Temporal trends in condition diagnoses ascertained from the EDC data were not discoverable in the ICD dataset. DISCUSSION Mining frequent temporal condition patterns from large electronic health record datasets may reveal previously unknown associations between diagnoses that could inform future research into causation or other relationships. Mapping sparsely coded medical concepts into homogenous groups was essential to discovering potentially useful information from our dataset. CONCLUSIONS We expect that the presented methodology is applicable to the study of diagnostic trajectories for other clinical conditions and can be extended to study temporal patterns of other coded medical concepts such as medications and procedures. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association.The ghrelin receptor (GhrR) is known for its strong orexigenic effects in pharmacological doses and has long been considered as a promising target for the treatment of obesity. Several antagonists have been developed in order to decrease the orexigenic signaling, but none of these have been approved for the treatment of obesity due to adverse effects and lack of efficacy. Heterodimerization and biased signaling are important concepts for G-Protein Coupled Receptor (GPCR) signaling, and the influence of these aspects on the GhrR may be important for feeding behavior and obesity. GhrR has been described to heterodimerize with other GPCRs, such as the dopamine receptors 1 and 2, leading to a modulation of the signaling properties of both dimerization partners. Another complicating factor of GhrR mediated signaling is its ability to activate several different signaling pathways upon ligand stimulation. Importantly, some ligands have shown to be "biased" or "functionally selective", implying that the ligand favors a particular signaling pathway. These unique signaling properties could have sizeable impact on the physiological functions of the ghrelin receptor system. Importantly, heterodimerization may explain why the GhrR is expressed in areas of the brain that are difficult for peptide ligands to access. It is suggested as one possibility that the purpose of GhrR expression is to modulate the function of other receptors in addition to merely being independently activated. We suggest that a deeper understanding of the signaling properties of the GhrR will facilitate future drug discovery in the areas of obesity and weight management. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.OBJECTIVES To investigate the role of Major Facilitator Superfamily (MFS)-type transporters from Acinetobacter baumannii AYE in tigecycline efflux. METHODS Two putative tetracycline transporter genes of A. baumannii AYE (tetA and tetG) were heterologously expressed in Escherichia coli and drug susceptibility assays were conducted with tigecycline and three other tetracycline derivatives. The importance of TetA in tigecycline transport in A. baumannii was determined by complementation of tetA in WT and Resistance Nodulation cell Division (RND) gene knockout strains of A. baumannii ATCC 19606. Gene expression of the MFS-type tetA gene and RND efflux pump genes adeB, adeG and adeJ in A. baumannii AYE in the presence of tigecycline was analysed by quantitative real-time RT-PCR. RESULTS Overproduction of TetA or TetG conferred resistance to doxycycline, minocycline and tetracycline in E. coli. Cells expressing tetA, but not those expressing tetG, conferred resistance to tigecycline, implying that TetA is a determinant for tigecycline transport. A. baumannii WT and RND-knockout strains complemented with plasmid-encoded tetA are significantly less susceptible to tigecycline compared with non-complemented strains. Efflux pump genes tetA and adeG are up-regulated in A. baumannii AYE in the presence of subinhibitory tigecycline concentrations. CONCLUSIONS TetA plays an important role in tigecycline efflux of A. baumannii by removing the drug from cytoplasm to periplasm and, subsequently, the RND-type transporters AdeABC and AdeIJK extrude tigecycline across the outer membrane.  https://www.selleckchem.com/products/ptc-209.html  When challenged with tigecycline, tetA is up-regulated in A. baumannii AYE. Synergy between TetA and the RND-type transporters AdeABC and/or AdeIJK appears necessary for A. baumannii to confer higher tigecycline resistance via drug efflux. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email journals.permissions@oup.com.OBJECTIVES To characterize and compare resistance trends in clinical Escherichia coli isolates from humans, food-producing animals (poultry, cattle and swine) and pets (dogs and cats). METHODS Antibiogram results collected between January 2014 and December 2017 by MedQual [the French surveillance network for antimicrobial resistance (AMR) in bacteria isolated from the community] and RESAPATH (the French surveillance network for AMR in bacteria from diseased animals) were analysed, focusing on resistance to antibiotics of common interest to human and veterinary medicine. Resistance dynamics were investigated using generalized additive models. RESULTS In total, 743 637 antibiograms from humans, 48 170 from food-producing animals and 7750 from pets were analysed. For each antibiotic investigated, the resistance proportions of isolates collected from humans were of the same order of magnitude as those from food-producing animals or pets. However, resistance trends in humans differed from those observed in pets ans@oup.com.AIMS Myocardial fibrosis (MF) might represent a key player in pathophysiology of heart failure in aortic stenosis (AS). We aimed to assess its impact on left ventricular (LV) remodelling, recovery, and mortality after transcatheter aortic valve implantation (TAVI) in different AS subtypes. METHODS AND RESULTS One hundred patients with severe AS were prospectively characterized clinically and echocardiographically at baseline (BL), 6 months, 1 year, and 2 years following TAVI. Left ventricular biopsies were harvested after valve deployment. Myocardial fibrosis was assessed after Masson's trichrome staining, and fibrotic area was calculated as percentage of total tissue area. Patients were stratified according to MF above (MF+) or below (MF-) median percentage MF (≥11% or less then 11%). Myocardial fibrosis burden differed significantly between AS subtypes, with highest levels in low ejection fraction (EF), low-gradient AS and lowest levels in normal EF, high-gradient AS (29.5 ± 26.4% vs. 13.5 ± 16.1%, P = 0.003).