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Polygenic prediction via Bayesian regression and continuous shrinkage priors
Polygenic risk scores (PRS) have shown promise in predicting human complex traits and diseases. Here, we present PRS-CS, a polygenic prediction method that infers posterior effect sizes of single nucleotide polymorphisms (SNPs) using genome-wide association summary statistics and an external linkage disequilibrium (LD) reference panel. PRS-CS utilizes a high-dimensional Bayesian regression framework, and is distinct from previous work by placing a continuous shrinkage (CS) prior on SNP effect sizes, which is robust to varying genetic architectures, provides substantial computational advantages, and enables multivariate modeling of local LD patterns. Simulation studies using data from the UK Biobank show that PRS-CS outperforms existing methods across a wide range of genetic architectures, especially when the training sample size is large. We apply PRS-CS to predict six common complex diseases and six quantitative traits in the Partners HealthCare Biobank, and further demonstrate the improvement of PRS-CS in prediction accuracy over alternative methods.
Polygenic risk scores (PRS) have the potential to predict complex diseases and traits from genetic data. Here, Ge et al. develop PRS-CS which uses a Bayesian regression framework, continuous shrinkage (CS) priors and an external LD reference panel for polygenic prediction of binary and quantitative traits from GWAS summary statistics.
Journal Article
Secretome from estrogen-responding human placenta-derived mesenchymal stem cells rescues ovarian function and circadian rhythm in mice with cyclophosphamide-induced primary ovarian insufficiency
Background
Primary ovarian insufficiency (POI) is an early decline in ovarian function that leads to ovarian failure. Conventional treatments for POI are inadequate, and treatments based on mesenchymal stem cells (MSCs) have emerged as an option. However, the lack of consideration of the estrogen niche in ovarian tissue significantly reduces the therapeutic efficacy, with an unclear mechanism in the MSCs in POI treatment. Furthermore, the disruption of circadian rhythm associated with POI has not been previously addressed.
Methods
Conditioned medium (CM) and estradiol-conditioned medium (E2-CM) were generated from estrogen receptor positive MSCs (ER
+
pcMSCs). Chemotherapy-induced POI models were established using C57BL/6 mice (in vivo) and KGN cells (in vitro) treated with cyclophosphamide (CTX) or 4-hydroperoxycyclophosphamide (4-OOH-CP). Gene/protein expressions were detected using RT-qPCR, Western blotting, and immunohistochemistry assays. Locomotor activity was monitored for behavioral circadian rhythmicity. Cytokine arrays and miRNA analysis were conducted to analyze potential factors within CM/E2-CM.
Results
The secretome of ER
+
pcMSCs (CM and E2-CM) significantly reduced the CTX-induced defects in ovarian folliculogenesis and circadian rhythm. CM/E2-CM also reduced granulosa cell apoptosis and rescued angiogenesis in POI ovarian tissues. E2-CM had a more favorable effect than the CM. Notably, ER
+
pcMSC secretome restored CTX-induced circadian rhythm defects, including the gene expressions associated with the ovarian circadian clock (e.g.,
Rora, E4bp4, Rev-erbα
,
Per2
and
Dbp
) and locomotor activity. Additionally, the cytokine array analysis revealed a significant increase in cytokines and growth factors associated with immunomodulation and angiogenesis, including angiogenin. Neutralizing the angiogenin in CM/E2-CM significantly reduced its ability to promote HUVEC tube formation in vitro. Exosomal miRNA analysis revealed the miRNAs involved in targeting the genes associated with POI rescue (
PTEN
and
PDCD4
)
,
apoptosis (caspase-3, BIM), estrogen synthesis (
CYP19A1
), ovarian clock regulation (
E4BP4
,
REV-ERBα
) and fibrosis (
COL1A1
).
Conclusion
This study is the first to demonstrate that, in considering the estrogen niche in ovarian tissue, an estrogen-priming ER
+
pcMSC secretome achieved ovarian regeneration and restored the circadian rhythm in a CTX-induced POI mouse model. The potential factors involved include angiogenin and exosomal miRNAs in the ER
+
pcMSC secretome. These findings offer insights into potential stem cell therapies for chemotherapy-induced POI and circadian rhythm disruption.
Journal Article
Chinese Cinderella : the true story of an unwanted daughter
The daughter of a wealthy Hong Kong businessman describes her very difficult childhood and the psychological abuse she suffered at the hands of her stepmother.
BOOK
Deep learning-based endoscopic anatomy classification: an accelerated approach for data preparation and model validation
BackgroundPhotodocumentation during endoscopy procedures is one of the indicators for endoscopy performance quality; however, this indicator is difficult to measure and audit in the endoscopy unit. Emerging artificial intelligence technology may solve this problem, which requires a large amount of material for model development. We developed a deep learning-based endoscopic anatomy classification system through convolutional neural networks with an accelerated data preparation approach.Patients and methodsWe retrospectively collected 8,041 images from esophagogastroduodenoscopy (EGD) procedures and labeled them using two experts for nine anatomical locations of the upper gastrointestinal tract. A base model for EGD image multiclass classification was first developed, and an additional 6,091 images were enrolled and classified by the base model. A total of 5,963 images were manually confirmed and added to develop the subsequent enhanced model. Additional internal and external endoscopy image datasets were used to test the model performance.ResultsThe base model achieved total accuracy of 96.29%. For the enhanced model, the total accuracy was 96.64%. The overall accuracy improved with the enhanced model compared with the base model for the internal test dataset without narrowband images (93.05% vs. 91.25%, p < 0.01) or with narrowband images (92.74% vs. 90.46%, p < 0.01). The total accuracy was 92.56% of the enhanced model on the external test dataset.ConclusionsWe constructed a deep learning-based model with an accelerated approach that can be used for quality control in endoscopy units. The model was also validated with both internal and external datasets with high accuracy.
Journal Article
When the storm comes
Mali, Jonesey, Fara and Petey are reluctantly gathered in the library. They're not friends and they each have reasons they don't want to be there. As the rain starts, they do not bond as a group. Mali does not engage, Jonesy takes offence, Petey ridicules the others, Fara is silent, and their teacher Ms Devine is distracted. Outside, the bad weather steadily worsens. Soon they are trapped in the school, and pulling together may be the only way out when the storm comes.
CHILDBOOK
Methamphetamine Use Associated with Non-adherence to Antiretroviral Treatment in Men Who Have Sex with Men
Methamphetamine is a prevalent recreational drug among men who have sex with men (MSM) living with HIV and could cause the cognitive impairment and memory loss. However, studies on the association between methamphetamine use and adherence to antiretroviral treatment (ART) are limited and had inconsistent findings. This study aimed to determine the impact of methamphetamine use on adherence to ART among MSM living with HIV. From December 2018 to October 2019, MSM living with HIV were recruited (
N
= 351) and non-adherence to ART was defined as a Medication Adherence Report Scale score of <23. Overall, 16.0% of the participants reported methamphetamine use in the prior three months and 13.4% of the participants had non-adherence to ART. The proportion of non-adherence to ART among HIV-positive MSM were 28.6% and 10.5% with and without methamphetamine use, respectively. After controlling for demographics, illicit drug use, and co-morbidities, methamphetamine use during the prior three months was associated with a higher risk of non-adherence to ART (adjusted odds ratio = 3.08; 95% confidence intervals: 1.24–7.69). Compared with HIV-positive MSM with non-adherence to ART, HIV-positive MSM with good adherence to ART had a higher CD4 counts and were more likely to achieve an undetectable viral load. Since poor adherence to ART is associated with an increased HIV viral load and the risk of HIV transmission to others, our study suggests that it is imperative to screen HIV-positive patients for methamphetamine use and to provide effective therapy to reduce methamphetamine use and the associated non-adherence to ART.
Journal Article
Smart wearable devices as a psychological intervention for healthy lifestyle and quality of life
Purpose
Creating a healthy lifestyle is important across different life stages. Commercial smart wearable devices are an innovative and interesting approach as an early psychological intervention for modifying health-related behaviors. Therefore, the purpose of this study was to explore the effects of smart wearable devices on health-promoting lifestyles and quality of life.
Methods
The study design was a three-parallel randomized controlled trial with a 3-month intervention. Two commercial smart wearable devices (smartwatches and smart bracelets) with different levels of complicated functions were applied as a psychological intervention in comparison with a smartphone app as the control group. Participants were healthy young adults with a median age of 26 years. Outcome measurements were conducted by self-administered questionnaires. Chi-square tests and ANOVA were performed for testing the difference of participants at baseline, and generalized estimating equations were performed for testing the effect of the intervention.
Results
At the beginning, 81 participants were recruited and 73 participants completed the study. Results of a healthy lifestyle demonstrated significant group effects of exercise and a significant effect of the interaction for self-actualization and stress management in the experimental group with a smartwatch (Self-actualization: MD = 0.35[− 0.10,0.80]; Exercise: MD = 0.21[− 0.33 0.75]; Stress management: MD = 0.36[− 0.04,0.76]) by comparing with only using mobile app (Self-actualization: MD = − 0.03[− 0.25,0.18]; Exercise: MD = − 0.12[− 0.38,0.14]; Stress management, MD = − 0.28[− 0.55,0.00]). The significant effect of group-by-time interaction for self-actualization was found in the experimental group with a smart bracelet (MD = 0.05[− 0.30,0.20]) by comparing with the control group. The GEE-adjusted model indicated significant effects of the interaction on the comprehensive, physical, and mental quality of life in the experimental group with the smartwatch (Comprehensive: MD = 0.24[− 0.04,0.52]; Physical: MD = 0.67[0.26,1.09]; Mental: MD = 0.72[0.29,1.16]) by comparing with the control group (Comprehensive: MD = − 1.57[− 2.55, − 0.59]; Physical: MD = 0.25[0.00,0.50]; Mental: MD = 0.08[− 0.11,0.27]).
Conclusion
From a psychological perspective, smart wearable devices have potential benefits of shaping a healthy lifestyle and improving the quality of life. Enhancing the utility of commercial well-designed smart wearable devices is an innovative and effective strategy for promoting public health.
Journal Article