Single-cell RNA sequencing reveals cardiac fibroblast-specific transcriptomic changes in dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is the most common cause of heart failure, with a complex aetiology involving multiple cell types. We aimed to detect cell-specific transcriptomic alterations in DCM through analysis that leveraged recent advancements in single-cell analytical tools. Single-cell RNA sequencing (scRNA-seq) data from human DCM cardiac tissue were subjected to an updated bioinformatic workflow in which unsupervised clustering was paired with reference label transfer to more comprehensively annotate the dataset. Differential gene expression was detected primarily in the cardiac fibroblast population. Bulk RNA sequencing was performed on an independent cohort of human cardiac tissue and compared with scRNA-seq gene alterations to generate a stratified list of higher-confidence, fibroblast-specific expression candidates for further validation. Concordant gene dysregulation was confirmed in TGFβ-induced fibroblasts. Functional assessment of gene candidates showed that AEBP1 may play a significant role in fibroblast activation. This unbiased approach enabled improved resolution of cardiac cell-type-specific transcriptomic alterations in DCM.<br/

Effects of M dwarf magnetic fields on potentially habitable planets

A.A.V. acknowledges support from the Royal Astronomical Society through a post-doctoral fellowship. J.M. acknowledges support from a fellowship of the Alexander von Humboldt foundation. P.L. acknowledges funding from a STFC scholarship. AJBR is a Research Fellow of the Royal Commission for the Exhibition of 1851.We investigate the effect of the magnetic fields of M dwarf (dM) stars on potentially habitable Earth-like planets. These fields can reduce the size of planetary magnetospheres to such an extent that a significant fraction of the planet’s atmosphere may be exposed to erosion by the stellar wind. We used a sample of 15 active dM stars, for which surface magnetic-field maps were reconstructed, to determine the magnetic pressure at the planet orbit and hence the largest size of its magnetosphere, which would only be decreased by considering the stellar wind. Our method provides a fast means to assess which planets are most affected by the stellar magnetic field, which can be used as a first study to be followed by more sophisticated models. We show that hypothetical Earth-like planets with similar terrestrial magnetisation (~1 G) orbiting at the inner (outer) edge of the habitable zone of these stars would present magnetospheres that extend at most up to 6 (11.7) planetary radii. To be able to sustain an Earth-sized magnetosphere, with the exception of only a few cases, the terrestrial planet would either (1) need to orbit significantly farther out than the traditional limits of the habitable zone; or else, (2) if it were orbiting within the habitable zone, it would require at least a magnetic field ranging from a few G to up to a few thousand G. By assuming a magnetospheric size that is more appropriate for the young-Earth (3.4 Gyr ago), the required planetary magnetic fields are one order of magnitude weaker. However, in this case, the polar-cap area of the planet, which is unprotected from transport of particles to/from interplanetary space, is twice as large. At present, we do not know how small the smallest area of the planetary surface is that could be exposed and would still not affect the potential for formation and development of life in a planet. As the star becomes older and, therefore, its rotation rate and magnetic field reduce, the interplanetary magnetic pressure decreases and the magnetosphere of planets probably expands. Using an empirically derived rotation-activity/magnetism relation, we provide an analytical expression for estimating the shortest stellar rotation period for which an Earth-analogue in the habitable zone could sustain an Earth-sized magnetosphere. We find that the required rotation rate of the early- and mid-dM stars (with periods ≳37–202 days) is slower than the solar one, and even slower for the late-dM stars (≳63–263 days). Planets orbiting in the habitable zone of dM stars that rotate faster than this have smaller magnetospheric sizes than that of the Earth magnetosphere. Because many late-dM stars are fast rotators, conditions for terrestrial planets to harbour Earth-sized magnetospheres are more easily achieved for planets orbiting slowly rotating early- and mid-dM stars.Publisher PDFPeer reviewe

Correction: Epidemiology and outcomes of early-onset AKI in COVID-19-related ARDS in comparison with non-COVID-19-related ARDS: insights from two prospective global cohort studies (Critical Care, (2023), 27, 1, (3), 10.1186/s13054-022-04294-5)

Following publication of the original article [1], the authors identified that the collaborating authors part of the collaborating author group CCCC Consortium was missing. The collaborating author group is available and included as Additional file 1 in this article

Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis

Background: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. Methods: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2&nbsp;days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48&nbsp;h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. Results: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2&nbsp;years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90&nbsp;days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28&nbsp;days, VFD were 16 (IQR 0–25) and 25 (IQR 7–26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0–87) and 87 (IQR 0–88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). Conclusions: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting