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Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.  相似文献   
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Maternal and Child Health Journal - Early life exposures can have an impact on a child’s developmental trajectory and children born late preterm (34–36 weeks gestational age)...  相似文献   
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Academic output is just one aspect of a successful career as a plastic surgeon. However, for those with a strong interest in academia, the academic output of a department will likely be a key factor when deciding how to rank jobs. The aim of this study was to quantify and rank the academic output of plastic surgery units across the UK and Ireland. The Institute for Scientific Information (ISI) Web of Science Bibliometric analysis tool was used to collate cumulative (1950–2016), 10 year (2006–2016) and 3 years (2013–2015) research output data for plastic surgery units in the UK and Ireland. Sixty-six plastic surgery units were identified. Departments were ranked for each time period according to the number of papers produced, number of citations (Nc) and h-index (a measure of the impact of scientific output). The top 3 departments for number of papers in the last 10 years were The Royal Free Hospital, London (226) Broomfield Hospital, Chelmsford (218), and Morriston Hospital and Swansea (188). The top 3 for h-number were The Royal Free Hospital (21) Wythenshawe Hospital, Manchester (18) and Morriston Hospital (17). Academic output varies across plastic surgery units in the UK and Ireland. A number of departments have consistently maintained high academic outputs across the years and will be of interest to surgeons hoping to pursue a career in academia.  相似文献   
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Bulletin of Experimental Biology and Medicine - Ammonium, an end-product of catabolism, in low doses can promote adaptation of metabolic pathways in erythrocytes under conditions of extreme...  相似文献   
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