© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Ramucirumab plus docetaxel (RAM+DOC) is expected to prolong survival in patients with advanced non-small cell lung cancer (NSCLC); however, the efficacy and safety for older patients remains unknown.  https://www.selleckchem.com/products/zidesamtinib.html  The objective of this study was to evaluate the efficacy and safety of RAM+DOC in patients 75 years and older. METHODS We retrospectively reviewed consecutive patients with advanced NSCLC who had received RAM+DOC treatment at three institutions. We compared the efficacy and safety in patients 75 years and older to those under 75 years of age. RESULTS A total of 114 patients were identified. The median progression-free survival, time to treatment failure and overall survival was 3.6 (95% CI 0.4-6.7), 3.1 (95% CI 2.4-3.9) and 11.2 months (95% CI 5.6-16.8) in the older group (N = 23), and 4.2 (95% CI 3.3-5.0), 3.4 (95% CI 3.3-5.0) and 12.2 months (95% CI 9.1-15.4) in the younger group (N = 91), respectively. Survival curves were similar for each group, while the objective response rate was 30.4% (95% CI 1ia, Ltd.1-Deoxysphingolipids are a recently described class of sphingolipids, which have been shown to be associated with several disease states including diabetic and hereditary neuropathy. The identification and characterization of 1-deoxysphingolipids and their metabolites is therefore highly important. However, exact structure determination requires a combination of sophisticated analytical techniques due to the presence of various isomers, such as ketone/alkenol isomers, carbon-carbon double bond (C=C) isomers and hydroxylation-regioisomers. Here we demonstrate that cryogenic gas-phase infrared (IR) spectroscopy of ionized 1-deoxysphingolipids enables the identification and differentiation of isomers by their unique spectroscopic fingerprints. In particular, C=C bond positions and stereochemical configurations can be distinguished by specific interactions between the charged amine and the double bond. The results demonstrate the power of gas-phase IR spectroscopy to overcome the challenge of isomer resolution in conventional mass spectrometry and pave the way for deeper analysis of the lipidome. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Lysophosphatidic acid (LPA), a bioactive phospholipid released by activated platelets, can induce platelet shape changes and aggregation, which may play an important role in thrombosis. In contrast, the interaction of LPA with neutrophils in thrombosis has not been studied. Recently, neutrophil extracellular traps (NETs) have been shown to bind plasma proteins and activate platelets, which promotes thrombosis. OBJECTIVES To investigate whether LPA could activate neutrophils to release NETs, predisposing to thrombosis and promoting thrombus stability. METHODS Levels of neutrophils, NETs, and LPA were detected in 56 participants. Immunofluorescence of NETs and autotaxin, the LPA-producing ectoenzyme, were performed. Induction of NETs and signaling pathways were explored in vitro. RESULTS Patients with acute pulmonary embolism showed elevated levels of neutrophils, NETs (dsDNA, MPO-DNA, citrullinated histone H3, and nucleosomes), LPA181, and LPA204. NETs were present in human intrapulmonary thrombi and were surrounded by autotaxin. LPA181 induced rapid release of NETs from human neutrophils via a peptidylarginine deiminase 4-dependent pathway. LPA-induced NETs provided a scaffolding for plasma protein binding and generated a tPA-resistant blood clot. Addition of deoxyribonuclease I to tPA significantly accelerated the lysis of clots and human intrapulmonary thrombi. Furthermore, LPA-induced NETs could activate platelets to release LPA. CONCLUSION This is the first study to implicate LPA in regulating the stability of thrombus by inducing rapid release of NETs in vitro and ex vivo, which could be a new mechanism of thrombosis. These findings provide new insight into the prevention and therapy of venous thromboembolic disease by targeting LPA-NETs signaling pathway. This article is protected by copyright. All rights reserved.BACKGROUND High-flow nasal cannula (HFNC) therapy is widely used for respiratory support within paediatrics, most commonly used as a supportive measure in acute respiratory failure, aiming to avoid invasive mechanical ventilation (IMV). It is increasingly being used following extubation of critically ill children potentially at a higher risk of requiring re-intubation. Less data indicate the use for post-extubation HFNC therapy or possible clinical outcomes of this therapy. AIMS AND OBJECTIVES To identify reasons for, and variables to predict, the use of HFNC therapy post-extubation. DESIGN This was a retrospective case-control study. METHODS All children admitted to a nine-bedded regional paediatric intensive care unit requiring IMV between 18 December 2017 and 28 November 2018 were identified. The demographic data and bedside clinical and laboratory variables of the patients requiring HFNC therapy were compared with those who did not require HFNC. RESULTS There was no statistical difference in the median agtical Care Nurses.The occurrence of Crimean-Congo haemorrhagic fever (CCHF) in humans is linked with animals living in close vicinity, and information on the incidence of CCHF at the human-animal interface is scarce. Therefore, the current study was designed to identify the high-risk groups of individuals linked with animals in the Chakwal district of Pakistan having a history of CCHF cases in humans. In subject matter, coupled with risk factor analysis, we performed a sero-based CCHF surveillance in three selected risk groups of humans including abattoir workers (n = 137), milkmen (n = 169) and animal handlers (n = 147). Sera samples and questionnaire-based data were collected from each of the participants and screened for anti-CCHFV IgG antibodies using enzyme-linked immunosorbent assay. The highest seroprevalence was observed in animal handlers (n = 14, 9.52%, 95% CI 4.68-13.99) followed by abattoir workers (n = 9, 6.57%, 95% CI 2.42-10.72) and milkmen (n = 3, 1.78%, 95% CI 0.24-4.24). The risk of seropositivity was significantly associated with humans linked with tick-infested animals (OR 11.