Complex effects of sequence variants on lipid levels and coronary artery disease.

Many sequence variants have additive effects on blood lipid levels and, through that, on the risk of coronary artery disease (CAD). We show that variants also have non-additive effects and interact to affect lipid levels as well as affecting variance and correlations. Variance and correlation effects are often signatures of epistasis or gene-environmental interactions. These complex effects can translate into CAD risk. For example, Trp154Ter in FUT2 protects against CAD among subjects with the A1 blood group, whereas it associates with greater risk of CAD in others. His48Arg in ADH1B interacts with alcohol consumption to affect lipid levels and CAD. The effect of variants in TM6SF2 on blood lipids is greatest among those who never eat oily fish but absent from those who often do. This work demonstrates that variants that affect variance of quantitative traits can allow for the discovery of epistasis and interactions of variants with the environment.

Accurate Prediction of Rat Acute Oral Toxicity and Reference Dose for Thousands of Polycyclic Aromatic Hydrocarbon Derivatives Based on Chemometric QSAR and Machine Learning.

Acute oral toxicity is currently not available for most polycyclic aromatic hydrocarbons (PAHs), especially their derivatives, because it is cost-prohibitive to experimentally determine all of them. Here, quantitative structure-activity relationship (QSAR) models using machine learning (ML) for predicting the toxicity of PAH derivatives were developed, based on oral toxicity data points of 788 individual substances of rats. Both the individual ML algorithm gradient boosting regression trees (GBRT) and the stacking ML algorithm (extreme gradient boosting + GBRT + random forest regression) provided the best prediction results with satisfactory determination coefficients for both cross-validation and the test set. It was found that those PAH derivatives with fewer polar hydrogens, more large-sized atoms, more branches, and lower polarizability have higher toxicity. Software based on the optimal ML-QSAR model was successfully developed to expand the application potential of the developed model, obtaining reliable prediction of pLD50 values and reference doses for 6893 external PAH derivatives. Among these chemicals, 472 were identified as moderately or highly toxic; 10 out of them had clear environment detection or use records. The findings provide valuable insights into the toxicity of PAHs and their derivatives, offering a standard platform for effectively evaluating chemical toxicity using ML-QSAR models.

A systematic comparison of additive and interaction approaches to modeling the effects of syndemic problems on HIV outcomes in South Africa.

Much of the research on the effects of syndemics on HIV outcomes has utilized an additive approach. However, interaction effects may better account for syndemic synergy than an additive approach, but it remains difficult to specify interaction effects without empirical guidance. We sought to systematically compare additive and interaction effects approaches to modeling the effects of syndemic problems on antiretroviral therapy (ART) using empirically specified interaction terms. Participants were 194 people with HIV (PWH) who received HIV care in Khayelitsha, South Africa. In a series of linear regression models, we examined ten syndemic problems: depression, alcohol use, intimate partner violence (IPV), post-traumatic stress, social anxiety, substance use, food insecurity, poverty, housing instability, and structural barriers to care. Depression, substance use, and food insecurity were selected for interaction terms based on a prior network analysis, which found these problems to be most central. The additive models did not produce statistically significant findings. However, the interaction effects models yielded significant interaction terms in both the full model and a parsimonious model. There was a statistically significant effect of the interaction between depression and food insecurity on ART adherence (b = 0.04, Robust SE = 0.02, 95%CI [0.001-0.08], p = .012). This pattern of results was replicated in the parsimonious model. Findings suggest that when feasible, interaction effects approaches may be a helpful syndemic modeling technique. Results may inform future intervention targets, such as depression and food insecurity, and the importance of addressing both structural and psychosocial syndemic problems.

Strong Bases and beyond: The Prominent Contribution of Neutral Push-Pull Organic Molecules towards Superbases in the Gas Phase.

In this review, the principles of gas-phase proton basicity measurements and theoretical calculations are recalled as a reminder of how the basicity PA/GB scale, based on Brønsted-Lowry theory, was constructed in the gas-phase (PA-proton affinity and/or GB-gas-phase basicity in the enthalpy and Gibbs energy scale, respectively). The origins of exceptionally strong gas-phase basicity of some organic nitrogen bases containing N-sp3 (amines), N-sp2 (imines, amidines, guanidines, polyguanides, phosphazenes), and N-sp (nitriles) are rationalized. In particular, the role of push-pull nitrogen bases in the development of the gas-phase basicity in the superbasicity region is emphasized. Some reasons for the difficulties in measurements for poly-functional nitrogen bases are highlighted. Various structural phenomena being in relation with gas-phase acid-base equilibria that should be considered in quantum-chemical calculations of PA/GB parameters are discussed. The preparation methods for strong organic push-pull bases containing a N-sp2 site of protonation are briefly reviewed. Finally, recent trends in research on neutral organic superbases, leaning toward catalytic and other remarkable applications, are underlined.

Risk Factors and Moderators of Intimate Partner Violence Victimization Versus Perpetration Among Women in Spain.

Bidirectional intimate partner violence (IPV) appears highly prevalent, but the extant literature, which has been dominated by work in North America, has not adequately accounted for how victimization overlaps with perpetration and how potential resources may interact with risk factors. A community sample of Spanish women completed measures of IPV approval, mental health risk factors (psychological distress and problematic substance use), and interpersonal resources (partner and social satisfaction). Using Mplus accounting for victimization and perpetration overlap, findings indicate that greater psychological distress and substance use were associated with IPV perpetration, and lower IPV approval was linked to victimization. Stronger partner satisfaction did not serve a buffering role but rather interacted to increase IPV perpetration; low social support was associated with victimization and exacerbated risk of perpetration.

Coupled effect of load weights and belt use on male shoulder pressure redistribution.

Shoulder pressure redistribution is jointly affected by backpack loads and belt support. However, the combined effect of both factors has rarely been fully evaluated. Here, we studied the coupled effect of backpack loads and belt support on shoulder pressure redistribution. All twenty-eight healthy male subjects underwent eight loading conditions with both chest and hip belts fastened (CH) and unfastened (CON) in four conditions where the backpack weighed 7.5, 15, 22.5, and 30% of body weight (BW). Shoulder pressure distribution was quantified through a pressure-sensing vest mat. The results showed that using the hip belt and chest belt was effective in relieving the high pressure in the lateral clavicle and medial trapezius region and strengthening the load-bearing capacity of shoulder. However, the assistance in pressure relief of using belt was weakened when load increased to 30% BW. This study also showed that the belt use can be effective in improving pressure asymmetry on both sides.

Compression caused by loads may result in shoulder injuries. An in-depth analysis of shoulder pressure distribution is necessary. This study showed that the hip-belt and chest-belt use was effective in relieving the high pressure in the lateral clavicle region and medial trapezius region and strengthening the load-bearing capacity of shoulder.

The contribution of functional HNF1A variants and polygenic susceptibility to risk of type 2 diabetes in ancestrally diverse populations.

AIMS/HYPOTHESIS: We examined the contribution of rare HNF1A variants to type 2 diabetes risk and age of diagnosis, and the extent to which their impact is affected by overall genetic susceptibility, across three ancestry groups. METHODS: Using exome sequencing data of 160,615 individuals of the UK Biobank and 18,797 individuals of the BioMe Biobank, we identified 746 carriers of rare functional HNF1A variants (minor allele frequency ≤1%), of which 507 carry variants in the functional domains. We calculated polygenic risk scores (PRSs) based on genome-wide association study summary statistics for type 2 diabetes, and examined the association of HNF1A variants and PRS with risk of type 2 diabetes and age of diagnosis. We also tested whether the PRS affects the association between HNF1A variants and type 2 diabetes risk by including an interaction term. RESULTS: Rare HNF1A variants that are predicted to impair protein function are associated with increased risk of type 2 diabetes in individuals of European ancestry (OR 1.46, p=0.049), particularly when the variants are located in the functional domains (OR 1.89, p=0.002). No association was observed for individuals of African ancestry (OR 1.10, p=0.60) or Hispanic-Latino ancestry (OR 1.00, p=1.00). Rare functional HNF1A variants were associated with an earlier age at diagnosis in the Hispanic-Latino population (ß=-5.0 years, p=0.03), and this association was marginally more pronounced for variants in the functional domains (ß=-5.59 years, p=0.03). No associations were observed for other ancestries (African ancestry ß=-2.7 years, p=0.13; European ancestry ß=-3.5 years, p=0.20). A higher PRS was associated with increased odds of type 2 diabetes in all ancestries (OR 1.61-2.11, p<10-5) and an earlier age at diagnosis in individuals of African ancestry (ß=-1.4 years, p=3.7 × 10-6) and Hispanic-Latino ancestry (ß=-2.4 years, p<2 × 10-16). Furthermore, a higher PRS exacerbated the effect of the functional HNF1A variants on type 2 diabetes in the European ancestry population (pinteraction=0.037). CONCLUSIONS/INTERPRETATION: We show that rare functional HNF1A variants, in particular those located in the functional domains, increase the risk of type 2 diabetes, at least among individuals of European ancestry. Their effect is even more pronounced in individuals with a high polygenic susceptibility. Our analyses highlight the importance of the location of functional variants within a gene and an individual's overall polygenic susceptibility, and emphasise the need for more genetic data in non-European populations.

Bayesian interaction selection model for multimodal neuroimaging data analysis.

Multimodality or multiconstruct data arise increasingly in functional neuroimaging studies to characterize brain activity under different cognitive states. Relying on those high-resolution imaging collections, it is of great interest to identify predictive imaging markers and intermodality interactions with respect to behavior outcomes. Currently, most of the existing variable selection models do not consider predictive effects from interactions, and the desired higher-order terms can only be included in the predictive mechanism following a two-step procedure, suffering from potential misspecification. In this paper, we propose a unified Bayesian prior model to simultaneously identify main effect features and intermodality interactions within the same inference platform in the presence of high-dimensional data. To accommodate the brain topological information and correlation between modalities, our prior is designed by compiling the intermediate selection status of sequential partitions in light of the data structure and brain anatomical architecture, so that we can improve posterior inference and enhance biological plausibility. Through extensive simulations, we show the superiority of our approach in main and interaction effects selection, and prediction under multimodality data. Applying the method to the Adolescent Brain Cognitive Development (ABCD) study, we characterize the brain functional underpinnings with respect to general cognitive ability under different memory load conditions.

An efficient model-free approach to interaction screening for high dimensional data.

An innovated model-free interaction screening procedure called the MCVIS is proposed for high dimensional data analysis. Specifically, we adopt the introduced MCV index for quantifying the importance of an interaction effect among predictors. Our proposed method is fully nonparametric and is capable of successfully selecting interactions even if the signal of parental main effects is weak. The MCVIS procedure has many distinctive features: (i) it can work with discrete, categorical and continuous covariates; (ii) it can deal with both categorical and continuous response, even handle the missing response; (iii) it is robust for heavy-tailed distributions, thus well accommodates heterogeneity typically caused by high dimensionality; (iv) it enjoys the sure screening and ranking consistency properties, therefore achieves dimension reduction without information loss. In another respect, computational feasibility is a top concern in high dimensional data analysis, by transforming our MCV into several variants, the MCVIS procedure is simple and fast to implement. Extensive numerical experiments and comparisons confirm the effectiveness and wide applicability of our MCVIS procedure. We further illustrate the proposed methodology by empirical study of two real datasets. Supplementary materials are available online.

Improving hospital quality risk-adjustment models using interactions identified by hierarchical group lasso regularisation.

BACKGROUND: Risk-adjustment (RA) models are used to account for severity of illness in comparing patient outcomes across hospitals. Researchers specify covariates as main effects, but they often ignore interactions or use stratification to account for effect modification, despite limitations due to rare events and sparse data. Three Agency for Healthcare Research and Quality (AHRQ) hospital-level Quality Indicators currently use stratified models, but their variable performance and limited interpretability motivated the design of better models. METHODS: We analysed patient discharge de-identified data from 14 State Inpatient Databases, AHRQ Healthcare Cost and Utilization Project, California Department of Health Care Access and Information, and New York State Department of Health. We used hierarchical group lasso regularisation (HGLR) to identify first-order interactions in several AHRQ inpatient quality indicators (IQI) - IQI 09 (Pancreatic Resection Mortality Rate), IQI 11 (Abdominal Aortic Aneurysm Repair Mortality Rate), and Patient Safety Indicator 14 (Postoperative Wound Dehiscence Rate). These models were compared with stratum-specific and composite main effects models with covariates selected by least absolute shrinkage and selection operator (LASSO). RESULTS: HGLR identified clinically meaningful interactions for all models. Synergistic IQI 11 interactions, such as between hypertension and respiratory failure, suggest patients who merit special attention in perioperative care. Antagonistic IQI 11 interactions, such as between shock and chronic comorbidities, illustrate that naïve main effects models overestimate risk in key subpopulations. Interactions for PSI 14 suggest key subpopulations for whom the risk of wound dehiscence is similar between open and laparoscopic approaches, whereas laparoscopic approach is safer for other groups. Model performance was similar or superior for composite models with HGLR-selected features, compared to those with LASSO-selected features. CONCLUSIONS: In this application to high-profile, high-stakes risk-adjustment models, HGLR selected interactions that maintained or improved model performance in populations with heterogeneous risk, while identifying clinically important interactions. The HGLR package is scalable to handle a large number of covariates and their interactions and is customisable to use multiple CPU cores to reduce analysis time. The HGLR method will allow scholars to avoid creating stratified models on sparse data, improve model calibration, and reduce bias. Future work involves testing using other combinations of risk factors, such as vital signs and laboratory values. Our study focuses on a real-world problem of considerable importance to hospitals and policy-makers who must use RA models for statutorily mandated public reporting and payment programmes.

Wind Energy Harvesting with Vertically Aligned Piezoelectric Inverted Flags.

Wind-energy-harvesting generators based on inverted flag architecture are an attractive option to replace batteries in low-power wireless electronic devices and deploy-and-forget distributed sensors. This study examines two important aspects that have been overlooked in previous research: the interaction between an inverted flag and a neighboring solid boundary and the interaction among multiple contiguous inverted flags arranged in a vertical row. Systematic tests have been carried out with metal-only 'baseline' flags as well as a 'harvester' variant, i.e., the baseline metal flag covered with PVDF (polyvinylidene difluoride) piezoelectric polymer elements. In each case, dynamic response and power generation were measured and assessed. For baseline metal flags, the same qualitative trend is observed when the flag approaches an obstacle, whether this is a wall or another flag. As the gap distance reduces, the wind speed range at which flapping occurs gradually shrinks and shifts towards lower velocities. The increased damping introduced by attaching PVDF elements to the baseline metal flags led to a considerable narrowing of the flapping wind speed range, and the wall-to-flag or flag-to-flag interaction led to a power reduction of up to one order of magnitude compared to single flags. The present findings highlight the strong dependence of the power output on the flapping frequency, which decreases when the flag approaches a wall or other flags mounted onto the same pole. Minimum flag-to-flag and flag-to-wall spacing values are suggested for practical applications to avoid power reduction in multi-flag arrangements (2-3H and 1-2H respectively, where H is flag height).

Association of insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD in obese children. / èƒ°å²›ç´ ä¿¡å·é€šè·¯ç›¸å ³åŸºå› å¤šæ€æ€§å’ŒåŸºå› -åŸºå› äº¤äº’ä½œç”¨ä¸Žè‚¥èƒ–å„¿ç«¥MAFLDçš„å ³è”.

OBJECTIVES: Insulin signaling pathway plays an important role in metabolic associated fatty liver disease (MAFLD), however, the association between polymorphisms of genes related to insulin signaling pathway and MAFLD remains unclear. This study aims to investigate the association between insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD susceptibility in obese children so as to provide scientific basis for further study of genetic mechanism. METHODS: A total of 502 obese children with MAFLD who admitted to Hunan Provincial Children's Hospital from September 2019 to October 2021, were recruited as a case group, and 421 obese children with non-MAFLD admitted during the same period were recruited as a control group. Socio-demographic information, preterm birth history, eating habits, and exercise status of the subjects were collected by inquiry survey, and anthropometric information was collected by physical measurement. At the same time, 2 mL of venous blood was collected to extract DNA, and the polymorphism of insulin signaling pathway-related genes (5 representative candidate genes, 12 variants) was detected. Multivariate Logistic regression analysis was used to investigate the association between insulin signaling pathway-related gene polymorphisms and MAFLD in obese children. RESULTS: After adjusting for confounder factors, INS rs3842748 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 1.749 (1.053 to 2.905), 1.909 (1.115 to 3.267), 1.862 (1.098 to 3.157), all P<0.05]; INS rs3842752 was significantly associated with the risk of MAFLD in obese children in heterozygous and dominant models [OR and 95% CI 1.736 (1.028 to 2.932), 1.700 (1.015 to 2.846), all P<0.05]. NR1H3 rs3758674 was significantly correlated with the risk of MAFLD in obese children in allele model [OR and 95% CI 0.716 (0.514 to 0.997), P<0.05]. SREBP-1c rs2297508 was significantly associated with the risk of MAFLD in obese children in allele and dominant models [OR and 95% CI 0.772 (0.602 to 0.991) and 0.743 (0.557 to 0.991), all P<0.05]. SREBP-1c rs8066560 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 0.759 (0.589 to 0.980), 0.733 (0.541 to 0.992), 0.727 (0.543 to 0.974), all P<0.05]. NR1H3 rs3758674 mutant C and SREBP-1c rs2297508 mutant G had interaction in the development of MAFLD in obese children [OR and 95% CI 0.407 (0.173 to 0.954), P<0.05]. CONCLUSIONS: The INS, NR1H3, and SREBP-1c gene polymorphisms in the insulin signaling pathway are associated with the susceptibility of MAFLD in obese children, but the functions and mechanisms of these genes need to be further studied.

Sex-Dependent Effects of the APOE ɛ4 Allele on Behavioral Traits and White Matter Structures in Young Adults.

The APOE ɛ4 allele is associated with a risk of Alzheimer's disease in the elderly, with the association being pronounced in females. Conversely, findings of the effects of the APOE ɛ4 allele in young adults are mixed. Here, we investigated the sex-genotype interaction effects of the APOE ɛ4 allele on cognitive functions as well as brain structures among 1258 young adults. After adjusting for multiple comparisons, there were significant effects of the interaction between sex and the number of APOE ɛ4 allele on some speed tasks (e.g., simple processing speed tasks and the reverse Stroop task) as well as on regional white matter volume (rWMV). The observed sex-genotype interaction conferred better cognitive performance and greater rWMV in the anterior frontal and precentral white matter areas in females having more APOE ɛ4 alleles and reduced rWMV in the same areas in male having more APOE ɛ4 alleles. These findings support the long-debated antagonistic pleiotropic effects of the APOE ɛ4 allele in females.

Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.

BACKGROUND: MTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations. METHODS: A case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association. RESULTS: Mothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13-2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57-3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01-2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38-4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01-2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02-2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure. CONCLUSIONS: Maternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings. TRIAL REGISTRATION: Registration number: ChiCTR1800016635 .

Parent-perceived neighbourhood environment, parenting practices and preschool-aged children physical activity and screen time: a cross-sectional study of two culturally and geographically diverse cities.

BACKGROUND: Preschool-aged children's physical activity (PA) and screen time (ST) are important health-related behaviours likely influenced by PA opportunities, parental perceptions of neighbourhood safety and parenting practices pertaining to PA and ST. How these factors interact to impact on young children's PA and ST, and whether their effects are generalisable across cultures and geographical location is not known. This study addressed these knowledge gaps by conducting pooled analyses of comparable data from two culturally and geographically diverse samples - Chinese parent-child dyads from an ultra-dense city (Hong Kong, China) and Latino parent-child dyads from a low-density city (Houston, USA). METHODS: The analytical sample consisted of 164 Hong Kong Chinese and 84 US Latino parent-child dyads with data on socio-demographic characteristics, parent-perceived neighbourhood destinations and facilities for children's PA, physical and social safety-related neighbourhood attributes, PA-related parenting practices and child's ST and accelerometer-assessed PA. Generalised linear models with robust standard errors accounting for neighbourhood-level clustering were used to estimate associations and interaction effects. RESULTS: Hong Kong Chinese children accumulated less PA than US Latino children, although the latter had more ST. Hong Kong Chinese parents reported more parenting practices promoting inactivity. Neighbourhood PA opportunities were positively related to children's PA only if parental perceptions of neighbourhood safety were favourable, and the associations of physical neighbourhood environment characteristics with children's PA and ST depended on PA-related parenting practices. Community cohesion was positively related to children's PA and negatively related to ST, while parental promotion of ST was positively associated with children's ST. Correlates of children's PA and ST did not differ by city. CONCLUSIONS: The substantial differences in activity patterns between Hong Kong Chinese and US Latino preschool-aged children observed in this study are likely due to a combination of cultural and built environmental factors. However, the fact that no between-city differences in correlates of PA and ST were detected indicates that both populations of children are equally affected by parent-perceived neighbourhood environmental characteristics and parenting practices. Overall, this study highlights the importance of considering how various individual-, home- and neighbourhood physical and social factors interact to influence young children's health-promoting activity levels.

Does gender matter to promote mental health through community engagement among older adults?

Objectives: Community engagement is critical for healthy aging. However, how gender plays a role in mental health promotion of late life is less understood. The study objectives were to examine the association between community engagement and mental health and the effect of gender on this association in older adults.Methods: A door-to-door interviewer-administered survey was conducted with 497 older adults in a public housing town in Singapore. The survey used measures of General Health Questionnaire (GHQ-12), Community Integration Measure (CIM), FRAIL Index, Lubben Social Network, and community participation. Multiple regressions were conducted for psychological distress and social dysfunction, assessed by GHQ-12. After testing the main effects, the moderating effects of gender were explored in the regression models.Results: None of the demographic characteristics, except gender, was associated with psychological distress; men reported poorer mental health than women. In regressions, female, community attachment (assessed by CIM), and participation were associated with decreased psychological distress; social networks and community participation were associated with decreased social dysfunction. Interaction effects of gender and community participation were found in psychological distress, not social dysfunction. The reduction of psychological distress by community engagement was higher among males than females.Conclusions: The findings suggest that, besides the importance of community engagement on mental health among older adults, greater efforts should be placed on the development of gender-tailored community interventions for older adults to maximize its benefits.

A two-way additive model with unknown group-specific interactions applied to gene expression data.

We propose a two-way additive model with group-specific interactions, where the group information is unknown. We treat the group membership as latent information and propose an EM algorithm for estimation. With a single observation matrix and under the situation of diverging row and column numbers, we rigorously establish the estimation consistency and asymptotic normality of our estimator. Extensive simulation studies are conducted to demonstrate the finite sample performance. We apply the model to the triple negative breast cancer (TNBC) gene expression data and provide a new way to classify patients into different subtypes. Our analysis detects the potential genes that may be associated with TNBC.

Heterogeneous Effects of Intergenerational Social Mobility: An Improved Method and New Evidence.

Intergenerational social mobility has immense implications for individuals' well-being, attitudes, and behaviors. However, previous methods may be unreliable for estimating heterogeneous mobility effects, especially in the presence of moderate- or large-scale intergenerational mobility. We propose an improved method, called the "mobility contrast model" (MCM). Using simulation evidence, we demonstrated that the MCM is more flexible and reliable for estimating and testing heterogeneous mobility effects, and the results are robust to the scale of intergenerational mobility. We revisited the debate about the effect of mobility on fertility and analyzed data from the 1962 Occupational Changes in a Generation Study (OCG-1) and more recent data from the 1974 through 2018 General Social Survey (GSS) using both previous models and the MCM. The MCM suggested a small association between fertility and occupational mobility in the GSS data but substantial and heterogeneous educational mobility effects on fertility in the OCG-1 and the GSS. Such effects were difficult to pinpoint using previous methods because mobility effects of different magnitudes and opposite directions among mobility groups may cancel out. The new method can be extended to investigate the effect of intergenerational mobility across multiple generations and other research areas including immigrant assimilation and heterogamy.

Effects of daily mean temperature and other meteorological variables on bacillary dysentery in Beijing-Tianjin-Hebei region, China.

BACKGROUND: Although previous studies have shown that meteorological factors such as temperature are related to the incidence of bacillary dysentery (BD), researches about the non-linear and interaction effect among meteorological variables remain limited. The objective of this study was to analyze the effects of temperature and other meteorological variables on BD in Beijing-Tianjin-Hebei region, which is a high-risk area for BD distribution. METHODS: Our study was based on the daily-scale data of BD cases and meteorological variables from 2014 to 2019, using generalized additive model (GAM) to explore the relationship between meteorological variables and BD cases and distributed lag non-linear model (DLNM) to analyze the lag and cumulative effects. The interaction effects and stratified analysis were developed by the GAM. RESULTS: A total of 147,001 cases were reported from 2014 to 2019. The relationship between temperature and BD was approximately liner above 0 °C, but the turning point of total temperature effect was 10 °C. Results of DLNM indicated that the effect of high temperature was significant on lag 5d and lag 6d, and the lag effect showed that each 5 °C rise caused a 3% [Relative risk (RR) = 1.03, 95% Confidence interval (CI): 1.02-1.05] increase in BD cases. The cumulative BD cases delayed by 7 days increased by 31% for each 5 °C rise in temperature above 10 °C (RR = 1.31, 95% CI: 1.30-1.33). The interaction effects and stratified analysis manifested that the incidence of BD was highest in hot and humid climates. CONCLUSIONS: This study suggests that temperature can significantly affect the incidence of BD, and its effect can be enhanced by humidity and precipitation, which means that the hot and humid environment positively increases the incidence of BD.

Association of periconceptional folate supplements and FOLR1 and FOLR2 gene polymorphisms with risk of congenital heart disease in offspring: A hospital-based case-control study. / æ¯äº²å›´å­•æœŸæœç”¨å¶é ¸åŠFOLR1和FOLR2åŸºå› å¤šæ€æ€§ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— å ³è”çš„ç— ä¾‹å¯¹ç §ç ”ç©¶.

OBJECTIVES: Maternal periconceptional folic acid supplement is by far the most effective primary prevention strategy to reduce the incidence of congenital heart disease (CHD) in offspring. It was revealed that the underlying mechanisms are complex, including a combination of genetic and environmental factors. The purpose of this study is to investigate the association between periconceptional folic acid supplement, the genetic polymorphisms of maternal folic acid receptor 1 gene (FOLR1) and folic acid receptor 2 gene (FOLR2) and the impact of their interaction on the risk of CHD in offspring, and to provide epidemiological evidence for individualized folic acid dosing in hygienic counseling. METHODS: A case-control study on 569 mothers of CHD infants and 652 mothers of health controls was performed. The interesting points were periconceptional folate supplements, single nucleotide polymorphisms (SNPs) of maternal FOLR1 gene and FOLR2 gene. RESULTS: Mothers who took folate in the periconceptional period were observed a decreased risk of CHD [adjusted odds ratio (aOR)=0.58, 95% CI 0.35 to 0.95]. Our study also found that polymorphisms of maternal FOLR1 gene at rs2071010 (G/A vs G/G: aOR=0.67, 95% CI 0.47 to 0.96) and FOLR2 gene at rs514933 (T/C vs T/T: aOR=0.60, 95% CI 0.43 to 0.84; C/C vs T/T: aOR=0.55, 95% CI 0.33 to 0.90; the dominant model: T/C+ C/C vs T/T: aOR=0.59, 95% CI 0.43 to 0.81; and the addictive model: C/C vs T/C vs T/T: aOR=0.70, 95% CI 0.56 to 0.88) were significantly associated with lower risk of CHD [all P<0.05, false discovery rate P value (FDR_P)<0.1]. Besides, significant interaction between periconceptional folate supplements and rs2071010 G→A (aOR=0.59, 95% CI 0.41-0.86) and rs514933 T→C (aOR=0.52, 95% CI 0.37 to 0.74) on CHD risk were observed (all P<0.05, FDR_P<0.1). CONCLUSIONS: Periconceptional folate supplements, polymorphisms of FOLR1 gene and FOLR2 gene and their interactions are significantly associated with risk of CHD. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.