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Noncystic fibrosis bronchiectasis is a chronic respiratory disease that carries high socioeconomic and medical burdens and is caused by diverse respiratory illnesses. To improve clinical outcomes, early recognition, active treatment of exacerbations, and prevention of further exacerbations are essential. However, evidence for the treatment and prevention of acute exacerbation of noncystic fibrosis bronchiectasis, especially in children, is lacking. Therefore, the evidence- and consensus-based guidelines for medical and nonmedical treatment strategies for noncystic fibrosis bronchiectasis in children and adolescents were developed by the Korean Academy of Pediatric Allergy and Respiratory Disease using the methods recommended by the Grading of Recommendations Assessment, Development, and Evaluation working group with evidence published through July 2, 2020. This guideline encompasses evidence-based treatment recommendations as well as expert opinions, addressing crucial aspects of the treatment and management of non-cystic fibrosis bronchiectasis in children. This includes considerations for antibiotics and airway clearance strategies, particularly in areas where evidence may be limited. Large, well-designed, and controlled studies are required to accumulate further evidence of management strategies for noncystic fibrosis bronchiectasis in children and adolescents.

Abstract Background Digital therapeutics (DTx) is a treatment option that uses computer software to provide evidence-based interventions for medical disorders. DTx platforms are digital services that facilitate interactions among stakeholders of DTx treatment within a standardized structure. However, there is still a lack of overall awareness regarding the effectiveness and usage of DTx and DTx platforms. This study aimed to investigate insomnia patients’ recognition, thoughts, feelings, and demands for conventional treatments versus DTx for insomnia. Methods Nine participants, aged 19–50 years, who had experience with professional medical interventions for insomnia, were recruited through purposive sampling. Two online focus group interviews, each lasting 1.5 h, were conducted. The interview questions focused on difficulties encountered during conventional treatment, inadequate recognition of DTx, and concerns and demands regarding DTx and its platform. The data were analyzed using thematic analysis. Results The participants reported subjective difficulties associated with receiving conventional treatment, including concerns about drug side effects and dependence, social stigma, and lack of perceived necessity for treatment. They expressed concerns about DTx, such as cost-effectiveness, evidence on efficacy, and concerns about breach of personal information. Additionally, their demands included convenience of use, reduction in social stigma related to the use of DTx, compatibility of DTx with other healthcare systems, and enhanced communication with healthcare providers when using DTx platforms. Conclusions The focus group highlighted the need for increased awareness, demonstrated efficacy, cost-effectiveness, cybersecurity measures, and accessibility of insomnia DTx and its platforms. Tailored approaches considering patient characteristics are crucial for widespread adoption of insomnia DTx and its platforms.

Abstract This systematic review and meta-analysis aimed to investigate the prevalence of self-reported sleep disturbances in people living with HIV considering the effects of age, depression, anxiety, CD4 cell counts, time since HIV diagnosis, study region, and the instruments used to measure sleep disturbances. We searched PubMed, PsycINFO, and EMBASE to include eligible articles. In this meta-analysis of 43 studies, the pooled prevalence of self-reported sleep disturbances was 52.29% (95% confidence interval 47.69–56.87). The subgroup analyses revealed that variations in the sleep measurements and study region significantly contributed to the observed heterogeneity. In the meta-regression analyses, higher proportions of participants with depression or anxiety and longer times since HIV diagnosis were significantly associated with a higher prevalence of self-reported sleep disturbances after adjusting for mean age. Our findings emphasise the substantial burden of sleep disturbances in people living with HIV and identified comorbid depression and anxiety and the time since HIV diagnosis as significant moderators. These results underscore the importance of considering these factors when designing tailored screening programmes for high-risk patients and implementing early interventions to prevent and mitigate sleep disturbances in people living with HIV.

BackgroundA global-scale pandemic, such as the COVID-19 pandemic, greatly impacted communities of color. Moreover, physical distancing recommendations during the height of the COVID-19 pandemic negatively affected people’s sense of social connection, especially among young individuals. More research is needed on the use of social media and communication about depression, with a specific focus on young Black Americans. ObjectiveThis paper aims to examine whether there are any differences in social-networking characteristics before and during the pandemic periods (ie, pre–COVID-19 pandemic vs peri–COVID-19 pandemic) among the students of historically black colleges and universities (HBCUs). For the study, the researchers focus on the students who have posted a depression-related tweet or have retweeted such posts on their timeline and also those who have not made such tweets. This is done to understand the collective patterns of both groups. MethodsThis paper analyzed the social networks on Twitter (currently known as X; X Corp) of HBCU students through comparing pre–COVID-19 and peri–COVID-19 pandemic data. The researchers quantified the structural properties, such as reciprocity, homophily, and communities, to test the differences in internet-based socializing patterns between the depression-related and non–depression related groups for the 2 periods. ResultsDuring the COVID-19 pandemic period, the group with depression-related tweets saw an increase in internet-based friendships, with the average number of friends rising from 1194 (SD 528.14) to 1371 (SD 824.61; P

Objective We aimed to improve the performance of sleep prediction algorithms by increasing the data amount, adding variables reflecting psychological state, and adjusting the data length.Materials and Methods We used ActiGraph GT3X+® and Galaxy Watch Active2™ to collect physical activity and light exposure data. We collected heart rate variability (HRV) data with the Galaxy Watch. We evaluated the performance of sleep prediction algorithms based on different data sources (wearable devices only, sleep diary only, or both), data lengths (1, 2, or 3 days), and analysis methods. We defined the target outcome, ‘good sleep’, as ≥90% sleep efficiency.Results Among 278 participants who denied having sleep disturbance, we used data including 2136 total days and nights from 230 participants. The performance of the sleep prediction algorithms improved with an increased amount of data and added HRV data. The model with the best performance was the extreme gradient boosting model; XGBoost, using both sources combined data with HRV, and 2-day data (accuracy=.85, area under the curve =.80).Conclusions The results show that the performance of the sleep prediction models improved by increasing the data amount and adding HRV data. Further studies targeting insomnia patients and applied researches on non-pharmacological insomnia treatment are needed.

Background: Atopic dermatitis and autoimmune diseases are highly heritable conditions that may co-occur from an early age. Methods: The primary study is a national administrative cohort study involving 499,428 children born in 2002, tracked until 2017. Atopic dermatitis was defined as five or more principal diagnoses of atopic dermatitis and two or more topical steroid prescriptions. We estimated the risks for the occurrence of 41 autoimmune diseases, controlling for risk factors. In addition, we sourced a gene library from the National Library of Medicine to conduct a comprehensive gene ontology. We used Gene Weaver to identify gene set similarity and clustering, and used GeneMania to generate a network for shared genes. Results: Exposed and unexposed groups included 39,832 and 159,328 children, respectively. During a mean follow-up of 12 years, the exposed group had an increased risk of autoimmune disease (hazard ratio, 1.27 [95 % confidence interval, 1.23–1.32]) compared to the unexposed group. The hazard ratios of autoimmune illnesses consistently increased with two- and five years lag times and alternative atopic dermatitis definitions. Shared genes between atopic dermatitis and autoimmune diseases were associated with comorbidities such as asthma, bronchiolitis, and specific infections. Genetic interactions of these shared genes revealed clustering in Th1, Th2, Th17, and non-classifiable pathways. Conclusions: Atopic dermatitis was significantly associated with an increased risk of subsequent autoimmune disease. we identified the genetically associated disease in atopic dermatitis patients comorbid with autoimmune disease and demonstrated a genetic network between atopic dermatitis and autoimmune diseases.

Abstract Link prediction algorithms are indispensable tools in many scientific applications by speeding up network data collection and imputing missing connections. However, in many systems, links change over time and it remains unclear how to optimally exploit such temporal information for link predictions in such networks. Here, we show that many temporal topological features, in addition to having high computational cost, are less accurate in temporal link prediction than sequentially stacked static network features. This sequential stacking link prediction method uses 41 static network features that avoid detailed feature engineering choices and is capable of learning a highly accurate predictive distribution of future connections from historical data. We demonstrate that this algorithm works well for both partially observed and completely unobserved target layers, and on two temporal stochastic block models achieves near-oracle-level performance when combined with other single predictor methods as an ensemble learning method. Finally, we empirically illustrate that stacking multiple predictive methods together further improves performance on 19 real-world temporal networks from different domains.

The ongoing COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study is a prospective birth cohort investigating the origin and natural courses of childhood allergic diseases, including atopic dermatitis, food allergy, allergic rhinitis and asthma, with long-term prognosis. Initiated under the premise that allergic diseases result from a complex interplay of immune development alterations, environmental exposures, and host susceptibility, the COCOA study explores these dynamic interactions during prenatal and postnatal periods, framed within the hygiene and microbial hypotheses alongside the developmental origins of health and disease (DOHaD) hypothesis. The scope of the COCOA study extends to genetic predispositions, indoor and outdoor environmental variables affecting mothers and their offsprings such as outdoor and indoor air pollution, psychological factors, diets, and the microbiomes of skin, gut, and airway. We have embarked on in-depth investigations of diverse risk factors and the pathophysiological underpinnings of allergic diseases. By employing multi-omics approaches—proteomics, transcriptomics, and metabolomics—we gain deeper insights into the distinct pathophysiological processes across various endotypes of childhood allergic diseases, incorporating the exposome using extensive resources within the COCOA study. Integration with large-scale datasets, such as national health insurance records, enhances robustness and mitigates potential limitations inherent to birth cohort studies. As part of global networks focused on childhood allergic diseases, the COCOA study fosters collaborative research across multiple cohorts. The findings from the COCOA study are instrumental in informing precision medicine strategies for childhood allergic diseases, underpinning the establishment of disease trajectories.

Abstract Ballet, a mainstream performing art predominantly associated with women, exhibits significant gender imbalances in leading positions. However, the collaboration’s structural composition vis-à-vis gender representation in the field remains unexplored. Our study investigates the gendered labor force composition and collaboration patterns in ballet creations. Our findings reveal gender disparities in ballet creations aligned with gendered collaboration patterns and women’s occupation of more peripheral network positions than men. Productivity disparities show women accessing 20–25% of ballet creations compared to men. Mathematically derived perception errors show the underestimation of women artists’ representation within ballet collaboration networks, potentially impacting women’s careers in the field. Our study highlights the structural imbalances that women face in ballet creations and emphasizes the need for a more inclusive and equal professional environment in the ballet industry. These insights contribute to a broader understanding of structural gender imbalances in artistic domains and can inform cultural organizations about potential affirmative actions toward a better representation of women leaders in ballet.

Real-world network datasets are typically obtained in ways that fail to capture all edges. The patterns of missing data are often non-uniform as they reflect biases and other shortcomings of different data collection methods. Nevertheless, uniform missing data is a common assumption made when no additional information is available about the underlying missing-edge pattern, and link prediction methods are frequently tested against uniformly missing edges. To investigate the impact of different missing-edge patterns on link prediction accuracy, we employ 9 link prediction algorithms from 4 different families to analyze 20 different missing-edge patterns that we categorize into 5 groups. Our comparative simulation study, spanning 250 real-world network datasets from 6 different domains, provides a detailed picture of the significant variations in the performance of different link prediction algorithms in these different settings. With this study, we aim to provide a guide for future researchers to help them select a link prediction algorithm that is well suited to their sampled network data, considering the data collection process and application domain.

Abstract Despite research into the development of digital cognitive behavioral therapy for insomnia (dCBT-I), research into the outcomes of dCBT-I on insomnia and the associated clinical conditions of depression and anxiety have been limited. The PubMed, PsycINFO (Ovid), Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) on adult patients with insomnia also having reported measures of depressive or anxiety symptoms. In total, 2504 articles were identified after duplicate removal, and 22 RCTs were included in the final meta-analysis. At the post-treatment assessment, the dCBT-I group had a small to moderate effect in alleviating depressive (standardized mean difference (SMD) = −0.42; 95% CI: −0.56, −0.28; p

Background Human coronaviruses (HCoV) cause mild upper respiratory infections; however, in 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, causing an acute respiratory disease pandemic. Coronaviruses exhibit marked epidemiological and clinical differences. Purpose This study compared the clinical, laboratory, and radiographic findings of children infected with SARS-CoV-2 versus HCoV. Methods SARS-CoV-2 data were obtained from the Korea Disease Control and Prevention Agency (KDCA) registry and 4 dedicated coronavirus disease 2019 (COVID-19) hospitals. Medical records of children admitted with a single HCoV infection from January 2015 to March 2020 were collected from 10 secondary/tertiary hospitals. Clinical data included age, sex, underlying disease, symptoms, test results, imaging findings, treatment, and length of hospital stay. Results We compared the clinical characteristics of children infected with HCoV (n=475) to those of children infected with SARS-CoV-2 (272 from KDCA, 218 from COVID-19 hospitals). HCoV patients were younger than KDCA patients (older than 9 years:3.6% vs. 75.7%; P

Abstract Liver cancer, comprised primarily of hepatocellular carcinoma (HCC), is the third leading cause of cancer deaths worldwide and increasing in Western countries. We previously identified the transcription factor zinc fingers and homeoboxes 2 (Zhx2) as a regulator of hepatic gene expression, and many Zhx2 target genes are dysregulated in HCC. Here, we investigate HCC in Zhx2‐deficient mice using the diethylnitrosamine (DEN)–induced liver tumor model. Our study using whole‐body Zhx2 knockout (Zhx2KO) mice revealed the complete absence of liver tumors 9 and 10 months after DEN exposure. Analysis soon after DEN treatment showed no differences in expression of the DEN bioactivating enzyme cytochrome P450 2E1 (CYP2E1) and DNA polymerase delta 2, or in the numbers of phosphorylated histone variant H2AX foci between Zhx2KO and wild‐type (Zhx2wt) mice. The absence of Zhx2, therefore, did not alter DEN bioactivation or DNA damage. Zhx2KO livers showed fewer positive foci for Ki67 staining and reduced interleukin‐6 and AKT serine/threonine kinase 2 expression compared with Zhx2wt livers, suggesting that Zhx2 loss reduces liver cell proliferation and may account for reduced tumor formation. Tumors were reduced but not absent in DEN‐treated liver‐specific Zhx2 knockout mice, suggesting that Zhx2 acts in both hepatocytes and nonparenchymal cells to inhibit tumor formation. Analysis of data from the Cancer Genome Atlas and Clinical Proteomic Tumor Consortium indicated that ZHX2 messenger RNA and protein levels were significantly higher in patients with HCC and associated with clinical pathological parameters. Conclusion: In contrast to previous studies in human hepatoma cell lines and other HCC mouse models showing that Zhx2 acts as a tumor suppressor, our data indicate that Zhx2 acts as an oncogene in the DEN‐induced HCC model and is consistent with the higher ZHX2 expression in patients with HCC.

p21-Activated kinase 4 (PAK4), one of the serine/threonine kinases activated by Rho-family GTPases, has been widely studied as an oncogenic protein that is overexpressed in many types of cancers. In our recent study, PAK4 upregulation was observed in mice exhibiting hepatic ischaemia-reperfusion (I/R) and in liver transplantation patients. Liver I/R injury was also attenuated in Pak4 KO mice. Herein, we report a novel series of pyrazolo[3,4-d]pyrimidine derivatives of type I ½ PAK4 inhibitors. The most potent compound SPA7012 was evaluated to determine the pharmacological potential of PAK4 inhibitor in I/R injury in mice. Mice with I/R injury showed typical patterns of liver damage, as demonstrated by increases in serum levels of aminotransferases and proinflammatory cytokines, hepatocellular necrosis and apoptosis, and inflammatory cell infiltration, relative to sham mice. Conversely, intraperitoneal administration of SPA7012 dramatically attenuated biochemical and histopathologic changes. Mechanistically, stabilisation of nuclear factor-erythroid 2-related factor 2 (Nrf2), a master regulator of anti-oxidative response, was observed following SPA7012 treatment. SPA7012 treatment in primary hepatocytes also attenuated hypoxia-reoxygenation-induced apoptotic cell death and inflammation. Together, these results provide experimental evidence supporting the use of PAK4 inhibitors for alleviation of I/R-induced liver damage.

In the early days of the coronavirus disease 2019 (COVID-19) pandemic, allergic diseases, especially asthma, were considered to be risk factors for severe COVID-19 infection, hospitalization, and death. These concerns stemmed from the idea that individuals with allergic diseases are generally more susceptible to respiratory virus infections, which are major causes of exacerbation of allergic diseases. However, epidemiologic data with mechanistic studies showed that the associations between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes of allergic diseases are complex and affected by diverse factors such as allergic disease severity, phenotypes, and control status with current medications. In addition, children generally have less severe clinical outcomes of COVID-19 than those of adults, which complicates the association between allergic diseases and COVID-19-related outcomes among them. The present review summarizes the potential association between allergic diseases and COVID-19-related outcomes and discusses the factors requiring consideration. The findings viewed herein will aid the management of allergic diseases in patients with SARS-CoV-2 infection and the establishment of medical polices for managing patients with allergic diseases.

Abstract Background Subjective cognitive decline (SCD) is a target for Alzheimer’s disease prediction. Plasma amyloid-beta oligomer (AβO), the pathogenic form of Aβ in blood, has recently been proposed as a novel blood-based biomarker of AD prediction by representing brain Aβ deposition. The relationship between plasma AβO, brain Aβ deposition, and SCD in individuals with normal objective cognition has not been investigated. Methods In this cross-sectional study, we analyzed 126 participants with normal objective cognition. More SCD symptoms were expressed as higher scores of the Subjective Cognitive Decline Questionnaire (SCDQ) and Memory Age-associated Complaint Questionnaire (MACQ). The plasma AβO level of each participant was measured twice for validation and expressed as a concentration (ng/mL) and a ratio relative to the mean value of two internal standards. Brain Aβ deposition was assessed by [18F] flutemetamol positron emission tomography (PET) and expressed as standard uptake value ratio (SUVR). Associations of SCDQ and MACQ with plasma AβO levels or SUVR were analyzed in multiple linear regression models. The association between plasma AβO level and flutemetamol PET positivity was assessed in logistic regression and receiver operative characteristic analyses. Results Overall, participants were 73.3 years old with female predominance (69.0%). After adjustment for confounders, high SCDQ and MACQ scores were associated with the high plasma AβO levels as both concentrations and ratios (ratios: standardized coefficient = 0.246 and p = 0.023 for SCDQ, standardized coefficient = 0.209 and p = 0.029 for MACQ; concentrations: standardized coefficient = 0.257 and p = 0.015 for SCDQ, standardized coefficient = 0.217 and p = 0.021 for MACQ). In contrast, SCDQ and MACQ were not significantly associated with SUVRs (p = 0.134 for SCDQ, p = 0.079 for MACQ). High plasma AβO levels were associated with flutemetamol PET (+) with an area under the curve of 0.694 (ratio) or 0.662 (concentration). Combined with APOE e4, plasma AβO presented area under the curves of 0.789 (ratio) and 0.783 (concentration). Conclusions Our findings indicate that the high plasma AβO level could serve as a potential surrogate biomarker of severe SCD and the presence of brain Aβ deposition in individuals with normal objective cognition.

Abstract Introduction Macrolide‐resistant Mycoplasma pneumoniae (MRMP) has become prevalent in children. This study investigated the clinical and laboratory variables of MRMP and macrolide‐sensitive M. pneumoniae (MSMP) and identified factors associated with prolonged hospital admission in children. Methods A prospective multicenter study was conducted in 1063 children

Abstract Background Although individuals with dementia have a high risk of developing seizures, whether seizures are associated with cholinesterase inhibitors, which are commonly prescribed to treat individuals with dementia, remains unknown. This study investigated the risk of incident seizure following cholinesterase inhibitor use in patients with dementia. Methods A nationwide, nested case-control study was conducted using data from the Korean Health Insurance Review and Assessment Service (HIRA) from 2014 through 2018. A total of 13,767 participants aged 65–95 years who experienced incident seizure were propensity score-matched for medical comorbidities and drug exposure at a 1:3 ratio with a control group of 39,084 participants. The study examined the incidence of seizures in patients diagnosed with dementia within one year after receiving cognitive enhancers. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for seizure incidence according to cholinesterase inhibitor use were analyzed using a multivariable conditional logistic regression model. Results There was no statistically significant association between duration of cholinesterase inhibitors use and seizure risk. Although there was slight increased seizure risk in patient after receiving donepezil for 1 year compared to memantine, subgroup analyses stratified age and sex did not reveal any significant association between cholinesterase inhibitors use and late-onset seizure. Conclusions Our findings suggest no immediate increase in seizure risk is associated with cholinesterase inhibitor use, although the risk of seizure in patients with dementia did increase after one year of continued medication intake. Further study is required to obtain confirmatory results on the seizure-related safety of cognitive enhancers in patients with dementia.

Abstract Background The prevalence of refractory Mycoplasma pneumoniae (MP) pneumonia has been increasing. However, few studies have investigated the impact of respiratory virus coinfection in patients with MP pneumonia, and their results have been inconclusive. This study aimed to investigate the impact of respiratory virus coinfection in children hospitalized with MP pneumonia. Methods This study enrolled 145 children hospitalized with MP pneumonia between May 2019 and March 2020. The patients were divided into two groups: the respiratory virus coinfection and non-coinfection groups. All the children underwent polymerase chain reaction testing for respiratory virus infection. Information on clinical, laboratory, and radiologic findings were obtained retrospectively via medical chart reviews. Results Children in the respiratory virus coinfection group were younger than those in the non-coinfection group. Respiratory virus coinfection in children hospitalized with MP pneumonia was significantly associated with persistence of fever more than 6 days (adjusted odds ratio [aOR], 2.394; 95% confidence interval [95% CI], 1.172–4.892), severe pneumonia (aOR, 4.602; 95% CI, 1.154–18.353), and poor response to the stepwise approach for MP pneumonia (aOR, 4.354; 95% CI, 1.374–13.800). In addition, higher levels of liver enzymes and lactate dehydrogenase at admission were associated with respiratory virus coinfection in children with MP pneumonia. Conclusions The results of this study suggest that respiratory virus coinfection in children hospitalized with MP pneumonia may be associated with refractory MP pneumonia.

Abstract The interplay between schizophrenia liability and environmental influences has been considered to be responsible for the development of schizophrenia. Recent neuroimaging studies have linked aberrant functional connectivity (FC) between the default-mode network (DMN) and the frontoparietal network (FPN) in the resting-state to the underlying neural mechanism of schizophrenia. By using schizotypy as the proxy for genetic-based liability to schizophrenia and methylation of brain-derived neurotrophic factor (BDNF) to represent environmental exposure, this study investigated the impact of the interaction between vulnerability and the environment on the neurobiological substrates of schizophrenia. Participants in this study included 101 healthy adults (HC) and 46 individuals with ultra-high risk for psychosis (UHR). All participants were tested at resting-state by functional magnetic resonance imaging, and group-independent component analysis was used to identify the DMN and the FPN. The Perceptual Aberration Scale (PAS) was used to evaluate the schizotypy level. The methylation status of BDNF was measured by pyrosequencing. For moderation analysis, the final sample consisted of 83 HC and 32 UHR individuals. UHR individuals showed reduced DMN-FPN network FC compared to healthy controls. PAS scores significantly moderated the relationship between the percentage of BDNF methylation and DMN-FPN network FC. The strength of the positive relationship between BDNF methylation and the network FC was reduced when the schizotypy level increased. These findings support the moderating role of schizotypy on the neurobiological mechanism of schizophrenia in conjunction with epigenetic changes.

Abstract Background The present study aimed to identify the clinical significance of Mycoplasma pneumoniae (MP)-specific immunoglobulin M (IgM) titer, in addition to a diagnosis of MP infection, in children with MP pneumonia. Methods This study was performed in 155 children hospitalized with MP pneumonia. The clinical features and laboratory and radiographic findings on admission in children with positive or negative MP-specific IgM titers were retrospectively reviewed from the electronic medical records. Results The mean age of the included children was 6.0 years, and 118 (76.1%) of the children were positive for MP-specific IgM. A longer duration between symptom onset and admission (adjusted odds ratio [aOR] 1.47, 95% confidence interval [CI] 1.24–1.75), longer duration of symptoms during the illness (aOR 1.15, 95% CI 1.02–1.30), and development of extra-pulmonary manifestations (aOR 9.16, 95% CI 1.96–42.81) were significantly associated with a positive MP-specific IgM titer. Serum lactate dehydrogenase levels (aOR 1.00, 95% CI 1.00–1.01) and pneumonic infiltration involving > 50% of the total lung volume on chest radiography (aOR 4.68, 95% CI 1.12–19.55) were associated with positive MP-specific IgM in children with MP pneumonia. A poor response to stepwise treatment for MP pneumonia was more common in children with a positive MP-specific IgM titer than those with a negative MP-specific IgM titer on admission. Conclusions A positive MP-specific IgM titer at diagnosis of MP pneumonia may partially suggest an exaggerated immune response with a higher disease burden compared to children with MP pneumonia with a negative MP-specific IgM titer.

Abstract Background Respiratory infections among children, particularly community-acquired pneumonia (CAP), is a major disease with a high frequency among outpatient and inpatient visits. The causes of CAP vary depending on individual susceptibility, the epidemiological characteristics of the community, and the season. We performed this study to establish a nationwide surveillance network system and identify the causative agents for CAP and antibiotic resistance in Korean children with CAP. Methods The monitoring network was composed of 28 secondary and tertiary medical institutions. Upper and lower respiratory samples were assayed using a culture or polymerase chain reaction (PCR) from August 2018 to May 2020. Results A total of 1023 cases were registered in patients with CAP, and PCR of atypical pneumonia pathogens revealed 422 cases of M. pneumoniae (41.3%). Respiratory viruses showed a positivity rate of 65.7% by multiplex PCR test, and human rhinovirus was the most common virus, with 312 cases (30.5%). Two hundred sixty four cases (25.8%) were isolated by culture, including 131 cases of S. aureus (12.8%), 92 cases of S. pneumoniae (9%), and 20 cases of H. influenzae (2%). The cultured, isolated bacteria may be colonized pathogen. The proportion of co-detection was 49.2%. The rate of antibiotic resistance showed similar results as previous reports. Conclusions This study will identify the pathogens that cause respiratory infections and analyze the current status of antibiotic resistance to provide scientific evidence for management policies of domestic respiratory infections. Additionally, in preparation for new epidemics, including COVID-19, monitoring respiratory infections in children and adolescents has become more important, and research on this topic should be continuously conducted in the future.

Abstract Recurrent bacterial infection causes frequent bronchiectasis (BE) exacerbations. The effectiveness and safety of long-term administration of macrolides in BE remain controversial, especially in children who require minimal treatment to prevent exacerbation. We conducted this meta-analysis to determine the usefulness of long-term macrolide use in pediatric BE. We searched PubMed, Cochrane Library databases, Embase, KoreaMed, Igaku Chuo Zasshi, and Chinese National Knowledge Infrastructure databases. We identified randomized controlled trials (RCTs) which elucidated long-term macrolide treatment (≥ 4 weeks) in non-cystic fibrosis BE in children aged

Background: Experiences of negative social interactions and childhood trauma (CT) can lead to aberrant hypothalamic–pituitary–adrenal functions. Poor theory of mind (ToM) ability is related to increased social stress levels; however, studies on the relationship between ToM and cortisol remain scarce. Objective: This study aimed to evaluate the relationship between ToM and the hair cortisol concentration (HCC) in healthy young adults considering the moderating role of CT. Method: A total of 206 healthy young adults were divided into two groups based on an experience of moderate-to-severe childhood trauma (CT+ and CT–). To determine whether CT moderated the relationship between ToM and HCC, moderation analysis was conducted controlling for age, sex, years of education, and scores of perceived stress, depression, and anxiety. Results: CT+ individuals reported higher subjective stress perception and depressive symptoms than CT– individuals, whereas anxiety-related symptoms, ToM, and HCC were not different between the groups. The experience of CT significantly moderated the relationship between ToM and HCC. The association between poorer ToM ability and higher HCC was significant only in CT+ group. Conclusion: CT is a moderator of the association between ToM and HCC, indicating the importance of CT in social cognition and the stress response.

Highlights Associations between hair cortisol level and psychological factors have been inconclusive. In healthy young adults, the hair cortisol concentration was not significantly different between sexes. The association between emotion dysregulation and hair cortisol was only found in women, but not in men. The role of sex should be considered in utilizing hair cortisol as a biomarker for psychological stress response.

Abstract Faculty hiring networks—who hires whose graduates as faculty—exhibit steep hierarchies, which can reinforce both social and epistemic inequalities in academia. Understanding the mechanisms driving these patterns would inform efforts to diversify the academy and shed new light on the role of hiring in shaping which scientific discoveries are made. Here, we investigate the degree to which structural mechanisms can explain hierarchy and other network characteristics observed in empirical faculty hiring networks. We study a family of adaptive rewiring network models, which reinforce institutional prestige within the hierarchy in five distinct ways. Each mechanism determines the probability that a new hire comes from a particular institution according to that institution’s prestige score, which is inferred from the hiring network’s existing structure. We find that structural inequalities and centrality patterns in real hiring networks are best reproduced by a mechanism of global placement power, in which a new hire is drawn from a particular institution in proportion to the number of previously drawn hires anywhere. On the other hand, network measures of biased visibility are better recapitulated by a mechanism of local placement power, in which a new hire is drawn from a particular institution in proportion to the number of its previous hires already present at the hiring institution. These contrasting results suggest that the underlying structural mechanism reinforcing hierarchies in faculty hiring networks is a mixture of global and local preference for institutional prestige. Under these dynamics, we show that each institution’s position in the hierarchy is remarkably stable, due to a dynamic competition that overwhelmingly favors more prestigious institutions. These results highlight the reinforcing effects of a prestige-based faculty hiring system, and the importance of understanding its ramifications on diversity and innovation in academia.

The timing of complementary food (CF) introduction is closely related to childhood health, and it may vary depending on the region, culture, feeding type, or health condition. Despite numerous studies on the benefits of breastfeeding and the optimal timing of CF introduction, there have been limited investigations regarding delayed CF introduction in exclusively breastfed children. We compared an exposed group (CF introduction ≥7 months) with a reference group (CF introduction at 4 –< 7 months) regarding hospital admission, disease burden, and growth until age 10. Data from a nationwide population-based cohort study involving children born between 2008 and 2012 in the South Korea were analyzed. The final cohort comprised 206,248 children (165,925 in the exposed group and 40,323 in the reference group). Inverse probability of treatment weighting with propensity score matching was used to balance baseline health characteristics in the comparison groups. We estimated the incident risk ratios (IRR) for outcomes using modified Poisson regression and weighted odds ratios (weighted ORs) and their 95% confidence intervals (CIs) using multinomial logistic regression. The exposed group was associated with low height-for-age z-score (HAZ) (IRR (95% CI) for −1.64 < HAZ ≤ −1.03: 1.11 (1.08 to 1.14); HAZ ≤ −1.64: 1.21 (1.14 to 1.27)) and frequent (≥6 events) hospitalizations (weighted OR 1.18 (1.09 to 1.29). The rates of hospital admission, death, and specific medical conditions did not differ between groups. However, delaying the introduction of CF until seven months in exclusively breastfed infants was associated with frequent hospitalization events and lower heights.

(1) Background: Feeding behavior habits have a pattern with a certain tendency during infancy. We aimed to identify the associations between feeding patterns in infancy and the subsequent 10-year childhood disease burden. (2) Methods: Data from 236,372 infants were obtained from the national health insurance and screening program records in South Korea. Parent-administered questionnaires during infancy provided details on the feeding type and types/frequency of complementary food for analyzing feeding patterns. The outcomes were all-cause hospitalization and the development of 15 representative childhood diseases until the age of 10 years. Anthropometric measurements obtained at 6 years of age were analyzed. To estimate outcome risks while considering multiple risk factors, we employed a Cox proportional hazard and modified Poisson regression. (3) Results: Three clusters were identified: high prevalence of breastfeeding with regular exposure to a variety of solid foods (n = 116,372, cluster 1), similar prevalence of breastfeeding and formula feeding with less exposure to solid foods (n = 108,189, cluster 2), and similar prevalence of breastfeeding and formula feeding with the least exposure to solid foods in infancy (n = 11,811, cluster 3). Compared with cluster 1, children in clusters 2 and 3 had increased risks of all-cause hospitalization (hazard ratio (HR), (95% confidence interval (CI)), 1.04 (1.03–1.06) and 1.08 (1.05–1.11), respectively). Children in clusters 2 and 3 had an increased risk of upper respiratory infection, pneumonia, and gastroenteritis, as well as neurobehavioral diseases. Overweight/obesity at the age of 6 years was associated with clusters 2 and 3. (4) Conclusions: Feeding patterns in infancy were associated with an increased risk of childhood disease burden.

Abstract Cognitive complaints after chemotherapy are common in breast cancer patients, but the neural bases for these complaints remain unclear. This pilot study explored resting-state functional connectivity (FC) as a marker of subtle cognitive changes in breast cancer patients who experience cognitive complaints. Chemotherapy-treated (n = 20, at least 6 months off therapy) and untreated (n = 17, disease-control) female breast cancer patients with cognitive complaints and healthy controls (n = 20) were recruited. The FC of the right dorsolateral prefrontal cortex was calculated, and any correlations between this FC and neuropsychological assessments were determined. Chemotherapy-treated patients with cognitive complaints displayed increased FC between the right dorsolateral prefrontal cortex and both the contralateral cerebellar lobule VII and the cerebellar vermis XI, compared to the disease-control and healthy-control groups, despite unimpaired neuropsychological performance. The increased FC was negatively correlated with executive function and attention in breast cancer survivors with cognitive complaints. Our pilot study findings provide evidence that cerebellar-cortical FC changes may be a pathophysiological basis for chemotherapy-related cognitive complaints. In addition, the FC changes have the potential to reflect minor or compensated cognitive function impairment in breast cancer patients.

ObjectivesHostile attribution bias is reportedly common from non-clinical population to those with serious mental illness, such as schizophrenia, and is known to be closely related to theory of mind (ToM). This study aimed to investigate whether ToM skills mediate the relationship among neurocognitive ability, personality traits, and attribution bias.MethodsA total of 198 (101 females) non-clinical youths were recruited. To assess their neurocognitive ability and ToM skills, the participants were asked to complete Raven’s Standard Progressive Matrices (SPM) and the Korean version of the Reading the Mind in Eyes Test (K-RMET). To determine their personality traits, the Eysenck Personality Questionnaire (psychoticism) and interpersonal reactivity index (perspective taking) were used. To evaluate hostile attribution bias, the Ambiguous Intentions Hostility Questionnaire was administered. Path analysis and bias-corrected percentile bootstrap methods were used to estimate model fit and the parameters of the mediating effects.ResultsBased on model comparison, the best model characterized (1) two direct pathways from psychoticism and the K-RMET to hostility attribution bias and (2) three indirect pathways, wherein SPM, perspective taking, and psychoticism influenced hostile attribution bias through K-RMET. The final model fit indices were good [x2/df = 1.126; comparative fit index = 0.996; root mean square error of approximation = 0.026; standard root mean square residual = 0.026 and Akaike information criterion = 28.251] and the K-RMET fully mediated the association between SPM, perspective taking, psychoticism, and hostile attribution bias.ConclusionThe main findings suggested that ToM skills, such as the RMET, play an important role in explaining the relationship among neurocognitive ability, personality traits, and hostile attribution bias. ToM skills and a remediation strategy may need to be developed to balance the enhanced hostility bias that underlies the paranoia.

Triple negative breast cancer (TNBC) is an aggressive disease with a 5-y relative survival rate of 11% after distant metastasis. To survive the metastatic cascade, tumor cells remodel their signaling pathways by regulating energy production and upregulating survival pathways. AMP-activated protein kinase (AMPK) and Akt regulate energy homeostasis and survival, however, the individual or synergistic role of AMPK and Akt isoforms during lung colonization by TNBC cells is unknown. The purpose of this study was to establish whether targeting Akt, AMPKα or both Akt and AMPKα isoforms in circulating cancer cells can suppress TNBC lung colonization. Transient silencing of Akt1 or Akt2 dramatically decreased metastatic colonization of lungs by inducing apoptosis or inhibiting invasion, respectively. Importantly, transient pharmacologic inhibition of Akt activity with MK-2206 or AZD5363 inhibitors did not prevent colonization of lung tissue by TNBC cells. Knockdown of AMPKα1, AMPKα2, or AMPKα1/2 also had no effect on metastatic colonization of lungs. Taken together, these findings demonstrate that transient decrease in AMPK isoforms expression alone or in combination with Akt1 in circulating tumor cells does not synergistically reduce TNBC metastatic lung colonization. Our results also provide evidence that Akt1 and Akt2 expression serve as a bottleneck that can challenge colonization of lungs by TNBC cells.

Abstract Propyl-paraben exposure is associated with aeroallergen sensitization, but its association with atopic dermatitis (AD) is inconclusive. No studies have been conducted on the metabolomic pathways underlying these associations. We investigated the associations between propyl-paraben exposure and aeroallergen sensitization, AD, and Eczema Area and Severity Index (EASI) score and identified the underlying pathways using untargeted metabolomics analysis. We enrolled 455 children in a general population study. Skin prick tests were performed with the assessment of EASI score. Urinary propyl-, butyl-, ethyl-, and methyl-paraben levels were measured. Untargeted metabolomics analysis was performed on the first and fifth urine propyl-paraben quintile groups. The highest urine propyl-paraben quintile group was associated with aeroallergen sensitization, but not with AD. Glycine, threonine, serine, ornithine, isoleucine, arabinofuranose, d-lyxofuranose, citrate, and picolinic acid levels were higher, whereas palmitic acid and 2-palmitoylglycerol levels were lower in the highest quintile propyl-paraben group, than in the lowest quintile group. The propyl-paraben-induced metabolic perturbations were associated with serine and glycine metabolisms, branched-chain amino acid metabolism, and ammonia recycling. Propyl-paraben exposure was associated with aeroallergen sensitization and EASI score, partially via metabolomic changes related with oxidative stress, mTOR, peroxisome proliferator-activated receptors pathway, aryl hydrocarbon receptor signaling pathways, and tricarboxylic acid cycle.

Exposure to environmental factors can cause interstitial lung diseases (ILDs); however, such types of ILDs are rare. From 2007 to 2011, an ILD epidemic occurred in South Korea owing to inhalational exposure to toxic chemicals in humidifier disinfectants (HDs). HD-associated ILDs (HD-ILDs) are characterized by rapidly progressing respiratory failure with pulmonary fibrosis and a high mortality rate of 43.8%−58.0%. Although 18.1%−31.1% of the general population used HDs, only a small proportion of HD users were diagnosed with HD-ILDs. This finding suggests that investigation of the pathophysiologies underlying HD-ILDs is needed in addition to the identification of susceptibility to HD-ILDs. Further, there have been several concerns regarding the diverse health effects of exposure to toxic chemicals in HDs, including those that have not been identified, and long-term prognoses in terms of pulmonary function and residual pulmonary lesions observed on follow-up chest images. In this review, we summarize the clinical features, pathologic findings, and changes in radiologic findings over time in patients with HD-ILDs and the results of previous experimental research on the mechanisms underlying the effects of toxic chemicals in HDs. Studies are currently underway to identify the pathophysiologies of HD-ILDs and possible health effects of exposure to HDs along with the development of targeted therapeutic strategies. The experience of identification of HD-ILDs has encouraged stricter control of safe chemicals in everyday life.

Abstract Background Community–acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. Methods We conducted a retrospective study in 30,994 children (aged 0–18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. Results MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children

Objective: Mold exposure in early life may be associated with development of atopic dermatitis; however, studies of this link are inconclusive and evidence for the underlying mechanism(s) is lacking. This study identified the association between the time of mold exposure and development of atopic dermatitis and investigated the underlying mechanisms. Method: The association between atopic dermatitis and mold exposure was examined in the Cohort for Childhood Origin of Asthma and Allergic Diseases birth cohort study (n = 1446). Atopic dermatitis was diagnosed at 1 year of age by pediatric allergists. Exposure to mold was assessed by questionnaire. The Illumina MiSeq platform was used to examine the environmental mycobiome in 20 randomly selected healthy infants and 20 infants with atopic dermatitis at 36 weeks of gestation. Results: Prenatal, but not postnatal, mold exposure was significantly associated with atopic dermatitis (adjusted odds ratio, 1.36; 95% confidence interval, 1.01-1.83). Levels of total serum IgE at 1 year of age were higher in infants with atopic dermatitis exposed to mold during pregnancy than in healthy infants not exposed to mold during pregnancy (p = 0.021). The relative abundance of uncultured Ascomycota was higher in infants with atopic dermatitis than in healthy infants. The relative abundance of uncultured Ascomycota correlated with total serum IgE levels at 1 year of age (r = 0.613, p

Abstract Background Use of humidifier disinfectants (HD) at home leads to chemical airborne exposure, causing HD associated lung injury (HDLI) with high mortality. However, the lung function in children diagnosed with HDLI is not well studied. We investigated the effect of HD exposure on lung function, prognosis, and exposure characteristics associated with the lung function phenotype in children. Methods Eighty-one children diagnosed with HDLI in a nationwide cohort were tested for spirometry and diffusing capacity of the lung for carbon monoxide (DLco) from July 2013 and followed up with at five time points over 2 years. The results were compared with 122 children without HD exposure as controls. Home investigation and questionnaire analysis were conducted to assess HD inhalation exposure. Results HDLI survivor’s mean percent of predicted forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and corrected DLco were significantly lower compared with the control group. On longitudinal assessment, FVC was within the normal range, but flattened, and spirometry showed a predominantly restrictive pattern. Corrected DLco did not normalize above 80% despite increasing age. The persistently low phenotype of lung function was associated with initial exposure age, especially less than 12 months of age. Higher density HD exposure during sleep and close distance between the bed and the humidifier were significantly associated with persistently low corrected DLco. Conclusions HD exposure affects prolonged decrement in lung function, especially DLco, particularly among children who are exposed within the first year of life. These results suggested that early-life HD exposure determines long-term prognosis of lung function in children.

Owing to the rarity of post-infectious bronchiolitis obliterans (PIBO), pulmonary function in children with PIBO has been mainly investigated in small-sample sized studies. This systematic review and meta-analysis investigated pulmonary function in children with PIBO, regardless of age at respiratory insult and PIBO diagnosis. A systematic literature search revealed 16 studies reporting pulmonary function data in 480 children with PIBO. Levels of key pulmonary function parameters were summarized by pooled mean difference (MD) only in children with PIBO, and a random effect model was used. Pooled MDs (95% confidence interval [CI]) for FEV1, FVC, and FEF25–75% were 51.4, (44.2 to 58.5), 68.4 (64.4 to 72.3), and 26.5 (19.3 to 33.6) % predicted, respectively, with FEV1/FVC of 68.8% (62.2 to 75.4). Pooled MDs (95% CI) of the z-scores for FEV1, FVC, and FEF25–75% were −2.6 (−4.2 to −0.9), −1.9 (−3.2 to −0.5), and −2.0 (−3.6 to −0.4). Pooled MD (95% CI) for the diffusion capacity of the lungs for carbon monoxide from two studies was 64.9 (45.6 to 84.3) % predicted. The post-bronchodilator use change in the FEV1 in three studies was 6.1 (4.9 to 7.2). There was considerable heterogeneity across the studies. PIBO is associated with moderately impaired pulmonary function, and this review facilitates an understanding of PIBO pathophysiology in children.

Post-infectious bronchiolitis obliterans (PIBO), one of the major complications of respiratory tract infection, is commonly underdiagnosed. To identify the risk groups that may develop PIBO and avoid misdiagnoses, we investigated the risk factors associated with the development of PIBO. We searched PubMed, Embase, and MEDLINE databases for studies that included risk factors for the development of PIBO published from inception to 13 June 2022. We limited our search to studies that reported the estimates of odds ratio (OR), hazard ratio (HR), or relative risks for developing PIBO. A fixed-effect and a random-effect model were used. We included seven studies reporting data on the risk factors for PIBO in 344 children with PIBO and 1310 control children. Twenty-two variables, including sex, age, respiratory pathogens, symptoms, laboratory and radiologic findings, and mechanical ventilation, were mentioned in at least one study. The significant risk factors mentioned in two or more studies included elevated lactate dehydrogenase levels, pleural effusion, hypoxemia, sex, and mechanical ventilation. The significance of the duration of hospitalization and fever as risk factors for PIBO differed when the studies were classified according to the statistical method. In addition, the risk factors differed according to respiratory infection pathogens. This meta-analysis identified potential risk factors associated with the development of PIBO. The results of this study highlight the importance of avoiding misdiagnosis and help establish management strategies for patients at a high risk of developing PIBO.

Objective: Feelings of shame and guilt have rarely been investigated in people at ultra-high risk (UHR) for psychosis. We aimed to outline differences in shame and guilt in relation to empathy and theory of mind (ToM) in young people, particularly those at UHR for psychosis. Methods: First, 166 young healthy controls were assessed for their proneness to shame and guilt using the Test of Self-Conscious Affect, empathy and its four subdomains (perspective taking, fantasy, empathic concern, and personal distress) using the Interpersonal Reactivity Index (IRI), ToM using the ToM picture stories task, and neurocognitive performance using the Raven's Standard Progressive Matrices (SPM). Next, we evaluated shame and guilt in 24 UHR individuals comparing them to 24 age- and sex-matched healthy controls. Finally, we explored relationships for shame and guilt in relation to empathy and ToM in the UHR individuals. Results: In the healthy youth, a regression analysis showed fantasy and personal distress in IRI to be significant determinants of shame, while perspective taking and empathic concern in IRI, ToM, and SPM were independent predictors of guilt. Meanwhile, compared to the healthy controls, individuals with UHR exhibited higher levels of shame, which was associated with increased personal distress. Discussion: Our findings showed that four subdomains of empathy, ToM, and neurocognition were differentially associated with shame and guilt in healthy young people. Given the correlation between excessive feelings of shame and high levels of the personal distress dimension of empathy in UHR for psychosis, redressing the tendency to focus on self-oriented negative emotions upon witnessing distress of others could possibly reduce self-blame or self-stigma of help-seeking individuals.

In this study, our objective was to assess the association of body mass in preschool children with the use of antibiotics within 6 months after birth. National administrative databases were used to examine all children born between 2008 and 2009 in Korea. Exposure was defined as the use of systemic antibiotics during the first 6 months of age. The observed outcomes were stunting (height for age [HFA] z score < −2.0), short stature (HFA z score < −1.64), overweight (body mass index [BMI] for age z score ≥ 1.04), and obesity (BMI for age z score ≥ 1.64), and the children’s height and body weight were measured from three to six years of age. To balance characteristics between the antibiotic user and non-user groups, propensity score matching was performed. The outcomes were evaluated using a generalized estimation equation with the logit link function. Analysis of antibiotic use by children during the first 6 months of life indicated there were 203,073 users (54.9%) and 166,505 non-users (45.1%). After PS matching, there were 72,983 antibiotic users and 72,983 non-users. Antibiotic use was significantly associated with stunting (aOR = 1.198, 95% CI = 1.056 to 1.360) and short stature (aOR = 1.043, 95% CI = 1.004 to 1.083), and had significant negative association with HFA z score (weighted β = −0.023). The use of an antibiotic for 14 days or more had a marked association with stunting. Antibiotic use was also associated with overweight, obesity, and increased BMI for age z score. Antibiotic use during the first 6 months of life increased the risk of stunting, short stature, overweight, and obesity in preschool children.

Allergic diseases, including allergic rhinitis, asthma, and atopic dermatitis, are common heterogeneous diseases that encompass diverse phenotypes and different pathogeneses. Phenotype studies of allergic diseases can facilitate the identification of risk factors and their underlying pathophysiology, resulting in the application of more effective treatment, selection of better treatment responses, and prediction of prognosis for each phenotype. In the early phase of phenotype studies in allergic diseases, artificial classifications were usually performed based on clinical features, such as triggering factors or the presence of atopy, which can result in the biased classification of phenotypes and limit the characterization of heterogeneous allergic diseases. Subsequent phenotype studies have suggested more diverse phenotypes for each allergic disease using relatively unbiased statistical methods, such as cluster analysis or latent class analysis. The classifications of phenotypes in allergic diseases may overlap or be unstable over time due to their complex interactions with genetic and encountered environmental factors during the illness, which may affect the disease course and pathophysiology. In this review, diverse phenotype classifications of allergic diseases, including atopic dermatitis, asthma, and wheezing in children, allergic rhinitis, and atopy, are described. The review also discusses the applications of the results obtained from phenotype studies performed in other countries to Korean children. Consideration of changes in the characteristics of each phenotype over time in an individual’s lifespan is needed in future studies.

Abstract Background Asthma is a syndrome composed of heterogeneous disease entities. Although it is agreed that proper asthma endo-typing and appropriate type-specific interventions are crucial in the management of asthma, little data are available regarding pediatric asthma. Methods We designed a cluster-based, prospective, observational cohort study of asthmatic children in Korea (Korean childhood Asthma Study [KAS]). A total of 1000 Korean asthmatic children, aged from 5 to 15 years, will be enrolled at the allergy clinics of the 19 regional tertiary hospitals from August 2016 to December 2018. Physicians will verify the relevant histories of asthma and comorbid diseases, as well as airway lability from the results of spirometry and bronchial provocation tests. Questionnaires regarding subjects’ baseline characteristics and their environment, self-rating of asthma control, and laboratory tests for allergy and airway inflammation will be collected at the time of enrollment. Follow-up data regarding asthma control, lung function, and environmental questionnaires will be collected at least every 6 months to assess outcome and exacerbation-related aggravating factors. In a subgroup of subjects, peak expiratory flow rate will be monitored by communication through a mobile application during the overall study period. Cluster analysis of the initial data will be used to classify Korean pediatric asthma patients into several clusters; the exacerbation and progression of asthma will be assessed and compared among these clusters. In a subgroup of patients, big data-based deep learning analysis will be applied to predict asthma exacerbation. Discussion Based on the assumption that asthma is heterogeneous and each subject exhibits a different subset of risk factors for asthma exacerbation, as well as a different disease progression, the KAS aims to identify several asthma clusters and their essential determinants, which are more suitable for Korean asthmatic children. Thereafter we may suggest cluster-specific strategies by focusing on subjects’ personalized aggravating factors during each exacerbation episode and by focusing on disease progression. The KAS will provide a good academic background with respect to each interventional strategy to achieve better asthma control and prognosis.

Purpose: Hair cortisol is emerging as a reliable biomarker for measuring retrospective stress hormone levels. Given that social connectedness can buffer psychobiological stress reactivity, increasing attention is being paid to the specific types of social networks associated with the stress response. This study investigated the role played by two components of social life, emotional closeness and network size, to probe which aspects of social networks were related to stress measures. Methods: The scalp hair cortisol level was used to assess the cumulative cortisol production in 179 community-dwelling older adults, in the Korean Social Life, Health, and Aging Project (KSHAP). Multivariate regression approach was used to examine the link between the stress measures (cortisol and perceived stress scale) and social relationships (social network size and emotional closeness). Results: Emotional closeness (the average level of what one feels about one’s relationship) was significantly associated with decreased levels of hair cortisol, whereas no such relationship was found with the network size. Conclusions: The current findings underscore the role of emotional support on reducing cumulative cortisol, thus providing potential resilience mechanisms for the psychobiological stress response.

BackgroundPatients with schizophrenia and individuals at ultra-high risk for psychosis (UHR) have been reported to exhibit impaired recognition of facial emotion expressions. This impairment has involved both inaccuracy and negative bias of facial emotion recognition. The present study aimed to investigate whether UHR individuals display both types of impaired facial emotion recognition and to explore correlations between these impairments and schizotypy, as well as paranoia levels, in these individuals.MethodsA total of 43 UHR individuals and 57 healthy controls (HC) completed a facial emotion recognition task consisting of 60 standardized facial photographs. To explore correlations, we assessed schizotypy using the Revised Physical Anhedonia Scale and Magical Ideation Scale and paranoia level using the Paranoia Scale and persecution/suspicious item of the Positive and Negative Syndrome Scale in UHR individuals.ResultsCompared with HC, UHR individuals exhibited less accuracy for facial emotion recognition (70.6% vs. 75.6%, p=0.010) and a higher rate of “fear” responses for neutral faces (14.5% vs. 6.0%, p=0.003). In UHR individuals, inaccuracy was significantly correlated with schizotypy scores, but not with paranoia level. Conversely, “disgust” response for neutral faces was the only fear response correlated with paranoia level, and no threat-related emotion response correlated with schizotypy scores.DiscussionUHR individuals exhibited inaccuracy and negative bias of facial emotion recognition. Furthermore, schizotypy scores were associated with inaccuracy but not with negative bias of facial emotion recognition. Paranoia level was correlated with “disgust” responses for neutral faces but not with inaccuracy. These findings suggest that inaccuracy and negative bias of facial emotion recognition reflect different underlying processes, and that inaccuracy may be a vulnerability marker for schizophrenia.

Sleep misperception has long been a major issue in the field of insomnia research. Most studies of sleep misperception examine sleep underestimation by comparing the results of polysomnography conducted in a laboratory environment with patients' sleep diary entries. We aimed to investigate psychosocial characteristics of adults who underestimated or overestimated sleep time in a nonclinical, middle-aged community-dwelling population. We collected one week of sleep data with wrist-worn accelerometers. We used egocentric social network analysis to analyze the effects of psychosocial factors. Among 4,060 study participants, 922 completed the accelerometer substudy. Underestimation was defined as an accelerometer-measured sleep time ≥ 6 h and a subjective sleep time < 6 h. Overestimation was defined as an objective sleep time < 6 h and a subjective sleep time ≥ 6 h. Psychosocial characteristics of the sleep misperception group were evaluated using multivariate regression analysis. A total of 47 participants underestimated sleep time, and 420 overestimated sleep time. Regression analysis revealed that women, living with spouse, economic satisfaction, and bridging potential had protective effects against sleep underestimation. Blame from a spouse involved a 3.8-times higher risk of underestimation than the control group (p = 0.002). In men, discussing concerns with a spouse had a protective effect against underestimation (p < 0.001). Economic satisfaction, feeling social network-based intimacy, and support from a spouse were associated with overestimation in women. In men, feeling social network-based intimacy was also associated with overestimation (p < 0.001). We found that social relationship quality was related to sleep overestimation and underestimation. This association was marked in women. Good social relationships may have positive effects on sleep misperception via attenuation of negative emotional reactions and effects on emotional regulation.

Background: Breastfeeding is recommended due to its beneficial effects on human health. However, the effect of breastfeeding on health differs, resulting in various childhood diseases. Objective: Our purpose was to investigate the association between breastfeeding at least in the first 4 months and the subsequent development of 15 certainly defined childhood diseases until 10 years of age, the all-cause hospitalization rate and growth at 6–7 years of age. Methods: Participants included propensity-score matched 188,052 children born between January 2008 and December 2009, who were followed up till 10 years of age. Data were taken from the National Investigation of birth Cohort in Korea study 2008 database. Risk ratios were obtained using a modified Poisson regression and weighted risk differences using binomial regression. Results: Compared to formula feeding, breastfeeding was associated with decreased risks of febrile convulsion, attention deficit hyperactivity disorder and autism spectrum disorder, pneumonia, acute bronchiolitis, hypertrophic pyloric stenosis, asthma, all-cause hospitalization, overweight/obesity and short stature. Exclusive breastfeeding at 4 to 6 months of age had similar results to exclusive breastfeeding over 6 months of age. Conclusions: Breastfeeding in early infancy reduces the risk for various childhood diseases, all-cause hospitalization rate, obesity, and short stature during childhood.

Interactions between elements, which are usually represented by networks, have to delineate potentially unequal relationships in terms of their relative importance or direction. The intrinsic unequal relationships of such kind, however, are opaque or hidden in numerous real systems. For instance, when a node in a network with limited interaction capacity spends its capacity to its neighboring nodes, the allocation of the total amount of interactions to them can be vastly diverse. Even if such potentially heterogeneous interactions epitomized by weighted networks are observable, as a result of the aforementioned egocentric allocation of interactions, the relative importance or dependency between two interacting nodes can only be implicitly accessible. In this work, we precisely pinpoint such relative dependency by proposing the framework to discover hidden dependent relations extracted from weighted networks. For a given weighted network, we provide a systematic criterion to select the most essential interactions for individual nodes based on the concept of information entropy. The criterion is symbolized by assigning the effective number of neighbors or the effective out-degree to each node, and the resultant directed subnetwork decodes the hidden dependent relations by leaving only the most essential directed interactions. We apply our methodology to two time-stamped empirical network data, namely, the international trade relations between nations in the world trade web (WTW) and the network of people in the historical record of Korea, Annals of the Joseon Dynasty (AJD). Based on the data analysis, we discover that the properties of mutual dependency encoded in the two systems are vastly different. The nations in the WTW show much more asymmetric dependent relations than its random counterpart, which implies the global economic inequality in international trades. In contrast, the relationships of people in the AJD are much more mutual than the nations in the WTW. The difference comes from nontrivial correlations (or lack thereof) in the networks, for which we provide the relevant network properties and representative example nations in the case of the WTW.