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The Relationship Between Total Serum Cholesterol and Hypertensive Outcomes Among Women 50-60 Years Old: Findings From the Framingham Heart Study
Get PDFObjective: To assess whether total serum cholesterol (TSC) among middle-aged women is associated with subsequent hypertension while accounting for potential confounders.
Methods: A sample of 853 adults who identify as women, aged 50-60, from the Framingham Heart Study 1948-1972 cohort was selected for this study. Participants\u27 TSC was measured at baseline, and they were followed for 24 years for cardiovascular disease outcomes or death. The outcome of interest in this study was hypertension. A multivariable logistic regression was used to analyze the relationship between TSC and hypertension while controlling for age, glucose, systolic, and diastolic blood pressure.
Results: Compared to participants with normal (\u3c 200mg/dL) TSC at baseline, participants with borderline high (200-239 mg/dL) and high (\u3e239 mg/dL) TSC had higher odds of having hypertension during follow-up after controlling for age and systolic blood pressure (1.39 CI: 0.61-3.18 and 1.24 CI: 0.58-2.68, respectively); however, these associations were not statistically significant. Conclusion: This study found no significant association between TSC at baseline and hypertension during the follow-up period among women aged 50-60
Integrative Genomic and Transcriptomic Analysis Reveals Targetable Vulnerabilities in Angioimmunoblastic T-Cell Lymphoma
Get PDFNodal follicular helper T-cell (TFH) lymphoma of the angioimmunoblastic (AITL) subtype has a dismal prognosis. Using whole-exome sequencing (n = 124), transcriptomic (n = 78), and methylation (n = 40) analysis, we identified recurrent mutations in known epigenetic drivers (TET2, DNMT3A, IDH2R172) and novel ones (TET3, KMT2D). TET2, IDH2R172, DNMT3A co-mutated AITLs had poor prognosis (p \u3c 0.0001). Genes regulating T-cell receptor (TCR) signaling (CD28, PLCG1, VAV1, FYN) or activation (RHOAG17V) or regulators of the PI3K-pathway (PIK(3)C members, PTEN, PHLPP1, PHLPP2) were mutated. CD28 mutation/fusion was associated with poor prognosis (p = 0.02). WES of purified, neoplastic T-cell (CD3+PD1+) demonstrated high concordance with whole tumor biopsies and validated the presence of TET2 and DNMT3A in tumor and non-lymphoid cells, but other mutations (CD28, RHOAG17V, IDH2R172, PLCG1) in neoplastic cells. Integrated DNA-methylation and mRNA expression analysis revealed epigenetic alterations in genes regulating TCR, cytokines, PI3K-signaling, and apoptosis. RNA-seq analysis identified fusion transcripts regulating TCR-activation (8%), revealed a restricted TCR-repertoire (α = 87%, β = 72%), and showed the presence of Epstein-Barr virus transcriptome (73%). GEP demonstrated the association of B-cells or dendritic cells in the tumor milieu with prognosis (p \u3c 0.01). RNA-seq and WES analysis of 12 AITL-patient-derived-xenografts (PDX) showed that bi-allelic TET2 and DNMT3A mutations or sub-clonal mutations (PLCG1, PHLPP2) propagated in sequential passages, and gene signatures related to TFH and TCM (central-memory) were well-maintained through passages. Gene expression signatures associated with late PDX passages (3rd-5th) were enriched with proliferation and metabolic reprogramming-related genes and predicted prognosis in an independent AITL series. Low PHLPP2 mRNA expression predicted poor prognosis (p = 0.05) and engineered PHLPP2 or TET2 loss in CD4+ T-cells showed enhanced PI(3)K activation, thus uncovering a therapeutic target for clinical trials
Improving Diagnostic Precision in Thyroid Pathology by Synergistic Use of AI and Molecular Markers
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Pediatric Intracranial Non-germinomatous Germ Cell Tumor With Extracranial Extension: A Case Report
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Impact of Associations With Travel Distance on Staging at Initial Presentation and Survival in Oral and Oropharyngeal Cancer
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