Research on the impact of ESG performance on carbon emissions from the perspective of green credit.

Utilizing panel data from 30 Chinese provinces, this research examines the non-linear relationship between regional environmental, social, and governance (ESG) performance and carbon emissions (CE) from the viewpoint of green credit. The study reveals a single threshold effect between ESG performance and CE, with green credit acting as the threshold variable. When the amount of green credit in a region exceeds the threshold, the growth rate of CE in that region begins to decline with higher ESG scores. Furthermore, green credit acts as a catalyst, playing a negative moderating role between ESG performance and CE, validated by both threshold regression and fixed effects models on panel data. Green credit indirectly influences carbon emissions by supporting green innovation, thus facilitating the transition to a greener economic development framework. Lastly, regional disparities are found in the moderating influence of green credit between ESG performance and CE. In regions with high ESG performance, the moderating impact of green credit is smaller, while in regions with low ESG performance, the effect is more significant. The research findings offer theoretical backing for policymakers regarding the efficacy of ESG in achieving carbon neutrality objectives, and offer valuable strategic recommendations for the diversified formulation of green credit strategies on both national and provincial scales. Regional heterogeneity test results provide valuable support for formulating policies that encourage green credit in provinces with low ESG performance.

Factors associated with patients' healthcare-seeking behavior and related clinical outcomes under China's hierarchical healthcare delivery system.

Introduction: The hierarchical healthcare delivery system is an important measure to improve the allocation of medical resources and promote equitable distribution of basic medical and health services. It is one of the key factors in the success or failure of China's medical reform. This study aims to analyze the factors influencing patients' healthcare-seeking behaviors, including socioeconomic and clinical outcomes, under China's hierarchical healthcare delivery system, and to provide potential solutions. Methods: Patients receiving outpatient treatment in the past 14 days and inpatient care in the past 1 year were investigated. The multivariate logistic regression was used to analyze the influencing factors of patient's medical treatment behavior selection, and to compare whether the clinical outcomes of primary medical institutions and grade A hospitals are the same. Results: Nine thousand and ninety-eight person-times were included in the study. Of these, 4,538 patients were outpatients, 68.27% of patients were treated in primary medical institutions; 4,560 patients were hospitalized, 58.53% chose to be hospitalized in grade A hospitals. Provinces and cities, urban and rural areas, occupation, education level, medical insurance type, income, whether there are comorbid diseases, and doctors' medical behavior are the factors affecting the choice of medical treatment behavior. Patients who choose primary medical institutions and grade A hospitals have different control levels and control rate for the blood pressure, blood lipids, blood glucose. Conclusion: Under the hierarchical diagnosis and treatment system, the patients' choice of hospital is mainly affected by their level of education, medical insurance types, and the inpatients are also affected by whether there are comorbid conditions. Clinical outcomes of choosing different levels of hospitals were different.

Frequency and Distribution of Ophthalmic Surgical Procedures among Patients with Inherited Retinal Diseases.

OBJECTIVE: In this study, we aimed to characterize the frequency and distribution of ocular surgeries in patients with inherited retinal diseases (IRDs) and evaluate associated patient and disease factors. DESIGN: Retrospective cohort. PARTICIPANTS: Subjects aged ≥ 18 years who were followed at the Johns Hopkins Genetic Eye Disease Center. METHODS: We studied a retrospective cohort of patients with an IRD diagnosis to analyze the occurrence of laser and incisional surgeries. Subjects were categorized into 2 groups: central dysfunction (macular/cone/cone-rod dystrophy, "MCCRD group") and panretinal or peripheral dysfunction (retinitis pigmentosa-like, "RP group"). Genetic testing status was recorded. The association of patient and disease factors on the frequency, distribution, and timing of surgeries was analyzed. MAIN OUTCOME MEASURES: Prevalence, prevalence odds ratio (POR), hazard ratio (HR) of ophthalmic procedures by phenotype. RESULTS: A total of 1472 eyes of 736 subjects were evaluated. Among them, 31.3% (n = 230) had undergone ocular surgery, and 78.3% of those (n = 180/230) had a history of more than 1 surgery. A total of 602 surgical procedures were analyzed. Cataract extraction with intraocular lens implantation (CEIOL) was the most common (51.2%), followed by yttrium aluminum garnet capsulotomy, refractive surgery, retinal surgery, and others. Cataract extraction with intraocular lens implantation occurred more frequently in RP than in MCCRD subjects (POR, 2.59; P = 0.002). Retinitis pigmentosa subjects underwent CEIOL at a younger age than patients with MCCRD (HR, 2.11; P < 0.001). CONCLUSIONS: Approximately one-third of patients with IRD had a history of laser or incisional surgery. Cataract extraction with intraocular lens implantation was the most common surgery; its frequency and timing may be associated with the IRD phenotype. This data may inform the design of prospective research. Such efforts may illuminate routine clinical decision-making and contribute to surgical strategy development for cell and gene therapy delivery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Implementation and impact of the World Health Organization integrated care for older people (ICOPE) program in China: a randomised controlled trial.

BACKGROUND: Fragmentation of services increases health and social care burden as people live longer with higher prevalence of diseases, frailty and dependency. Local evidence for implementing person-centred integrated care is urgently needed to advance practice and policies to achieve healthy ageing. OBJECTIVE: To test the feasibility and impact of World Health Organization's (WHO) Integrated Care for Older People (ICOPE) approach in China. DESIGN: A randomised controlled trial examining the feasibility of implementing ICOPE approach, evaluating its impact on health outcomes and health resource utilisation. SETTING: Primary care setting in urban and suburban communities of Chaoyang District, Beijing, China. SUBJECTS: Community-dwelling older adults screened as at-risk of functional declines and randomised into intervention (537) and control (1611) groups between September 2020 and February 2021. METHODS: A 6-month intervention program following WHO's ICOPE care pathways implemented by integrated care managers compared to standard available care. RESULTS: After 1 to 1 propensity score matching, participants in intervention and control groups (totally 938) had comparable baseline characteristics, demonstrated feasibility of implementing ICOPE with satisfaction by participants (97-99%) and providers (92-93%). All outcomes showed improvements after a 6-month intervention, while statistically significant least-squares mean differences (control-intervention) in vitality (Mini-Nutritional Assessment Short Form to measure vitality, -0.21, 95% CI, -0.40-0.02), mobility (Short Physical Performance Battery to measure mobility, -0.29, 95% CI, -0.44-0.14) and psychological health (Geriatric Depression Scale five items to measure psychological health, 0.09, 95% CI, 0.03-0.14) were observed (P < 0.05). CONCLUSIONS: It is feasible to localise and implement WHO's ICOPE approach in regions with fragmented resources such as China. Preliminary evidence supports its acceptance among key stakeholders and impact on health outcomes.

Functional data analysis to characterize disease patterns in frequent longitudinal data: application to bacterial vaginal microbiota patterns using weekly Nugent scores and identification of pattern-specific risk factors.

BACKGROUND: Technology advancement has allowed more frequent monitoring of biomarkers. The resulting data structure entails more frequent follow-ups compared to traditional longitudinal studies where the number of follow-up is often small. Such data allow explorations of the role of intra-person variability in understanding disease etiology and characterizing disease processes. A specific example was to characterize pathogenesis of bacterial vaginosis (BV) using weekly vaginal microbiota Nugent assay scores collected over 2 years in post-menarcheeal women from Rakai, Uganda, and to identify risk factors for each vaginal microbiota pattern to inform epidemiological and etiological understanding of the pathogenesis of BV. METHODS: We use a fully data-driven approach to characterize the longitudinal patters of vaginal microbiota by considering the densely sampled Nugent scores to be random functions over time and performing dimension reduction by functional principal components. Extending a current functional data clustering method, we use a hierarchical functional clustering framework considering multiple data features to help identify clinically meaningful patterns of vaginal microbiota fluctuations. Additionally, multinomial logistic regression was used to identify risk factors for each vaginal microbiota pattern to inform epidemiological and etiological understanding of the pathogenesis of BV. RESULTS: Using weekly Nugent scores over 2 years of 211 sexually active and post-menarcheal women in Rakai, four patterns of vaginal microbiota variation were identified: persistent with a BV state (high Nugent scores), persistent with normal ranged Nugent scores, large fluctuation of Nugent scores which however are predominantly in the BV state; large fluctuation of Nugent scores but predominantly the scores are in the normal state. Higher Nugent score at the start of an interval, younger age group of less than 20 years, unprotected source for bathing water, a woman's partner's being not circumcised, use of injectable/Norplant hormonal contraceptives for family planning were associated with higher odds of persistent BV in women. CONCLUSION: The hierarchical functional data clustering method can be used for fully data driven unsupervised clustering of densely sampled longitudinal data to identify clinically informative clusters and risk-factors associated with each cluster.

A new class of potent liver injury protective compounds: Structural elucidation, total synthesis and bioactivity study.

A new class of potent liver injury protective compounds, phychetins A-D (1-4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2-4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1-4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2-4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1ß. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.

HIF-1α inhibition in macrophages preserves acute liver failure by reducing IL-1ß production.

The development of acute liver failure (ALF) is dependent on its local inducer. Inflammation is a high-frequency and critical factor that accelerates hepatocyte death and liver failure. In response to injury stress, the expression of the transcription factor hypoxia-inducible factor-1α (HIF-1α) in macrophages is promoted by both oxygen-dependent and oxygen-independent mechanisms, thus promoting the expression and secretion of the cytokine interleukin-1ß (IL-1ß). IL-1ß further induces hepatocyte apoptosis or necrosis by signaling through the receptor (IL-1R) on hepatocyte. HIF-1α knockout in macrophages or IL-1R knockout in hepatocytes protects against liver failure. However, whether HIF-1α inhibition in macrophages has a protective role in ALF is unclear. In this study, we revealed that the small molecule HIF-1α inhibitor PX-478 inhibits the expression and secretion of IL-1ß, but not tumor necrosis factor α (TNFα), in bone marrow-derived macrophages (BMDMs). PX-478 pretreatment alleviates liver injury in LPS/D-GalN-induced ALF mice by decreasing the hepatic inflammatory response. In addition, preventive or therapeutic administration of PX-478 combined with TNFα neutralizing antibody markedly improved LPS/D-GalN-induced ALF. Taken together, our data suggest that PX-478 administration leads to HIF-1α inhibition and decreased IL-1ß secretion in macrophages, which represents a promising therapeutic strategy for inflammation-induced ALF.

Perinatal Factors and Emotional, Cognitive, and Behavioral Dysregulation in Childhood and Adolescence.

OBJECTIVE: This cohort study assessed perinatal factors known to be related to maternal and neonatal inflammation and hypothesized that several would be associated with emotional, cognitive, and behavioral dysregulation in youth. METHOD: The Environmental influences on Child Health Outcomes (ECHO) is a research consortium of 69 pediatric longitudinal cohorts. A subset of 18 cohorts that had both Child Behavior Checklist (CBCL) data on children (6-18 years) and information on perinatal exposures including maternal prenatal infections was used. Children were classified as having the CBCL-Dysregulation Profile (CBCL-DP) if the sum of their T scores for 3 CBCL subscales (attention, anxious/depressed, and aggression) was ≥180. Primary exposures were perinatal factors associated with maternal and/or neonatal inflammation, and associations between these and outcome were assessed. RESULTS: Approximately 13.4% of 4,595 youth met criteria for CBCL-DP. Boys were affected more than girls (15.1% vs 11.5%). More youth with CBCL-DP (35%) were born to mothers with prenatal infections compared with 28% of youth without CBCL-DP. Adjusted odds ratios indicated the following were significantly associated with dysregulation: having a first-degree relative with a psychiatric disorder; being born to a mother with lower educational attainment, who was obese, had any prenatal infection, and/or who smoked tobacco during pregnancy. CONCLUSION: In this large study, a few modifiable maternal risk factors with established roles in inflammation (maternal lower education, obesity, prenatal infections, and smoking) were strongly associated with CBCL-DP and could be targets for interventions to improve behavioral outcomes of offspring. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Mixed Methods, Implementation Science Evaluation of a Community Health Worker Strategy for HIV Service Engagement in Uganda.

BACKGROUND: A trial found that a community health worker (CHW) strategy using "Health Scouts" improved HIV care uptake and ART coverage. To better understand outcomes and areas for improvement, we conducted an implementation science evaluation. METHODS: Using the RE-AIM framework, quantitative methods included analyses of a community-wide survey (n = 1903), CHW log books, and phone application data. Qualitative methods included in-depth interviews (n = 72) with CHWs, clients, staff, and community leaders. RESULTS: Thirteen Health Scouts logged 11,221 counseling sessions; 2532 unique clients were counseled. 95.7% (1789 of 1891) of residents reported awareness of the Health Scouts. Overall, reach (self-reported receipt of counseling) was 30.7% (580 of 1891). Unreached residents were more likely to be male and HIV seronegative ( P < 0.05). Qualitative themes included the following: (1) reach was promoted by perceived usefulness but deterred by busy client lifestyles and stigma, (2) effectiveness was enabled through good acceptability and consistency with the conceptual framework, (3) adoption was facilitated by positive impacts on HIV service engagement, and (4) implementation fidelity was initially promoted by the CHW phone application but deterred by mobility. Maintenance showed consistent counseling sessions over time. The findings suggested the strategy was fundamentally sound but had suboptimal reach. Future iterations could consider adaptations to improve reach to priority populations, testing the need for mobile health support, and additional community sensitization to reduce stigma. CONCLUSIONS: A CHW strategy to promote HIV services was implemented with moderate success in an HIV hyperendemic setting and should be considered for adoption and scale-up in other communities as part of comprehensive HIV epidemic control efforts. TRIAL REGISTRATION: ClinicalTrials.gov Trial Number NCT02556957.

Global Trends in Blindness and Vision Impairment Resulting from Corneal Opacity 1984-2020: A Meta-analysis.

TOPIC: We provide global estimates of the prevalence of corneal blindness and vision impairment in adults 40 years of age and older and examine the burden by age, sex, and geographic region from 1984 through 2020. CLINICAL RELEVANCE: Corneal opacities (COs) are among the top 5 causes of blindness worldwide, yet the global prevalence, regional differences, and risk factors are unclear. METHODS: Abstracted data from the published literature and surveys were obtained from the Global Burden of Disease Vision Loss Expert Group. We supplemented this by an independent systematic literature search of several databases. Studies that provided CO vision impairment data based on population-based surveys for those 40 years of age or older were included, for a total of 244. For each of the 4 outcomes of blindness and moderate to severe vision impairment (MSVI) caused by trachomatous and nontrachomatous CO (NTCO), time trends and differences in prevalence by region, age, and sex were evaluated using a Poisson log-linear model with a generalized estimating equation method. Age-standardized estimates of global prevalence of blindness and MSVI were calculated using the 2015 United Nations standard populations. RESULTS: The global prevalence of blindness resulting from NTCO in those 40 years and older was 0.081% (95% confidence interval [CI], 0.049%-0.315%); that of MSVI was 0.130% (95% CI, 0.087%-0.372%). A significant increase with age was found (prevalence rate ratio, 2.15; 95% CI, 1.99-2.32). Latin America and Europe showed the lowest rates, with 2- to 8-fold higher rates of blindness or MSVI in other regions. The global prevalence of blindness resulting from trachomatous CO in those 50 years and older was 0.0094% (95% CI, 0%-0.0693%); that from MSVI was 0.012% (95% CI, 0%-0.0761%). Blindness resulting from trachomatous CO and MSVI increased with age and female sex, and rates were significantly higher in the African regions. A decrease in trachomatous blindness rates over time was found (prevalence rate ratio, 0.91; 95% CI, 0.86-0.96). DISCUSSION: An estimated 5.5 million people worldwide are bilaterally blind or have MSVI resulting from CO, with an additional 6.2 million unilaterally blind. Blindness resulting from trachomatous CO is declining over time, likely because of the massive scaleup of the global trachoma elimination program and overall socioeconomic development. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Progression of Stargardt Disease as Determined by Fundus Autofluorescence Over a 24-Month Period (ProgStar Report No. 17).

PURPOSE: To estimate the progression rate of atrophic lesions in Stargardt disease derived from fundus autofluorescence (FAF). DESIGN: International, multicenter, prospective cohort study. METHODS: A total of 259 participants aged ≥6 years with disease-causing variants in the ABCA4 gene were enrolled from 9 centers and followed over a 24-month period. FAF images were obtained every 6 months, and areas of definitely decreased autofluorescence (DDAF) and decreased autofluorescence (DAF) were quantified. Progression rates were estimated from linear mixed models with time as the independent variable. RESULTS: A total of 488 study eyes of 259 participants (88.8% with both eyes) were enrolled and images from 432 eyes were followed for 24 months. The overall estimated progression of DDAF was 0.74 mm2/y (95% CI 0.64-0.85, P < .0001) and that of DAF was 0.64 mm2/y (95% CI 0.57-0.71) over a 24-month period in univariate analysis. Growth rates were strongly dependent on baseline lesion area. After square root transformation, the DDAF growth rate was not dependent on baseline lesion radius (P = .11), whereas the DAF growth rate was dependent (P < .0001). Genotype was not found to significantly impact the growth rate of DDAF or DAF lesions. CONCLUSIONS: FAF may serve as a convenient monitoring tool and suitable end point for interventional clinical trials that aim to slow disease progression. DDAF and DAF lesion sizes at baseline are strong predicting factors for lesion area growth and can be partially accounted for by square root transformation.

Effects of COVID-19 Financial and Social Hardships on Infants' and Toddlers' Development in the ECHO Program.

BACKGROUND: The financial hardships and social isolation experienced during the COVID-19 pandemic have been found to adversely affect children's developmental outcomes. While many studies thus far have focused on school-aged children and the pandemic-related impacts on their academic skills and behavior problems, relatively less is known about pandemic hardships and associations with children's development during their early years. Using a racially and economically diverse sample, we examined whether hardships experienced during the pandemic were associated with children's development with a particular focus on communication and socioemotional development. METHODS: Participants from eight cohorts of the Environmental influences on Child Health Outcomes program provided data on pandemic-related financial and social hardships as well as child developmental outcomes. Financial hardship was defined as at least one parent experiencing job loss or change, and social hardship was defined as families' quarantining from household members or extended family and friends. The development of children under 4 was assessed longitudinally, before and during the pandemic (N = 684), using the Ages and Stages Questionnaire (ASQ). The Generalized Estimating Equations, which accounted for within-child correlation, were used for analysis. RESULTS: Families from minority backgrounds and low socioeconomic status disproportionately experienced pandemic-related hardships. Male children had higher odds of experiencing negative changes in communication and personal social skills from pre- to during-pandemic visits (ORs ranged between 2.24 and 3.03 in analysis with binary ASQ outcomes and ranged from -0.34-0.36 in analyses with ASQ z-scores, ps = 0.000). Pandemic-related hardships in the social and financial areas did not explain within-individual changes in children's developmental outcomes. CONCLUSION: Negative developmental changes from pre- to during-pandemic were found in boys, yet we did not find any associations between increased experience of pandemic-related hardships and children's development. E how pandemic hardships affect development using a larger sample size and with longer follow-up is warranted.

Comparing Generalized Estimating Equation and Linear Mixed Effects Model for Estimating Marginal Association with Bivariate Continuous Outcomes.

PURPOSE: Both linear regression with generalized estimating equations (GEE) and linear mixed-effects models (LMEM) can be used to estimate the marginal association of an exposure with clustered continuous outcomes. This study compares their performance for bivariate continuous outcomes which are common in eye studies. METHODS: Parametric and non-parametric simulations were used to compare the GEE models including independent, exchangeable, and unstructured working correlation structures and LMEM including random intercept only and random intercept and slope models in R and SAS. Data generation referenced the data distributions from a real-world study for estimating ocular structure-visual function relationships in patients with retinitis pigmentosa. RESULTS: From both parametric and non-parametric simulations, comparing the random intercept LMEM and GEE exchangeable model, bias was similar; coverage probability of the 95% confidence interval (CI) from the random intercept LMEM was often closer to 95%, especially when the sample size was small; the power for testing the association of the exposure was higher from the GEE exchangeable model, but its type-I error rate might be inflated especially when the sample size was small. The type-I error rate from the random intercept LMEM was closer to 0.05, but it might be under 0.05 and coverage probability might be over 95%. The GEE independent model performed worst and the LMEM with both random intercept and slope might not converge. CONCLUSION: To estimate marginal exposure-outcome association with bivariate continuous outcomes, the random intercept LMEM may be preferred. It has the best coverage probability of 95% CI and is the only model with correct type-I error rates in this study. However, it may have low power and overly wide CI in studies with small sample size or low inter-eye correlation.

Trusted information sources in the early months of the COVID-19 pandemic predict vaccination uptake over one year later.

INTRODUCTION: COVID-19 vaccine uptake has been a major barrier to stopping the pandemic in many countries with vaccine access. This longitudinal study examined the capability to predict vaccine uptake from data collected early in the pandemic before vaccines were available. METHODS: 493 US respondents completed online surveys both at baseline (March 2020) and wave 6 (June 2021), while 390 respondents completed baseline and wave 7 (November 2021) surveys. The baseline survey assessed trust in sources of COVID-19 information, social norms, perceived risk of COVID-19, skepticism about the pandemic, prevention behaviors, and conspiracy beliefs. Multivariable logistic models examined factors associated with the receipt of at least one COVID-19 vaccine dose at the two follow-ups. RESULTS: In the adjusted model of vaccination uptake at wave 6, older age (aOR = 1.02, 95 %CI = 1.00-1.04) and greater income (aOR = 1.69, 95 %CI = 1.04-2.73) was associated with positive vaccination status. High trust in state health departments and mainstream news outlets at baseline were positively associated with vaccination at wave 6, while high trust in the Whitehouse (aOR = 0.42, 95 %CI = 0.24-0.74) and belief that China purposely spread the virus (aOR = 0.66, 95 %CI = 0.46-0.96) at baseline reduced the odds of vaccination. In the adjusted model of vaccination uptake at wave 7, increased age was associated with positive vaccination status, and Black race (compared to white) was associated with negative vaccination status. High trust in the CDC and mainstream news outlets at baseline were both associated with being vaccinated at wave 7, while high trust in the Whitehouse (aOR = 0.24, 95 %CI = 0.11-0.51) and belief that the virus was spread purposefully by China (aOR = 0.60, 95 %CI = 0.39-0.93) were negatively associated with vaccination. CONCLUSIONS: These findings indicated that vaccine uptake could be predicted over a year earlier. Trust in specific sources of COVID-19 information were strong predictors, suggesting that future pandemic preparedness plans should include forums for news media, public health officials, and diverse political leaders to meet and develop coherent plans to communicate to the public early in a pandemic so that antivaccine attitudes do not flourish and become reinforced.

Multi­institutional development and validation of a nomogram to predict prognosis of early-onset gastric cancer patients.

Background: Early-onset gastric cancer (EOGC, ≤45 years old) is characterized with increasing incidence and more malignant phenotypes compared with late-onset gastric cancer, which exhibits remarkable immune cell infiltration and is potential immunotherapeutic population. Till now, restricted survival information of EOGC is available due to limited case numbers. This study established a novel nomogram to help evaluate cancer-specific survival (CSS) of EOGC patients who underwent gastrectomy, and may provide evidence for predicting patients' survival. Methods: We retrospectively enrolled a cohort containing 555 EOGC cases from five independent medical centers in China, among which 388 cases were randomly selected into a training set while the other 167 cases were assigned into the internal validation set. Asian or Pacific Islander (API) patients diagnosed with EOGC during 1975-2016 were retrieved from the SEER database (n=299) and utilized as the external validation cohort. Univariate and multivariate analyses were conducted to test prognostic significances of clinicopathological factors in the training set. Accordingly, two survival nomogram models were established and compared by concordance index (C-index), calibration curve, receiver operating characteristics (ROC) curves and decision curve analyses (DCA). Results: The 5-year CSS rate of training cohort was 61.3% with a median survival time as 97.2 months. High consistency was observed on calibration curves in all three cohorts. Preferred nomogram was selected due to its better performance on ROC and DCA results. Accordingly, a novel predicative risk model was introduced to better stratify high-risk EOGC patients with low-risk patients. In brief, the 5-year CSS rates for low-risk groups were 92.9% in training set, 83.1% in internal validation set, 89.9% in combined NQSQS cohort, and 85.3% in SEER-API cohort. In contrast, the 5-year CSS rates decreased to 38.5%, 44.3%, 40.5%, and 36.9% in the high-risk groups of the four cohorts above, respectively. The significant survival difference between high-risk group (HRG) and low-risk group (LRG) indicated the precise accuracy of our risk model. Furthermore, the risk model was validated in patients with different TNM stages, respectively. Finally, an EOGC web-based survival calculator was established with public access, which can help predict prognosis. Conclusions: Our data provided a precise nomogram on predicting CSS of EOGC patients with potential clinical applicability.

Lung Cancer Recurrence Risk Prediction through Integrated Deep Learning Evaluation.

Background: Prognostic risk factors for completely resected stage IA non-small-cell lung cancers (NSCLCs) have advanced minimally over recent decades. Although several biomarkers have been found to be associated with cancer recurrence, their added value to TNM staging and tumor grade are unclear. Methods: Features of preoperative low-dose CT image and histologic findings of hematoxylin- and eosin-stained tissue sections of resected lung tumor specimens were extracted from 182 stage IA NSCLC patients in the National Lung Screening Trial. These features were combined to predict the risk of tumor recurrence or progression through integrated deep learning evaluation (IDLE). Added values of IDLE to TNM staging and tumor grade in progression risk prediction and risk stratification were evaluated. Results: The 5-year AUC of IDLE was 0.817 ± 0.037 as compared to the AUC = 0.561 ± 0.042 and 0.573 ± 0.044 from the TNM stage and tumor grade, respectively. The IDLE score was significantly associated with cancer recurrence (p < 0.0001) even after adjusting for TNM staging and tumor grade. Synergy between chest CT image markers and histological markers was the driving force of the deep learning algorithm to produce a stronger prognostic predictor. Conclusions: Integrating markers from preoperative CT images and pathologist's readings of resected lung specimens through deep learning can improve risk stratification of stage 1A NSCLC patients over TNM staging and tumor grade alone. Our study suggests that combining markers from nonoverlapping platforms can increase the cancer risk prediction accuracy.

Child Mental Health and Sleep Disturbances During the Early Months of the COVID-19 Pandemic in the United States.

Many children have experienced unprecedented levels of stress as a result of the COVID-19 pandemic due to school closures, strained resources, and excess morbidity and mortality. The current study examines change in children's mental health and sleep during the early months of the US pandemic and identifies risk and protective factors. In May 2020, a total of 225 parents reported on the mental health and sleep of each child (N = 392 children) living in their household prior to the onset of the COVID-19 pandemic and about their functioning in the past month. McNemar's test examined change in mental health and sleep disturbance across developmental stage. Bivariate and multivariate generalized estimating equations examined predictors of change in mental health and sleep. Each age group showed a significant change in mental health and sleep outcomes, but the development of mental health problems was greater for older children. Parental caregiving strain (adjusted odds ratio [aOR] = 2.42; 95% confidence interval [CI], 1.11-5.27) was identified as a risk factor associated with children developing anxiety, and income loss was associated with developing sleep disturbances (aOR = 2.34; 95% CI, 1.06-5.17). Parental receipt of emotional support was identified as a protective factor for all child health outcomes. Policies and interventions that promote access to mental health services, provide financial safety nets, and strengthen social support networks for families are needed.

Impact of community health worker intervention on PrEP knowledge and use in Rakai, Uganda: A mixed methods, implementation science evaluation.

BACKGROUND: Effective models of support for HIV pre-exposure prophylaxis (PrEP) are needed for populations at elevated risk. In a hyperendemic Ugandan fishing community, PrEP counseling was provided through a situated Information, Motivation, and Behavioral Skills (sIMB)-based community health worker (CHW) intervention. We evaluated the intervention using a mixed-methods, implementation science design. METHODS: We surveyed all community members aged 15-49 through the Rakai Community Cohort Study. We used multivariable logistic regressions with generalized estimating equations to estimate the intervention's effect on PrEP knowledge and utilization. To understand intervention experiences and mechanisms, we conducted 74 qualitative interviews with 5 informant types (clients, CHWs, program staff, community leaders, health clinic staff) and analyzed data using an iterative, deductive approach. A mobile phone application provided intervention process implementation data. RESULTS: Individuals self-reporting receipt of the CHW intervention showed significantly higher PrEP knowledge (N = 1848, PRR: 1.10, 95% CI: 1.06-1.14, p = <.0001), PrEP ever use (N = 1176, PRR: 1.77, 95% CI: 1.33-2.36, p = <.0001), and PrEP current use (N = 1176, PRR: 1.86, 95% CI: 1.22-2.82, p = 0.0039) compared to those who did not. Qualitative findings attributed positive PrEP outcomes to CHW counseling and effective use of motivational interviewing skills by CHWs. Salient themes across the RE-AIM framework included support for the CHW intervention and PrEP across clients, community, and implementers. Mobile application data demonstrated consistent delivery of the PrEP module throughout implementation. CONCLUSIONS: CHWs improved PrEP knowledge and use among clients in an HIV hyperendemic fishing community. Mixed-methods, implementation science evaluations can inform adaptation of similar PrEP implementation strategies.

Analysis of Early-Life Growth and Age at Pubertal Onset in US Children.

Importance: Earlier pubertal onset may be associated with an increased risk of chronic diseases. However, the extent to which growth in the first 5 years of life-an important developmental life stage that lays the foundation for later health outcomes-is associated with pubertal onset remains understudied. Objective: To assess whether changes in weight, length or height, and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) during the first 5 years of life are associated with earlier pubertal onset. Design, Setting, and Participants: This cohort study used data from 36 cohorts participating in the Environmental Influences on Child Health Outcomes program from January 1, 1986, to December 31, 2015. Participant inclusion required at least 1 anthropometric measure in the first 5 years of life and at least 1 measure of pubertal onset. Data were analyzed from January 1 to June 30, 2021. Exposures: Standardized velocities of weight, length or height, and BMI gain in early infancy (0-0.5 years), late infancy (0.5-2 years), and early childhood (2-5 years). Main Outcomes and Measures: Markers of pubertal onset for boys and girls, including age at peak height velocity (APHV), time to puberty score greater than 1, time to Tanner pubic hair stage greater than 1, and time to menarche. Multivariable regression models were used to estimate mean differences in APHV by growth periods. Results: Of 7495 children included in the study, 3772 (50.3%) were girls, 4505 (60.1%) were White individuals, and 6307 (84.1%) were born during or after the year 2000. Girls had a younger APHV (10.8 vs 12.9 years) than boys. In boys, faster weight gain (per 1-SD increase) in early infancy (ß, -0.08 years; 95% CI, -0.10 to -0.06), late infancy (ß, -0.10 years; 95% CI, -0.12 to -0.08), and early childhood (ß, -0.07 years; 95% CI, -0.08 to -0.05) was associated with younger APHV after adjusting for the child's birth year, race, and Hispanic ethnicity as well as maternal age at delivery; educational level during pregnancy; annual household income during pregnancy; prenatal cigarette smoking; whether the mother was nulliparous; whether the mother had gestational diabetes, hypertension, or preeclampsia; mode of delivery; prepregnancy BMI; gestational weight gain; and gestational age at delivery. Similar associations were observed for length or height and BMI gains during the same age periods. In girls, faster gains (per 1-SD increase) in weight (ß, -0.03 years; 95% CI, -0.05 to -0.01) and height (ß, -0.02 years; 95% CI, -0.04 to 0.00) in early childhood were associated with younger APHV. Faster BMI gain in late infancy was associated with earlier time to menarche, whereas faster BMI gain in early childhood was associated with earlier time to Tanner pubic hair stage greater than 1. Conclusions and Relevance: This cohort study found that faster gains in weight, length or height, or BMI in early life were associated with earlier pubertal onset. The results suggest that children who experience faster early growth should be monitored closely for earlier onset of puberty and referred as appropriate for supportive services.