Evaluating Linkage Quality of Population-Based Administrative Data for Health Service Research.

BACKGROUND: To overcome the limitations of relying on data from a single institution, many researchers have studied data linkage methodologies. Data linkage includes errors owing to legal issues surrounding personal information and technical issues related to data processing. Linkage errors affect selection bias, and external and internal validity. Therefore, quality verification for each connection method with adherence to personal information protection is an important issue. This study evaluated the linkage quality of linked data and analyzed the potential bias resulting from linkage errors. METHODS: This study analyzed claims data submitted to the Health Insurance Review and Assessment Service (HIRA DATA). The linkage errors of the two deterministic linkage methods were evaluated based on the use of the match key. The first deterministic linkage uses a unique identification number, and the second deterministic linkage uses the name, gender, and date of birth as a set of partial identifiers. The linkage error included in this deterministic linkage method was compared with the absolute standardized difference (ASD) of Cohen's according to the baseline characteristics, and the linkage quality was evaluated through the following indicators: linked rate, false match rate, missed match rate, positive predictive value, sensitivity, specificity, and F1-score. RESULTS: For the deterministic linkage method that used the name, gender, and date of birth as a set of partial identifiers, the true match rate was 83.5 and the missed match rate was 16.5. Although there was bias in some characteristics of the data, most of the ASD values were less than 0.1, with no case greater than 0.5. Therefore, it is difficult to determine whether linked data constructed with deterministic linkages have substantial differences. CONCLUSION: This study confirms the possibility of building health and medical data at the national level as the first data linkage quality verification study using big data from the HIRA. Analyzing the quality of linkages is crucial for comprehending linkage errors and generating reliable analytical outcomes. Linkers should increase the reliability of linked data by providing linkage error-related information to researchers. The results of this study will serve as reference data to increase the reliability of multicenter data linkage studies.

Non-coding de novo mutations in chromatin interactions are implicated in autism spectrum disorder.

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD). We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions. Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development. Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

Epigenetic Insights into Autism Spectrum Disorder: DNA Methylation Levels of NR3C1, ASCL1, and FOXO3 in Korean Autism Spectrum Disorder Sibling Pairs.

Objective: Previous research on autism spectrum disorder (ASD) in Koreans has primarily focused on genetic diversity because of its high heritability. However, the emerging recognition of transgenerational epigenetic changes has recently shifted research attention towards epigenetic perspectives. Methods: This study investigated the DNA methylation patterns of the promoter regions of candidate genes such as NR3C1, ASCL1, and FOXO3 in blood samples from ASD probands and their unaffected siblings. The analysis included 54 families (ASD proband group: 54; unaffected biological sibling group: 63). The diagnostic process involved screening the probands and their siblings for ASD based on the Diagnostic and Statistical Manual of Mental Disorders 5th edition. Intelligence, social ability, and medical history were thoroughly assessed using various scales and questionnaires. Genomic DNA from blood samples was analyzed using a methylation-sensitive quantitative polymerase chain reaction to examine the DNA methylation status of candidate genes. Results: Methylation levels in candidate gene promoter regions differed significantly between the proband and sibling groups for all candidate genes. Correlation analysis between the proband and sibling groups revealed strong and significant correlations in NR3C1 and ASCL1 methylation. Additionally, in the analysis of the relationship between DNA and ASD phenotypes, FOXO3 methylation correlated with social quotient in probands, and ASCL1 methylation was associated with nonverbal communication, and daily living skills as measured by the Korean Vineland Adaptive Behavior Scale. Notably, ASCL1 methylation was significantly associated with parental age at pregnancy. Conclusion: This study proposes DNA methylation of NR3C1, ASCL1, and FOXO3 in peripheral blood samples is a potential epigenetic biomarker of ASD.

Mood and Emotional Changes After PEERS® Program in Parents of Young Adults With Autism Spectrum Disorder.

Objectives: This study examined the changes in anxiety and depressive symptoms in the parents of Korean adults with autism spectrum disorder (ASD) after participating in the Korean version of the Program for the Education and Enrichment of Relational Skills for Young Adults (PEERS®-YA-K). Methods: Forty-six parents were enrolled (mean age 54.7 years; 22 fathers and 24 mothers), of whom 27 participated in the PEERS®- YA-K as social coaches. Participants completed self-report scales, including the Test of Young Adult Social Skills Knowledge (TYASSK), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Symptom Check-List-90-R (SCL-90-R). The scales were administered three times: before and after the 16-week program and 4 months after the program ended. Differences between participant variables at pretreatment, post-treatment, and follow-up were analyzed using paired-sample t-tests. Results: Participants showed a significant improvement in their social skills knowledge (TYASSK) (p<0.01). There was a significant improvement in the BAI and BDI scores of parents with severe depressive and anxiety symptoms at the baseline (p<0.05). Paternal paranoia and maternal hostility results also significantly improved on the SCL-90-R. Conclusion: This study suggests that PEERS®-YA-K can reduce parental anxiety and depressive symptoms. To the best of our knowledge, this is the first to compare the degree of depression and anxiety after PEERS®-YA-K in parents of adults with ASD.

Identification of the Porcine Vascular Endothelial Cell-Specific Promoter ESAM1.0 Using Transcriptome Analysis.

The vascular endothelium of xenografted pig organs represents the initial site of rejection after exposure to recipient immune cells. In this study, we aimed to develop a promoter specific to porcine vascular endothelial cells as a step toward overcoming xenograft rejection. Transcriptome analysis was performed on porcine aortic endothelial cells (PAECs), ear skin fibroblasts isolated from GGTA knockout (GTKO) pigs, and the porcine renal epithelial cell line pk-15. RNA sequencing confirmed 243 differentially expressed genes with expression changes of more than 10-fold among the three cell types. Employing the Human Protein Atlas database as a reference, we identified 34 genes exclusive to GTKO PAECs. The endothelial cell-specific adhesion molecule (ESAM) was selected via qPCR validation and showed high endothelial cell specificity and stable expression across tissues. We selected 1.0 kb upstream sequences of the translation start site of the gene as the promoter ESAM1.0. A luciferase assay revealed that ESAM1.0 promoter transcriptional activity was significant in PAECs, leading to a 2.8-fold higher level of expression than that of the porcine intercellular adhesion molecule 2 (ICAM2) promoter, which is frequently used to target endothelial cells in transgenic pigs. Consequently, ESAM1.0 will enable the generation of genetically modified pigs with endothelium-specific target genes to reduce xenograft rejection.

Delusional parasitosis as premotor symptom of parkinson's disease: A case report.

BACKGROUND: Delusional parasitosis is characterized by a false belief of being infested with parasites, insects, or worms. This illness is observed in patients with Parkinson's disease and is usually related to dopaminergic treatment. To our knowledge, no cases of delusional parasitosis have been reported as a premotor symptom or non-motor symptom of Parkinson's disease. CASE SUMMARY: A 75-year-old woman presented with a complaint of itching that she ascribed to the presence of insects in her skin, and she had erythematous plaques on her trunk, arms, buttocks, and face. These symptoms started two months before the visit to the hospital. She took medication, including antipsychotics, with a diagnosis of delusional parasitosis, and the delusion improved after three months. A year later, antipsychotics were discontinued, and anxiety and depression were controlled with medication. However, she complained of bradykinesia, masked face, hand tremor, and mild rigidity, and we performed fluorinated N-3-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane positron emission tomography (PET), which showed mildly decreased DAT binding in the right anterior putamen and caudate nucleus. Parkinson's disease was diagnosed on the basis of PET and clinical symptoms. CONCLUSION: In conclusion, delusional parasitosis can be considered a non-motor sign of Parkinson's disease along with depression, anxiety, and constipation.

Remofuscin induces xenobiotic detoxification via a lysosome-to-nucleus signaling pathway to extend the Caenorhabditis elegans lifespan.

Lipofuscin is a representative biomarker of aging that is generated naturally over time. Remofuscin (soraprazan) improves age-related eye diseases by removing lipofuscin from retinal pigment epithelium (RPE) cells. In this study, the effect of remofuscin on longevity in Caenorhabditis elegans and the underlying mechanism were investigated. The results showed that remofuscin significantly (p < 0.05) extended the lifespan of C. elegans (N2) compared with the negative control. Aging biomarkers were improved in remofuscin-treated worms. The expression levels of genes related to lysosomes (lipl-1 and lbp-8), a nuclear hormone receptor (nhr-234), fatty acid beta-oxidation (ech-9), and xenobiotic detoxification (cyp-34A1, cyp-35A1, cyp-35A2, cyp-35A3, cyp-35A4, cyp-35A5, cyp-35C1, gst-28, and gst-5) were increased in remofuscin-treated worms. Moreover, remofuscin failed to extend the lives of C. elegans with loss-of-function mutations (lipl-1, lbp-8, nhr-234, nhr-49, nhr-8, cyp-35A1, cyp-35A2, cyp-35A3, cyp-35A5, and gst-5), suggesting that these genes are associated with lifespan extension in remofuscin-treated C. elegans. In conclusion, remofuscin activates the lysosome-to-nucleus pathway in C. elegans, thereby increasing the expression levels of xenobiotic detoxification genes resulted in extending their lifespan.

Diagnostic validity of Autism Diagnostic Observation Schedule, second edition (K-ADOS-2) in the Korean population.

BACKGROUND: Although the Korean version of the Autism Diagnostic Observation Schedule-2 (K-ADOS-2) is widely being used to diagnose autism spectrum disorder (ASD) in South Korea, no previous study has examined the validity and reliability of all modules of K-ADOS-2 across a wide age range, particularly older children, adolescents, and adults. METHOD: Data from 2,158 participants were included (mean age = 79.7 months; 73.6% male): 1473 participants with ASD and 685 participants without ASD (Toddler Module, n = 289; Module 1, n = 642; Module 2 n = 574; Module 3 n = 411; Module 4, n = 242). Participants completed a battery of tests, including the K-ADOS or K-ADOS-2 and other existing diagnostic instruments. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, positive predictive value (PPV), negative predictive value (NPV), Cohen's kappa (k), and agreement with existing diagnostic instruments were computed. Cronbach's α values were also calculated. RESULTS: All developmental cells of the K-ADOS-2 showed sufficient ranges of sensitivity 85.4-100.0%; specificity, 80.4-96.8%; area under the ROC curve, .90-.97; PPV, 77.8-99.3%; NPV, 80.6-100.0%; and k values, .83-.92. The kappa agreements of developmental cells with existing diagnostic instruments ranged from .20 to .90. Cronbach's α values ranged from .82 to .91 across all developmental cells. LIMITATION: The best-estimate clinical diagnoses made in this study were not independent of the K-ADOS-2 scores. Some modules did not include balanced numbers of participants in terms of gender and diagnostic status. CONCLUSION: The K-ADOS-2 is a valid and reliable instrument in diagnosing ASD in South Korea. Future studies exploring the effectiveness of the K-ADOS-2 in capturing restricted, repetitive behaviors and differentiating ASD from other developmental disabilities are needed.

Validation of Social Responsiveness Scale for Korean Preschool Children With Autism.

OBJECTIVE: This cross-cultural study aims to examine the psychometric properties of the Social Responsiveness Scale (SRS) and to determine the best-estimate-cut-off scores for the diagnosis of autism spectrum disorder (ASD) in Korean preschool children. METHODS: A total of 563 children was recruited from multiple sources, including Seoul National University Bundang Hospital. Participants were assessed by a multidisciplinary research team using multiple diagnostic tools based on DSM-5 diagnostic criteria. Discriminative validity was tested by comparing the difference in SRS scores between ASD and non-ASD groups. Convergent validity was tested by examining correlations between SRS scores with other diagnostic instruments. A receiver operation characteristic curve analysis was conducted to test the sensitivity and specificity of SRS and to determine the best-estimate-cut-off scores for screening ASD in Korean preschool children. RESULTS: There were significant differences in the total SRS scores between the ASD (n=242) and non-ASD group (n=321) (p<0.01, 95% confidence interval [CI]: 14.08-17.24). The differences were significant even after adjusting for age. SRS scores were significantly correlated with other prescreening diagnostic tools for ASD. The best-estimate cut-off score to screen ASD was 55 (area under curve=0.88, sensitivity 78.1%, specificity 86.6%). CONCLUSION: The SRS is a valid and reliable instrument to screen and aid in the diagnosis of ASD in Korean preschool children. The adjusted cut-off scores, notably lower than in the original U.S. version, may yield a more accurate diagnosis by reflecting transcultural differences.

Validating the Autism Diagnostic Interview-Revised in the Korean Population.

OBJECTIVE: This study aimed to examine the validity of the Korean version of the Autism Diagnostic Interview-Revised (K-ADI-R) and determine its efficacy in identifying individuals with autism spectrum disorder (ASD). METHODS: Data were pooled from several past and ongoing studies as well as clinical records acquired at Seoul National University Bundang Hospital from 2008 to 2017. The K-ADI-R were administered and scored by trained research reliable examiners. Measurements to investigate the validity of the K-ADI-R was through sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and Cohen's kappa. RESULTS: A total of 1,271 (age 88.9±62.42 months, male=927) participants were included. The K-ADI-R yielded strong psychometric properties with high sensitivity (86.06-99.27%), specificity (84.75-99.55%), PPV (92.33-99.72%), and NPV (79.43-98.64%). There were significant differences in item scores across the K-ADI-R diagnostic algorithm regardless of age and sex (p<0.001). Agreement between the K-ADI-R and other ASD related measurements ranged between levels of good to excellent. CONCLUSION: Despite language or cultural boundaries, the K-ADI-R demonstrated high levels of sensitivity, specificity, PPV, and NPV within a wide range of participants; hence, suggesting promising usage as a valuable diagnostic instrument for individuals with ASD.

Predicting Dementia With Prefrontal Electroencephalography and Event-Related Potential.

Objective: To examine whether prefrontal electroencephalography (EEG) can be used for screening dementia. Methods: We estimated the global cognitive decline using the results of Mini-Mental Status Examination (MMSE), measurements of brain activity from resting-state EEG, responses elicited by auditory stimulation [sensory event-related potential (ERP)], and selective attention tasks (selective-attention ERP) from 122 elderly participants (dementia, 35; control, 87). We investigated that the association between MMSE and each EEG/ERP variable by using Pearson's correlation coefficient and performing univariate linear regression analysis. Kernel density estimation was used to examine the distribution of each EEG/ERP variable in the dementia and non-dementia groups. Both Univariate and multiple logistic regression analyses with the estimated odds ratios were conducted to assess the associations between the EEG/ERP variables and dementia prevalence. To develop the predictive models, five-fold cross-validation was applied to multiple classification algorithms. Results: Most prefrontal EEG/ERP variables, previously known to be associated with cognitive decline, show correlations with the MMSE score (strongest correlation has |r| = 0.68). Although variables such as the frontal asymmetry of the resting-state EEG are not well correlated with the MMSE score, they indicate risk factors for dementia. The selective-attention ERP and resting-state EEG variables outperform the MMSE scores in dementia prediction (areas under the receiver operating characteristic curve of 0.891, 0.824, and 0.803, respectively). In addition, combining EEG/ERP variables and MMSE scores improves the model predictive performance, whereas adding demographic risk factors do not improve the prediction accuracy. Conclusion: Prefrontal EEG markers outperform MMSE scores in predicting dementia, and additional prediction accuracy is expected when combining them with MMSE scores. Significance: Prefrontal EEG is effective for screening dementia when used independently or in combination with MMSE.

Anti-asthma and antitussive effects of a fermented extract of a mixture of Ramulus mori, Anthriscus sylvestris, and Salvia plebeian.

Respiratory immunity is getting more important recently due to outbreak of respiratory diseases and increasing the concentration of fine dust. The aim of this study was to investigate respiratory protection effect of a fermented extract of medicinal plants (FEMP) containing Ramulus mori, Salvia plebeia, and Anthriscus sylvestris. The expression levels of IL-8 and IL-17 in LPS/poly-L-arginine (PLA) and FEMP-cotreated A549 cells were lower than those in LPS/PLA only-treated cells. The levels of IgE, IL-17, and IL-4 in the bronchoalveolar lavage fluid (BALF) and serum of FEMP-treated mice with ovalbumin/LPS-induced asthma were lower than the control levels. The lung inflammation score and the number of inflammatory cells in the BALF decreased by FEMP treatment. In the citric acid-induced coughing guinea pig, the FEMP treatment decreased the number of coughs. Therefore, FEMP shows anti-asthmatic and antitussive activities without hepatotoxicity and can be used as a compound aiming to improve respiratory health. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00955-3.

A Randomized Controlled Trial of the Korean Version of the Program for the Education and Enrichment of Relational Skills for Young Adults (PEERS®-YA-K) With Autism Spectrum Disorder: A Pilot Study.

Evidence-based social skills interventions for young adults are limited, despite social difficulties in autism spectrum disorder (ASD) persisting after transition to adulthood. The Program for the Education and Enrichment of Relational Skills for Young Adults (PEERS®-YA) is an evidence-based intervention found to be effective in improving relational skills in young adults with ASD. To translate the original American version of the PEERS®-YA treatment manual into Korean, intensive interviews were performed. Based on results from interviews, several rules of dating etiquette and social activities were modified to be culturally sensitive and linguistically appropriate. Next, young adults diagnosed with ASD (18-35 years of age; IQ > 70) and their social coaches were recruited for the randomized controlled trial (RCT). Participants were randomly assigned either to a treatment group (TG; n = 19) or a delayed treatment group (DTG; n = 18). In the analysis of group differences in the TG and DTG, social skills knowledge was improved. The within group analyses showed positive effects of improving social skills knowledge on reducing depression and anxiety symptoms. After modest cultural adaptations focusing on dating and social activities, the implementation of the PEERS®-YA-K was found feasible for the Korean community. This is one of only a few cross-cultural validation trials establishing evidence-based treatment in young adults with ASD. Clinical Trial Registration: This trial was registered at ClinicalTrials.gov, identifier: NCT03310775.

Phylogeography and Antioxidant Activity of Proso Millet (Panicum miliaceum L.).

Proso millet (Panicum miliaceum L.) or broomcorn millet is among the most important food crops to be domesticated by humans; it is widely distributed in America, Europe, and Asia. In this study, we genotyped 578 accessions of P. miliaceum using 37 single-sequence repeat (SSR) markers, to study the genetic diversity and population structure of each accession. We also investigated total phenolic content (TPC) and superoxide dismutase (SOD) activity and performed association analysis using SSR markers. The results showed that genetic diversity and genetic distance were related to geographic location and the fixation index (Fst). Population structure analysis divided the population into three subpopulations. Based on 3 subpopulations, the population is divided into six clusters in consideration of geographical distribution characteristics and agronomic traits. Based on the genetic diversity, population structure, pairwise Fst, and gene flow analyses, we described the topological structure of the six proso millet subpopulations, and the geographic distribution and migration of each cluster. Comparison of the published cluster (cluster 1) with unique germplasms in Japan and South Korea suggested Turkey as a possible secondary center of origin and domestication (cluster 3) for the cluster. We also discovered a cluster domesticated in Nepal (cluster 6) that is adapted to high-latitude and high-altitude cultivation conditions. Differences in phenotypic characteristics, such as TPC, were observed between the clusters. The association analysis showed that TPC was associated with SSR-31, which explained 7.1% of the total variance, respectively. The development of markers associated with TPC and SOD will provide breeders with new tools to improve the quality of proso millet through marker-assisted selection.

Short caregiver interview and play observation for early screening of autism spectrum disorder: Behavior development screening for toddlers (BeDevel).

This study validates behavior development screening for toddlers (BeDevel), which utilizes a combination of short caregiver interviews (BeDevel-I) and semistructured play observations (BeDevel-P). The data of 431 toddlers (male 66.2%; mean age (SD) = 29.11 (8.59) months; ASD, n = 201; developmental delay, n = 46; typically developing, n = 184), aged 18 ~ 42 months, were included in the validation of BeDevel. The best clinical estimate diagnosis, screening rate, validity, sensitivity, and reliability of BeDevel were determined based on data cross-sectionally collected using BeDevel and existing diagnostic/screening instruments: autism diagnostic observation schedule (ADOS), autism diagnostic interview (ADI-R), Vineland adaptive behavior scales-II (VABS-II), social response scales (SRS), sequenced language scale for infants (SELSI), Korean childhood autism rating scale (K-CARS), and Korean social communication questionnaire (K-SCQ). The k values of BeDevel-I and BeDevel-P were 0.055 ~ 0.732 and 0.291 ~ 0.752, respectively. Items related to social referencing in BeDevel-P had a particularly high diagnostic validity (k = 0.483 ~ 0.684). Reliabilities of BeDevel-I and BeDevel-P were sufficient (Cronbach's alpha = 0.86 ~ 0.88 and 0.92 ~ 0.95, respectively). BeDevel-I and BeDevel-P showed high sensitivity (BeDevel-I: 85.00 ~ 89.29%; BeDevel-P: 85.00 ~ 91.75%), specificity (BeDevel-I: 77.55 ~ 89.55%; BeDevel-P: 85.09 ~ 97.01%), PPV (BeDevel-I: 70.83 ~ 88.54%; BeDevel-P: 81.52 ~ 94.68%), and NPV (BeDevel-I: 76.00 ~ 95.24%; BeDevel-P: 84.62 ~ 95.45%). The agreement between the composite BeDevel score and ADOS, ADI-R, K-CARS, and K-SCQ was >67.6% (range = 67.6 ~ 90.8%). Combining a short caregiver interview and direct play observation is a valid and reliable screening process. More studies on social referencing as an important early marker are needed. BeDevel can be utilized as a secondary screening instrument before diagnostic confirmation in clinical and community settings. LAY SUMMARY: BeDevel, which consists of a short caregiver interview and direct play observation, is a valid and reliable screening instrument for autism spectrum disorder (ASD). We suggest that BeDevel can be utilized as a secondary instrument before administering diagnostic assessments in clinical and community settings. More studies examining social referencing as a potential behavioral marker of ASD are needed.

Higher Lactate Level and Lactate-to-Pyruvate Ratio in Autism Spectrum Disorder.

Mitochondrial dysfunction is considered one of the pathophysiological mechanisms of autism spectrum disorder (ASD). However, previous studies of biomarkers associated with mitochondrial dysfunction in ASD have revealed inconsistent results. The objective of this study was to evaluate biochemical markers associated with mitochondrial dysfunction in subjects with ASD and their unaffected family members. Lactate and pyruvate levels, as well as the lactate-to-pyruvate ratio, were examined in the peripheral blood of probands with ASD (Affected Group, AG) and their unaffected family members (biological parents and unaffected siblings, Unaffected Group, UG). Lactate ≥22 mg/dl, pyruvate ≥1.4 mg/dl, and lactate-topyruvate ratio >25 were defined as abnormal. The clinical variables were compared between subjects with higher (>25) and lower (≤25) lactate-topyruvate ratios within the AG. The AG (n=59) had a significantly higher lactate and lactate-to-pyruvate ratio than the UG (n=136). The frequency of subjects with abnormally high lactate levels and lactate-to-pyruvate ratio was significantly higher in the AG (lactate 31.0% vs. 9.5%, ratio 25.9% vs. 7.3%, p<0.01). The relationship between lactate level and the repetitive behavior domain of the Autism Diagnostic Interview-Revised was statistically significant. These results suggest that biochemical markers related to mitochondrial dysfunction, especially higher lactate levels and lactateto- pyruvate ratio, might be associated with the pathophysiology of ASD. Further larger studies using unrelated individuals are needed to control for the possible effects of age and sex on chemical biomarker levels.

The veA gene is necessary for the negative regulation of the veA expression in Aspergillus nidulans.

The veA gene is one of the key genes in regulating sexual development of Aspergillus nidulans. During the study on the veA gene, it was observed that the veA expression level is slightly higher in a veA1 mutant than in a wild type at 37 degrees C, suggesting that the wild type veA gene is necessary for the negative regulation of the veA expression. In the veA1 mutant, the veA expression was higher than in a wild type grown at 42 degrees C but equal at 30 degrees C. Furthermore, in a veA deletion mutant having its own promoter and the N-terminus of the VeA ORF, expression of the N-terminus by the veA promoter was highly up-regulated, supporting the possibility that the veA gene is important for the negative regulation of the veA expression. Analyses of the lacZ transcript and the beta-galactosidase activity from the reporter strains in the veA1 background, which were constructed by transformation of the lacZ reporter plasmids containing the lacZ gene under the control of the intact or the truncated veA promoters from the -943 to +262 bp region, showed that the truncated promoters produced more veA transcript and higher beta-galactosidase activity than the intact one at 30 degrees C, but equal at 42 degrees C. In addition, the serial-deletion analysis of the veA promoter identified a crucial region in the promoter from -943 to -740 bp for this derepression of the veA expression. Taken together, these results indicated that the veA gene is necessary for the negative regulation of the veA expression. Moreover, the veA expression was derepressed in the light-illuminated condition, where the VeA protein is hardly transported into the nucleus.

Age as a Moderator of Social Skills Intervention Response Among Korean Adolescents with Autism Spectrum Disorder.

Few studies have investigated the effect of age on treatment effectiveness of evidence-based social skills training in autism spectrum disorder (ASD) adolescents. This study evaluated the effectiveness of Program for the Education and Enrichment of Relational Skills (PEERS®) in different ages of ASD adolescents. A total of 110 ASD adolescents aged 11-19 years were divided into early, middle, and late adolescence groups, and the changes in outcome measures following intervention were compared among the three groups. We found that the improvements in social competence after PEERS® were significant, but the treatment effects were not significantly different among the three age groups. The findings suggest that PEERS® is beneficial for ASD adolescents regardless of patient age and adolescence stage.

Differences in Personality, Defense Styles, and Coping Strategies in Individuals with Depressive Disorder According to Age Groups Across the Lifespan.

OBJECTIVE: This study aimed to examine the differences in personality, defense style, and coping styles among patients with depression according to age groups. METHODS: A total of 211 participants ranging from 19 to 81 years old were recruited for the study. To assess participants' five dimensions of personality, the Neuroticism-Extraversion-Openness Personality Inventory-Revised (NEO-PI-R) was administered. In addition, the Korean-Defense Style Questionnaire and the Korean version of the coping checklist were administered to examine the defense and coping style. RESULTS: In the analysis of NEO-PI-R, the mean value of Agreeableness, Conscientiousness, and Neuroticism showed significant differences between the young adult age group (20-34 years) and the late middle age group (50-64 years) (p<0.05). The young age group used more immature defense styles and made less use of problem-focused coping strategy than the old age patients (65 years and older) (p<0.05). CONCLUSION: In the young age group associations with lower Agreeableness and Conscientiousness, as well as higher Neuroticism than the late middle age group were observed. Moreover, the young age group had a higher usage of immature defense style, and restricted use of problem-focused coping style than other age groups.

The Feasibility and Validity of Autism Spectrum Disorder Screening Instrument: Behavior Development Screening for Toddlers (BeDevel)-A Pilot Study.

Although early screening is critical for individuals with autism spectrum disorder (ASD) in order to receive early intervention and improve function later in life, screening is often delayed. Limitations of existing screening instruments, and the need for a culturally appropriate early screening tool in Korean children, led us to develop Behavior Development Screening for Toddlers (BeDevel). The BeDevel assessment consists of two parts: BeDevel-Interview, a structured interview measure for parents/primary caregivers; and BeDevel-Play, a play-based semi-structured observational measure in children. To examine the feasibility and validity of BeDevel, 155 children (N = 75 ASD, N = 55 typical development, N = 25 developmentally delayed) aged 18-42 months (M = 31.54 months, SD = 7.60) were examined through parent-reported screening questionnaires, BeDevel, and standard diagnostic assessments. When BeDevel items were analyzed using Cohen's kappa statistics, most items in BeDevel-Interview and all items in BeDevel-Play were reasonably consistent with diagnoses. We identified primary items, which were significantly interacted with actual diagnosis in the chi-squared test (P < 0.05, range = 0.000-0.032). Using cutoff numbers of items determined using the receiver operating characteristics curve, BeDevel showed satisfactory levels of sensitivity (83.33%-100%), specificity (81.25%-100%), positive predictive values (80.65%-100%), and negative predictive values (83.87%-100%), as well as high internal consistency (Cronbach's α = 0.866-959). The agreement between BeDevel and most other screening/diagnostic instruments was moderate (k = 0.419-1.000). These results suggest that BeDevel can be a useful instrument for early screening of ASD. Autism Res 2019, 12: 1112-1128. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Although early screening is critical for individuals with autism spectrum disorder (ASD) in order to receive early intervention and improve function later in life, screening is often delayed. Limitations of existing screening instruments and the need for a culturally appropriate early screening tool in Korean children led us to develop Behavior Development Screening for Toddlers (BeDevel). The BeDevel assessment consists of two parts: BeDevel-Interview, a structured interview measure for parents/primary caregivers; and BeDevel-Play, a play-based, semi-structured observational measure in children. In order to test the feasibility and validity of BeDevel, we analyzed preliminary data of total 155 children aged 18-42 months, examined through parent-reported screening questionnaires, BeDevel, and standard diagnostic assessments. When individual items were analyzed, responses of all BeDevel-Interview items and of most BeDevel-Play items well matched actual diagnoses, and we identified primary items, which were particularly useful in differentiating between the ASD group and the non-ASD group. With the optimal screening criteria determined, the BeDevel was able to identify individuals with a diagnosis of ASD and those without it, all at satisfactory levels. Lastly, BeDevel items were closely related as a set, and the BeDevel screening results were reasonably consistent with the results of most other screening/diagnostic instruments. These results suggest that BeDevel can be a useful instrument for early screening of ASD.