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BACKGROUND Hepatocellular carcinoma (HCC) constitutes 0.5% of childhood malignancies and exhibits poor prognosis. Complete tumor extirpation either by partial liver resection (LR) or liver transplantation (LT) is the only curative treatment. Due to the poor initial outcomes of LT, LR has remained the mainstay of treatment for all but select children fulfilling the Milan criteria (originally designed for adults). METHODS Retrospective cohort study of pediatric HCC patients ( less then 18 years) registered in the Surveillance, Epidemiology, and End Results database between 2004-2015. Survival analysis was performed by means of Kaplan-Meier methods, two-sided stratified log-rank tests, and Cox regression models. RESULTS Out of 127 children with HCC, 46 did not undergo surgery (36.2%), 32 underwent LT (25.2%), and 49 underwent LR (38.6%). Using Kaplan-Meier method, the 5-year cancer-specific survival (CSS) rates for LT and LR were 87%, and 63%, respectively. LT exhibited superior CSS vs. LR (log-rank, P=0.007). For T1 stage, LT showed equivalent CSS when compared to LR (log-rank, P=0.23), while for T2 and T3 stage, LT exhibited superior CSS (log-rank, P=0.047, and P=0.01, respectively). On multivariable Cox regression model, T3/T4 stage (adjusted HR 13.63, 95%CI 2.9-64.07; P=0.001), and LR (adjusted HR 7.51, 95%CI 2.07-27.29; P=0.002) were found to be independently associated with cancer-specific mortality. Fibrolamellar histology and lymph node status were not found to be associated with mortality. CONCLUSIONS Our findings suggest that children diagnosed with non-metastatic advanced-stage HCC shows a favorable prognosis after LT when compared to LR. Early inclusion of a LT consultation after initial diagnosis is warranted, especially in children with unresectable HCC or when complete tumor extirpation with LR is not feasible. Embryonic diapause is a conserved reproductive strategy in which development arrests at the blastocyst phase. Recently mammalian target of rapamycin (mTOR) inhibition was shown to induce diapause on mouse blastocysts and a paused-like state on mouse embryonic stem cells (mESCs). In this work, we aimed to further characterize this new paused-pluripotent state, focusing on its glycolytic and oxidative metabolic function. We therefore exposed mESCs, to the mTOR inhibitor INK-128 and evaluated proliferation, pluripotency status and energy-related metabolism, as well as the mTOR inhibition status and translational function. Unexpectedly, in our hands INK-128 did not inhibit the phosphorylation of mTOR or its downstream targets after 48 h. Accordingly, no alterations on protein translational function were observed. Nonetheless, INK-128 could still successfully induce a paused-like state in naïve mESCs regardless of their culturing conditions, by greatly slowing proliferation without affecting pluripotency status. This effect was more prevalent in 2i cultured cells. Interestingly, in this paused-like state, mESCs present a glucose-related hypometabolic profile, which is a hallmark of diapaused blastocysts, with decreased glycolytic and oxidative metabolism and decreased nutrient uptake. Despite the lack of mTOR inhibition and translational suppression, INK-128 still induced a paused-like pluripotent state through cell cycle and metabolic modulation, rather than by translational suppression, suggesting more than one avenue for this type of pluripotent phenotype. BACKGROUND In recent years, there has been a growing interest in the formation of copolymer-lipid hybrid self-assemblies, which allow combining and improving the main features of pure lipid-based and copolymer-based systems known for their potential applications in the biomedical field. As the most common method used to obtain giant vesicles is electroformation, most systems so far used low Tg polymers for their flexibility at room temperature. METHODS Copolymers used in the hybrid vesicles have been synthesized by a modified version of the ATRP, namely the Activators ReGenerated by Electron Transfer ATRP and characterized by NMR and DSC. Giant hybrid vesicles have been obtained using electroformation and droplet transfer method. Confocal fluorescence microscopy was used to image the vesicles. RESULTS Electroformation enabled to obtain hybrid vesicles in a narrow range of compositions (15 mol% was the maximum copolymer content). This range could be extended by the use of a droplet transfer method, which enabled obtaining hybrid vesicles incorporating a methacrylate-based polymer in a wide range of compositions. Proof of the hybrid composition was obtained by fluorescence microscopy using labeled lipids and copolymers. CONCLUSIONS This work describes for the first time, to the best of our knowledge, the formation of giant hybrid polymer/lipid vesicles formed with such a content of a polymethylmethacrylate copolymer, the glass temperature of which is above room temperature. GENERAL SIGNIFICANCE This work shows that polymer structures, more complex than the ones mostly employed, can be possibly included in giant hybrid vesicles by using the droplet transfer method. This will give easier access to functionalized and stimuli-responsive giant vesicles and to systems exhibiting a tunable permeability, these systems being relevant for biological and technological applications. PURPOSE The present controlled laboratory study aimed to assess whether the anatomical repair preserving remnant tendon tissue can enhance tendon-to-bone healing biomechanically and histologically in a rabbit rotator cuff tear model. METHODS Bilateral infraspinatus tenotomy from the greater tuberosity, with remnant tendon on the footprint, was performed on 26 New Zealand white rabbits. https://www.selleckchem.com/products/blu-285.html The open transosseous technique was used to perform bilateral infraspinatus tendon repair 1 week later. Preservation and removal of the remaining tendon were performed on the left and right sides, respectively. Seven rabbits each were sacrificed for biomechanical testing, and six rabbits each were sacrificed for histological evaluation at 4 and 12 weeks. RESULTS Significantly superior biomechanical properties were shown in the remnant tissue preservation group at 4 and 12 weeks in terms of maximum load (93.3 ± 25.1 N vs 68.2 ± 20.7 N P = 0.048, 120.8 ± 27.5 N vs 89.6 ± 24.3 N P = 0.035) and stiffness(25.3 ± 3.4 N/mm vs 17.7 ± 5.
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