Gutenberg Open Science

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ZeitschriftenaufsatzAccess status: Open Access ,
Global and regional DNA methylation patterns in heart failure : a case-control analysis
(2026)
Krolevets, Mykhailo
;
ten Cate, Vincent
;
Prochaska, Jürgen H.
;
Schulz, Andreas
;
Rapp, Steffen
Background: Heart failure (HF) is a syndrome of heterogeneous aetiology and multiple exposomal causes. The role of DNA methylation (DNAm) changes in symptomatic HF and its phenotypes is unclear. This work addresses global and regional DNAm patterns and epigenetic ageing in HF. Methods: Patients with HF were included from the MyoVasc Study, an investigator-initiated prospective cohort study. Individuals without HF were included from a population-based Gutenberg Health Study. DNAm was measured using the Illumina Infinium MethylationEPIC assay. Epigenetic ageing was calculated using GrimAge and Hannum methylation clocks. Findings: Global DNAm patterns were analysed across 767,735 CpG sites in a dataset of N = 2155 individuals. HF was associated with an increase of epigenetic age by on average 19.0 [11.0; 29.0] years and with a global decrease in methylation across all phenotypes (Odds ratio [OR]: 1.33 [95% CI: 1.17–1.51], p < 0.0001). Epigenetic clocks strongly predicted incident worsening of HF and mortality. Methylation differences varied across chromosomes and were most pronounced in shore (OR: 1.41 [95% CI: 1.25–1.61], p < 0.0001) region. CpG island methylation had a weaker association with HF status (p = 0.0122), but strongly interacted with methylation in adjacent regions. Interpretation: This work highlights accelerated ageing, global and regional methylation patterns as key features associated with the presence, severity, and consequences of HF. HF-related methylation exhibited diverse patterns across chromosomes, the genome, and gene regions. CpG islands lacked strong discriminatory capacity, but their potential regulatory role is a novel finding. Funding: SHARP, BMBF, DZHK, CTVB, DIASyM, Stiftung Rheinland-Pfalz für Innovation, ReALity, curATime.
ZeitschriftenaufsatzAccess status: Open Access ,
Comparative validation of ENVI-met versions 5.6 and 5.9 against high-resolution in-situ air temperature measurements
(2026)
Sinsel, Tim
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Schöneberger, Peer
;
Simon, Helge
;
Bruse, Michael
Microclimate simulations are critical for assessing urban heat mitigation strategies, yet they face ongoing challenges regarding computational cost and physical parameterization. This study evaluates the performance of the three-dimensional microclimate model ENVI-met, comparing air temperature prediction of the legacy Version 5.6 against the updated Version 5.9. The updated kernel introduces a revised formulation for surface-to-air sensible heat exchange alongside code optimizations. The validation utilizes a high-resolution air temperature dataset collected around a standalone office building in Aalborg, Denmark, covering a 7-day period with varying meteorological conditions. Detailed statistical analysis, including daytime and nighttime stratification, reveals that both model versions reproduce diurnal temperature cycles with a coefficient of determination (R2) exceeding 0.94. The updated Version 5.9 demonstrated a reduction in the aggregated Root Mean Square Error (RMSE) from 0.89 K to 0.78 K and successfully reduced systemic Mean Bias Error (MBE) across the domain, with the most distinct improvements observed in the immediate boundary layer of sun-exposed façades. Additionally, the simulation runtime for the observed period decreased by a factor of approximately three. These findings indicate that the algorithmic updates improve physical consistency in resolving near-surface temperature gradients while significantly lowering the computational resources required for microclimate modeling.
ZeitschriftenaufsatzAccess status: Open Access ,
Immunoadsorption versus sham treatment for Post-COVID syndrome : a randomised sham-controlled crossover trial
(2026)
Stortz, Marco
;
Kommer, Andreas
;
Meineck, Myriam
;
Boedecker-Lips, Simone Cosima
;
Claßen, Paul
Background: Post-Covid syndrome is a debilitating condition which may be caused and/or aggravated by autoantibodies. The current study aimed to determine whether autoantibody depletion by immunoadsorption is effective to reduce the symptom burden of patients with post-Covid syndrome. Methods: IAMPOCO was a randomised, patient-blinded, sham-controlled crossover trial of immunoadsorption with tryptophan adsorbers versus sham treatment in patients with post-Covid syndrome at a tertiary academic care centre. The primary outcome was the difference in change in symptom severity before and after the respective therapies. Secondary outcomes included treatment safety, prevalence of autoantibodies against G protein-coupled receptors (adrenergic and muscarinergic receptors), and the influence of treatment on autoantibody levels. Findings: 40 patients with post-Covid syndrome and a symptom severity of at least 2 on the Post-Covid-19 Functional Scale were included and randomised to a treatment sequence. There was no difference in change in symptom severity between immunoadsorption and sham; odds ratio in Post-Covid-19 Functional Scale, OR = 1.17 (95% CI, 0.41–3.36; p = 0.771), mean difference in MFI-20 2.4 (95% CI, −3.7–8.5; p = 0.437), in CFS 0.09 (95% CI, −4.5 to 4.7; p = 0.970), in Bell-Scale −2.6 (95% CI, −6.9 to 1.8; p = 0.246), in MoCA score −0.01 (95% CI, −1.2 to 1.1, p = 0.993) and in Handgrip-strength deviation from individual normal value 1.3 (−0.83 to 3.5, p = 0.234). 34 adverse events occurred, 10 during or after sham treatment and 24 during or after immunoadsorption. Autoantibodies against G protein-coupled receptors were depleted by immunoadsorption but not sham treatment. Interpretation: Immunoadsorption was not effective in reducing symptom burden in post-Covid syndrome. Funding: Ministry of Health, state of Rhineland-Palatinate; Mainz University Medical Centre; DIAMED Medical Technology. Trial Registration: ClinicalTrials.gov, number NCT05841498.