Inflammation activity affects liver stiffness measurement by magnetic resonance elastography in MASLD.

BACKGROUND: Magnetic resonance elastography (MRE) is recognized as the most precise imaging technology for assessing liver fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to investigate the clinical factors and pathological characteristics that may impact LSM in MASLD patients. METHODS: This cross-sectional study recruited 124 patients who concurrently performed MRE, MRI-PDFF, and biopsy-proven MASLD. Linear regression models, Spearman's correlation, and subgroup analysis were employed to identify the variables affecting LSM. RESULTS: The AUROC (95 % CI) of MRE for diagnosing fibrosis stage ≥ 1, 2, 3, and 4 was 0.80 (0.70-0.90), 0.76 (0.66-0.85), 0.92 (0.86-0.99), and 0.99 (0.99-1.00), with corresponding cutoffs of 2.56, 2.88, 3.35, and 4.76 kPa, respectively. Multivariate analyses revealed that AST was the only independent clinical variable significantly correlated with LSM. Furthermore, LSM exhibited a notable association with the grade of lobular inflammation and hepatocellular ballooning. Subgroup analysis showed that when AST ≥ 2 ULN or inflammation grade ≥ 2, LSM of patients with early fibrosis stages showed a slight but significant increase. CONCLUSION: MRE demonstrates significant diagnostic accuracy in predicting liver fibrosis stages for MASLD patients, especially for advanced liver fibrosis and cirrhosis. However, elevated AST and the severity of liver inflammation may impact its accuracy in staging early liver fibrosis.

Sex differences in 3- to 5-year-old children's motor competence: A pooled cross-sectional analysis of 6241 children.

There is some, albeit inconsistent, evidence supporting sex differences in preschoolers' motor competence (MC), with these observations not uniform when analyzed by age, and cultural groups. Thus, this study examined sex differences across ages in 3- to 5-year-old children's MC. A cross-country pooled sample of 6241 children aged 3-5 years (49.6% girls) was assessed for MC using the Test of Gross Motor Development-2nd/3rd edition, and children were categorized into groups of age in months. Multiple linear regression models and predictive margins were calculated to explore how sex and age in months affect scores of MC (i.e., locomotor and ball skills), with adjustments for country and BMI. The Chow's Test was used to test for the presence of a structural break in the data. Significant differences in favor of girls were seen at 57-59 and 66-68 months of age for locomotor skills; boys performed better in ball skills in all age periods, except for 42-44 and 45-47 months of age. The higher marginal effects were observed for the period between 45-47 and 48-50 months for locomotor skills (F = 30.21; and F = 25.90 for girls and boys, respectively), and ball skills (F = 19.01; and F = 42.11 for girls and boys, respectively). A significantly positive break point was seen at 45-47 months, highlighting the age interval where children's MC drastically improved. The identification of this breakpoint provides an evidence-based metric for when we might expect MC to rapidly increase, and an indicator of early delay when change does not occur at that age.

Association between diabetes mellitus and primary biliary cholangitis: a two-sample Mendelian randomization study.

Background: Previous observational studies have demonstrated a link between diabetes mellitus(DM) and primary biliary cholangitis (PBC). Nevertheless, since these relationships might be confused, whether there is any causal connection or in which direction it exists is unclear. Our investigation aimed to identify the causal associations between DM and PBC. Methods: We acquired genome-wide association study (GWAS) datasets for PBC, Type 1 diabetes(T1DM), and Type 2 diabetes(T2DM) from published GWASs. Inverse variance-weighted (IVW), MR-Egger, weighted median (WM), Simple mode, and weighted mode methods were used to determine the causal relationships between DM(T1DM or T2DM) and PBC. Sensitivity analyses were also carried out to ensure the results were robust. To determine the causal relationship between PBC and DM(T1DM or T2DM), we also used reverse MR analysis. Results: T1DM was associated with a higher risk of PBC (OR 1.1525; 95% CI 1.0612-1.2517; p = 0.0007) in the IVW method, but no evidence of a causal effect T2DM on PBC was found (OR 0.9905; 95% CI 0.8446-1.1616; p = 0.9071) in IVW. Results of the reverse MR analysis suggested genetic susceptibility that PBC was associated with an increased risk of T1DM (IVW: OR 1.1991; 95% CI 1.12-1.2838; p = 1.81E-07), but no evidence of a causal effect PBC on T2DM was found (IVW: OR 1.0101; 95% CI 0.9892-1.0315; p = 0.3420). Conclusion: The current study indicated that T1DM increased the risk of developing PBC and vice versa. There was no proof of a causal connection between PBC probability and T2DM. Our results require confirmation through additional replication in larger populations.

Food insecurity and academic performance in Spanish adolescents: Results from the EHDLA study.

Introduction: Food insecurity is a growing global issue that affects both developed and developing nations, and mounting evidence suggests that decreased consumption of healthy foods has been linked to lower academic performance in adolescents. The present study aimed to examine the relationship between food insecurity and academic performance in a sample of Spanish adolescents aged 12-17 years from the Valle de Ricote (Region of Murcia, Spain). Methods: The present study analyzed data from the Eating Healthy and Daily Life Activities study, which included a sample of 777 adolescents (55.3 % girls). The Spanish Child Food Security Survey Module was used to assess food insecurity, and academic performance was evaluated using school records provided by the schools. Linear regression models (fitted by robust methods) were used to compare the relationships between food insecurity status and academic performance-related indicators. Results: Adolescents with the highest levels of food insecurity reported the lowest academic performance in language (mean [M] = 4.7; 95 % confidence interval [CI] 3.6 to 5.7), math (M = 4.6; 95 % CI 3.5 to 5.8), foreign language (M = 4.8; 95 % CI 3.8 to 5.8), and grade point average (M = 5.7; 95 % CI 4.9 to 6.5). Conversely, adolescents with the lowest levels of food insecurity reported the highest academic performance in language (M = 6.2; 95 % CI 6.0 to 6.5), math (M = 5.9; 95 % CI 5.5 to 6.2), foreign language (M = 6.2; 95 % CI 5.9 to 6.4), and grade point average (M = 6.7; 95 % CI 6.5 to 6.9) compared to those with higher food security. Conclusions: Living in a more food-insecure household could explain the lower academic performance of adolescents. Food insecurity should always be on the agenda of public policies. The availability of quality basic food essentials must be ensured in permanently satisfactory quantities without compromising access to other fundamental needs.

Health Benefits of Different Sports: a Systematic Review and Meta-Analysis of Longitudinal and Intervention Studies Including 2.6 Million Adult Participants.

BACKGROUND: Several reviews have examined the health benefits of participation in specific sports, such as baseball, cricket, cross-country skiing, cycling, downhill skiing, football, golf, judo, rugby, running and swimming. However, new primary studies on the topic have recently been published, and the respective meta-analytic evidence needs to be updated. OBJECTIVES: To systematically review, summarise and appraise evidence on physical health benefits of participation in different recreational sports. METHODS: Searches for journal articles were conducted in PubMed/MEDLINE, Scopus, SpoLit, SPORTDiscus, Sports Medicine & Education Index and Web of Science. We included longitudinal and intervention studies investigating physical health outcomes associated with participation in a given sport among generally healthy adults without disability. RESULTS: A total of 136 papers from 76 studies conducted among 2.6 million participants were included in the review. Our meta-analyses of available evidence found that: (1) cycling reduces the risk of coronary heart disease by 16% (pooled hazard ratio [HR] = 0.84; 95% confidence interval [CI]: 0.80, 0.89), all-cause mortality by 21% (HR = 0.79; 95% CI: 0.73, 0.84), cancer mortality by 10% (HR = 0.90; 95% CI: 0.85, 0.96) and cardiovascular mortality by 20% (HR = 0.80; 95% CI: 0.74, 0.86); (2) football has favourable effects on body composition, blood lipids, fasting blood glucose, blood pressure, cardiovascular function at rest, cardiorespiratory fitness and bone strength (p < 0.050); (3) handball has favourable effects on body composition and cardiorespiratory fitness (p < 0.050); (4) running reduces the risk of all-cause mortality by 23% (HR = 0.77; 95% CI: 0.70, 0.85), cancer mortality by 20% (HR = 0.80; 95% CI: 0.72, 0.89) and cardiovascular mortality by 27% (HR = 0.73; 95% CI: 0.57, 0.94) and improves body composition, cardiovascular function at rest and cardiorespiratory fitness (p < 0.010); and (5) swimming reduces the risk of all-cause mortality by 24% (HR = 0.76; 95% CI: 0.63, 0.92) and improves body composition and blood lipids (p < 0.010). CONCLUSIONS: A range of physical health benefits are associated with participation in recreational cycling, football, handball, running and swimming. More studies are needed to enable meta-analyses of health benefits of participation in other sports. PROSPERO registration number CRD42021234839.

Major depressive disorder recognition by quantifying EEG signal complexity using proposed APLZC and AWPLZC.

BACKGROUND: Seeking objective quantitative indicators is important for accurately recognizing major depressive disorder (MDD). Lempel-Ziv complexity (LZC), employed to characterize neurological disorders, faces limitations in tracking dynamic changes in EEG signals due to defects in the coarse-graining process, hindering its precision for MDD objective quantitative indicators. METHODS: This work proposed Adaptive Permutation Lempel-Ziv Complexity (APLZC) and Adaptive Weighted Permutation Lempel-Ziv Complexity (AWPLZC) algorithms by refining the coarse-graining process and introducing weight factors to effectively improve the precision of LZC in characterizing EEGs and further distinguish MDD patients better. APLZC incorporated the ordinal pattern, while False Nearest Neighbor and Mutual Information algorithms were introduced to determine and adjust key parameters adaptively. Furthermore, we proposed AWPLZC by assigning different weights to each pattern based on APLZC. Thirty MDD patients and 30 healthy controls (HCs) were recruited and their 64-channel resting EEG signals were collected. The complexities of gamma oscillations were then separately computed using LZC, APLZC, and AWPLZC algorithms. Subsequently, a multi-channel adaptive K-nearest neighbor model was constructed for identifying MDD patients and HCs. RESULTS: LZC, APLZC, and AWPLZC algorithms achieved accuracy rates of 78.29 %, 90.32 %, and 95.13 %, respectively. Sensitivities reached 67.96 %, 85.04 %, and 98.86 %, while specificities were 88.62 %, 95.35 %, and 89.92 %, respectively. Notably, AWPLZC achieved the best performance in accuracy and sensitivity, with a specificity limitation. LIMITATION: The sample size is relatively small. CONCLUSION: APLZC and AWPLZC algorithms, particularly AWPLZC, demonstrate superior effectiveness in differentiating MDD patients from HCs compared with LZC. These findings hold significant clinical implications for MDD diagnosis.

Cross-sectional association between 24-hour movement guidelines and depressive symptoms in Chinese university students.

Background: The world's first 24-h movement guidelines for adults were released on 15 October 2020 in Canada, though evidence of their associations with health indicators in young adults is sparse. This study aimed to report the prevalence of meeting the 24-h movement guidelines and associations with depressive symptoms in a sample of Chinese university students. Methods: Cross-sectional data from 1,793 Chinese university students (mean age = 20.7 years, 63.6% female) were used. Sociodemographic information, movement behaviors (physical activity, sedentary behavior, and sleep duration), and depressive symptoms were collected using a self-reported questionnaire. Results: The prevalence of meeting the 24-h movement guidelines was 27.8% in Chinese university students. Logistic regression results show that compared to those who met the 24-h movement guidelines, odds ratio (OR) for depressive symptoms in those who met fewer recommendations contained in the 24-h movement guidelines were significantly higher (OR for none = 3.4, 95% CI [2.1-5.5], p < 0.001; OR for one = 2.7, 95% CI [2.0-3.8], p < 0.001; OR for two = 1.5, 95% CI [1.1-2.1], p = 0.013). Conclusion: The prevalence of meeting the 24-h movement guidelines in Chinese university students was relatively low and should be enhanced through multiple strategies. Meeting the 24-h movement guidelines was associated with lower risk for depression in Chinese young adults. It is suggested that moving more, sitting less and sleeping well in this population may reduce the occurrence of depression.

The validity of the Physical Literacy in Children Questionnaire in children aged 4 to 12.

BACKGROUND: Given the growing evidence on the health benefits associated with physical literacy (PL), it is necessary to develop sound measures to assess the levels of PL in children. The Physical Literacy in Children Questionnaire (PL-C Quest) is the first self-report pictorial-based scale to assess children's perceived PL. It has good validity and reliability in Australian children aged 7 to 12 years, but little is known in younger children and in other cultural contexts. The aim of this study was to examine the validity and reliability in an expanded age range. METHODS: A total of 1,870 Chinese children (girls, n = 871; 46.6%), aged 4 to 12 years (M = 8.07 ± 2.42) participated in validity testing. Structural equation modeling with the Weighted Least Squares with Mean and Variance approach was used to assess construct validity. The hypothesized theoretical model used the 30 items and four hypothesized factors: physical, psychological, social and cognitive capabilities. Multigroup confirmatory factor analysis was used to assess sex and age group (4-6 years, 7-9 years and 10-12 years) measurement invariance. Internal consistency analyses were conducted using polychoric alpha. A random subsample (n = 262) was selected to determine test-retest reliability using Intra-Class Correlations (ICC). RESULTS: All items except one (moving with equipment-skateboarding) loaded on sub-domains with λ > 0.45. The hypothesized model had a good fit (CFI = 0.954, TLI = 0.950, RMSEA = 0.042), with measurement equivalence across sex and age groups separately. Internal consistency values were good to excellent (overall: α = 0.94; physical: α = 0.86; psychological: α = 0.83; social: α = 0.81; cognitive: α = 0.86). Test-retest reliability was adequate to excellent (overall: ICC = 0.90, physical: ICC = 0.86, psychological: ICC = 0.75, social: ICC = 0.71, cognitive: ICC = 0.72). CONCLUSION: The Chinese version of the PL-C Quest is valid and reliable for testing the self-reported PL of Chinese children aged 4 to 12. This study provides the first evidence of validity for this tool in children aged 4-6 years and also evidence that the PL-C Quest would be a meaningful instrument to assess PL in Chinese children.

Trends in adherence to the 24-h movement guidelines among US adolescents from 2011 to 2019: Evidence from repeated cross-sectional cycles of the Youth Risk Behavior Surveillance System.

BACKGROUND: Adherence to the 24-h movement guidelines is associated with various health benefits, but given the novelty of these integrative recommendations, little is known about year-to-year trends in guideline adherence in adolescents. This study investigated trends of adherence to the 24-h movement guidelines among US adolescents. METHODS: Data from 2011 to 2019 cycles of the Youth Risk Behavior Surveillance System were used, which included 62 589 US adolescents aged 14-17 years (female: unweighted sample size = 31 876, 51%; weighted% = 50.1%). Participants self-reported their demographic information (i.e., sex, age, race/ethnicity), physical activity, screen time and sleep duration. Meeting the 24-h movement guidelines was operationalized as simultaneously engaging in 60 min or more of moderate-to-vigorous physical activity, no more than 2 h of screen time, and 8-10 h of sleep per day. Trend analysis was used to examine the secular changes in adherence to the integrated guidelines from 2011 to 2019. RESULTS: Downward trends in adherence to the 24-h movement guidelines were observed among adolescents from 2011 (3.6%) to 2019 (2.6%). After stratification by sex, age, and race/ethnicity, similar downward trends in the guideline adherence were observed in females and Black/African American adolescents. The lowest prevalence of meeting the individual guidelines was for the PA guidelines (25.6%). Movement guideline adherence was consistently lowest among females, older adolescents, and those who identified as Black/African American. CONCLUSIONS: Adherence to the 24-h movement guidelines has declined among US adolescents over the past decade. Interventions should prioritize an integrative approach that could increase concurrent adherence to each of the 24-h movement guideline, particularly among female, older and minority adolescents.

Prevalence of meeting 24-hour movement guidelines and its associations with health indicators in people with disabilities: A systematic review and meta-analysis.

BACKGROUND: Meeting the 24-h movement guidelines (i.e., physical activity, sedentary behavior, sleep) could generate health benefits to people with disabilities. However, no systematic reviews or meta-analyses have examined the prevalence of meeting these guidelines and associations with health indicators in this group. OBJECTIVE: This systematic review and meta-analysis aimed to examine the prevalence of meeting the 24-h movement guidelines and associations with health indicators among people with disabilities. METHODS: Six electronic databases were searched for studies published in English from inception to May 31, 2023. Meta-analyses with the random-effects model were used to determine the prevalence of meeting the 24-h movement guidelines. Qualitative syntheses were employed to describe the associations between meeting the guidelines and health indicators. RESULTS: Twenty-four studies comprising 77510 participants (41.6% females) with disabilities aged 6-65 years from eight countries were identified. Overall, 6.97% of the participants with disabilities met all 24-h movement guidelines, and 16.65% met none of the guidelines. Significant age (P = 0.006) and disability type (P = 0.001) differences were found in meeting all guidelines. Participants with disabilities who met all guidelines reported better psychosocial health indicators (9/9 studies) than those met none or only one of the guidelines. There was limited evidence or research for other health indicators. CONCLUSION: There is some evidence showing that the prevalence of meeting all 24-h movement guidelines in people with disabilities is low. Meanwhile, there is preliminary evidence suggesting that meeting all guidelines is associated with better psychosocial health than meeting none of the guidelines.

Pilot randomized controlled trial of a game-based intervention for teaching basketball in Chinese primary school physical education.

This study aimed to examine the preliminary efficacy and feasibility of implementing a tailored version of the MASTER coach education programme in Chinese primary schools to support physical education (PE) teachers' basketball lesson design and delivery. A total of 20 primary schools in Beijing, China were recruited, with one PE teacher and their class (N = 715 students aged 10-13 yrs) from each school included in the study and randomly allocated to the MASTER intervention (n = 10) or control group (n = 10). Compared to the control group, a significant difference was observed in the MASTER group for the proportion of playing-form activities delivered during PE (27.65, 95% CI [20.27, 35.03]) and for teachers' perceptions of confidence (23.92, 95% CI [15.87, 31.92]) and competence (24.12, 95% CI [10.28, 24.71]) to teach. Significant differences between groups were observed for students' perceived athletic competence (3.56%; 95% CI [3.15, 3.96]), enjoyment (11.83%; 95% CI [10.98, 12.69]), well-being (8.51%; 95% CI [7.02, 10.00]), intrinsic motivation (+0.74%; 95% CI [0.30, 1.17]), introjected motivation (-2.24%; 95% CI [-2.77, -1.70]), and external motivation (-0.49%; 95% CI [-0.90, -0.08]). The MASTER programme was effective in improving teaching practices in Chinese primary schools, and in facilitating improvements in teacher and student outcomes.

Is adherence to the 24-h movement guidelines associated with greater academic-related outcomes in children and adolescents? A systematic review and meta-analysis.

The purpose of this systematic review was to synthesise the evidence for the association of adherence to the 24-h movement guidelines with academic-related outcomes in children and adolescents. This systematic review was based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. PubMed, PsycINFO, Scopus, WOS, SPORTDiscus, and EMBASE were searched from their inception to 12 December 2023. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to assess the risk of bias of included studies. In total, 4326 records were identified through database searches; 10 articles met the inclusion criteria and were included in this systematic review. There were eight cross-sectional studies and two longitudinal studies; the main academic-related outcomes were academic achievement and cognitive function. A small association between adherence to all three recommendations and academic achievement (k = 5, r = 0.17, 95% CI = 0.10-0.24, I2 = 49%) was found compared to those who did not adhere to any recommendations.   Conclusion: Findings from this systematic review and meta-analysis reveal a small association between adherence to all three recommendations and greater academic achievement in children and adolescents. Nevertheless, it is imperative to underscore the need for more studies to establish robust evidence underpinning this relationship.   Trial registration: PROSPERO (CRD42021295403). What is Known: • Regular physical activity, reduced screen time, and optimal sleep duration are independently associated with improved academic-related outcomes in children and adolescents. • The associations between adherence to the 24-h movement guidelines and academic-related outcomes in children and adolescents have not been quantitatively synthesised. What is New: • There is a small but positive association between adherence to all three recommendations of the 24-h movement guidelines and greater academic achievement in children and adolescents. • Further well-designed research is needed to focus on academic achievement, cognitive function and classroom behaviours in young individuals.

Coronary artery calcium and cardiovascular outcomes in patients with lymphoma undergoing autologous hematopoietic cell transplantation.

BACKGROUND: Patients undergoing autologous hematopoietic cell transplantation (HCT) have a >2-fold risk of developing cardiovascular disease (CVD; heart failure, myocardial infarction, and stroke), compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in nononcology patients but is not as well studied in patients who underwent HCT and survivors of HCT.The objective of this study was to examine the association between CAC and CVD risk and outcomes after HCT in patients with lymphoma. METHODS: This was a retrospective cohort study of 243 consecutive patients who underwent a first autologous HCT for lymphoma between 2009 and 2014. CAC (Agatston score) was determined from chest computed tomography obtained <60 days from HCT. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CIs), adjusted for covariates (age, conventional risk factors [e.g., hypertension and dyslipidemia], and cancer treatment). RESULTS: The median age at HCT was 55.7 years (range, 18.5-75.1 years), 59% were male, and 60% were non-Hispanic White. The prevalence of CAC was 37%. The 5-year CVD incidence for the cohort was 12%, and there was an incremental increase in the incidence according to CAC score: 0 (6%), 1-100 (20%), and >100 (32%) (p = .001). CAC was significantly associated with CVD risk (HR, 3.0; 95% CI, 1.2-7.5) and worse 5-year survival (77% vs. 50%; p < .001; HR, 2.0; 95% CI, 1.1-3.4), compared to those without CAC. CONCLUSIONS: CAC is independently associated with CVD and survival after HCT. This highlights the importance of integrating readily available imaging information in risk stratification and decision-making in patients undergoing HCT, which sets the stage for strategies to optimize outcomes after HCT.

Temporal hyper-connectivity and frontal hypo-connectivity within gamma band in schizophrenia: A resting state EEG study.

OBJECTIVE: The brain network serves as the physiological foundation for information processing of the brain. Many studies have reported abnormalities of gamma oscillations in Schizophrenia. The aim of this study was to investigate the gamma-band connectivity in Schizophrenia patients. METHODS: We recorded the resting state electroencephalogram (EEG) for 15 schizophrenia patients with refractory auditory hallucinations and 14 healthy controls, with eyes open and closed. The brain network was constructed based on weighted phase lag index for gamma band. Whole scalp metrics (clustering coefficient, global efficiency and local efficiency) and local region metrics (degree and betweenness centrality) in the frontal and temporal lobes were computed. Correlation analyses between network metrics and symptom scales were examined to find associations with symptom severity. RESULTS: Schizophrenia patients had larger global efficiency and local efficiency (p < 0.05) with eyes closed, probably representing greater brain activity and information exchange. For degree and betweenness centrality, schizophrenia patients showed an increase (p < 0.05) in the temporal lobe but a decrease (p < 0.05) in the frontal lobe with eyes closed and open, potentially account for the patients' symptoms such as hallucinations and thought disorders. Local efficiency and frontal lobe degree were positively and negatively correlated with the scales, respectively (both p < 0.05). CONCLUSIONS: Altered connectivity of the resting state brain network has been revealed and may be associated with the core symptoms of schizophrenia. Our study provides promising evidence for the investigation of the pathological basis of Schizophrenia and could aid in objective diagnosis.

Effect of carvedilol versus placebo on cardiac function in anthracycline-exposed survivors of childhood cancer (PREVENT-HF): a randomised, controlled, phase 2b trial.

BACKGROUND: Carvedilol improves cardiac function in patients with heart failure but remains untested as cardioprotective therapy in long-term childhood cancer survivors (ie, those who have completed treatment for childhood cancer and are in remission) at risk for heart failure due to high-dose anthracycline exposure. We aimed to evaluate the activity and safety of low-dose carvedilol for heart failure risk reduction in childhood cancer survivors at highest risk for heart failure. METHODS: PREVENT-HF was a randomised, double-blind, phase 2b trial done at 30 hospitals in the USA and Canada. Patients were eligible if they had any cancer diagnosis that resulted in at least 250 mg/m2 cumulative exposure to anthracycline by age 21 years; completed their cancer treatment at least 2 years previously; an ejection fraction of at least 50% or fractional shortening of at least 25%, or both; and bodyweight of at least 40 kg. Patients were randomly assigned (1:1) with automated computer-generated permuted block randomisation (block size of 4), stratified by age at diagnosis, time since diagnosis, and history of chest-directed radiotherapy, to carvedilol (up-titrated from 3·125 g per day to 12·5 mg per day) or placebo orally for 2 years. Participants, staff, and investigators were masked to study group allocation. The primary endpoint was to establish the effect of carvedilol on standardised left ventricular wall thickness-dimension ratio Z score (LVWT/Dz). Treatment effects were analysed with a linear mixed-effects model for normally distributed data with a linear time effect and testing the significance of treatment*time interaction in the modified intention-to-treat (mITT) cohort (ie, all randomly assigned participants who had a baseline and at least one subsequent echocardiogram measurement). Safety was assessed in the ITT population (ie, all randomly assigned participants). This trial was registered with ClinicalTrials.gov, NCT027175073, and enrolment and follow-up are complete. FINDINGS: Between July 3, 2012, and June 22, 2020, 196 participants were enrolled, of whom 182 (93%) were eligible and randomly assigned to either carvedilol (n=89) or placebo (n=93; ITT population). Median age was 24·7 years (IQR 19·6-36·6), 91 (50%) participants were female, 91 (50%) were male, and 119 (65%) were non-Hispanic White. As of data cutoff (June 10, 2022), median follow-up was 725 days (IQR 378-730). 151 (n=75 in the carvedilol group and n=76 in the placebo group) of 182 participants were included in the mITT population, among whom LVWT/Dz was similar between the two groups (-0·14 [95% CI -0·43 to 0·16] in the carvedilol group vs -0·45 [-0·77 to -0·13] in the placebo group; difference 0·31 [95% CI -0·10 to 0·73]; p=0·14). Two (2%) of 89 patients in the carvedilol group two adverse events of grade 2 or higher (n=1 shortness of breath and n=1 arthralgia) and none in the placebo group. There were no adverse events of grade 3 or higher and no deaths. INTERPRETATION: Low-dose carvedilol appears to be safe in long-term childhood cancer survivors at risk for heart failure, but did not result in significant improvement of LVWT/Dz compared with placebo. These results do not support the use of carvedilol for secondary heart failure prevention in anthracycline-exposed childhood cancer survivors. FUNDING: National Cancer Institute, Leukemia & Lymphoma Society, St Baldrick's Foundation, Altschul Foundation, Rally Foundation, American Lebanese Syrian Associated Charities.

Development and Validation of Data-Level Innovation Data-Balancing Machine Learning Models for Predicting Optimal Implantable Collamer Lens Size and Postoperative Vault.

INTRODUCTION: There are only four sizes of implantable collamer lens (ICL) available for selection, which cannot completely fit all patients as a result of the discontinuity of ICL sizes. Sizing an optimal ICL and predicting postoperative vault are still unresolved problems. This study aimed to develop and validate innovative data-level data-balancing machine learning-based models for predicting ICL size and postoperative vault. METHODS: The patients were randomly assigned to training and internal validation sets in a 4:1 ratio. Feature selection was performed using analysis of variance (ANOVA) and Kruskal-Wallis feature importance methods. Traditional linear regression model and machine learning-based models were used. The accuracy of models was assessed using the area under the curve (AUC) and confusion matrix. RESULTS: A total of 564 patients (1127 eyes) were eligible for this study, consisting of 808 eyes in the training set, 202 eyes in the internal validation set, and 117 eyes in the external validation set. Compared with the traditional linear regression method, the machine learning model bagging tree showed the best performance for ICL size selection, with an accuracy of 84.5% (95% confidence interval (CI) 83.2-85.8%), and the AUC ranged from 0.88 to 0.99; the prediction accuracy of 12.1 mm and 13.7 mm ICL sizes was improved by 49% and 59%, respectively. The bagging tree model achieved the best accuracy [90.2%, (95% CI 88.9-91.5%)] for predicting the postoperative vault, and the AUC ranged from 0.90 to 0.94. The prediction accuracies of internal and external validation dataset for ICL sizing were 82.2% (95% CI 81.1-83.3%) and 82.1% (95% CI 81.1-83.1%), respectively. CONCLUSIONS: The innovative data-level data balancing-based machine learning model can be used to predict ICL size and postoperative vault more accurately, which can assist surgeons in choosing optimal ICL size, thus reducing risks of postoperative complications and secondary surgery.

Motor Competence and Body Mass Index in the Preschool Years: A Pooled Cross-Sectional Analysis of 5545 Children from Eight Countries.

BACKGROUND AND OBJECTIVE: One in five preschool children are overweight/obese, and increased weight status over time increases the risks of poorer future health. Motor skill competence may be a protective factor, giving children the ability to participate in health-enhancing physical activity. Yet, we do not know when the relationship between motor competence and weight status first emerges or whether it is evident across the body mass index (BMI) spectrum. This study examined the association between motor skill competence and BMI in a multi-country sample of 5545 preschoolers (54.36 ± 9.15 months of age; 50.5% boys) from eight countries. METHODS: Quantile regression analyses were used to explore the associations between motor skill competence (assessed using the Test of Gross Motor Development, Second/Third Edition) and quantiles of BMI (15th; 50th; 85th; and 97th percentiles), adjusted for sex, age in months, and country. RESULTS: Negative associations of locomotor skills, ball skills, and overall motor skill competence with BMI percentiles (p < 0.005) were seen, which became stronger at the higher end of the BMI distribution (97th percentile). Regardless of sex, for each raw score point increase in locomotor skills, ball skills, and overall motor skill competence scores, BMI is reduced by 8.9%, 6.8%, and 5.1%, respectively, for those preschoolers at the 97th BMI percentile onwards. CONCLUSIONS: Public health policies should position motor skill competence as critical for children's obesity prevention from early childhood onwards. Robust longitudinal and experimental designs are encouraged to explore a possible causal pathway between motor skill competence and BMI from early childhood.

Association between meeting the 24-h movement guidelines and psychosocial health in children: A cross-sectional study.

OBJECTIVE: Emerging evidence suggests that meeting the 24-h movement guidelines is associated with optimal mental health. However, there remains some uncertainty regarding this association in children. Therefore, this study aimed to examine the association between meeting the 24-h movement guidelines and psychosocial health in children. METHODS: A cross-sectional study design was employed to investigate 2005 children aged 9-12 years from four districts of Shanghai, China. The 24-h movement behaviours were assessed using selected items from the Health Behaviour in School-aged Children (HBSC) survey questionnaire. Children's self-rated psychosocial health was evaluated using the Strengths or Difficulties Questionnaire (SDQ). Generalised Linear Models with the ordinal logistic module were employed to analyse the association between meeting the 24-h movement guidelines and psychosocial health. RESULTS: The overall prevalence of meeting all three 24-h movement recommendations was 10.2%. Among children, 7.9% of them exhibited abnormal total difficulties, with a notable difference between sex (boys: 11.2%, girls: 7.0%, p = 0.001). Meeting all three 24-h movement behaviour recommendations was associated with reduced total difficulties, emotional symptoms, conduct problems, hyperactivity and peer problems. Furthermore, a dose-response association was observed, indicating that meeting a greater number of 24-h movement behaviour recommendations was associated with enhanced psychosocial health, particularly in boys. CONCLUSION: The findings of this study highlight the positive association between meeting the 24-h movement guidelines and psychosocial health in children. Notably, meeting more of these recommendations was associated with a lower likelihood of experiencing psychosocial problems, with greater benefits observed in boys compared with girls.

Recurrent de-novo gain-of-function mutation in SPTLC2 confirms dysregulated sphingolipid production to cause juvenile amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) leads to paralysis and death by progressive degeneration of motor neurons. Recently, specific gain-of-function mutations in SPTLC1 were identified in patients with juvenile form of ALS. SPTLC2 encodes the second catalytic subunit of the serine-palmitoyltransferase (SPT) complex. METHODS: We used the GENESIS platform to screen 700 ALS whole-genome and whole-exome data sets for variants in SPTLC2. The de-novo status was confirmed by Sanger sequencing. Sphingolipidomics was performed using liquid chromatography and high-resolution mass spectrometry. RESULTS: Two unrelated patients presented with early-onset progressive proximal and distal muscle weakness, oral fasciculations, and pyramidal signs. Both patients carried the novel de-novo SPTLC2 mutation, c.203T>G, p.Met68Arg. This variant lies within a single short transmembrane domain of SPTLC2, suggesting that the mutation renders the SPT complex irresponsive to regulation through ORMDL3. Confirming this hypothesis, ceramide and complex sphingolipid levels were significantly increased in patient plasma. Accordingly, excessive sphingolipid production was shown in mutant-expressing human embryonic kindney (HEK) cells. CONCLUSIONS: Specific gain-of-function mutations in both core subunits affect the homoeostatic control of SPT. SPTLC2 represents a new Mendelian ALS gene, highlighting a key role of dysregulated sphingolipid synthesis in the pathogenesis of juvenile ALS. Given the direct interaction of SPTLC1 and SPTLC2, this knowledge might open new therapeutic avenues for motor neuron diseases.

Comprehensive analysis of differentially expressed mRNA, lncRNA and miRNA, and their ceRNA networks in the regulation of shell color in the Manila clam (Ruditapes philippinarum).

The regulatory mechanism of ceRNA network plays an important role in molecular function and biological processes, however, the molecular mechanism in the shell color of Ruditapes philippinarum has not yet been reported. In this study, we performed transcriptome sequencing on the mantle of R. philippinarum with different shell colors, and screened for mRNA, miRNA, and lncRNA. A total of 61 mRNAs, 3725 lncRNAs and 90 miRNAs were obtained from all the shell color comparison groups (all mRNAs, lncRNAs and miRNAs P < 0.05), and 7 mRNAs, 8 lncRNAs, and 4 miRNAs of the porphyrin pathway and melanin pathway were screened for competitive endogenous RNA (ceRNA) network construction. The results indicate that the ceRNA network composed of mRNA and lncRNA, centered around efu-miR-101, mle-bantam-3p, egr-miR-9-5p, and sma-miR-75p, may play a crucial regulatory role in shell color formation. This study reveals for the first time the mechanism of ceRNA regulatory networks in the shell color of R. philippinarum and providing important reference data for molecular breeding of shell color in R. philippinarum.