Association between concurrence of multiple risk factors and under-5 mortality: a pooled analysis of data from Demographic and Health Survey in 61 low-and-middle-income countries.

Background: Exposure to multiple risk factors is prevalent in low-and middle-income countries (LMICs), challenging one-directional strategies to address preventable under-5 mortality (U5M). This study aims to assess the associations between concurrence of multiple risk factors and U5M in LMICs. Methods: We extracted data from the Demographic and Health Surveys conducted between 2010 and 2021 across 61 LMICs. Our primary outcome was U5M, defined as deaths from birth to 59 months. Binary logistic regression model was applied to ascertain the association between U5M and a total of 20 critical risk factors. Upon identifying the risk factors demonstrating the strongest associations, we investigated the simultaneous presence of multiple risk factors in each individual and assessed their combined effects on U5M with logistic regression models. Findings: Of the 604,372 under-5 children, 18,166 (3.0%) died at the time of the survey. Unsatisfied family planning needs was the strongest risk factor for U5M (odds ratio [OR]: 2.0, 95% confidence interval [CI]: 1.9-2.1), followed by short birth interval (<18 months; OR: 2.0, 95% CI: 1.9-2.1), small birth size (OR: 2.0, 95% CI: 1.8-2.1), never breastfed or delayed breastfeeding (OR: 2.0, 95% CI: 1.9-2.0), and low maternal education (OR: 1.6, 95% CI: 1.4-1.8). 66.7% (66.6%-66.8%) of the children had 2 or more leading risk factors simultaneously. Simultaneous presence of multiple leading risk factors was significantly associated with elevated risk of U5M and children presenting with all 5 leading risk factors exhibited an exceedingly high risk of U5M (OR: 5.2, 95% CI: 4.3-6.3); a dose-response relationship between the number of risk factors and U5M was also observed-with the increment of numbers of leading risk factors, the U5M showed an increasing trend (p-trend < 0.001). Interpretation: Exposure to multiple risk factors is very common in LMICs and underscores the necessity of developing multisectoral and integrated approaches to accelerate progress in reducing U5M in line with the SDG 3.2. Funding: This research is funded by Research Fund, Vanke School of Public Health, Tsinghua University.

Prognostic predictive value of urothelial carcinoma of the bladder after TURBT based on multiphase CT radiomics.

OBJECTIVE: To investigate multiphase computed tomography (CT) radiomics-based combined with clinical factors to predict overall survival (OS) in patients with bladder urothelial carcinoma (BLCA) who underwent transurethral resection of bladder tumor (TURBT). METHODS: Data were retrospectively collected from 114 patients with primary BLCA from February 2016 to February 2018. The regions of interest (ROIs) of the plain, arterial, and venous phase images were manually segmented. The Cox regression algorithm was used to establish 3 basic models for the plain phase (PP), arterial phase (AP), and venous phase (VP) and 2 combination models (AP + VP and PP + AP + VP). The highest-performing radiomics model was selected to calculate the radiomics score (Rad-score), and independent risk factors affecting patients' OS were analyzed using Cox regression. The Rad-score and clinical risk factors were combined to construct a joint model and draw a visualized nomogram. RESULTS: The combined model of PP + AP + VP showed the best performance with the Akaike Information Criterion (AIC) and Consistency Index (C-index) in the test group of 130.48 and 0.779, respectively. A combined model constructed with two independent risk factors (age and Ki-67 expression status) in combination with the Rad-score outperformed the radiomics model alone; AIC and C-index in the test group were 115.74 and 0.840, respectively. The calibration curves showed good agreement between the predicted probabilities of the joint model and the actual (p < 0.05). The decision curve showed that the joint model had good clinical application value within a large range of threshold probabilities. CONCLUSION: This new model can be used to predict the OS of patients with BLCA who underwent TURBT.

Adaptive Individual Q-Learning-A Multiagent Reinforcement Learning Method for Coordination Optimization.

Multiagent reinforcement learning (MARL) has been extensively applied to coordination optimization for its task distribution and scalability. The goal of the MARL algorithms for coordination optimization is to learn the optimal joint strategy that maximizes the expected cumulative reward of all agents. Some cooperative MARL algorithms exhibit exciting characteristics in empirical studies. However, the majority of the convergence results are confined to repeated games. Moreover, few MARL algorithms consider adaptation to the switched environments such as the alternation between peak hours and off-peak hours of urban traffic flow or an obstacle suddenly appearing on the planned route for the automated guided vehicle. To this end, we propose a cooperative MARL algorithm known as adaptive individual Q-learning (A-IQL). Each agent updates the Q -function of its own action with period T to adapt to the switched environments. Convergence analysis shows that the optimal joint strategy can be obtained in stochastic games with deterministic state transitions occurring in chronological order. The influence of period T on convergence is studied through a fictitious stochastic game. The efficacy of the A-IQL algorithm is validated through two switched environments-the distributed sensor network (DSN) task and the target transportation task.

Meals, Education, and Gardens for In-School Adolescents: A Cluster Randomized Trial of an Adolescent Nutrition Intervention Package in Tanzania.

PURPOSE: This study aimed to implement and evaluate integrated, school-based nutrition intervention packages for adolescents in Dodoma, Tanzania. METHODS: A cluster randomized controlled trial was conducted among six secondary schools in Dodoma, Tanzania. Two schools received the full-intervention package of school meals, nutrition education, school gardens, and community workshops. Two schools received the partial-intervention package without the school meals component. Two schools served as the controls and did not receive any intervention. The intervention was implemented over one academic year. The analytical sample included 534 adolescents aged 14 to 17 at baseline and 286 parents. Outcomes included nutrition knowledge, food preferences, diet quality, food insecurity, physical activity, growth, and anemia. Linear models were used to estimate mean differences, and logistic regression models were used to estimate odds ratios (ORs). RESULTS: Compared to the control, both the partial (OR: 0.59; 95% confidence interval [CI]: 0.35, 1.00) and full (OR: 0.49; 95% CI: 0.40, 0.59) interventions were associated with lower odds of poor diet quality among adolescents. Among the parents, both the partial (OR: 0.28; 95% CI: 0.20, 0.40) and full (OR: 0.28; 95% CI: 0.13, 0.58) interventions were associated with lower odds of poor diet quality. The partial (OR: 0.29; 95% CI: 0.18, 0.47) and full (OR: 0.47; 95% CI: 0.30, 0.72) interventions were associated with lower odds of adolescent overweight or obesity. DISCUSSION: School-based nutritional intervention packages incorporating multiple actions may improve the diet quality of adolescents and their household members and reduce the double burden of adolescent malnutrition.

Child, family and household characteristics associated with physical activity in Samoan children aged 3-8 years: A cross-sectional study.

Physical activity is a key component of many obesity prevention strategies. The aim of this analysis was to identify child, family, and household characteristics associated with parent-reported physical activity in Samoan children aged 3-8 years. Children (n = 445; 51.2% female, mean age 5.4 years) were part of an ongoing, mixed-longitudinal study of child growth, development, and wellbeing (the Ola Tuputupua'e cohort). Bivariate analyses and multivariate generalized linear regressions were conducted to investigate the relationship of child, family, and household characteristics with physical activity level, measured using the Netherlands Physical Activity Questionnaire (NPAQ). Children were classified as being 'highly active' if they had NPAQ scores in the 75th percentile or above. Among the n = 111 children classified as 'highly active', n = 67 (60.4%) were boys. After adjusting for child, family, and household-level characteristics, hours of child sleep per night was the only variable significantly associated with odds of being highly active. Compared to children who slept less than 9 hours at night, those who slept 10-10.99 hours (OR: 5.97, 95% CI: 2.14-18.13) and 11+ hours (OR: 25.75, 95% CI: 8.14-90.12) had higher odds of being 'highly active'. Future research should examine the mechanisms driving the relationship between nighttime sleep and physical activity among Samoan children. Intervening on sleep duration and quality may improve physical activity and, in turn, obesity risk in this setting.

Associations of childhood BMI traits with blood pressure and glycated haemoglobin in 6-9-year-old Samoan children.

INTRODUCTION: Prevalence and risk factors for elevated glycated haemoglobin (HbA1c) and blood pressure (BP) are poorly understood among Pacific children. We examined associations of HbA1c and BP in 6-9 year-olds with body mass index (BMI) at ages 2, 5, and BMI velocity between 2-9 years in Samoa. METHODS: HbA1c (capillary blood) and BP were measured in n = 410 Samoan children who were part of an ongoing cohort study. Multilevel models predicted BMI trajectory characteristics. Generalized linear regressions assessed associations of childhood characteristics and BMI trajectories with HbA1c and BP treated as both continuous and categorical outcomes. Primary caregiver-reported childhood characteristics were used as covariates. RESULTS: Overall, 12.90% (n = 53) of children had high HbA1c (≥5.7%) and 33.17% (n = 136) had elevated BP. BMI at 5-years and BMI velocity were positively associated with high HbA1c prevalence in males. A 1 kg/m2 per year higher velocity was associated with a 1.71 (95% CI: 1.07, 2.75) times higher prevalence of high HbA1c. In females, higher BMI at 5-years and greater BMI velocity were associated with higher BP at 6-9 years (95% CI: 1.12, 1.40, and 1.42, 2.74, respectively). CONCLUSION: Monitoring childhood BMI trajectories may inform cardiometabolic disease screening and prevention efforts in this at-risk population.

Clinical Application of Tonsillectomy with Preservation of Capsule and Support Tissue.

Objective: The clinical effect of tonsillectomy with the preservation of tonsillar capsule and stent tissue and punctuated suture of tonsillar capsule and stent tissue was analyzed retrospectively. Methods: From January 2013 to January 2022, a total of 960 patients underwent tonsillectomy, consisting of 530 males and 430 females with ages ranging from 4 to 60 years (median age: 11 years). The capsule and scaffold tissues were preserved in all patients during the operation, and the surrounding mucosa, capsule, and scaffold tissues were sutured without tension. Indexes such as operation time, intraoperative blood loss, tonsillar white membrane, incidence of postoperative bleeding, postoperative pain score, and incidence of tonsillar remnant were recorded, and the school attendance of children (≤12 years old) was recorded. Results: The mucosal covering of tonsillar fossa healed well in all patients, and the sutures were completely removed at 4 weeks after reexamination. All patients were followed up for 1-8 years, and there was no residual hyperplasia or residual inflammation. Children under 12 years old could return to school 4 days after surgery without any postoperative complications. Conclusion: Tonsillectomy, preserving the tonsillar capsule and scaffold tissue followed by punctate suturing, offered several advantages: it resulted in less intraoperative blood loss and postoperative pain. Patients could resume a normal diet 6 hours after the surgery without an increased risk of complications. Moreover, it significantly reduced the risk of postoperative bleeding.

The effects of prenatal and postnatal high-dose vitamin B-12 supplementation on human milk vitamin B-12: a randomized, double-blind, placebo-controlled trial in Tanzania.

BACKGROUND: Vitamin B-12 status in human milk (HM) has critical implications for infant growth and development. Few studies have separately evaluated the effects of prenatal and postnatal maternal high-dose vitamin B-12 supplementation on HM vitamin B-12 concentration. OBJECTIVES: This randomized controlled trial aimed to assess the effects of prenatal and postnatal vitamin B-12 supplementation on HM vitamin B-12 at 6 wk and 7 mo postpartum. METHODS: Pregnant women were enrolled in Dar es Salaam, Tanzania, between 2001 and 2004. From recruitment (12-27 weeks of gestation) through 6 wk postpartum, participants were randomly assigned to daily oral multiple micronutrient supplementation or placebo. From 6 wk to 18 mo postpartum, a subset of participants was randomly assigned to a postnatal supplement or placebo. The supplement included 50 µg/d of vitamin B-12 and various other vitamins. HM vitamin B-12 concentrations were analyzed at 6 wk and 7 mo postpartum for 412 participants. RESULTS: The prevalence of HM vitamin B-12 of <310 pmol/L was 73.3% and 68.4% at 6 wk and 7 mo postpartum, respectively. Prenatal supplementation increased HM vitamin B-12 concentration (percent difference: 34.4; 95% CI: 17.0, 54.5; P < 0.001) at 6 wk; this effect was not present at 7 mo. Postnatal supplementation increased HM vitamin B-12 concentration (percent difference: 15.9; 95% CI: 1.91, 31.9; P = 0.025) at 7 mo. Effect modification between prenatal and postnatal supplementation on HM vitamin B-12 status at 7 mo was found, with the effects of prenatal and postnatal supplements more pronounced among those receiving control during the other period; the prenatal supplement had a greater effect with postnatal control, and the postnatal supplement had a greater effect with prenatal control. CONCLUSIONS: Prenatal maternal vitamin B-12 supplementation has benefits on short-term HM status, and postnatal maternal vitamin B-12 supplementation has benefits on long-term HM status. This trial was registered at clinicaltrials.gov as NCT00197548. https://clinicaltrials.gov/ct2/show/NCT00197548.

The Impact of Excluding Adverse Neonatal Outcomes on the Creation of Gestational Weight Gain Charts Among Women from Low- and Middle-income Countries with Normal and Overweight BMI.

BACKGROUND: Existing gestational weight gain (GWG) charts vary considerably in their choice of exclusion/inclusion criteria, and it is unclear to what extent these criteria create differences in the charts' percentile values. OBJECTIVES: We aimed to establish the impact of including/excluding pregnancies with adverse neonatal outcomes when constructing GWG charts. METHODS: This is an individual participant data analysis from 31 studies from low- and middle-income countries. We created a dataset that included all participants and a dataset restricted to those with no adverse neonatal outcomes: preterm < 37 wk, small or large for gestational age, low birth weight < 2500 g, or macrosomia > 4000 g. Quantile regression models were used to create GWG curves from 9 to 40 wk, stratified by prepregnancy BMI, in each dataset. RESULTS: The dataset without the exclusion criteria applied included 14,685 individuals with normal weight and 4831 with overweight. After removing adverse neonatal outcomes, 10,479 individuals with normal weight and 3466 individuals with overweight remained. GWG distributions at 13, 27, and 40 wk were virtually identical between the datasets with and without the exclusion criteria, except at 40 wk for normal weight and 27 wk for overweight. For the 10th and 90th percentiles, the differences between the estimated GWG were larger for overweight (∼1.5 kg) compared with normal weight (<1 kg). Removal of adverse neonatal outcomes had minimal impact on GWG trajectories of normal weight. For overweight, the percentiles estimated in the dataset without the criteria were slightly higher than those in the dataset with the criteria applied. Nevertheless, differences were <1 kg and virtually nonexistent at the end of pregnancy. CONCLUSIONS: Removing pregnancies with adverse neonatal outcomes has little or no influence on the GWG trajectories of individuals with normal and overweight.

Intratumoral and peritumoral CT-based radiomics for predicting the microsatellite instability in gastric cancer.

PURPOSE: To investigate the value of intratumoral and peritumoral radiomics based on contrast-enhanced computer tomography (CECT) to preoperatively predict microsatellite instability (MSI) status in gastric cancer (GC) patients. METHODS: A total of 189 GC patients, including 63 patients with MSI-high (MSI-H) and 126 patients with MSI-low/stable (MSI-L/S), were randomly divided into the training cohort and validation cohort. Intratumoral and 5-mm peritumoral regions' radiomics features were extracted from CECT images. The features were standardized by Z-score, and the Inter- and intraclass correlation coefficient, univariate logistic regression analysis, and least absolute shrinkage and selection operator (LASSO) were applied to select the optimal radiomics features. Radiomics scores (Rad-score) based on intratumoral regions, peritumoral regions, and intratumoral + 5-mm peritumoral regions were calculated by weighting the linear combination of the selected features with their respective coefficients to construct the intratumoral model, peritumoral model, and intratumoral + peritumoral model. Logistic regression was used to establish a combined model by combining clinical characteristics, CT semantic features, and Rad-score of intratumoral and peritumoral regions. RESULTS: Eleven radiomics features were selected to establish a radiomics intratumoral + peritumoral model. CT-measured tumor length and tumor location were independent risk factors for MSI status. The established combined model obtained the highest area under the receiver operating characteristic (ROC) curve (AUC) of 0.830 (95% CI, 0.727-0.906) in the validation cohort. The calibration curve and decision curve demonstrated its good model fitness and clinical application value. CONCLUSION: The combined model based on intratumoral and peritumoral CECT radiomics features and clinical factors can predict the MSI status of GS with moderate accuracy before surgery, which helps formulate personalized treatment strategies.

HDAC6-Activatable Multifunctional Near-Infrared Probe for Glioma Cell Detection and Elimination.

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor associated with limited treatment options and high drug resistance, presenting significant challenges in the pursuit of effective treatment strategies. Epigenetic modifications have emerged as promising diagnostic biomarkers and therapeutic targets for GBM. For instance, histone deacetylase 6 (HDAC6) has been identified as a potential pharmacological target for GBM. Furthermore, the overexpression of monoamine oxidase A (MAO A) in glioma has been linked to tumor progression, making it an attractive target for therapy. In this study, we successfully engineered HDAC-MB, an activatable multifunctional small-molecule probe with the goal of efficiently detecting and killing glioma cells. HDAC-MB can be selectively activated by HDAC6, leading to the "turn on" of near-infrared fluorescence and effective inhibition of MAO A, along with potent photodynamic therapy (PDT) effects. Consequently, HDAC-MB not only enables the imaging of HDAC6 in live glioma cells but also exhibits the synergistic effect of MAO A inhibition and PDT, effectively inhibiting glioma invasion and inducing cellular apoptosis. The distinctive combination of features displayed by HDAC-MB positions it as a versatile and highly effective tool for the accurate diagnosis and treatment of glioma cells. This opens up opportunities to enhance therapy outcomes and explore future applications in glioma theranostics.

Enzyme-Directed and Organelle-Specific Sphere-to-Fiber Nanotransformation Enhances Photodynamic Therapy in Cancer Cells.

Employing responsive nanoplatforms as carriers for photosensitizers represents an effective strategy to overcome the challenges associated with photodynamic therapy (PDT), including poor solubility, low bioavailability, and high systemic toxicity. Drawing inspiration from the morphology transitions in biological systems, a general approach to enhance PDT that utilizes enzyme-responsive nanoplatforms is developed. The transformation of phosphopeptide/photosensitizer co-assembled nanoparticles is first demonstrated into nanofibers when exposed to cytoplasmic enzyme alkaline phosphatase. This transition is primarily driven by alkaline phosphatase-induced changes of the nanoparticles in the hydrophilic and hydrophobic balance, and intermolecular electrostatic interactions within the nanoparticles. The resulting nanofibers exhibit improved ability of generating reactive oxygen species (ROS), intracellular accumulation, and retention in cancer cells. Furthermore, the enzyme-responsive nanoplatform is expanded to selectively target mitochondria by mitochondria-specific enzyme sirtuin 5 (SIRT5). Under the catalysis of SIRT5, the succinylated peptide/photosensitizer co-assembled nanoparticles can be transformed into nanofibers specifically within the mitochondria. The resulting nanofibers exhibit excellent capability of modulating mitochondrial activity, enhanced ROS formation, and significant anticancer efficacy via PDT. Consequently, the enzyme-instructed in situ fibrillar transformation of peptide/photosensitizers co-assembled nanoparticles provides an efficient pathway to address the challenges associated with photosensitizers. It is envisaged that this approach will further expand the toolbox for enzyme-responsive biomaterials for cancer therapy.

Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.

OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

Boosting chemotherapy of bladder cancer cells by ferroptosis using intelligent magnetic targeting nanoparticles.

A versatile nano-delivery platform was reported to enhance the tumor suppression effect of chemotherapy by augmenting tumor cells' ferroptosis. The platform consists of pomegranate-like magnetic nanoparticles (rPAE@SPIONs) fabricated by encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) within a reduced poly(ß-amino ester)s-PEG amphiphilic copolymer (rPAE). The resulting platform exhibits several functionalities. Firstly, it promotes the doxorubicin (DOX) release by leveraging the mild hyperthermia generated by NIR irradiation. Secondly, it triggers ferroptosis in tumor cells, inducing their demise. Thirdly, it induces polarization of macrophages towards an anti-tumor M1 phenotype, contributing to ferroptosis of tumor cells and enhanced tumor cell suppression. This study effectively capitalizes on the versatility of SPIONs and offers a simple yet powerful strategy for developing a new nanosized ferroptosis-inducing agent, ultimately improving the inhibition of bladder cancer cells.

Identification of hub genes and pathways associated with cellular senescence in diabetic foot ulcers via comprehensive transcriptome analysis.

This research aimed to find important genes and pathways related to cellular senescence (CS) in diabetic foot ulcers (DFU) and to estimate the possible pathways through which CS affects diabetic foot healing. The GSE80178 dataset was acquired from the Gene Expression Omnibus (GEO) database, containing six DFU and three diabetic foot skin (DFS) samples. The limma package was used to identify differentially expressed genes (DEGs). At the same time, DEGs associated with CS (CS-DEGs) were found using the CellAge database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the CS-DEGs. A protein-protein interaction (PPI) network was built using the String database, and the cytoHubba plug-in within Cytoscape helped identify hub genes. Lastly, the miRNA-TF-mRNA regulatory network for these hub genes was established. In total, 66 CS-DEGs were obtained. These genes mainly focus on CS, Kaposi sarcoma-associated herpesvirus infection and Toll-like receptor signalling pathway. Eight hub genes were identified to regulate cell senescence in DFU, including TP53, SRC, SIRT1, CCND1, EZH2, CXCL8, AR and CDK4. According to miRNA-TF-mRNA regulatory network, hsa-mir-132-3p/SIRT1/EZH2 axis is involved in senescence cell accumulation in DFU.

Preoperative Noninvasive Evaluation of Tumor Budding in Rectal Cancer Using Multiparameter MRI Radiomics.

RATIONALE AND OBJECTIVES: To assess the value of a multiparametric magnetic resonance imaging (MRI)-based model integrating radiomics features with clinical and MRI semantic features for preoperative evaluation of tumor budding (TB) in rectal cancer. MATERIALS AND METHODS: A total of 120 patients with pathologically confirmed rectal cancer were retrospectively analyzed. The patients were randomized into training and validation cohorts in a 6:4 ratio. Radiomics features were extracted and selected from preoperative T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced T1-weighted imaging (T1CE) sequences, after which the corresponding radiomics score (RS) was calculated, and the radiomics models (T2WI model, DWI model, and T1CE model) were constructed. Logistic regression analysis was selected to develop a combined model integrated RST2WI, RSDWI, RST1CE, and clinical and MRI semantic features. The efficacy of each model in diagnosing TB grade was observed by the receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to assess the clinical benefits of the models. RESULTS: Seven features were extracted and selected from each T2WI, DWI, and T1CE sequence to calculate the corresponding RS and construct the corresponding radiomics model. MRI reported N stage was an independent risk factor for TB. The area under the ROC curve of the combined model was 0.961 and 0.891 in the training and validation cohorts, respectively. The combined model showed better performance than the other models. DCA showed that the net benefit of the combined model was better than that of the other models in the vast majority of threshold probabilities. CONCLUSION: A combined model integrating radiomics features and MRI semantic features allows for noninvasive preoperative evaluation of TB grading in patients with rectal cancer.

The Effects of Antenatal Interventions on Gestational Weight Gain in Low- and Middle-Income Countries: Protocol for a Systematic Review.

BACKGROUND: Gestational weight gain (GWG) is a crucial determinant of maternal and child outcomes yet remains an underused target for antenatal interventions in low- and middle-income countries (LMICs). OBJECTIVE: This systematic review aims to identify and summarize educational, behavioral, nutritional, and medical interventions on GWG from randomized controlled trials conducted in LMICs. METHODS: Randomized controlled trials that documented the effects of antenatal interventions on GWG in LMICs will be included. The interventions of interest will be educational, behavioral, nutritional, or medical. A systematic literature search will be conducted using PubMed, Embase, Web of Science, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the Cochrane Library from the inception of each database through October 2022 (with an updated search in January 2024). A total of 2 team members will independently perform the screening of studies and data extraction. A narrative synthesis of all the included studies will be provided. The risk of bias will be assessed using the Cochrane Risk of Bias tool. The certainty of the evidence for each homogeneous group of interventions will be assessed using the GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach. A narrative synthesis of the included studies will be conducted to summarize mean differences (with 95% CIs) for continuous outcomes and risk ratios, rate ratios, hazard ratios, or odds ratios (with 95% CIs) for dichotomous or categorical outcomes. Available information on the costs of interventions will also be summarized to facilitate the adoption and scale-up of effective GWG interventions. RESULTS: The development of the research questions, search strategy, and search protocol was started on September 20, 2022. The database searches and the importation of the identified records into Covidence were performed on October 7, 2022. As of September 2023, the title and abstract screening was ongoing. The target completion time of this systematic review is April 2024. CONCLUSIONS: Without effective interventions to manage GWG, the potential to improve maternal and child health through optimal GWG remains unrealized in LMICs. This systematic review will inform the design and implementation of antenatal interventions to prevent inadequate and excessive GWG in resource-limited settings. TRIAL REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews) CRD42022366354; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=366354. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48234.

Acteoside ameliorates learning and memory impairment in APP/PS1 transgenic mice by increasing Aß degradation and inhibiting tau hyperphosphorylation.

Alzheimer's disease (AD) is a neurodegenerative disease. Senile plaques and intracellular neurofibrillary tangles are pathological hallmarks of AD. Recent studies have described the improved cognitive and neuroprotective functions of acteoside (AS). This study aimed to investigate whether the improved cognition of AS was mediated by Aß degradation and tau phosphorylation in APP/PS1 mice. The open field, Y maze, and novel object recognition tests were used to assess cognitive behavioral changes. We evaluated the levels of Aß40 and Aß42 in serum, cortex, and hippocampus, and Aß-related scavenging enzymes, phosphorylated GSK3ß and hyperphosphorylated tau in the cortex and hippocampus of APP/PS1 mice by western blotting. Our results revealed that AS treatment ameliorated anxious behaviors, spatial learning, and memory impairment in APP/PS1 mice and significantly reduced Aß deposition in their serum, cortex, and hippocampus. AS significantly increased Aß degradation, inhibited the hyperphosphorylation of tau, and significantly decreased the activity of GSK3ß, which is involved in tau phosphorylation. Altogether, these findings indicated that the beneficial effects of AS on AD-associated anxious behaviors and cognitive impairments could be attributed to promoting Aß degradation and inhibiting tau hyperphosphorylation, which might be partly mediated by GSK3ß.

School-based supplementation with iron-folic acid or multiple micronutrient tablets to address anemia among adolescents in Burkina Faso: a cluster-randomized trial.

BACKGROUND: Iron-deficiency anemia is a leading cause of morbidity among adolescents (aged 10-19 y), especially in low- and middle-income settings. Few policies and programs have targeted adolescent health. OBJECTIVES: This study aimed to evaluate the effectiveness of school-based supplementation with iron-folic acid (IFA) or multiple micronutrient supplements (MMSs) in addressing anemia among adolescents in Burkina Faso. METHODS: In this cluster-randomized trial, 3123 secondary school students aged 10 to 18 y in Burkina Faso were either supplemented with weekly IFA, daily MMSs, or received standard nutrition education as controls. Supplementation occurred between April 2021 and April 2022 over 2 supplementation periods (10 wk, then 16 wk) separated by a gap of 20 wk without supplementation. Hemoglobin was evaluated 4 times: at baseline prior to each supplementation period and at the end of each period. Anemia was categorized by the World Health Organization hemoglobin level cutoffs as none, mild, moderate, or severe. Associations between treatment arm and anemia or continuous hemoglobin (g/dL) were assessed using multilevel mixed effects generalized linear models with schools as a random effect, controlling for baseline hemoglobin or anemia status. RESULTS: Baseline anemia prevalence was similar across study arms, with 32.7% in IFA, 31.2% in MMS, and 29.5% in the control arm. Over the full study period, adolescents provided IFA had hemoglobin levels higher than those in the control arm (adjusted ß: 0.32; 95% CI: 0.02, 0.62). No significant associations were observed for MMS or for anemia outcomes; however, the direction and magnitude of nonsignificant associations indicate potential protective effects of IFA and MMSs on anemia. CONCLUSIONS: The results do not provide strong evidence that weekly IFA or daily MMS alone is effective, but supplementation may play a role in addressing adolescent anemia if combined with cointerventions. Additional research is required to determine the best strategy to address anemia. This trial was registered at clinicaltrials.gov as NCT04657640.

Suboptimal gestational weight gain and neonatal outcomes in low and middle income countries: individual participant data meta-analysis.

OBJECTIVE: To estimate the associations between gestational weight gain (GWG) during pregnancy and neonatal outcomes in low and middle income countries. DESIGN: Individual participant data meta-analysis. SETTING: Prospective pregnancy studies from 24 low and middle income countries. MAIN OUTCOME MEASURES: Nine neonatal outcomes related to timing (preterm birth) and anthropometry (weight, length, and head circumference) at birth, stillbirths, and neonatal death. ANALYSIS METHODS: A systematic search was conducted in PubMed, Embase, and Web of Science which identified 53 prospective pregnancy studies published after the year 2000 with data on GWG, timing and anthropometry at birth, and neonatal mortality. GWG adequacy was defined as the ratio of the observed maternal weight gain over the recommended weight gain based on the Institute of Medicine body mass index specific guidelines, which are derived from data in high income settings, and the INTERGROWTH-21st GWG standards. Study specific estimates, adjusted for confounders, were generated and then pooled using random effects meta-analysis models. Maternal age and body mass index before pregnancy were examined as potential modifiers of the associations between GWG adequacy and neonatal outcomes. RESULTS: Overall, 55% of participants had severely inadequate (<70%) or moderately inadequate (70% to <90%) GWG, 22% had adequate GWG (90-125%), and 23% had excessive GWG (≥125%). Severely inadequate GWG was associated with a higher risk of low birthweight (adjusted relative risk 1.62, 95% confidence interval 1.51 to 1.72; 48 studies, 93 337 participants; τ2=0.006), small for gestational age (1.44, 1.36 to 1.54; 51 studies, 93 191 participants; τ2=0.016), short for gestational age (1.47, 1.29 to 1.69; 40 studies, 83 827 participants; τ2=0.074), and microcephaly (1.57, 1.31 to 1.88; 31 studies, 80 046 participants; τ2=0.145) compared with adequate GWG. Excessive GWG was associated with a higher risk of preterm birth (1.22, 1.13 to 1.31; 48 studies, 103 762 participants; τ2=0.008), large for gestational age (1.44, 1.33 to 1.57; 47 studies, 90 044 participants; τ2=0.009), and macrosomia (1.52, 1.33 to 1.73; 29 studies, 68 138 participants; τ2=0) compared with adequate GWG. The direction and magnitude of the associations between GWG adequacy and several neonatal outcomes were modified by maternal age and body mass index before pregnancy. CONCLUSIONS: Inadequate and excessive GWG are associated with a higher risk of adverse neonatal outcomes across settings. Interventions to promote optimal GWG during pregnancy are likely to reduce the burden of adverse neonatal outcomes, however further research is needed to assess optimal ranges of GWG based on data from low and middle income countries.