Human transcriptome array analysis and diffusion tensor imaging in attention-deficit/hyperactivity disorder.

The mRNA markers identified using microarray assay and diffusion tensor magnetic resonance imaging (DTI) were applied to elucidate the pathophysiology of attention-deficit hyperactivity disorder (ADHD). First, we obtained total RNA from leukocytes from three children with ADHD and three healthy controls for analysis with microarray assays. Subsequently, we applied real-time quantitative polymerase chain reaction (qRT‒PCR) assays to validate the differential expression of 7 genes (COX7B, CYCS, TFAM, UTP14A, ZNF280C, IFT57 and NDUFB5) between 130 ADHD patients and 70 controls, and we built an ADHD prediction model based on the ΔCt values of aforementioned seven genes (AUROC = 0.98). Finally, in a validation group (28 patients with ADHD and 27 healthy controls), mRNA expression of the above seven genes also significantly differentiated ADHD patients from controls (AUROC value = 0.91). The DTI analysis showed increased fractional anisotropy (FA) of the forceps minor, superior corona radiata, posterior corona radiata and anterior corona radiata in ADHD patients. Moreover, the FA of the right superior corona radiata tract was positively correlated with ΔCt levels of the COX7B gene and the IFT57 gene. The results shed a new light on a genetic profile of ADHD that may help in deciphering the white matter microstructural features in disease pathogenesis.

The Benefit of Hydrogen Gas as an Adjunctive Therapy for Chronic Obstructive Pulmonary Disease.

Background and Objectives: Recent studies suggest that hydrogen gas possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. This study aimed to explore the therapeutic potential of hydrogen gas and assess its safety and tolerability in individuals with chronic obstructive pulmonary disease (COPD). Materials and Methods: Enrolled COPD patients received standard treatments along with additional hydrogen inhalation for 30 min in the morning, afternoon, and evening over a 30-day period. The assessment included changes in the COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) Dyspnea Scale, lung function, sleep quality, inflammation markers, and oxidative stress markers before and after hydrogen inhalation. Results: Six patients participated in this study. Patients 2, 3, 4, 5, and 6 demonstrated improvements in CAT scores following hydrogen gas intervention, with patients 2, 4, 5, and 6 also showing improvements in mMRC scores. Statistically, this study revealed significant improvements in CAT [15.5 (10.5-19.75) vs. 8.5 (3-13.5); p = 0.043] and mMRC scores [2.5 (1-4) vs. 2 (0-3.25); p = 0.046] before and after intervention, respectively. However, no significant differences were observed in lung function, DLCO, sleep quality, and 6 MWT before and after hydrogen therapy. CBC examination showed a significant difference in platelet count before and after treatment [247 (209.75-298.75) vs. 260 (232.75-314.5); p = 0.043], respectively, while other blood tests, inflammation markers, and oxidative stress markers did not exhibit significant differences before and after hydrogen therapy. All patients experienced no obvious side-effects. Conclusions: Adjuvant therapy with hydrogen gas demonstrated symptom improvements in specific COPD patients, and no significant adverse effects were observed in any of the patients. Hydrogen gas may also exert a modulatory effect on platelet count.

Positive Echocardiographic Association between Carotid Artery and Coronary Artery Diameter and Z-Score in a Mouse Model of Kawasaki Disease.

Kawasaki disease (KD) occurs in young children, has an unknown etiology, and can cause such life-threatening complications as coronary artery aneurysm. A mouse model using Lactobacillus casei cell wall extract (LCWE) with intraperitoneal injection was established for KD years ago. Histological examination of coronary artery lesions indicated features similar to those of vascular lesions of patients with KD. Since animals must be sacrificed during histological examination, the longitudinal survey of coronary artery lesions (CALs) is difficult. The aim of this study was to survey the vasculitis status of the coronary artery and the carotid artery in a KD mouse model. METHOD: LCWE was intraperitoneally injected into 5-week-old male C57BL/6 mice to induce CALs. We studied the longitudinal status of the carotid and coronary arteries and analyzed the Z-score of coronary artery diameter. RESULTS: Carotid artery wall thickness (day 7) and diameter (day 14) significantly increased in the LCWE group with a dose-dependent effect (p < 0.05). Aortic diameter and wall thickness demonstrated significant increases on day 28 and day 7, respectively (p < 0.05). Carotid artery outer diameter and wall thickness were positively associated with coronary artery diameter on day 28 (p < 0.01). Coronary artery diameter significantly increased in the LCWE group after day 7 (p < 0.05). The percentage of Z > 3.0 indicated was more than 80% in the high-dose LCWE group and 0% in the control group. CONCLUSIONS: This report is the first to use coronary artery Z-score in a mouse model of KD by echocardiography and to find a positive association between carotid artery and coronary artery diameter.

Molecular Hydrogen: Emerging Treatment for Stroke Management.

Ischemic stroke is a major cause of death and disability worldwide. However, only intravenous thrombolysis using mechanical thrombectomy or tissue plasminogen activator is considered an effective and approved treatment. Molecular hydrogen is an emerging therapeutic agent and has recently become a research focus. Molecular hydrogen is involved in antioxidative, anti-inflammatory, and antiapoptotic functions in normal physical processes and may play an important role in stroke management; it has been evaluated in numerous preclinical and clinical studies in several administration formats, including inhalation of hydrogen gas, intravenous or intraperitoneal injection of hydrogen-enriched solution, or drinking of hydrogen-enriched water. In addition to investigation of the underlying mechanisms, the safety and efficacy of using molecular hydrogen have been carefully evaluated, and favorable outcomes have been achieved. All available evidence indicates that molecular hydrogen may be a promising treatment option for stroke management in the future. This review aimed to provide an overview of the role of molecular hydrogen in the management of stroke and possible further modifications of treatment conditions and procedures in terms of dose, duration, and administration route.

Kawasaki Disease, MIS-C and COVID-19.

Kawasaki disease (KD) is a form of systemic vasculitis characterized by inflammation of blood vessels throughout the body, and its exact cause remains unknown [...].

Echocardiography and laboratory outcomes of COVID-19 in children with a history of Kawasaki disease: a preliminary observation.

Background: Infection with SARS-CoV-2 virus has been associated with cardiovascular sequelae including multisystem inflammatory syndrome (MIS-C) in children. Patients with a prior history of Kawasaki disease, may be more susceptible to changes in echocardiographic or laboratory findings after COVID-19. The objective of this study was to investigate the echocardiographic and laboratory findings in children with a prior history of Kawasaki disease after SARS-CoV-2 infection. Materials and methods: In this study, we performed a retrospective chart review of 41 children younger than 18 years old who were diagnosed with COVID-19 from April to August of 2022 and had a prior history KD. We included echocardiography and blood draw data obtained at the last outpatient follow-up at our hospital for KD, and within 4 months of SARS-CoV-2 infection. Echocardiographic data obtained from 82 age-matched and gender matched controls were also included for comparison. Results: We found that COVID-19 resulted in slightly higher RCA Z-scores within the first month after infection (mean ± SE, 1.20 ± 0.18 vs. 0.83 ± 0.18, p = 0.030), although this increase did not result in coronary artery dilatation, defined as a Z-score of at least 2.5. In addition, we found that degree of RCA dilatation after COVID-19 infection was negatively correlated with the change in monocyte percentage (Pearson's correlation coefficient-0.363, p = 0.020). Moreover, RCA Z-score changes were lower in patients who received at least one dose of mRNA COVID-19 vaccine when compared those who did not receive any (mean ± SE, -0.23 ± 0.16 vs. 0.39 ± 0.17, p = 0.031). Conclusion: In this pilot study we found that COVID-19 infection resulted in slightly higher RCA Z-scores in children with a prior history of KD, although not large enough to be classified as coronary aneurysms. While these changes could be the result of measurement imprecision or interobserver variation, further study of the cardiac outcomes of COVID-19 infection in children with a prior history of KD are needed in the future.

Diagnosis, Progress, and Treatment Update of Kawasaki Disease.

Kawasaki disease (KD) is an acute inflammatory disorder that primarily affects children and can lead to coronary artery lesions (CAL) if not diagnosed and treated promptly. The original clinical criteria for diagnosing KD were reported by Dr. Tomisaku Kawasaki in 1967 and have been used for decades. However, research since then has highlighted the limitations of relying solely on these criteria, as they might lead to underdiagnosis or delayed diagnosis, potentially increasing the risk of coronary artery complications. This review appears to discuss several important aspects related to KD diagnosis and management. The current diagnostic methods for KD might need updates, especially considering cases that do not fit the typical clinical criteria. Recognizing diagnostic pitfalls and distinguishing KD from other conditions that might have similar clinical presentations is essential. The differences and similarities between KD and Multisystem Inflammatory Syndrome in Children (MIS-C), another inflammatory condition that has been associated with COVID-19, were also reviewed. The review explores the potential role of eosinophil count, new biomarkers, microRNA panels, and scoring systems in aiding the diagnosis of KD. Overall, the review article provides a comprehensive overview of the evolving landscape of KD diagnosis and management, incorporating new diagnostic methods, biomarkers, and treatment approaches to improve patient outcomes and reduce the risk of complications.

Sex differences in vitamin D and behavioral profiles among children with allergic diseases.

Previous studies have suggested that vitamin D has a protective effect on allergic diseases, while an individual's sex may have a moderating effect on the relationship between vitamin D and allergic-related immunity. This study aimed to determine the role of vitamin D in children with coexisting allergic diseases in the context of sex differences and to explore the behavioral profiles of these patients. We recruited a total of 103 children with atopic diseases and divided them into four groups: males with one allergic disease (MA1, n = 20), males with two or more allergic diseases (MA2, n = 26), females with one allergic disease (FA1, n = 30), and females with two or more allergic diseases (FA2, n = 27). We measured serum calcium levels using the colorimetric method and serum 25-OH vitamin D total levels using electrochemiluminescence immunoassay. We found that MA2 had significantly lower vitamin D levels than MA1 and FA2. The levels of IgE were negatively correlated with vitamin D in females, whereas the levels of IgE were not significantly correlated with vitamin D in males. Furthermore, serum IgE was significantly correlated with children's adaptive skills, and different sexes were associated with different aspects of adaptive skills. Our findings suggest a protective role of vitamin D in the development of one allergic disease against the coexistence of allergic diseases in males, as well as extend the evidence for sex differences in immunity by demonstrating a sex-different correlation between IgE and vitamin D and the relationship between IgE and children's adaptive skills.

Prevalence of antecedent Kawasaki disease in young adults with suspected acute coronary syndrome in high incidence cohort.

Background: Acute coronary syndrome (ACS) in early adulthood (<40 years old) may be associated with unrevealed diagnoses of Kawasaki disease (KD) in childhood. Daniels et al. showed that 5% of young adults with acute coronary syndrome might have antecedent Kawasaki disease in a cohort with Kawasaki disease incidence rates ranging from about 9 to 20 per 100,000 children under 5 years of age. However, there is no relevant research from the cohort with higher incidence rates (>80-100 per 100,000 children under 5 years of age) of Kawasaki disease. Methods: We conducted a multicenter, retrospective study by reviewing medical records and angiographic data from two institutions (middle and southern Taiwan, respectively) of adults <40 years of age who underwent coronary angiography for clinically suspected acute coronary syndrome (2009-2019). Angiographic images were independently analyzed by three cardiologists who were blinded to the medical records. Demographic and laboratory data and risk factors of coronary artery disease were integrated to assess the likelihood of antecedent KD. Results: All 323 young adults underwent coronary angiography, and 27 had coronary aneurysms. The patients' clinical and angiographic characteristics were evaluated, and 7.4% had aneurysms likely to be associated with KD. Most subjects were male (23/24), and their low-density lipoprotein (LDL) levels were significantly higher (p = 0.028) than those of subjects unlikely to have KD. Conclusion: This study proposed that the cohort with higher Kawasaki disease incidence rates may have a higher prevalence of young adult ACS associated with antecedent KD. The importance of determining the clinical therapeutic significance of antecedent Kawasaki disease in young adult ACS warrants advanced research. Higher LDL levels may have a long-term cardiovascular impact in KD patients with persistent coronary aneurysms.

Profiling humoral responses to COVID-19 immunization in Kawasaki disease using SARS-CoV-2 variant protein microarrays.

Kawasaki disease (KD) is a form of acute systemic vasculitis syndrome that predominantly occurs in children under the age of 5 years. Its etiology has been postulated due to not only genetic factors but also the presence of foreign antigens or infectious agents. To evaluate possible associations between Kawasaki disease (KD) and COVID-19, we investigated humoral responses of KD patients against S-protein variants with SARS-CoV-2 variant protein microarrays. In this study, plasma from a cohort of KD (N = 90) and non-KD control (non-KD) (N = 69) subjects in categories of unvaccinated-uninfected (pre-pandemic), SARS-CoV-2 infected (10-100 days after infection), and 1-dose, 2-dose, and 3-dose BNT162b2 vaccinated (10-100 days after vaccination) was collected. The principal outcomes were non-KD-KD differences for each category in terms of anti-human/anti-His for binding antibodies and neutralizing percentage for surrogate neutralizing antibodies. Binding antibodies against spikes were lower in the KD subjects with 1-dose of BNT162b2, and mean differences were significant for the P.1 S-protein (non-KD-KD, 3401; 95% CI, 289.0 to 6512; P = 0.0252), B.1.617.2 S-protein (non-KD-KD, 4652; 95% CI, 215.8 to 9087; P = 0.0351) and B.1.617.3 S-protein (non-KD-KD, 4874; 95% CI, 31.41 to 9716; P = 0.0477). Neutralizing antibodies against spikes were higher in the KD subjects with 1-dose of BNT162b2, and mean percentage differences were significant for the 1-dose BNT162b2 B.1.617.3 S-protein (non-KD-KD, -22.89%; 95% CI, -45.08 to -0.6965; P = 0.0399), B.1.1.529 S-protein (non-KD-KD, -25.96%; 95% CI, -50.53 to -1.376; P = 0.0333), BA.2.12.1 S-protein (non-KD-KD, -27.83%; 95% CI, -52.55 to -3.115; P = 0.0195), BA.4 S-protein (non-KD-KD, -28.47%; 95% CI, -53.59 to -3.342; P = 0.0184), and BA.5 S-protein (non-KD-KD, -30.42%; 95% CI, -54.98 to -5.869; P = 0.0077). In conclusion, we have found that KD patients have a comparable immunization response to healthy individuals to SARS-CoV-2 infection and COVID-19 immunization.

Smoking cessation and influenza vaccination can reduce the healthcare burden of COPD.

INTRODUCTION: Influenza vaccination (INV) and smoking cessation (SC) have individual positive effects on COPD, but their synergistic impact has yet to be extensively studied. This retrospective study aimed to assess the combined effect of SC and IV on the medical burden of COPD, including medical visits, hospitalization, medical expenses, and the occurrence of respiratory failure. METHODS: Patients with COPD who visited our medical center between January and October 2018 were included in the study. The patients were categorized into four groups: Group I (no SC or INV), Group II (INV only), Group III (SC only), and Group IV (both SC and INV). The outcomes analyzed were emergency utilization, hospital utilization, and occurrence of respiratory failure. Airflow limitation was stratified according to GOLD guidelines, and successful smoking cessation was defined as not smoking for at least one year. RESULTS: A total of 357 patients were included in the study. Group I (119 patients) neither smoking cessation nor influenza vaccination; Group II (66 patients) had only influenza vaccination; Group III (94 patients), had only smoking cessation, Group IV (78 patients), with both smoking cessation and influenza vaccination. Group IV had lower odds of emergency utilization (OR=0.13; 95% CI: 0.07-0.25), hospital utilization (OR=0.13; 95% CI: 0.05-0.30, p<0.001), and occurrence of respiratory failure (OR=0.13; 95% CI: 0.04-0.40, p<0.001). CONCLUSIONS: Combined smoking cessation and influenza vaccination are more effective in reducing the medical burden of COPD compared to either intervention alone or neither. These findings highlight the importance of promoting both smoking cessation and influenza vaccination in the management of COPD.

Basophils Predict Mite Sensitization in Patients with Kawasaki Disease.

Background: Patients with Kawasaki disease (KD) are at a significantly increased risk of allergic diseases. Immunoglobulin E (IgE) is an immunoglobulin that mediates allergic sensitization to various allergens and is related to various allergic diseases. However, few studies have analyzed specific IgE on allergy biomarkers after KD is diagnosed. Objective: This study aimed to investigate the pattern of specific IgE levels against food and inhalant allergens. Methods: This retrospective study was conducted in Taiwan to identify patients admitted with KD. A subset of 453 admitted KD children younger than or equal to five years of age with intravenous immunoglobulin (IVIG) was followed up at our clinic with available specific IgE data. Results: The most common allergens were Dermatophagoides farina or pteronyssinus, house-dust, and cockroach mix. Positive specific IgE for Dermatophagoides farina or pteronyssinus was less common in children diagnosed with KD who were two years old or younger (p = 0.028). KD patients with higher basophils before IVIG (p = 0.010 and 0.018 for two different mites) and higher C-reactive protein (CRP, p = 0.030 and 0.028) after IVIG were at higher risk of mite sensitization. Integrated mite sensitization demonstrated higher basophils before IVIG, age at KD diagnosis, and the male sex to be clinically meaningful after logistic regression models. Conclusions: This study is the first to suggest that specific IgE in KD patients may be correlated with age at KD diagnosis, as well as basophils. Further longitudinal prospective studies are warranted to clarify the unique profile of specific IgE in KD patients.

The state of play in tools for predicting immunoglobulin resistance in Kawasaki disease.

INTRODUCTION: Intravenous immunoglobulin (IVIG) resistance is an independent risk factor for the development of coronary artery lesions (CAL) in patients with Kawasaki disease (KD). Accurate identification of IVIG-resistant patients is one of the biggest clinical challenges in the treatment of KD. AREAS COVERED: In this review article, we will go over current IVIG resistance scoring systems and other biological markers of IVIG resistance, with a particular focus on advances in machine-based learning techniques and high-throughput omics data. EXPERT OPINION: Traditional scoring models, which were developed using logistic regression, including the Kobayashi score and Egami score, are inadequate at identifying IVIG resistance in non-Japanese populations. Newer machine-learning methods and high-throughput technologies including transcriptomic and epigenetic arrays have identified several potential targets for IVIG resistance including gene expression of the Fc receptor, and components of the interleukin (IL)-1ß and pyroptosis pathways. As we enter an age where access to big data has become more commonplace, interpretation of large data sets that are able take into account complexities in patient populations will hopefully usher in a new era of precision medicine, which will enable us to identify and treat KD patients with IVIG resistance with increased accuracy.

Evaluation of Formosa score and diagnostic sensitivity and specificity of four Asian risk scores for predicting intravenous immunoglobulin resistance in Kawasaki disease: a bivariate meta-analysis.

Background: In 2016, Lin et al. developed a prediction score of non-responsiveness to intravenous immunoglobulin (IVIG) in patients with Kawasaki disease (KD) (Lin et al., 2016). Various studies have attempted to validate the Formosa score, but inconsistent results have given us new opportunities and challenges. The aim of this meta-analysis is to explore the role of the Formosa score as a risk score in detecting IVIG-resistant KD patients and then compare the pooled sensitivity and specificity of four Asian risk scores, Egami, Formosa, Kobayashi, and Sano risk scores. Methods: A comprehensive search of Cochrane, Embase, and PubMed was conducted through 20 December 2021, using key terms relevant to the research question "What are the sensitivities and specificities of the four Asian predicting scores, Egami, Formosa, Kobayashi, and Sano, in Kawasaki disease patients with IVIG resistance?" The reference lists of the included studies were manually reviewed to identify pertinent references. A random-effects bivariate model was used to estimate the summary of sensitivity and specificity of the tools. Results: We found 41 relevant studies of the four Asian risk scores that were eligible to analyze for pooled accuracy. Eleven studies involving 5,169 KD patients reported the diagnostic performance of the Formosa score for the risk of IVIG resistance. The overall performance of the Formosa score was as follows: pooled sensitivity, 0.60 [95% confidence interval (CI), 0.48-0.70]; pooled specificity, 0.59 (95% CI, 0.50-0.68); and area under the hierarchical summary receiver operating characteristic curve, 0.62. The Formosa score exhibited the highest sensitivity 0.76 (95% CI, 0.70-0.82) for detecting IVIG-resistant KD patients among the 21,389 children included in the 41 studies. In terms of specificity estimates, Formosa had the lowest specificity of 0.46 (95% CI, 0.41-0.51). Conclusion: Patients at high risk for IVIG resistance may receive adjunctive treatment to reduce coronary lesions and thus also cardiovascular morbidity. Among all of the included studies, we found Formosa score to have the best sensitivity (0.76) but unsatisfactory specificity (0.46) for predicting IVIG resistance in Kawasaki disease. In the future, network meta-analysis should also incorporate the accuracy of the new scores after they have undergone a certain degree of validation around the world. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO CRD42022341410.

General Anesthesia in Early Childhood Significantly Reduces Asthma Incidence and Clinical Visits: A Nationwide Population-Based Cohort Study.

Few studies have focused on the consequence of exposure to general anesthesia (GA) in children's early life with the risk of asthma and disease outcomes. The present study examines the correlation between exposure to GA under three years old and the subsequent course of asthma in a nationwide population-based cohort study. Our cases were acquired from Taiwan's National Health Insurance Research Database (NHIRD). Children under three years old with either GA exposure or not during in-patient treatment from 1997 to 2008 were included. The study group was age- and sex-matched with a ratio of 1:2 to create the control group for comparison. The cohort included 2261 cases with GA and 4522 cases without GA as a control group. The incidence of asthma onset was significantly reduced in patients with GA exposure under 3 three years old (hazard ratio 0.64 (95% confidence interval 0.57~0.72), p < 0.001). In addition, regardless of whether the asthmatic clinical visits were before or after GA exposure, asthma onset patients before GA exposure have significantly fewer clinical visits than those without GA exposure (both p < 0.001, respectively). Using the Kaplan-Meier method, we also demonstrated that GA exposure was associated with favorable clinical visits in patients with asthma, whether their asthma was onset before GA (p = 0.0102) or after GA exposure (p = 0.0418) compared to non-GA-exposed controls. In the present study, we demonstrated that children with early GA exposure under three years old were at a reduced risk of developing asthma compared to the general population. Furthermore, we first reported that GA exposure significantly reduced clinical visits in patients with asthma regardless of whether their asthma onset was before or after GA exposure. It is indicated that GA exposure at a younger age could have potential clinical benefits for asthma than non-GA-exposed controls.

Gut mycobiome dysbiosis and its impact on intestinal permeability in attention-deficit/hyperactivity disorder.

BACKGROUND: Dysbiosis in the gut microbial community might be involved in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The fungal component of the gut microbiome, namely the mycobiota, is a hyperdiverse group of multicellular eukaryotes that can influence host intestinal permeability. This study therefore aimed to investigate the impact of fungal mycobiome dysbiosis and intestinal permeability on ADHD. METHODS: Faecal samples were collected from 35 children with ADHD and from 35 healthy controls. Total DNA was extracted from the faecal samples and the internal transcribed spacer regions were sequenced using high-throughput next-generation sequencing (NGS). The fungal taxonomic classification was analysed using bioinformatics tools and the differentially expressed fungal species between the ADHD and healthy control groups were identified. An in vitro permeability assay (Caco-2 cell layer) was used to evaluate the biological effects of fungal dysbiosis on intestinal epithelial barrier function. RESULTS: The ß-diversity (the species diversity between two communities), but not α-diversity (the species diversity within a community), reflected the differences in fungal community composition between ADHD and control groups. At the phylum level, the ADHD group displayed a significantly higher abundance of Ascomycota and a significantly lower abundance of Basidiomycota than the healthy control group. At the genus level, the abundance of Candida (especially Candida albicans) was significantly increased in ADHD patients compared to the healthy controls. In addition, the in vitro cell assay revealed that C. albicans secretions significantly enhanced the permeability of Caco-2 cells. CONCLUSIONS: The current study is the first to explore altered gut mycobiome dysbiosis using the NGS platform in ADHD. The findings from this study indicated that dysbiosis of the fungal mycobiome and intestinal permeability might be associated with susceptibility to ADHD.

Impact of COVID-19 pandemic on business operations of Taiwan High Speed Rail and 7-Eleven stores.

Governmental non-pharmaceutical interventions (NPIs) and concerns regarding COVID-19 infection greatly affected population mobility during the COVID-19 pandemic. This study analyzed the effect of the COVID-19 pandemic on the business operations of Taiwan High Speed Rail (THSR) and 7-Eleven stores in Taiwan. We collected data from COVID-19 Mobility Reports published by Google, the Our World in Data website, and the monthly financial reports of THSR and 7-Eleven stores. The findings revealed that the mean population mobility at transit stations decreased by over 50% during the pandemic. Changes in population mobility were significantly associated with the reproduction rate (7-day rolling average) and with the daily number of new confirmed cases per million people (7-day rolling average). The operating income of THSR was significantly associated with the decrease in population mobility at transit stations. The monthly and annual operating income of THSR in 2020, 2021, and 2022 (during the pandemic) were significantly lower than those in 2019 (before the pandemic). THSR's monthly operating income was lowest compared with the 2019 value during the Alpha variant period (89.89% lower). No significant correlation was noted between the operating income of 7-Eleven stores and population mobility. Moreover, no significant differences were discovered between the monthly and annual operating incomes of 7-Eleven stores in 2019 and those in 2020, 2021, and 2022. Implementation of the policy of coexistence with the virus by the Taiwanese government began in May 2022, and from May 2022 to October 2022, the monthly income of 7-Eleven stores was higher than that in 2019 whereas the monthly income of THSR began lower than and then slowly increased to the level in 2019. In conclusion, the operating performance of THSR was closely related to population mobility and government NPIs, whereas the operating performance of 7-Eleven stores was less strongly affected by NPIs. These stores increased their operating income by providing e-commerce and delivery services; they thus remained popular in the community.

Use of Machine Learning to Differentiate Children With Kawasaki Disease From Other Febrile Children in a Pediatric Emergency Department.

Importance: Early awareness of Kawasaki disease (KD) helps physicians administer appropriate therapy to prevent acquired heart disease in children. However, diagnosing KD is challenging and relies largely on subjective diagnosis criteria. Objective: To develop a prediction model using machine learning with objective parameters to differentiate children with KD from other febrile children. Design, Setting, and Participants: This diagnostic study included 74 641 febrile children younger than 5 years who were recruited from 4 hospitals, including 2 medical centers and 2 regional hospitals, between January 1, 2010, and December 31, 2019. Statistical analysis was performed from October 2021 to February 2023. Main Outcomes and Measures: Demographic data and laboratory values from electronic medical records, including complete blood cell count with differential, urinalysis, and biochemistry, were collected as possible parameters. The primary outcome was whether the febrile children fulfilled the diagnostic criteria of KD. The supervised eXtreme Gradient Boosting (XGBoost) machine learning method was applied to establish a prediction model. The confusion matrix and likelihood ratio were used to evaluate the performance of the prediction model. Results: This study included a total of 1142 patients with KD (mean [SD] age, 1.1 [0.8] years; 687 male patients [60.2%]) and 73 499 febrile children (mean [SD] age, 1.6 [1.4] years; 41 465 male patients [56.4%]) comprising the control group. The KD group was predominantly male (odds ratio, 1.79; 95% CI, 1.55-2.06) with younger age (mean difference, -0.6 years [95% CI, -0.6 to -0.5 years]) compared with the control group. The prediction model's best performance in the testing set was able to achieve 92.5% sensitivity, 97.3% specificity, 34.5% positive predictive value, 99.9% negative predictive value, and a positive likelihood ratio of 34.0, which indicates outstanding performance. The area under the receiver operating characteristic curve of the prediction model was 0.980 (95% CI, 0.974-0.987). Conclusions and Relevance: This diagnostic study suggests that results of objective laboratory tests had the potential to be predictors of KD. Furthermore, these findings suggested that machine learning with XGBoost can help physicians differentiate children with KD from other febrile children in pediatric emergency departments with excellent sensitivity, specificity, and accuracy.