In memory of Bruce McEwen: a gentle giant of neuroscience

On 2 January 2020, the neuroscience community lost not only a pioneering figure, but also a generous and influential thought leader. Bruce Sherman McEwen, head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at the Rockefeller University, passed away at age 81, following a short illness. A member of the National Academy of Sciences, National Academy of Medicine and American Academy of Arts & Sciences, and former president of the Society for Neuroscience, Bruce will be remembered for his profound scientific impact, measured not only by output of papers, but also by the large family of neuroscientists he trained over a career spanning nearly six decades. Above all, Bruce will be remembered for his generosity, kindness, gentleness of soul, and for being an extraordinary mentor.Diabetes mellitus: pathophysiological changes and therap

Machine learning based on biomarker profiles identifies distinct subgroups of heart failure with preserved ejection fraction

Aims: The lack of effective therapies for patients with heart failure with preserved ejection fraction (HFpEF) is often ascribed to the heterogeneity of patients with HFpEF. We aimed to identify distinct pathophysiologic clusters of HFpEF based on circulating biomarkers. Methods and results: We performed an unsupervised cluster analysis using 363 biomarkers from 429 patients with HFpEF. Relative differences in expression profiles of the biomarkers between clusters were assessed and used for pathway over-representation analyses. We identified four distinct patient subgroups based on their biomarker profiles: cluster 1 with the highest prevalence of diabetes mellitus and renal disease; cluster 2 with oldest age and frequent age-related comorbidities; cluster 3 with youngest age, largest body size, least symptoms and lowest N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels; and cluster 4 with highest prevalence of ischaemic aetiology, smoking and chronic lung disease, most symptoms, as well as highest NT-proBNP and troponin levels. Over a median follow-up of 21 months, the occurrence of death or heart failure hospitalization was highest in clusters 1 and 4 (62.1% and 62.8%, respectively) and lowest in cluster 3 (25.6%). Pathway over-representation analyses revealed that the biomarker profile of patients in cluster 1 was associated with activation of inflammatory pathways while the biomarker profile of patients in cluster 4 was specifically associated with pathways implicated in cell proliferation regulation and cell survival. Conclusion: Unsupervised cluster analysis based on biomarker profiles identified mutually exclusive subgroups of patients with HFpEF with distinct biomarker profiles, clinical characteristics and outcomes, suggesting different underlying pathophysiological pathways. © 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology

Dephosphorylation of YB-1 is required for nuclear localisation during G2 phase of the cell cycle

10.3390/cancers12020315Cancers12231