The Reduced Gut Lachnospira Species Is Linked to Liver Enzyme Elevation and Insulin Resistance in Pediatric Fatty Liver Disease.

The objective of this study was to investigate gut dysbiosis and its metabolic and inflammatory implications in pediatric metabolic dysfunction-associated fatty liver disease (MAFLD). This study included 105 children and utilized anthropometric measurements, blood tests, the Ultrasound Fatty Liver Index, and fecal DNA sequencing to assess the relationship between gut microbiota and pediatric MAFLD. Notable decreases in Lachnospira spp., Faecalibacterium spp., Oscillospira spp., and Akkermansia spp. were found in the MAFLD group. Lachnospira spp. was particularly reduced in children with MAFLD and hepatitis compared to controls. Both MAFLD groups showed a reduction in flavone and flavonol biosynthesis sequences. Lachnospira spp. correlated positively with flavone and flavonol biosynthesis and negatively with insulin levels and insulin resistance. Body weight, body mass index (BMI), and total cholesterol levels were inversely correlated with flavone and flavonol biosynthesis. Reduced Lachnospira spp. in children with MAFLD may exacerbate insulin resistance and inflammation through reduced flavone and flavonol biosynthesis, offering potential therapeutic targets.

Investigating the mechanisms underlying U46619-induced contraction on porcine lower esophageal sphincter.

Gastroesophageal reflux disease (GERD) is associated with an incompetent lower esophageal sphincter (LES), resulting in the reflux of gastric contents into the esophagus. U46619, a thromboxane A2 (TXA2) receptor agonist, induces contractions in various smooth muscles. Therefore, this study aimed to investigate the effects and mechanisms of action of U46619 on the porcine LES. To achieve this, contractions of the clasp and sling strips of the porcine LES, induced by U46619 were measured using isometric transducers. Furthermore, the contractile mechanism of U46619 in the porcine LES was investigated by pretreating the strips with atropine (a muscarinic receptor antagonist), tetrodotoxin (a neuronal sodium channel blocker), nifedipine (a calcium channel blocker), and Ca2+-free Krebs-Henseleit solution. Additionally, reverse transcription polymerase chain reaction and immunohistochemistry (IHC) were performed to determine the presence of the TXA2 receptor in porcine LES. The results of this study demonstrated that U46619 caused marked concentration-dependent contractions in both porcine sling and clasp strips. The mechanism of U46619-induced contraction of the porcine LES was found to be related to calcium channels. Furthermore, the reverse transcription PCR analysis and IHC revealed that the TXA2 receptor was expressed in the clasp and sling fibers of porcine LES. Consequently, this study suggests that U46619 mediates the contraction of porcine LES through calcium channels and has potential as a therapeutic approach for treating GERD. Significance Statement This study establishes that U46619 induces concentration-dependent contractions in porcine LES, primarily mediated by calcium channels. The presence of the TXA2 receptor in LES clasp and sling fibers is confirmed. These findings highlight U46619's potential as a GERD therapeutic by targeting calcium channels for LES contraction modulation.

The joint effect of gestational diabetes mellitus and hypertension contribute to higher risk of diabetes mellitus after delivery: a nationwide population-based study.

BACKGROUND: Gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) are known risk factors for postpartum diabetes mellitus (DM) and hypertension, respectively. This study aimed to examine the association between the co-occurrence of GDM and PIH and the subsequent development of diabetes mellitus (DM), hypertension, and metabolic syndrome. METHODS: A cohort study was conducted using data from the Taiwan National Health Insurance Research Database (TNHIRD). The study population included 2,297,613 pregnant women with no history of certain medical conditions who gave birth between 2004 and 2015. The women were classified into four cohorts based on their medical history: GDM cohort, PIH cohort, both GDM and PIH cohort, and normal cohort (without GDM and PIH). RESULTS: The GDM cohort had a higher risk of developing DM, hypertension, and metabolic syndrome than the normal cohort, with hazard ratios of 7.07, 1.54, and 2.51, respectively. The PIH cohort also had an increased risk for these conditions compared with the normal cohort, with hazard ratios of 3.41, 7.26, and 2.68, respectively. The cohort with both GDM and PIH had the highest risk of developing postpartum DM, hypertension, and metabolic syndrome, with hazard ratios of 21.47, 8.02, and 5.04, respectively, compared with the normal cohort. CONCLUSION: The cohort of patients with both GDM and PIH had the highest impact on developing postpartum DM compared with either condition alone cohort. Furthermore, the co-occurrence of both conditions increases the risk, with a higher likelihood of developing postpartum DM than hypertension or metabolic syndrome.

The novel roles of YULINK in the migration, proliferation and glycolysis of pulmonary arterial smooth muscle cells: implications for pulmonary arterial hypertension.

BACKGROUND: Abnormal remodeling of the pulmonary vasculature, characterized by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) along with dysregulated glycolysis, is a pathognomonic feature of pulmonary arterial hypertension (PAH). YULINK (MIOS, Entrez Gene: 54468), a newly identified gene, has been recently shown to possess pleiotropic physiologic functions. This study aims to determine novel roles of YULINK in the regulation of PAH-related pathogenesis, including PASMC migration, proliferation and glycolysis. RESULTS: Our results utilized two PAH-related cell models: PASMCs treated with platelet-derived growth factor (PDGF) and PASMCs harvested from monocrotaline (MCT)-induced PAH rats (PAH-PASMCs). YULINK modulation, either by knockdown or overexpression, was found to influence PASMC migration and proliferation in both models. Additionally, YULINK was implicated in glycolytic processes, impacting glucose uptake, glucose transporter 1 (GLUT1) expression, hexokinase II (HK-2) expression, and pyruvate production in PASMCs. Notably, YULINK and GLUT1 were observed to colocalize on PASMC membranes under PAH-related pathogenic conditions. Indeed, increased YULINK expression was also detected in the pulmonary artery of human PAH specimen. Furthermore, YULINK inhibition led to the suppression of platelet-derived growth factor receptor (PDGFR) and the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), and protein kinase B (AKT) in both cell models. These findings suggest that the effects of YULINK are potentially mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: Our findings indicate that YULINK appears to play a crucial role in the migration, proliferation, and glycolysis in PASMCs and therefore positioning it as a novel promising therapeutic target for PAH.

Kawasaki disease in children with Bacillus Calmette-Guérin scar reactivity: Focus on coronary outcomes.

BACKGROUND: /Purpose: Reactivity at the Bacillus Calmette-Guérin (BCG) scar is a pathognomonic feature of Kawasaki disease (KD). However, its value in predicting KD outcomes has not been emphasized. This study explored the clinical significance of BCG scar redness with respect to coronary artery outcomes. METHODS: This retrospective study collected data on children with KD from 13 hospitals in Taiwan during 2019-2021. Children with KD were categorized into four groups based on the KD type and BCG scar reactivity. Risk factors of coronary artery abnormalities (CAA) were analyzed in all groups. RESULTS: BCG scar redness occurred in 49% of 388 children with KD. BCG scar redness was associated with younger age, early intravenous immunoglobulin (IVIG) treatment, hypoalbuminemia, and CAA at the first echocardiogram (p < 0.01). BCG scar redness (RR 0.56) and pyuria (RR 2.61) were independent predictors of any CAA within 1 month (p < 0.05). Moreover, pyuria (RR 5.85, p < 0.05) in children with complete KD plus BCG scar redness was associated with CAA at 2-3 months; first IVIG resistance (RR 15.2) and neutrophil levels ≥80% (RR 8.37) in children with complete KD plus BCG scar non-redness were associated with CAA at 2-3 months (p < 0.05). We failed to detect any significant risk factors of CAA at 2-3 months in children with incomplete KD. CONCLUSION: BCG scar reactivity contributes to diverse clinical features in KD. It can be effectively applied to determine the risk factors of any CAA within 1 month and CAA at 2-3 months.

Epicardial Adipose Tissue Was Highly Associated with Reduction in Left Ventricular Diastolic Function as Early as in Adolescence.

Background: Epicardial adipose tissue (EAT) is increased in adolescents with obesity and may play a role in early cardiovascular pathophysiological changes. There is a lack of evidence focusing on the association between EAT and cardiac function in adolescents. This study explored associations between EAT, left ventricle (LV) geometric, and LV functional changes in adolescents. Methods: Adolescent volunteers between 10 and 20 years of age were included. Body mass index (BMI) was presented as age- and sex-specific BMI z-scores. Blood samples for glucose metabolism, lipid profiles, and high-sensitivity C-reactive protein (hs-CRP) were obtained. EAT thickness, LV hypertrophy, and LV diastolic function were measured by echocardiography. Results: The mean age of the 276 adolescents was 13.51 ± 2.44 years. BMI z-score was strongly associated with EAT thickness (r = 0.77; p < 0.001). Multivariable analysis revealed that age, insulin resistance, total cholesterol to high-density lipoprotein cholesterol ratio, and hs-CRP were independent predictors of increased EAT thickness. After adjusting for sex, age, and BMI z-score by multivariable analysis, EAT thickness was a strong predictor of higher LV mass indexed to height2.7, higher relative wall thickness, lower mitral annulus e'/a', and higher E/e' of the mitral annulus. There was no association between EAT and LV ejection fraction. Conclusions: EAT was highly associated with LV hypertrophy and reduction in LV diastolic function, independent of BMI z-score in the enrolled adolescents. Of note, the negative impacts of EAT on LV geometry and diastolic function occurred as early as in adolescence. This highlights the importance of preventing obesity and EAT deposition early in life.

P68 RNA helicase promotes invasion of glioma cells through negatively regulating DUSP5.

Gliomas are the most common central nervous system tumors. They show malignant characteristics indicating rapid proliferation and a high invasive capacity and are associated with a poor prognosis. In our previous study, p68 was overexpressed in glioma cells and correlated with both the degree of glioma differentiation and poor overall survival. Downregulating p68 significantly suppressed proliferation in glioma cells. Moreover, we found that the p68 gene promoted glioma cell growth by activating the nuclear factor-κB signaling pathway by a downstream molecular mechanism that remains incompletely understood. In this study, we found that dual specificity phosphatase 5 (DUSP5) is a downstream target of p68, using microarray analysis, and that p68 negatively regulates DUSP5. Upregulating DUSP5 in stably expressing cell lines (U87 and LN-229) suppressed proliferation, invasion, and migration in glioma cells in vitro, consistent with the downregulation of p68. Furthermore, upregulating DUSP5 inhibited ERK phosphorylation, whereas downregulating DUSP5 rescued the level of ERK phosphorylation, indicating that DUSP5 might negatively regulate ERK signaling. Additionally, we show that DUSP5 levels were lower in high-grade glioma than in low-grade glioma. These results suggest that the p68-induced negative regulation of DUSP5 promoted invasion by glioma cells and mediated the activation of the ERK signaling pathway.

Assessing utility of exercise test in determining exercise prescription in adolescent and adult patients with repaired tetralogy of fallot.

Parameters from cardiopulmonary exercise test (CPET) are useful prognostic factors for patients with repaired tetralogy of fallot (TOF). Its application in exercise prescription remains unclear. This study sought to define its role. We made current exercise recommendations in repaired TOF patients according to European Society of Cardiology (ESC) guideline, which were based on ventricular function, pressure/volume load, pulmonary artery pressure, hypoxemia and arrhythmic burden both at rest and during exercise. CPET parameters (peak oxygen consumption, oxygen uptake efficiency plateau, and E/CO2 slope), along with cardiothoracic ratio, ventricular arrhythmia, QRS duration and NYHA functional status, were used to calculate "score to exercise". 112 repaired TOF adolescent and adult aged 32.6 ± 10.8 (14.05- to 56.99-year-old, median 30.1) years received exercise recommendations by ESC guideline, which suggested high, moderate and low intensity sports for 45 (40.2 %), 45 (40.2 %), and 22 (19.6 %) patients, respectively. The optimal cut-off values were 67 and 77 % for peak VO2, 86 and 100 % for OUEP, 22 and 28 for E/CO2 slope to correlate to the exercise intensity recommendation. But, individual CPET parameter had low consistency (41-46 %) in making decisions of exercise intensity compared to ESC recommendations. Using the "score to exercise", the consistency rate could be increased to 74.1 %. With "score to exercise" recommended exercise intensity, follow-up result revealed no adverse event related to sports. Individual CPET parameter did not correlate well to the exercise recommendation from ESC. We proposed a scoring system, "score to exercise", which incorporates three CPET parameters with cardiothoracic ratio, ventricular arrhythmia, QRS duration and NYHA functional status. Score to exercise is easy to be assessed and provides useful information for exercise recommendation in patients with repaired TOF.

Assessing Late Cardiopulmonary Function in Patients with Repaired Tetralogy of Fallot Using Exercise Cardiopulmonary Function Test and Cardiac Magnetic Resonance.

BACKGROUND: Patients with repaired tetralogy of Fallot (TOF) usually experience progressive right ventricle (RV) dysfunction due to pulmonary regurgitation (PR). This could further worsen the cardiopulmonary function. This study aimed to compare the changes in patient exercise cardiopulmonary test and cardiac magnetic resonance imaging, and consider the implication of these changes. METHODS: Our study examined repaired TOF patients who underwent cardiopulmonary exercise test (CPET) to obtain maximal (peak oxygen consumption, peak VO2) and submaximal parameters (oxygen uptake efficiency plateau, oxygen uptake efficiency plateau (OUEP), and ratio of minute ventilation to carbon dioxide production, VE/VCO2 slope). Additionally, the hemodynamic status was assessed by using cardiac magnetic resonance. Criteria for exclusion included TOF patients with pulmonary atresia, atrioventricular septal defect, or absence of pulmonary valve syndrome. RESULTS: We enrolled 158 patients whose mean age at repair was 7.8 ± 9.1 years (range 0.1-49.2 years) and the mean patient age at CPET was 29.5 ± 12.2 years (range 7.0-57.0 years). Severe PR (PR fraction ≥ 40%) in 53 patients, moderate in 55, and mild (PR fraction < 20%) in 50 patients were noted. The mean RV end-diastolic volume index (RVEDVi) was 113 ± 35 ml/m(2), with 7 patients observed to have a RVEDVi > 163 ml/m(2). The mean left ventricular ejection fraction (LVEF) was 63 ± 8%, left ventricular end-diastolic volume index (LVEDVi) was 65 ± 12 ml/m(2), and LVESVi was 25 ± 14 ml/m(2). CPET revealed significantly decreased peak VO2 (68.5 ± 14.4% of predicted), and fair OUEP (90.3 ± 14.1% of predicted) and VE/VCO2 slope (27.1 ± 5.3). PR fraction and age at repair were negatively correlated with maximal and submaximal exercise indicators (peak VO2 and OUEP). Left ventricular (LV) function and size were positively correlated with peak VO2 and OUEP. CONCLUSIONS: The results of CPET showed that patients with repaired TOF had a low maximal exercise capacity (peak VO2), but a fair submaximal exercise capacity (OUEP and VE/VCO2 slope), suggesting limited exercise capability in high intensity circumstances. PR, LV function and age at total repair were the most important determinants of CPET performance. KEY WORDS: Cardiac magnetic resonance; Cardiopulmonary exercise function; Pulmonary regurgitation; Surgical age; Tetralogy of Fallot.

Ventricular geometric characteristics and functional benefit of mild right ventricular outflow tract obstruction in patients with significant pulmonary regurgitation after repair of tetralogy of Fallot.

BACKGROUND: Right ventricular (RV) outflow tract obstruction (RVOTO) might protect the RV from adverse remodeling caused by significant pulmonary regurgitation (PR) in patients with repaired tetralogy of Fallot (rTOF), but the underlying mechanisms and influences on exercise tolerance remain unclear. This study sought to investigate the impacts from mild RVOTO on ventricular remodeling and exercise capacity in rTOF. METHODS: Eighty-five rTOF patients with a PR fraction ≥20% were assessed with cardiac magnetic resonance, cardiopulmonary exercise test, and echocardiography. Patients with a peak RVOT pressure gradient 20-50 mmHg were considered to have mild RVOTO (n = 29), while those with a gradient <20 mmHg had isolated PR (n = 56). RESULTS: Comparing to patients with isolated PR, patients with combined PR and mild RVOTO had smaller RV and RVOT dimension, better RV and left ventricular (LV) ejection fraction (EF), and superior exercise capacity. PR severity and RV mass/volume ratio were similar between these 2 groups. LVEF coupled with RVEF only in patients with isolated PR. In multivariate analysis, smaller RVOT dimension was independently related to smaller RV dimension (P < .001) and higher RVEF (P = .005). Furthermore, mild RVOTO was independently associated with higher peak oxygen consumption (P = .014) and oxygen uptake efficiency slope (P = .005). CONCLUSIONS: Patients with combined PR and mild RVOTO had better RV remodeling and exercise capacity compared to those with isolated PR. Our findings confirm the benefits from mild residual RVOTO support a policy of conservative RVOTO relief at repair.

Increased expression of ABCB6 enhances protoporphyrin IX accumulation and photodynamic effect in human glioma.

BACKGROUND: Glioma recurrence usually occurs close to the tumor resection margins as a result of residual infiltrating glioma cells. 5-aminolevulinic acid (ALA) fluorescence-guided resection of gliomas has been demonstrated to enhance discrimination of tumor tissue and to improve survival. ALA-based photodynamic therapy is an effective albeit still experimental adjuvant treatment option for gliomas. However, insufficient protoporphyrin IX (PpIX) accumulation may limit the benefits of fluorescence-guided resection and photodynamic therapy. METHODS: We investigated the expression of the ATP-binding cassette transporter ABCB6, which regulates porphyrin synthesis, in surgical specimens from human gliomas and manipulated ABCB6 in human glioma cell lines. RESULTS: Our findings demonstrated that expression levels of ABCB6 were greatly elevated in human gliomas compared with normal brain tissues and correlated with World Health Organization histologic grade. A previously undescribed finding was that ABCB6 mRNA expression in solidly fluorescing tumor tissues was higher than that in vaguely fluorescing tumors, suggesting that ABCB6 may be at least in part responsible for PpIX accumulation in glioma cells. Accordingly, ABCB6 overexpression in glioma cell lines caused a marked increase in intracellular levels of PpIX, and was more sensitive to ALA-induced photodynamic therapy-events that could be prevented by silencing ABCB6 via siRNA treatment. CONCLUSIONS: Our findings indicate a crucial role of ABCB6 in ALA metabolism and accumulation of PpIX in glioma. ABCB6 overexpression is a potential approach to enhance accumulation of PpIX for optimizing the subjective discrimination of vague fluorescence and improving the efficacy of ALA-based photodynamic therapy.

Early-Term Neonates Demonstrate a Higher Likelihood of Requiring Phototherapy Compared to Those Born Full-Term.

Early-term neonates (with a gestational age (GA) of 37 and 0/7 weeks to 38 and 6/7 weeks) face higher morbidities, including respiratory and neurodevelopmental issues, than full-term (39 and 0/7 weeks to 40 and 6/7 weeks) infants. This study explores whether hyperbilirubinemia necessitating phototherapy also differs between these groups. A retrospective study was conducted on neonates born from January 2021-June 2022, excluding those with specific conditions. Evaluated factors included GA, birth weight, bilirubin levels, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and feeding type, with phototherapy given as per AAP guidelines. Of 1085 neonates, 356 met the criteria. When stratifying the neonates based on the need for phototherapy, a higher proportion of early-term neonates required phototherapy compared to full-term (p < 0.05). After factoring in various risks (GA; birth weight; gender; feeding type; G6PD deficiency; transcutaneous bilirubin levels at 24 h and 24-48 h postpartum; maternal diabetes; and the presence of caput succedaneum or cephalohematoma), early-term neonates were more likely to need phototherapy than full-term babies (OR: 2.15, 95% CI: 1.21 to 3.80). The optimal cut-off for transcutaneous bilirubin levels 24-48 h postpartum that were used to predict phototherapy need was 9.85 mg/dl. In conclusion, early-term neonates are at a greater risk for developing jaundice and requiring phototherapy than full-term neonates. Monitoring bilirubin 24-48 h postpartum enhances early prediction and intervention.

Changing patterns of infectious diseases in children during the COVID-19 pandemic.

Each infectious disease has had its own epidemic pattern and seasonality for decades. However, public health mitigation measures during the coronavirus disease 2019 (COVID-19) pandemic have resulted in changing epidemic patterns of infectious diseases. Stringent measures resulted in low incidences of various infectious diseases during the outbreak of COVID-19, including influenza, respiratory syncytial virus, pneumococcus, enterovirus, and parainfluenza. Owing to the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and subsequent immunity development, decreasing virulence of SARS-CoV-2, and worldwide immunization against SARS-CoV-2 in children beyond 6 months of age, mitigation measures are lifted country by country. Consequently, the immunity debt to infectious respiratory viruses other than SARS-CoV-2 contributed to the "off-season," "see-saw," and "upsurge" patterns of various infectious diseases in children. Moreover, apart from the persistence of SARS-CoV-2, the coexistence of other circulating viruses or bacterial outbreaks may lead to twindemics or tripledemics during the following years. Therefore, it is necessary to maintain hand hygiene and immunization policies against various pathogens to alleviate the ongoing impact of infectious diseases on children.

Cross-protective humoral immunity to coronaviruses from SARS coronavirus 2-naïve sera of children with Kawasaki disease.

OBJECTIVES: SARS coronavirus 2 (SARS-CoV-2)-associated multi-system inflammatory syndrome in children indicates that viruses can trigger a Kawasaki disease (KD)-like hyperinflammation. A plausible hypothesis was that coronavirus-specific 'holes' in humoral immunity could cause both diseases. METHODS: To determine whether SARS-CoV-2-naïve patients with KD have inferior humoral immunity for the novel coronavirus, sera of children with KD and control children from year 2015 to 2021 were subjected to ELISA, microwestern, and neutralization assays to evaluate the capabilities in recognizing the receptor-binding domain of SARS-CoV-2, spotting spike proteins of three respiratory syndromic coronaviruses, and blocking SARS-CoV-2 from binding to angiotensin-converting enzyme 2 receptors in vitro, respectively. RESULTS: 29 patients with KD before 2019, 74 patients with KD in 2019 or 2020, 54 non-febrile controls, and 24 febrile controls were included in the study. SARS-CoV-2 was recognized on ELISA for both patients with KD in 2016 and those with KD in 2020. Microwestern demonstrated cross-reactive IgG in an all-or-none manner towards three spike proteins of syndromic coronaviruses regardless of sample year or KD status. The ratio between the sera that recognized all spike proteins and those that recognized none (51 vs. 47) was significantly higher from patients with KD than from non-febrile controls (17 vs. 32; p 0.047) but not from febrile controls (13 vs. 11; p 0.85). Most positive sera (12 of 17 controls, 5 of 8 patients with KD before 2019, and 28 of 33 patients with KD in 2019 or 2020) offered protection comparable to low-titre sera from the WHO reference panel. DISCUSSION: Humoral immunity of SARS-CoV-2-naïve children with KD was not inferior to that of controls in offering cross-protection against the novel coronavirus.

Natural and unnatural history of tetralogy of Fallot repaired during adolescence and adulthood.

Surgical repair of tetralogy of Fallot (TOF) in countries with sound medical care systems is seldom delayed until adolescence. This study investigated the clinical profile and the surgical outcomes in such a population from Taiwan. Between 1970 and 2009, 179 TOF patients (56% male) received total repair at 19.2 ± 8.3 (10-49) years of age. We reviewed the medical records and interviewed the patients concerning their current status. The survival was ascertained in all by a link to our national health database. Major morbidities before cardiac repair included atrial arrhythmia (1.1%), ventricular arrhythmia (3.9%), infective endocarditis (6.7%), brain abscess (4.6%) and pulmonary tuberculosis (3.3%). Ventricular arrhythmia and pulmonary tuberculosis occurred mainly after 20 years of age. Thirty patients (16.8%) received a palliative shunt. The preoperative QRS duration increment was 0.6 ms/year. Early mortality occurred in 4 (2.2%) and was related to previous shunt surgery (OR = 16.5, p < 0.05) and coronary artery crossing RVOT (OR 17.6, p < 0.05). After repair, the functional class improved in all patients. The median age at latest follow-up was 31.8 (32.8 ± 12.3) years. The survival was 92.7 and 89.3% at 20 and 30 years after operation, respectively. Late cardiovascular death could be predicted by the length of postoperative intensive care unit stay (OR = 1.3, p < 0.001). The freedom from ventricular arrhythmia 30 years after repair was 84.1% and was associated with a final QRS longer than 160 ms. Unrepaired TOF patients were at high risk of infective endocarditis, brain abscess, pulmonary tuberculosis and arrhythmias during their adolescence and adulthood. Cardiac repair in this age group was still safe and effective.

A Metabolic Plasticity-Based Signature for Molecular Classification and Prognosis of Lower-Grade Glioma.

BACKGROUND: Glioma is one of the major health problems worldwide. Biomarkers for predicting the prognosis of Glioma are still needed. METHODS: The transcriptome data and clinic information on Glioma were obtained from the CGGA, TCGA, GDC, and GEO databases. The immune infiltration status in the clusters was compared. The genes with differential expression were identified, and a prognostic model was developed. Several assays were used to detect RPH3A's role in Glioma cells, including CCK-8, colony formation, wound healing, and transwell migration assay. RESULTS: Lower Grade Glioma (LGG) was divided into two clusters. The immune infiltration difference was observed between the two clusters. We screened for genes that differed between the two groups. WGCNA was used to construct a co-expressed network using the DEGs, and four co-expressed modules were identified, which are blue, green, grey, and yellow modules. High-risk patients have a lower overall survival rate than low-risk patients. In addition, the risk score is associated with histological subtypes. Finally, the role of RPH3A was detected. The overexpression of RPH3A in LGG cells can significantly inhibit cell proliferation and migration and regulate EMT-regulated proteins. CONCLUSION: Our study developed a metabolic-related model for the prognosis of Glioma cells. RPH3A is a potential therapeutic target for Glioma.

Augmented detection of septal defects using advanced optical coherence tomography network-processed phonocardiogram.

Background: Cardiac auscultation is a traditional method that is most frequently used for identifying congenital heart disease (CHD). Failure to diagnose CHD may occur in patients with faint murmurs or obesity. We aimed to develop an intelligent diagnostic method of detecting heart murmurs in patients with ventricular septal defects (VSDs) and atrial septal defects (ASDs). Materials and methods: Digital recordings of heart sounds and phonocardiograms of 184 participants were obtained. All participants underwent echocardiography by pediatric cardiologists to determine the type of CHD. The phonocardiogram data were classified as normal, ASD, or VSD. Then, the phonocardiogram signal was used to extract features to construct diagnostic models for disease classification using an advanced optical coherence tomography network (AOCT-NET). Cardiologists were asked to distinguish normal heart sounds from ASD/VSD murmurs after listening to the electronic sound recordings. Comparisons of the cardiologists' assessment and AOCT-NET performance were performed. Results: Echocardiography results revealed 88 healthy participants, 50 with ASDs, and 46 with VSDs. The AOCT-NET had no advantage in detecting VSD compared with cardiologist assessment. However, AOCT-NET performance was better than that of cardiologists in detecting ASD (sensitivity, 76.4 vs. 27.8%, respectively; specificity, 90 vs. 98.5%, respectively). Conclusion: The proposed method has the potential to improve the ASD detection rate and could be an important screening tool for patients without symptoms.