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Background The validity of circulating tumour DNA (ctDNA) as an indicator of disease progression compared to medical imaging in patients with metastatic melanoma requires detailed evaluation.Methods Here, we carried out a retrospective ctDNA analysis of 108 plasma samples collected at the time of disease progression. We also analysed a validation cohort of 66 metastatic melanoma patients monitored prospectively after response to systemic therapy.Results ctDNA was detected in 62% of patients at the time of disease progression. For 67 patients that responded to treatment, the mean ctDNA level at progressive disease was significantly higher than at the time of response (P < 0.0001). However, only 30 of these 67 (45%) patients had a statistically significant increase in ctDNA by Poisson test. A validation cohort of 66 metastatic melanoma patients monitored prospectively indicated a 56% detection rate of ctDNA at progression, with only two cases showing increased ctDNA prior to radiological progression. Finally, a correlation between ctDNA levels and metabolic tumour burden was only observed in treatment naïve patients but not at the time of progression in a subgroup of patients failing BRAF inhibition (N = 15).Conclusions These results highlight the low efficacy of ctDNA to detect disease progression in melanoma when compared mainly to standard positron emission tomography imaging.Subject terms: Tumour biomarkers, Biomarkers  相似文献   
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Type 2 diabetes mellitus (T2DM) is a major health problem, worldwide, that is associated with increased morbidity and mortality. Several randomized controlled clinical trials (RCTs) have investigated the effect of nettle (Urtica dioica) supplementation on markers of glycemic status in patients with T2DM, with conflicting results. Therefore, the present study assessed the effect of nettle on some glycemic parameters in patients with T2DM. A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science, from database inception up to June 2019, to identify RCTs investigating the effect of nettle supplementation on glycemic markers, including fasting blood sugar (FBS) concentrations, insulin levels, homeostasis model assessment‐estimated insulin resistance index, and glycosylated hemoglobin percentage in adults with T2DM. The Cochrane Collaboration tool was used to assess the methodological quality of the included studies. Results of this meta‐analysis were reported based on the random effects model. Eight RCTs, comprising 401 participants, were included in the present systematic review and meta‐analysis. Based on the Cochrane Collaboration risk of bias tool, five studies were considered as good quality, one was fair, and two studies were poor, respectively. The results of the meta‐analysis revealed a significant reduction in FBS concentrations (weighted mean difference [WMD]: ?18.01 mg/dl, 95% confidence interval [CI]: ?30.04 to ?5.97, p < .001, I2 = 94.6%) following nettle supplementation. However, no significant reduction was observed in insulin levels (WMD: 0.83 Hedges' g, 95% CI: ?0.26 to 1.92, p = .13, I2 = 89.4%), homeostasis model assessment‐estimated insulin resistance index (WMD: ?0.22, 95% CI: ?0.83 to 0.40, p = .49, I2 = 69.2%), or glycosylated hemoglobin percentage (WMD: ?0.77%, 95% CI: ?1.77 to 0.22, p = .12, I2 = 83.0%). The findings of the present study suggest that nettle supplementation may be effective in controlling FBS for T2DM patients. However, further studies are needed to confirm the veracity of these results.  相似文献   
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WM. Munk 《Lancet》1840,34(878):480-483
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Dentinal hypersensitivity is a painful condition that occurs following periodontal treatment. Many treatment alternatives have been considered for this problem, including treatments with laser and dentinal adhesives. This study compared the sealing ability of Nd:YAG laser versus a new resin in scanning electron microscopy (SEM) micrographs. Ten human premolars were sectioned yielding 30 specimens of each premolar, which were randomly divided into three groups. The laser group was irradiated by Nd:YAG laser (1 W, 10 Hz, 60 s), the resin group was treated with the new Seal & Protect resin according to the manufacturer’s instructions, and the third group served as the control group and did not receive any interventions. After preparation and gold coating of the samples, they were photographed by SEM at two magnifications (1500× and 4000×). The number and diameter (μm) of the dentinal tubules were recorded in selected fields, and analysis of variance (ANOVA) and Tukey tests were used to determine significant differences between groups. The ANOVA results revealed significant differences in both the mean number (P < 0.001) and diameter (P < 0.05) among the three groups. Further statistical analysis showed a significant difference between the laser group and the resin group in both outcome measures (P < 0.05). Thus, both Nd:YAG laser and the new resin reduced the number and diameter of open dentinal tubules, a result that also explains the desensitization mechanism of these interventions. We further conclude that application of the new resin is more effective than Nd:YAG laser in minimizing the number and diameter of exposed dentinal tubules.  相似文献   
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