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67° ± 0.04°, Rotation Y (RY) direction 1.06° ± 0.06°, Rotation Z (RZ) direction 0.78° ± 0.05°; and the single maximum error in three rotation directions were 2.8°, 3.8°, and 2.9°, respectively. On three directions (X, Y, Z axis), the extended distance from clinical target volume (CTV) to planning target volume (PTV) was 3.45, 3.17, and 3.90 mm by calculating, respectively. Then, for the dosimetric analysis, the parameters, including plan sum PTV D98 and D95, planning gross tumor volume D98 and D95, V100% of the plan sum were significantly lower than the treatment plan. Moreover, Dmax of the spinal cord was significantly higher than the treatment plan. CONCLUSION 6D set-up error correction system should be used for accurate position calibration of precise radiotherapy for patients with malignant tumor of the cervical spine. © 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.INTRODUCTION There is limited evidence about the prognostic value of FDG-PET/CT metrics in small cell lung cancer (SCLC) patients staged with TNM staging system. OBJECTIVES The aim of this study is to examine the prognostic value of pretreatment FDG-SUVmax in patients with SCLC staged with 8th TNM staging system. METHODS A total of 344 (292 male) SCLC patients with pretreatment FDG- PET/CT were included. One hundred fifty-three of cases were stages I-III, 191 were stage IV. SUVmax values were obtained for primary tumour, lymph nodes and metastases. Univariate and multivariate analysis were performed to determine the effect of pretreatment SUVmax, with cut-off value of median, on progression-free and overall survival (PFS and OS). RESULTS Median OS and PFS for patients with stages I-III were 16.50 and 11.00 months, respectively. Median OS and PFS for patients with stage IV were 10.00 and 7.00 months, respectively. SUVmax of the primary tumour (PT), lymph nodes or metastasis were not associated with OS and PFS on univariate analysis. On multivariate analysis, SUVmax -PT with cut-off value of 11.60 was found to be an independent prognostic factor for OS in patients with stages I-III (HR;1.88, 95% CI1.15-3.08, P = .012). But the SUVmax -PT (HR; 1.60, 95% CI 0.99-2.60; P = .057) for PFS was found to be a prognostic factor with marginal significance. SUVmax were not significantly associated with OS and PFS in patients with stage IV disease. CONCLUSION Pretreatment SUVmax -PT (median cut-off 11.6) may have a prognostic value of OS and PFS in patients with TNM staged I-III SCLC. © 2020 John Wiley & Sons Ltd.Cyclin D1 is a key regulatory factor of the G1 to S transition during cell cycle progression. Aberrant cyclin D gene amplification and abnormal protein expression have been linked to hepatocellular carcinoma (HCC) tumorigenesis. Intrabodies, effective anticancer therapies that specifically inhibit target protein function within all intracellular compartments, may block cyclin D1 function. Here, a single-chain variable fragment (scFv) antibody against cyclin D1 (ADκ) selected from a human semi-synthetic phage display scFv library is expressed in Escherichia coli as soluble ADκ. Purified ADκ specifically binds to recombinant and endogenous cyclin D1 with high affinity. To enable blocking of intracellular cyclin D1 activity, an endoplasmic reticulum (ER) retention signal sequence is added to the ADκ sequence to encode anti-cyclin D1 intrabody ER-ADκ. read more Transfection of HepG2 cells with expression vector encoding ER-ADκ elicited intracellular ER-ADκ expression leading to cyclin D1 binding, significant G1 phase arrest, and apoptosis that are mechanistically tied to decreased intracellular phosphorylated retinoblastoma protein (Rb) levels. Meanwhile, ER-ADκ dramatically inhibited subcutaneous human HCC xenografts growth in nude mice in vivo after injection of tumors with expression vector encoding ER-ADκ. These results demonstrate the potential of intrabody-based cyclin D1 targeting therapy as a promising treatment for HCC. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Localization-based super-resolution microscopy relies on the detection of individual molecules cycling between fluorescent and non-fluorescent states. These transitions are commonly regulated by high-intensity illumination, imposing constrains to imaging hardware and producing sample photodamage. Here, we propose single-molecule self-quenching as a mechanism to generate spontaneous photoswitching. To demonstrate this principle, we developed a new class of DNA-based open-source super-resolution probes named super-beacons, with photoswitching kinetics that can be tuned structurally, thermally and chemically. The potential of these probes for live-cell compatible super-resolution microscopy without high-illumination or toxic imaging buffers is revealed by imaging interferon inducible transmembrane proteins (IFITMs) at sub-100 nm resolutions. © 2020 The Authors. Traffic published by John Wiley & Sons Ltd.BACKGROUND Since direct oral anticoagulants (DOACs) have been introduced for treatment and prevention of thrombo-embolic diseases, patients on vitamin K antagonists (VKA) have to decide whether to remain on VKA or switch to DOAC. The goal of this study was to evaluate treatment satisfaction, preferences and concerns among those who already switched from VKA to DOAC. METHODS A questionnaire was sent to 2920 former patients of three anticoagulation clinics in the Netherlands, who switched from VKA to DOAC (2016-2017). Questions concerned demographics, treatment satisfaction, concerns, perspectives on antidotes and monitoring. To identify predictors for being concerned about adverse events, logistic regression was used to estimate crude- and adjusted (age and sex) odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS 1399 questionnaires (response rate 48%) were used for analysis. DOAC treatment satisfaction was high (mean 8.8 of a maximum 10-point score). A quarter of patients expressed concerns about adverse events. Predictors for being concerned were age 75 years, OR 4.1, 95%CI 2.6-6.4), female sex (OR 1.3, 95%CI 1.0-1.6), and high education (OR 1.6, 95%CI 1.2-2.2). link2 59% of all patients indicated antidote availability as important, 73% would be willing to participate in DOAC monitoring. CONCLUSIONS DOAC treatment satisfaction was high. A substantial part of patients expressed concerns about adverse events, especially women, patients aged less then 60 years, or highly educated patients. Our findings among patients who already switched to DOAC may assist in the process of shared decision-making when switching a patient from VKA to DOAC is considered. This article is protected by copyright. All rights reserved.WHAT IS KNOWN AND OBJECTIVE Combination regimens of six-month duration may increase the incidence of anti-tuberculosis drug-induced liver injury (ATLI), which is clinically characterized by mild cholestasis and hepatocanalicular lesions. UGT2B4 is a predominant UDP-glucuronosyltransferase enzyme in the human liver that plays an important role in the detoxification of bile acids, which yields water-soluble inactive compounds that can easily be excreted in the bile or urine. This study aimed to investigate the potential association between UGT2B4 variants and the susceptibility to ATLI. METHODS Genomic DNA was extracted from whole blood sample of each patient, and all SNPs were genotyped using an improved multiplex ligation detection reaction method. Clinical symptoms and laboratory results were recorded regularly. Five genetic variants at UGT2B4 (rs1131878, rs1966151, rs28361541, rs4557343 and rs79407331) were identified in a prospective study of 118 ATLI cases and 628 non-ATLI controls. All participants were treated by first-line anti-TB drugs in Western China Hospital. The potential association between SNPs, ATLI risk and clinical phenotypes were determined based on the distribution of allelic frequencies and different genetic models. RESULTS AND DISCUSSION Statistical comparisons of cases and controls after correction for multiple testing did not yield any significant association between genetic variants at UGT2B4 and risk of ATLI via the analyses of single locus and subgroup differences. WHAT IS NEW AND CONCLUSION This is the first study aimed to investigate the association of UGT2B4 polymorphisms with ATLI risk. Our results revealed that UGT2B4 genetic variants are unlikely to confer susceptibility to ATLI in the Western Chinese Han population. © 2020 John Wiley & Sons Ltd.Current therapies for chronic hepatitis B (CHB) include nucleos(t)ide analogues (NAs) and interferon (IFN), but their relative efficacy as monotherapy or in combination has not been examined systematically for HBsAg loss (functional cure). Hence, we systematically reviewed the evidence for HBsAg loss in CHB patients treated with IFN, NA or the combination. We searched PubMed, EMBASE and abstracts from EASL, Asia Pacific Association for study of the Liver and American Association for the Study of Liver Disease for randomized controlled trials of CHB patients, comparing NA, IFN or the combination. The Cochrane Risk of Bias tool v2.0 and GRADE method were used. link3 Analyses were stratified by NA genetic barrier, cirrhosis, type of combination therapy, HBeAg, treatment naivety, IFN dosage/duration and outcome duration. Sensitivity analysis was performed for selected strata, and HBsAg loss was measured at the end-of-study (EOS), end-of-treatment (EOT) or end-of-follow-up (EOF). Effects were reported as risk differences (RD) with 95% confidence intervals (CI) using a random-effects model. Forty-five studies were included, all with low risk of bias. For HBsAg loss at EOS, when comparing combination vs IFN, RD = 1%, 95%CI-1%, 2%; combination vs NA, RD = 5%, 95%CI 3%,7%; IFN vs NA, RD = 3%, 95%CI 2%,5%. Subgroup analysis showed a significant effect of standard IFN dose vs nonstandard; IFN duration ≥48 weeks vs 2 years of follow-up. Similar findings were seen in HBsAg seroconversion, but only three studies reported HBsAg seroreversion. In conclusion, IFN monotherapy/combination had a small but significant increase in HBsAg loss over NA, associated with standard dose of IFN and ≥48 weeks of therapy, although this effect faded over time. © 2020 John Wiley & Sons Ltd.Always on the lookout for articles from the European Journal of Neurology, one in particular has attracted a lot of attention because the results are really fascinating. Although replication is needed, Alves and colleagues addressed a priority issue in clinical research demonstrating that Parkinson's disease (PD) was associated with an increased risk of stroke but the risk of myocardial infarction (MI) and cardiovascular mortality was not significantly increased However, a very important issue and still neglected by neuroscientists are the aspects related to sudden death in PD (SUDPAR). SUDPAR is defined as unexpected death of a PD patient without an evident cause on autopsy. This article is protected by copyright. All rights reserved.Oral squamous cell carcinoma is associated with many known risk factors including tobacco smoking, chronic alcoholism, poor oral hygiene, unhealthy dietary habits and microbial infection. Previous studies have highlighted Candida albicans host tissue infection as a risk factor in the initiation and progression of oral cancer. C. albicans invasion induces several cancerous hallmarks, such as activation of proto-oncogenes, induction of DNA damage and overexpression of inflammatory signalling pathways. However, the molecular mechanisms behind these responses remain unclear. A recently discovered fungal toxin peptide, candidalysin has been reported as an essential molecule in epithelial damage and host recognition of C. albicans infection. Candidalysin has a clear role in inflammasome activation and induction of cell damage. Several inflammatory molecules such as IL-6, IL-17, NLRP3 and GM-CSF have been linked to carcinogenesis. Candidalysin is encoded by the ECE1 gene, which has been linked to virulence factors of C.