BackgroundMammalian species exhibit a wide range of lifespans. To date, a robust and dynamic molecular readout of these lifespan differences has not yet been identified. Recent studies have established the existence of ageing-associated differentially methylated positions (aDMPs) in human and mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesise that aDMPs are pan-mammalian and are a dynamic molecular readout of lifespan variation among different mammalian species.ResultsA large-scale integrated analysis of aDMPs in six different mammals reveals a strong negative relationship between rate of change of methylation levels at aDMPs and lifespan. This relationship also holds when comparing two different dog breeds with known differences in lifespans. In an ageing cohort of aneuploid mice carrying a complete copy of human chromosome 21, aDMPs accumulate far more rapidly than is seen in human tissues, revealing that DNA methylation at aDMP sites is largely shaped by the nuclear trans-environment and represents a robust molecular readout of the ageing cellular milieu.ConclusionsOverall, we define the first dynamic molecular readout of lifespan differences among mammalian species and propose that aDMPs will be an invaluable molecular tool for future evolutionary and mechanistic studies aimed at understanding the biological factors that determine lifespan in mammals.Electronic supplementary materialThe online version of this article (10.1186/s13059-018-1397-1) contains supplementary material, which is available to authorized users.
BackgroundAn absent word of a word y of length n is a word that does not occur in y. It is a minimal absent word if all its proper factors occur in y. Minimal absent words have been computed in genomes of organisms from all domains of life; their computation also provides a fast alternative for measuring approximation in sequence comparison. There exists an -time and -space algorithm for computing all minimal absent words on a fixed-sized alphabet based on the construction of suffix automata (Crochemore et al., 1998). No implementation of this algorithm is publicly available. There also exists an -time and -space algorithm for the same problem based on the construction of suffix arrays (Pinho et al., 2009). An implementation of this algorithm was also provided by the authors and is currently the fastest available.ResultsOur contribution in this article is twofold: first, we bridge this unpleasant gap by presenting an -time and -space algorithm for computing all minimal absent words based on the construction of suffix arrays; and second, we provide the respective implementation of this algorithm. Experimental results, using real and synthetic data, show that this implementation outperforms the one by Pinho et al. The open-source code of our implementation is freely available at http://github.com/solonas13/maw.ConclusionsClassical notions for sequence comparison are increasingly being replaced by other similarity measures that refer to the composition of sequences in terms of their constituent patterns. One such measure is the minimal absent words. In this article, we present a new linear-time and linear-space algorithm for the computation of minimal absent words based on the suffix array.
Aims Patients with cardiovascular disease appear particularly susceptible to severe COVID‐19 disease, but the impact of COVID‐19 infection on patients with heart failure (HF) is not known. This study aimed to quantify the impact of COVID‐19 infection on mortality in hospitalized patients known to have HF. Methods and results We undertook a retrospective analysis of all patients admitted with a pre‐existing diagnosis of HF between 1 March and 6 May 2020 to our unit. We assessed the impact of concomitant COVID‐19 infection on in‐hospital mortality, incidence of acute kidney injury, and myocardial injury. One hundred and thirty‐four HF patients were hospitalized, 40 (29.9%) with concomitant COVID‐19 infection. Those with COVID‐19 infection had a significantly increased in‐hospital mortality {50.0% vs. 10.6%; relative risk [RR] 4.70 [95% confidence interval (CI) 2.42–9.12], P < 0.001} and were more likely to develop acute kidney injury [45% vs. 24.5%; RR 1.84 (95% CI 1.12–3.01), P = 0.02], have evidence of myocardial injury [57.5% vs. 31.9%; RR 1.81 (95% CI 1.21–2.68), P < 0.01], and be treated for a superadded bacterial infection [55% vs. 32.5%; RR 1.67 (95% CI 1.12–2.49), P = 0.01]. Conclusions Patients with HF admitted to hospital with concomitant COVID‐19 infection have a very poor prognosis. This study highlights the need to regard patients with HF as a high‐risk group to be shielded to reduce the risks of COVID‐19 infection.
BackgroundThe new category of heart failure (HF), Heart Failure with mid range Ejection Fraction (HFmrEF) has recently been proposed with recent publications reporting that HFmrEF represents a transitional phase. The aim of this study was to determine the prevalence and clinical characteristics of patients with HFmrEF and to establish what proportion of patients transitioned to other types of HF, and how this affected clinical outcomes.Methods and resultsPatients were diagnosed with HF according to the 2016 ESC guidelines. Clinical outcomes and variables were recorded for all consecutive in-patients referred to the heart failure service. In total, 677 patients with new HF were identified; 25.6% with HFpEF, 21% with HFmrEF and 53.5% with HFrEF. While clinical characteristics and prognostic factors of HFmrEF were intermediate between HFrEF and HFpEF, HFmrEF patients had the best outcome, with higher mortality in the HFrEF population (p 0.02) and higher HF rehospitalisation rates in the HFpEF population (p < 0.01).38.7% of the HFmrEF patients transitioned (56.4% to HFpEF and 43.6% to HFrEF) with fewest deaths in the patients that transitioned to HFpEF (p 0.04), and fewest HF readmissions in the patients that remained as HFmrEF (<0.01)ConclusionHFmrEF patients had the best outcomes, compared to high rates of mortality seen in patients with HFrEF and high rates of HF readmissions seen in patients with HFpEF. Only 1/3 of HFmrEF patients transitioned during follow up, with the lowest mortality seen in patients transitioning to HFpEF.
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