Subgroup Heterogeneity Research Articles

Adverse Childhood Experiences are associated with Mental Health Problems later in life: An Umbrella Review of Systematic Review and Meta-analysis.

Evidence suggested a link between early adversity and mental health problems. However, it is unclear how much adverse childhood experiences (ACEs) contribute to mental health problems because researchers have produced inconsistent findings. Therefore, the objective of this umbrella review was to combine the contradictory data regarding the effect of ACEs on the development of mental health problems later in life in the global context. PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Scopus, and Google Scholar which reported the effect of ACEs on the development of mental health problems were searched. The quality of the included studies was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR). A weighted inverse variance random-effects model was applied to find the pooled estimates. The subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also assessed. Forty-three SRM with 14707614 study participants were included. The pooled effect of ACEs on the development of mental health problems later in life in the global context is found to be (AOR=1.66 (1.46, 1.87)). Subgroup analysis based on country revealed (AOR=1.67(1.23, 2.11)) in UK, (AOR=0.61(0.41, 0.81)) in Canada, (AOR=1.55(1.40, 1.69)) in Brazil, (AOR=5.65(4.12, 7.18)) in Ethiopia, (AOR=1.92(1.45, 2.38)) in USA, (AOR=2.30(1.89, 2.72)) in Australia and (AOR=1.66(1.46, 1.87)) in irland. While subgroup analysis based on types of adverse childhood adverse experience: domestic violence ((AOR=4.13(1.96, 6.30)), maltreatment (AOR=1.5(0.79, 2.21)), physical abuse(AOR=1.56(1.43,1.63), sexual abuse (AOR=2.07(1.63, 2.51)), child abuse (AOR=5.66(4.12,7.18)), parental mental health problem (AOR=1.73(1.39,2.08)), bullying (AOR=1.99(1.69, 2.29), neglect(AOR=2.11(1.53,2.69)), and parental divorce (AOR=1.66(1.46,1.87)). Based on the type of mental health problem the pooled effect size is 1.87(1.45, 2.30) for depression and 1.67(1.22, 2.13) for anxiety. This umbrella review revealed that adverse childhood experience is significantly associated (with 66% increased risk) with anxiety and depression later in life in a global context. This association is most noticeable when one is subjected to domestic violence, maltreatment, physical abuse, sexual abuse, child abuse, parental mental health problems, bullying, neglect, and parental divorce. Childhood periods are a critical window of opportunity for reducing the risk of developing mental illness in the future and for implementing intervention measures. Preventing childhood maltreatment and addressing psychiatric risk factors can prevent psychopathology. Longitudinal studies are needed to optimize healthcare responses to ACEs. Increased awareness and public health interventions are needed to prevent childhood adversity and prevent mental problems among these victims. To optimize healthcare responses to unfavorable outcomes of childhood adversities, longitudinal and intervention research findings, more public health initiatives, and awareness are required.

Multivariate Environmental Factors and Seasonal Spatial Dynamics Affecting the Phytoplankton Community in Yazhou Bay, South China Sea

This study investigated phytoplankton and water environmental factors in Yazhou Bay, South China Sea, during the winter, spring, and summer of 2023. It examined phytoplankton community structure, subgroup heterogeneity, and key environmental drivers. Phytoplankton abundance ranged from 0.08 to 14.30 × 10⁴ cells·L−1, with high concentrations in estuary and nearshore zones. In summer, currents carry phytoplankton offshore, with stratification leading to high sedimentation in southern offshore waters. RDA results indicated that in winter and spring, inorganic nitrogen mainly influences phytoplankton distribution, while silicate is the primary factor in summer. Although seasonal differences in total phytoplankton abundance are minimal, significant horizontal and vertical distribution variations exist. Diverse preferences of different phytoplankton species for temperature, salinity, nitrogen, and phosphorus result in high species diversity. The Shannon–Wiener diversity index (H′) averages 3.96 ± 0.09, and the Pielou evenness index (J) averages 0.82 ± 0.01. Dominant species include Pseudo-nitzschia pungens, Skeletonema costatum, and Rhizosolenia sinica. Influenced by external oceanic water masses, estuary input, and islands, phytoplankton subgroups show regional and seasonal variations. Despite recorded harmful algal blooms (HABs) in adjacent waters, Yazhou Bay’s high biodiversity and low cell density suggest a low HAB risk, though future risks due to climate change and human activities remain.

HIP: a method for high-dimensional multi-view data integration and prediction accounting for subgroup heterogeneity.

Epidemiologic and genetic studies in many complex diseases suggest subgroup disparities (e.g. by sex, race) in disease course and patient outcomes. We consider this from the standpoint of integrative analysis where we combine information from different views (e.g. genomics, proteomics, clinical data). Existing integrative analysis methods ignore the heterogeneity in subgroups, and stacking the views and accounting for subgroup heterogeneity does not model the association among the views. We propose Heterogeneity in Integration and Prediction (HIP), a statistical approach for joint association and prediction that leverages the strengths in each view to identify molecular signatures that are shared by and specific to a subgroup. We apply HIP to proteomics and gene expression data pertaining to chronic obstructive pulmonary disease (COPD) to identify proteins and genes shared by, and unique to, males and females, contributing to the variation in COPD, measured by airway wall thickness. Our COPD findings have identified proteins, genes, and pathways that are common across and specific to males and females, some implicated in COPD, while others could lead to new insights into sex differences in COPD mechanisms. HIP accounts for subgroup heterogeneity in multi-view data, ranks variables based on importance, is applicable to univariate or multivariate continuous outcomes, and incorporates covariate adjustment. With the efficient algorithms implemented using PyTorch, this method has many potential scientific applications and could enhance multiomics research in health disparities. HIP is available at https://github.com/lasandrall/HIP, a video tutorial at https://youtu.be/O6E2OLmeMDo and a Shiny Application at https://multi-viewlearn.shinyapps.io/HIP_ShinyApp/ for users with limited programming experience.

Cluster analysis of 100 Marfan patients based on aortic 4D flow MRI and Z-score: insights into disease heterogeneity and stratification of subgroups.

4D flow MRI-derived variables from Marfan patients are highly heterogeneous. Our aim was to identify distinct Marfan patient subgroups based on aortic 4D flow MRI and Z-score for stratification of distinct hemodynamic profiles and clinical features by means of hierarchical cluster analysis. One hundred Marfan patients underwent baseline aortic 4D flow MRI at 3 T. Z-scores, degree of helical and vortical flow, wall shear stress, flow displacement, and peak velocity were determined in the ascending aorta. Sex, age, BMI, antihypertensive medication, and dural ectasia were recorded. Hierarchical cluster analysis was performed using 4D flow MRI variables and Z-scores as input. Cluster analysis resulted in three distinct clusters characterized by different Z-scores (mean ± SD); cluster 1: 0.4 ± 1.1 vs. cluster 2: 3.1 ± 1.1 vs. cluster 3: 3.6 ± 1.9. The three clusters delivered differences in helical and vortical flow patterns (global p = 0.003 and p < 0.001, respectively), wall shear stress (0.49 ± 0.11 vs. 0.44 ± 0.12 vs. 0.37 ± 0.09 N/m2, global p < 0.001), flow displacement (0.11 ± 0.05 vs. 0.16 ± 0.08 vs. 0.15 ± 0.07, global p = 0.006), and peak velocity (76.3 ± 9.0 vs. 60.1 ± 7.3 vs. 56.0 ± 7.8 cm/s, global p < 0.001). Patients in cluster 1 and 2 were relevantly younger than in cluster 3 (32.3 ± 13.8 vs. 32.8 ± 12.6 vs. 40.2 ± 15.0 years, all pairwise ∆p < 0.0297). Hierarchical cluster analysis based on aortic 4D flow MRI and Z-score revealed three distinct subgroups of Marfan patients, each characterized by specific hemodynamic profiles and clinical features. Follow-up of our patients is warranted to assess if 4D flow MRI- and Z-score-based stratification can predict future aortic diameter growth and ultimately improve outcomes. A combination of Z-score and 4D flow MRI-derived parameters may help identify subgroups of Marfan patients representing different stages or phenotypes of aortic disease, which require specific management strategies. Four-dimensional (4D) flow MRI-derived variables of Marfan patients are highly heterogeneous across varying Z-scores. Cluster analysis based on 4D flow MRI and Z-score revealed three distinct subgroups of Marfan patients. A combination of Z-score and 4D flow MRI-derived parameters may identify different stages of aortic disease in Marfan patients.

Longitudinal course of inflammatory-cognitive subgroups across first treatment severe mental illness and healthy controls.

While inflammation is associated with cognitive impairment in severe mental illnesses (SMI), there is substantial heterogeneity and evidence of transdiagnostic subgroups across schizophrenia (SZ) and bipolar (BD) spectrum disorders. There is however, limited knowledge about the longitudinal course of this relationship. Systemic inflammation (C-Reactive Protein, CRP) and cognition (nine cognitive domains) was measured from baseline to 1 year follow-up in first treatment SZ and BD (n = 221), and healthy controls (HC, n = 220). Linear mixed models were used to evaluate longitudinal changes separately in CRP and cognitive domains specific to diagnostic status (SZ, BD, HC). Hierarchical clustering was applied on the entire sample to investigate the longitudinal course of transdiagnostic inflammatory-cognitive subgroups. There were no case-control differences or change in CRP from baseline to follow-up. We confirm previous observations of case-control differences in cognition at both time-points and domain specific stability/improvement over time regardless of diagnostic status. We identified transdiagnostic inflammatory-cognitive subgroups at baseline with differing demographics and clinical severity. Despite improvement in cognition, symptoms and functioning, the higher inflammation - lower cognition subgroup (75% SZ; 48% BD; 38% HC) had sustained inflammation and lower cognition, more symptoms, and lower functioning (SMI only) at follow-up. This was in comparison to a lower inflammation - higher cognition subgroup (25% SZ, 52% BD, 62% HC), where SMI participants showed cognitive functioning at HC level with a positive clinical course. Our findings support heterogenous and transdiagnostic inflammatory-cognitive subgroups that are stable over time, and may benefit from targeted interventions.

Preconception Folic Acid and Multivitamin Supplementation for the Prevention of Neural Tube Defect: An Umbrella Review of Systematic Review and Meta-analysis.

Previous reviews explored the association between maternal use of folic acid and multivitamin supplements and risk of neural tube defect (NTD) in children, with no definitive conclusion. These reviews had produced contradictory results, and there had been no umbrella review. Therefore, the objective of this umbrella review is to combine the inconsistent data on the effect of prenatal folic acid and/or multivitamin supplementation for the prevention of NTD in offspring. Using the PRISMA guideline, PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Scopus, and Google Scholar reported that the effects of folic acid and/or multivitamin supplementation for the prevention of NTD in offspring were searched. The quality of the included studies was assessed using Assessment of Multiple Systematic Reviews (AMSTAR). A weighted inverse variance random-effects model was applied to find the pooled estimates. The subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also assessed. Ten SRM with 296,816 study participants were included. The random-effects model analysis from 10 included systematic review and meta-analysis revealed that the pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD globally is found to be 0.43 (95% CI: 0.29, 0.58) (I2 = 93.50%; p ≤0.001). In the subgroup analysis, the pooled effect was found to be 0.23 (0.09, 0.37) in folic acid group, while this estimate is 0.63 (0.53, 0.72) and 0.61 (0.46, 0.75) in groups who took multivitamin. The pooled effect of prevention of NTD was found to be 0.50 (0.34, 0.66) in SRMs aimed at occurrence prevention (primary prevention) group, while this estimate is 0.20 (-0.01, 0.41) among SRMs, which aimed at reoccurrence (secondary) prevention, and 0.61 (0.46, 0.75) among those SRMs aimed to assess the effect folic acid or multivitamin for the prevention of both occurrence and reoccurrence. The pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD was found to be 0.45 (0.03, 0.87) in SRMs of observational studies, while this estimate is 0.43 (0.32, 0.54) among SRMs of randomized controlled trials. This umbrella review of systematic review and meta-analysis found that prenatal folic acid and/or multivitamin supplementation was associated with a 57% reduction in NTD. Participants who took folic acid supplementation were associated with a slightly higher (77%) percentage of reduction in NTD compared with those who took multivitamin (37%). Reductions of 80% and 50% were observed for reoccurrence and occurrence prevention of NTD. Reductions of 57% and 55% of NTD have been found in SRM of RCTs and observational studies. This umbrella review revealed that both folic acid and multivitamin were associated with significantly lower levels of NTD in children. Considering the incorporation of those supplements in NTD prevention strategies during the preconception period is recommended. More large-scale prospective cohort and RCTs are needed to understand the protective effect of multivitamins and/or folic acid on NTD risk addressing the molecular mechanisms and to determine the optimal dose, duration, and timing of maternal multivitamin and folic acid intake for best child NTD risk reduction.

Restricted health service utilization and subsequent positive self-care behavior during the early COVID-19 pandemic in China.

The reallocation of health resources, epidemic prevention and control measures during the COVID-19 pandemic triggered widespread restricted health service utilization, some residents and patients tried positive self-care behavior to maintain their health, yet the efficacy of this intervention remains unclear. Based on the reasoned action approach (RAA) theory, this study aimed to investigate the correlation between self-care behavior and restricted health service utilization among adults in China, trying to discover the vulnerable groups and external and intrinsic factors that affect self-care behavior among Chinese adults. Data on demographics, socioeconomic, health status, and self-care behavior were collected in "The Early China COVID-19 Survey," a cross-sectional anonymous online survey of the general population in China. Self-care behavior was measured by four indicators: weight control (WC), physical activity (PA), prevention behavior (PB), and online medical consultation (OMC). The multiple linear models and binary logistic regression were used to examine whether restricted health service utilization (RHSU) is associated with self-care behaviors; also, adjusted multivariate logistic regression was used to analyze subgroup heterogeneity. In total, 8,428 adult participants completed the survey, the mean OMC score was 1.51 (SD 1.34), the mean PB score was 18.17 (SD 3.44), and the proportion of participants who engaged in WC and PA was 42.30 and 62.57%, respectively. According to the multiple regression model, the RHSU was significantly positively correlated with all four indicators of self-care (WC: OR = 1.34, p < 0.001, PA: OR = 1.34, p < 0.05, MC: OR = 1.30, p < 0.001, PB: coef = 0.16, p < 0.05). We also observed some significant differences in the intensity of this relationship by subgroup analysis, precisely, OMC (high vs. moderate vs. low infection-risk level: OR = 1.48; 1.41; 1.19, p < 0.1), PA (male vs. female: OR = 1.27;1.06; p < 0.05, high vs. Moderate and low infection-risk level: OR = 1.51; 1.17; 1.02, p < 0.05), PB (Chronic disease groups vs. no: coef = 0.46; 0.1, p < 0.05). Restricted health service utilization predicts more positive self-care behavior, and the intensity of partial correlation was significantly different in the subgroups of sex, actual infection risk level of the living area, and chronic diseases. These findings highlight the urgent demand for self-care behavior among Chinese adults during the pandemic and provide new insights for developing self-care and reducing the burden on the healthcare system in the long term.

Subgroup analyses and heterogeneity of treatment effects in randomized trials: a primer for the clinician.

To date, most randomized clinical trials in critical care report neutral overall results. However, research as to whether heterogenous responses underlie these results and give opportunity for personalized care is gaining momentum but has yet to inform clinical practice guidance. Thus, we aim to provide an overview of methodological approaches to estimating heterogeneity of treatment effects in randomized trials and conjecture about future paths to application in patient care. Despite their limitations, traditional subgroup analyses are still the most reported approach. More recent methods based on subphenotyping, risk modeling and effect modeling are still uncommonly embedded in primary reports of clinical trials but have provided useful insights in secondary analyses. However, further simulation studies and subsequent guidelines are needed to ascertain the most efficient and robust manner to validate these results for eventual use in practice. There is an increasing interest in approaches that can identify heterogeneity in treatment effects from randomized clinical trials, extending beyond traditional subgroup analyses. While prospective validation in further studies is still needed, these approaches are promising tools for design, interpretation, and implementation of clinical trial results.

ETMR-14. THE SINGLE-CELL LANDSCAPE OF PINEOBLASTOMA IDENTIFIES AN ONCOGENIC PHOTORECEPTOR PROGRAM AS A TUMORIGENIC VULNERABILITY UNIFYING DISTINCT EMBRYONAL CNS TUMOR ENTITIES

Abstract BACKGROUND Pineoblastoma (PB) is a rare and aggressive childhood brain tumor with highly variable outcomes. PB is diagnostically characterized by expression of the photoreceptor identity transcription factor CRX, while tumors can be further classified into molecular subgroups (PB-miRNA1, PB-miRNA2, PB-MYC/FOXR2, and PB-RB1), each marked by unique clinico-molecular features. However, developmental origins of PB subgroup heterogeneity and mechanisms governing malignancy remain unknown. METHODS We assembled a single-nucleus RNA-sequencing cohort (n=25) of primary PB tumors, including cases from all subgroups. A single-cell transcriptional atlas of the mouse pineal gland, covering 11 developmental stages (E11-P21), was created as a reference to map PB subgroup origins. Developmental trajectory analysis in the pineal gland showed a progression from pinealocyte progenitors to an early-, mid- and mature stage of pinealocyte differentiation. RESULTS Cross-species bioinformatics identified significant associations between PB subgroups and pinealocyte progenitors, mitotic cells expressing Crx, Otx2 and Neurod1. Single-nuclei gene regulatory networks in PB tumors identified CRX, OTX2, and NEUROD1 as master regulators of an oncogenic photoreceptor program conserved across PB subgroups. Surprisingly, this photoreceptor program was also highly expressed in retinoblastoma (RETB) and Group3 medulloblastoma (G3-MB). The molecular association between PB, RETB and G3-MB was further supported by DNA methylation and bulk RNA-seq, suggesting up-regulation of the oncogenic photoreceptor program is a unifying molecular connection of distinct CNS tumor entities. Querying this photoreceptor program across the developing pineal gland, retina, and cerebellum, identified conserved yet transient expression within each developmental lineage, suggesting the photoreceptor program may be a developmental vulnerability. In-vivo dependency assays for Otx2 and Neurod1 performed in a novel genetically engineered mouse model of the PB-RB subgroup confirmed their selective essentiality in photoreceptor-positive tumors. CONCLUSIONS Collectively, these findings uncover the photoreceptor program as a shared oncogenic dependency underlying anatomically distinct embryonal CNS tumors and provide a path towards rational clinical translation.

Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis

Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature. We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables. From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6-64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27-0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14-0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04-0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014-0·057) compared with 0·006 (0·002-0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial. Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm. None.

Can platform use patterns be an indicator of HIV-related risk and sub-group heterogeneity among men who have sex with men in Singapore: a latent class analysis.

Low-level HIV epidemic settings like Singapore face the challenge of reaching men at-risk who have less contact with programmes. We investigated patterns of meeting platform use by men seeking male sexual partners (MSM) as potential marker of risk to differentiate sub-groups for interventions. Latent Class Analysis (LCA) was applied to a survey sample of MSM recruited from bars/clubs, saunas and a smartphone application, using purposive sampling. The best-fit LCA model which identified homogeneous sub-groups with similar patterns of meeting platform was factored in multivariable regression to identify associations with risk behaviors on the pathway to HIV infection. Overall 1,141 MSM were recruited from bars/clubs (n = 426), saunas (n = 531), and online (n = 184). Five patterns emerged, reflecting salient platform use characteristics: Sauna-centric (SC; n = 413), App-centric (AC; n = 276), Multiple-platforms (MP; n = 123), Platform-inactive (PI; n = 257), and "Do not hook up" (DNH; n = 72) classes. Men in the SC and MP classes had high probabilities of using saunas to meet partners; SC were older and less likely to have disclosed their sexual orientation. The MP class had high probabilities of connecting across all platforms in addition to saunas and more likely to have disclosed their sexual orientation, than the PI class. Men in the SC and MP classes had twice the odds of reporting multiple sex partners (aORSC = 2.1; 95%CI: 1.33.2; aORMP = 2.2; 95%CI: 1.14.6). Single/non-partnered MSM and those using alcohol/drugs during sex had 1.7 (95%CI: 1.22.5) and 3.2 (95%CI: 2.05.1) the odds respectively, of reporting multiple sex partners. The SC and MP classes had higher odds of engaging in group sex while MSM using alcohol/drugs during sex had twice the odds of reporting group sex. Alcohol/drugs and group sex were independently associated with condomless sex (as was lower education). Group sex, alcohol/drugs during sex, disclosure of sexual orientation or being Singaporean/permanent resident were associated with recent testing for HIV. The five distinct risk profiles identified can help tailor differentiated HIV interventions-combined with field knowledge and other prevention-to expand HIV self-testing, Pre-Exposure Prophylaxis and other services (e.g., Mpox vaccination) to sub-groups at risk.

U.S. Fertility in Life Course Context: A Research Note on Using Census-Held Linked Administrative Records for Geographic and Sociodemographic Subgroup Estimation

Fertility is a life course process that is strongly shaped by geographic and sociodemographic subgroup contexts. In the United States, scholars face a choice: they can situate fertility in a life course perspective using panel data, which is typically representative only at the national level; or they can attend to subnational contexts using rate schedules, which do not include information on life course statuses. The method and data source we introduce here, Census-Held Linked Administrative Records for Fertility Estimation (CLAR-FE), permits both. It derives fertility histories and rate schedules from U.S. Census Bureau–held data for the nation and by state, racial and ethnic subgroups, and the important life course status of parity. We generate three types of rates for 2000–2020 at the national and state levels by race and ethnicity: age-specific rates and both unconditional and conditional parity- and age-specific rates. Where possible, we compare these rates with those produced by the National Center for Health Statistics. Our new rate schedules illuminate state and racial and ethnic differences in transitions to parenthood, providing evidence of the important subgroup heterogeneity that characterizes the United States. CLAR-FE covers nearly the entire U.S. population and is available to researchers on approved projects through the Census Bureau's Federal Statistical Research Data Centers.

Measuring SARS-CoV-2 RNA concentrations in neighborhood wastewater

Longitudinal wastewater sampling during the COVID-19 pandemic was an important aspect of disease surveillance, adding to a more complete understanding of infection dynamics and providing important data for community public health monitoring and intervention planning. This was largely accomplished by testing SARS-CoV-2 RNA concentrations in samples from municipal wastewater treatment plants (WWTPs). We evaluated the utility of testing for virus levels upstream from WWTP within the residential neighborhoods that feed into the WWTP. We propose that monitoring virus dynamics across residential neighborhoods could reveal important public health-relevant information about community sub-group heterogeneity in virus concentrations. Principal resultsVirus concentration patterns display heterogeneity within neighborhoods and between neighborhoods over time. Sewage SARS-CoV-2 RNA concentrations as measured by RT-qPCR also corresponded closely to verified COVID-19 infection counts within individual neighborhoods. More importantly, our data suggest the loss of disease-relevant public health information when sampling occurs only at the level of WWTP instead of upstream in neighborhoods. Spikes in SARS-CoV-2 RNA concentrations in neighborhoods are often masked by dilution from other neighborhoods in the WWTP samples. Major conclusionsWastewater-based epidemiology (WBE) employed at WWTP reliably detects SARS-CoV-2 in a city-sized population but provides less actionable public health information about neighborhoods experiencing greater viral infection and disease. Neighborhood sewershed sampling reveals important population-based information about local virus dynamics and improves opportunities for public health intervention. Longitudinally employed, neighborhood sewershed surveillance may provide a 3–6 day early warning of SARS-CoV-2 infection spikes and, importantly, highly specific information on subpopulations in a community particularly at higher risk at different points in time. Sampling in neighborhoods may thus provide timely and cost-saving information for targeted interventions within communities.

Effect of gender identity on the association between gender dysphoria and suicidality via appearance anxiety among transgender and gender-diverse young people: moderated mediation study.

Gender dysphoria is associated with suicidality among transgender and gender-diverse (TGD) people. Gender dysphoria also results in a stress on appearance. The objectives of this study were to examine: (a) whether appearance anxiety mediates the effect of gender dysphoria on suicidality; and (b) whether gender identity moderates the mediating effect of appearance anxiety. A total of 117 769 college and university students were recruited in this cross-sectional study from Jilin Province, China. After screening based on participants' gender identity, 2352 TGD young people (aged from 15 to 25 years) were divided into three subgroups: female to male (FTM), male to female (MTF) and non-binary. Self-report inventories measured gender dysphoria, suicidality and appearance anxiety. A structural equation model was run to examine the relationships among TGD gender identity, gender dysphoria, appearance anxiety and suicidality. Among TGD young people, gender dysphoria was significantly positively associated with suicidality (β = 0.15, 95% CI = 0.11-0.18, P < 0.001). Appearance anxiety partially mediated the association between gender dysphoria and suicidality (β = 0.07, 95% CI = 0.05-0.08, P < 0.001). Gender identity moderated the mediating effects: compared with individuals with FTM identity, among those with MTF and non-binary identities, gender dysphoria showed stronger positive effects on appearance anxiety, and appearance anxiety showed greater effects in mediating the association between gender dysphoria and suicidality. Among TGD young people, gender dysphoria is significantly associated with suicidality via appearance anxiety, with gender identity moderating the mediating effects. Diverse treatments should consider the heterogeneity of TGD subgroups, with the aim of limiting the tendency of gender dysphoria to trigger appearance anxiety, thus further buffering against the risk of suicide.

Clinical Features and Immunogenetic Risk Factors Associated With Additional Autoantibodies in Anti-Transcriptional Intermediary Factor 1γ Juvenile-Onset Dermatomyositis.

Novel autoantibody specificities including anti-CCAR1 were recently discovered in adult patients with anti-transcriptional intermediary factor (TIF1)-positive dermatomyositis (DM) and were associated with attenuated cancer emergence. The aims of the present study were to examine whether these autoantibodies occur in patients with juvenile-onset DM (JDM) and to determine their associated features. Sera from 150 patients with anti-TIF1γ autoantibody-positive JDM in a cross-sectional cohort and 90 juvenile healthy controls were assayed for anti-CCAR1, anti-C1Z1, anti-IMMT, anti-TBL1XR1, and anti-Sp4 autoantibodies. Demographics, myositis autoantibodies, clinical features, medications, outcomes, and HLA-DRB1 and HLA-DQA1 alleles were compared between those with and without these autoantibodies. Any one of the anti-TIF1γ-associated autoantibodies was present in 44 patients (29%) overall, including 25 (17%) with anti-Sp4, 22 (15%) with anti-TBL1XR1, 14 (9%) with anti-CCAR1, 2 (1%) with anti-C1Z1, and 2 (1%) with anti-IMMT autoantibodies. These anti-TIF1γ-associated autoantibodies frequently co-occurred. Patients with any of the anti-TIF1γ-associated autoantibodies had less frequent falling (34% [15] vs. 53% [56], P = 0.032) and lower peak muscle enzymes. None of the patients had cancer. Among White patients, HLA-DRB1*03 was protective against an anti-TIF1γ-associated autoantibody (odds ratio 0.20, 95% confidence interval 0.07-0.52). Autoantibodies associated with anti-TIF1γ were found in isolation and in combination among a subset of patients with JDM. Patients with these autoantibodies had less severe muscle disease and were not enriched for HLA-DRB1*03. Additional autoantibodies among patients with positive anti-TIF1γ with JDM likely contribute to the heterogeneity of the anti-TIF1γ serologic subgroup.

Racial differences in parent response to COVID schooling policies.

This paper examines whether school COVID-19 policies influenced enrollment differently by student age and race/ethnicity. Unlike much prior research, we i) analyze enrollments for virtually the entire U.S. public school population for both the 2020-2021 and 2021-2022 school years, ii) compare enrollment trends within districts in order to isolate subgroup heterogeneity from district characteristics, and iii) account for district selection into preferred learning modes. Analyzing data on over 9,000 districts that serve more than 90% of public school students in the United States, we find enrollment responses to COVID policies differed notably. We find that White enrollments declined more than Black, Hispanic, and Asian enrollments in districts that started the 2020-2021 school year virtually, but in districts that started in-person the reverse was true: Non-White enrollments declined more than White enrollments. Moreover, Black, Hispanic, and Asian families responded more than White families to higher COVID-19 death rates in the months preceding the start of the 2021 school year. In 2021-2022, enrollment differences by the previous year's learning mode persisted. Racial/ethnic differences did not vary by whether the district required masking in classrooms. These findings are consistent with the greater risk faced by communities of color during the pandemic and demonstrate an additional source of disparate impact from COVID policies.

Treatment of gouty arthritis with traditional Chinese medicine decoction: Meta-analysis, network pharmacology analysis, and molecular docking.

Previous studies have shown that traditional Chinese medicine decoction (TCMD) could ameliorate the clinical symptoms and laboratory indicators of gouty arthritis (GA) patients. However, few investigations have been conducted on the efficacy and safety of TCMD for GA, the underlying mechanism of TCMD for GA, and the relationship between the TCMD active ingredients and GA targets. Randomized controlled trials of TCMD for GA were retrieved from Chinese and English databases. Meta-analysis was conducted by Stata 17 software. Potential sources of heterogeneity were identified through subgroup analysis, meta-regression, and heterogeneity test. Publication bias was assessed by Egger's test and funnel plots. The ingredients and targets related to TCMD and GA were obtained from multiple databases, such as TCMSP and DrugBank. The protein-protein interaction network, GO and KEGG analysis was constructed using STRING and DAVID. Molecular docking and visualization of the results were completed by AutoDock and PyMOL software. Eighty-four studies were included, involving 7151 patients and 10 outcome indicators. Meta-analysis showed that, compared to routine treatment, TCMD could better reduce the incidence of adverse events and the level of laboratory indicators including blood uric acid (BUA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 1β (IL-1β), and tumor necrosis factor-α (TNF-α). In the section of network pharmacology, we retrieved 150 active ingredients and 303 target genes from the top 10 herbs in 84 studies, as well as 3082 disease targets and 195 cross targets of the herbs and GA. The top ranked ingredients, intersection targets, and signaling pathways included quercetin, kaempferol, and wogonin; AKT1, TNF, and TP53; as well as IL-17, HIF-1, and PI3K-AKT, etc. Among the 81 molecular docking results, we visualized 10 results with low binding energy, including IL1B and beta-sitosterol, MYC and beta-sitosterol, etc. TCMD could be a satisfactory complementary and alternative therapy for GA. However, it should be verified by further studies. Future research could be conducted from the following active ingredients, targets, and signal pathways, such as wogonin, sitosterol, and sitosterol; AKT1, TNF, IL6, and TP53; and IL-17, HIF-1, and PI3K-AKT signaling pathway.

Global COVID-19 vaccine acceptance level and its determinants: an umbrella review

BackgroundThe COVID-19 vaccination is essential for reducing disease burden on a worldwide scale. The success of this strategy will largely depend on how well vaccines are received. Previous reviews had produced contradictory results, and there had been no umbrella review. Therefore, the objective of this umbrella review was to combine the contradictory data regarding the COVID-19 vaccination’s global acceptance rate and its contributing factors.MethodsUsing PRISMA guideline, PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Scopus and Google Scholar which reported COVID-19 vaccine acceptance and/or its determinants were searched. The quality of the included studies was assessed using Assessment of Multiple Systematic Reviews (AMSTAR). A weighted inverse variance random-effects model was applied to find the pooled estimates. The subgroup analysis, heterogeneity, publication bias and sensitivity analysis were also assessed.ResultTwenty-two SRM with 10,433,306 study participants were included. The pooled COVID-19 vaccine acceptance rate globally is found to be 60.23 (95% CI: 58.27, 62.18). In low-income countries, the pooled level of COVID-19 vaccine acceptance was found to be 54.07(50.31, 57.83) while this magnitude is 64.32 (62.24,66.40) among studies across the globe. Higher level of education (AOR =1.96; 95% CI:1.20, 2.73), good level of knowledge (2.20; 95% CI:1.36, 3.03), favourable attitude (AOR =4.50; 95% CI:2.89, 6.12), previous history of COVID-19 infection (AOR =3.41; 95% CI:1.77, 5.06), male sex (AOR =1.62; 95% CI:1.47, 1.77), and chronic disease (AOR =1.54; 95% CI:1.18, 1.90) were predictors of COVID-19 vaccine acceptance.ConclusionThe pooled level of COVID-19 vaccine acceptance highly varied and found to be unacceptably low particularly in low-income countries. Higher level of education, good level of knowledge, favourable attitude, previous history of COVID-19, male sex, and chronic disease were factors of COVID-19 vaccine acceptance rate. A collaborative effort of stakeholders such as policymakers, and vaccine campaign program planners is needed to improve the acceptance rate of COVID-19 vaccine.

VISPUR: Visual Aids for Identifying and Interpreting Spurious Associations in Data-Driven Decisions.

Big data and machine learning tools have jointly empowered humans in making data-driven decisions. However, many of them capture empirical associations that might be spurious due to confounding factors and subgroup heterogeneity. The famous Simpson's paradox is such a phenomenon where aggregated and subgroup-level associations contradict with each other, causing cognitive confusions and difficulty in making adequate interpretations and decisions. Existing tools provide little insights for humans to locate, reason about, and prevent pitfalls of spurious association in practice. We propose VISPUR, a visual analytic system that provides a causal analysis framework and a human-centric workflow for tackling spurious associations. These include a CONFOUNDER DASHBOARD, which can automatically identify possible confounding factors, and a SUBGROUP VIEWER, which allows for the visualization and comparison of diverse subgroup patterns that likely or potentially result in a misinterpretation of causality. Additionally, weproposea REASONING STORYBOARD, which uses a flow-based approach to illustrate paradoxical phenomena, as well as an interactive DECISION DIAGNOSIS panel that helps ensure accountable decision-making. Through an expert interview and a controlled user experiment, our qualitative and quantitative results demonstrate that the proposed "de-paradox" workflow and the designed visual analytic system are effective in helping human users to identify and understand spurious associations, as well as to make accountable causal decisions.

Resilience after adversity: an umbrella review of adversity protective factors and resilience-promoting interventions.

Resilience is the dynamic adaptive process of maintaining or recovering mental health from stressors, such as trauma, challenging life circumstances, critical transitions, or physical illnesses. Resilience after adversity can be fostered through protective factors and the implementation of interventions that promote resilience. Hence, it is essential to investigate both protective and vulnerable factors to reduce the negative effects of unfavorable life events and increase resilience through positive risk-response interventions. To assess the effect of previous adversity, protecting factors, and resilience-promoting interventions to possess resilience after adversity in a global context. The study included English language articles sourced from PubMed, Embase, Scopus, Web of Sciences, the Cochrane Database of Systematic Reviews, Scopus, and Google Scholar published before 15 April 2024. These articles reported the effect of adversity, protecting factors, and/or resilience-promoting interventions to possess resilience after adversity in a global context without a population age limitation. The quality of the included studies was assessed using the Assessment of Multiple Systematic Reviews. A weighted inverse-variance random-effects model was applied to find the pooled estimates. The subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also assessed. A total of 44 articles (n = 556,920 participants) were included in this umbrella review. From the random-effects model analysis, the pooled effect of adversity on the development of resilience was 0.25 (p < 0.001). The pooled effects of adversity-protective factors and resilience-promoting interventions after adversity were 0.31 (p < 0.001) and 0.42 (p < 0.001), respectively. The pooled effects of specific adversity protective factors were 0.26, 0.09, 0.05, 0.34, 0.23, and 0.43 for the availability of support, cognitive ability, community cohesion, positive self-perception, religious involvement, and self-regulation, respectively. The pooled effects of specific resilience-promoting interventions were 0.30, 0.21, 0.51, and 0.52 for cognitive behavior therapy (CBT) interventions, mindfulness-based interventions, mixed interventions, and resilience-promoting interventions, respectively. The findings of this umbrella review revealed that people who experienced early adversity can develop resilience later in life. The study highlights the need to consider adversity protective factors, such as availability of support (family, friends, and school), cognitive ability, community cohesion, positive self-perception, religious involvement, and self-regulation, and resilience-promoting interventions, including CBT interventions, mindfulness-based interventions, and mixed interventions, to enhance resilience promotion programs.