Combined treatment of malignant salivary gland tumours with intensity-modulated radiation therapy (IMRT) and carbon ions: COSMIC

<p>Abstract</p> <p>Background</p> <p>Local control in malignant salivary gland tumours is dose dependent. High local control rates in adenoid cystic carcinomas could be achieved by highly conformal radiotherapy techniques and particle (neutron/carbon ion) therapy. Considering high doses are needed to achieve local control, all malignant salivary gland tumours probably profit from the use of particle therapy, which in case of carbon ion treatment, has been shown to be accompanied by only mild side-effects.</p> <p>Methods/design</p> <p>The COSMIC trial is a prospective, mono-centric, phase II trial evaluating toxicity (primary endpoint: mucositis ≥ CTCAE°3) and efficacy (secondary endpoint: local control, disease-free survival) in the combined treatment with IMRT and carbon ion boost in 54 patients with histologically proved (≥R1-resected, inoperable or Pn+) salivary gland malignancies. Patients receive 24 GyE carbon ions (8 fractions) and IMRT (50 Gy at 2.0 Gy/fraction).</p> <p>Discussion</p> <p>The primary objective of COSMIC is to evaluate toxicity and feasibility of the proposed treatment in all salivary gland malignancies.</p> <p>Trial Registration</p> <p>Clinical trial identifier NCT 01154270</p

Seeing Through the Ring: Near-infrared Photometry of V582 Mon (KH 15D)

We examine the light and color evolution of the T Tauri binary KH 15D through photometry obtained at wavelengths between 0.55 and 8.0 μm. The data were collected with A Novel Dual Imaging CAMera (ANDICAM) on the 1.3 m SMARTS telescope at Cerro-Tololo Inter-American Observatory and with InfraRed Array Camera on the Spitzer Space Telescope. We show that the system's circumbinary ring, which acts as a screen that covers and uncovers different portions of the binary orbit as the ring precesses, has reached an orientation where the brighter component (star B) fully or nearly fully emerges during each orbital cycle. The fainter component (star A) remains fully occulted by the screen at all phases. The leading and trailing edges of the screen move across the sky at the same rate of ~15 m s^(−1), consistent with expectation for a ring with a radius and width of ~4 au and a precession period of ~6500 years. Light and color variations continue to indicate that the screen is sharp edged and opaque at VRIJH wavelengths. However, we find an increasing transparency of the ring edge at 2.2, 3.6, and 4.5 μm. Reddening seen at the beginning of the eclipse that occurred during the CSI 2264 campaign particularly suggests selective extinction by a population of large dust grains. Meanwhile, the gradual bluing observed while star B is setting is indicative of forward scattering effects at the edge of the ring. The spectral energy distribution of the system at its bright phase shows no evidence of infrared excess emission that can be attributed to radiation from the ring or other dust component out to 8 μm

Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

BACKGROUND: Diets that restrict carbohydrate (CHO) have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. METHODS: We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy). A total of 27 single nucleotide polymorphisms (SNPs) were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. RESULTS: Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF), hepatic glycogen synthase (GYS2), cholesteryl ester transfer protein (CETP) and galanin (GAL) genes were significantly associated with weight loss. CONCLUSION: A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction

Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat

<p>Abstract</p> <p>Background</p> <p>Genetic factors that predict responses to diet may ultimately be used to individualize dietary recommendations. We used physiogenomics to explore associations among polymorphisms in candidate genes and changes in relative body fat (Δ%BF) to low fat and low carbohydrate diets.</p> <p>Methods</p> <p>We assessed Δ%BF using dual energy X-ray absorptiometry (DXA) in 93 healthy adults who consumed a low carbohydrate diet (carbohydrate ~12% total energy) (LC diet) and in 70, a low fat diet (fat ~25% total energy) (LF diet). Fifty-three single nucleotide polymorphisms (SNPs) selected from 28 candidate genes involved in food intake, energy homeostasis, and adipocyte regulation were ranked according to probability of association with the change in %BF using multiple linear regression.</p> <p>Results</p> <p>Dieting reduced %BF by 3.0 ± 2.6% (absolute units) for LC and 1.9 ± 1.6% for LF (p < 0.01). SNPs in nine genes were significantly associated with Δ%BF, with four significant after correction for multiple statistical testing: rs322695 near the retinoic acid receptor beta (<it>RARB</it>) (p < 0.005), rs2838549 in the hepatic phosphofructokinase (<it>PFKL</it>), and rs3100722 in the histamine N-methyl transferase (<it>HNMT</it>) genes (both p < 0.041) due to LF; and the rs5950584 SNP in the angiotensin receptor Type II (<it>AGTR2</it>) gene due to LC (p < 0.021).</p> <p>Conclusion</p> <p>Fat loss under LC and LF diet regimes appears to have distinct mechanisms, with <it>PFKL </it>and <it>HNMT </it>and <it>RARB </it>involved in fat restriction; and <it>AGTR2 </it>involved in carbohydrate restriction. These discoveries could provide clues to important physiologic mechanisms underlying the Δ%BF to low carbohydrate and low fat diets.</p

Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease

The COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respiratory infections to the common cold. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of a range of human coronavirus diseases. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant drug repurposing candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.We gratefully acknowledge funding that supported this research support from the Ryerson University Faculty of Science (CNA), as well as funding support in the form of a CIFAR Catalyst Grant (JPJ and CNA), an NSERC Alliance Grant (CNA) and the Ryerson COVID-19 SRC Response Fund award (CNA). BW is partly supported by CIFAR AI Chairs Program. This work was also supported by a Mitacs award (BW), the European Union’s Horizon 2020 research and innovation program under a Marie Sklodowska-Curie grant (ER), by the CIFAR Azrieli Global Scholar program (JPJ), by the Ontario Early Researcher Awards program (JPJ and CNA), and by the Canada Research Chairs program (JPJ). We also thank Dr. James Rini (University of Toronto) for the kind gift of the 9.8E12 antibody used to detect the 229E Spike protein, and Dr. Scott Gray-Owen (University of Toronto) for the kind gift of the NL63 human coronavirus.Peer reviewe

Near-Infrared Variability in the Orion Nebula Cluster

Using the United Kingdom Infrared Telescope on Mauna Kea, we have carried out a new near-infrared J, H, K monitoring survey of almost a square degree of the star-forming Orion Nebula Cluster with observations on 120 nights over three observing seasons, spanning a total of 894 days. We monitored ~15,000 stars down to J=20 using the WFCAM instrument, and have extracted 1203 significantly variable stars from our data. By studying variability in young stellar objects (YSOs) in the H-K, K color-magnitude diagram, we are able to distinguish between physical mechanisms of variability. Many variables show color behavior indicating either dust-extinction or disk/accretion activity, but we find that when monitored for longer periods of time, a number of stars shift between these two variability mechanisms. Further, we show that the intrinsic timescale of disk/accretion variability in young stars is longer than that of dust-extinction variability. We confirm that variability amplitude is statistically correlated with evolutionary class in all bands and colors. Our investigations of these 1203 variables have revealed 73 periodic AA Tau type variables, many large-amplitude and long-period (P > 15 day) YSOs, including three stars showing widely-spaced periodic brightening events consistent with circumbinary disk activity, and four new eclipsing binaries. These phenomena and others indicate the activity of long-term disk/accretion variability processes taking place in young stars. We have made the light curves and associated data for these 1203 variables available online.Comment: Corrected typo in author nam