Del-NOTCH mut was not linked with prognosis in TCGA cohorts and chemotherapeutic response, but was independently associated with immunotherapeutic benefit, delineating the predictive, but not prognostic utility of del-NOTCH mut Conclusion This work distinguishes del-NOTCH mut as a potential predictor to favorable ICI response in NSCLC, highlighting the importance of genomic profiling in immunotherapy. More importantly, our results unravel a possibility of personalized combination immunotherapy as adding NOTCH inhibitor to ICI regimen in NSCLC, for the optimization of ICI treatment in clinical practice. Copyright ©2020, American Association for Cancer Research.PURPOSE Generation of antigen-specific T cells from cancer patients employs large numbers of peripheral blood cells and/or tumor infiltrating cells to generate antigen-presenting and effector cells commonly requiring multiple rounds of re-stimulation ex vivo We used a novel paramagnetic, nanoparticle-based artificial antigen presenting cell (nano-aAPC) that combines anti-CD28 co-stimulatory and human MHC class I molecules that are loaded with antigenic peptides to rapidly expand tumor antigen-specific T cells from melanoma patients. EXPERIMENTAL DESIGN Nano-aAPC expressing HLA-A*0201 molecules and costimulatory anti-CD28 antibody and loaded with MART-1 or gp100 class I restricted peptides were used to stimulate CD8 T cells purified from the peripheral blood of treatment-naïve or PD-1 antibody-treated patients with stage IV melanoma. Expanded cells were re-stimulated with fresh peptide-pulsed nano-aAPC at day 7. Phenotype analysis and functional assays including cytokine release, cytolysis, and measurement of avidity were conducted. RESULTS MART-1-specific CD8 T cells rapidly expanded up to 1000-fold by day 14 after exposure to peptide-pulsed nano-aAPC. Expanded T cells had a predominantly stem cell memory CD45RA+/CD62L+/CD95+phenotype, expressed ICOS, PD-1, Tim3, and LAG3 and lacked CD28. Cells from patients with melanoma were polyfunctional, highly avid, expressed IL-2, IFN-gamma, TNF-alpha and exhibited cytolytic activity against tumor cell lines. They expanded 2-3-fold after exposure to PD-1 antibody in vivo, and expressed a highly diverse TCR V beta repertoire. CONCLUSIONS Peptide-pulsed nanoparticle aAPC rapidly expanded polyfunctional antigen-specific CD8 T cells with high avidity, potent lytic function and a stem-memory phenotype from melanoma patients. Copyright ©2020, American Association for Cancer Research.Proteomics is the study of a large number of proteins in biological systems. We aim to introduce the complex field to paediatricians and present some recent examples of applications to paediatric problems. Various approaches have been used to study proteomes. The current mainstay is tandem mass spectrometry of enzymatically digested proteins ('bottom-up proteomics'), and we describe the experimental and computational approach further. Proteomics can offer advantages over transcriptomics by giving direct information about proteins rather than RNA; however, typically data are obtained at lower depth and the confident identification of mass spectra can be challenging. Proteomics frequently complements transcriptomics and other -omics. Used effectively, proteomics offers promise to help answer important clinical and biological questions. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To evaluate the cost-effectiveness of two rates of enteral feed advancement (18 vs 30 mL/kg/day) in very preterm and very low birth weight infants.  https://www.selleckchem.com/products/AdipoRon.html  DESIGN Within-trial economic evaluation alongside a multicentre, two-arm parallel group, randomised controlled trial (Speed of Increasing milk Feeds Trial). SETTING 55 UK neonatal units from May 2013 to June 2015. PATIENTS Infants born less then 32 weeks' gestation or less then 1500 g, receiving less than 30 mL/kg/day of milk at trial enrolment. Infants with a known severe congenital anomaly, no realistic chance of survival, or unlikely to be traceable for follow-up, were ineligible. INTERVENTIONS When clinicians were ready to start advancing feed volumes, infants were randomised to receive daily increments in feed volume of 30 mL/kg (intervention) or 18 mL/kg (control). MAIN OUTCOME MEASURE Cost per additional survivor without moderate to severe neurodevelopmental disability at 24 months of age corrected for prematurity. RESULTS Average costs per infant were slightly higher for faster feeds compared with slower feeds (mean difference £267, 95% CI -6928 to 8117). Fewer infants achieved the principal outcome of survival without moderate to severe neurodevelopmental disability at 24 months in the faster feeds arm (802/1224 vs 848/1246). The stochastic cost-effectiveness analysis showed a likelihood of worse outcomes for faster feeds compared with slower feeds. CONCLUSIONS The stochastic cost-effectiveness analysis shows faster feeds are broadly equivalent on cost grounds. However, in terms of outcomes at 24 months age (corrected for prematurity), faster feeds are harmful. Faster feeds should not be recommended on either cost or effectiveness grounds to achieve the primary outcome. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.Fatty acid amide hydrolase (FAAH) is a key enzyme in the endocannabinoid system. N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide ([11C]DFMC) was developed as an irreversible-type positron emission tomography (PET) ligand for FAAH. Here, we attempted to noninvasively estimate rate constant k3 as a direct index for FAAH in the rat brain. First, the two-tissue compartment model analysis including three parameters (K1-k3, 2TCMi) in PET study with [11C]DFMC was conducted, which provided 0.21 ± 0.04 mL·cm-3·min-1 of the net uptake value (Ki), an indirect index for FAAH, in the FAAH-richest region (the cingulate cortex). Subsequently, to noninvasively estimate Ki value, the reference model analysis (Patlak Reference, PGAREF) was tried using a time-activity curve of the spinal cord. In that result, the noninvasive Ki value (KREF) was concisely estimated with high correlation (r > 0.95) to Ki values based on 2TCMi. Using estimated KREF value, we tried to obtain calculated-k3 based on previously defined equations.