Myoepithelial Cell Carcinoma
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Lai, MC, primary and Tan, MH, additional
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- 2016
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7. High Pressure Diesel-Like Injections for GDI Engine: Experimental and Numerical Approach
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Allocca, L, DE VITA, Angelo, and Lai, Mc
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- 2004
8. Youths with ADHD with and without tic disorders: Comorbid psychopathology, executive function and social adjustment.
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Lin YJ, Lai MC, and Gau SS
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- 2012
9. Intraventricular hemorrhage in term neonates caused by sinovenous thrombosis.
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Wu YW, Hamrick SEG, Miller SP, Haward MF, Lai MC, Callen PW, Barkovich AJ, and Ferriero DM
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- 2003
10. The Link between Autism and Sex-Related Neuroanatomy, and Associated Cognition and Gene Expression
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'Floris DL, Peng H, Warrier V, Lombardo MV, Pretzsch CM, Moreau C, Tsompanidis A, Gong W, Mennes M, Llera A, van Rooij D, Oldehinkel M, Forde NJ, Charman T, Tillmann J, Banaschewski T, Moessnang C, Durston S, Holt RJ, Ecker C, Dell'Acqua F, Loth E, Bourgeron T, Murphy DGM, Marquand AF, Lai MC, Buitelaar JK, Baron-Cohen S, Beckmann CF
11. Scanning Electron Microscopy of Tracheal Epithelium of Chickens Infected with Velogenic Viscerotropic Newcastle Disease Virus
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Ibrahim Al and Lai Mc
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Submucosal glands ,Pathology ,medicine.medical_specialty ,Tracheal Epithelium ,General Immunology and Microbiology ,biology ,respiratory system ,Hyperplasia ,medicine.disease ,biology.organism_classification ,Mucus ,Newcastle disease ,Epithelium ,Virus ,medicine.anatomical_structure ,Food Animals ,medicine ,Ultrastructure ,Animal Science and Zoology - Abstract
Ultrastructural changes in the tracheal epithelium of chickens infected intranasally with velogenic viscerotropic Newcastle disease virus were examined by scanning electron microscopy. Hypertrophy of the mucus-secreting, or goblet, cells was the first sign of change, followed by disoriented and deformed cilia, hemorrhage, and hyperplasia of goblet cells accompanied by an increase in mucus. By day 7 postinfection, there was a marked decrease in the number of ciliated cells. Submucosal glands and some collagen fibers were exposed to the surface, an indication of loss of the epithelial cells. Macrophages and cell debris were abundant, and hyperplasia of the basal cells was evident in the later stages of infection, probably in an attempt to regenerate the lost epithelium. However, all chickens died 10 days postinfection, before any further work could be done.
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- 1983
12. Evaluating the effectiveness of illness script teaching on clinical reasoning skills in post-baccalaureate nursing students.
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Wu YL, Lai MC, Chang WP, and Lin YH
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Background: Typically, nurse education curricula are separated into the teaching of theoretical knowledge and practical skills. This separation may hinder nursing students' development of clinical reasoning skills, making it difficult for them to prioritize tasks and make decisions about interventions. Illness scripts have been shown to help medical students improve their clinical reasoning skills; however, they are rarely used in nurse education., Objectives: To evaluate the influence of illness script teaching method on post-baccalaureate nursing students' clinical reasoning skills., Design: The study adopted a single-arm quantitative pre-experimental research design and incorporated qualitative focus group discussions., Settings/participants: This study was conducted at a university in northern Taiwan. Participants included 35 post-baccalaureate nursing students who were enrolled in an elective course focused on clinical skills., Methods: To enhance nursing students' clinical reasoning skills, illness scripts for five clinical scenarios were developed and implemented as part of their curriculum. The Nurses Clinical Reasoning Scale was utilized to assess self-rated clinical reasoning abilities, while dual-teacher scoring was used to evaluate clinical reasoning objectively. The VARK learning preference questionnaire was used to examine how learning preferences affect learning outcomes. After the course, semi-structured focus groups were held to collect student feedback on the effectiveness of the teaching methods and the learning outcomes., Results: This study's quantitative and qualitative results show that illness script-based teaching improves nursing students' clinical reasoning. Quantitative results showed significant objective reasoning score improvements. However, minimal changes in self-rated scores suggest a learning style-influenced gap between perceived and actual abilities. Qualitative findings showed that students valued linking clinical issues to practical applications but struggled with knowledge gaps and engagement., Conclusions: The illness script teaching method improved students' understanding of clinical scenarios and enhanced their clinical reasoning abilities. Incorporating illness scripts into nurse education was beneficial for nursing students., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yu-Huei Lin reports financial support was provided by Ministry of Education, Taiwan. If there are other authors, they 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 © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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13. Task-based functional neural correlates of social cognition across autism and schizophrenia spectrum disorders.
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Oliver LD, Moxon-Emre I, Hawco C, Dickie EW, Dakli A, Lyon RE, Szatmari P, Haltigan JD, Goldenberg A, Rashidi AG, Tan V, Secara MT, Desarkar P, Foussias G, Buchanan RW, Malhotra AK, Lai MC, Voineskos AN, and Ameis SH
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- Humans, Male, Female, Adult, Adolescent, Young Adult, Brain diagnostic imaging, Brain physiopathology, Schizophrenia physiopathology, Schizophrenia diagnostic imaging, Autism Spectrum Disorder physiopathology, Autism Spectrum Disorder diagnostic imaging, Autism Spectrum Disorder psychology, Autistic Disorder physiopathology, Autistic Disorder psychology, Brain Mapping, Case-Control Studies, Social Cognition, Magnetic Resonance Imaging
- Abstract
Background: Autism and schizophrenia spectrum disorders (SSDs) both feature atypical social cognition. Despite evidence for comparable group-level performance in lower-level emotion processing and higher-level mentalizing, limited research has examined the neural basis of social cognition across these conditions. Our goal was to compare the neural correlates of social cognition in autism, SSDs, and typically developing controls (TDCs)., Methods: Data came from two harmonized studies in individuals diagnosed with autism or SSDs and TDCs (aged 16-35 years), including behavioral social cognitive metrics and two functional magnetic resonance imaging (fMRI) tasks: a social mirroring Imitate/Observe (ImObs) task and the Empathic Accuracy (EA) task. Group-level comparisons, and transdiagnostic analyses incorporating social cognitive performance, were run using FSL's PALM for each task, covarying for age and sex (1000 permutations, thresholded at p < 0.05 FWE-corrected). Exploratory region of interest (ROI)-based analyses were also conducted., Results: ImObs and EA analyses included 164 and 174 participants, respectively (autism N = 56/59, SSD N = 50/56, TDC N = 58/59). EA and both lower- and higher-level social cognition scores differed across groups. While canonical social cognitive networks were activated, no significant whole-brain or ROI-based group-level differences in neural correlates for either task were detected. Transdiagnostically, neural activity during the EA task, but not the ImObs task, was associated with lower- and higher-level social cognitive performance., Limitations: Despite attempting to match our groups on age, sex, and race, significant group differences remained. Power to detect regional brain differences is also influenced by sample size and multiple comparisons in whole-brain analyses. Our findings may not generalize to autism and SSD individuals with co-occurring intellectual disabilities., Conclusions: The lack of whole-brain and ROI-based group-level differences identified and the dimensional EA brain-behavior relationship observed across our sample suggest that the EA task may be well-suited to target engagement in novel intervention testing. Our results also emphasize the potential utility of cross-condition approaches to better understand social cognition across autism and SSDs., (© 2024. The Author(s).)
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- 2024
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14. Factors mediating pre-existing autism diagnosis and later suicidal thoughts and behaviors: A follow-up cohort study.
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Chang JC, Lai MC, Chang SS, and Gau SS
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- Humans, Male, Adolescent, Female, Follow-Up Studies, Young Adult, Risk Factors, Child, Case-Control Studies, Cohort Studies, Autistic Disorder psychology, Suicidal Ideation, Bullying psychology, Bullying statistics & numerical data, Autism Spectrum Disorder psychology, Autism Spectrum Disorder epidemiology, Executive Function
- Abstract
Lay Abstract: Autistic people are more likely to experience suicidal thoughts and behaviors. The underlying relationships between potential risk factors and suicidal thoughts and behaviors in autistic individuals remain unclear. To understand this, we investigated whether specific factors in childhood/youth explain the effects of pre-existing autism spectrum disorder (ASD) diagnoses on later suicidal thoughts and behaviors in adolescence/adulthood. We assessed internalizing and externalizing problems, bullying experiences, and executive functions (including cognitive flexibility, sustained attention, and spatial working memory) at an average baseline age of 13.4 years and suicidal thoughts and behaviors at an average follow-up age of 19.2 years among 129 autistic and 121 typically developing (TD) individuals. During the follow-up period in adolescence/adulthood, autistic individuals were more likely to report suicidal thoughts than TD individuals. Being bullied partially accounted for the relationship between a pre-existing ASD diagnosis and later-reported higher suicidal thoughts. Contrary to our hypothesis, higher (instead of lower) cognitive flexibility in some autistic young people appeared to partially explain their higher rates of suicidal thoughts compared with typically developing young people. The findings imply that school bullying prevention and tailored intervention programs for autistic people, especially those with higher cognitive flexibility, are warranted to reduce their risks of experiencing suicidal thoughts., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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15. Gender diversity is correlated with dimensional neurodivergent traits but not categorical neurodevelopmental diagnoses in children.
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Mo K, Anagnostou E, Lerch JP, Taylor MJ, VanderLaan DP, Szatmari P, Crosbie J, Nicolson R, Georgiadis S, Kelley E, Ayub M, Brian J, Lai MC, and Palmert MR
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- Humans, Male, Female, Child, Preschool, Child, Autism Spectrum Disorder physiopathology, Autistic Disorder physiopathology, Gender Identity, Neurodevelopmental Disorders epidemiology, Attention Deficit Disorder with Hyperactivity physiopathology, Attention Deficit Disorder with Hyperactivity epidemiology
- Abstract
Background: Gender clinic and single-item questionnaire-based data report increased co-occurrence of gender diversity and neurodevelopmental conditions. The nuances of these associations are under-studied. We used a transdiagnostic approach, combining categorical and dimensional characterization of neurodiversity, to further the understanding of its associations with gender diversity in identity and expression in children., Methods: Data from 291 children (Autism N = 104, ADHD N = 104, Autism + ADHD N = 17, neurotypical N = 66) aged 4-12 years enrolled in the Province of Ontario Neurodevelopmental Network were analyzed. Gender diversity was measured multi-dimensionally using a well-validated parent-report instrument, the Gender Identity Questionnaire for Children (GIQC). We used gamma regression models to determine the significant correlates of gender diversity among age, puberty, sex-assigned-at-birth, categorical neurodevelopmental diagnoses, and dimensional neurodivergent traits (using the Social Communication Questionnaire and the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scales). Internalizing and externalizing problems were included as covariates., Results: Neither a categorical diagnosis of autism nor ADHD significantly correlated with current GIQC-derived scores. Instead, higher early-childhood dimensional autistic social-communication traits correlated with higher current overall gender incongruence (as defined by GIQC-14 score). This correlation was potentially moderated by sex-assigned-at-birth: greater early-childhood autistic social-communication traits were associated with higher current overall gender incongruence in assigned-males-at-birth, but not assigned-females-at-birth. For fine-grained gender diversity domains, greater autistic restricted-repetitive behavior traits were associated with greater diversity in gender identity across sexes-assigned-at-birth; greater autistic social-communication traits were associated with lower stereotypical male expression across sexes-assigned-at-birth., Conclusions: Dimensional autistic traits, rather than ADHD traits or categorical neurodevelopmental diagnoses, were associated with gender diversity domains across neurodivergent and neurotypical children. The association between early-childhood autistic social-communication traits and overall current gender diversity was most evident in assigned-males-at-birth. Nuanced interrelationships between neurodivergence and gender diversity should be better understood to clarify developmental links and to offer tailored support for neurodivergent and gender-diverse populations., (© 2024 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)
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- 2024
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16. Camouflaging, internalized stigma, and mental health in the general population.
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Ai W, Cunningham WA, and Lai MC
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Background: Camouflaging, the strategies that some autistic people use to hide their differences, has been hypothesized to trigger mental health ramifications. Camouflaging might reflect ubiquitous impression management experiences that are not unique to autistic people and similarly impact the mental health of non-autistic people., Aims: We first examined whether individuals in the general population camouflage and manage impressions while experiencing mental health repercussions, and how gender and neurodivergent traits modified these associations. We then assessed how camouflaging and impression management arose from internalized stigma, and their inter-relationships in shaping mental health outcomes., Methods: Data were collected from 972 adults from a representative U.S. general population sample, with measures pertaining to camouflaging, impression management, mental health, internalized stigma, and neurodivergent traits. Multivariate hierarchical regression and moderated mediation analyses were used to address the two research aims., Results: Both camouflaging and self-presentation (a key component of impression management) were associated with mental health presentations in the general population, which overlapped with those previously reported in autistic people. These associations were more pronounced in women compared with men and were of different directions for individuals with higher autistic traits versus higher ADHD traits. Internalized stigma might be a key stressor that could elicit camouflaging and impression management through social anxiety, which in turn might lead to adverse mental health outcomes., Conclusions: These findings advance the conceptual clarity and clinical relevance of camouflaging and impression management across social and neurodiverse groups in the general population. The ramifications of camouflaging and impression management underscore the need to alleviate internalized stigma for better mental health across human groups.
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- 2024
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17. Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology.
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Bedford SA, Lai MC, Lombardo MV, Chakrabarti B, Ruigrok A, Suckling J, Anagnostou E, Lerch JP, Taylor M, Nicolson R, Stelios G, Crosbie J, Schachar R, Kelley E, Jones J, Arnold PD, Courchesne E, Pierce K, Eyler LT, Campbell K, Barnes CC, Seidlitz J, Alexander-Bloch AF, Bullmore ET, Baron-Cohen S, and Bethlehem RAI
- Abstract
Background: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Population modelling, often referred to as normative modelling, provides a unified framework for studying age-specific and sex-specific divergences in brain development., Methods: Here we used population modelling and a large, multi-site neuroimaging dataset (N = 4255 after quality control) to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of average brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD)., Results: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume, that was localised to the superior temporal cortex, whereas individuals with ADHD showed more global increases in cortical thickness, but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only., Conclusions: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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18. Social and Emotional Functioning of Pediatric Brain Tumor Survivors and Typically Developing Youth Following the Onset of the Pandemic.
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Desjardins L, Hancock K, Lai MC, Bartels U, Vorstman J, and Barrera M
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- Humans, Adolescent, Child, Female, Male, Emotions, Anxiety psychology, Pandemics, Brain Neoplasms psychology, Cancer Survivors psychology, COVID-19 psychology, COVID-19 epidemiology
- Abstract
Background : Social competence is a domain in which pediatric brain tumour survivors (PBTS) are at risk of challenges. To follow-up on our earlier work, in this study we assessed specific social interaction behaviors and emotional functioning in PBTS relative to typically developing youth (TD). The study coincided with the onset of the global pandemic. Methods : Sixteen PBTS and 16 typically developing youth (TD) between 8-16 years old participated in the study. Youth completed an assessment of social behavior and parents completed online surveys regarding child social and emotional adjustment. Results : PBTS experienced greater impairments in social interaction behaviors and on indices of social adjustment relative to TD. PBTS and TD experienced similar levels of emotional problems. Social behavior challenges were associated with indices of anxiety, rather than depression. Time since pandemic onset was not associated with social emotional outcomes. Conclusions : It will be important to monitor and support the social adjustment of populations such as PBTS, as well as the emotional adjustment across PBTS and TD youth, following the pandemic.
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- 2024
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19. Chromosome X-Wide Common Variant Association Study (XWAS) in Autism Spectrum Disorder.
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Mendes M, Chen DZ, Engchuan W, Leal TP, Thiruvahindrapuram B, Trost B, Howe JL, Pellecchia G, Nalpathamkalam T, Alexandrova R, Salazar NB, McKee EA, Alfaro NR, Lai MC, Bandres-Ciga S, Roshandel D, Bradley CA, Anagnostou E, Sun L, and Scherer SW
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Autism Spectrum Disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2 , DDX3X , and DMD . The "female protective effect" in ASD suggests that females may require a higher genetic burden to manifest similar symptoms as males, yet the mechanisms remain unclear. Despite technological advances in genomics, the complexity of the biological nature of sex chromosomes leave them underrepresented in genome-wide studies. Here, we conducted an X chromosome-wide association study (XWAS) using whole-genome sequencing data from 6,873 individuals with ASD (82% males) across Autism Speaks MSSNG, Simons Simplex Cohort SSC, and Simons Foundation Powering Autism Research SPARK, alongside 8,981 population controls (43% males). We analyzed 418,652 X-chromosome variants, identifying 59 associated with ASD (p-values 7.9×10
-6 to 1.51×10-5 ), surpassing Bonferroni-corrected thresholds. Key findings include significant regions on chrXp22.2 (lead SNP=rs12687599, p=3.57×10-7 ) harboring ASB9 / ASB11 , and another encompassing DDX53/PTCHD1-AS long non-coding RNA (lead SNP=rs5926125, p=9.47×10-6 ). When mapping genes within 10kb of the 59 most significantly associated SNPs, 91 genes were found, 17 of which yielded association with ASD ( GRPR , AP1S2 , DDX53 , HDAC8 , PCDH19 , PTCHD1 , PCDH11X , PTCHD1-AS , DMD , SYAP1 , CNKSR2 , GLRA2 , OFD1 , CDKL5 , GPRASP2 , NXF5 , SH3KBP1 ). FGF13 emerged as a novel X-linked ASD candidate gene, highlighted by sex-specific differences in minor allele frequencies. These results reveal significant new insights into X chromosome biology in ASD, confirming and nominating genes and pathways for further investigation., Competing Interests: At the time of this study and its publication, S.W.S. served on the Scientific Advisory Committee of Population Bio. Intellectual property from aspects of his research held at The Hospital for Sick Children are licensed to Athena Diagnostics and Population Bio. These relationships did not influence data interpretation or presentation during this study but are disclosed for potential future considerations.- Published
- 2024
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20. Transdiagnostic Neurobiology of Social Cognition and Individual Variability as Measured by Fractional Amplitude of Low-Frequency Fluctuation in Schizophrenia and Autism Spectrum Disorders.
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Bagheri S, Yu JC, Gallucci J, Tan V, Oliver LD, Dickie EW, Rashidi AG, Foussias G, Lai MC, Buchanan RW, Malhotra AK, Voineskos AN, Ameis SH, and Hawco C
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Fractional amplitude of low-frequency fluctuation (fALFF) is a validated measure of resting-state spontaneous brain activity. Previous fALFF findings in autism and schizophrenia spectrum disorders (ASDs and SSDs) have been highly heterogeneous. We aimed to use fALFF in a large sample of typically developing control (TDC), ASD and SSD participants to explore group differences and relationships with inter-individual variability of fALFF maps and social cognition. fALFF from 495 participants (185 TDC, 68 ASD, and 242 SSD) was computed using functional magnetic resonance imaging as signal power within two frequency bands (i.e., slow-4 and slow-5), normalized by the power in the remaining frequency spectrum. Permutation analysis of linear models was employed to investigate the relationship of fALFF with diagnostic groups, higher-level social cognition, and lower-level social cognition. Each participant's average distance of fALFF map to all others was defined as a variability score, with higher scores indicating less typical maps. Lower fALFF in the visual and higher fALFF in the frontal regions were found in both SSD and ASD participants compared with TDCs. Limited differences were observed between ASD and SSD participants in the cuneus regions only. Associations between slow-4 fALFF and higher-level social cognitive scores across the whole sample were observed in the lateral occipitotemporal and temporoparietal junction. Individual variability within the ASD and SSD groups was also significantly higher compared with TDC. Similar patterns of fALFF and individual variability in ASD and SSD suggest some common neurobiological deficits across these related heterogeneous conditions., Competing Interests: Competing Interest The authors declare no competing interests.
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- 2024
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21. Six novel species of the genus Methanoculleus isolated from various environments in Taiwan.
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Lai SJ, Lai MC, Lin S, You YT, Wei WH, Chen YW, Lan ZH, Fan CH, Wu SY, Hung CC, Ding JY, Zhang WL, Deng YC, Lee YC, Shih CJ, Wu YC, Zhao J, Li Y, and Chen SC
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- Taiwan, Methanomicrobiaceae genetics, Methanomicrobiaceae classification, Methanomicrobiaceae isolation & purification, Base Composition, Hot Springs microbiology, RNA, Ribosomal, 16S genetics, Phylogeny, Geologic Sediments microbiology, Sequence Analysis, DNA, DNA, Archaeal genetics
- Abstract
Taiwan is situated in the subtropical region and its geographical location and topographical features contribute to a rich ecological diversity and scenic landscapes. We investigated the diversity of methanogens in different environments of Taiwan using a culture-dependent method. This report presents the characterization and taxonomy of six hydrogenotrophic methanogens obtained from cold seep sediments (strain FWC-SCC1
T and FWC-SCC3T ), marine sediments (strain CWC-02T and YWC-01T ), estuarine sediments (strain Afa-1T ), and a hot spring well (strain Wushi-C6T ) in Taiwan. The proposed names of the six novel species are Methanoculleus frigidifontis (type strain FWC-SCC1T =BCRC AR10056T =NBRC 113993T ), Methanoculleus oceani (CWC-02T =BCRC AR10055T =NBRC 113992T ), Methanoculleus methanifontis (FWC-SCC3T =BCRC AR10057T =NBRC 113994T ), Methanoculleus nereidis (YWC-01T =BCRC AR10060T =NBRC 114597T ), Methanoculleus formosensis (Afa-1T =BCRC AR10054T =NBRC 113995T ), and Methanoculleus caldifontis (Wushi-06T =BCRC AR10059T = NBRC 114596T ).- Published
- 2024
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22. Comparing the stability and reproducibility of brain-behavior relationships found using canonical correlation analysis and partial least squares within the ABCD sample.
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Nakua H, Yu JC, Abdi H, Hawco C, Voineskos A, Hill S, Lai MC, Wheeler AL, McIntosh AR, and Ameis SH
- Abstract
Canonical correlation analysis (CCA) and partial least squares correlation (PLS) detect linear associations between two data matrices by computing latent variables (LVs) having maximal correlation (CCA) or covariance (PLS). This study compared the similarity and generalizability of CCA- and PLS-derived brain-behavior relationships. Data were accessed from the baseline Adolescent Brain Cognitive Development (ABCD) dataset ( N > 9,000, 9-11 years). The brain matrix consisted of cortical thickness estimates from the Desikan-Killiany atlas. Two phenotypic scales were examined separately as the behavioral matrix; the Child Behavioral Checklist (CBCL) subscale scores and NIH Toolbox performance scores. Resampling methods were used to assess significance and generalizability of LVs. LV
1 for the CBCL brain relationships was found to be significant, yet not consistently stable or reproducible, across CCA and PLS models (singular value: CCA = .13, PLS = .39, p < .001). LV1 for the NIH brain relationships showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, p < .001). The current study suggests that stability and reproducibility of brain-behavior relationships identified by CCA and PLS are influenced by the statistical characteristics of the phenotypic measure used when applied to a large population-based pediatric sample., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2024 Massachusetts Institute of Technology.)- Published
- 2024
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23. Negative and Positive Experiences During the COVID-19 Pandemic in Canadians With Developmental Disabilities: A One-Year Ontario-Based Survey.
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Kassee C, Jachyra P, Mahalingam V, Tint A, Lin HY, Ameis SH, Di Martino A, Lunsky Y, and Lai MC
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- Humans, Adult, Adolescent, Female, Male, Middle Aged, Young Adult, Ontario epidemiology, Child, Caregivers psychology, Surveys and Questionnaires, Qualitative Research, North American People, Developmental Disabilities epidemiology, COVID-19 epidemiology, COVID-19 psychology
- Abstract
Purpose: Understanding the experiences of people with developmental disabilities during the initial period of COVID-19 pandemic., Methods: Individuals with developmental disabilities and their caregivers completed baseline and up to five follow-up online surveys using the CRISIS-AFAR measures, between July 2020 and September 2021. We used qualitative (thematic analysis) and quantitative (MANOVA) analytic methods., Results: One hundred and eighteen participants (64 caregivers on individuals 6-62 years, 54 self-reporting individuals aged 17-55 years) completed baseline survey; 46 participants (23 caregivers, 23 self-reporting adults) completed ≥1 follow-up. Qualitative themes included uncertainty, and negative and positive influences on behaviours and routines, daily life and mental wellness. Those experiencing positive impacts did not stably perceive so longitudinally., Conclusions: Despite both negative and positive influences on individuals with developmental disabilities and their families, the prolonged pandemic had wide-ranging repercussions. Emergency preparedness planning should consider the disruptive effects of public health measures on routine and support for this vulnerable population., (© 2024 The Author(s). Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.)
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- 2024
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24. Sex differences in social brain neural responses in autism: temporal profiles of configural face-processing within data-driven time windows.
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Del Bianco T, Lai MC, Mason L, Johnson MH, Charman T, Loth E, Banaschewski T, Buitelaar J, Murphy DGM, and Jones EJH
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- Humans, Female, Male, Adolescent, Child, Adult, Young Adult, Evoked Potentials physiology, Facial Recognition physiology, Sex Characteristics, Autistic Disorder physiopathology, Electroencephalography, Brain physiopathology
- Abstract
Face-processing timing differences may underlie visual social attention differences between autistic and non-autistic people, and males and females. This study investigates the timing of the effects of neurotype and sex on face-processing, and their dependence on age. We analysed EEG data during upright and inverted photographs of faces from 492 participants from the Longitudinal European Autism Project (141 neurotypical males, 76 neurotypical females, 202 autistic males, 73 autistic females; age 6-30 years). We detected timings of sex/diagnosis effects on event-related potential amplitudes at the posterior-temporal channel P8 with Bootstrapped Cluster-based Permutation Analysis and conducted Growth Curve Analysis (GCA) to investigate the timecourse and dependence on age of neural signals. The periods of influence of neurotype and sex overlapped but differed in onset (respectively, 260 and 310 ms post-stimulus), with sex effects lasting longer. GCA revealed a smaller and later amplitude peak in autistic female children compared to non-autistic female children; this difference decreased in adolescence and was not significant in adulthood. No age-dependent neurotype difference was significant in males. These findings indicate that sex and neurotype influence longer latency face processing and implicates cognitive rather than perceptual processing. Sex may have more overarching effects than neurotype on configural face processing., (© 2024. The Author(s).)
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- 2024
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25. Utility of a virtual small group cognitive behaviour program for autistic children during the pandemic: evidence from a community-based implementation study.
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Lee V, Vashi N, Roudbarani F, Modica PT, Pouyandeh A, Sellitto T, Ibrahim A, Ameis SH, Elkader A, Gray KM, Kerns CM, Lai MC, Lake J, Thomson K, and Weiss JA
- Subjects
- Humans, Male, Female, Child, SARS-CoV-2, Pandemics, Adult, Emotional Regulation, COVID-19 epidemiology, Autistic Disorder therapy, Autistic Disorder psychology, Cognitive Behavioral Therapy methods
- Abstract
Background: Autistic children often experience socioemotional difficulties relating to emotion regulation and mental health problems. Supports for autistic children involve the use of adapted interventions that target emotion regulation and social skills, alongside mental health symptoms. The Secret Agent Society Small Group (SAS: SG), an adapted cognitive behavioural program, has demonstrated efficacy through lab-delivered randomized control trials. However, research is still needed on its effectiveness when delivered by publicly funded, community-based autism providers under real-world ecologically valid conditions, especially within the context of a pandemic. The COVID-19 pandemic has disrupted access to community-based supports and services for autistic children, and programs have adapted their services to online platforms. However, questions remain about the feasibility and clinical utility of evidence-based interventions and services delivered virtually in community-based settings., Methods: The 9-week SAS: SG program was delivered virtually by seven community-based autism service providers during 2020-2021. The program included the use of computer-based games, role-playing tasks, and home missions. Caregivers completed surveys at three timepoints: pre-, post-intervention, and after a 3-month follow-up session. Surveys assessed caregivers' perception of the program's acceptability and level of satisfaction, as well as their child's social and emotional regulation skills and related mental health challenges., Results: A total of 77 caregivers (94% gender identity females; Mean = 42.1 years, SD = 6.5 years) and their children (79% gender identity males; Mean = 9.9 years, SD = 1.3 years) completed the SAS: SG program. Caregivers agreed that the program was acceptable (95%) and were highly satisfied (90%). Caregivers reported significant reduction in their child's emotion reactivity from pre- to post-intervention (-1.78 (95% CI, -3.20 to -0.29), p = 0.01, d = 0.36), that continued to decrease after the 3-month booster session (-1.75 (95% CI, -3.34 to -0.16), p = 0.02, d = 0.33). Similarly, improvements in anxiety symptoms were observed (3.05 (95% CI, 0.72 to 5.36), p = 0.006, d = 0.39)., Conclusions: As online delivery of interventions for autistic children remains popular past the pandemic, our findings shed light on future considerations for community-based services, including therapists and agency leaders, on how best to tailor and optimally deliver virtually based programming., Trial Registration: This study has been registered with ISRCTN Registry (ISRCTN98068608) on 15/09/2023. The study was retroactively registered., (© 2024. The Author(s).)
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- 2024
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26. Sex-differential patterns of neuropsychological functioning in adults with attention-deficit/hyperactivity disorder.
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Lin YJ, Lai MC, Yang LK, and Gau SS
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- Adult, Infant, Newborn, Humans, Male, Female, Executive Function physiology, Memory, Short-Term physiology, Neuropsychological Tests, Attention, Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity epidemiology, Attention Deficit Disorder with Hyperactivity complications
- Abstract
Background: The sex-differential prevalence of attention-deficit/hyperactivity disorder (ADHD) varies across the lifespan, but little is known about sex differences in executive functions in adults with ADHD., Methods: We assessed 261 adults, aged 18-40 years, diagnosed with ADHD (170 males [assigned at birth], aged 25.81 ± 5.49; 91 females, aged 27.76 ± 5.42) and 308 neurotypical adults (176 males, aged 24.62 ± 5.14; 132 female, aged 25.37 ± 5.42) via psychiatric interviews to confirm ADHD and other psychiatric diagnoses. They were assessed by the Cambridge Neuropsychological Testing Automated Battery (CANTAB) on Reaction Time (arousal/processing speed), Rapid Visual Information Processing (sustained attention), Spatial Span (spatial memory), Spatial Working Memory, Intradimentional/Extradimensional Shift (set-shifting), and Stocking of Cambridge (spatial planning). The primary analyses were adjusted for age, full-scale IQ, and co-occurring psychiatric conditions., Results: Adults with ADHD had various co-occurring psychiatric conditions without sex differences in ADHD-neurotypical differences. Both adult males and females with ADHD performed poorer in all CANTAB tasks than same-sex neurotypical adults. Significant sex-moderating effects were observed in neuropsychological performance, including greater ADHD-neurotypical differences in arousal for females than males and in location memory for spatial tasks in males than females., Conclusion: There were no sex-moderating effects in the presence of co-occurring psychiatric conditions in adult ADHD. However, there were sex-moderating effects on how ADHD related to neuropsychological functioning in adulthood. ADHD was associated with more challenges in arousal/processing speed in females and more challenges in strategy use or inhibition in spatial memory in males., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest about the design, implementation of the study, and publication of the results., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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27. Origins and Importance of Intragranular Cracking in Layered Lithium Transition Metal Oxide Cathodes.
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Morzy JK, Dose WM, Vullum PE, Lai MC, Mahadevegowda A, De Volder MFL, and Ducati C
- Abstract
Li-ion batteries have a pivotal role in the transition toward electric transportation. Ni-rich layered transition metal oxide (LTMO) cathode materials promise high specific capacity and lower cost but exhibit faster degradation compared with lower Ni alternatives. Here, we employ high-resolution electron microscopy and spectroscopy techniques to investigate the nanoscale origins and impact on performance of intragranular cracking (within primary crystals) in Ni-rich LTMOs. We find that intragranular cracking is widespread in charged specimens early in cycle life but uncommon in discharged samples even after cycling. The distribution of intragranular cracking is highly inhomogeneous. We conclude that intragranular cracking is caused by local stresses that can have several independent sources: neighboring particle anisotropic expansion/contraction, Li- and TM-inhomogeneities at the primary and secondary particle levels, and interfacing of electrochemically active and inactive phases. Our results suggest that intragranular cracks can manifest at different points of life of the cathode and can potentially lead to capacity fade and impedance rise of LTMO cathodes through plane gliding and particle detachment that lead to exposure of additional surfaces to the electrolyte and loss of electrical contact., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)
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- 2024
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28. γ-Oryzanol from Rice Bran Antagonizes Glutamate-Induced Excitotoxicity in an In Vitro Model of Differentiated HT-22 Cells.
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Chen LC, Lai MC, Hong TY, and Liu IM
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- Animals, Mice, Cell Line, Oryza chemistry, Membrane Potential, Mitochondrial drug effects, Cell Differentiation drug effects, Cell Survival drug effects, Memantine pharmacology, Apoptosis drug effects, Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism, Neurons drug effects, Neurons metabolism, Glutamic Acid toxicity, Phenylpropionates pharmacology, Neuroprotective Agents pharmacology, Reactive Oxygen Species metabolism, Mitochondria drug effects, Mitochondria metabolism
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The excessive activation of glutamate in the brain is a factor in the development of vascular dementia. γ-Oryzanol is a natural compound that has been shown to enhance brain function, but more research is needed to determine its potential as a treatment for vascular dementia. This study investigated if γ-oryzanol can delay or improve glutamate neurotoxicity in an in vitro model of differentiated HT-22 cells and explored its neuroprotective mechanisms. The differentiated HT-22 cells were treated with 0.1 mmol/L glutamate for 24 h then given γ-oryzanol at appropriate concentrations or memantine (10 µmol/L) for another 24 h. Glutamate produced reactive oxygen species and depleted glutathione in the cells, which reduced their viability. Mitochondrial dysfunction was also observed, including the inhibition of mitochondrial respiratory chain complex I activity, the collapse of mitochondrial transmembrane potential, and the reduction of intracellular ATP levels in the HT-22 cells. Calcium influx triggered by glutamate subsequently activated type II calcium/calmodulin-dependent protein kinase (CaMKII) in the HT-22 cells. The activation of CaMKII-ASK1-JNK MAP kinase cascade, decreased Bcl-2/Bax ratio, and increased Apaf-1-dependent caspase-9 activation were also observed due to glutamate induction, which were associated with increased DNA fragmentation. These events were attenuated when the cells were treated with γ-oryzanol (0.4 mmol/L) or the N-methyl-D-aspartate receptor antagonist memantine. The results suggest that γ-oryzanol has potent neuroprotective properties against glutamate excitotoxicity in differentiated HT-22 cells. Therefore, γ-oryzanol could be a promising candidate for the development of therapies for glutamate excitotoxicity-associated neurodegenerative diseases, including vascular dementia.
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- 2024
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29. Methanooceanicella nereidis gen. nov., sp. nov., the first oceanic Methanocellaceae methanogen, isolated from potential methane hydrate bearing area offshore southwestern Taiwan.
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Zhang WL, Lai MC, Lin S, Chen WC, Deng YC, Lai SJ, Wu SY, Hung CC, Ding JY, and Chen SC
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- Base Composition, Phylogeny, RNA, Ribosomal, 16S genetics, Taiwan, Sequence Analysis, DNA, DNA, Bacterial genetics, Bacterial Typing Techniques, Fatty Acids chemistry, Methane, Carbon Dioxide, Euryarchaeota
- Abstract
A novel mesophilic, hydrogenotrophic methanogen, strain CWC-04
T , was obtained from a sediment sample extracted from a gravity core retrieved at station 22 within the KP-9 area off the southwestern coast of Taiwan during the ORIII-1368 cruise in 2009. Cells of strain CWC-04T were rod-shaped, 1.4-2.9 µm long by 0.5-0.6 µm wide, and occurred singly. Strain CWC-04T utilized formate, H2 /CO2 , 2-propanol/CO2 or 2-butanol/CO2 as catabolic substrates. The optimal growth conditions were 42 °C, 0.17 M NaCl and pH 5.35. The genomic DNA G+C content calculated from the genome sequence of strain CWC-04T was 46.19 mol%. Phylogenetic analysis of 16S rRNA gene revealed that strain CWC-04T is affiliated with the genus Methanocella . The 16S rRNA gene sequences similarities within strains Methanocella arvoryzae MRE50T , Methanocella paludicola SANAET and Methanocella conradii HZ254T were 93.7, 93.0 and 91.3 %, respectively. In addition, the optical density of CWC-04T culture dropped abruptly upon entering the late-log growth phase, with virus-like particles (150 nm in diameter) being observed on and around the cells. This observation suggests that strain CWC-04T harbours a lytic virus. Based on these phenotypic, phylogenetic and genomic results, we propose that strain CWC-04T represents a novel species of a novel genus in the family Methanocellaceae , for which the name Methanooceanicella nereidis gen. nov., sp. nov. is proposed. The type strain is CWC-04T (=BCRC AR10050T =NBRC 113165T ).- Published
- 2024
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30. Dorsal Striatal Functional Connectivity and Repetitive Behavior Dimensions in Children and Youths With Neurodevelopmental Disorders.
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Choi EJ, Vandewouw MM, Taylor MJ, Stevenson RA, Arnold PD, Brian J, Crosbie J, Kelley E, Liu X, Jones J, Lai MC, Schachar RJ, Lerch JP, and Anagnostou E
- Subjects
- Child, Humans, Adolescent, Brain Mapping, Cognition, Autism Spectrum Disorder, Obsessive-Compulsive Disorder, Neurodevelopmental Disorders
- Abstract
Background: Impairing repetitive behaviors are one of the core diagnostic symptoms in autism spectrum disorder and obsessive-compulsive disorder, but they also manifest in attention-deficit/hyperactivity disorder. Although the dorsal striatal circuit has been implicated in repetitive behaviors, extensive heterogeneity in and cross-diagnostic manifestations of these behaviors have suggested phenotypic and likely neurobiological heterogeneity across neurodevelopmental disorders (NDDs)., Methods: Intrinsic dorsal striatal functional connectivity was examined in 3 NDDs (autism spectrum disorder, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder) and typically developing control participants in a large single-cohort sample (N = 412). To learn how diagnostic labels and overlapping behaviors manifest in dorsal striatal functional connectivity measured with functional magnetic resonance imaging, the main and interaction effects of diagnosis and behavior were examined in 8 models (2 seed functional connectivity [caudate and putamen] × 4 sub-behavioral domains [sameness/ritualistic, self-injury, stereotypy, and compulsions])., Results: The obsessive-compulsive disorder group demonstrated distinctive patterns in visual and visuomotor coordination regions compared with the other diagnostic groups. Lower-order repetitive behaviors (self-injury and stereotypy) manifesting across all participants were implicated in regions involved in motor and cognitive control, although the findings did not survive effects of multiple comparisons, suggesting heterogeneity in these behavioral domains. An interaction between self-injurious behavior and an attention-deficit/hyperactivity disorder diagnosis were observed on caudate-cerebellum functional connectivity., Conclusions: These findings confirmed high heterogeneity and overlapping behavioral manifestations in NDDs and their complex underlying neural mechanisms. A call for diagnosis-free symptom measures that can capture not only observable symptoms and severity across NDDs but also the underlying functions and motivations of such behaviors across diagnoses is needed., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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31. White matter microstructure in transmasculine and cisgender adolescents: A multiparametric and multivariate study.
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Thurston LT, Skorska MN, Lobaugh NJ, Zucker KJ, Chakravarty MM, Lai MC, Chavez S, and VanderLaan DP
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- Male, Infant, Newborn, Humans, Female, Adolescent, Brain, Gender Identity, Diffusion Magnetic Resonance Imaging, Estradiol, White Matter
- Abstract
Adolescence is a sensitive developmental period for neural sex/gender differentiation. The present study used multiparametric mapping to better characterize adolescent white matter (WM) microstructure. WM microstructure was investigated using diffusion tensor indices (fractional anisotropy; mean, radial, and axial diffusivity [AD]) and quantitative T1 relaxometry (T1) in hormone therapy naïve adolescent cisgender girls, cisgender boys, and transgender boys (i.e., assigned female at birth and diagnosed with gender dysphoria). Diffusion indices were first analyzed for group differences using tract-based spatial statistics, which revealed a group difference in AD. Thus, two multiparametric and multivariate analyses assessed AD in conjunction with T1 relaxation time, and with respect to developmental proxy variables (i.e., age, serum estradiol, pubertal development, sexual attraction) thought to be relevant to adolescent brain development. The multivariate analyses showed a shared pattern between AD and T1 such that higher AD was associated with longer T1, and AD and T1 strongly related to all five developmental variables in cisgender boys (10 significant correlations, r range: 0.21-0.73). There were fewer significant correlations between the brain and developmental variables in cisgender girls (three correlations, r range: -0.54-0.54) and transgender boys (two correlations, r range: -0.59-0.77). Specifically, AD related to direction of sexual attraction (i.e., gynephilia, androphilia) in all groups, and T1 related to estradiol inversely in cisgender boys compared with transgender boys. These brain patterns may be indicative of less myelination and tissue density in cisgender boys, which corroborates other reports of protracted WM development in cisgender boys. Further, these findings highlight the importance of considering developmental trajectory when assessing the subtleties of neural structure associated with variations in sex, gender, and sexual attraction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Thurston 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.)
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- 2024
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32. Neuroimaging and Biosample Collection in the Toronto Adolescent and Youth Cohort Study: Rationale, Methods, and Early Data.
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Dickie EW, Ameis SH, Boileau I, Diaconescu AO, Felsky D, Goldstein BI, Gonçalves V, Griffiths JD, Haltigan JD, Husain MO, Rubin-Kahana DS, Iftikhar M, Jani M, Lai MC, Lin HY, MacIntosh BJ, Wheeler AL, Vasdev N, Vieira E, Ahmadzadeh G, Heyland L, Mohan A, Ogunsanya F, Oliver LD, Zhu C, Wong JKY, Charlton C, Truong J, Yu L, Kelly R, Cleverley K, Courtney DB, Foussias G, Hawke LD, Hill S, Kozloff N, Polillo A, Rotenberg M, Quilty LC, Tempelaar W, Wang W, Nikolova YS, and Voineskos AN
- Subjects
- Child, Humans, Adolescent, Cohort Studies, Neuroimaging, Brain, Proteomics, Psychotic Disorders
- Abstract
Background: The Toronto Adolescent and Youth (TAY) Cohort Study will characterize the neurobiological trajectories of psychosis spectrum symptoms, functioning, and suicidality (i.e., suicidal thoughts and behaviors) in youth seeking mental health care. Here, we present the neuroimaging and biosample component of the protocol. We also present feasibility and quality control metrics for the baseline sample collected thus far., Methods: The current study includes youths (ages 11-24 years) who were referred to child and youth mental health services within a large tertiary care center in Toronto, Ontario, Canada, with target recruitment of 1500 participants. Participants were offered the opportunity to provide any or all of the following: 1) 1-hour magnetic resonance imaging (MRI) scan (electroencephalography if ineligible for or declined MRI), 2) blood sample for genomic and proteomic data (or saliva if blood collection was declined or not feasible) and urine sample, and 3) heart rate recording to assess respiratory sinus arrhythmia., Results: Of the first 417 participants who consented to participate between May 4, 2021, and February 2, 2023, 412 agreed to participate in the imaging and biosample protocol. Of these, 334 completed imaging, 341 provided a biosample, 338 completed respiratory sinus arrhythmia, and 316 completed all 3. Following quality control, data usability was high (MRI: T1-weighted 99%, diffusion-weighted imaging 99%, arterial spin labeling 90%, resting-state functional MRI 95%, task functional MRI 90%; electroencephalography: 83%; respiratory sinus arrhythmia: 99%)., Conclusions: The high consent rates, good completion rates, and high data usability reported here demonstrate the feasibility of collecting and using brain imaging and biosamples in a large clinical cohort of youths seeking mental health care., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
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- 2024
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33. The Toronto Adolescent and Youth Cohort Study: Study Design and Early Data Related to Psychosis Spectrum Symptoms, Functioning, and Suicidality.
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Cleverley K, Foussias G, Ameis SH, Courtney DB, Goldstein BI, Hawke LD, Kozloff N, Quilty LC, Rotenberg M, Wheeler AL, Andrade BF, Aitken M, Mahleka D, Jani M, Frayne M, Wong JKY, Kelly R, Dickie EW, Felsky D, Haltigan JD, Lai MC, Nikolova YS, Tempelaar W, Wang W, Battaglia M, Husain MO, Kidd S, Kurdyak P, Levitan RD, Lewis SP, Polillo A, Szatmari P, van der Miesen AIR, Ahmadzadasl M, and Voineskos AN
- Subjects
- Humans, Adolescent, Child, Young Adult, Adult, Suicidal Ideation, Cohort Studies, Longitudinal Studies, Suicide psychology, Psychotic Disorders epidemiology, Psychotic Disorders psychology
- Abstract
Background: Psychosis spectrum symptoms (PSSs) occur in a sizable percentage of youth and are associated with poorer cognitive performance, poorer functioning, and suicidality (i.e., suicidal thoughts and behaviors). PSSs may occur more frequently in youths already experiencing another mental illness, but the antecedents are not well known. The Toronto Adolescent and Youth (TAY) Cohort Study aims to characterize developmental trajectories in youths with mental illness and understand associations with PSSs, functioning, and suicidality., Methods: The TAY Cohort Study is a longitudinal cohort study that aims to assess 1500 youths (age 11-24 years) presenting to tertiary care. In this article, we describe the extensive diagnostic and clinical characterization of psychopathology, substance use, functioning, suicidality, and health service utilization in these youths, with follow-up every 6 months over 5 years, including early baseline data., Results: A total of 417 participants were enrolled between May 4, 2021, and February 2, 2023. Participants met diagnostic criteria for an average of 3.5 psychiatric diagnoses, most frequently anxiety and depressive disorders. Forty-nine percent of participants met a pre-established threshold for PSSs and exhibited higher rates of functional impairment, internalizing and externalizing symptoms, and suicidality than participants without PSSs., Conclusions: Initial findings from the TAY Cohort Study demonstrate the feasibility of extensive clinical phenotyping in youths who are seeking help for mental health problems. PSS prevalence is much higher than in community-based studies. Our early data support the critical need to better understand longitudinal trajectories of clinical youth cohorts in relation to psychosis risk, functioning, and suicidality., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
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- 2024
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34. Exploring camouflaging by the Chinese version Camouflaging Autistic Traits Questionnaire in Taiwanese autistic and non-autistic adolescents: An initial development.
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Liu CH, Chen YL, Chen PJ, Ni HC, and Lai MC
- Subjects
- Adolescent, Female, Humans, Male, Asian People, Self Report, Surveys and Questionnaires, Autism Spectrum Disorder, Autistic Disorder
- Abstract
Lay Abstract: Camouflaging is a coping strategy used by some autistic and other neurodivergent people to fit in neurotypical social contexts. The self-reported Camouflaging Autistic Traits Questionnaire has been validated for use in research with adults in some Western societies, but not in non-Western cultural-ethnic groups. We translated Camouflaging Autistic Traits Questionnaire into traditional Chinese and examined the use of this measure in Taiwanese adolescents via both self-report and caregiver-report in 100 autistic and 105 non-autistic adolescents. Both self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire were composed of two factors (i.e. a "compensation-masking" subscale and an "assimilation" subscale). Both adolescent self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire total score and subscales were reliable in measurement, and they highly correlated with each other. Taiwanese autistic adolescents were more likely to camouflage than non-autistic adolescents, especially on assimilation. Female autistic adolescents showed higher assimilation than male autistic adolescents. Higher camouflaging, especially assimilation, was associated with higher stress in autistic and non-autistic adolescents alike. Both self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire were reliable and offered meaningful information to help us understand the social coping experiences of autistic and non-autistic adolescents., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: None of the authors have conflict of biomedical interests related to this work. M.-C.L. serves as an editor of the journal Autism and has received editorial honorarium from SAGE Publications.
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- 2024
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35. Short report: Recommendations for education, clinical practice, research, and policy on promoting well-being in autistic youth and adults through a positive focus on sexuality and gender diversity.
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Dewinter J, Onaiwu MG, Massolo ML, Caplan R, Van Beneden E, Brörmann N, Crehan ET, Croen LA, Faja S, Gassner DL, Graham Holmes L, Hughes C, Hunter M, Huysamen M, Jelonche P, Lai MC, Noens I, Pukki H, Stokes MA, Strang JF, and van der Miesen AI
- Subjects
- Adult, Humans, Female, Adolescent, Male, Gender Identity, Sexuality, Policy, Autistic Disorder, Autism Spectrum Disorder
- Abstract
Lay Abstract: In this article, we propose recommendations on what we can do to promote that autistic people can enjoy their sexuality and gender identity, because that contributes to overall well-being.First, we briefly summarize the existing research on sexuality and gender diversity in autistic individuals.Next, we propose recommendations for how to promote sexual and gender diversity-related health and well-being. Based on what is known about sexuality, gender diversity, and relationships in autistic adolescents and adults, we convened an international group of autistic and non-autistic researchers, advocates, parents, and professionals to develop recommendations to promote sexual and gender health in autistic people.The resulting recommendations were checked through an online survey distributed to autistic people across the world. The online participants endorsed the importance of eight final recommendations related to:1. Providing education and information on sexuality, relationships, and gender diversity to autistic individuals and their families;2. Improving expertise in and accessibility to healthcare for sexuality, relationships, and gender-related questions, with specific attention to prevention of and support after sexual victimization; and3. Meaningfully including the autism community in future research that addresses well-being relating to sexuality, relationships, and gender diversity.These community-driven recommendations aim to promote sexual health and well-being in autistic individuals internationally., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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36. Conserved molecular chaperone PrsA stimulates protective immunity against group A Streptococcus.
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Lai CY, Xie JX, Lai MC, Wu ZY, Lin JS, Huang YT, Chi CY, Chiang-Ni C, Walker MJ, and Chang YC
- Abstract
Group A Streptococcus (GAS) is a significant human pathogen that poses a global health concern. However, the development of a GAS vaccine has been challenging due to the multitude of diverse M-types and the risk of triggering cross-reactive immune responses. Our previous research has identified a critical role of PrsA1 and PrsA2, surface post-translational molecular chaperone proteins, in maintaining GAS proteome homeostasis and virulence traits. In this study, we aimed to further explore the potential of PrsA1 and PrsA2 as vaccine candidates for preventing GAS infection. We found that PrsA1 and PrsA2 are highly conserved among GAS isolates, demonstrating minimal amino acid variation. Antibodies specifically targeting PrsA1/A2 showed no cross-reactivity with human heart proteins and effectively enhanced neutrophil opsonophagocytic killing of various GAS serotypes. Additionally, passive transfer of PrsA1/A2-specific antibodies conferred protective immunity in infected mice. Compared to alum, immunization with CFA-adjuvanted PrsA1/A2 induced higher levels of Th1-associated IgG isotypes and complement activation and provided approximately 70% protection against invasive GAS challenge. These findings highlight the potential of PrsA1 and PrsA2 as universal vaccine candidates for the development of an effective GAS vaccine., (© 2024. The Author(s).)
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- 2024
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37. The Human Phenotype Ontology in 2024: phenotypes around the world.
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Gargano MA, Matentzoglu N, Coleman B, Addo-Lartey EB, Anagnostopoulos AV, Anderton J, Avillach P, Bagley AM, Bakštein E, Balhoff JP, Baynam G, Bello SM, Berk M, Bertram H, Bishop S, Blau H, Bodenstein DF, Botas P, Boztug K, Čady J, Callahan TJ, Cameron R, Carbon SJ, Castellanos F, Caufield JH, Chan LE, Chute CG, Cruz-Rojo J, Dahan-Oliel N, Davids JR, de Dieuleveult M, de Souza V, de Vries BBA, de Vries E, DePaulo JR, Derfalvi B, Dhombres F, Diaz-Byrd C, Dingemans AJM, Donadille B, Duyzend M, Elfeky R, Essaid S, Fabrizzi C, Fico G, Firth HV, Freudenberg-Hua Y, Fullerton JM, Gabriel DL, Gilmour K, Giordano J, Goes FS, Moses RG, Green I, Griese M, Groza T, Gu W, Guthrie J, Gyori B, Hamosh A, Hanauer M, Hanušová K, He YO, Hegde H, Helbig I, Holasová K, Hoyt CT, Huang S, Hurwitz E, Jacobsen JOB, Jiang X, Joseph L, Keramatian K, King B, Knoflach K, Koolen DA, Kraus ML, Kroll C, Kusters M, Ladewig MS, Lagorce D, Lai MC, Lapunzina P, Laraway B, Lewis-Smith D, Li X, Lucano C, Majd M, Marazita ML, Martinez-Glez V, McHenry TH, McInnis MG, McMurry JA, Mihulová M, Millett CE, Mitchell PB, Moslerová V, Narutomi K, Nematollahi S, Nevado J, Nierenberg AA, Čajbiková NN, Nurnberger JI Jr, Ogishima S, Olson D, Ortiz A, Pachajoa H, Perez de Nanclares G, Peters A, Putman T, Rapp CK, Rath A, Reese J, Rekerle L, Roberts AM, Roy S, Sanders SJ, Schuetz C, Schulte EC, Schulze TG, Schwarz M, Scott K, Seelow D, Seitz B, Shen Y, Similuk MN, Simon ES, Singh B, Smedley D, Smith CL, Smolinsky JT, Sperry S, Stafford E, Stefancsik R, Steinhaus R, Strawbridge R, Sundaramurthi JC, Talapova P, Tenorio Castano JA, Tesner P, Thomas RH, Thurm A, Turnovec M, van Gijn ME, Vasilevsky NA, Vlčková M, Walden A, Wang K, Wapner R, Ware JS, Wiafe AA, Wiafe SA, Wiggins LD, Williams AE, Wu C, Wyrwoll MJ, Xiong H, Yalin N, Yamamoto Y, Yatham LN, Yocum AK, Young AH, Yüksel Z, Zandi PP, Zankl A, Zarante I, Zvolský M, Toro S, Carmody LC, Harris NL, Munoz-Torres MC, Danis D, Mungall CJ, Köhler S, Haendel MA, and Robinson PN
- Subjects
- Humans, Phenotype, Genomics, Algorithms, Rare Diseases, Biological Ontologies
- Abstract
The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2024
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38. The dimensional structure of the Camouflaging Autistic Traits Questionnaire (CAT-Q) and predictors of camouflaging in a representative general population sample.
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Ai W, Cunningham WA, and Lai MC
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- Humans, Surveys and Questionnaires, Emotions, Motivation, Fear, Autistic Disorder diagnosis, Autistic Disorder epidemiology, Autistic Disorder psychology
- Abstract
Objectives: Some autistic people "camouflage" their differences by modeling neurotypical behaviors to survive in a neurotypical-dominant social world. It remains elusive whether camouflaging is unique to autism or if it entails similar experiences across human groups as part of ubiquitous impression management (IM). Here we examined camouflaging engagement and theoretical drivers in the general population, drawing on the transactional IM framework and contextualizing findings within both contemporary autism research and the past IM literature., Methods: A large representative U.S. general population sample (N = 972) completed this survey study. We combined exploratory item factor analysis and graph analysis to triangulate the dimensional structure of the Camouflaging Autistic Traits Questionnaire (CAT-Q) and examined its correspondence with prior autism-enriched psychometric findings. We then employed hierarchical regression and elastic-net regression to identify the predictors of camouflaging, including demographic (e.g., age, gender), neurodivergence (i.e., autistic and ADHD traits), socio-motivational, and cognitive factors., Results: We found a three-factor/dimensional structure of the CAT-Q in the general population, nearly identical to that found in previous autism-enriched samples. Significant socio-motivational predictors of camouflaging included greater social comparison, greater public self-consciousness, greater internalized social stigma, and greater social anxiety. These camouflaging drivers overlap with findings in recent autistic camouflaging studies and prior IM research., Conclusions: The novel psychometric and socio-motivational evidence demonstrates camouflaging as a shared social coping experience across the general population, including autistic people. This continuity guides a clearer understanding of camouflaging and has key implications for autism scholars, clinicians, and the broader clinical intersecting with social psychology research. Future research areas are mapped to elucidate how camouflaging/IM manifests and functions within person-environment transactions across social-identity and clinical groups., Competing Interests: Declaration of Competing Interest W. Ai: No conflicts of interest directly related to this work. W. Cunningham: No conflicts of interest directly related to this work. M.-C. Lai: No conflicts of interest directly related to this work. M.-C. Lai has received editorial honorarium from SAGE Publications., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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39. Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology.
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Bedford SA, Lai MC, Lombardo MV, Chakrabarti B, Ruigrok A, Suckling J, Anagnostou E, Lerch JP, Taylor M, Nicolson R, Stelios G, Crosbie J, Schachar R, Kelley E, Jones J, Arnold PD, Courchesne E, Pierce K, Eyler LT, Campbell K, Barnes CC, Seidlitz J, Alexander-Bloch AF, Bullmore ET, Baron-Cohen S, and Bethlehem RAI
- Abstract
Background: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Normative modelling provides a unified framework for studying age-specific and sex-specific divergences in neurodivergent brain development., Methods: Here we use normative modelling and a large, multi-site neuroimaging dataset to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of typical brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD)., Results: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume localised to the superior temporal cortex, whereas individuals with ADHD showed more global effects of cortical thickness increases but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only., Conclusions: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence., Competing Interests: Disclosures EB reports consultancy work for Boehringer Ingelheim, Sosei Heptares, SR One, GlaxoSmithKline. EB, RAIB, JS, AFA-B are co-founders of Centile Bioscience. PAD receives research support from Biohaven Pharmaceuticals. M-C Lai has received editorial honorarium from SAGE Publications. RN reported receiving grants from Brain Canada, Hoffman La Roche, Otsuka Pharmaceuticals, and Maplight Therapeutics outside the submitted work. EA reported receiving grants from Roche and Anavex; receiving nonfinancial support from AMO Pharma and CRA-Simons Foundation; and receiving personal fees from Roche, Impel, Ono, and Quadrant outside the submitted work; in addition, EA had a patent for Anxiety Meter issued 14/755/084 (United States) and a patent for Anxiety Meter pending 2,895,954 (Canada) as well as receiving royalties from APPI and Springer. All other authors report no biomedical financial interests or potential conflicts of interest.
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- 2023
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40. Improving autism identification and support for individuals assigned female at birth: clinical suggestions and research priorities.
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Lai MC, Amestoy A, Bishop S, Brown HM, Giwa Onaiwu M, Halladay A, Harrop C, Hotez E, Huerta M, Kelly A, Miller D, Nordahl CW, Ratto AB, Saulnier C, Siper PM, Sohl K, Zwaigenbaum L, and Goldman S
- Subjects
- Infant, Newborn, Humans, Male, Female, Gender Identity, Research, Interpersonal Relations, Prevalence, Autistic Disorder diagnosis, Autistic Disorder epidemiology, Autistic Disorder psychology
- Abstract
Emerging evidence suggests that the higher prevalence of autism in individuals who are assigned male than assigned female at birth results from both biological factors and identification biases. Autistic individuals who are assigned female at birth (AFAB) and those who are gender diverse experience health disparities and clinical inequity, including late or missed diagnosis and inadequate support. In this Viewpoint, an international panel of clinicians, scientists, and community members with lived experiences of autism reviewed the challenges in identifying autism in individuals who are AFAB and proposed clinical and research directions to promote the health, development, and wellbeing of autistic AFAB individuals. The recognition challenges stem from the interplay between cognitive differences and nuanced or different presentations of autism in some AFAB individuals; expectancy, gender-related, and autism-related biases held by clinicians; and social determinants. We recommend that professional development for clinicians be supported by health-care systems, professional societies, and governing bodies to improve equitable access to assessment and earlier identification of autism in AFAB individuals. Autistic AFAB individuals should receive tailored support in education, identity development, health care, and social and professional sense of belonging., Competing Interests: Declaration of interests M-CL has received research funding support from the Canadian Institutes of Health Research Sex and Gender Science Chair (GSB 171373), and editorial honorarium from SAGE Publications. SB has received royalties from Western Psychological Services for sales of the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), consulting fees from Janssen, and honoraria for trainings on best diagnostic practices for autism, as well as trainings on use of the ADOS-2 and the Autism Diagnostic Interview-Revised (ADI-R). MGO is supported by the Ford Foundation and Next for Autism. AH is an employee of the Autism Science Foundation, has received honoraria for serving as a reviewer for the US Centers for Disease Control and Prevention, has received travel support from Emory University, serves as the Chair of a Data Safety Monitoring Board for a project at Drexel University, and is a member of both the Phelan McDermid Syndrome Foundation and the Interagency Autism Coordinating council (both unpaid). CH has received research funding support from the US National Institute of Child and Human Development, US National Center for Advancing Translational Sciences, the Eagles Autism Foundation, the Autism Science Foundation, and the Organization for Autism Research, and has received honoraria for serving as a reviewer for the US National Institutes of Health and US Department of Defense. CWN has received research funding support from the US National Institute of Mental Health (R01MH127046). ABR has received research funding support from the US National Institute of Mental Health (R01MH10028–12). CS has received royalties from Pearson Assessments for the Vineland Adaptive Behavior Scales, Third Edition and Wiley for two books related to autism and adaptive behaviour. KS has received research funding support from the US National Institutes of Health, Department of Defense, Missouri Department of Mental Health, Autism Speaks, and Cognoa; grants or contracts from the American Board of Pediatrics, University of Idaho, and University of New Mexico; consulting fees from Autism Navigator and Quadrant Biosciences; honoraria from WebMD/Medscape; payment for expert testimony from Missouri Board of Healing Arts; and has a leadership or fiduciary role in the American Academy of Pediatrics. LZ has received funding support from the Stollery Children's Hospital Foundation Chair in Autism. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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41. The Primary Prevention of Poststroke Epilepsy in Patients With Middle Cerebral Artery Infarct: Protocol for a Randomized Controlled Trial.
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Chen YS, Sung PS, Lai MC, and Huang CW
- Abstract
Background: Poststroke epilepsy poses a significant clinical challenge for individuals recovering from strokes, leading to a less favorable long-term outlook and increased mortality rates. Existing studies have primarily concentrated on administering antiseizure or anticonvulsant treatments only after the onset of late-onset seizures, without intervening during the epileptogenesis phase following a stroke., Objective: This research protocol is designed to conduct a randomized controlled trial to assess whether the early, preventive introduction of low-dose antiepileptic drug therapy (levetiracetam [LEV] or perampanel [PER]) in patients who have experienced middle cerebral artery (MCA) infarction can reduce the risk of developing poststroke epilepsy (primary prevention)., Methods: Participants with MCA infarction, either with or without reperfusion treatments, will be recruited and promptly receive preventive intervention within 72 hours of the stroke occurrence. These participants will be randomly assigned to receive either PER (4 mg per day), LEV (1000 mg per day), or a placebo that matches the active drugs. This treatment will continue for 12 weeks after allocation. Brain magnetic resonance imaging will be used to confirm the presence of MCA territory infarction, and an electroencephalography will be used to ensure the absence of epileptiform discharges or electrographic seizures at the time of the stroke. All participants will undergo follow-up assessments for 72 weeks after allocation., Results: The primary outcome under evaluation will be the incidence of poststroke epilepsy in the 3 groups following the 18-month study period. Secondary outcomes will encompass the time to the occurrence of the first seizure, the severity of seizures, any treatment-related adverse events, and the modified Rankin scale score at 3 and 18 months. Exploratory outcomes will involve comparing the effectiveness and safety of PER and LEV., Conclusions: We anticipate that the intervention groups will experience a lower incidence and reduced severity of poststroke epilepsy compared to the control group after 18 months. We aim to establish evidence supporting the potential preventive effects of LEV and PER on poststroke seizures and epilepsy in patients with MCA infarction, as well as to explore the antiepileptogenic potential of both LEV and PER in patients with major ischemic strokes., Trial Registration: ClinicalTrials.gov NCT04858841; https://clinicaltrials.gov/study/NCT04858841., International Registered Report Identifier (irrid): DERR1-10.2196/49412., (©Yu-Shiue Chen, Pi-Shan Sung, Ming-Chi Lai, Chin-Wei Huang. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 24.11.2023.)
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- 2023
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42. Methanovulcanius yangii gen. nov., sp. nov., a hydrogenotrophic methanogen, isolated from a submarine mud volcano in the offshore area of southwestern Taiwan.
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Chien HH, Lai MC, Weng CY, Chen MF, Wu SY, Lin S, and Chen SC
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- Base Composition, Phylogeny, RNA, Ribosomal, 16S genetics, Taiwan, Sequence Analysis, DNA, DNA, Bacterial genetics, Bacterial Typing Techniques, Fatty Acids chemistry, Hydrogen Peroxide, Methanomicrobiaceae, Sodium Chloride, Euryarchaeota
- Abstract
A novel mesophilic, hydrogenotrophic methanogen, strain CYW5
T , was isolated from a sediment sample of a piston core collected from submarine mud volcano MV5 located in the offshore area of southwestern Taiwan. Cells of strain CYW5T were irregular coccids, 0.5-1.0 µm in diameter and lysed easily by 0.01 % sodium dodecyl sulphate (SDS) treatment. Strain CYW5T utilized formate or hydrogen plus carbon dioxide as catabolic substrates for methanogenesis. The optimal growth conditions were 37 °C, 0.043-0.085 M NaCl and pH 6.02-7.32. The genomic DNA G+C content calculated from the genome sequence of strain CYW5T was 56.2 mol%. The results of phylogenetic analysis of 16S rRNA gene sequences indicated that strain CYW5T represented a member of the family Methanomicrobiaceae in the order Methanomicrobiales , and was closely related to the members of the genus Methanogenium . The most closely related species was Methanogenium cariaci JR1T (94.9 % of 16S rRNA gene sequence identity). The average nucleotide identity and average amino acid identity values between strain CYW5T and members of the family Methanomicrobiaceae were 74.7-78.5 % and 49.1-64.9%, respectively. Although many of the morphological and physiological characteristics of strain CYW5T and the species of the genus Methanogenium were similar, they were distinguishable by the differences in genomic G+C content and temperature, NaCl and pH ranges for growth. Based on these phenotypic, phylogenetic and genomic results, we propose that strain CYW5T represents a novel species, of a novel genus, named Methanovulcanius yangii gen. nov., sp. nov. The type strain is CYW5T (=BCRC AR10048T =DSM 100756T =NBRC 111404T ).- Published
- 2023
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43. Enhancing access to autism diagnostic services for children in the community.
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Penner M and Lai MC
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- 2023
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44. The impact of quality control on cortical morphometry comparisons in autism.
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Bedford SA, Ortiz-Rosa A, Schabdach JM, Costantino M, Tullo S, Piercy T, Lai MC, Lombardo MV, Di Martino A, Devenyi GA, Chakravarty MM, Alexander-Bloch AF, Seidlitz J, Baron-Cohen S, and Bethlehem RAI
- Abstract
Structural magnetic resonance imaging (MRI) quality is known to impact and bias neuroanatomical estimates and downstream analysis, including case-control comparisons, and a growing body of work has demonstrated the importance of careful quality control (QC) and evaluated the impact of image and image-processing quality. However, the growing size of typical neuroimaging datasets presents an additional challenge to QC, which is typically extremely time and labour intensive. One of the most important aspects of MRI quality is the accuracy of processed outputs, which have been shown to impact estimated neurodevelopmental trajectories. Here, we evaluate whether the quality of surface reconstructions by FreeSurfer (one of the most widely used MRI processing pipelines) interacts with clinical and demographic factors. We present a tool, FSQC, that enables quick and efficient yet thorough assessment of outputs of the FreeSurfer processing pipeline. We validate our method against other existing QC metrics, including the automated FreeSurfer Euler number, two other manual ratings of raw image quality, and two popular automated QC methods. We show strikingly similar spatial patterns in the relationship between each QC measure and cortical thickness; relationships for cortical volume and surface area are largely consistent across metrics, though with some notable differences. We next demonstrate that thresholding by QC score attenuates but does not eliminate the impact of quality on cortical estimates. Finally, we explore different ways of controlling for quality when examining differences between autistic individuals and neurotypical controls in the Autism Brain Imaging Data Exchange (ABIDE) dataset, demonstrating that inadequate control for quality can alter results of case-control comparisons., Competing Interests: J.S., R.A.I.B., and A.F.A.-B. hold shares in and are directors of Centile Bioscience Inc. A.F.A.-B. receives consulting income from Octave Bioscience. Other authors report no related funding support, financial or potential conflicts of interest., (© 2023 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)
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- 2023
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45. Mental health challenges faced by autistic people.
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Lai MC
- Subjects
- Humans, Mental Health, Cognition, Autistic Disorder psychology
- Abstract
Mental health challenges impede the well-being of autistic people. This Review outlines contributing neurodevelopmental and physical health conditions, rates and developmental trajectories of mental health challenges experienced by autistic people, as well as unique clinical presentations. A framework is proposed to consider four contributing themes to aid personalized formulation: social-contextual determinants, adverse life experiences, autistic cognitive features, and shared genetic and early environmental predispositions. Current evidence-based and clinical-knowledge-informed intervention guidance and ongoing development of support are highlighted for specific mental health areas. Tailored mental health support for autistic people should be neurodivergence-informed, which is fundamentally humanistic and compatible with the prevailing bio-psycho-social frameworks. The personalized formulation should be holistic, considering physical health and transdiagnostic neurodevelopmental factors, intellectual and communication abilities, and contextual-experiential determinants and their interplay with autistic cognition and biology, alongside resilience. Supporting family well-being is integral. Mutual empathic understanding is fundamental to creating societies in which people across neurotypes are all empowered to thrive., (© 2023. Springer Nature Limited.)
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- 2023
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46. Characterizing Subcortical Structural Heterogeneity in Autism.
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MacDonald DN, Bedford SA, Olafson E, Park MTM, Devenyi GA, Tullo S, Patel R, Anagnostou E, Baron-Cohen S, Bullmore ET, Chura LR, Craig MC, Ecker C, Floris DL, Holt RJ, Lenroot R, Lerch JP, Lombardo MV, Murphy DGM, Raznahan A, Ruigrok ANV, Smith E, Shinohara RT, Spencer MD, Suckling J, Taylor MJ, Thurm A, Lai MC, and Chakravarty MM
- Abstract
Autism presents with significant phenotypic and neuroanatomical heterogeneity, and neuroimaging studies of the thalamus, globus pallidus and striatum in autism have produced inconsistent and contradictory results. These structures are critical mediators of functions known to be atypical in autism, including sensory gating and motor function. We examined both volumetric and fine-grained localized shape differences in autism using a large ( n =3145, 1045-1318 after strict quality control), cross-sectional dataset of T1-weighted structural MRI scans from 32 sites, including both males and females (assigned-at-birth). We investigated three potentially important sources of neuroanatomical heterogeneity: sex, age, and intelligence quotient (IQ), using a meta-analytic technique after strict quality control to minimize non-biological sources of variation. We observed no volumetric differences in the thalamus, globus pallidus, or striatum in autism. Rather, we identified a variety of localized shape differences in all three structures. Including age, but not sex or IQ, in the statistical model improved the fit for both the pallidum and striatum, but not for the thalamus. Age-centered shape analysis indicated a variety of age-dependent regional differences. Overall, our findings help confirm that the neurodevelopment of the striatum, globus pallidus and thalamus are atypical in autism, in a subtle location-dependent manner that is not reflected in overall structure volumes, and that is highly non-uniform across the lifespan., Competing Interests: Conflict of Interest EO is an employee of Genentech, Inc. DGMM has served on advisory Boards to Roche and Servier. He also receives a stipend for editorial work from Springer. M-CL serves as an editor of the journal Autism and has received editorial honorarium from SAGE Publications.
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- 2023
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47. Identification of New Antiseizure Medication Candidates in Preclinical Animal Studies.
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Yang CS, Wu MC, Lai MC, Wu SN, and Huang CW
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- Animals, Seizures drug therapy, Drug Resistant Epilepsy
- Abstract
Epilepsy is a multifactorial neurologic disease that often leads to many devastating disabilities and an enormous burden on the healthcare system. Until now, drug-resistant epilepsy has presented a major challenge for approximately 30% of the epileptic population. The present article summarizes the validated rodent models of seizures employed in pharmacological researches and comprehensively reviews updated advances of novel antiseizure candidates in the preclinical phase. Newly discovered compounds that demonstrate antiseizure efficacy in preclinical trials will be discussed in the review. It is inspiring that several candidates exert promising antiseizure activities in drug-resistant seizure models. The representative compounds consist of derivatives of hybrid compounds that integrate multiple approved antiseizure medications, novel positive allosteric modulators targeting subtype-selective γ-Aminobutyric acid type A receptors, and a derivative of cinnamamide. Although the precise molecular mechanism, pharmacokinetic properties, and safety are not yet fully clear in every novel antiseizure candidate, the adapted approaches to design novel antiseizure medications provide new insights to overcome drug-resistant epilepsy.
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- 2023
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48. Unilateral non-lesional temporal lobe epilepsy presenting as isolated ictal vertigo: a case report.
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Tsai CH, Chen TS, Lai MC, and Huang CW
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- Humans, Female, Dizziness, Vertigo complications, Vertigo diagnosis, Seizures complications, Seizures diagnosis, Electroencephalography, Epilepsy, Temporal Lobe complications, Epilepsy, Temporal Lobe diagnosis
- Abstract
Temporal lobe epilepsy is the most common focal epilepsy syndrome and has a broad spectrum of presentations. Nevertheless, isolated vestibular symptoms without other symptoms typical of temporal lobe seizures are relatively rare. Here, we report one female patient who suffered from chronic refractory vertigo and had inappropriate pharmacotherapy for several years. Eventually, epileptic vertigo and dizziness (ictal vertigo) were accurately diagnosed by detailed history taking and serial examinations assisted by sphenoid electroencephalography. Awareness of this unique syndrome is important in the diagnosis of patients with epileptic vertigo and dizziness.
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- 2023
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49. Self-Harm Events and Suicide Deaths Among Autistic Individuals in Ontario, Canada.
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Lai MC, Saunders NR, Huang A, Artani A, Wilton AS, Zaheer J, Ameis SH, Brown HK, and Lunsky Y
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- Male, Female, Humans, Adolescent, Young Adult, Adult, Child, Preschool, Child, Cohort Studies, Ontario epidemiology, Autistic Disorder epidemiology, Intellectual Disability, Suicide psychology, Self-Injurious Behavior epidemiology, Self-Injurious Behavior psychology
- Abstract
Importance: Reasons for elevated suicide risks among autistic people are unclear, with insufficient population-based research on sex-specific patterns to inform tailored prevention and intervention., Objectives: To examine sex-stratified rates of self-harm events and suicide death among autistic individuals compared with nonautistic individuals, as well as the associated sociodemographic and clinical risk factors., Design, Setting, and Participants: This population-based matched-cohort study using linked health administrative databases in Ontario, Canada included all individuals with physician-recorded autism diagnoses from April 1, 1988, to March 31, 2018, each matched on age and sex to 4 nonautistic individuals from the general population. Self-harm events resulting in emergency health care from April 1, 2005, to December 31, 2020, were examined for one cohort, and death by suicide and other causes from April 1, 1993, to December 31, 2018, were examined for another cohort. Statistical analyses were conducted between October 2021 and June 2023., Exposure: Physician-recorded autism diagnoses from 1988 to 2018 from health administrative databases., Main Outcomes and Measures: Autistic and nonautistic individuals who were sex stratified a priori were compared using Andersen-Gill recurrent event models on self-harm events, and cause-specific competing risk models on death by suicide or other causes. Neighborhood-level income and rurality indices, and individual-level broad diagnostic categories of intellectual disabilities, mood and anxiety disorders, schizophrenia spectrum disorders, substance use disorders, and personality disorders were covariates., Results: For self-harm events (cohort, 379 630 individuals; median age at maximum follow-up, 20 years [IQR, 15-28 years]; median age of first autism diagnosis claim for autistic individuals, 9 years [IQR, 4-15 years]; 19 800 autistic females, 56 126 autistic males 79 200 nonautistic females, and 224 504 nonautistic males), among both sexes, autism diagnoses had independent associations with self-harm events (females: relative rate, 1.83; 95% CI, 1.61-2.08; males: relative rate, 1.47; 95% CI, 1.28-1.69) after accounting for income, rurality, intellectual disabilities, and psychiatric diagnoses. For suicide death (cohort, 334 690 individuals; median age at maximum follow-up, 19 years [IQR, 14-27 years]; median age of first autism diagnosis claim for autistic individuals, 10 years [IQR, 5-16 years]; 17 982 autistic females, 48 956 autistic males, 71 928 nonautistic females, 195 824 nonautistic males), there was a significantly higher crude hazard ratio among autistic females (1.98; 95% CI, 1.11-3.56) and a nonsignificantly higher crude hazard ratio among autistic males (1.34; 95% CI, 0.99-1.82); the increased risks were associated with psychiatric diagnoses., Conclusions and Relevance: This cohort study suggests that autistic individuals experienced increased risks of self-harm events and suicide death. Psychiatric diagnoses were significantly associated with the increased risks among both sexes, especially for suicide death, and in partially sex-unique ways. Autism-tailored and autism-informed clinical and social support to reduce suicide risks should consider multifactorial mechanisms, with a particular focus on the prevention and timely treatment of psychiatric illnesses.
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- 2023
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50. Health conditions and service use of autistic women and men: A retrospective population-based case-control study.
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Tint A, Chung H, Lai MC, Balogh R, Lin E, Durbin A, and Lunsky Y
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- Adult, Humans, Male, Female, Retrospective Studies, Case-Control Studies, Ontario, Autistic Disorder, Autism Spectrum Disorder
- Abstract
Lay Abstract: This study used administrative data from Ontario, Canada to compare the health conditions and service use of autistic women and men with adults with other developmental disabilities and with adults without developmental disabilities. Autistic women and men were more likely to have physical and mental health conditions compared to adults without developmental disabilities. Rates of health conditions were similar or lower among autistic adults compared to adults with other developmental disabilities, except more autistic adults had psychiatric conditions. Autistic women and men used higher rates of psychiatric services compared to all other groups. When comparing autistic women with same aged autistic men, sex differences were found for specific physical (Crohn's disease/colitis, rheumatoid arthritis) and psychiatric conditions (psychotic disorders, non-psychotic disorders), as well differences in service use (emergency department visits, hospitalizations, family doctor and neurologist visits). These results further highlight the high health needs and service use of autistic women and men, as well as adults with other developmental disabilities. It is critical for future research to focus on mental health support for autistic adults and to better understand how to tailor supports to best serve autistic women.
- Published
- 2023
- Full Text
- View/download PDF
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