The association between fibrinogen levels and severity of coronary artery disease and long-term prognosis following percutaneous coronary intervention in patients with type 2 diabetes mellitus

BackgroundFibrinogen is a potential risk factor for the prognosis of CAD and is associated with the complexity of CAD. There is limited research specifically investigating the predictive role of fibrinogen in determining the severity of CAD among patients with T2DM, as well as its impact on the prognosis following PCI.MethodsThe study included 675 T2DM patients who underwent PCI at the Third People’s Hospital of Chengdu between April 27, 2018, and February 5, 2021, with 540 of them remaining after exclusions. The complexity of CAD was assessed using the SYNTAX score. The primary endpoint of the study was the incidence of MACCEs.ResultsAfter adjusting for multiple confounding factors, fibrinogen remained a significant independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 1.184, 95% CI 1.022-1.373, P = 0.025). Additionally, a dose-response relationship between fibrinogen and the risk of complicated CAD was observed (SYNTAX score > 22; nonlinear P = 0.0043). The area under the receiver operating characteristic curve(AUROC) of fibrinogen for predicting mid/high SYNTAX score was 0.610 (95% CI 0.567–0.651, P = 0.0002). The high fibrinogen group (fibrinogen > 3.79 g/L) had a higher incidence of calcified lesions and an elevated trend of more multivessel disease and chronic total occlusion. A total of 116 patients (21.5%) experienced MACCEs during the median follow-up time of 18.5 months. After adjustment, multivariate Cox regression analysis confirmed that fibrinogen (HR, 1.138; 95% CI 1.010-1.284, P = 0.034) remained a significant independent risk factor for MACCEs. The AUROC of fibrinogen for predicting MACCEs was 0.609 (95% CI 0.566-0.650, P = 0.0002). Individuals with high fibrinogen levels (fibrinogen > 4.28 g/L) had a higher incidence of acute myocardial infarction (P < 0.001), MACCEs (P < 0.001), all-cause death (P < 0.001), stroke (P = 0.030), and cardiac death (P = 0.002). Kaplan-Meier analysis revealed a higher incidence of MACCEs in the high fibrinogen group (Log-Rank test: P < 0.001).ConclusionsElevated fibrinogen levels were associated with increased coronary anatomical complexity (as quantified by the SYNTAX score) and a higher incidence of MACCEs after PCI in patients with T2DM

Data Interpreter: An LLM Agent For Data Science

Large Language Model (LLM)-based agents have demonstrated remarkable effectiveness. However, their performance can be compromised in data science scenarios that require real-time data adjustment, expertise in optimization due to complex dependencies among various tasks, and the ability to identify logical errors for precise reasoning. In this study, we introduce the Data Interpreter, a solution designed to solve with code that emphasizes three pivotal techniques to augment problem-solving in data science: 1) dynamic planning with hierarchical graph structures for real-time data adaptability;2) tool integration dynamically to enhance code proficiency during execution, enriching the requisite expertise;3) logical inconsistency identification in feedback, and efficiency enhancement through experience recording. We evaluate the Data Interpreter on various data science and real-world tasks. Compared to open-source baselines, it demonstrated superior performance, exhibiting significant improvements in machine learning tasks, increasing from 0.86 to 0.95. Additionally, it showed a 26% increase in the MATH dataset and a remarkable 112% improvement in open-ended tasks. The solution will be released at https://github.com/geekan/MetaGPT

A Syndemic of Psychosocial Problems Places the MSM (Men Who Have Sex with Men) Population at Greater Risk of HIV Infection

Background: The MSM (Men who have sex with men) population suffers from very high rates of concurrent psychosocial problems. Together, these problems comprise a syndemic that increases the risk of HIV infection for this community. The precise mechanisms through which this syndemic can raise the likelihood of HIV infection warrant further exploration. Methodology/Principal Findings: A total of 522 MSM were enrolled via a multiframe sampling approach and were asked to report psychosocial problems, risky sexual behaviors and HIV test results. A count of psychosocial health problems was calculated to test the additive relationship of these factors on HIV risk. Adjusting analysis and restriction analysis were used to determine a proposed intermediate pathway. Psychosocial health problems are highly concurrent and intercorrelated among urban MSM. Greater numbers of health problems are significantly and positively associated with HIV infection, which is mediated, at least partially, by risky sexual behaviors. Conclusions/Significance: MSM experience concurrent psychosocial health problems that correlate with HIV infection in this community. We recommend the development of coping strategies for this population to deal with these psychosocial problems, both in prevention research and health policy

Problematic Internet Use in High School Students in Guangdong Province, China

BACKGROUND: Problematic Internet Use (PIU) is a growing problem in Chinese adolescents. There are many risk factors for PIU, which are found at school and at home. This study was designed to investigate the prevalence of PIU and to investigate the potential risk factors for PIU among high school students in China. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was conducted. A total of 14,296 high school students were surveyed in four cities in Guangdong province. Problematic Internet Use was assessed by the 20-item Young Internet Addiction Test (YIAT). Information was also collected on demographics, family and school-related factors and Internet usage patterns. Of the 14,296 students, 12,446 were Internet users. Of those, 12.2% (1,515) were identified as problematic Internet users (PIUs). Generalized mixed-model regression revealed that there was no gender difference between PIUs and non-PIUs. High study-related stress, having social friends, poor relations with teachers and students and conflictive family relationships were risk factors for PIU. Students who spent more time on-line were more likely to develop PIU. The habits of and purposes for Internet usage were diverse, influencing the susceptibility to PIU. CONCLUSIONS/SIGNIFICANCE: PIU is common among high school students, and risk factors are found at home and at school. Teachers and parents should pay close attention to these risk factors. Effective measures are needed to prevent the spread of this problem

Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease.

BACKGROUND: The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS: Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS: We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P=4.2×10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P=4.0×10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P=0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P=0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P=2.0×10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P=2.5×10(-7)). CONCLUSIONS: We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease. (Funded by the National Institutes of Health and others.).Supported by a career development award from the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH) (K08HL114642 to Dr. Stitziel) and by the Foundation for Barnes–Jewish Hospital. Dr. Peloso is supported by the National Heart, Lung, and Blood Institute of the NIH (award number K01HL125751). Dr. Kathiresan is supported by a Research Scholar award from the Massachusetts General Hospital, the Donovan Family Foundation, grants from the NIH (R01HL107816 and R01HL127564), a grant from Fondation Leducq, and an investigator-initiated grant from Merck. Dr. Merlini was supported by a grant from the Italian Ministry of Health (RFPS-2007-3-644382). Drs. Ardissino and Marziliano were supported by Regione Emilia Romagna Area 1 Grants. Drs. Farrall and Watkins acknowledge the support of the Wellcome Trust core award (090532/Z/09/Z), the British Heart Foundation (BHF) Centre of Research Excellence. Dr. Schick is supported in part by a grant from the National Cancer Institute (R25CA094880). Dr. Goel acknowledges EU FP7 & Wellcome Trust Institutional strategic support fund. Dr. Deloukas’s work forms part of the research themes contributing to the translational research portfolio of Barts Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute for Health Research (NIHR). Drs. Webb and Samani are funded by the British Heart Foundation, and Dr. Samani is an NIHR Senior Investigator. Dr. Masca was supported by the NIHR Leicester Cardiovascular Biomedical Research Unit (BRU), and this work forms part of the portfolio of research supported by the BRU. Dr. Won was supported by a postdoctoral award from the American Heart Association (15POST23280019). Dr. McCarthy is a Wellcome Trust Senior Investigator (098381) and an NIHR Senior Investigator. Dr. Danesh is a British Heart Foundation Professor, European Research Council Senior Investigator, and NIHR Senior Investigator. Drs. Erdmann, Webb, Samani, and Schunkert are supported by the FP7 European Union project CVgenes@ target (261123) and the Fondation Leducq (CADgenomics, 12CVD02). Drs. Erdmann and Schunkert are also supported by the German Federal Ministry of Education and Research e:Med program (e:AtheroSysMed and sysINFLAME), and Deutsche Forschungsgemeinschaft cluster of excellence “Inflammation at Interfaces” and SFB 1123. Dr. Kessler received a DZHK Rotation Grant. The analysis was funded, in part, by a Programme Grant from the BHF (RG/14/5/30893 to Dr. Deloukas). Additional funding is listed in the Supplementary Appendix.This is the author accepted manuscript. The final version is available from the Massachusetts Medical Society via http://dx.doi.org/10.1056/NEJMoa150765

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis

In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.Peer reviewe

Associations between depression risk, bullying and current smoking among Chinese adolescents: Modulated by gender.

This school-based study aimed to investigate the prevalence of being at risk for depression, bullying behavior, and current smoking among Chinese adolescents in order to explore gender differences in the vulnerability of adolescents with these behaviors to develop a smoking habit. A total of 35,893 high school students sampled from high schools in eighteen cities in China participated in the study from 2011 to 2012. Overall, the prevalence of current smoking was estimated at 6.4%. In total, 1.7% (618) of the participants admitted to bullying others, 5.8% (2071) reported being bullied, 3.5% (1269) were involved in both bullying others and being bullied, and 5.6% (2017) were at high risk for depression. Logistic regression analysis indicated that among girls, with high depression risk, bullying others, being bullied, and both bullying others and being bullied were independently and positively associated with current smoking habits, while the final results among boys showed that bullying others and both bullying others and being bullied were independently associated with an increased risk of current smoking. School-based prevention programs are highly recommended, and we should focus on high-risk students, particularly girls with high risk of depression or involved in school bullying and boys who are involved in school bullying.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Peroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivo

Abstract Background PPAR agonists are often used in HBV infected patients with metabolic disorders. However, as liver-enriched transcriptional factors, PPARs would activate HBV replication. Risks exsit in such patients. This study aimed to assess the influence of commonly used synthetic PPAR agonists on hepatitis B virus (HBV) transcription, replication and expression through HBV replicative mouse models, providing information for physicians to make necessary monitoring and therapeutic adjustment when HBV infected patients receive PPAR agonists treatment. Methods The HBV replicative mouse model was established by hydrodynamic injection of HBV replicative plasmid and the mice were divided into four groups and treated daily for 3 days with saline, PPAR pan-agonist (bezafibrate), PPARα agonist (fenofibrate) and PPARγ agonist (rosiglitazone) respectively. Their serum samples were collected for ECLIA analysis of HBsAg and HBeAg and real-time PCR analysis of Serum HBV DNA. The liver samples were collected for DNA (Southern) filter hybridization of HBV replication intermediates, real-time PCR analysis of HBV mRNA and immunohistochemistry (IHC) analysis of hepatic HBcAg. The alternation of viral transcription, replication and expression were compared in these groups. Result Serum HBsAg, HBeAg and HBV DNA were significantly elevated after PPAR agonist treatment. So did the viral replication intermediates in mouse livers. HBV mRNA was also significantly increased by these PPAR agonists, implying that PPAR agonists activate HBV replication at transcription level. Moreover, hepatic HBcAg expression in mouse livers with PPAR agonist treatment was elevated as well. Conclusion Our in vivo study proved that synthetic PPAR agonists bezafibrate, fenofibrate and rosiglitazone would increase HBV replication. It suggested that when HBV infected patients were treated with PPARs agonists because of metabolic diseases, HBV viral load should be monitored and regimens may need to be adjusted, an antiviral therapy may be added