Optimization of immunosuppression strategies for the establishment of chronic hepatitis E virus infection in rabbits.

Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of chronic hepatitis E virus (HEV) infection is linked to the type of immunosuppressant used. Animal models are crucial for the study of pathogenesis of chronic hepatitis E. We previously established a stable chronic HEV infection rabbit model using cyclosporine A (CsA), a calcineurin inhibitor (CNI)-based immunosuppressant. However, the immunosuppression strategy and timing may be optimized, and how different types of immunosuppressants affect the establishment of chronic HEV infection in this model is still unknown. Here, we showed that chronic HEV infection can be established in 100% of rabbits when CsA treatment was started at HEV challenge or even 4 weeks after. Tacrolimus or prednisolone treatment alone also contributed to chronic HEV infection, resulting in 100% and 77.8% chronicity rates, respectively, while mycophenolate mofetil (MMF) only led to a 28.6% chronicity rate. Chronic HEV infection was accompanied with a persistent activation of innate immune response evidenced by transcriptome analysis. The suppressed adaptive immune response evidenced by low expression of genes related to cytotoxicity (like perforin and FasL) and low anti-HEV seroconversion rates may play important roles in causing chronic HEV infection. By analyzing HEV antigen concentrations with different infection outcomes, we also found that HEV antigen levels could indicate chronic HEV infection development. This study optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits and highlighted the potential association between the development of chronic HEV infection and immunosuppressants.IMPORTANCEOrgan transplant recipients are at high risk of chronic hepatitis E and generally receive a CNI-based immunosuppression regimen containing CNI (tacrolimus or CsA), MMF, and/or corticosteroids. Previously, we established stable chronic HEV infection in a rabbit model by using CsA before HEV challenge. In this study, we further optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits. Chronic HEV infection can also be established when CsA treatment was started at the same time or even 4 weeks after HEV challenge, clearly indicating the risk of progression to chronic infection under these circumstances and the necessity of HEV screening for both the recipient and the donor preoperatively. CsA, tacrolimus, or prednisolone instead of MMF significantly contributed to chronic HEV infection. HEV antigen in acute infection phase indicates the development of chronic infection. Our results have important implications for understanding the potential association between chronic HEV infection and immunosuppressants.

New molecular insights into ferroptosis in lung adenocarcinoma progression and pharmacological compounds for targeted therapy.

BACKGROUND: The involvement of ferroptosis has been found in many pathological conditions of the lung. The genetic engineering of ferroptosis-related genes may provide a potential target for the treatment of lung adenocarcinoma (LUAD). METHODS: Nine ferroptosis regulators and markers were collected from FerrDb and their somatic mutations and expressions were analyzed based on The Cancer Genome Atlas (TCGA)-LUAD cohort data. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis were performed to screen genes significantly associated with ferroptosis. The ferroptosis-related gene signature was constructed using TCGA-LUAD cohort data and was verified using the GSE cohort with pooled data for GSE30219, GSE31210, GSE37745 and GSE50081. Immune microenvironment component and mutation analysis were performed for genes in the ferroptosis-related gene signature. RESULTS: All nine ferroptosis regulators and markers were differentially expressed between normal LUAD tumor tissues and adjacent normal tissues and were related to copy number variation. The expression of 1329 genes were significantly associated with nine ferroptosis regulators and markers in the TCGA-LUAD dataset, five (ALDOA, PLK1, CD47, CENPC and TMOD3) of which were integrated into a ferroptosis-related gene signature to calculate the risk score of LUAD samples, showing a significant correlation with the abundance of immune cell infiltration and the immune score. Molecular docking showed the binding activity of natural active compound quercetin to target proteins ALDOA and CD47, as well as the binding activity of aristolochic acid to PLK1 protein and TMOD3 protein. CONCLUSIONS: In the present study, a ferroptosis-related gene signature with predictive value for LUAD prognosis was constructed, in which the gene was a potential therapeutic target for LUAD. Quercetin and aristolochic acid were potential candidates for inhibiting these targets by directly binding to them and showing high affinity and strong stability.

Long-term abuse of caffeine sodium benzoate induces endothelial cells injury and leads to coagulation dysfunction.

Our hospital admitted a patient who had difficulty in coagulation even after blood replacement, and the patient had abused caffeine sodium benzoate (CSB) for more than 20 years. Hence, we aimed to explore whether CSB may cause dysfunction in vascular endothelial cells and its possible mechanism. Low, medium, and high concentrations of serum of long-term CSB intake patients were used to treat HUVECs, with LPS as the positive control. MTT and CCK8 were performed to verify CSB's damaging effect on HUVECs. The expression of ET-1, ICAM-1, VCAM-1, and E-selectin were measured by ELISA. TUNEL assay and Matrigel tube formation assay were carried out to detect apoptosis and angiogenesis of HUVECs. Flow cytometry was applied to analyze cell cycles and expression of CD11b, PDGF, and ICAM-1. Expression of PDGF-BB and PCNA were examined by western blot. The activation of MAPK signaling pathway was detected by qRT-PCR and western blot. Intracellular Ca2+ density was detected by fluorescent probes. CCK8 assay showed high concentration of CSB inhibited cell viability. Cell proliferation and angiogenesis were inhibited by CSB. ET-1, ICAM-1, VCAM-1, and E-selectin upregulated in CSB groups. CSB enhanced apoptosis of HUVECs. CD11b, ICAM-1 increased and PDGF reduced in CSB groups. The expression level and phosphorylation level of MEK, ERK, JUN, and p38 in MAPK pathway elevated in CSB groups. The expression of PCNA and PDGF-BB was suppressed by CSB. Intracellular Ca2+ intensity was increased by CSB. Abuse of CSB injured HUVECs and caused coagulation disorders.

Evaluating joint confidence region of hypervolume under ROC manifold and generalized Youden index.

In biomarker evaluation/diagnostic studies, the hypervolume under the receiver operating characteristic manifold ( HUM K $$ {\mathrm{HUM}}_K $$ ) and the generalized Youden index ( J K $$ {J}_K $$ ) are the most popular measures for assessing classification accuracy under multiple classes. While HUM K $$ {\mathrm{HUM}}_K $$ is frequently used to evaluate the overall accuracy, J K $$ {J}_K $$ provides direct measure of accuracy at the optimal cut-points. Simultaneous evaluation of HUM K $$ {\mathrm{HUM}}_K $$ and J K $$ {J}_K $$ provides a comprehensive picture about the classification accuracy of the biomarker/diagnostic test under consideration. This article studies both parametric and non-parametric approaches for estimating the confidence region of HUM K $$ {\mathrm{HUM}}_K $$ and J K $$ {J}_K $$ for a single biomarker. The performances of the proposed methods are investigated by an extensive simulation study and are applied to a real data set from the Alzheimer's Disease Neuroimaging Initiative.

Unanticipated Enhancement of Intestinal TG Output by Apoc3 ASO Inhibition.

BACKGROUND: The objective of this study was to investigate whether apoC3 (apolipoprotein C3) inhibition with an antisense oligonucleotide (ASO) modulates intestinal triglyceride secretion. METHODS: Sprague-Dawley rats were treated with subcutaneous injections of apoC3 ASO 25 mg/kg twice weekly or inactive ASO for 4 weeks before the assessment of lymph flow, triglyceride and apoB48 (apolipoprotein B48) appearance in the lymph. Rats were surgically implanted with catheters in the mesenteric lymph duct and duodenum. Following an overnight fast, an intraduodenal lipid bolus (1.5-mL intralipid) was administered. Lymph fluid was collected for the following 4 hours to compare effects on lymph flow, lymph triglyceride and apoB48 concentration, and secretion. To assess suppression of apoC3 expression and protein abundance by apoC3 ASO compared with inactive ASO (placebo), intestinal and hepatic tissues were collected from a subset of animals before (fasting) and after an enteral lipid bolus (post-lipid). RESULTS: ApoC3 ASO significantly reduced apoC3 mRNA expression in the liver compared with inactive ASO (fasting: 42%, P=0.0048; post-lipid: 66%, P<0.001) and in the duodenum (fasting: 29%, P=0.0424; post-lipid: 53%, P=0.0120). As expected, plasma triglyceride also decreased significantly (fasting: 74%, P<0.001; post-lipid: 33%, P=0.0276). Lymph flow and cumulative lymph volume remained unchanged following apoC3 ASO therapy; however, lymph triglyceride, but not apoB48 output, increased by 38% (ANOVA, P<0.001). Last, no changes were observed in stool triglyceride, intestinal fat (quantified via oil red O staining), and expression of mRNAs involved in triglyceride synthesis, lipid droplet formation, and chylomicron transport and secretion. CONCLUSIONS: Despite the marked reduction in plasma triglyceride concentration that occurs with apoC3 ASO inhibition, intestinal triglyceride output surprisingly increased rather than decreased. These data demonstrate that the reduction of intestinal triglyceride output does not contribute to the potent plasma triglyceride-lowering observed with this novel therapy for hypertriglyceridemia. Further studies are required to explore the mechanism of this intestinal effect.

Understanding the Tail Current Behavior of Electroactive Biofilms Realizes the Rapid Measurement of Biochemical Oxygen Demand.

The use of microbial electrochemical sensors, with electroactive biofilms (EABs) as sensing elements, is a promising strategy to timely measure the biochemical oxygen demand (BOD) of wastewater. However, accumulation of Coulombic yield over a complete degradation cycle is time-consuming. Therefore, understanding the correlation between current output and EAB metabolism is urgently needed. Here, we recognized a tail stage (TS) on a current-time curve according to current increase rate─a period with the least electron harvesting efficiency. EAB adopted a series of metabolic compensation strategies, including slow metabolism of residual BOD, suspended growth, reduced cell activity, and consumption of carbon storage polymers, to cope with substrate deficiency in TS. The supplementary electrons provided by the decomposition of glycogen and fatty acid polymers increased the Coulombic efficiencies of TS to >100%. The tail current produced by spontaneous metabolic compensation showed a trend of convergent exponential decay, independent of BOD concentration. Therefore, we proposed the TS prediction model (TSPM) to predict Coulombic yield, which shortened BOD measurement time by 96% (to ∼0.5 h) with deviation <4 mg/L when using real domestic wastewater. Our findings on current output in TS give insights into bacterial substrate storage and consumption, as well as regulation in substrate-deficient environment, and provide a basis for developing BOD sensors.

Impact of cash transfers on the association between prenatal exposures to high temperatures and low birthweight: Retrospective analysis from the LEAP 1000 study.

OBJECTIVE: To explore the associations between prenatal temperature exposures and low birthweight (LBW) and modification by cash transfer (CT) receipt. DESIGN: Retrospective cohort study. SETTING: Five rural districts in Northern Ghana. POPULATION OR SAMPLE: A total of 3016 infants born to women interviewed as part of the Livelihood Empowerment Against Poverty (LEAP 1000) impact evaluation between 2015 and 2017. METHODS: Birthweight was collected using household surveys administered to LEAP 1000 eligible women. We used a UNICEF-developed multiple imputation approach to address missingness of birthweight and applied an empirical heaping correction to the multiply imputed birthweight data. Survey data were linked to the European Centre for Medium-Range Weather Forecasts Reanalysis 5-hourly temperature averaged to weeks for 2011-2017 using community centroids. Using distributed-lag nonlinear models, we explored the lag-specific associations between weekly average temperatures greater than 30°C and LBW, and stratified by LEAP 1000 treatment. MAIN OUTCOME MEASURES: Low birthweight (<2.5 kg). RESULTS: Twelve percent (n = 365) of infants were LBW; the mean ± SD birthweight was 3.02 ± 0.37 kg. Overall, increasing temperatures were associated with increased odds of LBW, with the greatest odds observed in the 3 weeks before birth (odds ratio 1.005-1.025). These positive associations were even larger among comparison infants and null among treatment infants. CONCLUSIONS: Our study found increased odds of LBW with high weekly average temperatures throughout pregnancy and the preconception period and demonstrate mitigated effects by the LEAP 1000 CT program. More evidence on the potential of CTs to serve as adaptation interventions in low- and middle-income countries is needed to protect pregnant persons and their infants from the impacts of climate change.

Co-developmental trajectories of aggression and rule-breaking from middle childhood to early adolescence: individual and environmental predictors.

This study examined the heterogeneous co-developmental trajectories of aggression and rule-breaking from middle childhood to early adolescence, as well as how these identified, distinct trajectories related to individual and environmental predictors. A total of 1944 Chinese elementary school students in grade 4 (45.5% girls, Mage = 10.06, SD = 0.57) completed measures on five occasions across two and a half years, using six-month intervals. Findings included: (a) Parallel process latent class growth modeling revealed four distinct co-developmental trajectory groups of aggression and rule-breaking: congruent-low (84.0%); moderate-decreasing aggression and high-decreasing rule-breaking (3.8%); moderate-increasing aggression (5.9%); and moderate-increasing rule-breaking (6.3%); (b) Multivariate logistic regression analyses revealed that children belonging to the high risk groups were more likely to experience multiple individual and environmental difficulties. Implications for prevention of aggression and rule-breaking were discussed.

Understanding general and specific associations between cyberbullying and psychopathological symptoms in adolescents: a latent dimensional approach.

Cyberbullying (perpetration and victimization) is a prevalent public health problem associated with a wide variety of psychopathological symptoms (e.g., depression, anxiety, delinquent behaviors, and substance use). However, the generality and specificity of relations between cyberbullying involvement and psychopathological symptoms have not been investigated. Thus, the current study used a latent dimensional approach to examine how cyberbullying (perpetration and victimization) is associated with underlying dimensions of psychopathology as well as with specific symptoms. General and specific associations were estimated by a series of structural equation models with data from 654 Chinese adolescents (52.4% girls, Mage = 12.96 years, SD = 0.67) in a three-wave study. Results indicated that cyberbullying (perpetration and victimization) was significantly and positively associated with latent internalizing and externalizing dimensions. Cyberbullying involvement was non-significantly associated with most specific symptom domains after accounting for the impact of the latent internalizing and externalizing factors. In a few cases, cyberbullying involvement was directly and uniquely associated with specific symptoms. Findings of significant general and symptom-specific associations have important implications for efforts to develop more efficient and targeted strategies for preventing and treating mental health problems associated with cyberbullying.

Longitudinal associations among basic psychological need satisfaction at school, self-esteem, and suicidal ideation from middle childhood to early adolescence: Disentangling between­ and within­person associations.

INTRODUCTION: The current study aimed to examine the longitudinal associations among basic psychological need satisfaction at school (BPNSS), self-esteem, and suicidal ideation (SI), including whether self-esteem functioned as a mediator of the relations between BPNSS and SI at the within-person level after disentangling between- and within-person associations encompassing middle childhood to early adolescence. METHODS: A total of 650 Chinese students (53.54% boys, Mage = 9.95, SD = 0.75 at Time 1) completed measures on four occasions across 1.5 years, using 6-month intervals. Random intercept cross-lagged panel models were applied to disaggregate between- and within-person effects, thus providing greater confidence in elucidating the causal relations among study variables. RESULTS: The results showed that at the within-person level: (a) BPNSS negatively predicted SI; (b) BPNSS positively predicted self-esteem; (c) Self-esteem negatively predicted SI; and (d) BPNSS indirectly predicted SI via self-esteem. CONCLUSION: These findings advanced the literature by demonstrating longitudinal associations among BPNSS, self-esteem, and SI at the within-person level, and highlighting the significance of distinguishing between- and within-person effects in developing prevention and intervention programs aimed at reducing SI over time from middle childhood to early adolescence.

Optimal Cut-Point Selection Methods Under Binary Classification When Subclasses Are Involved.

In practice, we often encounter binary classification problems where both main classes consist of multiple subclasses. For example, in an ovarian cancer study where biomarkers were evaluated for their accuracy of distinguishing noncancer cases from cancer cases, the noncancer class consists of healthy subjects and benign cases, while the cancer class consists of subjects at both early and late stages. This article aims to provide a large number of optimal cut-point selection methods for such setting. Furthermore, we also study confidence interval estimation of the optimal cut-points. Simulation studies are carried out to explore the performance of the proposed cut-point selection methods as well as confidence interval estimation methods. A real ovarian cancer data set is analyzed using the proposed methods.

Risk factors associated with higher mortality in patients with cardiac implantable electronic device infection.

INTRODUCTION: Cardiac Implantable Electronic Devices (CIEDs) are widely used for the management of advanced heart failure and ventricular arrhythmias. CIED-Infection (CIED-I) has very high mortality, especially in the subsets of patients with limited health-care access and delayed presentation. The purpose of this study is to identify the risk-predictors mortality in subjects with CIED-I. METHODS: We performed a retrospective cohort study of a regional database in patients presenting with CIED infections to tertiary care medical centers across Western New York, USA from 2012 to 2020. The clinical outcomes included recurrent device infection (any admission for CIED-I after the first hospitalization for device infection), septic complications (pulmonary embolism, respiratory failure, septic shock, decompensated HF, acute kidney injury) and mortality outcomes (death during hospitalization, within 30 days from CIED-I, and within 1 year from CIED-I). We studied associations between categorical variables and hard outcomes using χ2 tests and used one-way analysis of variance to measure between-groups differences. RESULTS: We identified 296 patients with CIED-I, among which 218 (74%) were male, 237 (80%) were white and the mean age at the time of infection was 69.2 ± 13.7 years. One-third of the patients were referred from the regional facilities. Staphylococcus aureus was responsible for most infections, followed by Enterococcus fecalis. On multivariate analysis, the covariates associated with significantly increased mortality risk included referral from regional facility (OR: 2.0;1.0-4.0), hypertension (Odds ratio, OR: 3.2;1.3-8.8), right ventricular dysfunction (OR: 2.6;1.2-5.1), end-stage renal disease (OR: 2.6;1.1-6.2), immunosuppression (OR: 11.4;2.5-53.3), and septic shock as a complication of CIED-I (OR: 3.9;1.3-10.8). CONCLUSION: Hypertension, right ventricular dysfunction, immunosuppression, and end-stage renal disease are associated with higher mortality after CIED-I. Disproportionately higher mortality was also noted in subjects referred from the regional facilities. This underscores the importance of early clinical risk-assessment, and the need for a robust referral infrastructure to improve patient outcomes.

Follicle-stimulating hormone is associated with low bone mass in postmenopausal women.

We evaluated the influence of two endogenous hormones on bone health in older women. Higher FSH was associated with bone disease, especially in lower estradiol environments. FSH attenuated the relationship between estradiol and bone. This may provide a mechanism through which future clinical research intervenes on bone loss. INTRODUCTION/PURPOSE: Despite preclinical evidence for an inverse association of follicle-stimulating hormone (FSH) and bone mineral density (BMD), no large epidemiologic studies have evaluated the separate and joint influences of FSH and estradiol on bone in postmenopausal women. METHODS: In a cross-sectional study of 675 postmenopausal women, we evaluated associations of serum FSH and dual X-ray absorptiometry (DXA)-classified areal BMD as well as low bone mass or osteoporosis (T-score < - 1.0) of the femoral neck and total hip. We stratified this analysis by serum estradiol (cut at the median). We tested whether FSH mediates the association of estradiol and BMD using the Sobel test. RESULTS: In linear regression models, there was a significant inverse association of serum FSH with both femoral neck and total hip BMD (both p < 0.01) when adjusted for age, hormone therapy (HT) use, and diabetes. In fully adjusted logistic regression models, women in the highest FSH tertile had higher odds of low bone mass/osteoporosis at the femoral neck (OR = 2.98; 95% CI = 1.86-4.77) and at the total hip (OR = 1.74; 95% CI = 1.06-2.84) compared to those in the lowest FSH tertile. We report evidence of effect modification by estradiol in stratified models and an interaction term. FSH met all criteria of a mediator, including an estimated 70% attenuation of the estradiol-BMD relationship (Sobel p value < 0.001). CONCLUSIONS: FSH is associated with higher odds of having low bone mass/osteoporosis even after accounting for HT use. FSH is a mediator of the relationship between estradiol and BMD in healthy postmenopausal women. Larger, prospective studies of FSH concentrations and bone health are needed.

A new accuracy metric under three classes when subclasses are involved and its confidence interval estimation.

"Compound multi-class classification" refers to the setting where three or more main classes are involved and at least one of the main classes have multiple subclasses. A common practice in evaluating biomarker performance under "compound multi-class classification" is "subclasses pooling." In this article, we first explore the downsides of accuracy metrics based on pooled data. Then we propose a new accuracy measure proper for "compound multi-class classification" with three ordinal main classes, namely "volume under compound R O C $$ ROC $$ surface ( V U S C $$ VU{S}_C $$ )." The proposed V U S C $$ VU{S}_C $$ evaluates the accuracy of a biomarker appropriately by identifying main classes without requiring specification of an ordering for marker values of subclasses within each main class. For confidence interval estimation of V U S C $$ VU{S}_C $$ , both parametric and nonparametric methods are studied, and simulation studies are carried out to assess coverage probabilities. A subset of Alzheimer's Disease Neuroimaging Initiative study dataset is analyzed.

Insights into Health Risks of Face Paint Application to Opera Performers: The Release of Heavy Metals and Stage-Light-Induced Production of Reactive Oxygen Species.

Face paints used by opera performers have been shown to contain high levels of heavy metals. However, whether frequent exposure, via dermal contact and inadvertent oral ingestion, results in occupational diseases is unknown, as is the potential exacerbation of toxicity by high-intensity irradiation from stage lights. In this study, we examined the release of Cr, Cu, Pb, and Zn from 40 face paints and the consequent health risks posed by different practical scenarios involving their use. The results showed that the in vitro bioaccessibility (IVBA) of Cr, Cu, Pb, and Zn in the tested products was, on average, 7.0, 5.5, 19.9, and 7.9% through oral ingestion and 1.1, 2.2, 1.6, and 1.2% through dermal contact, respectively. Stage light irradiation significantly increased the IVBA associated with dermal contact, to the average of 4.8, 34.9, 5.7, and 1.9% for Cr, Cu, Pb, and Zn, respectively. The increase was mainly due to the light-induced generation of reactive oxygen species, particularly hydroxyl free radicals. The vitality and transcriptional response of 3D skin models as well as a quantitative risk assessment of skin sensitization indicated that dermal contact with face paints may induce predictable skin damage and potentially other skin diseases. Long-term exposure to face paints on stage may also pose a non-carcinogenic health risk. The demonstrated health risks to opera performers of face paint exposure should lead to strict regulations regarding the content of theatrical face paints.

Indoor air pollution exposure and early childhood development in the Upstate KIDS Study.

BACKGROUND: Limited human studies have investigated the impact of indoor air pollution on early childhood neurodevelopment among the US population. We aimed to examine the associations between prenatal and postnatal indoor air pollution exposure and early childhood development in a population-based birth cohort. METHODS: This analysis included 4735 mother-child pairs enrolled between 2008 and 2010 in the Upstate KIDS Study. Indoor air pollution exposure from cooking fuels, heating fuels, and passive smoke during pregnancy, and at 12 and 36 months after birth were assessed by questionnaires. Five domains of child development were assessed by the Ages and Stages Questionnaire at 4, 8, 12, 18, 24, 30, and 36 months. Generalized estimating equations were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: Exposure to unclean cooking fuels (natural gas, propane, or wood) throughout the study period was associated with increased odds of failing any development domain (OR = 1.28, 95% CI 1.07, 1.53), the gross motor domain (OR = 1.52, 95% CI: 1.09, 2.13), and the personal-social domain (OR = 1.36, 95% CI: 1.00, 1.85), respectively. Passive smoke exposure throughout the study period increased the odds of failing the problem-solving domain by 71% (OR = 1.71, 95% CI 1.01, 2.91) among children of non-smoking mothers. No association was found between heating fuel use and failing any or specific domains. CONCLUSION: Unclean cooking fuel use and passive smoke exposure during pregnancy and early life were associated with developmental delays in this large prospective birth cohort.

The dose-response association between LEAP 1000 and birthweight - no clear mechanisms: a structural equation modeling approach.

BACKGROUND: Birthweight is an important indicator of maternal and fetal health globally. The multifactorial origins of birthweight suggest holistic programs that target biological and social risk factors have great potential to improve birthweight. In this study, we examine the dose-response association of exposure to an unconditional cash transfer program before delivery with birthweight and explore the potential mediators of the association. METHODS: Data for this study come from the Livelihood Empowerment Against Poverty (LEAP) 1000 impact evaluation conducted between 2015 and 2017 among a panel sample of 2,331 pregnant and lactating women living in rural households of Northern Ghana. The LEAP 1000 program provided bi-monthly cash transfers and premium fee waivers to enroll in the National Health Insurance Scheme (NHIS). We used adjusted and unadjusted linear and logistic regression models to estimate the associations of months of LEAP 1000 exposure before delivery with birthweight and low birthweight, respectively. We used covariate-adjusted structural equation models (SEM) to examine mediation of the LEAP 1000 dose-response association with birthweight by household food insecurity and maternal-level (agency, NHIS enrollment, and antenatal care) factors. RESULTS: Our study included a sample of 1,439 infants with complete information on birthweight and date of birth. Nine percent of infants (N = 129) were exposed to LEAP 1000 before delivery. A 1-month increase in exposure to LEAP 1000 before delivery was associated with a 9-gram increase in birthweight and 7% reduced odds of low birthweight, on average, in adjusted models. We found no mediation effect by household food insecurity, NHIS enrollment, women's agency, or antenatal care visits. CONCLUSIONS: LEAP 1000 cash transfer exposure before delivery was positively associated with birthweight, though we did not find any mediation by household- or maternal-level factors. The results of our mediation analyses may serve to inform program operations and improve targeting and programming to optimize health and well-being among this population. TRIAL REGISTRATION: The evaluation is registered in the International Initiative for Impact Evaluation's (3ie) Registry for International Development Impact Evaluations (RIDIESTUDY- ID-55942496d53af) and in the Pan African Clinical Trial Registry (PACTR202110669615387).

Gender-specific co-developmental trajectories of internalizing and externalizing problems from middle childhood to early adolescence: Environmental and individual predictors.

This study aimed to identify gender-specific co-developmental trajectories of internalizing and externalizing problems from middle childhood to early adolescence, along with key environmental and individual predictors among Chinese youth. A total of 1653 Chinese elementary school students (M age = 9.40; SD = 0.51; 54.57% boys) participated in assessments at six time points, using 6-month assessment intervals. Parallel process latent class growth modeling identified four trajectories for boys: Congruent-low (65.74%), moderate-decreasing internalizing and moderate-stable externalizing problems (18.40%), high increasing-internalizing and low-stable externalizing problems (8.20%), and high decreasing-internalizing and low-stable externalizing problems (7.65%). Three trajectories were identified for girls: Congruent-low (81.09%), moderate co-occurring (7.19%), and high increasing-internalizing and low-stable externalizing problems (11.72%). Multivariate logistic regression analyses revealed that peer victimization served as an environmental risk predictor for the adverse co-developmental trajectories of internalizing and externalizing problems for boys and girls. High sensation-seeking and low self-control served as individual risk variables predicting the trajectories of high increasing-internalizing and low-stable externalizing problems, and low self-control also predicted the trajectories of high decreasing-internalizing and low-stable externalizing problems for boys. The findings highlight the importance of gender differences in understanding the progression of internalizing and externalizing problems and inform effective strategies for prevention and intervention.

Global and domain-specific self-esteem from middle childhood to early adolescence: Co-developmental trajectories and directional relations.

OBJECTIVE: The study used both person-centered (i.e., parallel process latent class growth modeling) and variable-centered (i.e., random intercept cross-lagged panel modeling) approaches to examine developmental changes in global and domain-specific self-esteem from middle childhood to early adolescence. METHOD: A total of 715 Chinese youth participated (54.3% boys; 45.7% girls; Mage = 9.96; SD = 0.51) in a 6-wave longitudinal study with 6-month intervals. RESULTS: Parallel process latent class growth modeling identified three co-developmental trajectories of global and domain-specific self-esteem: Congruent high increasing and then flattening global and domain-specific self-esteem, congruent moderate domain-specific self-esteem with convex global self-esteem, and congruent low with concave appearance and global self-esteem. Results from random intercept cross-lagged panel modeling found reciprocal within-person associations between academic self-esteem and global self-esteem; global self-esteem significantly predicted social self-esteem, while physical appearance self-esteem significantly predicted global self-esteem. CONCLUSION: Evidence was provided for top-down and bottom-up effects of self-esteem among Chinese youth. The findings provided new insight into the development of self-esteem in youth.

Longitudinal Association and Mediating Mechanism Between Externalizing and Internalizing Problems Among Children: A Within-Person Analysis.

OBJECTIVE: In this multi-informant, 3-year longitudinal study, the bidirectional relations between externalizing and internalizing problems were investigated, along with whether peer victimization and academic achievement mediated their relations after separating between-person effects from within-person effects. METHOD: A sample of 3238 Chinese children (55.02% boys; Mage T1 = 9.89 years) reported semiannually on peer victimization and both externalizing and internalizing problems, and parents reported on their children's externalizing and internalizing problems. Students' objective academic achievement data (i.e. final exam scores) were obtained from school records. RESULTS: Random intercepts cross-lagged panel modeling (RI-CLPM) revealed that neither academic achievement nor peer victimization mediated the relations between externalizing and internalizing problems in both self and parent reports at the within-person level. The cross-lagged panel models (CLPM) results supported that peer victimization (but not academic achievement) mediated the relations from internalizing to externalizing problems or externalizing to internalizing problems, whether self-reported or parent-reported. This study also identified meaningful sex differences in focal relations among children. CONCLUSIONS: Findings illustrate the importance of distinguishing within-person and between- person associations, with within- person findings failing to support the hypothesized mediating pathways of the Dual Failure or Acting Out Models among children.