Additional file 1: Figure S1. of Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70Â years

A comparison of droplet digital PCR and QPCR for CMV viral load. (A): Classic quantitative PCR (Q-PCR) was calibrated using a series dilution of plasmid standards for CMV. The Ct value was correlated with copy number in each dilution. (B): The serially diluted standard plasmids were then assessed by ddPCR and the absolute copy number obtained was correlated with the expected CMV copy number. (C): Q-PCR was used to assess CMV load within the 44 samples of monocyte DNA from healthy donors. The CMV copy number of the 13 donors that were positive by both methods (Q-PCR and ddPCR) were then correlated. (PDF 381 kb

Proteomics-Based Strategies To Identify Proteins Relevant to Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL), a malignant B-cell disorder, is characterized by a heterogeneous clinical course. Two-dimensional nano liquid chromatography (2D-nano–LC) coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) (LC–MALDI) was used to perform qualitative and quantitative analysis on cellular extracts from 12 primary CLL samples. We identified 728 proteins and quantified 655 proteins using isobaric tag-labeled extracts. Four strategies were used to identify disease-related proteins. First, we integrated our CLL proteome with published gene expression data of normal B-cells and CLL cells to highlight proteins with preferential expression in the transcriptome of CLL. Second, as CLL’s outcome is heterogeneous, our quantitative proteomic data were used to indicate heterogeneously expressed proteins. Third, we used the quantitative data to identify proteins with differential abundance in poor prognosis CLL samples. Fourth, hierarchical cluster analysis was applied to identify hidden patterns of protein expression. These strategies identified 63 proteins, and 4 were investigated in a CLL cohort (39 patients). Thyroid hormone receptor-associated protein 3, T-cell leukemia/lymphoma protein 1A, and S100A8 were associated with high-risk CLL. Myosin-9 exhibited reduced expression in CLL samples from high-risk patients. This study shows the usefulness of proteomic approaches, combined with transcriptomics, to identify disease-related proteins

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure.People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window).Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p Background Methods Findings Interpretation Funding</p