Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction.

Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model.

A Modified Debiased Inverse-Variance Weighted Estimator in Two-Sample Summary-Data Mendelian Randomization.

Mendelian randomization uses genetic variants as instrumental variables to estimate the causal effect of exposure on outcome from observational data. A common challenge in Mendelian randomization is that many genetic variants are only modestly or even weakly associated with the exposure of interest, a setting known as many weak instruments. Conventional methods, such as the popular inverse-variance weighted (IVW) estimator, could be heavily biased toward zero when the instrument strength is weak.

9-HODE associates with thalamic atrophy and predicts white matter damage in multiple sclerosis.

Background: Multiple sclerosis (MS) is characterized by extensive tissue damage leading to a range of complex symptoms, including physical disability and cognitive dysfunction. Recent work has indicated the clinical relevance of bioactive lipid mediators (LMs), which are known to orchestrate inflammation and its resolution and are deregulated in MS. However, it is unknown whether LM profiles relate to white matter (WM) damage.

The effectiveness of a positive psychological intervention for promoting preschool teachers' well-being and professional competence: EASP intervention program.

The present study investigated the effectiveness of the Early Advancement in Social-Emotional Health and Positivity (EASP) program, a positive psychological intervention promoting preschool teachers' well-being and the motivational aspect of professional competence. Participants were 273 in-service preschool teachers (M = 34.56 years, SD = 9.

Inflammation-induced TRPV4 channels exacerbate blood-brain barrier dysfunction in multiple sclerosis.

Background: Blood-brain barrier (BBB) dysfunction and immune cell migration into the central nervous system (CNS) are pathogenic drivers of multiple sclerosis (MS). Ways to reinstate BBB function and subsequently limit neuroinflammation present promising strategies to restrict disease progression. However, to date, the molecular players directing BBB impairment in MS remain poorly understood.

Can a multicomponent positive psychological intervention promote well-being in parents of young children? A randomized controlled trial study in Hong Kong.

The present research examined the effects of an Early Advancement in Social-Emotional Health and Positivity (EASP) multicomponent positive psychological intervention on parents' well-being in Hong Kong. Participants were parents of young children (N = 120; M  = 37.19 years, SD = 4.

Well-Being Profiles of Pre-service Teachers in Hong Kong: Associations with Teachers' Self-Efficacy During the COVID-19 Pandemic.

The present study aims to (1) identify the profiles of subjective well-being (SWB) and psychological well-being (PWB) in a sample of pre-service teachers during the second wave of the COVID-19 pandemic in Hong Kong, and (2) explore how different profiles are linked with teachers' self-efficacy. Participants were 291 pre-service teachers ( = 21.295, = 2.

Robust association tests for quantitative traits on the X chromosome.

The genome-wide association study is an elementary tool to assess the genetic contribution to complex human traits. However, such association tests are mainly proposed for autosomes, and less attention has been given to methods for identifying loci on the X chromosome due to their distinct biological features. In addition, the existing association tests for quantitative traits on the X chromosome either fail to incorporate the information of males or only detect variance heterogeneity.

Prospering in the midst of the COVID-19 pandemic: The effects of PROSPER-based intervention on psychological outcomes among preschool teachers.

The growing concerns regarding the risks of transmitting the COVID-19 virus have intensified the job-related stressors commonly encountered by teachers in various cultural contexts. Evidence shows how the COVID-19 crisis has negatively impacted teachers' mental health outcomes such as stress, depression, and quality of life, which highlights the significance of designing psychological programs to boost teachers' well-being. This study examined the effects of a well-being intervention based on the Positivity, Relationship, Outcomes, Strength, Purpose, Engagement, and Resilience (PROSPER) framework on well-being outcomes among 76 in-service teachers (M = 26.

A novel penalized inverse-variance weighted estimator for Mendelian randomization with applications to COVID-19 outcomes.

Mendelian randomization utilizes genetic variants as instrumental variables (IVs) to estimate the causal effect of an exposure variable on an outcome of interest even in the presence of unmeasured confounders. However, the popular inverse-variance weighted (IVW) estimator could be biased in the presence of weak IVs, a common challenge in MR studies. In this article, we develop a novel penalized inverse-variance weighted (pIVW) estimator, which adjusts the original IVW estimator to account for the weak IV issue by using a penalization approach to prevent the denominator of the pIVW estimator from being close to zero.

Oncostatin M triggers brain inflammation by compromising blood-brain barrier integrity.

Oncostatin M (OSM) is an IL-6 family member which exerts neuroprotective and remyelination-promoting effects after damage to the central nervous system (CNS). However, the role of OSM in neuro-inflammation is poorly understood. Here, we investigated OSM's role in pathological events important for the neuro-inflammatory disorder multiple sclerosis (MS).

BEXCIS: Bayesian methods for estimating the degree of the skewness of X chromosome inactivation.

Background: X chromosome inactivation (XCI) is an epigenetic phenomenon that one of two X chromosomes in females is transcriptionally silenced during early embryonic development. Skewed XCI has been reported to be associated with some X-linked diseases. There have been several methods measuring the degree of the skewness of XCI.

Parental self-efficacy: Examining its mediating and reciprocally predictive roles in supportive emotion socialization.

This longitudinal study examined the associations between child negative affect, parental self-efficacy (PSE), and parents' approaches to the provision of supportive socialization. It also investigated the bidirectionality between PSE, problem-focus socialization, and emotion-focus socialization across two time points separated by one year. Participants were 757 Hong Kong Chinese parents (47.

MRCIP: a robust Mendelian randomization method accounting for correlated and idiosyncratic pleiotropy.

Mendelian randomization (MR) is a powerful instrumental variable (IV) method for estimating the causal effect of an exposure on an outcome of interest even in the presence of unmeasured confounding by using genetic variants as IVs. However, the correlated and idiosyncratic pleiotropy phenomena in the human genome will lead to biased estimation of causal effects if they are not properly accounted for. In this article, we develop a novel MR approach named MRCIP to account for correlated and idiosyncratic pleiotropy simultaneously.

Penalized Fieller's confidence interval for the ratio of bivariate normal means.

Constructing a confidence interval for the ratio of bivariate normal means is a classical problem in statistics. Several methods have been proposed in the literature. The Fieller method is known as an exact method, but can produce an unbounded confidence interval if the denominator of the ratio is not significantly deviated from 0; while the delta and some numeric methods are all bounded, they are only first-order correct.

Mathematics, executive functioning, and visual-spatial skills in Chinese kindergarten children: Examining the bidirectionality.

This study examined the bidirectional relationships among Chinese children's mathematics, executive functioning, and visual-spatial skills during their transition from kindergarten to primary school. Participants were 172 Cantonese-speaking Hong Kong children (mean age at Time 1 = 62.75 months; 88 male) and their parents.

Evaluation of marker selection methods and statistical models for chronological age prediction based on DNA methylation.

In forensic investigation, retrieving biological information from DNA evidence is a promising field of interest. One of the applications is on the estimation of the age of the donor based on DNA methylation. A large number of studies focused on age prediction using the 450 K Human Methylation Beadchip.

A robust test for X-chromosome genetic association accounting for X-chromosome inactivation and imprinting.

The X chromosome is known to play an important role in many sex-specific diseases. However, only a few single-nucleotide polymorphisms on the X chromosome have been found to be associated with diseases. Compared to the autosomes, conducting association tests on the X chromosome is more intractable due to the difference in the number of X chromosomes between females and males.

X-chromosome genetic association test incorporating X-chromosome inactivation and imprinting effects.

Studies have shown that many complex diseases are sex-determined. When conducting genetic association studies on X-chromosome, there are two important epigenetic factors which should be considered simultaneously: X-chromosome inactivation and genomic imprinting. Currently, there have been several association tests accounting for the information on X-chromosome inactivation.

Two Powerful Tests for Parent-of-Origin Effects at Quantitative Trait Loci on the X Chromosome.

Parent-of-origin effects, which describe an occurrence where the expression of a gene depends on its parental origin, are an important phenomenon in epigenetics. Statistical methods for detecting parent-of-origin effects on autosomes have been investigated for 20 years, but the development of statistical methods for detecting parent-of-origin effects on the X chromosome is relatively new. In the literature, a class of Q-XPAT-type tests are the only tests for the parent-of-origin effects for quantitative traits on the X chromosome.

A statistical measure for the skewness of X chromosome inactivation based on case-control design.

Background: Skewed X chromosome inactivation (XCI), which is a non-random process, is frequently observed in both healthy and affected females. Furthermore, skewed XCI has been reported to be related to many X-linked diseases. However, no statistical method is available in the literature to measure the degree of the skewness of XCI for case-control design.

A robust and powerful test for case-control genetic association study on X chromosome.

Hundreds of genome-wide association studies were conducted to map the disease genes on autosomes in human beings. It is known that many complex diseases are sex-determined and X chromosome is expected to play an important role. However, only a few single-nucleotide polymorphisms on X chromosome were found to be significantly associated with the diseases under study.

Evaluation of parentage testing accuracy of child trafficking cases: Combining the exclusion probability and likelihood ratio approaches.

The Chinese government established a national anti-trafficking DNA database in 2009 to help reunite trafficked children with their families. The database collects DNA information from missing children's parents, trafficked and homeless children, then conducts parentage testing using 18 or more loci to find matched pairs. This article evaluates the matching accuracy of parentage testing in child-trafficking cases, under both Hardy-Weinberg equilibrium and population substructure.